Supporting Online Material for

www.sciencemag.org/cgi/content/full/science.1199844/dc1 Supporting Online Material for Dynamic Control of Chiral Space in a Catalytic Asymmetric Reaction Using a Molecular Motor Jiaobing Wang and Ben L. Feringa* *To whom correspondence should be addressed. E-mail: b.l.feringa@rug.nl This PDF file includes: SOM Text Figs. S1 to S12 References Published 10 February 2011 on Science Express DOI: 10.1126/science.1199844

Supporting Material Dynamic Control of Chiral Space in a Catalytic Asymmetric Reaction using a Molecular Motor Jiaobing Wang, Ben L. Feringa* Centre for Systems Chemistry, Stratingh Institute for Chemistry and Zernike Institute for Advanced Materials, University of Groningen, Nijenborgh 4, 9747 AG, Groningen, The Netherlands E-mail: b.l.feringa@rug.nl General remarks Chemicals were purchased from Aldrich or Fluka. Dichloromethane (DCM), Tetrahydrofuran (THF), and toluene were freshly distilled before use. Technical grade solvents were used for extraction and chromatography. Merck silica gel 60 (230-400 mesh ASTM) was used in flash chromatography. UV measurements were performed on a Jasco V-630 spectrophotometer. CD measurements were performed on a Jasco J-815 CD spectrophotometer. UV irradiation experiments were carried out using a Spectroline model ENB-280C/FE lamp. NMR spectra were obtained using a Varian Mercury Plus (400 MHz) and a Varian VXR-300S (300 MHz). Contents: Pages Synthesis.....2 Unidirectional rotation followed by Chiral HPLC... 7 Kinetic study for the thermal isomerizing step-2. 8 Kinetics of the catalytic reactions followed by 1 H-NMR spectroscopy 9 Kinetic and chiral HPLC data for the catalytic reaction using the in situ formed catalyst 10 Molecular modeling of compound 1 in each isomerizing state 11 Chiral HPLC data of the product using catalysts with (2S,2 S)- absolute configuration. 12 1 H-NMR, 13 C-NMR and Mass Spectra 13 1

Synthesis: Fig. S1. Synthesis of the integrated motor catalyst 1 starting from the racemic precursor 5. The enantiopure compounds (2R,2 R)-(P,P)-trans-1 and (2S,2 S)-(M,M)-trans-1 were obtained by preparative chiral HPLC, and the absolute configuration of the stereogenic centre was confirmed by asymmetric synthesis (see Fig. S3). Note S1 Compound 6. To a solution of racemic compound 5 ((2S,2 S)-(M,M)-trans-5/(2R,2 R)-(P,P)-trans-5 = 1/1, 1.0 g, 2.1 mmol) (see S1), 4-nitrophenylboronic acid (1.0 g, 6 mmol), K 2 CO 3 (2.0 g, 14.5 mmol), and Pd(PPh 3 ) 4 (200 mg, 0.17 mmol) in 60 ml toluene was added 20 ml absolute alcohol. The solution was stirred under N 2 at 90 C in a sealed flask for 3h. After cooling to room temperature, the mixture was poured into 200 ml water and extracted with dichloromethane (DCM, 2 100 ml). The combined organic phase was dried and the solvent was removed under vacuum. The residue was purified by silica gel column chromatography using pentane/dcm (1/1) as the eluant affording 970 mg (83%) of the nitro compound as a yellow solid. mp: 193.8-194.6 C. 1 H NMR (CD 2 Cl 2 ): δ = 8.30 (d, J = 8.7 Hz, 4H), 7.62 (d, J = 8.7 Hz, 4H), 6.99 (s, 2H), 3.05 (m, 2H), 2.80 (dd, J = 14.7, 5.7 Hz, 2H), 2.36 (m, 14H), 1.40 (d, J = 6.6Hz, 6H). 13 C NMR (CD 2 Cl 2 ): 149.9, 146.9, 143.2, 142.6, 142.4, 139.2, 132.1, 130.7, 129.7, 128.6, 123.5, 42.7, 39.1, 21.2, 18.9, 18.1. HRMS: m/z calcd for C 36 H 35 N 2 O 4 [M+H] + : 559.2591; found: 559.2583. To a suspension of the above nitro compound (0.8 g, 1.4 mmol) and SnCl 2-2H 2 O (4.0 g, 17.8 mmol) in 100 ml ethyl acetate was added 0.5 ml of distilled water. The mixture was heated at 75 C under N 2 for 3h. After cooling down to room temperature, the mixture was poured into 300 ml water and extracted with ether (2 100 ml). The combined organic phase was dried and the solvent was removed under vacuum. The residue was purified by silica gel column chromatography using DCM/MeOH (100/1) as the eluant affording 500 mg (70%) of compound 6 as a slight yellow solid. mp: 176.5-178.8 C. 1 H NMR (CD 2 Cl 2 ): δ = 7.21 (d, J = 8.4 Hz, 4H), 6.94 (s, 2H), 6.76 (d, J = 8.4 Hz, 4H), 3.78 (br, 4H), 3.02 (m, 2H), ), 2.74 (dd, J = 14.1, 5.4 Hz, 2H), 2.32 (m, 8H), 2.24 (s, 6H), 1.13 (d, J = 6.3Hz, 6H). 13 C NMR (CD 2 Cl 2 ): 145.6, 142.3, 2

141.3, 141.1, 132.8, 131.4, 130.6, 129.8, 129.0, 114.7, 42.6, 39.0, 21.4, 19.1, 18.1. HRMS: m/z calcd for C 36 H 39 N 2 [M+H] + : 499.3108; found: 499.3097. Compound 7. 2-Bromo-4-pyridyl(dimethyl)amine (203 mg, 1.02 mmol), 6 (506 mg, 1.02 mmol), Pd 2 dba 3 (100 mg, 0.11 mmol), 1,3-bis(diphenylphosphino)propane (91 mg, 0.22 mmol), and NaOtBu (210 mg, 2.2 mmol) were dissolved in 30 ml dry toluene. The mixture was heated at 85 C in a sealed flask under N 2 for 3h. Then the mixture was cooled down and the solvent was evaporated under vacuum. The residue was purified by silica gel column chromatography using ethyl acetate/triethylamine (100/3) as the eluant affording 202 mg (32%) of 7 as a light yellow solid. mp: 173.4-174.5 C. 1 H NMR (CD 2 Cl 2 ): δ = 9.52 (br, 1H), 7.61 (d, J = 7.2 Hz, 1H), 7.47 (d, J = 8.8 Hz, 2H), 7.41 (d, J = 8.8 Hz, 2H), 7.21 (d, J = 8.4 Hz, 2H), 6.99 (s, 1H), 6.94 (s, 1H), 6.76 (d, J = 8.4 Hz, 2H), 6.25 (dd, J = 7.2, 2.4 Hz, 1H), 6.08 (d, J = 2.4 Hz, 1H), 3.80 (br, 2H), 3.05 (m, 8H), 2.80-2.70 (m, 2H), 2.39-2.30 (m, 8H), 2.26 (s, 3H), 2.24 (s, 3H), 1.14 (d, J = 6.8 Hz, 6H). 13 C NMR (CD 2 Cl 2 ) δ 156.6, 155.7, 145.4, 142.2, 142.1, 142.0, 141.9, 141.4, 141.1, 140.9, 140.7, 139.2, 136.9, 132.6, 131.3, 131.2, 130.3, 129.6, 129.5, 128.8, 128.7, 119.8, 114.4, 107.9, 105.0, 100.7, 89.0, 42.4, 39.2, 38.8, 29.7, 21.2, 21.1, 18.8, 17.9. HRMS: m/z calcd for C 43 H 47 N 4 [M+H] + : 619.3795; found: 619.3781. Compound 1. 3,5-Bis(trifluoromethyl)phenyl isothiocyanate (130 mg, 0.48 mmol) was added to a solution of compound 7 (150 mg, 0.24 mmol) in 10 ml dry THF. The mixture was stirred at room temperature for 12 h. Then the solvent was evaporated under vacuum. The residue was purified by silica gel column chromatography using ethyl acetate/triethylamine (100/3) as the eluant affording 122 mg (57%) of compound 1 as a white solid. mp: 163.8-165.4 C. 1 H NMR (CD 2 Cl 2 ): δ = 8.10 (s, 2H), 7.88 (d, J = 6.0 Hz, 2H), 7.73 (s, 1H), 7.56 (d, J = 8.0 Hz, 2H), 7.45 (d, J = 6.8 Hz, 2H), 7.43 (d, J = 6.8 Hz, 2H), 7.36 (d, J = 8.0 Hz, 2H), 6.99 (s, 1H), 6.98 (s, 1H), 6.19 (d, J = 6.0 Hz, 1H), 6.14 (s, 1H), 3.10-2.90 (m, 8H), 2.80-2.70 (m, 2H), 2.42-2.20 (m, 14H), 1.13 (d, J = 6.8 Hz, 6H). 13 C NMR (CD 2 Cl 2 ) δ 180.1, 156.6, 156.3, 147.6, 142.4, 142.3, 142.1, 142.0, 141.7, 141.3, 140.7, 140.4, 149.9, 139.8, 136.3, 135.1, 131.9, 131.5, 131.3, 131.2, 131.1, 130.2, 129.7, 129.5, 128.7, 128.5, 125.9, 124.4, 124.3, 120.5, 119.4, 100.9, 89.7, 42.4, 39.1, 38.8, 21.2, 21.0, 18.8, 17.9. HRMS: m/z calcd for C 52 H 50 F 6 N 5 [M+H] + : 890.3686; found: 890.3680. Enantiopure compounds were obtained by preparative HPLC on chiralpak AD column (4.6 250 mm); eluant 70:30 n-heptane/2-propanol; 40 C; flow rate 1 ml/min; λ = 300 nm; t R = 3.9 min, (2S,2 S)-(M,M)- trans-1, t R = 6.2 min, (2R,2 R)-(P,P)-trans-1. The absolute configuration of the stereogenic centres was assigned by asymmetric synthesis, see Fig S3 in the next page. CD spectra of both enantiomers are shown in Fig S2. Fig. S2. CD spectra of compounds (2R,2 R)-(P,P)-trans-1 and (2S,2 S)-(M,M)-trans-1 recorded in THF at 20 C. 3

Fig. S3. Asymmetric synthesis (see also S2,3) of the precursor compound (2R,2 R)-(P,P)-trans-5, which was used for the asymmetric synthesis of (2R,2 R)-(P,P)-trans-1 following the procedure shown in Fig S1. Note S2 Compound 8. LiAlH 4 (5.2 ml, 10.4 mmol, 2.0 M in THF) was added slowly at 0 C to a stirred solution of 2,5-dimethylbenzoic acid (1.5 g, 10 mmol) in dry THF (100 ml), and the solution was refluxed under N 2 for 2h. After cooling to room temperature, the reaction mixture was quenched by adding 5 ml water and THF was removed under vacuum. The product was extracted with ether to afford 1.3 g (95%) (2,5- dimethylphenyl)methanol as a colorless oil. 1 H NMR (CDCl 3 ): δ = 7.18 (s, 1H), 7.08 (d, J = 8.0 Hz, 1H), 7.04 (d, J = 8.0 Hz, 1H), 4.60 (s, 2H), 2.35 (s, 3H), 2.31 (s, 3H). 13 C NMR (CDCl 3 ): 138.6, 135.4, 132.7, 130.2, 128.3, 128.2, 63.1, 21.0, 18.1. Triphenylphosphine (28.8 g, 110 mmol) and CBr 4 (18.3 g, 55 mmol) were added at 0 C to a solution of (2,5-dimethylphenyl)methanol (6.8 g, 50 mmol) in 100 ml dry DCM. The mixture was stirred at room temperature for 40 min. Then the solvent was evaporated under vacuum. The residue was purified by silica gel column chromatography using hexane as the eluant affording 6.3 g (64%) of 8 as a colorless oil. 1 H NMR (CDCl 3 ): δ = 7.20-7.00 (m, 3H), 4.49 (s, 2H), 2.37 (s, 3H), 2.30 (s, 3H). 13 C NMR (CDCl 3 ): 135.9, 135.3, 134.1, 130.7, 130.6, 129.7, 32.5, 21.2, 17.8. Compound (S,R)-10. LDA (2.65 ml, 5.3 mmol, 2.0 M in THF) was added at -80 C to a solution of (S)-9 (1.2 g, 5.1 mmol) in 40 ml dry THF (Note: compound (S)-9 was synthesized from a commercialy available chiral precursor following an established method, see S2 and S3). The mixture was stirred at -80 C for 2 h. The solution was then warmed up to 0 C and 8 (2.0 g, 10 mmol) in 5 ml dry THF was added. The solution was stirred for an additional 6 h. The reaction mixture was then quenched with NH 4 Cl solution (100 ml) and extracted with CH 2 Cl 2 (2 100 ml). The combined organic phase was dried with Na 2 SO 4 and the solvent was removed under vacuum. The residue was purified by silica gel column chromatography using pentane/dcm (2/3) as the eluant affording 1.0 g (57%) of (S,R)-10 as a colorless oil. 1 H NMR (CD 2 Cl 2 ): δ = 7.31-7.20 (m, 3H), 7.08-6.98 (m, 4H), 6.92 (d, J = 8.0 Hz, 1H), 4.75-4.62 (m, 1H), 4.28-4.02 (m, 3H), 3.11-3.02 (m, 2H), 2.73 (dd, J = 13.6, 8.8 Hz, 1H), 2.54 (dd, J = 13.6, 9.2 Hz, 1H), 2.34 (s, 3H), 2.25 (s, 3H), 1.21 (d, J = 6.8 Hz, 3H). 13 C NMR (CD 2 Cl 2 ): 177.0, 153.0, 137.1, 135.2, 135.1, 133.5, 130.7, 130.2, 129.3, 128.9, 127.3, 127.2, 65.8, 55.0, 38.0, 37.7, 37.0, 20.9, 19.1, 17.3. HRMS: m/z calcd for C 22 H 26 NO [M+H] + : 352.1907; found: 352.1917. 4

Compound (R)-11. To a solution of (S,R)-10 (4.5 g, 12.8 mmol) in THF/water (70 ml, 4/1) was added H 2 O 2 (30% solution in water, 5.2 ml, 50.5 mmol) at 0 C under N 2 in a period of 5 min. Then LiOH (0.41 g, 20.5 mmol) in 10 ml water was added. The mixture was stirred at 0 C under N 2 for 1 h, aqueous solution (30 ml) of Na 2 SO 3 (8 g, 64 mmol) was added. The reaction mixture was then stirred for 30 min and acidified with 2 N aq. HCl (80 ml). The mixture was extracted with DCM (2 100 ml). The combined organic phase was dried with Na 2 SO 4 and the solvent was evaporated under vacuum. The residue was purified by silica gel column chromatography using pentane/ethyl acetate (5/2) as the eluant affording 1.9 g (77%) of (R)-11 as a colorless oil. 1 H NMR (CDCl 3 ): δ = 11.49 (br, 1H), 7.10 (d, J = 8.1 Hz, 1H ), 7.10 (d, J = 8.1 Hz, 1H ), 7.10-6.89 (m, 3H), 3.15 (dd, J = 13.5, 6.0 Hz, 1H), 2.90-2.74 (m, 1H), 2.67 (dd, J = 13.5, 6.0 Hz, 1H), 2.35 (s, 6H), 1.25 (d, J = 8.1 Hz, 3H). 13 C NMR (CDCL 3 ) δ 183.5, 137.4, 135.5, 133.4, 130.7, 130.6, 127.5, 40.4, 36.8, 21.2, 19.2, 16.8. HRMS: m/z calcd for C 12 H 15 O 2 [M-H] - : 191.1077; found: 191.1073. Compound (R)-13. To a solution of compound (R)-11 (1.91 g, 10.0 mmol) in 40 ml acetonitrile was added aqueous H 2 SO 4 (15%, 40 ml) at room temperature followed by NBS (1.78 g, 10 mmol). The solution was stirred at 70 C for 5h. After cooling to room temperature, the mixture was poured into 200 ml water and extracted with dichloromethane (DCM, 2 100 ml). The combined organic phase was dried and the solvent was removed under vacuum. The residue was purified by silica gel column chromatography using pentane/ethyl acetate (5/2) as the eluant affording 2.4 g colorless oil. Further purification was not performed at this stage. The mixture contains about 60% of the desired product (R)-12 and is used directly in the next step. 1 H NMR (CDCl 3 ): δ = 7.35 (s, 1H ), 7.02 (s, 1H ), 3.01 (dd, J = 13.5, 6.0 Hz, 1H), 2.80-2.70 (m, 1H), 2.61 (dd, J = 13.5, 6.0 Hz, 1H), 2.26 (s, 6H), 1.21 (d, J = 8.1 Hz, 3H). HRMS: m/z calcd for C 12 H 14 BrO 2 [M-H] - : 269.0182; found: 269.0173. A mixture of the above product (1.35 g) in a solution of SOCl 2 (3.5 ml), DMF (2 drops) and CH 2 Cl 2 (50 ml) was heated at reflux for 1h. The volatiles were removed under reduced pressure and the remaining yellow oil was dissolved in dichloroethane (100 ml) at 0 C. Then AlCl 3 (1.4 g, 10.5 mmol) was added, and the solution was stirred for 20 min. The reaction was quenched with saturated aqueous solution of NaHCO 3 (200 ml), extracted with CH 2 Cl 2 (2 100 ml), and dried with Na 2 SO 4. The solvent was evaporated under vacuum. The residue was purified by a silica gel column chromatography using pentane/ch 2 Cl 2 (5/3) as the eluant affording (R)-13 (0.63 g, 2.5 mmol, 50% for 2 steps) as a slight yellow solid. 1 H NMR (CDCl 3 ): δ = 7.54 (s, 1H), 3.18 (dd, J = 17.2, 7.6 Hz, 1H), 2.67 (m, 4H), 2.48 (dd, J = 16.0, 4.0 Hz, 1H), 2.28 (s, 3H), 1.30 (d, J = 7.6 Hz, 3H). The chemical shifts were identical with that of the authentic racemic sample (S1). This compound was obtained in 96% ee. The enantiomeric excess was determined by chiral HPLC (see below, Fig S4, C,D). The UV-vis and CD spectra were also recorded (Fig S4, A, B). Fig. S4. UV-vis (Fig S4, A), CD (Fig S4, B), and chiral HPLC data (Fig S4, C) for the intermediate compound (R)-13. Chiral HPLC data for the racemate 13 is shown in Fig S4, D. UV-vis/CD spectra were recorded in THF at 20 C. HPLC conditions: Chiralpak OJ-H column [n-heptane/2-propanol 98:2]; flow rate 0.5 ml/min; λ = 254 nm; 40 C; t R (minor) = 13.68 min (S), t R (major) = 15.16 min (R). 5

Compound (2R,2 R)-(P,P)-trans-5. To a suspension of zinc powder (3.0 g, 47.0 mmol) in 50 ml dry THF was added 2.45 ml TiCl 4 at 0 C. The mixture was heated at reflux under N 2 for 2h. After cooling down to room temperature, anhydrous pyridine (0.48 ml, 6 mmol) was added. The solution was stirred for 5 min, and then compound (R)-13 (3.0 g, 12.0 mmol) was added. The mixture was again heated at reflux under N 2 for 12h. After cooling to room temperature, the mixture was directly charged onto a silica gel column using DCM as eluant to remove the metal salts. The product was further purified by chromatography on silica gel using pentane/dcm (3/1) as eluant. The product was obtained as a mixture of the trans/cis isomers in a 1:1 ratio (0.43 g, 15%). Separation of geometrical isomers was not achieved at this stage. 1 H NMR (CDCl 3 ): δ = 7.28 (s, 2H ), 2.89-2.76 (m, 2H ), 2.58 (dd, J = 14.7, 6.0 Hz, 2H), 2.46 (s, 6H), 2.24 (d, J = 14.7, 2H), 2.17 (s, 6H), 1.10 (d, J = 6.0 Hz, 6H). The chemical shifts were identical with that of the authentic racemic sample (S1). Chiral HPLC analysis (Fig S5) indicates that no racemization happened under the above conditions for the McMurry coupling. Fig. S5. HPLC chromatograms of the racemic compounds trans-5 (A) obtained following a literature procedure (S1) and the product (2R,2 R)-(P,P)-trans-5 (B) obtained following the procedure shown in Fig S3. Note: the retention times of compounds (2R,2 R)-(P,P)-trans-5, (2S,2 S)-(M,M)-trans-5, and (2R,2 R)- (P,P)-cis-5 are quite close to each other. But a closer examination (see dashed line) of the HPLC data indicates the absence of a significant amount of the coupling product with (S)-configuration. HPLC conditions: AD-H column [n-heptane]; flow rate 0.25 ml/min; λ = 322 nm; 40 C; t R (major) = 16.98 min, (2R,2 R)-(P,P)-trans-5. Note S3 The other intermediate compounds for the asymmetric synthesis of (2R,2 R)-trans-1 were obtained by following the procedure shown in Fig S1. 1 H NMR analysis (data not shown) confirmed the identity of these compounds. Some key UV-vis, CD, and HPLC data are shown below. These data confirm the absolute configuration of the stereogenic centres (methyl groups) on the motor scaffold. 6

Fig. S6. UV-vis, CD and HPLC data for the intermediate compound 7 (A) and the target compound 1 (B). The UV-vis, and CD spectra were measured for the compounds with (R)-absolute configuration, which were obtained from the asymmetric synthesis (Fig S3, S1). HPLC chromatograms of the racemic compounds (obtained following the procedure shown in Fig S1), are shown in Fig Ad, Bd. All UV-vis/CD spectra were recorded in THF at 20 C. HPLC conditions: AD-H column [n-heptane-isopropanol, 70/30]; flow rate 0.5 ml/min; 40 C. Unidirectional rotation: The 4-step unidirectional isomerization of compound 1 could be followed by the chiral HPLC analysis. Chiralpak AD-H column (4.6 250 mm); eluant 65:35 n-heptane/2-propanol; 20 C; flow rate 0.5 ml/min; λ detection was set at the isosbestic point of each step, respectively. 7

Fig. S7. HPLC data for the 4-step unidirectional isomerizing process. (a) (2R,2 R)-(P,P)-trans-1, t R = 14.67 min; (b) (2R,2 R)-(M,M)-cis-1, t R = 7.83 min, yield >99%; (c) (2R,2 R)-(P,P)-cis-1, t R = 7.49 min, yield 76%, the minor band (t R = 15.77 min) resulted from some decomposition of thiourea. Dotted line: Purified (2R,2 R)-(P,P)-cis-1 by using preparative HPLC, which was used for step-3, and -4; (d) (2R,2 R)-(P,P)- trans-1, t R = 14.67 min. Note: the unidirectional isomerizing behaviour was marked with the arrow (gray, solid). Compound (2R,2 R)-(P,P)-trans-1 returns to its initial state after a 4-step isomerizing process, which is indicated by the double arrow between Fig S7-a,d. HPLC chromatogram of compound (2R,2 R)-(M,M)- trans-1 could not be recorded because of its short half life at rt (< 10 min). Conditions for each isomerizing step: step-1, UV irradiation at 312 nm for 1 min in THF at 20 C; step-2, heating in THF/isopropanal (2/1) at 70 C in a sealed vial for 40 min; step-3, UV irradiation at 312 nm for 5 min in THF at -60 o C; step-4, warming up the solution of step-3 to 20 C for 10 min. Fig. S8. Kinetic study for the thermal isomerizing step-2. The isomerization from (2R,2 R)-(M,M)-cis-1 to (2R,2 R)-(P,P)-cis-1 was followed by absorption changes at 350 nm at four different temperatures (50, 55, 60 and 65 C, A). The rate constants k of the first-order decay at different temperatures were obtained using the equation A = A 0 e -κt (A and A 0 are the absorbance at different time t). Analysis of these data using the conventional form of the absolute rate equation (Δ G = RT [ln (k B /h) - ln (k/t)], where k B is the Boltzmann constant and h the Planck constant (k B /h = 2.08358 10 10 K 1 s 1 )) provides the standard Gibbs energy of activation (Δ G = 104.1 kj/mol). The long half life (120 days at 0 C, obtained by linear fit of lnk/t and 1/T, B) of compound (2R,2 R)-(M,M)-cis-1 is favorable for the study of its catalytic behavior. 8

Catalytic behavior: Fig. S9. Reaction kinetics from 0 to 15 h followed by 1 H-NMR (CD 2 Cl 2, -15 C) spectroscopy. The reaction was very slow when the trans-isomer (2R,2 R)-(P,P)-trans-1 was employed (A). The cis-isomers (2R,2 R)-(M,M)-cis-1 (B) and (2R,2 R)-(P,P)-cis-1 (C) displayed significant catalytic activity. The product formation could be followed by the increased resonance signal for proton H b at 2.63 ppm. Note S4 Reactions were carried out on a 0.1 mmol scale of enone and thiol, respectively. The enone (0.1 mmol, 100 μl 1.0 M stock solution in CD 2 Cl 2 ) was added to a mixture of thiol (0.1 mmol, 100 μl 1.0 M stock solution in CD 2 Cl 2 ) and catalyst (3.0 10-4 mmol, 300 μl 1.0 mm stock solution in CD 2 Cl 2 ) at -15 C. The product formation was followed by in-situ 1 H-NMR spectroscopy (Fig S9). After 15 h, the reaction mixture was directly charged onto a silica gel column using CHCl 3 /heptane (1/1) as eluant to provide the product as a colorless oil. 1 H NMR (CDCl 3 ): δ = 7.39 (d, J = 8.4 Hz, 1H), 7.28 (t, J = 8.4 Hz, 1H), 6.91 (t, J = 7.6 Hz, 1H), 6.89 (d, J = 7.6 Hz, 1H), 3.89 (s, 3H), 3.60-3.50 (m, 1H ), 2.65 (dd, J = 14.4, 4.4 Hz, 1H), 2.42-2.26 (m, 3H), 2.20-2.07 (m, 2H), 1.79-1.65 (m, 2H). The chemical shifts were identical with that reported in literature (S4). Catalyst (2R,2 R)-(M,M)-cis-1 was obtained by irradiating (λ irr = 312 nm, 3 min) the stock solution of (2R,2 R)-(P,P)-trans-1 in CD 2 Cl 2 without further purification due to high photoequilibrium (> 99%). Catalyst (2R,2 R)-(P,P)-cis-1 was obtained by preparative HPLC after the thermal isomerization step-2, see Fig S7, (c). Note: For preparative HPLC, an analytical AD-H column (chiralpak AD-H (4.6 250 mm) was used; eluant 70:30 heptane-isopropanol; flow rate 0.5 ml/min; temperature 20 C). With this method, 1.5 mg of (2R,2 R)-(P,P)-cis-1 was obtained in 24 h. 9

A B 16 h 12 h 8 h 4 h 0.2 h C D (S) (R) Fig. S10. Switching-on the catalyst s enantioselectivity in situ with light. The non-enantioselective catalyst (2R,2 R)-(P,P)-trans-1 is switched to the enantioselective catalyst (2R,2 R)-(M,M)-cis-1 by irradiation at 312 nm for 2 min (under an argon atmosphere) in the presence of methoxy thiophenol (0.2 M) and cyclohexenone (0.2 M). (A) The switching was monitored by UV-vis spectroscopy (spectra after 0 (black), 0.5 (blue), 1.0 (red), and 2.0 (green) min irradiation). The inset shows an expansion of the 1 H NMR spectrum showing that a mixture of (2R,2 R)-(P,P)-trans-1 (3.06 ppm) and (2R,2 R)-(M,M)-cis-1 (3.01 and 1.51 and 1.39 ppm) is formed. (B) 1 H-NMR (CD 2 Cl 2, -15 C) spectroscopy is used to follow the asymmetric Michael addition with the mixture of catalysts (2R,2 R)-(P,P)-trans-1 and (2R,2 R)-(M,M)-cis- 1 (the total catalyst loading is 0.3 mol%) formed by in situ irradiation. For labeling H a /H b see figure S9. (C) A significant rate enhancement compared with the non-irradiated reaction mixture (see Figure 3 for comparison) was observed with a 40 % conversion after 15 h. (D) The reaction was stopped after 18 h. Chiral HPLC analysis (Chiralpak AD-H column (4.6 250 mm); eluant 98:2 heptane-isopropanol; flow rate 0.5 ml/min; detection at 254 nm, temperature 40 C) shows that the reaction is stereoselective with an e.r. of 74/26 (S/R). 10

Fig. S11. Molecular modeling of compound 1 in each isomerizing state, (A) (2R,2 R)-(P,P)-trans-1, (B) (2R,2 R)-(M,M)-cis-1, (C) (2R,2 R)-(P,P)-cis-1, (D) (2R,2 R)-(M,M)-trans-1. The closer distance between the thiourea and DMAP functional groups in the cis isomer (about 10 Å, distance defined between nitrogen of the DMAP unit and carbon of thiourea unit), distinct from that of the trans isomer (about 20 Å), supports the experimental observation that the cis isomer shows higher catalytic activity. Note S5 The calculations were performed with the HyperChem 8.0 (HyperChem(TM), Hypercube, Inc., 1115 NW 4th Street, Gainesville, FL 32601, USA) software package at the RM1 level of theory. Default convergence and integration settings were used. The motor units of the four isomers were built from the crystal structures of the first generation motors (S2, S5,S6). 11

Fig. S12. Chiral HPLC chromatograms of the product using the (S)-catalysts. Isomer (2S,2 S)-(P,P)-cis-1 preferentially gives the (R)-product (Fig. A, e.r., S/R, 25/75), while isomer (2S,2 S)-(M,M)-cis-1 displays an opposite stereoselectivity (Fig. B, e.r., S/R, 76/24). Conditions for HPLC: chiralpak AD-H column (4.6 250 mm); eluant 98:2 heptane-isopropanol; flow rate 0.5 ml/min; detection at 254 nm, temperature 40 C. The absolute configuration of the adduct product in the catalytic reaction was confirmed by chiral HPLC analysis using OB-H (chiralpak OB-H, 4.6 250 mm) column following a literature procedure (S4). Reference: S1. J. Wang, A. Kulago, W. R. Browne, B. L. Feringa, J. Am. Chem. Soc. 132, 4191 (2010). S2. M. K. J. ter Wiel, Ph.D. Thesis, University of Groningen, (2004). S3. M. K. J. ter Wiel, N. Koumura, R. A. van Delden, A. Meetsma, N. Harada, B. L. Feringa, Chirality 12, 734 (2000). S4. N. K. Rana, S. Selvakumar, V. K. Singh, J. Org. Chem. 75, 2089 (2010). 12

S5. M. M. Pollard, A. Meetsma, B. L. Feringa, Org. Biomol. Chem. 6, 507 (2008). S6. M. K. J. ter Wiel, R. A. van Delden, A. Meetsma, B. L. Feringa, J. Am. Chem. Soc. 127, 14208 (2005). NMR and Mass Spectra 1 H-NMR of compound 6 13 C-NMR of compound 6 13

1 H-NMR of compound 7 13 H-NMR of compound 7 14

1 H-NMR of (2R,2 R)-(P,P)-trans-1 13 C-NMR of (2R,2 R)-(P,P)-trans-1 15

HRMS of Compound 7 HRMS of Compound 1 16

1 H-NMR of (S,R)-10 13 C-NMR of (S,R)-10 17

1 H-NMR of (R)-11 13 C-NMR of (R)-11 18

1 H-NMR of (R)-12 Note: As mentioned in Note S2, purification of (R)-12 was not achieved, 1 H-NMR measurement was performed using the crude product. The protons that are assigned to (R)-12 are marked with an arrow. 1 H-NMR of (R)-13 19

1 H-NMR spectrum of the Michael addition product 4, identical with that reported in literature (S4) 20