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A sustainable catalytic pyrrole synthesis Stefan Michlik, 1 Rhett Kempe* 1 1 Lehrstuhl Anorganische Chemie II, Universität Bayreuth, 95440 Bayreuth, Germany *To whom correspondence should be addressed. E-mail: kempe@uni-bayreuth.de Contents General Considerations... 2 Screening Reactions... 2 Ligand and Complex Syntheses... 7 Reaction of 1-Phenylethanol with various Amino Alcohols... 12 Reaction of 2-Amino-3-phenyl-propan-1-ol with various Secondary Alcohols... 17 Reaction of 2-Amino-3-phenyl-propan-1-ol with various Cyclic Alcohols... 25 Reaction of Hexane-2,5-diol with various Amino Alcohols to Symmetric and Unsymmetric Bipyrroles... 32 Syntheses of -protected Amino Alcohols and their Conversion with 2-Amino-3-phenyl-propan-1-ol... 34 Mechanistic Studies... 41 Crystal Structure of [(4-Ph)Tr(P( i Pr) 2 )(HP( i Pr) 2 )Ir(cod)] (Catalyst II)... 48 Crystal Structure of [(4-Ph)Tr(HP(iPr) 2 )IrH 3 ] (catalyst resting state)... 60 MR-Data... 81 ATURE CHEMISTRY www.nature.com/naturechemistry 1 2013 Macmillan Publishers Limited. All rights reserved.

General Considerations All reactions were carried out in a dry argon or nitrogen atmosphere using standard Schlenk techniques or glove box techniques. Halogenated solvents were dried over P 2 O 5, and nonhalogenated solvents were dried over sodium benzophenone ketyl. Deuterated solvents were ordered from Cambridge Isotope Laboratories, vented, stored over molecular sieves and distilled. All chemicals were purchased from commercial sources with purity with over 97% and used without further purification. MR spectra were received using an IOVA 400 and 300 MHz spectrometer at 298 K or a BRUKER 300 MHz spectrometer at 300 K. Chemical shifts are reported in ppm relative to the deuterated solvent. Elemental analyses were carried out on a Vario elementar EL III. GC analyses were carried out on an Agilent 6890 etwork GC system equipped with a HP-5 column (30 m x 0.32 µm x 0.25 µm). GC/MS analyses were carried out on a Thermo Focus GC/Trace DSQ system equipped with a HP-5MS column (30 m x 0.32 µm x 0.25 µm). X-ray crystal structure analyses were performed with a STOE-IPDS II equipped with an Oxford Cryostream low-temperature unit. Screening Reactions General screening procedure: In a pressure tube catalyst, solvent, secondary alcohol, amino alcohol and base were combined. The pressure tube was closed with a Teflon cap or a semipermeable membrane and stirred for 24 h. The reaction mixture was cooled to room temperature and quenched by addition of 2 ml of water. Dodecane as internal standard was added and after shaking, a small fraction of the organic phase was analysed by GC. The following reaction was investigated. Supplementary Figure S1. Screening reaction of 1-phenylethanol with 2-amino-1-butanol ATURE CHEMISTRY www.nature.com/naturechemistry 2 2013 Macmillan Publishers Limited. All rights reserved.

Supplementary Table S1. Base Screening Base Yield [%] KO t Bu 55 KOH 32 K(SiMe 3 ) 2 0 KOSiMe 3 0 K 3 PO 4 4 KH 47 K 2 CO 3 0 KOAc 0 ao t Bu 37 ah 2 25 aoac 0 a 2 CO 3 0 LiH 0 Li t Bu 12 Mg(O(C 2 H 5 )) 2 0 Reaction conditions: 1.0 eq. 1-phenylethanol (120 µl), 1.1 eq. 2-amino-1-butanol (104 µl), 1.1 eq. base, 3.0 ml THF, 1 mol% catalyst I, 24 h, 110 C (reaction tubes closed with Teflon caps). Yields determined by GC analyses with dodecane as internal standard. Supplementary Table S2. Solvent Screening Solvent Yield [%] THF 55 DME 54 toluene 41 hexane 49 DMSO 0 diglyme 45 dioxane 48 Reaction conditions: 1.0 eq. 1-phenylethanol (120 µl), 1.1 eq. 2-amino-1-butanol (104 µl), 1.1 eq. KO t Bu, 3.0 ml solvent, 1 mol% catalyst I, 24 h, 110 C (reaction tubes closed with Teflon caps). Yields determined by GC analyses with dodecane as internal standard. Supplementary Table S3. Amount of KO t Bu Base Amount According to Secondary Alcohol [eq.] Yield [%] 3.0 8 2.0 19 1.1 55 1.0 53 0.5 32 without base 0 Reaction conditions: 1.0 eq. 1-phenylethanol (120 µl), 1.1 eq. 2-amino-1-butanol (104 µl), 3.0 ml solvent, KO t Bu, 1 mol% catalyst I, 24 h, 110 C (reaction tubes closed with Teflon caps). Yields determined by GC analyses with dodecane as internal standard. Supplementary Table S4. Alcohol Ratio Amino Alcohol /Secondary Alcohol [eq.] Yield [%] 3.0 / 1.0 34 2.0 / 1.0 51 ATURE CHEMISTRY www.nature.com/naturechemistry 3 2013 Macmillan Publishers Limited. All rights reserved.

1.1 / 1.0 55 1.0 / 1.0 54 1.0 / 1.1 56 1.0 / 2.0 72 1.0 / 3.0 77 1.0/ 4.0 77 Reaction conditions: 1.1 mmol KO t Bu, 3.0 ml THF, 1 mol% catalyst I, 24 h, 110 C (reaction tubes closed with Teflon caps). Yields determined by GC analyses with dodecane as internal standard. Supplementary Table S5. Solvent Amount Solvent Amount [ml] Yield [%] 4.0 77 3.0 77 2.0 70 1.0 65 0.5 56 0.25 51 Reaction conditions: 2.0 eq. 1-phenylethanol (240 µl), 1.0 eq. 2-amino-1-butanol (96 µl) 1.1eq. KO t Bu, 1 mol% catalyst I, 24 h, 110 C (reaction tubes closed with Teflon caps). Yields determined by GC analyses with dodecane as internal standard. Supplementary Table S6. Temperature Screening Temperature [ C] Oil Bath Yield [%] 150 76 130 76 110 76 90 40 80 23 70 6 Reaction conditions: 2.0 eq. 1-phenylethanol (240 µl), 1.0 eq. 2-amino-1-butanol (96 µl) 1.1 eq. KO t Bu, 1 mol% catalyst I, 24 h (reaction tubes closed with Teflon caps). Yields determined by GC analyses with dodecane as internal standard. Supplementary Table S7. Catalyst Loading Cat. Loading [mol%] Yield [%] 2.0 65 1.0 75 0.6 79 0.4 78 0.2 77 0.1 76 0.05 68 0.01 36 0.005 10 Reaction conditions: 2.0 eq. 1-phenylethanol (240 µl), 1.0 eq. 2-amino-1-butanol (96 µl) 1,1eq. KO t Bu, catalyst I, 24 h, 110 C (reaction tubes closed with Teflon caps). Yields determined by GC analyses with dodecane as internal standard. ATURE CHEMISTRY www.nature.com/naturechemistry 4 2013 Macmillan Publishers Limited. All rights reserved.

Supplementary Table S8. Iridium Catalyst Screening Catalyst Yield [%] I 10 II 63 III 33 IV 54 V [IrOMe(cod)] 2 2 VI [IrCl(cod)] 2 3 Reaction conditions: 2.0 eq. 1-phenylethanol (2.4 ml), 1.0 eq. 2-amino-1-butanol (0.96 ml) 1.1eq. KO t Bu (1.24 g), 0.01 mol% catalyst ( 1.0 ml, 0.001 M in THF), 10.0 ml THF, 24 h, 90 C (reaction tubes closed with a semipermeable membrane, for more details please see Supplementary Figure S2, next page). Yields determined by GC analyses with dodecane as internal standard. ATURE CHEMISTRY www.nature.com/naturechemistry 5 2013 Macmillan Publishers Limited. All rights reserved.

Supplementary Figure S2: Reaction flask with a semi-permeable membrane as used for the pyrrole syntheses. A silicone tube (Rotilabo ) inner diameter 7 mm, outer diameter 10 mm and 30 cm length was used as membrane. A maximum reaction temperature of 90 C was determined inside the reaction flask due to a pressure increase (1 bar overpressure) caused by the membrane. There are a few reasons for using the semi-permeable membrane. 1. low boiling substrates and 2. low boiling solvents which essentially means more solvent flexibility. Low boiling solvents are especially attractive in the work-up procedures since the solvent can be removed easily (also in the presence of products with rather low boiling points). Furthermore, a rather high throughput can be accomplished. One can easily run 60 flasks in a parallel fashion in a rather small fume hood. As a minor drawback the semi-permeable membrane means essentially adding a short rubber tube on top of the reaction flask. ATURE CHEMISTRY www.nature.com/naturechemistry 6 2013 Macmillan Publishers Limited. All rights reserved.

Ligand and Complex Syntheses Supplementary Figure S3: Ligand and complex syntheses Synthesis of PyHP(iPr) 2 2-Aminopyridine (20.0 mmol, 1.88 g) was dissolved in 100 ml THF and triethylamine (20.0 mmol, 2.8 ml) was added and the solution was cooled to 0 C. Then chlorodiisopropylphosphine (20.0 mmol, 3.2 ml) was added drop wise with a syringe. The solution was allowed to warm to room temperature and stirred over night at 50 C. The suspension was filtered over a glass filter frit with a pad of celite (4 cm) and washed with 50 ml of THF. The solvent was concentrated in vacuo to 10 ml and left to crystallize at -20 C. The supernatant solution was decanted and the solid washed with 5 ml of cold hexane and subsequently dried in vacuo yielding PyHP(iPr) 2 as a colorless solid (19.2 mmol = 96%). 1 H MR (400 MHz, C 6 D 6, 298 K): δ = 8.18 (ddd, J = 4.9, 1.8, 0.9 Hz, 1H), 7.27-7.23 (m, 1H), 7.10 (ddd, J = 8.5, 7.2, 1.7 Hz, 1H), 6.37 (ddd, J = 7.3, 7.1, 0.9 Hz, 1H), 4.86 (d, J = 10.6 Hz, 1H), 1.47-1.36 (m, 2H), 0.96-0.82 (m, 12H) ppm. 13 C MR (100 MHz, C 6 D 6, 298 K): δ = 161.6 (d, J = 20.0 Hz), 148.7 (d, J = 1.2 Hz), 137.3 (d, J = 2.3 Hz), 114.5, 108.6 (d, J = 18.6 Hz), 26.5 (d, J = 11.6 Hz), 18.7 (d, J = 20.4 Hz), 17.1 (d, J = 8.0 Hz) ppm. 31 P MR (161 MHz, C 6 D 6, 298 K): δ = 48.82 ppm. ATURE CHEMISTRY www.nature.com/naturechemistry 7 2013 Macmillan Publishers Limited. All rights reserved.

Synthesis of [(PyP(iPr) 2 )Ir(cod)] (Cat. I) PyHP(iPr) 2 (2.0 mmol, 420 mg) was dissolved in 20 ml THF, cooled to -30 C and n-buli (2.0 mmol, 1.6 M, 1.25 ml) was added drop wise with a syringe. The reaction mixture was stirred at -30 C for 30 min and was then allowed to warm to room temperature and stirred for 1h. Then the reaction mixture was added to a solution of [IrCl(cod)] 2 (1.0 mmol, 671 mg) (with a flexible tube). The reaction mixture was stirred for 30 min at room temperature before the solvent was removed in vacuo. The residue was suspended in diethyl ether and filtered over a glass filter frit with a pad of celite (1 cm) and washed with 10 ml of cold diethyl ether. Solvent was removed in vacuo and the residue was recrystallized from hexane affording dark red crystals (1.6 mmol, 80%). 1 H MR (400 MHz, C 6 D 6, 298 K): δ = 7.30 (d, J = 8.8 Hz, 1H), 7.20 (d, J = 6.4 Hz, 1H), 6.86-6.78 (m, 1H), 5.65 (t, J = 6.4 Hz, 1H), 4.49-4.41 (m, 2H), 3.78-3.72 (m, 2H), 2.19-2.06 (m, 4H), 1.96-1.78 (m, 4H), 1.61-1.48 (m, 2H), 1.23 (dd, J = 13.9, 7.0 Hz, 6H), 1.07 (dd, J = 13.9, 7.0 Hz, 6H) ppm. 13 C MR (100 MHz, C 6 D 6, 298 K): δ = 145.5 (d, J = 2.9 Hz), 137.6 (d, J = 2.5 Hz), 117.7 (d, J = 22.5 Hz,) 105.9, 88.3 (d, J = 11.3 Hz), 56.14, 34.4, (d, J = 2.3 Hz), 29.2 (d, J = 1.6 Hz), 28.57 (d, J = 38.9 Hz), 17.9 (d, J = 3.5 Hz), 17.5 ppm. 31 P MR (161 MHz, C 6 D 6, 298 K): δ = 94.70 ppm. elemental analysis calcd (%) for C 27 H 32 Ir 2 P: C 44.78, H 5.93, 5.50; found: C 44.77, H 5.68, 5.53. Synthesis of (4-Ph)Tr(HP(iPr) 2 ) 2 Benzoguanamine (30.0 mmol, 5.61 g) was dissolved in 150 ml THF and triethylamine (40.0 mmol, 2.8 ml) was added and the solution was cooled to 0 C. Then chlorodiisopropylphosphine (60.0 mmol, 9.6 ml) was added drop wise with a syringe. The ATURE CHEMISTRY www.nature.com/naturechemistry 8 2013 Macmillan Publishers Limited. All rights reserved.

solution was allowed to warm to room temperature and stirred over night at 50 C. The suspension was filtered over a glass filter frit with a pad of celite (4 cm) and washed with 50 ml of THF. The solvent was concentrated in vacuo, recrystallized in toluene yielding (4- Ph)Tr(HP(iPr) 2 ) 2 as colorless crystals (12.06 g = 28.8 mmol = 96%). 1 H MR (300 MHz, CD 2 Cl 2 ): δ = 8.43-8.29 (m, 2H), 7.54-7.42 (m, 3H), 5.25 (s_br, 2H), 1.99-1.82 (m, 4H), 1.16-1.11 (m, 24H) ppm. 13 C MR (75 MHz, CD 2 Cl 2 ): δ = 171.7, 170.4 (d, J = 12.7 Hz), 137.4, 132.0, 128.9, 128.8, 26.8 (d, J = 14.4 Hz), 19.2 (d, J = 21.0 Hz), 18.0 (d, J = 9.3 Hz) ppm. 31 P MR (161 MHz, C 6 D 6, 298 K): δ = 52.69, 49.47 ppm. 31 P MR (161 MHz, C 6 D 6, 353 K): δ = 54.33 ppm. elemental analysis: for C 21 H 35 5 P 2 : C 60.13, H 8.41, 16.70; found: C 60.12, H 8.13, 16.54. Synthesis of [(4-Ph)Tr(P(iPr) 2 )(HP(iPr) 2 )Ir(cod)] (Cat. II) [IrOMe(cod)] 2 (2.0 mmol, 1.32g) was dissolved in 40 ml THF and subsequently a solution of (4-Ph)Tr(HP(iPr) 2 ) 2 (4.0 mmol, 1.67 g) dissolved in THF was added drop wise. A red solution was obtained. The solution was stirred over night at 50 C. The solvent was removed in vacuo, yielding a deep red solid in quantitative yield. 1 H MR (300 MHz, CD 2 Cl 2 ): δ = 8.37-8.32 (m, 2H), 7.48-7.38 (m, 3H), 6.06 (s_br, 1H), 5.68-5.61 (m, 2H), 3.89 (s_br, 2H), 2.42-2.14 (m, 10H), 1.74-1.62 (m, 2H), 1.24-1.12 (m, 24H) ppm. 13 C MR (75 MHz, CD 2 Cl 2 ): δ = 170.0 (t, J = 2.2 Hz), 137.9, 131.6, 130.7, 129.1, 128.7, 55.0, 37.0 (t, J = 3.3 Hz), 32.5, 28.5 (s_br), 18.0 (s_br), 16.9 ppm. 31 P MR (161 MHz, C 6 D 6, 298 K): δ = 83.34, 83.11 ppm. elemental analysis (%) for C 29 H 46 Ir 5 P 2 calcd: C 48.45, H 6.45, 9.74; found: C 48.77, H 6.44, 9.77. ATURE CHEMISTRY www.nature.com/naturechemistry 9 2013 Macmillan Publishers Limited. All rights reserved.

Synthesis of Py(HP(iPr) 2 ) 2 2,6-Diaminopyridine (30.0 mmol, 3.24 g) was dissolved in 150 ml THF and triethylamine (40.0 mmol, 2.8 ml) was added and the solution was cooled to 0 C. Then chlorodiisopropylphosphine (60.0 mmol, 9.6 ml) was added drop wise with a syringe. The solution was allowed to warm to room temperature and stirred over night at 50 C. The suspension was filtered over a glass filter frit with a pad of celite (4 cm) and washed with 50 ml of THF. The solvent was concentrated in vacuo, recrystallized in hexane yielding Py(HP(iPr) 2 ) 2 as colorless crystals (6.14g = 18.0 mmol = 60%). 1 H MR (400 MHz, C 6 D 6 ): δ = 7.20 (t, J = 7.9 Hz, 1H), 6.72 (dd, J = 7.9, 1.8 Hz, 2H), 4.48 (d, J = 9.6 Hz, 2H), 1.50-1.40 (m, 4H), 0.99-0.86 (m, 24 H) ppm. 13 C MR (75 MHz, CD 2 Cl 2, 298 K): δ = 159,6 (d, J = 20.5 Hz), 140.1, 98.6 (d, J = 18.2Hz), 26.9 (d, J = 11.6 Hz), 19.0 (d, J = 19.9 Hz), 17.4 (d, J = 8.3 Hz) ppm. 31 P MR (161 MHz, C 6 D 6, 298 K): δ = 52.40, 49.32 ppm. 31 P MR (161 MHz, C 6 D 6, 353 K): δ = 53.73 ppm. Synthesis of [Py(P(iPr) 2 )(HP(iPr) 2 )Ir(cod)] (Cat. III) [IrOMe(cod)] 2 (1.0 mmol, 662 mg) was dissolved in 20 ml THF and subsequently a solution of Py(HP(iPr) 2 ) 2 (2.0 mmol, 682 mg) dissolved in THF was added drop wise. A red solution was obtained. The solution was stirred over night at 50 C. The solvent was removed in vacuo, yielding a deep red solid in quantitative yield. 1 H MR (300 MHz, CD 2 Cl 2 ): δ = 6.87 (tt, J = 7.9, 1.6 Hz, 1H), 5.77 (s_br, 2H), 5.64 (t, J = 4.1 Hz, 2 H), 4.84 (s_br, 1H), 3.65-3.76 (m, 2 H), 3.76-3.65 (m, 2H), 2.45-2.24 (m, 4H), 2.22-2.08 (m, 6H), 1.68-1.53 (m, 2 H), 1.26-1.06 (m, 24 H) ppm. 13 C MR (75 MHz, CD 2 Cl 2 ): δ = 138.7(t, J = 2.2 Hz), 130.8, 51.9, 37.2 (t, J = 3.9 Hz), 32.5, 30.0 (t, J = 16.5 Hz), 18.2( t, J = 2.2 Hz), 16.8 ppm. 31 P MR (161 MHz, C 6 D 6, 298 K): δ = 90.58 ppm. ATURE CHEMISTRY www.nature.com/naturechemistry 10 2013 Macmillan Publishers Limited. All rights reserved.

elemental analysis (%) for C 25 H 44 Ir 3 P 2 calcd: C 46.86, H 6.92, 6.56; found: C 46.98, H 6.89, 6.42. Synthesis of (4-Me)Tr(HP(iPr) 2 ) 2 6-Methyl-[1,3,5]triazine-2,4-diamine (30.0 mmol, 3.75 g) was dissolved in 150 ml THF and triethylamine (40.0 mmol, 2.8 ml) was added and the solution was cooled to 0 C. Then chlorodiisopropylphosphine (60.0 mmol, 9.6 ml) was added drop wise with a syringe. The solution was allowed to warm to room temperature and stirred over night at 50 C. The suspension was filtered over a glass filter frit with a pad of celite (4 cm) and washed with 50 ml of THF. The solvent was concentrated in vacuo, recrystallized in toluene yielding (4- Me)Tr(HP(iPr) 2 ) 2 as white crystals (12.06g = 28.8 mmol = 96%). 1 H MR (300 MHz, CD 2 Cl 2 ): δ = 5.11 (s_br, 2H), 2.23 (s, 3H), 1.97-1.71 (m, 4H), 1.17-0.97 (m, 24H) ppm. 13 C MR (75 MHz, CD 2 Cl 2 ): δ = 176.3, 169.8 (d, J = 13.2 Hz), 46.2, 26.6 (d, J = 14.4 Hz), 19.0 (d, J = 21.0 Hz), 17.9 (d, J = 8.9 Hz) ppm. elemental analysis (%) for C 16 H 33 5 P 2 calcd: C 53.77, H 9.31, 19.59; found: C 53.75, H 9.51, 19.23. 31 P MR (161 MHz, C 6 D 6, 298 K): δ = 52.13, 49.00 ppm. 31 P MR (161 MHz, C 6 D 6, 353 K): δ = 53.33 ppm. Synthesis of [(4-Me)Tr(P(iPr) 2 )(HP(iPr) 2 )Ir(cod)] (Cat. IV) [IrOMe(cod)] 2 (0.5 mmol, 332 mg) was dissolved in 40 ml THF and subsequently a solution of (4-Me)Tr(HP(iPr) 2 ) 2 (1.0 mmol, 357 mg) dissolved in THF was added drop wise. A red solution was obtained. The solution was stirred over night at 50 C. The solvent was removed in vacuo, yielding a deep red solid in quantitative yield. ATURE CHEMISTRY www.nature.com/naturechemistry 11 2013 Macmillan Publishers Limited. All rights reserved.

1 H MR (300 MHz, CD 2 Cl 2 ): δ = 6.87 (tt, J = 7.9, 1.6 Hz, 1H), 5.77 (s_br, 2H), 5.64 (t, J = 4.1 Hz, 2 H), 4.84 (s_br, 1H), 3.65-3.76 (m, 2 H), 3.76-3.65 (m, 2H), 2.45-2.24 (m, 4H), 2.22-2.08 (m, 6H), 1.68-1.53 (m, 2 H), 1.26-1.06 (m, 24 H) ppm. 13 C MR (75 MHz, CD 2 Cl 2 ): δ = 138.7, 130.8, 51.9, 37.2 (t, J = 3.9 Hz), 32.5, 30.0 (t, J = 16.5 Hz), 18.2( t, J = 2.2 Hz), 16.8 ppm. elemental analysis (%) for C 24 H 44 Ir 5 P 2 calcd: C 43.89, H 6.75, 10.66; found: C 43.86, H 6.52, 10.32. 31 P MR (161 MHz, C 6 D 6, 298 K): δ = 84.54, 83.67 ppm. Reaction of 1-Phenylethanol with various Amino Alcohols Supplementary Table S9: Reaction of 1-phenylethanol with various amino alcohols OH + HO R = aryl, alkyl R H 2 Cat. II 1.1 eq. KO t Bu, 24h, 90 C H R [mol% Cat. II] Product Yield [a] 1a 0.05 80% 1b 0.05 93% 1c 0.1 65% 1d 0.03 89% 1e 0.05 88% ATURE CHEMISTRY www.nature.com/naturechemistry 12 2013 Macmillan Publishers Limited. All rights reserved.

1f 0.1 69% 1g 0.2 86% 1h 0.05 79% [a] Isolated yield 1a: 2-methyl-5-phenyl-1H-pyrrole: Cat. II (0.5 ml, 0.005 mmol, 0.01 M in THF), 1-phenylethanol (2.4 ml, 20.0 mmol), 2-amino-propan-1-ol (797 µl, 10.0 mmol), 10 ml THF, KO t Bu (1.24 g, 11.0 mmol), 24 h at 90 C. Purification by column chromatography 40:1 10:1 pentane : Et 2 O; Yield: 1.26 g = 8.0 mmol = 80% as colorless solid. 1 H MR (300 MHz, CD 2 Cl 2 ): δ = 8.24 (s_br, 1H), 7.45-7.41 (m, 2H), 7.37-7.30 (m, 2H), 7.19-7.12 (m, 1H), 6.39-6.36 (m, 1H), 5.94-5.90 (m, 1H), 2.32 (s, 3H) ppm. 13 C MR (75 MHz, CD 2 Cl 2 ): δ = 133.5, 131.0, 129.7, 129.4, 126.1, 123.6, 108.4, 106.7, 13.4 ppm. MS (70 ev, EI); m/z (%): 157 (65, M + ), 156 (100), 104 (2), 77 (5). elemental analysis (%) for C 11 H 11 calcd C 84.04, H 7.05, 8.91; found: C 84.20 H 7.34 8.88 1b: 2-ethyl-5-phenyl-1H-pyrrole: Cat. II (0.5 ml, 0.005 mmol, 0.01 M in THF), 1- phenylethanol (2.4 ml, 20.0 mmol), 2-amino-butan-1-ol (960 µl, 10.0 mmol), 10 ml THF, KO t Bu (1.24 g, 11.0 mmol), 24 h at 90 C. Purification by column chromatography 40:1 pentane: Et 2 O; Yield: 1.59 g = 9.3 mmol = 93% as colorless solid. ATURE CHEMISTRY www.nature.com/naturechemistry 13 2013 Macmillan Publishers Limited. All rights reserved.

1 H MR (300 MHz, CD 2 Cl 2 ): δ = 8.23 (s_br, 1H), 7.46-7.42 (m, 2H), 7.38-7.31 (m, 2H), 7.19-7.13 (m, 1H), 6.61-6.38 (m, 1H), 5.97-5.93 (m, 1H), 2.68 (q, J = 7.6 Hz, 2H), 1.27 (t, J = 7.6 Hz, 3H) ppm. 13 C MR (75 MHz, CD 2 Cl 2 ): δ = 136.3, 133.6, 130.8, 129.4, 126.1, 123.7, 106.7, 21.5, 14.1 ppm. MS (70 ev, EI); m/z (%): 171 (38, M + ), 156 (100), 128 (8), 115 (6), 77 (5). elemental analysis (%) for C 12 H 13 calcd: C 84.17, H 7.65, 8.18; found: C 84.33, H 7.69, 8.10. 1c: 3-(5-phenyl-1H-pyrrol-2-ylmethyl)-1H-indole: Cat. II (1.0 ml, 0.01 mmol, 0.01 M in THF), 1-phenylethanol (2.4 ml, 20.0 mmol), 2-amino-3-(1H-indol-3-yl)-propan-1-ol (1.90 g, 10.0 mmol), 10 ml THF, KO t Bu (1.24 g, 11.0 mmol), 24 h at 90 C. Purification by column chromatography 20:1 10:1 pentane : Et 2 O;Yield: 1.76 g = 6.5 mmol = 65% as colorless solid. 1 H MR (300 MHz, CD 2 Cl 2 ): δ = 8.24 (s_br, 1H), 8.16 (s_br, 1H), 7.57-7.53 (m, 1H), 7.41-7.35 (m, 3H), 7.32-7.26 (m, 2H), 7.21-7.05 (m, 4H), 6.44-6.41 (m, 1H), 6.10-6.07 (m, 1H), 4.16 (s, 2H) ppm. 13 C MR (75 MHz, CD 2 Cl 2 ): δ = 137.1, 133.5, 133.3, 131.2, 129.3, 127.8, 126.1, 123.7, 123.0, 122.7, 120.0, 119.3, 114.1, 111.7, 108.2, 106.6, 24.5 ppm. MS (70 ev, EI); m/z (%): 272 (100, M + ), 270 (10), 167 (10), 136 (10), 117 (38), 77 (8). elemental analysis (%) for C 19 H 16 2 calcd: C 83.79, H 5.92, 10.29; found: C 83.62, H 5.98, 10.10. 1d: 2-isopropyl-5-phenyl-1H-pyrrole: Cat. II (0.3 ml, 0.003 mmol, 0.01 M in THF), 1- phenylethanol (2.4 ml, 20.0 mmol), 2-amino-3-methyl-butan-1-ol (1.03 g, 10.0 mmol), 10 ml THF, KO t Bu (1.24 g, 11.0 mmol), 24 h at 90 C. Purification by column chromatography 100:1 30:1 pentane : Et 2 O; Yield: 1.64 g = 8.9 mmol = 89% as colorless oil. 1 H MR (300 MHz, CD 2 Cl 2 ): δ = 8.23 (s_br, 1H), 7.47-7.43 (m, 2H), 7.38-7.31 (m, 2H), 7.20-7.14 (m, 1H), 6.42-6.38 (m, 1H), 5.98-5.94 (m, 1H), 3.06-2.90 (m, 1H), 1.30 (d, J = 6.7 Hz, 6H) ppm. 13 C MR (75 MHz, CD 2 Cl 2 ): δ = 141.0, 133.6, 130.7, 129.4, 126.1, 123.8, 106.4, 105.5, 27.8, 23.1 ppm. MS (70 ev, EI); m/z (%): 185 (28, M + ), 170 (100), 153 (5), 115 (8), 77 (5). ATURE CHEMISTRY www.nature.com/naturechemistry 14 2013 Macmillan Publishers Limited. All rights reserved.

elemental analysis (%) for C 13 H 15 calcd: C 84.28, H 8.16, 7.56; found: C 84.46, H 8.23, 7.64. 1e: 2-sec-butyl-5-phenyl-1H-pyrrole: Cat. II (0.5 ml, 0.005 mmol, 0.01 M in THF), 1-phenylethanol (2.4 ml, 20.0 mmol), 2-amino-3-methyl-pentan-1-ol (1.17 g, 10.0 mmol), 10 ml THF, KO t Bu (1.24 g, 11.0 mmol), 24 h at 90 C. Purification by column chromatography 60:1 30:1 pentane : Et 2 O; Yield: 1.84 g = 7.9 mmol = 79% as colorless oil. 1 H MR (300 MHz, CD 2 Cl 2 ): δ = 8.39-8.00 (s_br, 1H), 7.47-7.43 (m, 2H), 7.38-7.31 (m, 2H), 7.20-7.13 (m, 1H), 6.43-6.39 (m, 1H), 5.98-5.93 (m, 1H), 2.79-2.66 (m, 1H), 1.72-1.56 (m, 2H), 1.30-1.27 (m, 3H), 0.96-0.89 (m, 3H) ppm. 13 C MR (75 MHz, CD 2 Cl 2 ): δ = 139.9, 133.6, 130.5, 129.3, 126.1, 123.7, 106.4, 106.2, 35.0, 30.8, 20.5, 12.2 ppm. MS (70 ev, EI); m/z (%): 199 (22, M + ), 184 (8), 170 (100), 168 (10), 115 (6), 77 (5). elemental analysis (%) for C 14 H 17 calcd C 84.37, H 8.60, 7.03; found: C 84.66, H 8.89, 7.22. 1f: 2-isobutyl-5-phenyl-1H-pyrrole: Cat. II (1.0 ml, 0.01 mmol, 0.01 M in THF), 1-phenylethanol (2.4 ml, 20.0 mmol), 2-amino-4-methyl-pentan-1-ol (1.28 ml, 10.0 mmol), 10 ml THF, KO t Bu (1.24 g, 11.0 mmol), 24 h at 90 C. Purification by column chromatography 60:1 20:1 pentane : Et 2 O; Yield: 1.39 g = 6.9 mmol = 69% as colorless oil. 1 H MR (300 MHz, CD 2 Cl 2 ): δ = 8.19 (s_br, 1H), 7.47-7.42 (m, 2H), 7.38-7.31 (m, 2H), 7.19-7.13 (m, 1H), 6.43-6.39 (m, 1H), 5.96-5.93 (m, 1H), 2.50 (d, J = 7.0 Hz), 1.97-1.82 (m, 1H), 0.96 (d, J = 6.7 Hz, 6H) ppm. 13 C MR (75 MHz, CD 2 Cl 2 ): δ = 133.9, 133.6, 130.7, 129.4, 126.0, 123.6, 108.5, 106.6, 37.8, 29.8, 22.7 ppm. MS (70 ev, EI); m/z (%): 199 (18, M + ), 156 (100), 115 (5), 77 (5). elemental analysis (%) for C 14 H 17 calcd C 84.37, H 8.60, 7.03; found: C 84.46, H 8.50, 7.00. ATURE CHEMISTRY www.nature.com/naturechemistry 15 2013 Macmillan Publishers Limited. All rights reserved.

1g: 2,5-diphenyl-1H-pyrrole: Cat. II (2.0 ml, 0.02 mmol, 0.01 M in THF), 1-phenylethanol (2.4 ml, 20.0 mmol), 2-amino-2-phenyl-ethanol (1.37 g, 10.0 mmol), 10 ml THF, KO t Bu (1.24 g, 11.0 mmol), 24 h at 90 C. Purification by column chromatography 10:1 5:1 hexane : Et 2 O; Yield: 1.88 g = 8.6 mmol = 86% as colorless solid. 1 H MR (300 MHz, CD 2 Cl 2 ): δ = 8.72 (s_br, 1H), 7.58-7.54 (m, 4H), 7.47-7.35 (m, 4H), 7.31-7.18 (m, 2H), 6.59 (d, J = 2.6 Hz, 2H) ppm. 13 C MR (75 MHz, CD 2 Cl 2 ): δ = 133.0, 129.5, 127.3, 127.0, 124.2, 108.4 ppm. MS (70 ev, EI); m/z (%): 219 (100, M + ), 216 (14), 114 (24), 109 (12), 77 (4). elemental analysis (%) for C 16 H 13 calcd: C 87.64, H 5.98, 6.39; found: C 87.29 H 5.96 6.59 1h: 2-benzyl-5-phenyl-1H-pyrrole: Cat. II (0.5 ml, 0.005 mmol, 0.01 M in THF), 1-phenylethanol (2.4 ml, 20.0 mmol), 2-amino-3-phenyl-propan-1-ol (1.51 g, 10.0 mmol), 10 ml THF, KO t Bu (1.24 g, 11.0 mmol), 24 h at 90 C. Purification by column chromatography 40:1 5:1 pentane : Et 2 O; Yield: 1.84 g = 7.9 mmol = 79% as colorless solid. 1 H MR (300 MHz, CD 2 Cl 2 ): δ = 8.18 (s_br, 1H), 7.42-7.39 (m, 2H), 7.35-7.30 (m, 4H), 7.29-7.22 (m, 3H), 7.19-7.12 (m, 1H), 6.44-6.41 (m, 1H), 6.03-6.00 (m, 1H), 4.02 (s, 2H) ppm. 13 C MR (75 MHz, CD 2 Cl 2 ): δ = 140.2, 133.4, 132.9, 129.3, 129.2, 129.1, 127.0, 126.3, 123.8, 109.0, 106.6, 34.7 ppm. MS (70 ev, EI); m/z (%): 233 (84, M + ), 156 (100), 128 (15), 115 (8), 77 (6). elemental analysis (%) for C 17 H 15 calcd: C 87.52, H 6.48, 6.00; found: C 87.62, H 6.21, 6.02. ATURE CHEMISTRY www.nature.com/naturechemistry 16 2013 Macmillan Publishers Limited. All rights reserved.

Reaction of 2-Amino-3-phenyl-propan-1-ol with various Secondary Alcohols Supplementary Table S10. Reaction of 2-amino-3-phenyl-propan-1-ol with various secondary alcohols OH HO + Cat. II R H 1.1 eq. KO t H 2 Bu, 24h, 90 C R = aryl, alkyl R [mol% Cat. II] Product Yield [a] 1i 0.03 84% 1j 0.03 76% 1k 0.03 97% 1l 0.05 74% 1m 0.1 77% 1n 0.1 73% 1o 0.05 84% ATURE CHEMISTRY www.nature.com/naturechemistry 17 2013 Macmillan Publishers Limited. All rights reserved.

1p 0.05 75% 1q 0.2 75% 1r 0.2 78% 1s 0.5 42% 1t 0.5 57% 1u 0.1 70% 1v 0.1 55% [a] Isolated yield ATURE CHEMISTRY www.nature.com/naturechemistry 18 2013 Macmillan Publishers Limited. All rights reserved.

1i: 2-benzyl-5-methyl-1H-pyrrole: Cat. II (0.3 ml, 0.003 mmol, 0.01 M in THF), propan-2-ol (3.06 ml, 40.0 mmol), 2-amino-3-phenyl-propan-1-ol (1.51 g, 10.0 mmol), 10 ml THF, KO t Bu (1.24 g, 11.0 mmol), 24 h at 90 C. Purification by column chromatography 60:1 20:1 pentane : Et 2 O; Yield: 1.43 g = 8.4 mmol = 85% as colorless oil. 1 H MR (300 MHz, CD 2 Cl 2 ): δ = 7.59 (s_br, 1H), 7.34-7.27 (m, 2H), 7.25-7.19 (m, 3H), 5.79 (t, J = 2.9 Hz, 1H), 5.74-5.70 (m, 1H), 3.90(s, 2H), 2.18 (s, 3H) ppm. 13 C MR (75 MHz, CD 2 Cl 2 ): δ = 140.9, 129.8, 129.0, 127.4, 126.8, 106.9, 106.2, 34.7, 13.2 ppm. MS (70 ev, EI); m/z (%): 171 (100, M + ), 156 (72), 154 (18), 128 (8), 94 (100), 77 (8). elemental analysis (%) for C 12 H 13 calcd: C 84.17, H 7.65, 8.18; found: C 84.20, H 7.86, 8.42. 1j: 2-benzyl-5-butyl-1H-pyrrole: Cat. II (0.3 ml, 0.003 mmol, 0.01 M in THF), hexan-2-ol (2.52 ml, 20.0 mmol), 2-amino-3-phenyl-propan-1-ol (1.51 g, 10.0 mmol), 10 ml THF, KO t Bu (1.24 g, 11.0 mmol), 24 h at 90 C. Purification by column chromatography 40:1 30:1 pentane : Et 2 O; Yield: 1.62 g = 7.6 mmol = 76% as colorless oil. 1 H MR (300 MHz, CD 2 Cl 2 ): δ = 7.61 (s_br, 1H), 7.36-7.28 (m, 2H), 7.27-7.19 (m, 3H), 5.83-5.79 (m, 1H), 5.78-5.75 (m, 1H), 3.92 (s, 2H), 2.55-2.49 (m, 2H), 1.60-1.52 (m, 2H), 1.42-1.32 (m, 2H), 0.92 (t, J = 7.3 Hz, 3H) ppm. 13 C MR (75 MHz, CD 2 Cl 2 ): δ = 140.9, 132.7, 129.5, 129.1, 129.0, 126.7, 106.8, 105.2, 34.7, 32.5, 27.9, 23.0, 14.2 ppm. MS (70 ev, EI); m/z (%): 213 (60, M + ), 198 (20), 184 (100), 170 (35), 155 (10), 128 (6), 84 (4), 77 (6). elemental analysis (%) for C 15 H 19 calcd: C 84.46, H 8.98, 6.57; found: C 84.14 H 9.08 6.52. 1k: 2-benzyl-5-hexyl-1H-pyrrole: Cat. II (0.3 ml, 0.003 mmol, 0.01 M in THF), octan-2-ol (3.1 ml, 20.0 mmol), 2-amino-3-phenyl-propan-1-ol (1.51 g, 10.0 mmol), 10 ml THF, KO t Bu (1.24 g, 11.0 mmol), 24 h at 90 C. Purification by column chromatography 20:1 10:1 pentane : Et 2 O; Yield: 2.34 g = 9.7 mmol = 97% as colorless oil. ATURE CHEMISTRY www.nature.com/naturechemistry 19 2013 Macmillan Publishers Limited. All rights reserved.

1 H MR (300 MHz, CD 2 Cl 2 ): δ = 7.60 (s_br, 1H), 7.34-7.25 (m, 2H), 7.25-7.17 (m, 3H), 5.83-5.77 (m, 1H), 5.76-5.71 (m, 1H), 3.90 (s, 2H), 2.52-2.47 (m, 2H), 1.59-1.52 (m, 2H), 1.33-1.28 (m, 6H), 0.90-0.87 (m, 3H) ppm. 13 C MR (75 MHz, CD 2 Cl 2 ): δ = 140.9, 132.8, 129.5, 129.1, 126.7, 107.5, 106.8, 105.2, 34.7, 32.2, 30.3, 29.6, 28.3, 23.2, 14.4 ppm. MS (70 ev, EI); m/z (%): 241 (18, M + ), 170 (100), 167 (4), 93 (4), 91 (7), 80 (5). elemental analysis (%) for C 17 H 23 calcd: C 84.59, H 9.60, 5.80; found: C 84.28, H 9.86, 5.74. 1l: 2-benzyl-5-nonyl-1H-pyrrole: Cat. II (0.5 ml, 0.005 mmol, 0.01 M in THF), undecan-2-ol (4.16 ml, 20.0 mmol), 2-amino-3-phenyl-propan-1-ol (1.51 g, 10.0 mmol), 10 ml THF, KO t Bu (1.24 g, 11.0 mmol), 24 h at 90 C. Purification by column chromatography 60:1 40:1 pentane : Et 2 O; Yield: 2.09 g = 7.4 mmol = 74% as colorless oil. 1 H MR (300 MHz, CD 2 Cl 2 ): δ = 7.60 (s_br, 1H), 7.34-7.26 (m, 2H), 7.25-7.17 (m, 3H), 5.81-5.77 (m, 1H), 5.76-5.73 (m, 1H), 3.91 (s, 2H), 2.52-2.47 (m, 2H), 1.59-1.52(m, 2H), 1.32-1.27 (m, 12H), 0.92-0.87 (m, 3H) ppm. 13 C MR (75 MHz, CD 2 Cl 2 ): δ = 140.9, 132.8, 129.5, 129.1, 129.0, 126.7, 106.7, 105.2, 34.7, 32.5, 30.4, 30.1, 30.0, 30.0, 29.9, 28.3, 23.3, 14.5 ppm. MS (70 ev, EI); m/z (%): 283 (21, M + ), 184 (8), 170 (100), 156 (3), 106 (4), 91 (8), 80 (4). elemental analysis (%) for C 20 H 29 calcd: C 84.75, H 10.31, 4.94; found: C 84.85, H 10.52, 6.69. 1m: 2-benzyl-5-(4-methyl-pent-3-enyl)-1H-pyrrole: Cat. II (1.0 ml, 0.01 mmol, 0.01 M in THF), 6-methyl-hept-5-en-2-ol (3.04 ml, 20.0 mmol), 2-amino-3-phenyl-propan-1-ol (1.51 g, 10.0 mmol), 10 ml THF, KO t Bu (1.24 g, 11.0 mmol), 24 h at 90 C. Purification by column chromatography 70:1 40:1 pentane : Et 2 O; Yield: 1.84g = 7.7 mmol = 77% as colorless oil 1 H MR (300 MHz, CD 2 Cl 2 ): δ = 7.64 (s_br, 1H), 7.34-7.27 (m, 2H), 7.25-7.17 (m, 3H), 5.81-5.78 (m, 1H), 5.77-5.73 (m, 1H), 5.20-5.10 (m, 1H), 3.90 (s, 2H), 2.53 (t, J = 7.3 Hz, 2H), 2.23 (q, J = 7.3 Hz, 2H), 1.66 (d, J = 1.2 Hz, 3H), 1.54 (s, 3H) ppm. 13 C MR (75 MHz, CD 2 Cl 2 ): δ = 140.9, 133.0, 132.5, 129.7, 129.1, 129.0, 126.8, 124.4, 106.7, 105.4, 34.7, 28.9, 28.3, 26.0, ATURE CHEMISTRY www.nature.com/naturechemistry 20 2013 Macmillan Publishers Limited. All rights reserved.

17.9 ppm. MS (70 ev, EI); m/z (%): 239 (100, M + ), 224 (44), 184 (6), 170 (20), 148 (48), 133 (8), 94 (8), 91 (32). elemental analysis (%) for C 17 H 21 calcd: C 85.30, H 8.84, 5.85; found: C 85.65, H 9.13, 5.69. 1n: 2-benzyl-5-isopropyl-1H-pyrrole: Cat. II (1.0 ml, 0.01 mmol, 0.01 M in THF), 3-methylbutan-2-ol (2.15 ml, 20.0 mmol), 2-amino-3-phenyl-propan-1-ol (1.51 g, 10.0 mmol), 10 ml THF, KO t Bu (1.24 g, 11.0 mmol), 24 h at 90 C. Purification by column chromatography 60:1 30:1 pentane : Et 2 O; Yield: 1.45 g = 7.3 mmol = 73% as colorless oil. 1 H MR (300 MHz, CD 2 Cl 2 ): δ = 7.66 (s_br, 1H), 7.36-7.29 (m, 2H), 7.26-7.20 (m, 3H), 5.82-5.75 (m, 2H), 3.93 (s, 2H), 2.91-2.77 (m, 1H), 1.21 (d, J = 7.0 Hz, 6H) ppm. 13 C MR (75 MHz, CD 2 Cl 2 ): δ = 140.9, 138.8, 129.5, 129.1, 129.0, 126.7, 106.6, 103.3, 34.7, 27.6, 23.1 ppm. MS (70 ev, EI); m/z (%): 199 (52, M + ), 184 (100), 106 (16), 91 (26). elemental analysis (%) for C 14 H 17 calcd: C 84.37, H 8.60, 7.03; found: C 84.16, H 8.29, 7.05. 1o: 2-benzyl-5-(4-methoxy-phenyl)-1H-pyrrole: Cat. II (0.5 ml, 0.005 mmol, 0.01 M in THF), 1-(4-methoxy-phenyl)-ethanol (2.82 ml, 20.0 mmol), 2-amino-3-phenyl-propan-1-ol (1.51 g, 10.0 mmol), 10 ml THF, KO t Bu (1.24 g, 11.0 mmol), 24 h at 90 C. Purification by column chromatography 20:1 5:1 pentane : Et 2 O; Yield: 2.22 g = 8.4 mmol = 84% as colorless solid. 1 H MR (300 MHz, CD 2 Cl 2 ): δ = 8.07 (s_br, 1H), 7.36-7.29 (m, 4H), 7.28-7.19 (m, 3H), 6.90-6.85 (m, 2H), 6.31-6.26, (m, 1H), 6.00-5.95 (m, 1H), 4.00 (s, 2H), 3.79 (s, 3H) ppm. 13 C MR (75 MHz, CD 2 Cl 2 ): δ = 158.6, 140.3, 132.1, 131.8, 129.1, 126.9, 126.4, 125.2, 114.7, 108.8, 105.4, 105.3, 55.8, 34.7 ppm. MS (70 ev, EI); m/z (%): 263 (100, M + ), 248 (31), 219 (5), 186 (38), 143 (10), 102 (8), 77 (6). ATURE CHEMISTRY www.nature.com/naturechemistry 21 2013 Macmillan Publishers Limited. All rights reserved.

elemental analysis (%) for C 18 H 17 O calcd: C 82.10, H 6.51, 5.32; found: C 81.92, H 6.57, 5.01. 1p: 2-benzyl-5-(4-chloro-phenyl)-1H-pyrrole: Cat. II (0.5 ml, 0.005 mmol, 0.01 M in THF), 1-(4-chloro-phenyl)-ethanol (2.67 ml, 20.0 mmol), 2-amino-3-phenyl-propan-1-ol (1.51 g, 10.0 mmol), 10 ml THF, KO t Bu (1.24 g, 11.0 mmol), 24 h at 90 C. Purification by column chromatography 40:1 5:1 pentane : Et 2 O; Yield: 2.02 g = 7.5 mmol = 75% as colorless solid. 1 H MR (300 MHz, CD 2 Cl 2 ): δ = 8.14 (s_br, 1H), 7.37-7.20 (m, 9H), 6.44-6.40 (m, 1H), 6.06-5.98 (m, 1H), 4.01 (s, 1H) ppm. 13 C MR (75 MHz, CD 2 Cl 2 ): δ = 140.0, 133.4, 131.9, 131.5, 130.6, 129.4, 129.2, 129.1, 127.0, 125.0, 109.2, 107.2, 34.7 ppm. MS (70 ev, EI); m/z (%): 267 (100, M + ), 230 (5), 192 (22), 190 (82), 154 (18), 127 (12), 101 (8), 77 (8). elemental analysis (%) for C 17 H 14 Cl calcd: C 76.26, H 5.27, 5.23; found: C 76.26, H 5.43, 5.21. 1q: 2-benzyl-5-(4-bromo-phenyl)-1H-pyrrole: Cat. II (2.0 ml, 0.02 mmol, 0.01 M in THF), 1-(4-bromo-phenyl)-ethanol (4.0 g, 20.0 mmol), 2-amino-3-phenyl-propan-1-ol (1.51 g, 10.0 mmol), 10 ml THF, KO t Bu (1.24 g, 11.0 mmol), 24 h at 90 C. Purification by column chromatography 30:1 5:1 pentane : Et 2 O; Yield: 2.35 g = 7.5 mmol = 75% as colorless solid. 1 H MR (300 MHz, CD 2 Cl 2 ): δ = 8.15 (s_br, 1H), 7.49-7.40 (m, 2H), 7.36-7.21 (m, 7H), 6.47-6.38 (m, 1H), 6.05-5.99 (m, 1H), 4.00 (s, 2H) ppm. 13 C MR (75 MHz, CD 2 Cl 2 ): δ = 140.0, 133.5, 132.3, 130.6, 129.2, 129.1, 127.0, 125.3, 123.8, 119.5, 109.3, 107.3, 34.7 ppm. MS (70 ev, EI); m/z (%): 311 (100), 234 (95), 202 (10), 154 (77), 115 (27), 102 (22), 77 (17). elemental analysis (%) for C 17 H 14 Br calcd: C 65.40, H 4.52, 4.49; found C 65.54, H 4.60, 4.52. ATURE CHEMISTRY www.nature.com/naturechemistry 22 2013 Macmillan Publishers Limited. All rights reserved.

1r: 2-benzyl-5-ferrocenyl-1H-pyrrole: Cat. II (2.0 ml, 0.02 mmol, 0.01 M in THF), 1- ferrocenyl-ethanol (4.6 g, 20.0 mmol) 2-amino-3-phenyl-propan-1-ol (1.51 g, 10.0 mmol), 10 ml THF, KO t Bu (1.24 g, 11.0 mmol), 24 h at 90 C. Purification by column chromatography 40:1 20:1 pentane : Et 2 O; Yield: 2.67 g = 7.8 mmol = 78% deep red solid. 1 H MR (300 MHz, CD 2 Cl 2 ): δ = 7.84 (s_br, 1H), 7.37-7.31 (m, 2H), 7.27-7.21 (m, 3H), 6.10-6.07 (m, 1H), 5.90-5.87 (m, 1H), 4.40-4.39 (m, 2H), 4.20-4.19 (m, 2H), 4.02 (s, 5H), 3.98 (s_br, 2H) ppm. 13 C MR (75 MHz, CD 2 Cl 2 ): δ = 140.6, 130.8, 129.5, 129.1, 129.0, 126.9, 108.1, 105.7, 80.0, 69.7, 68.3, 65.5, 34.6 ppm. MS (70 ev, EI); m/z (%): 341 (100, M + ), 275 (18), 250 (27), 218 (9), 171 (9), 121 (12), 91 (5), 77 (3). elemental analysis (%) for C 21 H 19 Fe calcd: C 73.92, H 5.61, 4.10; found: C 74.19, H 5.77, 4.04 1s: 2-benzyl-5-furan-2-yl-1H-pyrrole: Cat. II (5.0 ml, 0.05 mmol, 0.01 M in THF), 1-furan-2- yl-ethanol (2.1 ml, 20.0 mmol), 2-amino-3-phenyl-propan-1-ol (1.51 g, 10.0 mmol), 10 ml THF, KO t Bu (1.24 g, 11.0 mmol), 24 h at 90 C. Purification by column chromatography 20:1 15:1 pentane : Et 2 O; Yield: 930 mg = 4.2 mmol = 42% as yellow oil. 1 H MR (300 MHz, CD 2 Cl 2 ): δ = 8.25 (s_br, 1H), 7.37-7.32 (m, 2H), 7.29-7.22 (m, 3H), 6.43 (dd, J = 3.4, 1.9 Hz, 1H), 6.36-6.33 (m, 1H), 6.30 (dd, J = 3.4, 0.7 Hz, 1H), 6.03-5.99 (m, 1H), 4.00 (s, 2H) ppm. 13 C MR (75 MHz, CD 2 Cl 2 ): δ = 149.0, 140.6, 140.1, 132.3, 129.2, 129.1, 127.0, 123.8, 112.0, 108.6, 106.1, 102.1, 34.5 ppm. MS (70 ev, EI); m/z (%): 223 (100, M + ), 146 (100), 117 (7), 91 (14), 77 (6). elemental analysis (%) for C 15 H 13 O calcd: C 80.69, H 5.87, 6.27; found: C 80.60, H 5.94, 6.55 ATURE CHEMISTRY www.nature.com/naturechemistry 23 2013 Macmillan Publishers Limited. All rights reserved.

1t: 2-benzyl-5-thiophen-2-yl-1H-pyrrole: Cat. II (5.0 ml, 0.05 mmol, 0.01 M in THF), 1- thiophen-2-yl-ethanol (2.56 ml, 20.0 mmol), 2-amino-3-phenyl-propan-1-ol (1.51 g, 10.0 mmol), 10 ml THF, KO t Bu (1.24 g, 11.0 mmol), 24 h at 90 C. Purification by column chromatography 20:1 15:1 pentane : Et 2 O; Yield: 1.36 g = 5.7 mmol = 57% as colorless solid. 1 H MR (300 MHz, CD 2 Cl 2 ): δ = 8.06 (s_br, 1H), 7.36-7.29 (m, 2H), 7.28-7.20 (m, 3H), 7.11 (dd, J = 5.1, 1.3 Hz, 1H), 7.00-6.94 (m, 2H), 6.31-6.28 (m, 1H), 5.99-5.96 (m, 1H), 3.99 (s, 2H) ppm. 13 C MR (75 MHz, CD 2 Cl 2 ): δ = 140.0, 137.0, 132.6, 129.2, 129.1, 128.1,127.0, 126.4, 122.7, 120.7, 108.9, 107.3, 34.6 ppm. MS (70 ev, EI); m/z (%): 239 (89, M + ), 204 (6), 162 (100), 102 (6), 91 (7). elemental analysis (%) for C 15 H 13 S calcd: C 75.28, H 5.47, 5.85; found: C 75.06, H 5.50, 5.90. 1u: 4-(5-benzyl-1H-pyrrol-2-yl)-butan-2-ol: Cat. II (1.0 ml, 0.01 mmol, 0.01 M in THF), hexane-2,5-diol (2.36 g, 20.0 mmol), 2-amino-3-phenyl-propan-1-ol (1.51 g, 10.0 mmol), 10 ml THF, KO t Bu (1.24 g, 10.0 mmol), 24 h at 90 C. Purification by column chromatography 2:1 1:1 pentane : Et 2 O; Yield: 1.60 g = 7.0 mmol = 70% as yellow oil. 1 H MR (300 MHz, CD 2 Cl 2 ): δ = 7.95 (br_s, 1H), 7.34-7.27 (m, 2H), 7.26-7.17 (m, 3H), 5.81-5.74 (m, 2H), 3.90 (s, 2H), 3.83-3.73 (m, 1H), 2.61 (dt, J = 7.7, 2.5 Hz, 1H), 1.71-1.65 (m, 2H), 1.59 (br_s, 1H), 1.18 (d, J = 6.4 Hz, 3H) ppm. 13 C MR (75 MHz, CD 2 Cl 2 ): δ = 140.9, 132.0, 129.9, 129.1, 129.0, 126.7, 106.7, 105.4, 68.1, 39.4, 34.7, 24.6, 24.0 ppm. MS (70 ev, EI); m/z (%): 229 (56, M + ), 184 (100), 170 (75), 156 (6), 128 (5), 106 (15), 91 (30), 80 (14), 65 (18). elemental analysis (%) for C 15 H 19 O calcd: C 78.56, H 8.35, 6.11; found: C 78.78, H 8.64, 5.89. ATURE CHEMISTRY www.nature.com/naturechemistry 24 2013 Macmillan Publishers Limited. All rights reserved.

1v: 2,2-dimethyl-5-phenyl-2H-pyrrole: Cat. II (1.0 ml, 0.01 mmol, 0.01 M in THF), 1- phenylethanol (2.4 ml, 20.0 mmol), 2-amino-2-methyl-propan-1-ol (1.1 ml, 10.0 mmol), 10 ml THF, KO t Bu (1.24 g, 11.0 mmol), 24 h at 90 C. Purification by column chromatography 40:1 2:1 pentane : Et 2 O; Yield: 0.94 g = 5.5 mmol = 55% as colorless oil. 1 H MR (300 MHz, CD 2 Cl 2 ): δ = 7.91-7.97 (m, 2H), 7.48-7.43 (m, 3H), 7.41 (d, J = 5.0 Hz, 1H), 6.79 (d, J = 5.0 Hz, 1H), 1.38 (s, 6H) ppm. 13 C MR (75 MHz, CD 2 Cl 2 ): δ = 169.6, 153.0, 135.0, 130.6, 129.1, 128.1, 123.3, 80.0, 23.7 ppm. MS (70 ev, EI); m/z (%): 171 (81, M + ), 170 (100), 156 (37), 129 (12), 104 (18), 77 (12). elemental analysis (%) for C 12 H 13 calcd: C 84.17, H 7.65, 8.18; found: C 84.03, H 7.88, 8.61. Reaction of 2-Amino-3-phenyl-propan-1-ol with various Cyclic Alcohols Supplementary Table S11: Reaction of 2-amino-3-phenyl-propan-1-ol with various secondary alcohols and cyclic alcohols [mol% Cat. II] Product Yield [a] 2a 0.5 66% 2b 0.1 63% 2c 0.5 52% 2d 0.5 56% 2e 0.1 78% ATURE CHEMISTRY www.nature.com/naturechemistry 25 2013 Macmillan Publishers Limited. All rights reserved.

2f 0.05 88% 2g 0.03 84% 2h 0.03 79% 2i 0.05 80% 2j 0.1 51% 2k 0.05 77% 2l 0.1 37% [a] Isolated yield 2a: 5-benzyl-3-methyl-2-phenyl-1H-pyrrole: Cat. II (0.5 ml, 0.005 mmol, 0.01 M in THF), 1- phenyl-propan-1-ol (2.74 ml, 20.0 mmol), 2-amino-3-phenyl-propan-1-ol (1.51 g, 10.0 mmol), 10 ml THF, KO t Bu (1.24 g, 11.0 mmol), 24 h at 90 C. Purification by column chromatography 60:1 20:1 hexane : Et 2 O; Yield: 1.55 g = 6.2 mmol = 63% as colorless solid. 1 H MR (300 MHz, CD 2 Cl 2 ): δ = 7.86 (s_br, 1H), 7.40-7.16 (m, 10H), 5.89 (d, J = 2.9 Hz, 1H), 3.97 (s, 2H), 2.23 (s,3h) ppm. 13 C MR (75 MHz, CD 2 Cl 2 ): δ = 140.3, 134.3, 131.3, 129.2, 129.1, 127.7, 127.0, 126.3, 126.0, 116.9, 111.3, 34.6, 12.9 ppm. MS (70 ev, EI); m/z (%): 247 (100, M + ), 232 (47), 170 (83), 128 (6), 115 (11), 77 (6) ATURE CHEMISTRY www.nature.com/naturechemistry 26 2013 Macmillan Publishers Limited. All rights reserved.

elemental analysis (%) for C 18 H 17 calcd: C 87.41, H 6.93, 5.66; found: C 87.31, H 7.01, 6.03. 2b: 5-benzyl-2-ethyl-3-methyl-1H-pyrrole: Cat. II (0.5 ml, 0.005 mmol, 0.01 M in THF), pentan-3-ol (2.16 ml, 20.0 mmol), 2-amino-3-phenyl-propan-1-ol (1.51 g, 10.0 mmol), 10 ml THF, KO t Bu (1.24 g, 11.0 mmol), 24 h at 90 C. Purification by column chromatography 30:1 hexane : Et 2 O; Yield: 1.31 g = 6.6 mmol = 66% as colorless oil. 1 H MR (300 MHz, CD 2 Cl 2 ): δ = 7.44 (s_br, 1H), 7.35-7.27 (m, 2H), 7.26-7.17 (m, 3H), 5.67 (d, J = 2.6 Hz, 1H), 3.87 (s, 2H), 2.50 (q, J = 7.6 Hz, 2H), 1.97 (s, 3H), 1.12 (t, J = 7.6 Hz, 3H) ppm. 13 C MR (75 MHz, CD 2 Cl 2 ): δ = 129.1, 129.0, 128.3, 126.7, 113.6, 108.8, 34.7, 19.4, 14.9, 11.0 ppm. MS (70 ev, EI); m/z (%): 199 (82, M + ), 184 (100), 169 (25), 107 (9), 91 (25), 77 (8). elemental analysis (%) for C 14 H 17 calcd: C 84.37, H 8.60, 7.03; found: C 84.18, H 8.74, 7.14 2c: 5-benzyl-2-butyl-3-propyl-1H-pyrrole: Cat. II (0.5 ml, 0.005 mmol, 0.01 M in THF), nonan-5-ol (3.49 ml, 20.0 mmol), 2-amino-3-phenyl-propan-1-ol (1.51 g, 10.0 mmol), 10 ml THF, KO t Bu (1.24 g, 11.0 mmol), 24 h at 90 C. Purification by column chromatography 60:1 pentane : Et 2 O; Yield: 1.33 g = 5.2 mmol = 52% as colorless oil. 1 H MR (300 MHz, CD 2 Cl 2 ): δ = 7.41 (s_br, 1H), 7.34-7.26 (m, 2H), 7.25-7.14 (m, 3H), 5.69 (d, J = 2.9 Hz, 1H), 3.88 (s, 2H), 2.49-2.43 (m, 2H), 2.33-2.28 (m, 2H), 1.52-1.44 (m, 4H), 1.36-1.29 (m, 2H), 0.95-0.89 (m, 6H) ppm. 13 C MR (75 MHz, CD 2 Cl 2 ): δ = 141.0, 129.1, 129.0, 128.4, 127.9, 126.7, 119.7, 107.4, 34.7, 33.3, 28.6, 25.9, 25.3, 23.1, 14.5, 14.3 ppm. MS (70 ev, EI); m/z (%): 255 (31, M + ), 226 (9), 212 (100), 184 (12), 91 (16) ppm. elemental analysis (%) for C 18 H 25 calcd: C 84.65, H 9.87, 5.48; found: C 84.33, H 10.11, 5.29 ATURE CHEMISTRY www.nature.com/naturechemistry 27 2013 Macmillan Publishers Limited. All rights reserved.

2d: 2-(1H-indol-3-ylmethyl)- 1,5,6,7,8,9-hexahydro-cyclohepta[b]pyrrole: Cat. II (5.0 ml, 0.05 mmol, 0.01 M in THF), cycloheptanol (2.4 ml, 20.0 mmol), 2-amino-3-(1H-indol-3-yl)- propan-1-ol (1.90 g, 10.0 mmol), 10 ml THF, KO t Bu (1.24 g, 11.0 mmol), 24 h at 90 C. Purification by column chromatography 10:1 2:1 pentane : Et 2 O; Yield: 1.49 g = 5.6 mmol = 56 % as colorless solid. 1 H MR (300 MHz, CD 2 Cl 2 ): δ = 8.07 (s_br, 1H), 7.59-7.53 (m, 1H), 7.46 (s_br, 1H), 7.40-7.36 (m, 1H), 7.23-7.16 (m, 1H), 7.12-7.06 (m, 1H), 7.06-7.03 (m, 1H), 5.74 (d, J = 2.9 Hz, 1H), 4.01 (s, 2H), 2.56-2.50 (m, 4H), 1.81-1.74 (m, 2H), 1.67-1.60 (m, 4H) ppm. 13 C MR (75 MHz, CD 2 Cl 2 ): δ = 137.0, 129.3, 127.9, 127.0, 122.8, 122.5, 121.7, 119.8, 119.4, 114.8, 111.7, 108.2, 32.6, 30.1, 29.6, 29.0, 28.8, 24.0 ppm. MS (70 ev, EI); m/z (%): 264 (100, M + ), 263 (85), 235 (15), 221 (32), 148 (51), 130 (16), 116 (23), 104 (22), 90 (6), 77 (8). elemental analysis (%) for C 18 H 20 2 calcd: C 81.78, H 7.63, 10.60; found: C 82.12, H 7.95, 10.49 H 2e: 2-methyl-1,5,6,7,8,9-hexahydro-cyclohepta[b]pyrrole: Cat. II (1.0 ml, 0.01 mmol, 0.01 M in THF), cycloheptanol (2.4 ml, 20.0 mmol), 2-amino-propan-1-ol (797 µl, 10.0 mmol), 10 ml THF, KO t Bu (1.24 g, 11.0 mmol), 24 h at 90 C. Purification by column chromatography 20:1 hexane : Et 2 O; Yield: 1.16 g = 7.8 mmol = 78% as colorless oil. 1 H MR (300 MHz, CD 2 Cl 2 ): δ = 7.42 (s_br, 1H), 5.57 (d, J = 2.93 Hz, 1H), 2.63-2.58 (m, 2H), 2.51-2.47 (m, 2H), 2.16 (s, 3H), 1.83-1.76 (m, 2H), 1.69-1.62 (m, 4H) ppm. 13 C MR (75 MHz, CD 2 Cl 2 ): δ = 129.1, 123.3, 121.8, 108.5, 32.7, 30.2, 29.6, 28.9, 13.0 ppm. MS (70 ev, EI); m/z (%): 149 (88, M + ), 148 (100), 134 (15), 120 (40), 107 (32), 94 (30), 91 (11), 77 (8). elemental analysis (%) for C 10 H 15 calcd: C 80.48, H 10.13, 9.39; found: C 80.85, H 10.30, 9.65 ATURE CHEMISTRY www.nature.com/naturechemistry 28 2013 Macmillan Publishers Limited. All rights reserved.

2f: 2-ethyl-1,5,6,7,8,9-hexahydro-cyclohepta[b]pyrrole: Cat. II (0.5 ml, 0.005 mmol, 0.01 M in THF), cycloheptanol (2.4 ml, 20.0 mmol), 2-amino-butan-1-ol (960 µl, 10.0 mmol), 10 ml THF, KO t Bu (1.24 g, 11.0 mmol), 24 h at 90 C. Purification by column chromatography 40:1 20:1 pentane : Et 2 O; Yield: 1.44 g = 8.8 mmol = 88% as yellow oil. 1 H MR (300 MHz, CD 2 Cl 2 ): δ = 7.45 (s_br, 1H), 5.58 (d, J = 2.9 Hz, 1H), 2.63-2.59 (m, 2H), 2.55-2.47 (m, 4H), 1.81-1.75 (m, 2H), 1.68-1.61 (m, 4H), 1.18 (t, J = 7.6 Hz, 3H) ppm. 13 C MR (75 MHz, CD 2 Cl 2 ): δ = 130.1, 128.9, 121.6, 106.9, 32.6, 30.2, 29.6, 29.0, 28.9, 21.2, 14.3 ppm. MS (70 ev, EI); m/z (%): 163 (50, M + ), 148 (100), 134 (26), 106 (10), 77 (8). elemental analysis (%) for C 11 H 17 calcd: C 80.93, H 10.50, 8.58; found: C 80.60, H 10.87, 8.83. 2g: 2-isopropyl-1,5,6,7,8,9-hexahydro-cyclohepta[b]pyrrole: Cat. II (0.3 ml, 0.003 mmol, 0.01 M in THF), cycloheptanol (2.4 ml, 20.0 mmol), 2-amino-3-methyl-butan-1-ol (1.1 ml, 10.0 mmol), 10 ml THF, KO t Bu (1.24 g, 11.0 mmol), 24 h at 90 C. Purification by column chromatography 60:1 40:1 pentane : Et 2 O; Yield: 1.49 g = 8.4 mmol = 84% as yellow oil. 1 H MR (300 MHz, CD 2 Cl 2 ): δ = 7.47 (s_br, 1H), 5.63-5.54 (d, J = 2.9 Hz, 1H), 2.90-2.72 (m, 1H), 2.64-2.58 (m, 2H), 2.52-2.46 (m, 2H), 1.83-1.74 (m, 2H), 1.70-1.61 (m, 4H), 1.20 (t, J = 6.7 Hz, 3H) ppm. 13 C MR (75 MHz, CD 2 Cl 2 ): δ = 134.8, 128.7, 121.3, 105.6, 32.6, 30.1, 29.6, 29.0, 28.9, 27.4, 23.2 ppm. MS (70 ev, EI); m/z (%): 177 (15, M + ), 162 (100), 106 (5), 77 (6). elemental analysis (%) for C 12 H 19 calcd: C 81.30, H 10.80, 7.90; found: C 81.40, H 11.14, 7.84. 2h: 2-sec-butyl-1,5,6,7,8,9-hexahydro-cyclohepta[b]pyrrole: Cat. II (0.3 ml, 0.003 mmol, 0.01 M in THF), cycloheptanol (2.4 ml, 20.0 mmol), 2-amino-3-methyl-pentan-1-ol (1.17 g, 10.0 mmol), 10 ml THF, KO t Bu (1.24 g, 11.0 mmol), 24 h at 90 C. Purification by column chromatography 60:1 40:1 pentane : Et 2 O; Yield: 1.52 g = 7.9 mmol = 79 % as colorless oil. 1 H MR (300 MHz, CD 2 Cl 2 ): δ = 7.43 (s_br, 1H), 5.57 (d, J = 2.9 Hz, 1H), 2.63-2.58 (m, 2H), 2.58-2.45 (m, 3H), 1.82-1.73 (m, 2H), 1.69-1.61 (m, 4H), 1.59-1.41 (m, 2H), 1.17 (d, J = 6.7 Hz, 3H), 0.89 (t, J = 7.5 Hz, 3H) ppm. 13 C MR (75 MHz, CD 2 Cl 2 ): δ = 133.7, 128.6, 121.2, 106.2, ATURE CHEMISTRY www.nature.com/naturechemistry 29 2013 Macmillan Publishers Limited. All rights reserved.

34.6, 32.6, 30.8, 30.1, 29.7, 29.1, 28.9, 20.5, 12.3 ppm. MS (70 ev, EI); m/z (%): 191 (10, M + ), 176 (7), 162 (100), 132 (4), 106 (3) 77 (2). elemental analysis (%) for C 13 H 21 calcd: C 81.61, H 11.06, 7.32; found: C 81.74, H 11.19, 7.32. 2i: 2-benzyl-1,5,6,7,8,9-hexahydro-cyclohepta[b]pyrrole: Cat. II (0.5 ml, 0.005 mmol, 0.01 M in THF), cycloheptanol (2.4 ml, 20.0 mmol), 2-amino-3-phenyl-propan-1-ol (1.51 g, 10.0 mmol), 10 ml THF, KO t Bu (1.24 g, 11.0 mmol), 24 h at 90 C. Purification by column chromatography 30:1 10:1 pentane : Et 2 O; Yield: 1.82 g = 8.0 mmol = 80% as colorless oil. 1 H MR (300 MHz, CD 2 Cl 2 ): δ = 7.40 (s_br, 1H), 7.34-7.27 (m, 2H), 7.26-7.17 (m, 3H), 5.65 (d, J = 2.9 Hz, 1H), 3.84 (s, 2H), 2.59-2.54 (m, 2H), 2.51-2.47 (m, 2H), 1.79-1.74 (m, 2H), 1.67-1.61 (m, 4H) ppm. 13 C MR (75 MHz, CD 2 Cl 2 ): δ = 141.0, 129.9, 129.1, 129.0, 126.8, 126.7, 121.8, 108.9, 34.6, 32.6, 30.1, 29.6, 28.9, 28.8 ppm. MS (70 ev, EI); m/z (%): 225 (100, M + ), 196 (28), 148 (20), 134 (30), 91 (40), 77 (10). elemental analysis (%) for C 16 H 19 calcd: C 85.28, H 8.50, 6.22; found: C 85.24, H 8.71, 6.40 2j: 2-benzyl-1,5,6,7-tetrahydro-cyclopenta[b]pyrrole: Cat. II (1.0 ml, 0.01 mmol, 0.01 M in THF), cyclopentanol (1.82 ml, 20.0 mmol), 2-amino-3-phenyl-propan-1-ol (1.51 g, 10.0 mmol), 10 ml THF, KO t Bu (1.24 g, 11.0 mmol), 24 h at 90 C. Purification by column chromatography 30:1 20:1 pentane : Et 2 O; Yield: 999 mg = 5.1 mmol = 51% as colorless oil. 1 H MR (300 MHz, CD 2 Cl 2 ): δ = 7.53 (s_br, 1H), 7.35-7.26 (m, 2H), 7.26-7.16 (m, 3H), 5.71 (d, J = 1.8 Hz, 1H), 3.90-3.88 (m, 4H), 2.39-2.31 (m, 2H) ppm. 13 C MR (75 MHz, CD 2 Cl 2 ): δ = 141.0, 135.9, 134.2, 129.1, 126.8, 126.7, 102.6, 35.4, 29.5, 26.1, 25.9 ppm. MS (70 ev, EI); m/z (%): 197 (93, M + ), 196 (100), 182 (10), 169 (25), 152 (5), 120 (81), 106 (22), 91 (34), 85 (15), 77 (13). elemental analysis (%) for C 14 H 15 calcd: C 85.24, H 7.66, 7.10; found: C 85.55, H 7.79, 6.97 ATURE CHEMISTRY www.nature.com/naturechemistry 30 2013 Macmillan Publishers Limited. All rights reserved.

2k: 2-benzyl-5,6,7,8,9,10-hexahydro-1H-cycloocta[b]pyrrole: Cat. II (0.5 ml, 0.005 mmol, 0.01 M in THF), cyclooctanol (2.64 ml, 20.0 mmol), 2-amino-3-phenyl-propan-1-ol (1.51 g, 10.0 mmol), 10 ml THF, KO t Bu (1.24 g, 11.0 mmol), 24 h at 90 C. Purification by column chromatography 40:1 20:1 pentane : Et 2 O; Yield: 1.85 g = 7.7 mmol = 77% as colorless oil. 1 H MR (300 MHz, CD 2 Cl 2 ): δ = 7.41 (s_br, 1H), 7.35-7.28 (m, 2H), 7.25-7.18 (m, 3H), 5.66 (d, J = 2.9 Hz, 1H), 3.89-3.88 (m, 2H), 2.63-2.59 (m, 2H), 2.55-2.51 (m, 2H), 1.64-1.59 (m, 4H), 1.46-1.42 (m, 4H) ppm. 13 C MR (75 MHz, CD 2 Cl 2 ): δ = 141.1, 129.1, 129.0, 128.1, 127.7, 126.6, 119.5, 108.0, 34.7, 31.3, 30.3, 26.6, 26.3, 25.9, 25.5 ppm. MS (70 ev, EI); m/z (%): 239 (100, M + ), 210 (62), 196 (45), 148 (35), 118 (10), 91 (52). elemental analysis (%) for C 16 H 19 calcd: C 85.30, H 8.84, 5.85; found: C 85.66, H 8.92, 5.87 2l: 2-benzyl-5,6,7,8,9,10,11,12,13,14-decahydro-1H-cyclododeca[b]pyrrole: Cat. II (1.0 ml, 0.01 mmol, 0.01 M in THF), cyclododecanol (3.68 g, 20.0 mmol), 2-amino-3-phenyl-propan-1- ol (1.51 g, 10.0 mmol), 10 ml THF, KO t Bu (1.24 g, 11.0 mmol), 24 h at 90 C. Purification by column chromatography 60:1 40:1 hexane : Et 2 O; Yield: 1.1 g = 3.74 mmol = 37% as colorless solid. 1 H MR (300 MHz, CD 2 Cl 2 ): δ = 7.37 (s_br, 1H), 7.33-7.26 (m, 2H), 7.25-7.15 (m, 3H), 5.68 (d, J = 2.9 Hz, 1H), 3.88 (s, 2H), 2.51 (t, J = 6.9 Hz, 2H), 2.36 (t, J = 6.9 Hz, 2H), 1.63 (m, 4H), 1.41-1.32 (m, 8H), 1.27-1.20 (m, 4H) ppm. 13 C MR (75 MHz, CD 2 Cl 2 ): δ = 141.0, 129.4, 129.1, 129.0, 128.1, 126.7, 120.5, 107.0, 34.8, 29.6, 28.6, 25.4, 25.2, 25.1, 25.0, 23.0, 22.9, 22.8, 22.5 ppm. MS (70 ev, EI); m/z (%): 295 (100, M + ), 266 (7), 252 (14), 238 (12), 210 (30), 204 (35), 196 (40), 184 (38), 171 (40), 91 (40). elemental analysis (%) for C 21 H 29 calcd: C 85.37, H 9.89, 4.74; found: C 85.11, H 10.11, 4.91. ATURE CHEMISTRY www.nature.com/naturechemistry 31 2013 Macmillan Publishers Limited. All rights reserved.

Reaction of Hexane-2,5-diol with various Amino Alcohols to Symmetric and Unsymmetric Bipyrroles Supplementary Table S12: Reaction of hexane-2,5-diol with various amino alcohols to symmetric and unsymmetric bipyrroles [mol% Cat. II] Product Yield [a] 3a 0.1 42% 3b 0.1 83% [a] Isolated yield 3a: 1,2-bis(5-benzyl-1H-pyrrol-2-yl)ethane: Cat. II (1.0 ml, 0.01 mmol, 0.01 M in THF), hexane-2,5-diol (1.18 g, 10.0 mmol), 2-amino-3-phenyl-propan-1-ol (6.04 g, 40.0 mmol), 20 ml THF, KO t Bu (2.48 g, 22.0 mmol), 24 h at 90 C. Purification by column chromatography 8:1 4:1 pentane : Et 2 O; Yield: 1.43 g = 4.2 mmol = 42% as colorless solid. ATURE CHEMISTRY www.nature.com/naturechemistry 32 2013 Macmillan Publishers Limited. All rights reserved.

1 H MR (300 MHz, CD 2 Cl 2 ): δ = 7.55 (s_br, 2H), 7.34-7.27 (m, 4H), 7.25-7.16 (m, 6H), 5.82-5.75 (m, 4H), 3.86 (s, 4H), 2.77 (s, 4H) ppm. 13 C MR (75 MHz, CD 2 Cl 2 ): δ = 140.7, 131.7, 130.0, 129.0, 126.8, 106.7, 105.8, 34.6, 28.5 ppm. MS (70 ev, EI); m/z (%): 340 (2, M + ), 325 (2), 249 (50), 183 (60), 170 (100), 156 (28), 91 (30). elemental analysis (%) for C 24 H 24 2 calcd: C 84.67, H 7.11, 8.23; found: C 84.42, H 7.17, 8.33. 3b: 2-benzyl-5-(2-(5-ethyl-1H-pyrrol-2-yl)ethyl)-1H-pyrrole: Cat. II (1.0 ml, 0.01 mmol, 0.01 M in THF), 4-(5-benzyl-1H-pyrrol-2-yl)-butan-2-ol (4.584 g, 20.0 mmol), 2-amino-1- butanol (960 µl, 10.0 mmol), 10 ml THF, KO t Bu (1.24 g, 11.0 mmol), 24 h at 90 C. Purification by column chromatography 8:1 4:1 pentane : Et 2 O; Yield: 2.31 g = 8.3 mmol = 83% as yellow oil. 1 H MR (300 MHz, CD 2 Cl 2 ): δ = 7.58 (s_br, 1H), 7.36-7.28 (m, 2H), 7.27-7.18 (m, 3H), 5.87-5.82 (m, 2H), 5.77-5.73 (m, 2H), 3.89 (s, 2H), 2.81 (s, 4H), 2.53 (q, J = 7.6 Hz, 2H), 1.20 (t, J = 7.6 Hz, 3H) ppm. 13 C MR (75 MHz, CD 2 Cl 2 ): δ = 140.7, 133.4, 131.9, 130.7, 130.1, 129.1, 129.0, 126.8, 106.7, 105.7, 105.6, 104.4, 34.7, 28.7, 28.6, 21.3, 14.2 ppm. MS (70 ev, EI); m/z (%): 278 (2, M + ), 186 (1), 170 (100), 108 (75), 93 (12). elemental analysis (%) for C 19 H 22 2 calcd: C 81.97, H 7.97, 10,06; found: C 81.83, H 8.25, 10.17. ATURE CHEMISTRY www.nature.com/naturechemistry 33 2013 Macmillan Publishers Limited. All rights reserved.

Syntheses of -protected Amino Alcohols and their Conversion with 2-Amino-3-phenyl-propan-1-ol Supplementary Table S13: Syntheses of -protected amino alcohols and their conversion with 2-amino-3-phenylpropan-1-ol R 1 R 1 X X X= CH, H H 2 + OH R 2 + HO HO R 2 OH R 3 H 2 cat. II KO t Bu cat. II 1.1 eq. KO t Bu, 24h, 90 C [mol% Cat. II] Product Yield [a] R 1 R 1 X X H H R 2 OH R 2 H R 3 0.5 92% 3c 0.1 83% 0.5 78% 3d 0.3 82% ATURE CHEMISTRY www.nature.com/naturechemistry 34 2013 Macmillan Publishers Limited. All rights reserved.

0.3 89% 3e 0.3 87% [a] Isolated yield 1-(phenylamino)propan-2-ol: Cat. II (0.4 mmol, 288 mg), aniline (7.28 ml, 80.0 mmol) propane-1,2-diol (23.6 ml, 320.0 mmol), 60 ml THF, KO t Bu (9.04 g, 80.0 mmol), 24 h at 110 C. Purification by HV distillation (3.0x 10-2 mbar, 96 C) 11.11g = 73.5 mmol = 92% as colorless oil. 1 H MR (300 MHz, CD 2 Cl 2 ): δ = 7.21-7.11 (m, 2H), 6.74-6.61 (m, 3H), 4.05 (s_br, 1H), 4.02-3.93 (m, 1H), 3.20 (d, J = 12.6 Hz, 1H), 2.97 (dd, J = 12.6, 8.6 Hz, 1H), 2.21 (s_br, 1H), 1.24 (d, J = 6.4 Hz, 3H) ppm. 13 C MR (75 MHz, CD 2 Cl 2 ): δ =149.1, 129.7, 118.0, 113.6, 66.9, 52.1, 21.3 ppm. 3c: 5-benzyl-2-methyl--phenyl-1H-pyrrol-3-amine: Cat. II (1.0 ml, 0.01 mmol, 0.01 M in THF), 1-phenylamino-propan-2-ol (3.02 g, 20.0 mmol), 2-amino-3-phenyl-propan-1-ol (1.51 g, 10.0 mmol), 10 ml THF, KO t Bu (1.24 g, 11.0 mmol), 24 h at 90 C. Purification by column chromatography 2:1 1:1 pentane : Et 2 O; Yield: 2.17 g = 8.3 mmol = 83% as deep red oil. 1 H MR (300 MHz, CD 2 Cl 2 ): δ = 7.51 (s_br, 1H), 7.40-7.30 (m, 2H), 7.30-7.21 (m, 3H), 7.17-7.12 (m, 2H), 6.68-6.64 (m, 3H), 5.82 (d, J = 2.9 Hz, 1H), 5.00 (s_br, 1H), 3.91 (s, 2H), 2.07 (s, 3H) ppm. 13 C MR (75 MHz, CD 2 Cl 2 ): δ = 149.2, 141.5, 129.6, 129.12, 129.10, 128.1, 126.9, ATURE CHEMISTRY www.nature.com/naturechemistry 35 2013 Macmillan Publishers Limited. All rights reserved.

122.0, 121.8, 117.6, 113.5, 105.6, 34.9, 10.6 ppm. MS (70 ev, EI); m/z (%): 262 (12, M + ), 217 (8), 185 (100), 169 (60), 143 (16), 131 (17), 115 (35), 104 (14), 91 (38), 77 (22). elemental analysis (%) for C 18 H 18 2 calcd: C 82.41, H 6.92, 10.68; found: C 82.22, H 6.71, 10.73. 1-(phenylamino)hexan-2-ol: Cat. II (0.4 mmol, 288 mg), aniline (7.28 ml, 80.0 mmol), hexane-1,2-diol (24.8 ml, 200.0 mmol), 40 ml THF, KO t Bu (9.94 g, 88.0 mmol), 72 h at 110 C. Purification by HV distillation ( 1.3 x 10-1 mbar, 133 C) 11.99g = 62 mmol = 78% as colorless oil. 1 H MR (300 MHz, CD 2 Cl 2 ): δ = 7.19-7.11 (m, 2H), 6.72-6.60 (m, 3H), 4.04 (s_br, 1H), 3.80 (s_br, 1H), 3.24 (dd, J = 12.6, 2.6 Hz, 1H), 2.97 (dd, J = 12.6, 8.6Hz, 1H), 1.95 (d, J = 1.9 Hz, 1H), 1.65-1.33 (m, 6H), 0.93 (t, J = 6.7 Hz, 3H) ppm. 13 C MR (75 MHz, CD 2 Cl 2 ): δ = 149.2, 129.7, 118.0, 113.6, 70.9, 50.8, 35.4, 28.4, 23.3, 14.4 ppm. MS (70 ev, EI); m/z (%): 193 (6, M + ), 118 (2), 106 (100), 93 (3), 77 (9). 3d: 5-benzyl-2-butyl--phenyl-1H-pyrrol-3-amine: Cat. II (3.0 ml, 0.03 mmol, 0.01 M in THF), 1-phenylamino-hexan-2-ol (3.86 g, 20.0 mmol), 2-amino-3-phenyl-propan-1-ol (1.51 g, 10.0 mmol), 10 ml THF, KO t Bu (1.24 g, 11.0 mmol), 24 h at 90 C. Purification by column chromatography 8:1 4:1 pentane : Et 2 O; Yield: 2.49 g = 8.2 mmol = 82% as deep red oil. 1 H MR (300 MHz, CD 2 Cl 2 ): δ = 7.51 (s_br, 1H), 7.36-7.30 (m, 2H), 7.27-7.20 (m, 3H), 7.15-7.08 (m, 2H), 6.67-6.63 (m, 3H), 5.79 (d, J = 2.9 Hz, 1H), 4.96 (s_br, 1H), 3.91 (s, 2H), 2.48-2.42 (m, 2H), 1.51-1.43 (m, 2H), 0.87 (t, J = 7.3 Hz, 3H) ppm. 13 C MR (75 MHz, CD 2 Cl 2 ): δ = 149.4, 140.5, 129.5, 129.08, 129.07, 128.1, 127.0, 126.8, 121.5, 117.5, 113.5, 105.7, 34.9, 32.4, 25.2, 23.0, 14.2 ppm. MS (70 ev, EI); m/z (%): 304 (1, M + ), 261 (66), 244 (13), 169 (100), 115 (15), 91 (15). elemental analysis (%) for C 21 H 24 2 calcd: C 82.85, H 7.95, 9.20; found: C 82.53, H 8.02, 9.15 ATURE CHEMISTRY www.nature.com/naturechemistry 36 2013 Macmillan Publishers Limited. All rights reserved.

1-(6-methylpyridin-2-ylamino)butan-2-ol: Cat. II (0.3 mmol, 215 mg), 6-methylpyridin-2- amine (10.8 g, 100.0 mmol) butane-1,2-diol (18.4 ml, 250.0 mmol), 60 ml THF, KO t Bu (12.4g, 110.0 mmol), 96 h at 110 C. Purification by HV distillation (2.6x 10-2 mbar, 122 C); Yield: 16.0 g = 89.0 mmol = 89% as colorless oil. 1 H MR (300 MHz, CD 2 Cl 2 ): δ = 7.29 (dd, J = 8.3,7.2 Hz, 1H), 6.43 (d, J = 7.2 Hz, 1H), 6.27 (d, J = 8.3 Hz, 1H), 4.98 (s_br, 1H), 3.68-3.57 (m, 1H), 3.45-3.36 (m, 1H), 3.30-3.20 (m, 1H), 2.32 (s, 3H), 1.52-1.45 (m, 2H), 0.94 (t, J = 7.6 Hz, 3H) ppm. 13 C MR (75 MHz, CD 2 Cl 2 ): δ =159.3, 156.5, 138.4, 112.4, 105.6, 74.3, 49.3, 28.7, 24.2, 10.5 ppm. 3e: -(5-benzyl-2-ethyl-1H-pyrrol-3-yl)-6-methylpyridin-2-amine: Cat. II (3.0 ml, 0.03 mmol, 0.01 M in THF), 1-(6-methyl-pyridin-2-ylamino)-butan-2-ol (3.60 g, 20.0 mmol), 2- amino-3-phenyl-propan-1-ol (1.51 g, 10.0 mmol), 10 ml THF, KO t Bu (1.24 g, 11.0 mmol), 24 h at 90 C. Purification by column chromatography 2:1 1:2 pentane : Et 2 O; Yield: 2.53 g = 8.7 mmol = 87% as deep red oil. 1 H MR (300 MHz, CD 2 Cl 2 ): δ = 8.14 (s_br, 1H), 7.37-7.21 (m, 6H), 6.46 (d, J = 7.0 Hz, 1H), 6.30 (s_br, 1H), 6.27 (d, J = 8.5 Hz, 1H), 5.83 (d, J = 2.9 Hz, 1H), 3.94 (s, 2H), 2.49 (q, J = 7.6 Hz, 2H), 2.34 (s, 3H), 1.11 (t, J = 7.6 Hz, 3H) ppm. 13 C MR (75 MHz, CD 2 Cl 2 ): δ = 16.1, 157.2, 140.5, 138.3, 129.1, 129.0, 128.6. 128.3, 126.8, 119.3, 112.5, 105.9, 103.3, 34.8, 24.4, 18.8, 14.4 ppm. MS (70 ev, EI); m/z (%): 291 (42, M + ), 276 (50), 184 (100), 168 (35), 142 (30), 115 (32), 91 (44). elemental analysis (%) for C 19 H 21 3 calcd C 78.32, H 7.26, 14.42; found: C 78.08, H 6.97 13.61. ATURE CHEMISTRY www.nature.com/naturechemistry 37 2013 Macmillan Publishers Limited. All rights reserved.

Supplementary Table S14: Reaction of 1-phenylethanol with 1-amino-alcohol to 4-substituted pyrroles [mol% Cat. II] Product Yield [a] 0.5 52% [a] Isolated yield 4-ethyl-2-phenyl-1H-pyrrole: Cat. II (5.0 ml, 0.05 mmol, 0.01 M in THF), 1-phenylethanol (2.4 ml, 20.0 mmol) 1-aminobutan-2-ol (960 µl, 10.0 mmol), 10 ml THF, KO t Bu (1.24 g, 11.0 mmol), 24 h at 90 C. Purification by column chromatography 10:1 pentane : Et 2 O; Yield: 889 mg = 5.2 mmol = 52% as colorless solid. 1 H MR (300 MHz, CD 2 Cl 2 ): δ = 8.28 (s_br, 1H), 7.49-7.42 (m, 2H), 7.39-7.31 (m, 2H), 7.22-7.15 (m, 1H), 6.68-6.61 (m, 1H), 6.43-6.36 (m, 1H), 2.53 (q, J = 7.5 Hz, 2H), 1.22 (t, J = 7.6 Hz, 3H) ppm. 13 C MR (75 MHz, CD 2 Cl 2 ): δ = 133.5, 132.1, 129.4, 128.6, 126.4, 124.0, 116.2, 106.5, 20.7, 15.7 ppm. MS (70 ev, EI); m/z (%): 171 (46), 156 (100), 128 (20), 115 (10), 78 (19). 2,5-diethylpyrazine: Cat. II (71 mg, 0.1 mmol), 2-aminobutan-1-ol (3.8 ml, 40.0 mmol), 10 ml THF, KO t Bu (2.5 g, 22.0 mmol), 24 h at 90 C. Purification by column chromatography 5:1 pentane : Et 2 O; Yield: 0.54 g = 3.9 mmol = 19% as yellow oil. 1 H MR (300 MHz, CD 2 Cl 2 ): δ = 8.33 (s, 2H), 2.77 (q, J = 7.6 Hz, 4H), 1.27 (t, J = 7.6 Hz, 6H) ppm. 13 C MR (75 MHz, CD 2 Cl 2 ): δ = 156.2,143.3, 28.7, 13.9 ppm. MS (70 ev, EI); m/z (%): 136, (55, M + ), 135 (100), 121 (96), 108 (8), 94 (4), 80 (5), 67 (6). ATURE CHEMISTRY www.nature.com/naturechemistry 38 2013 Macmillan Publishers Limited. All rights reserved.

2-(1-phenylethylideneamino)butan-1-ol: acetophenone (35.0 ml, 300.0 mmol) (±)2- aminobutan-1-ol (33.0 ml, 350.0 mmol), molecular sieve 3Ǻ (40 g), 200 ml THF, 48 h reflux. Purification by HV distillation (3.0 x 10-3, 52 C); Yield: 53.5 g = 279.0 mmol = 93% as colorless oil. 1 H MR (300 MHz, CD 2 Cl 2 ): δ = 7.60-7.54 (m, 2H), 7.41-7.21 (m, 3H), 4.09 (dd, J = 7.7, 6.9 Hz, 0.31 H), 3.76 (t, J = 7.3 Hz, 0.65H), 3.32 (t, J = 7.7 Hz, 0.69 H), 3.23-3.16 (m, 0.35 H), 1.85 (s_br, 1H), 1.68-1.31 (m, 5H), 0.97-0.92 (m, 3H) ppm. 13 C MR (75 MHz, CD 2 Cl 2 ): δ = 146.2, 128.5, 127.6, 126.4, 125.9, 71.2, 60.4, 29.9, 27.2, 11.8 ppm. MS (70 ev, EI); m/z (%): 190 (1), 176 (100), 160 (75), 145 (8), 132 (7), 114 (50), 105 (63), 91 (33), 77 (32). 2-(1-phenylpentylideneamino)butan-1-ol: valerophenone (20.0 ml, 120.0 mmol) (±)2- aminobutan-1-ol (19.0 ml, 200.0 mmol), molecular sieve 3Ǻ (20 g), 200 ml THF, 48 h reflux. Purification by HV distillation (3.8 x 10-2, 110 C); Yield: 21.5 g = 92.2 mmol = 76% as colorless oil. 1 H MR (300 MHz, CD 2 Cl 2 ): δ = 7.59-7.45 (m, 2H), 7.41-7.11 (m, 3H), 4.07-4.02 (m, 0.28H), 3.76 (t, J = 7.4 Hz, 0.71H), 3.37-3.16 (m, 1H), 3.02-2.83 (m, 1H), 1.95 (s_br, 1H), 1.89-1.76 (m, 2H), 1.71-1.56 (m, 1H), 1.56-1.35 (m, 1H), 1.30-1.10 (m, 4H), 0.98-0.88 (m, 3H), 0.88-0.78 (m, 3H) ppm. 13 C MR (75 MHz, CD 2 Cl 2 ): δ = 145.8, 128.2, 127.5, 127.1, 126.5, 71.1, 61.0, 60.1, 42.3, 26.9, 23.5, 14.3, 11.7 ppm. MS (70 ev, EI); m/z (%): 233 (1, M + ), 232 (1), 202 (11), 176 (100), 156 (6), 120 (7), 105 (35), 91 (12), 77 (16). 2-(phenylamino)ethanol: cat. II (0.5 mmol, 359 mg), aniline (23.3 ml, 250.0 mmol) ethane- 1,2-diol (50.0 ml, 800.0 mmol), 200 ml THF, KO t Bu (31.0 g, 275.0 mmol), 72 h at 110 C. Purification by HV distillation (2.3 x 10-1, 107 C); Yield: 10.95 g = 80.0 mmol = 32% as colorless oil. 1 H MR (300 MHz, CD 2 Cl 2 ): δ = 7.25-7.13 (m, 2H), 6.77-6.69 (m, 1H), 6.68-6.61 (m, 2H), 4.08 (s_br, 1H), 3.77 ( t, J = 5.3 Hz, 2H), 3.25 (t, J = 5.3 Hz, 2H), 2.44 (s_br, 1H) ppm. 13 C MR (75 MHz, CD 2 Cl 2 ): δ = 149.0, 129.7, 118.1, 113.6, 61.6, 46.6 ppm. MS (70 ev, EI); m/z (%): 137 (25, M + ), 106 (100), 77 (20). ATURE CHEMISTRY www.nature.com/naturechemistry 39 2013 Macmillan Publishers Limited. All rights reserved.

tert-butyl-1-hydroxybutan-2-ylcarbamate: To 2-aminobutan-1-ol (18.9 ml, 200 mmol) in 500 ml water and 400 ml THF was added a 2 CO 3 (70.0 g, 660 mmol). After cooling to 0 C, di-tert-butyl-dicarbonate (45.0 g, 206 mmol) dissolved in 100 ml THF was added drop wise. The solution was allowed to warm to room temperature and stirred for further 4h. The solution was extracted 4 times with Et 2 O. The combined organic phases were dried over a 2 SO 4, filtered and the solvent was removed by rotary evaporation. Purification by HV distillation (8.8 x 10-2 mbar, 99 C); Yield: 36.5 g = 192 mmol = 96% as colorless oil. 1 H MR (300 MHz, CD 2 Cl 2 ): δ = 4.73 (s_br, 1H), 3.64-3.55 (m, 1H), 3.55-3.42 (m, 2H), 2.67 (s_br, 1H), 1.62-1.46 (m, 2H), 1.42 (s, 9H), 0.93 (t, J = 7.6 Hz, 3H) ppm. 13 C MR (75 MHz, CD 2 Cl 2 ): δ = 157.1, 79.6, 65.6, 54.8, 28.7, 25.1, 10.9 ppm. (5-methylcyclohexa-1,3-diene-1,3,5-triyl)tribenzene: Cat. II (36 mg, 0.05 mmol), 1-phenyl-1- ethanol (2.4 ml, 20.0 mmol), 10 ml THF, KO t Bu (1.24 g, 11.0 mmol), 24 h at 90 C. Purification by column chromatography 100:1 pentane : Et 2 O 3:1 pentane : Et 2 O; Yield: = 527 mg = 1.6 mmol = 33% as colorless oil. 1 H MR (300 MHz, CD 2 Cl 2 ): δ = 7.62-7.24 (m, 15H), 6.79 (q, J = 1.5 Hz,1H)), 6.27 (d, J = 1.5 Hz, 1H), 3.18 (dd, J = 16.7, 1.5 Hz, 1H), 2.89 (dd, J = 16.7, 1.8 Hz, 1H), 1.64 (s, 3H) ppm. 13 C MR (75 MHz, CD 2 Cl 2 ): δ = 149.3, 141.5, 141.2, 137.6, 136.5, 132.7, 129.1, 129.0, 128.8, 128.0, 127.0, 126.7, 126.6, 126.4, 125.8, 121.9, 41.9, 40.9, 27.5 ppm. MS (70 ev, EI); m/z (%): 322 (100, M + ), 307 (80), 291 (14), 265 (8), 231 (24), 215 (31), 202 (12), 165 (8), 115 (9), 105 (29), 91 (17), 77 (10). ATURE CHEMISTRY www.nature.com/naturechemistry 40 2013 Macmillan Publishers Limited. All rights reserved.

Mechanistic Studies Synthesis of [(4-Ph)Tr(HP(iPr) 2 ) 2 IrH 3 ] Cat. II (1.0 mmol, 719 mg) was dissolved in 4 ml benzene-d 6 and stirred in a 60 bar H 2 atmosphere at 25 C for 2 days. An orange solution was obtained. Crystals suitable for X-Ray analysis were obtained from this solution. Due to the high reactivity of this compound MRanalyses was done directly from the reaction solution. 1 H MR (400 MHz, C 6 D 6 ): δ = 8.42-8.50 (m, 2H), 7.31-7.27 (m, 3H), 5.90 (s_br, 2H), 1.43-1.37 (m, 4H), 1.08-0.99 (m, 24H), -11.69 (dt, J = 18.3, 5.1 Hz, 2H), -18.04 (tt, J = 14.6, 5.1 Hz, 1H) ppm. 13 C MR (100 MHz, C 6 D 6 ): δ = 169.2 (t, J = 9.5 Hz), 168.4, 137.1, 132.2, 129.1, 129.0, 69.3, 30.8 (t, J = 16.2 Hz), 28.8, 26.2, 23.9, 19.5 (t, J = 4.4 Hz), 18.8 ppm. 31 P MR (161 MHz, C 6 D 6, 298 K): δ = 108.05 (dt, J = 13.0, 6.7 Hz) ppm. elemental analysis (%) for [C 21 H 35 Ir 5 P 2 ] x 0.4 C 6 D 6 calcd: C 43.35, H 6.65, 10.80; found: C 43.42, H 6.65, 10.50. ATURE CHEMISTRY www.nature.com/naturechemistry 41 2013 Macmillan Publishers Limited. All rights reserved.

Supplementary Figure S3: Formation of the catalyst resting state, an iridium trihydride complex. It can be formed quantitatively by reacting catalyst II with alcohols, H 2 or under catalytic conditions. 100 90 80 70 conversion [%] 60 50 40 30 20 10 0 0 4 8 12 16 20 24 reaction time [h] Supplementary Figure S4. Time conversion plot for the reaction of 1-phenylethanol with 2-amino-butan-1-ol. reaction conditions: 1-phenylethanol (2.4 ml, 20.0 mmol), 2-amino-butan-1-ol (1.92 ml, 20.0 mmol), KO t Bu (2.48 g, 22.0 mmol), cat. II (57 mg, 0.08 mmol), 20 ml dioxane, 1.125 ml dodecane as internal standard, 110 C 2-ethyl-5-phenyl-1H-pyrrole 1-phenylethanol acetophenone (5-methylcyclohexa-1,3-diene-1,3,5- triyl)tribenzene ATURE CHEMISTRY www.nature.com/naturechemistry 42 2013 Macmillan Publishers Limited. All rights reserved.

200 180 160 140 conversion [%] 120 100 80 60 40 20 0 0 4 8 12 16 20 24 reaction time [h] Supplementary Figure S5. Time conversion plot for the reaction of 1-phenylethanol with 2-amino-butan-1-ol. reaction conditions: 1-phenylethanol (4.8 ml, 40.0 mmol), 2-amino-butan-1-ol (1.92 ml, 20.0 mmol), KO t Bu (2.48 g, 22.0 mmol), cat. II (57 mg, 0.08 mmol), 20 ml dioxane, 1.125 ml dodecane as internal standard, 110 C 2-ethyl-5-phenyl-1H-pyrrole 1-phenylethanol acetophenone (5-methylcyclohexa-1,3-diene-1,3,5- triyl)tribenzene 1.1.1. Possible Reaction Pathways Supplementary Figure S6: Possible reaction pathways for the pyrrole synthesis ATURE CHEMISTRY www.nature.com/naturechemistry 43 2013 Macmillan Publishers Limited. All rights reserved.

1.1.2. Reactions which confirm Pathway A Supplementary Figure S7: Dehydrogenation of 1-phenylethanol Without base 1-phenylethanol is converted into acetophenone and H 2 by catalyst II, but with base, 1-phenylethanol is converted to acetophenone and several additional aldol condensation products (Supplementary Figure S7). Due to this fact the system 1-phenyl-1- pentanol/valerophenone was used for further mechanistic investigations (Supplementary Figure S9). Supplementary Figure S8: Conversion of 2-(1-phenylethylideneamino)butan-1-ol to 2-ethyl-5-phenyl-1H-pyrrole Under catalytic conditions 2-(1-phenylethylideneamino)butan-1-ol is converted to 2-ethyl-5- phenyl-1h-pyrrole in excellent yield (Supplementary Figure S8). If catalyst or base is used exclusively only a very poor conversion of the imine is observed. This fact clearly points out that both catalyst and base in combination are involved in the cyclisation reaction. ATURE CHEMISTRY www.nature.com/naturechemistry 44 2013 Macmillan Publishers Limited. All rights reserved.

Supplementary Figure S9: Dehydrogenation of 1-phenyl-1-pentanol to valerophenone under catalytic conditions Dehydrogenation of 1-phenyl-1-pentanol is fast. Under standard reaction conditions the secondary alcohol is completely converted to the corresponding ketone within 24 h (Supplementary Figure S9). Supplementary Figure S10: Dehydrogenation and condensation reaction of 2-amino-1-butanol to 2,5- diethylpyrazine In contrast the dehydrogenation and condensation reaction of the amino alcohol to 2,5- diethylpyrazine is very slow under the given reaction conditions (90 C), which was already shown in our previous work. 38 (Supplementary Figure S10) ATURE CHEMISTRY www.nature.com/naturechemistry 45 2013 Macmillan Publishers Limited. All rights reserved.

Supplementary Figure S11: Pathway A1: reaction of valerophenone with 2-amino-1-butanol under catalytic conditions (cat II, 0.5 mol%) Pathway A2: reaction of 2-(1-phenylpentylideneamino)butan-1-ol under catalytic conditions (cat II, 0.5 mol%) Regardless whether the reaction was started from ketone and amino alcohol (A1, Supplementary Figure S11), or from the preformed Schiff base (A2, Supplementary Figure S11), nearly identical yields were obtained. This indicates that the imine formation is very fast. 1.1.3. Reactions which contradict Pathway B Supplementary Figure S12: Under catalytic conditions no reaction of 1-phenylethanol with 2- (phenylamino)ethanol is observed ATURE CHEMISTRY www.nature.com/naturechemistry 46 2013 Macmillan Publishers Limited. All rights reserved.

Supplementary Figure S13: Under catalytic conditions no reaction of 1-phenylethanol with tert-butyl-1- hydroxybutan-2-ylcarbamate o ß-alkylation between 1-phenylethanol and the -protected amino alcohol was observed, regardless which protecting group was chosen (Supplementary Figure S12 and Supplementary Figure S13). These experiments show that under the given reaction conditions the ß-alkylation is very unlikely to be the first reaction step (pathway B, Supplementary Figure S6) in the pyrrole syntheses. ATURE CHEMISTRY www.nature.com/naturechemistry 47 2013 Macmillan Publishers Limited. All rights reserved.

Crystal Structure of [(4-Ph)Tr(P( i Pr) 2 )(HP( i Pr) 2 )Ir(cod)]; (Catalyst II) Supplementary Figure S14: Crystal structure of catalyst II data_t257ofma1 _audit_creation_method SHELXL-97 _chemical_name_systematic ;? ; _chemical_name_common? _chemical_melting_point? _chemical_formula_moiety? _chemical_formula_sum 'C29 H46 Ir 5 P2' _chemical_formula_weight 718.85 loop atom_type_symbol _atom_type_description _atom_type_scat_dispersion_real _atom_type_scat_dispersion_imag _atom_type_scat_source 'C' 'C' 0.0033 0.0016 'International Tables Vol C Tables 4.2.6.8 and 6.1.1.4' 'H' 'H' 0.0000 0.0000 'International Tables Vol C Tables 4.2.6.8 and 6.1.1.4' '' '' 0.0061 0.0033 ATURE CHEMISTRY www.nature.com/naturechemistry 48 2013 Macmillan Publishers Limited. All rights reserved.

'International Tables Vol C Tables 4.2.6.8 and 6.1.1.4' 'P' 'P' 0.1023 0.0942 'International Tables Vol C Tables 4.2.6.8 and 6.1.1.4' 'Ir' 'Ir' -1.4442 7.9887 'International Tables Vol C Tables 4.2.6.8 and 6.1.1.4' _symmetry_cell_setting _symmetry_space_group_name_h-m orthorhombic Fdd2 loop symmetry_equiv_pos_as_xyz 'x, y, z' '-x, -y, z' '-x+1/4, y+1/4, z+1/4' 'x+1/4, -y+1/4, z+1/4' 'x, y+1/2, z+1/2' '-x, -y+1/2, z+1/2' '-x+1/4, y+3/4, z+3/4' 'x+1/4, -y+3/4, z+3/4' 'x+1/2, y, z+1/2' '-x+1/2, -y, z+1/2' '-x+3/4, y+1/4, z+3/4' 'x+3/4, -y+1/4, z+3/4' 'x+1/2, y+1/2, z' '-x+1/2, -y+1/2, z' '-x+3/4, y+3/4, z+1/4' 'x+3/4, -y+3/4, z+1/4' _cell_length_a 19.8530(11) _cell_length_b 42.232(2) _cell_length_c 14.7820(12) _cell_angle_alpha 90.00 _cell_angle_beta 90.00 _cell_angle_gamma 90.00 _cell_volume 12393.7(14) _cell_formula_units_z 16 _cell_measurement_temperature 133(2) _cell_measurement_reflns_used 22085 _cell_measurement_2theta_min 3.56 _cell_measurement_2theta_max 45.95 _exptl_crystal_description block _exptl_crystal_colour red _exptl_crystal_size_max 0.28 _exptl_crystal_size_mid 0.19 _exptl_crystal_size_min 0.17 _exptl_crystal_density_meas? _exptl_crystal_density_diffrn 1.541 _exptl_crystal_density_method 'not measured' _exptl_crystal_f_000 5792 _exptl_absorpt_coefficient_mu 4.438 _exptl_absorpt_correction_type numerical _exptl_absorpt_correction_t_min 0.1283 _exptl_absorpt_correction_t_max 0.2351 _exptl_absorpt_process_details? _exptl_special_details ;? ; _diffrn_ambient_temperature 133(2) _diffrn_radiation_wavelength 0.71069 ATURE CHEMISTRY www.nature.com/naturechemistry 49 2013 Macmillan Publishers Limited. All rights reserved.

_diffrn_radiation_type _diffrn_radiation_source _diffrn_radiation_monochromator _diffrn_measurement_device_type _diffrn_measurement_method _diffrn_detector_area_resol_mean? _diffrn_standards_number? _diffrn_standards_interval_count? _diffrn_standards_interval_time? _diffrn_standards_decay_%? _diffrn_reflns_number 19287 _diffrn_reflns_av_r_equivalents 0.1141 _diffrn_reflns_av_sigmai/neti 0.0946 _diffrn_reflns_limit_h_min -23 _diffrn_reflns_limit_h_max 23 _diffrn_reflns_limit_k_min -49 _diffrn_reflns_limit_k_max 49 _diffrn_reflns_limit_l_min -17 _diffrn_reflns_limit_l_max 17 _diffrn_reflns_theta_min 1.78 _diffrn_reflns_theta_max 24.73 _reflns_number_total 5231 _reflns_number_gt 3973 _reflns_threshold_expression >2\s(I) MoK\a 'fine-focus sealed tube' graphite STOE-IPDSII Omega-Scan _computing_data_collection X-AREA-STOE _computing_cell_refinement X-AREA-STOE _computing_data_reduction X-RED32 _computing_structure_solution SIR-97 _computing_structure_refinement 'SHELXL-97 (Sheldrick, 2008)' _computing_molecular_graphics? _computing_publication_material? _refine_special_details ; Refinement of F^2^ against ALL reflections. The weighted R-factor wr and goodness of fit S are based on F^2^, conventional R-factors R are based on F, with F set to zero for negative F^2^. The threshold expression of F^2^ > 2\s(F^2^) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F^2^ are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger. ; _refine_ls_structure_factor_coef Fsqd _refine_ls_matrix_type full _refine_ls_weighting_scheme calc _refine_ls_weighting_details 'calc w=1/[\s^2^(fo^2^)+(0.0846p)^2^+0.0000p] where P=(Fo^2^+2Fc^2^)/3' _atom_sites_solution_primary direct _atom_sites_solution_secondary difmap _atom_sites_solution_hydrogens geom _refine_ls_hydrogen_treatment constr _refine_ls_extinction_method none _refine_ls_extinction_coef? _refine_ls_abs_structure_details 'Flack H D (1983), Acta Cryst. A39, 876-881' _refine_ls_abs_structure_flack 0.014(17) _refine_ls_number_reflns 5231 _refine_ls_number_parameters 318 _refine_ls_number_restraints 4 _refine_ls_r_factor_all 0.0810 _refine_ls_r_factor_gt 0.0641 ATURE CHEMISTRY www.nature.com/naturechemistry 50 2013 Macmillan Publishers Limited. All rights reserved.

_refine_ls_wr_factor_ref 0.1499 _refine_ls_wr_factor_gt 0.1434 _refine_ls_goodness_of_fit_ref 0.980 _refine_ls_restrained_s_all 0.980 _refine_ls_shift/su_max 0.001 _refine_ls_shift/su_mean 0.000 loop atom_site_label _atom_site_type_symbol _atom_site_fract_x _atom_site_fract_y _atom_site_fract_z _atom_site_u_iso_or_equiv _atom_site_adp_type _atom_site_occupancy _atom_site_symmetry_multiplicity _atom_site_calc_flag _atom_site_refinement_flags _atom_site_disorder_assembly _atom_site_disorder_group Ir1 Ir 0.53224(3) 0.218670(14) 0.95948(4) 0.04982(18) Uani 1 1 d... P1 P 0.6362(2) 0.19443(9) 0.9383(2) 0.0486(9) Uani 1 1 d... P2 P 0.45130(18) 0.25714(9) 0.9615(4) 0.0572(10) Uani 1 1 d... 1 0.5797(6) 0.3074(3) 0.8350(9) 0.050(3) Uani 1 1 d... 2 0.6776(6) 0.2748(3) 0.8203(8) 0.045(3) Uani 1 1 d... 3 0.5774(6) 0.2527(4) 0.8955(8) 0.062(4) Uani 1 1 d... 4 0.6755(6) 0.2242(3) 0.8796(8) 0.049(3) Uani 1 1 d... H1 H 0.7167 0.2210 0.8595 0.058 Uiso 1 1 calc R.. 5 0.4842(7) 0.2877(3) 0.9047(10) 0.064(4) Uani 1 1 d... C1 C 0.4587(9) 0.1830(4) 0.9842(11) 0.060(3) Uani 1 1 d... H1 H 0.4118 0.1916 0.9846 0.072 Uiso 1 1 calc R.. C2 C 0.4931(9) 0.1892(4) 1.0643(12) 0.060(3) Uani 1 1 d... H2 H 0.4648 0.2015 1.1077 0.072 Uiso 1 1 calc R.. C3 C 0.5354(9) 0.1651(4) 1.1118(12) 0.066(3) Uani 1 1 d... H3A H 0.5653 0.1761 1.1551 0.079 Uiso 1 1 calc R.. H3B H 0.5643 0.1544 1.0667 0.079 Uiso 1 1 calc R.. C4 C 0.4951(11) 0.1399(4) 1.1631(13) 0.077(4) Uani 1 1 d D.. H4A H 0.5157 0.1367 1.2234 0.092 Uiso 1 1 calc R.. H4B H 0.4486 0.1477 1.1725 0.092 Uiso 1 1 calc R.. C5 C 0.4924(18) 0.1082(5) 1.1134(17) 0.141(9) Uani 1 1 d D.. H5 H 0.5150 0.0906 1.1391 0.169 Uiso 1 1 calc R.. C6 C 0.4574(15) 0.1041(6) 1.0302(18) 0.141(9) Uani 1 1 d D.. H6 H 0.4614 0.0836 1.0043 0.169 Uiso 1 1 calc R.. C7 C 0.4148(10) 0.1272(4) 0.9763(13) 0.077(4) Uani 1 1 d D.. H7A H 0.3821 0.1380 1.0164 0.092 Uiso 1 1 calc R.. H7B H 0.3895 0.1159 0.9284 0.092 Uiso 1 1 calc R.. C8 C 0.4644(9) 0.1520(4) 0.9331(11) 0.066(3) Uani 1 1 d... H8A H 0.5112 0.1440 0.9365 0.079 Uiso 1 1 calc R.. H8B H 0.4529 0.1553 0.8686 0.079 Uiso 1 1 calc R.. C9 C 0.5482(7) 0.2824(4) 0.8758(10) 0.050(4) Uani 1 1 d... C10 C 0.6435(8) 0.3017(3) 0.8063(9) 0.048(4) Uani 1 1 d... C11 C 0.6760(8) 0.3272(4) 0.7583(11) 0.054(4) Uani 1 1 d... C12 C 0.6648(8) 0.3581(4) 0.7817(11) 0.054(4) Uani 1 1 d... H12 H 0.6355 0.3630 0.8306 0.065 Uiso 1 1 calc R.. C13 C 0.6959(8) 0.3823(4) 0.7347(11) 0.058(4) Uani 1 1 d... H13 H 0.6885 0.4037 0.7523 0.070 Uiso 1 1 calc R.. C14 C 0.7375(9) 0.3758(5) 0.6628(14) 0.071(5) Uani 1 1 d... H14 H 0.7568 0.3927 0.6292 0.085 Uiso 1 1 calc R.. C15 C 0.7516(8) 0.3441(4) 0.6384(11) 0.057(4) Uani 1 1 d... H15 H 0.7812 0.3394 0.5896 0.068 Uiso 1 1 calc R.. C16 C 0.7221(8) 0.3206(4) 0.6859(10) 0.056(4) Uani 1 1 d... H16 H 0.7321 0.2992 0.6712 0.068 Uiso 1 1 calc R.. ATURE CHEMISTRY www.nature.com/naturechemistry 51 2013 Macmillan Publishers Limited. All rights reserved.

C17 C 0.6463(7) 0.2517(3) 0.8634(9) 0.043(3) Uani 1 1 d... C18 C 0.6799(10) 0.2193(4) 1.0952(14) 0.067(5) Uani 1 1 d... H18A H 0.7043 0.2170 1.1524 0.101 Uiso 1 1 calc R.. H18B H 0.6317 0.2217 1.1075 0.101 Uiso 1 1 calc R.. H18C H 0.6964 0.2381 1.0632 0.101 Uiso 1 1 calc R.. C19 C 0.7673(9) 0.1852(4) 1.0167(12) 0.066(5) Uani 1 1 d... H19A H 0.7840 0.2024 0.9784 0.099 Uiso 1 1 calc R.. H19B H 0.7730 0.1649 0.9851 0.099 Uiso 1 1 calc R.. H19C H 0.7928 0.1848 1.0734 0.099 Uiso 1 1 calc R.. C20 C 0.6117(9) 0.1606(5) 0.7832(13) 0.069(5) Uani 1 1 d... H20A H 0.6190 0.1410 0.7490 0.104 Uiso 1 1 calc R.. H20B H 0.6234 0.1788 0.7453 0.104 Uiso 1 1 calc R.. H20C H 0.5643 0.1620 0.8011 0.104 Uiso 1 1 calc R.. C21 C 0.3869(12) 0.2359(6) 0.8051(14) 0.093(7) Uani 1 1 d... H21A H 0.3460 0.2272 0.7775 0.140 Uiso 1 1 calc R.. H21B H 0.4202 0.2190 0.8125 0.140 Uiso 1 1 calc R.. H21C H 0.4055 0.2525 0.7659 0.140 Uiso 1 1 calc R.. C22 C 0.6525(9) 0.1278(4) 0.9120(12) 0.066(4) Uani 1 1 d... H22A H 0.6069 0.1241 0.9351 0.098 Uiso 1 1 calc R.. H22B H 0.6848 0.1268 0.9621 0.098 Uiso 1 1 calc R.. H22C H 0.6637 0.1115 0.8672 0.098 Uiso 1 1 calc R.. C23 C 0.3259(10) 0.2795(5) 0.8941(16) 0.090(7) Uani 1 1 d... H23A H 0.2886 0.2757 0.8520 0.136 Uiso 1 1 calc R.. H23B H 0.3529 0.2974 0.8725 0.136 Uiso 1 1 calc R.. H23C H 0.3078 0.2844 0.9542 0.136 Uiso 1 1 calc R.. C24 C 0.3734(11) 0.2565(5) 1.1188(14) 0.081(6) Uani 1 1 d... H24A H 0.3878 0.2344 1.1247 0.122 Uiso 1 1 calc R.. H24B H 0.3313 0.2574 1.0845 0.122 Uiso 1 1 calc R.. H24C H 0.3664 0.2656 1.1790 0.122 Uiso 1 1 calc R.. C25 C 0.4898(11) 0.2803(6) 1.1263(14) 0.087(6) Uani 1 1 d... H25A H 0.5221 0.2936 1.0937 0.131 Uiso 1 1 calc R.. H25B H 0.5106 0.2597 1.1393 0.131 Uiso 1 1 calc R.. H25C H 0.4771 0.2906 1.1831 0.131 Uiso 1 1 calc R.. C26 C 0.4280(9) 0.2754(5) 1.0689(12) 0.065(5) Uani 1 1 d... H26 H 0.4090 0.2968 1.0551 0.078 Uiso 1 1 calc R.. C27 C 0.6910(8) 0.1906(4) 1.0377(9) 0.047(3) Uani 1 1 d... H27 H 0.6749 0.1718 1.0730 0.056 Uiso 1 1 calc R.. C28 C 0.3694(9) 0.2503(5) 0.8997(12) 0.071(5) Uani 1 1 d... H28 H 0.3436 0.2339 0.9341 0.086 Uiso 1 1 calc R.. C29 C 0.6560(8) 0.1605(4) 0.8676(9) 0.049(4) Uani 1 1 d... H29 H 0.7034 0.1634 0.8464 0.058 Uiso 1 1 calc R.. loop atom_site_aniso_label _atom_site_aniso_u_11 _atom_site_aniso_u_22 _atom_site_aniso_u_33 _atom_site_aniso_u_23 _atom_site_aniso_u_13 _atom_site_aniso_u_12 Ir1 0.0451(3) 0.0567(3) 0.0476(3) 0.0048(3) 0.0019(3) 0.0001(3) P1 0.049(2) 0.056(2) 0.042(2) 0.0055(16) 0.0001(16) 0.0024(17) P2 0.052(2) 0.063(2) 0.056(2) 0.014(3) 0.008(3) 0.0036(17) 1 0.040(7) 0.046(7) 0.065(8) 0.005(6) 0.000(6) 0.009(6) 2 0.042(7) 0.039(7) 0.054(7) -0.001(5) 0.001(6) -0.007(5) 3 0.048(7) 0.088(10) 0.050(7) -0.039(7) -0.009(6) 0.025(7) 4 0.044(7) 0.057(8) 0.046(7) -0.008(6) 0.002(6) 0.003(6) 5 0.060(9) 0.071(10) 0.061(9) 0.006(7) 0.005(7) 0.006(7) C1 0.071(8) 0.042(6) 0.068(8) -0.004(5) -0.007(6) 0.010(6) C2 0.071(8) 0.042(6) 0.068(8) -0.004(5) -0.007(6) 0.010(6) C3 0.068(8) 0.069(8) 0.061(7) -0.010(6) 0.010(6) -0.009(6) C4 0.085(9) 0.070(8) 0.075(9) -0.012(7) 0.016(8) -0.014(7) C5 0.22(3) 0.080(12) 0.124(16) 0.006(12) 0.010(18) -0.044(14) ATURE CHEMISTRY www.nature.com/naturechemistry 52 2013 Macmillan Publishers Limited. All rights reserved.

C6 0.22(3) 0.080(12) 0.124(16) 0.006(12) 0.010(18) -0.044(14) C7 0.085(9) 0.070(8) 0.075(9) -0.012(7) 0.016(8) -0.014(7) C8 0.068(8) 0.069(8) 0.061(7) -0.010(6) 0.010(6) -0.009(6) C9 0.034(8) 0.069(10) 0.048(8) -0.005(8) 0.001(6) 0.000(8) C10 0.055(9) 0.048(9) 0.041(7) 0.005(6) -0.005(7) 0.000(7) C11 0.044(9) 0.068(11) 0.050(8) 0.005(8) -0.001(7) 0.000(8) C12 0.043(9) 0.066(11) 0.052(9) -0.008(8) -0.005(7) 0.005(8) C13 0.047(9) 0.068(10) 0.059(11) 0.010(8) -0.003(7) 0.014(8) C14 0.052(10) 0.074(13) 0.087(13) 0.015(10) -0.007(10) -0.021(9) C15 0.050(9) 0.072(12) 0.047(8) 0.000(8) 0.004(7) 0.007(9) C16 0.058(9) 0.052(8) 0.059(11) -0.002(7) -0.002(8) -0.002(8) C17 0.050(8) 0.043(8) 0.036(7) -0.015(6) -0.002(6) 0.012(7) C18 0.056(11) 0.074(12) 0.072(12) 0.011(10) -0.007(9) -0.004(9) C19 0.070(12) 0.064(11) 0.064(10) 0.013(8) -0.018(9) 0.003(9) C20 0.054(10) 0.077(12) 0.077(11) -0.013(10) -0.003(9) 0.000(9) C21 0.078(14) 0.13(2) 0.073(13) 0.016(13) -0.002(11) -0.006(14) C22 0.056(10) 0.066(11) 0.074(11) 0.007(9) 0.006(9) 0.002(9) C23 0.057(11) 0.106(16) 0.109(16) 0.059(14) -0.008(11) -0.003(11) C24 0.102(16) 0.056(11) 0.086(13) 0.008(10) 0.038(12) 0.006(11) C25 0.077(13) 0.113(17) 0.072(12) -0.023(12) -0.001(10) 0.020(13) C26 0.047(10) 0.079(12) 0.071(11) -0.002(9) 0.006(8) 0.007(9) C27 0.047(8) 0.053(9) 0.040(8) 0.005(7) 0.005(6) -0.005(7) C28 0.067(11) 0.087(13) 0.060(11) 0.011(9) 0.018(9) 0.012(10) C29 0.042(8) 0.058(9) 0.046(8) 0.006(7) 0.001(7) -0.003(7) _geom_special_details ; All s.u.'s (except the s.u. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell s.u.'s are taken into account individually in the estimation of s.u.'s in distances, angles and torsion angles; correlations between s.u.'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell s.u.'s is used for estimating s.u.'s involving l.s. planes. ; loop geom_bond_atom_site_label_1 _geom_bond_atom_site_label_2 _geom_bond_distance _geom_bond_site_symmetry_2 _geom_bond_publ_flag Ir1 3 1.941(16).? Ir1 C1 2.128(17).? Ir1 C2 2.133(18).? Ir1 P2 2.285(4).? Ir1 P1 2.324(4).? P1 4 1.715(13).? P1 C29 1.817(16).? P1 C27 1.836(15).? P2 5 1.671(15).? P2 C26 1.825(18).? P2 C28 1.887(19).? 1 C10 1.356(19).? 1 C9 1.37(2).? 2 C17 1.323(18).? 2 C10 1.337(19).? 3 C9 1.41(2).? 3 C17 1.447(19).? 4 C17 1.321(18).? 5 C9 1.36(2).? C1 C2 1.39(2).? C1 C8 1.52(2).? ATURE CHEMISTRY www.nature.com/naturechemistry 53 2013 Macmillan Publishers Limited. All rights reserved.

C2 C3 1.50(2).? C3 C4 1.53(2).? C4 C5 1.528(17).? C5 C6 1.422(18).? C6 C7 1.520(17).? C7 C8 1.57(2).? C10 C11 1.44(2).? C11 C12 1.37(2).? C11 C16 1.44(2).? C12 C13 1.38(2).? C13 C14 1.37(2).? C14 C15 1.42(3).? C15 C16 1.35(2).? C18 C27 1.50(2).? C19 C27 1.56(2).? C20 C29 1.53(2).? C21 C28 1.56(3).? C22 C29 1.53(2).? C23 C28 1.51(3).? C24 C26 1.54(3).? C25 C26 1.51(3).? loop geom_angle_atom_site_label_1 _geom_angle_atom_site_label_2 _geom_angle_atom_site_label_3 _geom_angle _geom_angle_site_symmetry_1 _geom_angle_site_symmetry_3 _geom_angle_publ_flag 3 Ir1 C1 157.6(5)..? 3 Ir1 C2 162.6(5)..? C1 Ir1 C2 38.1(6)..? 3 Ir1 P2 78.7(4)..? C1 Ir1 P2 91.1(5)..? C2 Ir1 P2 98.6(5)..? 3 Ir1 P1 81.4(4)..? C1 Ir1 P1 108.7(5)..? C2 Ir1 P1 99.4(5)..? P2 Ir1 P1 159.88(14)..? 4 P1 C29 100.8(6)..? 4 P1 C27 101.5(6)..? C29 P1 C27 105.2(7)..? 4 P1 Ir1 98.6(5)..? C29 P1 Ir1 128.1(5)..? C27 P1 Ir1 117.3(5)..? 5 P2 C26 102.1(8)..? 5 P2 C28 102.2(8)..? C26 P2 C28 105.5(8)..? 5 P2 Ir1 105.5(5)..? C26 P2 Ir1 119.3(6)..? C28 P2 Ir1 119.4(6)..? C10 1 C9 115.2(12)..? C17 2 C10 117.5(13)..? C9 3 C17 110.4(14)..? C9 3 Ir1 124.6(10)..? C17 3 Ir1 125.0(11)..? C17 4 P1 122.4(11)..? C9 5 P2 113.4(12)..? C2 C1 C8 123.3(15)..? C2 C1 Ir1 71.1(11)..? C8 C1 Ir1 118.3(11)..? C1 C2 C3 123.2(15)..? ATURE CHEMISTRY www.nature.com/naturechemistry 54 2013 Macmillan Publishers Limited. All rights reserved.

C1 C2 Ir1 70.7(10)..? C3 C2 Ir1 122.3(13)..? C2 C3 C4 114.3(16)..? C5 C4 C3 112.8(17)..? C6 C5 C4 123(3)..? C5 C6 C7 130(2)..? C6 C7 C8 107.0(17)..? C1 C8 C7 109.0(13)..? 5 C9 1 116.1(14)..? 5 C9 3 117.8(14)..? 1 C9 3 126.0(13)..? 2 C10 1 125.2(13)..? 2 C10 C11 118.9(14)..? 1 C10 C11 115.9(13)..? C12 C11 C16 118.5(15)..? C12 C11 C10 121.1(15)..? C16 C11 C10 120.4(15)..? C11 C12 C13 120.4(15)..? C14 C13 C12 120.7(18)..? C13 C14 C15 120.3(18)..? C16 C15 C14 118.4(15)..? C15 C16 C11 121.5(15)..? 4 C17 2 122.1(13)..? 4 C17 3 112.5(14)..? 2 C17 3 125.4(13)..? C25 C26 C24 112.0(17)..? C25 C26 P2 110.0(12)..? C24 C26 P2 112.1(13)..? C18 C27 C19 111.9(14)..? C18 C27 P1 107.1(11)..? C19 C27 P1 115.4(10)..? C23 C28 C21 113.3(17)..? C23 C28 P2 113.3(15)..? C21 C28 P2 107.5(13)..? C20 C29 C22 109.1(14)..? C20 C29 P1 110.1(11)..? C22 C29 P1 117.1(11)..? _diffrn_measured_fraction_theta_max 0.988 _diffrn_reflns_theta_full 24.73 _diffrn_measured_fraction_theta_full 0.988 _refine_diff_density_max 2.759 _refine_diff_density_min -0.805 _refine_diff_density_rms 0.177 ATURE CHEMISTRY www.nature.com/naturechemistry 55 2013 Macmillan Publishers Limited. All rights reserved.

Crystal Structure of [(4-Ph)Tr(HP(iPr) 2 )IrH 3 ] (catalyst resting state) Supplementary Figure S15. Crystal Structure of [(4-Ph)Tr(HP(iPr) 2 )IrH 3 ] data_t356hpma _audit_creation_method SHELXL-97 _chemical_name_systematic ;? ; _chemical_name_common? _chemical_melting_point? _chemical_formula_moiety? _chemical_formula_sum 'C33 H47 Ir 5 P2' _chemical_formula_weight 767.90 loop atom_type_symbol _atom_type_description _atom_type_scat_dispersion_real _atom_type_scat_dispersion_imag _atom_type_scat_source 'C' 'C' 0.0033 0.0016 ATURE CHEMISTRY www.nature.com/naturechemistry 60 2013 Macmillan Publishers Limited. All rights reserved.

'International Tables Vol C Tables 4.2.6.8 and 6.1.1.4' 'H' 'H' 0.0000 0.0000 'International Tables Vol C Tables 4.2.6.8 and 6.1.1.4' '' '' 0.0061 0.0033 'International Tables Vol C Tables 4.2.6.8 and 6.1.1.4' 'P' 'P' 0.1023 0.0942 'International Tables Vol C Tables 4.2.6.8 and 6.1.1.4' 'Ir' 'Ir' -1.4442 7.9887 'International Tables Vol C Tables 4.2.6.8 and 6.1.1.4' _symmetry_cell_setting trigonal _symmetry_space_group_name_h-m P3(2) loop symmetry_equiv_pos_as_xyz 'x, y, z' '-y, x-y, z+2/3' '-x+y, -x, z+1/3' _cell_length_a 23.0010(4) _cell_length_b 23.0010(4) _cell_length_c 17.6210(3) _cell_angle_alpha 90.00 _cell_angle_beta 90.00 _cell_angle_gamma 120.00 _cell_volume 8073.4(2) _cell_formula_units_z 9 _cell_measurement_temperature 133(2) _cell_measurement_reflns_used 115727 _cell_measurement_2theta_min 2.31 _cell_measurement_2theta_max 51.92 _exptl_crystal_description prism _exptl_crystal_colour orange _exptl_crystal_size_max 0.44 _exptl_crystal_size_mid 0.21 _exptl_crystal_size_min 0.18 _exptl_crystal_density_meas? _exptl_crystal_density_diffrn 1.421 _exptl_crystal_density_method 'not measured' _exptl_crystal_f_000 3483 _exptl_absorpt_coefficient_mu 3.838 _exptl_absorpt_correction_type numerical _exptl_absorpt_correction_t_min 0.2158 _exptl_absorpt_correction_t_max 0.5425 _exptl_absorpt_process_details? _exptl_special_details ;? ; ATURE CHEMISTRY www.nature.com/naturechemistry 61 2013 Macmillan Publishers Limited. All rights reserved.

_diffrn_ambient_temperature 133(2) _diffrn_radiation_wavelength 0.71069 _diffrn_radiation_type MoK\a _diffrn_radiation_source 'fine-focus sealed tube' _diffrn_radiation_monochromator graphite _diffrn_measurement_device_type STOE-IPDSII _diffrn_measurement_method Omega-Scan _diffrn_detector_area_resol_mean? _diffrn_standards_number? _diffrn_standards_interval_count? _diffrn_standards_interval_time? _diffrn_standards_decay_%? _diffrn_reflns_number 57204 _diffrn_reflns_av_r_equivalents 0.0458 _diffrn_reflns_av_sigmai/neti 0.0504 _diffrn_reflns_limit_h_min -27 _diffrn_reflns_limit_h_max 27 _diffrn_reflns_limit_k_min -27 _diffrn_reflns_limit_k_max 27 _diffrn_reflns_limit_l_min -21 _diffrn_reflns_limit_l_max 21 _diffrn_reflns_theta_min 1.16 _diffrn_reflns_theta_max 25.55 _reflns_number_total 19972 _reflns_number_gt 18848 _reflns_threshold_expression >2\s(I) _computing_data_collection X-AREA-STOE _computing_cell_refinement X-AREA-STOE _computing_data_reduction X-AREA-STOE _computing_structure_solution SIR-97 _computing_structure_refinement 'SHELXL-97 (Sheldrick, 2008)' _computing_molecular_graphics? _computing_publication_material? _refine_special_details ; Refinement of F^2^ against ALL reflections. The weighted R-factor wr and goodness of fit S are based on F^2^, conventional R-factors R are based on F, with F set to zero for negative F^2^. The threshold expression of F^2^ > 2\s(F^2^) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F^2^ are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger. ; _refine_ls_structure_factor_coef Fsqd _refine_ls_matrix_type fullcycle _refine_ls_weighting_scheme calc _refine_ls_weighting_details ATURE CHEMISTRY www.nature.com/naturechemistry 62 2013 Macmillan Publishers Limited. All rights reserved.

'calc w=1/[\s^2^(fo^2^)+(0.0414p)^2^+0.0000p] where P=(Fo^2^+2Fc^2^)/3' _atom_sites_solution_primary direct _atom_sites_solution_secondary difmap _atom_sites_solution_hydrogens geom _refine_ls_hydrogen_treatment constr _refine_ls_extinction_method none _refine_ls_extinction_coef? _refine_ls_abs_structure_details 'Flack H D (1983), Acta Cryst. A39, 876-881' _refine_ls_abs_structure_flack -0.014(5) _refine_ls_number_reflns 19972 _refine_ls_number_parameters 881 _refine_ls_number_restraints 1 _refine_ls_r_factor_all 0.0328 _refine_ls_r_factor_gt 0.0303 _refine_ls_wr_factor_ref 0.0647 _refine_ls_wr_factor_gt 0.0641 _refine_ls_goodness_of_fit_ref 0.958 _refine_ls_restrained_s_all 0.958 _refine_ls_shift/su_max 0.003 _refine_ls_shift/su_mean 0.000 loop atom_site_label _atom_site_type_symbol _atom_site_fract_x _atom_site_fract_y _atom_site_fract_z _atom_site_u_iso_or_equiv _atom_site_adp_type _atom_site_occupancy _atom_site_symmetry_multiplicity _atom_site_calc_flag _atom_site_refinement_flags _atom_site_disorder_assembly _atom_site_disorder_group C1 C 0.9919(5) 0.9642(5) 0.0427(6) 0.029(2) Uani 1 1 d... C2 C 1.0124(5) 1.0566(5) -0.0243(5) 0.033(2) Uani 1 1 d... C3 C 1.0410(5) 1.1308(5) -0.0286(6) 0.035(2) Uani 1 1 d... C4 C 1.0156(5) 1.1581(4) -0.0795(6) 0.036(2) Uani 1 1 d... H4 H 0.9803 1.1297-0.1129 0.044 Uiso 1 1 calc R.. C5 C 1.0419(5) 1.2277(5) -0.0816(7) 0.051(3) Uani 1 1 d... H5 H 1.0226 1.2464-0.1140 0.061 Uiso 1 1 calc R.. C6 C 1.0953(6) 1.2684(5) -0.0369(7) 0.054(3) Uani 1 1 d... H6 H 1.1148 1.3157-0.0411 0.065 Uiso 1 1 calc R.. C7 C 1.1220(6) 1.2423(5) 0.0147(6) 0.046(3) Uani 1 1 d... H7 H 1.1590 1.2713 0.0458 0.056 Uiso 1 1 calc R.. C8 C 1.0935(5) 1.1723(5) 0.0200(6) 0.043(3) Uani 1 1 d... H8 H 1.1098 1.1534 0.0564 0.052 Uiso 1 1 calc R.. C9 C 0.9581(4) 0.9561(4) -0.0816(5) 0.0248(18) Uani 1 1 d... C10 C 0.7794(6) 0.8481(6) -0.1221(8) 0.057(3) Uani 1 1 d... ATURE CHEMISTRY www.nature.com/naturechemistry 63 2013 Macmillan Publishers Limited. All rights reserved.

H10A H 0.7309 0.8286-0.1296 0.085 Uiso 1 1 calc R.. H10B H 0.8031 0.8921-0.1470 0.085 Uiso 1 1 calc R.. H10C H 0.7895 0.8535-0.0677 0.085 Uiso 1 1 calc R.. C11 C 0.7532(5) 0.7295(5) -0.1311(7) 0.052(3) Uani 1 1 d... H11A H 0.7527 0.7273-0.0755 0.078 Uiso 1 1 calc R.. H11B H 0.7677 0.6992-0.1516 0.078 Uiso 1 1 calc R.. H11C H 0.7081 0.7159-0.1497 0.078 Uiso 1 1 calc R.. C12 C 0.9010(6) 0.8231(5) 0.1913(7) 0.046(3) Uani 1 1 d... H12 H 0.9282 0.8289 0.2379 0.055 Uiso 1 1 calc R.. C13 C 0.8456(7) 0.7488(6) 0.1849(7) 0.059(4) Uani 1 1 d... H13A H 0.8168 0.7360 0.2300 0.089 Uiso 1 1 calc R.. H13B H 0.8663 0.7205 0.1813 0.089 Uiso 1 1 calc R.. H13C H 0.8185 0.7425 0.1395 0.089 Uiso 1 1 calc R.. C14 C 0.8681(6) 0.8646(5) 0.1990(7) 0.051(3) Uani 1 1 d... H14A H 0.8493 0.8669 0.1500 0.077 Uiso 1 1 calc R.. H14B H 0.9014 0.9100 0.2154 0.077 Uiso 1 1 calc R.. H14C H 0.8321 0.8442 0.2368 0.077 Uiso 1 1 calc R.. C15 C 1.0845(7) 0.8670(7) 0.0885(8) 0.064(4) Uani 1 1 d... H15A H 1.1229 0.8669 0.1124 0.097 Uiso 1 1 calc R.. H15B H 1.0960 0.9133 0.0775 0.097 Uiso 1 1 calc R.. H15C H 1.0731 0.8412 0.0412 0.097 Uiso 1 1 calc R.. C16 C 1.0037(8) 0.7625(6) 0.1583(8) 0.077(4) Uani 1 1 d... H16A H 0.9932 0.7372 0.1107 0.116 Uiso 1 1 calc R.. H16B H 0.9639 0.7430 0.1909 0.116 Uiso 1 1 calc R.. H16C H 1.0403 0.7603 0.1843 0.116 Uiso 1 1 calc R.. C17 C 0.9997(5) 0.8490(6) -0.2207(8) 0.055(3) Uani 1 1 d... H17A H 1.0187 0.8400-0.1754 0.082 Uiso 1 1 calc R.. H17B H 1.0137 0.8968-0.2226 0.082 Uiso 1 1 calc R.. H17C H 1.0158 0.8368-0.2661 0.082 Uiso 1 1 calc R.. C18 C 0.8993(7) 0.7311(6) -0.2167(7) 0.059(4) Uani 1 1 d... H18A H 0.9226 0.7213-0.2569 0.088 Uiso 1 1 calc R.. H18B H 0.8508 0.7051-0.2253 0.088 Uiso 1 1 calc R.. H18C H 0.9099 0.7190-0.1674 0.088 Uiso 1 1 calc R.. C19 C 0.6872(6) 0.4896(6) 0.5157(7) 0.051(3) Uani 1 1 d... H19A H 0.7083 0.5075 0.4665 0.076 Uiso 1 1 calc R.. H19B H 0.6939 0.4522 0.5301 0.076 Uiso 1 1 calc R.. H19C H 0.7074 0.5251 0.5542 0.076 Uiso 1 1 calc R.. C20 C 0.5996(8) 0.5239(7) 0.5042(10) 0.078(5) Uani 1 1 d... H20A H 0.6241 0.5563 0.5446 0.117 Uiso 1 1 calc R.. H20B H 0.5514 0.5076 0.5093 0.117 Uiso 1 1 calc R.. H20C H 0.6152 0.5457 0.4547 0.117 Uiso 1 1 calc R.. C21 C 0.4443(5) 0.3875(6) 0.4360(7) 0.056(3) Uani 1 1 d... H21A H 0.4443 0.3948 0.3812 0.084 Uiso 1 1 calc R.. H21B H 0.4636 0.4306 0.4625 0.084 Uiso 1 1 calc R.. H21C H 0.3980 0.3582 0.4534 0.084 Uiso 1 1 calc R.. C22 C 0.4563(5) 0.2868(5) 0.4143(7) 0.047(3) Uani 1 1 d... H22A H 0.4073 0.2651 0.4151 0.071 Uiso 1 1 calc R.. H22B H 0.4703 0.2584 0.4409 0.071 Uiso 1 1 calc R.. H22C H 0.4720 0.2931 0.3616 0.071 Uiso 1 1 calc R.. C23 C 0.6318(5) 0.3415(4) 0.3719(6) 0.031(2) Uani 1 1 d... C24 C 0.6796(4) 0.2885(5) 0.3126(5) 0.031(2) Uani 1 1 d... ATURE CHEMISTRY www.nature.com/naturechemistry 64 2013 Macmillan Publishers Limited. All rights reserved.

C25 C 0.6654(4) 0.3654(4) 0.2487(5) 0.028(2) Uani 1 1 d... C26 C 0.3930(6) 0.8843(6) 0.1820(7) 0.059(3) Uani 1 1 d... H26A H 0.4282 0.9235 0.1552 0.088 Uiso 1 1 calc R.. H26B H 0.4083 0.8521 0.1912 0.088 Uiso 1 1 calc R.. H26C H 0.3834 0.8985 0.2305 0.088 Uiso 1 1 calc R.. C27 C 0.2937(5) 0.6702(5) 0.3591(6) 0.032(2) Uani 1 1 d... C28 C 0.1851(5) 0.6536(5) 0.0862(7) 0.047(3) Uani 1 1 d... H28A H 0.1691 0.6323 0.1359 0.071 Uiso 1 1 calc R.. H28B H 0.2220 0.6471 0.0693 0.071 Uiso 1 1 calc R.. H28C H 0.1482 0.6332 0.0495 0.071 Uiso 1 1 calc R.. C29 C 0.3215(6) 0.8106(6) 0.4992(7) 0.051(3) Uani 1 1 d... H29A H 0.3401 0.8340 0.4512 0.077 Uiso 1 1 calc R.. H29B H 0.3385 0.7799 0.5094 0.077 Uiso 1 1 calc R.. H29C H 0.3349 0.8434 0.5404 0.077 Uiso 1 1 calc R.. C30 C 0.1486(7) 0.7364(8) 0.1008(9) 0.060(4) Uani 1 1 d... H30A H 0.1176 0.7139 0.0586 0.089 Uiso 1 1 calc R.. H30B H 0.1630 0.7843 0.1003 0.089 Uiso 1 1 calc R.. H30C H 0.1260 0.7165 0.1489 0.089 Uiso 1 1 calc R.. C31 C 0.2157(7) 0.8163(7) 0.4960(9) 0.061(4) Uani 1 1 d... H31A H 0.2339 0.8463 0.5399 0.091 Uiso 1 1 calc R.. H31B H 0.1667 0.7898 0.5001 0.091 Uiso 1 1 calc R.. H31C H 0.2279 0.8431 0.4493 0.091 Uiso 1 1 calc R.. C32 C 0.5394(6) 0.3529(6) 0.0961(7) 0.048(3) Uani 1 1 d... H32A H 0.5200 0.3323 0.1452 0.072 Uiso 1 1 calc R.. H32B H 0.5683 0.3358 0.0778 0.072 Uiso 1 1 calc R.. H32C H 0.5033 0.3416 0.0594 0.072 Uiso 1 1 calc R.. C33 C 0.7731(5) 0.5574(5) 0.2011(7) 0.049(3) Uani 1 1 d... H33A H 0.8126 0.5939 0.1761 0.073 Uiso 1 1 calc R.. H33B H 0.7819 0.5209 0.2135 0.073 Uiso 1 1 calc R.. H33C H 0.7636 0.5742 0.2479 0.073 Uiso 1 1 calc R.. C34 C 0.1141(6) 0.5803(5) 0.4039(7) 0.051(3) Uani 1 1 d... H34A H 0.0709 0.5441 0.4225 0.076 Uiso 1 1 calc R.. H34B H 0.1496 0.5702 0.4165 0.076 Uiso 1 1 calc R.. H34C H 0.1119 0.5842 0.3487 0.076 Uiso 1 1 calc R.. C35 C 0.0750(5) 0.6622(6) 0.4197(8) 0.065(3) Uani 1 1 d... H35A H 0.0743 0.6674 0.3646 0.097 Uiso 1 1 calc R.. H35B H 0.0847 0.7042 0.4447 0.097 Uiso 1 1 calc R.. H35C H 0.0311 0.6260 0.4367 0.097 Uiso 1 1 calc R.. C36 C 0.2999(8) 0.8961(7) 0.1268(10) 0.089(5) Uani 1 1 d... H36A H 0.2878 0.9044 0.1774 0.133 Uiso 1 1 calc R.. H36B H 0.2596 0.8745 0.0949 0.133 Uiso 1 1 calc R.. H36C H 0.3329 0.9388 0.1039 0.133 Uiso 1 1 calc R.. C37 C 0.3612(5) 0.6392(5) 0.2958(5) 0.030(2) Uani 1 1 d... C38 C 0.3235(4) 0.6984(5) 0.2330(5) 0.0279(19) Uani 1 1 d... C39 C 0.6978(6) 0.5871(6) 0.1267(8) 0.060(3) Uani 1 1 d... H39A H 0.6746 0.5949 0.1687 0.090 Uiso 1 1 calc R.. H39B H 0.6687 0.5726 0.0818 0.090 Uiso 1 1 calc R.. H39C H 0.7395 0.6287 0.1152 0.090 Uiso 1 1 calc R.. C40 C 0.5348(6) 0.4578(7) 0.1107(7) 0.052(3) Uani 1 1 d... H40A H 0.5051 0.4432 0.0664 0.078 Uiso 1 1 calc R.. H40B H 0.5609 0.5069 0.1121 0.078 Uiso 1 1 calc R.. ATURE CHEMISTRY www.nature.com/naturechemistry 65 2013 Macmillan Publishers Limited. All rights reserved.

H40C H 0.5079 0.4411 0.1571 0.078 Uiso 1 1 calc R.. C41 C 0.8021(5) 0.8016(5) -0.1567(7) 0.042(2) Uani 1 1 d... H41 H 0.7988 0.8033-0.2132 0.051 Uiso 1 1 calc R.. C42 C 0.5817(5) 0.4304(5) 0.1054(7) 0.033(3) Uani 1 1 d... H42 H 0.6091 0.4490 0.0582 0.040 Uiso 1 1 calc R.. C43 C 1.0254(6) 0.8357(5) 0.1413(6) 0.045(3) Uani 1 1 d... H43 H 1.0405 0.8606 0.1904 0.053 Uiso 1 1 calc R.. C44 C 0.9226(6) 0.8071(5) -0.2175(7) 0.036(2) Uani 1 1 d... H44 H 0.9040 0.8169-0.2640 0.043 Uiso 1 1 calc R.. C45 C 0.6120(6) 0.4648(6) 0.5103(7) 0.043(3) Uani 1 1 d... H45 H 0.5895 0.4387 0.5572 0.051 Uiso 1 1 calc R.. C46 C 0.4862(5) 0.3541(5) 0.4532(6) 0.041(2) Uani 1 1 d... H46 H 0.4845 0.3463 0.5092 0.050 Uiso 1 1 calc R.. C47 C 0.4676(6) 0.5341(7) 0.2967(7) 0.062(3) Uani 1 1 d... H47 H 0.4893 0.5082 0.2934 0.075 Uiso 1 1 calc R.. C48 C 0.4899(6) 0.5879(6) 0.2537(7) 0.057(3) Uani 1 1 d... H48 H 0.5302 0.6041 0.2254 0.068 Uiso 1 1 calc R.. C49 C 0.4528(5) 0.6203(6) 0.2508(6) 0.050(3) Uani 1 1 d... H49 H 0.4652 0.6557 0.2153 0.060 Uiso 1 1 calc R.. C50 C 0.3991(5) 0.6030(5) 0.2973(5) 0.036(2) Uani 1 1 d... C51 C 0.3793(5) 0.5492(5) 0.3467(6) 0.045(2) Uani 1 1 d... H51 H 0.3426 0.5365 0.3804 0.053 Uiso 1 1 calc R.. C52 C 0.4152(6) 0.5137(6) 0.3458(7) 0.062(3) Uani 1 1 d... H52 H 0.4029 0.4765 0.3786 0.075 Uiso 1 1 calc R.. C53 C 0.7142(5) 0.5318(4) 0.1493(6) 0.042(2) Uani 1 1 d... H53 H 0.7272 0.5176 0.1016 0.050 Uiso 1 1 calc R.. C54 C 0.7009(5) 0.2371(5) 0.3142(5) 0.032(2) Uani 1 1 d... C55 C 0.7549(5) 0.2458(5) 0.2705(5) 0.037(2) Uani 1 1 d... H55 H 0.7766 0.2830 0.2371 0.044 Uiso 1 1 calc R.. C56 C 0.7773(5) 0.1996(5) 0.2757(6) 0.037(2) Uani 1 1 d... H56 H 0.8151 0.2067 0.2468 0.045 Uiso 1 1 calc R.. C57 C 0.7452(6) 0.1436(5) 0.3224(6) 0.052(3) Uani 1 1 d... H57 H 0.7594 0.1113 0.3244 0.062 Uiso 1 1 calc R.. C58 C 0.6924(5) 0.1366(5) 0.3657(6) 0.042(2) Uani 1 1 d... H58 H 0.6707 0.0995 0.3992 0.051 Uiso 1 1 calc R.. C59 C 0.6696(5) 0.1828(5) 0.3617(6) 0.043(2) Uani 1 1 d... H59 H 0.6326 0.1766 0.3919 0.052 Uiso 1 1 calc R.. C60 C 0.2442(5) 0.7702(6) 0.4939(8) 0.041(3) Uani 1 1 d... H60 H 0.2278 0.7419 0.5407 0.050 Uiso 1 1 calc R.. C61 C 0.1291(5) 0.6451(6) 0.4404(6) 0.047(3) Uani 1 1 d... H61 H 0.1284 0.6391 0.4967 0.056 Uiso 1 1 calc R.. C62 C 0.3292(6) 0.8511(6) 0.1334(6) 0.049(3) Uani 1 1 d... H62 H 0.3421 0.8445 0.0812 0.058 Uiso 1 1 calc R.. C63 C 0.2095(6) 0.7277(7) 0.0925(7) 0.047(3) Uani 1 1 d... H63 H 0.2330 0.7499 0.0442 0.056 Uiso 1 1 calc R.. C64 C 0.6475(4) 0.5332(3) 0.7104(5) 0.059(3) Uiso 1 1 d G.. H64 H 0.6532 0.4955 0.7186 0.071 Uiso 1 1 calc R.. C65 C 0.5838(3) 0.5257(3) 0.7136(5) 0.073(3) Uiso 1 1 d G.. H65 H 0.5459 0.4830 0.7239 0.088 Uiso 1 1 calc R.. C66 C 0.5754(3) 0.5808(3) 0.7016(5) 0.058(3) Uiso 1 1 d G.. H66 H 0.5318 0.5757 0.7037 0.069 Uiso 1 1 calc R.. ATURE CHEMISTRY www.nature.com/naturechemistry 66 2013 Macmillan Publishers Limited. All rights reserved.

C67 C 0.6308(3) 0.6434(3) 0.6864(5) 0.057(3) Uiso 1 1 d G.. H67 H 0.6251 0.6810 0.6782 0.068 Uiso 1 1 calc R.. C68 C 0.6946(3) 0.6508(3) 0.6833(5) 0.065(3) Uiso 1 1 d G.. H68 H 0.7324 0.6936 0.6729 0.078 Uiso 1 1 calc R.. C69 C 0.7029(3) 0.5957(4) 0.6953(5) 0.061(3) Uiso 1 1 d G.. H69 H 0.7465 0.6008 0.6931 0.073 Uiso 1 1 calc R.. C70 C 0.1973(4) 0.7961(3) 0.7083(5) 0.090(4) Uiso 1 1 d G.. H70 H 0.1675 0.7492 0.7032 0.108 Uiso 1 1 calc R.. C71 C 0.2662(4) 0.8219(4) 0.7033(5) 0.060(3) Uiso 1 1 d G.. H71 H 0.2835 0.7926 0.6948 0.072 Uiso 1 1 calc R.. C72 C 0.3098(3) 0.8906(4) 0.7108(5) 0.074(3) Uiso 1 1 d G.. H72 H 0.3569 0.9082 0.7074 0.088 Uiso 1 1 calc R.. C73 C 0.2845(4) 0.9334(3) 0.7233(6) 0.106(5) Uiso 1 1 d G.. H73 H 0.3143 0.9803 0.7284 0.127 Uiso 1 1 calc R.. C74 C 0.2156(5) 0.9076(4) 0.7283(6) 0.093(4) Uiso 1 1 d G.. H74 H 0.1982 0.9369 0.7368 0.111 Uiso 1 1 calc R.. C75 C 0.1720(3) 0.8389(5) 0.7208(6) 0.081(4) Uiso 1 1 d G.. H75 H 0.1249 0.8213 0.7242 0.097 Uiso 1 1 calc R.. C76 C 0.5897(3) 0.0783(4) 0.5541(6) 0.078(3) Uiso 1 1 d G.. H76 H 0.6371 0.1028 0.5486 0.093 Uiso 1 1 calc R.. C77 C 0.5553(4) 0.0087(4) 0.5499(6) 0.074(3) Uiso 1 1 d G.. H77 H 0.5792-0.0145 0.5415 0.089 Uiso 1 1 calc R.. C78 C 0.4859(4) -0.0271(3) 0.5580(5) 0.075(3) Uiso 1 1 d G.. H78 H 0.4624-0.0747 0.5551 0.090 Uiso 1 1 calc R.. C79 C 0.4509(3) 0.0068(4) 0.5702(5) 0.080(4) Uiso 1 1 d G.. H79 H 0.4034-0.0177 0.5757 0.096 Uiso 1 1 calc R.. C80 C 0.4852(4) 0.0765(4) 0.5744(6) 0.086(4) Uiso 1 1 d G.. H80 H 0.4613 0.0996 0.5827 0.103 Uiso 1 1 calc R.. C81 C 0.5546(4) 0.1122(3) 0.5663(5) 0.064(3) Uiso 1 1 d G.. H81 H 0.5781 0.1599 0.5692 0.077 Uiso 1 1 calc R.. C82 C 0.9606(4) 0.7725(3) 0.5797(5) 0.068(3) Uiso 1 1 d G.. H82 H 0.9692 0.8174 0.5786 0.081 Uiso 1 1 calc R.. C83 C 0.8953(3) 0.7194(4) 0.5714(5) 0.077(4) Uiso 1 1 d G.. H83 H 0.8594 0.7280 0.5647 0.092 Uiso 1 1 calc R.. C84 C 0.8827(3) 0.6537(3) 0.5730(6) 0.077(4) Uiso 1 1 d G.. H84 H 0.8381 0.6174 0.5674 0.093 Uiso 1 1 calc R.. C85 C 0.9353(4) 0.6410(3) 0.5828(6) 0.081(4) Uiso 1 1 d G.. H85 H 0.9267 0.5961 0.5839 0.097 Uiso 1 1 calc R.. C86 C 1.0006(4) 0.6941(4) 0.5911(6) 0.082(4) Uiso 1 1 d G.. H86 H 1.0366 0.6854 0.5978 0.099 Uiso 1 1 calc R.. C87 C 1.0132(3) 0.7598(4) 0.5896(6) 0.084(4) Uiso 1 1 d G.. H87 H 1.0578 0.7961 0.5952 0.101 Uiso 1 1 calc R.. C88 C 0.0387(4) 0.6652(4) 0.9176(6) 0.103(5) Uiso 1 1 d G.. H88 H -0.0060 0.6295 0.9248 0.123 Uiso 1 1 calc R.. C89 C 0.0902(5) 0.6513(4) 0.9049(6) 0.079(4) Uiso 1 1 d G.. H89 H 0.0806 0.6060 0.9035 0.094 Uiso 1 1 calc R.. C90 C 0.1555(4) 0.7035(5) 0.8944(6) 0.091(4) Uiso 1 1 d G.. H90 H 0.1907 0.6939 0.8857 0.110 Uiso 1 1 calc R.. C91 C 0.1695(4) 0.7696(4) 0.8965(7) 0.115(5) Uiso 1 1 d G.. H91 H 0.2142 0.8053 0.8893 0.138 Uiso 1 1 calc R.. C92 C 0.1181(5) 0.7836(4) 0.9091(6) 0.097(5) Uiso 1 1 d G.. ATURE CHEMISTRY www.nature.com/naturechemistry 67 2013 Macmillan Publishers Limited. All rights reserved.

H92 H 0.1276 0.8288 0.9106 0.116 Uiso 1 1 calc R.. C93 C 0.0527(5) 0.7314(5) 0.9197(6) 0.090(4) Uiso 1 1 d G.. H93 H 0.0175 0.7409 0.9283 0.108 Uiso 1 1 calc R.. C94 C 0.8754(6) 0.7901(3) 0.3895(7) 0.107(5) Uiso 1 1 d G.. H94 H 0.9002 0.8377 0.3919 0.128 Uiso 1 1 calc R.. C95 C 0.9086(4) 0.7540(4) 0.3801(6) 0.092(4) Uiso 1 1 d G.. H95 H 0.9561 0.7770 0.3759 0.111 Uiso 1 1 calc R.. C96 C 0.8722(5) 0.6843(4) 0.3767(6) 0.093(4) Uiso 1 1 d G.. H96 H 0.8949 0.6597 0.3702 0.112 Uiso 1 1 calc R.. C97 C 0.8027(5) 0.6507(3) 0.3828(6) 0.076(3) Uiso 1 1 d G.. H97 H 0.7778 0.6030 0.3805 0.091 Uiso 1 1 calc R.. C98 C 0.7695(4) 0.6867(5) 0.3922(6) 0.112(5) Uiso 1 1 d G.. H98 H 0.7219 0.6637 0.3964 0.134 Uiso 1 1 calc R.. C99 C 0.8058(6) 0.7564(5) 0.3956(7) 0.117(6) Uiso 1 1 d G.. H99 H 0.7831 0.7810 0.4021 0.140 Uiso 1 1 calc R.. 1 0.9606(4) 0.9234(4) -0.0174(4) 0.0296(16) Uani 1 1 d... 2 0.9843(4) 1.0228(4) -0.0871(5) 0.0306(17) Uani 1 1 d... 3 1.0196(3) 1.0322(3) 0.0418(5) 0.0269(16) Uani 1 1 d... 4 0.9277(4) 0.9151(4) -0.1430(4) 0.0297(17) Uani 1 1 d... H4A H 0.9276 0.9328-0.1873 0.036 Uiso 1 1 calc... 5 0.9946(4) 0.9327(4) 0.1049(5) 0.0323(18) Uani 1 1 d... H5A H 1.0158 0.9562 0.1453 0.039 Uiso 1 1 calc... 6 0.2919(4) 0.7002(4) 0.2959(5) 0.0315(17) Uani 1 1 d... 7 0.3590(4) 0.6676(4) 0.2310(5) 0.0327(17) Uani 1 1 d... 8 0.3297(4) 0.6385(4) 0.3614(5) 0.0280(16) Uani 1 1 d... 9 0.3177(4) 0.7295(4) 0.1702(5) 0.0336(18) Uani 1 1 d... H9 H 0.3391 0.7305 0.1284 0.040 Uiso 1 1 calc... 10 0.2617(4) 0.6743(4) 0.4181(5) 0.0334(18) Uani 1 1 d... H10 H 0.2647 0.6571 0.4615 0.040 Uiso 1 1 calc... 11 0.6366(4) 0.3774(4) 0.3096(4) 0.0336(19) Uani 1 1 d... 12 0.6871(4) 0.3211(4) 0.2479(5) 0.0286(17) Uani 1 1 d... 13 0.6525(4) 0.2967(4) 0.3767(4) 0.0277(16) Uani 1 1 d... 14 0.6703(4) 0.4024(4) 0.1849(5) 0.0310(18) Uani 1 1 d... H14 H 0.6891 0.3980 0.1435 0.037 Uiso 1 1 calc... 15 0.6058(4) 0.3548(4) 0.4335(5) 0.0311(17) Uani 1 1 d... H15 H 0.6045 0.3357 0.4773 0.037 Uiso 1 1 calc... P1 P 0.88910(13) 0.82826(12) -0.13308(14) 0.0328(5) Uani 1 1 d... P2 P 0.95640(15) 0.84538(14) 0.10707(15) 0.0355(6) Uani 1 1 d... P3 P 0.26845(15) 0.76760(14) 0.17158(16) 0.0359(6) Uani 1 1 d... P4 P 0.21326(13) 0.71265(14) 0.41332(14) 0.0341(5) Uani 1 1 d... P5 P 0.63988(12) 0.45757(12) 0.18585(14) 0.0330(5) Uani 1 1 d... P6 P 0.57469(13) 0.40947(12) 0.42648(17) 0.0327(6) Uani 1 1 d... Ir1 Ir 0.91608(4) 0.820888(17) -0.012122(15) 0.03438(10) Uani 1 1 d... Ir2 Ir 0.23332(3) 0.74869(3) 0.292513(18) 0.03516(10) Uani 1 1 d... Ir3 Ir 0.602948(17) 0.444914(17) 0.30609(3) 0.03180(7) Uani 1 1 d... loop atom_site_aniso_label _atom_site_aniso_u_11 _atom_site_aniso_u_22 _atom_site_aniso_u_33 ATURE CHEMISTRY www.nature.com/naturechemistry 68 2013 Macmillan Publishers Limited. All rights reserved.

_atom_site_aniso_u_23 _atom_site_aniso_u_13 _atom_site_aniso_u_12 C1 0.038(5) 0.040(5) 0.024(5) -0.002(4) -0.001(4) 0.030(4) C2 0.040(5) 0.038(5) 0.023(5) -0.002(4) 0.011(4) 0.020(4) C3 0.035(5) 0.035(4) 0.029(5) -0.001(4) 0.005(4) 0.012(4) C4 0.044(5) 0.030(4) 0.039(5) -0.003(4) 0.008(4) 0.021(4) C5 0.051(6) 0.040(5) 0.059(7) 0.005(5) 0.006(5) 0.021(5) C6 0.068(7) 0.028(5) 0.065(7) 0.014(5) 0.022(6) 0.022(5) C7 0.058(6) 0.039(6) 0.032(6) -0.002(4) 0.007(5) 0.017(5) C8 0.054(6) 0.034(6) 0.038(6) 0.004(4) 0.010(5) 0.020(5) C9 0.024(4) 0.025(4) 0.022(5) 0.000(4) -0.005(4) 0.010(4) C10 0.045(6) 0.060(7) 0.063(8) -0.006(6) 0.000(5) 0.026(5) C11 0.050(6) 0.042(6) 0.050(6) -0.008(5) -0.004(5) 0.014(5) C12 0.053(7) 0.036(6) 0.044(6) -0.002(5) -0.007(5) 0.019(5) C13 0.089(9) 0.055(7) 0.038(6) 0.018(5) 0.019(6) 0.039(7) C14 0.056(6) 0.045(6) 0.050(7) -0.005(5) 0.002(5) 0.024(5) C15 0.085(9) 0.082(9) 0.052(7) -0.018(7) -0.020(7) 0.061(8) C16 0.124(13) 0.072(9) 0.072(9) -0.006(7) -0.017(8) 0.076(10) C17 0.053(7) 0.059(7) 0.056(7) -0.003(6) 0.001(5) 0.031(5) C18 0.092(10) 0.040(7) 0.041(7) -0.018(5) 0.002(7) 0.031(6) C19 0.063(7) 0.050(6) 0.042(6) -0.014(5) -0.003(5) 0.030(5) C20 0.100(13) 0.079(10) 0.077(11) -0.030(8) -0.014(8) 0.061(9) C21 0.051(6) 0.061(7) 0.066(8) 0.025(6) 0.018(5) 0.036(5) C22 0.033(5) 0.060(6) 0.042(6) 0.003(5) 0.000(4) 0.019(5) C23 0.035(5) 0.029(4) 0.024(5) -0.002(4) -0.007(4) 0.012(4) C24 0.031(5) 0.043(5) 0.020(5) -0.006(4) -0.002(4) 0.021(4) C25 0.028(4) 0.031(4) 0.020(5) -0.003(4) -0.008(4) 0.012(4) C26 0.071(8) 0.042(6) 0.048(7) 0.005(5) 0.020(6) 0.017(6) C27 0.036(5) 0.032(5) 0.035(6) 0.000(4) -0.011(4) 0.021(4) C28 0.045(6) 0.050(6) 0.050(6) -0.012(5) -0.011(5) 0.026(5) C29 0.046(6) 0.057(7) 0.054(7) -0.023(6) -0.015(5) 0.028(6) C30 0.075(8) 0.089(9) 0.054(8) -0.008(7) -0.013(6) 0.070(8) C31 0.069(8) 0.073(9) 0.067(8) -0.022(7) -0.020(7) 0.055(8) C32 0.054(6) 0.053(6) 0.036(6) -0.005(5) -0.011(5) 0.027(5) C33 0.043(5) 0.048(5) 0.045(6) 0.004(5) 0.009(5) 0.014(4) C34 0.053(6) 0.045(6) 0.044(6) 0.004(5) 0.001(5) 0.016(5) C35 0.039(5) 0.079(8) 0.083(9) 0.006(7) 0.011(5) 0.035(6) C36 0.109(11) 0.065(8) 0.113(13) 0.042(8) 0.033(10) 0.060(8) C37 0.034(5) 0.041(5) 0.021(4) -0.008(4) -0.008(4) 0.023(4) C38 0.028(4) 0.036(5) 0.016(4) -0.006(4) -0.001(4) 0.013(4) C39 0.059(7) 0.046(6) 0.071(8) 0.017(5) 0.006(6) 0.024(5) C40 0.063(7) 0.076(8) 0.039(6) -0.007(6) -0.007(5) 0.052(6) C41 0.048(6) 0.041(6) 0.040(6) -0.011(4) -0.007(5) 0.024(5) C42 0.044(5) 0.038(5) 0.028(7) 0.006(4) 0.009(4) 0.028(5) C43 0.068(7) 0.039(5) 0.033(6) 0.001(4) -0.002(5) 0.032(5) C44 0.044(6) 0.021(5) 0.035(6) -0.005(4) -0.005(5) 0.011(5) C45 0.044(6) 0.048(6) 0.043(7) -0.007(5) 0.003(5) 0.029(5) C46 0.046(5) 0.052(6) 0.038(6) 0.010(5) 0.009(5) 0.033(5) C47 0.063(8) 0.090(10) 0.057(8) -0.023(7) -0.009(6) 0.056(7) C48 0.067(7) 0.073(8) 0.056(7) -0.011(6) 0.002(6) 0.054(7) ATURE CHEMISTRY www.nature.com/naturechemistry 69 2013 Macmillan Publishers Limited. All rights reserved.

C49 0.052(6) 0.067(7) 0.044(6) -0.001(5) -0.012(5) 0.040(6) C50 0.051(6) 0.047(5) 0.023(4) -0.004(4) -0.002(4) 0.033(4) C51 0.048(6) 0.049(6) 0.047(6) -0.006(5) -0.004(5) 0.032(5) C52 0.084(9) 0.065(7) 0.069(8) -0.013(6) -0.027(7) 0.060(7) C53 0.058(6) 0.033(5) 0.034(5) -0.004(4) -0.002(5) 0.023(4) C54 0.043(5) 0.043(5) 0.022(5) -0.002(4) -0.004(4) 0.030(4) C55 0.049(6) 0.041(5) 0.021(5) -0.001(4) -0.008(4) 0.023(5) C56 0.048(6) 0.042(5) 0.032(6) 0.000(4) 0.007(4) 0.030(5) C57 0.081(7) 0.053(6) 0.042(6) -0.003(5) 0.004(5) 0.049(6) C58 0.057(6) 0.041(5) 0.048(6) 0.008(4) 0.016(5) 0.039(5) C59 0.053(6) 0.054(6) 0.040(5) 0.007(4) 0.003(4) 0.040(5) C60 0.031(6) 0.041(6) 0.061(8) -0.003(5) 0.000(5) 0.024(5) C61 0.036(5) 0.060(7) 0.047(6) 0.008(5) 0.001(5) 0.026(5) C62 0.071(7) 0.052(6) 0.031(6) -0.003(5) 0.007(5) 0.037(6) C63 0.056(7) 0.068(9) 0.040(6) 0.009(6) 0.006(5) 0.048(7) 1 0.030(4) 0.052(4) 0.014(4) -0.003(4) 0.004(3) 0.026(4) 2 0.030(4) 0.025(4) 0.027(4) -0.002(3) -0.002(3) 0.006(3) 3 0.025(3) 0.023(3) 0.031(4) 0.001(3) 0.000(3) 0.010(3) 4 0.044(4) 0.034(4) 0.013(4) -0.003(3) -0.006(3) 0.021(3) 5 0.037(4) 0.034(4) 0.023(4) -0.006(3) -0.008(3) 0.016(3) 6 0.028(4) 0.034(4) 0.033(4) -0.006(4) 0.005(4) 0.015(3) 7 0.040(4) 0.037(4) 0.028(4) -0.007(3) -0.001(3) 0.024(3) 8 0.028(4) 0.031(4) 0.029(4) -0.002(3) -0.002(3) 0.018(3) 9 0.042(4) 0.040(5) 0.029(4) 0.002(3) 0.004(3) 0.027(4) 10 0.037(4) 0.038(4) 0.026(4) 0.002(3) 0.003(4) 0.020(4) 11 0.023(4) 0.057(5) 0.014(4) -0.003(4) -0.002(3) 0.015(4) 12 0.037(4) 0.025(3) 0.031(5) -0.003(3) -0.005(3) 0.021(3) 13 0.040(4) 0.030(4) 0.022(4) -0.008(3) -0.005(3) 0.025(3) 14 0.032(4) 0.044(5) 0.021(4) 0.007(3) 0.004(3) 0.023(3) 15 0.039(4) 0.037(4) 0.022(4) 0.004(3) 0.007(3) 0.023(4) P1 0.0400(13) 0.0269(11) 0.0286(12) -0.0019(10) -0.0042(10) 0.0146(10) P2 0.0507(15) 0.0358(13) 0.0252(12) -0.0021(11) -0.0058(12) 0.0254(13) P3 0.0487(15) 0.0379(13) 0.0315(13) 0.0037(11) 0.0034(11) 0.0293(13) P4 0.0390(13) 0.0421(13) 0.0288(12) 0.0014(11) 0.0029(10) 0.0261(11) P5 0.0409(13) 0.0360(12) 0.0256(12) 0.0023(10) 0.0025(10) 0.0220(10) P6 0.0400(12) 0.0419(14) 0.0255(14) 0.0023(11) 0.0035(10) 0.0274(11) Ir1 0.0471(2) 0.02830(17) 0.0277(2) -0.00181(15) -0.00538(19) 0.01881(17) Ir2 0.0460(2) 0.0417(2) 0.0300(2) 0.00256(18) 0.00342(17) 0.0311(2) Ir3 0.04037(17) 0.0370(2) 0.02678(17) 0.00249(17) 0.00282(19) 0.02587(14) _geom_special_details ; All s.u.'s (except the s.u. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell s.u.'s are taken into account individually in the estimation of s.u.'s in distances, angles and torsion angles; correlations between s.u.'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell s.u.'s is used for estimating s.u.'s involving l.s. planes. ; loop_ ATURE CHEMISTRY www.nature.com/naturechemistry 70 2013 Macmillan Publishers Limited. All rights reserved.

_geom_bond_atom_site_label_1 _geom_bond_atom_site_label_2 _geom_bond_distance _geom_bond_site_symmetry_2 _geom_bond_publ_flag C1 5 1.332(13).? C1 1 1.358(13).? C1 3 1.363(12).? C2 2 1.320(13).? C2 3 1.339(12).? C2 C3 1.493(13).? C3 C4 1.381(14).? C3 C8 1.397(15).? C4 C5 1.401(13).? C5 C6 1.362(17).? C6 C7 1.390(17).? C7 C8 1.405(14).? C9 2 1.342(11).? C9 4 1.374(12).? C9 1 1.376(12).? C10 C41 1.534(15).? C11 C41 1.534(14).? C12 C14 1.492(17).? C12 C13 1.542(16).? C12 P2 1.854(13).? C15 C43 1.500(17).? C16 C43 1.528(15).? C17 C44 1.539(16).? C18 C44 1.550(15).? C19 C45 1.528(16).? C20 C45 1.526(18).? C21 C46 1.534(13).? C22 C46 1.508(15).? C23 13 1.336(12).? C23 11 1.344(13).? C23 15 1.347(13).? C24 12 1.328(12).? C24 13 1.349(12).? C24 C54 1.489(13).? C25 12 1.339(12).? C25 11 1.361(13).? C25 14 1.380(12).? C26 C62 1.534(18).? C27 10 1.303(14).? C27 6 1.322(13).? C27 8 1.350(11).? C28 C63 1.510(16).? C29 C60 1.544(15).? C30 C63 1.516(15).? C31 C60 1.501(15).? C32 C42 1.555(15).? ATURE CHEMISTRY www.nature.com/naturechemistry 71 2013 Macmillan Publishers Limited. All rights reserved.

C33 C53 1.489(14).? C34 C61 1.496(16).? C35 C61 1.526(14).? C36 C62 1.495(15).? C37 7 1.331(13).? C37 8 1.360(12).? C37 C50 1.476(13).? C38 7 1.322(12).? C38 6 1.337(12).? C38 9 1.360(13).? C39 C53 1.549(14).? C40 C42 1.500(15).? C41 P1 1.823(11).? C42 P5 1.832(12).? C43 P2 1.813(11).? C44 P1 1.849(12).? C45 P6 1.857(12).? C46 P6 1.842(10).? C47 C48 1.318(18).? C47 C52 1.362(18).? C48 C49 1.385(14).? C49 C50 1.366(15).? C50 C51 1.389(14).? C51 C52 1.424(14).? C53 P5 1.825(10).? C54 C59 1.371(14).? C54 C55 1.389(14).? C55 C56 1.394(13).? C56 C57 1.390(15).? C57 C58 1.375(14).? C58 C59 1.402(12).? C60 P4 1.826(13).? C61 P4 1.839(11).? C62 P3 1.847(12).? C63 P3 1.838(13).? C64 C65 1.3900.? C64 C69 1.3900.? C65 C66 1.3900.? C66 C67 1.3900.? C67 C68 1.3900.? C68 C69 1.3900.? C70 C71 1.3900.? C70 C75 1.3900.? C71 C72 1.3900.? C72 C73 1.3900.? C73 C74 1.3900.? C74 C75 1.3900.? C76 C77 1.3900.? C76 C81 1.3900.? C77 C78 1.3900.? C78 C79 1.3900.? ATURE CHEMISTRY www.nature.com/naturechemistry 72 2013 Macmillan Publishers Limited. All rights reserved.

C79 C80 1.3900.? C80 C81 1.3900.? C82 C83 1.3900.? C82 C87 1.3900.? C83 C84 1.3900.? C84 C85 1.3900.? C85 C86 1.3900.? C86 C87 1.3900.? C88 C89 1.3900.? C88 C93 1.3900.? C89 C90 1.3900.? C90 C91 1.3900.? C91 C92 1.3900.? C92 C93 1.3900.? C94 C95 1.3900.? C94 C99 1.3900.? C95 C96 1.3900.? C96 C97 1.3900.? C97 C98 1.3900.? C98 C99 1.3900.? 1 Ir1 2.049(8).? 4 P1 1.743(8).? 5 P2 1.744(8).? 6 Ir2 2.137(7).? 9 P3 1.744(8).? 10 P4 1.734(8).? 11 Ir3 2.053(8).? 14 P5 1.728(8).? 15 P6 1.734(8).? P1 Ir1 2.250(3).? P2 Ir1 2.251(3).? P3 Ir2 2.243(3).? P4 Ir2 2.247(3).? P5 Ir3 2.247(2).? P6 Ir3 2.249(3).? loop geom_angle_atom_site_label_1 _geom_angle_atom_site_label_2 _geom_angle_atom_site_label_3 _geom_angle _geom_angle_site_symmetry_1 _geom_angle_site_symmetry_3 _geom_angle_publ_flag 5 C1 1 114.7(8)..? 5 C1 3 120.7(9)..? 1 C1 3 124.6(8)..? 2 C2 3 127.5(9)..? 2 C2 C3 115.9(9)..? 3 C2 C3 116.6(9)..? C4 C3 C8 120.3(9)..? ATURE CHEMISTRY www.nature.com/naturechemistry 73 2013 Macmillan Publishers Limited. All rights reserved.

C4 C3 C2 120.5(9)..? C8 C3 C2 119.1(9)..? C3 C4 C5 119.8(10)..? C6 C5 C4 119.8(10)..? C5 C6 C7 121.5(9)..? C6 C7 C8 119.0(11)..? C3 C8 C7 119.4(10)..? 2 C9 4 120.8(8)..? 2 C9 1 124.5(8)..? 4 C9 1 114.7(7)..? C14 C12 C13 108.3(10)..? C14 C12 P2 113.2(9)..? C13 C12 P2 108.7(8)..? 13 C23 11 125.0(9)..? 13 C23 15 119.6(8)..? 11 C23 15 115.4(8)..? 12 C24 13 125.4(9)..? 12 C24 C54 117.6(8)..? 13 C24 C54 117.0(8)..? 12 C25 11 124.6(9)..? 12 C25 14 121.0(9)..? 11 C25 14 114.5(8)..? 10 C27 6 117.9(8)..? 10 C27 8 122.5(9)..? 6 C27 8 119.6(9)..? 7 C37 8 125.7(8)..? 7 C37 C50 118.2(8)..? 8 C37 C50 116.1(8)..? 7 C38 6 121.9(9)..? 7 C38 9 120.6(8)..? 6 C38 9 117.5(8)..? C11 C41 C10 108.4(9)..? C11 C41 P1 112.6(8)..? C10 C41 P1 111.9(7)..? C40 C42 C32 108.6(10)..? C40 C42 P5 111.3(8)..? C32 C42 P5 113.9(8)..? C15 C43 C16 111.7(10)..? C15 C43 P2 111.9(8)..? C16 C43 P2 112.2(9)..? C17 C44 C18 110.3(11)..? C17 C44 P1 111.5(8)..? C18 C44 P1 109.6(8)..? C20 C45 C19 110.6(11)..? C20 C45 P6 109.0(9)..? C19 C45 P6 110.8(8)..? C22 C46 C21 110.2(9)..? C22 C46 P6 111.9(7)..? C21 C46 P6 110.9(7)..? C48 C47 C52 123.3(11)..? C47 C48 C49 118.2(12)..? ATURE CHEMISTRY www.nature.com/naturechemistry 74 2013 Macmillan Publishers Limited. All rights reserved.

C50 C49 C48 122.0(11)..? C49 C50 C51 118.9(9)..? C49 C50 C37 121.8(10)..? C51 C50 C37 119.3(9)..? C50 C51 C52 118.5(10)..? C47 C52 C51 118.5(12)..? C33 C53 C39 112.4(8)..? C33 C53 P5 113.3(7)..? C39 C53 P5 111.1(7)..? C59 C54 C55 119.6(9)..? C59 C54 C24 120.2(8)..? C55 C54 C24 120.1(9)..? C54 C55 C56 119.9(9)..? C57 C56 C55 121.2(9)..? C58 C57 C56 117.7(8)..? C57 C58 C59 121.9(9)..? C54 C59 C58 119.7(9)..? C31 C60 C29 110.6(10)..? C31 C60 P4 112.5(9)..? C29 C60 P4 113.4(8)..? C34 C61 C35 110.0(10)..? C34 C61 P4 110.5(7)..? C35 C61 P4 111.7(8)..? C36 C62 C26 110.5(11)..? C36 C62 P3 112.3(9)..? C26 C62 P3 110.6(8)..? C28 C63 C30 108.0(11)..? C28 C63 P3 112.6(8)..? C30 C63 P3 111.1(9)..? C65 C64 C69 120.0..? C64 C65 C66 120.0..? C67 C66 C65 120.0..? C66 C67 C68 120.0..? C69 C68 C67 120.0..? C68 C69 C64 120.0..? C71 C70 C75 120.0..? C70 C71 C72 120.0..? C73 C72 C71 120.0..? C72 C73 C74 120.0..? C75 C74 C73 120.0..? C74 C75 C70 120.0..? C77 C76 C81 120.0..? C78 C77 C76 120.0..? C77 C78 C79 120.0..? C80 C79 C78 120.0..? C81 C80 C79 120.0..? C80 C81 C76 120.0..? C83 C82 C87 120.0..? C82 C83 C84 120.0..? C83 C84 C85 120.0..? C84 C85 C86 120.0..? ATURE CHEMISTRY www.nature.com/naturechemistry 75 2013 Macmillan Publishers Limited. All rights reserved.

C87 C86 C85 120.0..? C86 C87 C82 120.0..? C89 C88 C93 120.0..? C88 C89 C90 120.0..? C91 C90 C89 120.0..? C90 C91 C92 120.0..? C93 C92 C91 120.0..? C92 C93 C88 120.0..? C95 C94 C99 120.0..? C96 C95 C94 120.0..? C97 C96 C95 120.0..? C96 C97 C98 120.0..? C97 C98 C99 120.0..? C98 C99 C94 120.0..? C1 1 C9 114.5(8)..? C1 1 Ir1 123.2(6)..? C9 1 Ir1 122.2(6)..? C2 2 C9 114.9(8)..? C2 3 C1 113.9(8)..? C9 4 P1 120.0(6)..? C1 5 P2 120.7(7)..? C27 6 C38 121.6(8)..? C27 6 Ir2 119.2(6)..? C38 6 Ir2 119.1(7)..? C38 7 C37 115.3(8)..? C27 8 C37 115.9(8)..? C38 9 P3 120.8(7)..? C27 10 P4 121.9(7)..? C23 11 C25 114.7(8)..? C23 11 Ir3 122.9(7)..? C25 11 Ir3 122.4(6)..? C24 12 C25 115.3(8)..? C23 13 C24 115.0(8)..? C25 14 P5 120.5(7)..? C23 15 P6 119.8(7)..? 4 P1 C41 101.9(4)..? 4 P1 C44 100.5(4)..? C41 P1 C44 105.0(5)..? 4 P1 Ir1 100.3(3)..? C41 P1 Ir1 119.3(4)..? C44 P1 Ir1 125.1(4)..? 5 P2 C43 100.5(4)..? 5 P2 C12 102.5(5)..? C43 P2 C12 102.9(6)..? 5 P2 Ir1 100.1(3)..? C43 P2 Ir1 123.8(4)..? C12 P2 Ir1 122.5(4)..? 9 P3 C63 104.0(4)..? 9 P3 C62 100.0(5)..? C63 P3 C62 103.2(5)..? 9 P3 Ir2 100.2(3)..? ATURE CHEMISTRY www.nature.com/naturechemistry 76 2013 Macmillan Publishers Limited. All rights reserved.

C63 P3 Ir2 121.3(4)..? C62 P3 Ir2 124.0(4)..? 10 P4 C60 102.4(5)..? 10 P4 C61 103.3(5)..? C60 P4 C61 105.9(6)..? 10 P4 Ir2 99.6(3)..? C60 P4 Ir2 122.4(4)..? C61 P4 Ir2 119.5(4)..? 14 P5 C53 98.6(4)..? 14 P5 C42 103.7(4)..? C53 P5 C42 103.2(5)..? 14 P5 Ir3 100.3(3)..? C53 P5 Ir3 124.8(3)..? C42 P5 Ir3 121.4(4)..? 15 P6 C46 101.1(4)..? 15 P6 C45 102.9(5)..? C46 P6 C45 104.1(5)..? 15 P6 Ir3 100.4(3)..? C46 P6 Ir3 120.7(4)..? C45 P6 Ir3 123.4(4)..? 1 Ir1 P1 82.4(2)..? 1 Ir1 P2 81.3(2)..? P1 Ir1 P2 163.69(10)..? 6 Ir2 P3 82.4(2)..? 6 Ir2 P4 81.2(2)..? P3 Ir2 P4 163.57(9)..? 11 Ir3 P5 82.3(2)..? 11 Ir3 P6 81.2(2)..? P5 Ir3 P6 163.44(8)..? _diffrn_measured_fraction_theta_max 0.996 _diffrn_reflns_theta_full 25.55 _diffrn_measured_fraction_theta_full 0.996 _refine_diff_density_max 1.067 _refine_diff_density_min -0.493 _refine_diff_density_rms 0.109 ATURE CHEMISTRY www.nature.com/naturechemistry 77 2013 Macmillan Publishers Limited. All rights reserved.