SUPPORTING INFORMATION

Transcription

1 SUPPORTING INFORMATION Expedient Synthesis of 1,5-Diketones by Rhodium-Catalyzed Hydroacylation Enabled by C-C Bond Cleavage Rui Guo, Guozhu Zhang State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, University of Chinese Academy of Sciences, Chinese Academy of Sciences, 345 Lingling Road, Shanghai , P. R. China CONTENTS 1. General Experiment Information General Procedures Synthesis and Characterization of Materials Synthesis and Characterization of Products Deuterium-Labeling Experiments In-Situ IR Experiments Control Experiments References Copies of 1 H and 13 C NMR Spectra S 1

2 1. General Experiment Information NMR spectra were recorded at room temperature on the following spectrometers: Agilent (400 MHz) and VARIAN (400 MHz). Chemical shifts are given in ppm and coupling constants in Hz. 1 H spectra were calibrated in relation to the reference measurement of TMS (0.00 ppm). 13 C spectra were calibrated in relation to deuterated solvents, namely CDCl 3 (77.16 ppm). The following abbreviations were used for 1 H NMR spectra to indicate the signal multiplicity: s (singlet), d (doublet), t (triplet), q (quartet) and m (multiplet) as well as combinations of them. When combinations of multiplicities are given the first character noted refers to the largest coupling constant. For DART-HR and EI-HR (GC-TOF) spectrometer was applied. Infrared Spectroscopy (IR) was processed on an FT-IR spectrometer named Nicolet 380. The method is denoted in brackets. For the most significant bands the wave number ṽ (cm -1 ) is given. Chemicals were purchased from commercial suppliers. Unless stated otherwise, all the substrates and solvents were purified and dried according to standard methods prior to use. Reactions requiring inert conditions were carried out in glove box. S 2

3 2. General Procedures (1) General Procedure A: Synthesis of starting materials Synthesis of 1a 1c, 1f, 1i 1l To a solution of cyclobutanone (20.0 mmol) in THF (40mL) at 0 C was added alkenyl magnesium bromide (22.0 mmol) over 10 min. The mixture was stirred at 0 C for 2 h. The reaction was quenched by the addition of a saturated solution of NH 4 Cl. The organic layer was extracted with diethyl ether. The combined organics were washed with brine, dried (MgSO 4 ) and concentrated in vacuo. The product was purified by flash column chromatography to afford the product. Synthesis of 1d, 1e A 100 ml two-neck round bottomed flask equipped with an addition funnel, a condenser and a stir bar was charged with Mg turnings (0.5 g, 20.8 mmol). Anhydrous THF (6 ml) were added via syringe. Then iodine (40 mg, mmol) was added under nitrogen. After stirring at rt for 5 min, alkenyl bromide (20 mmol) in anhydrous THF (20 ml) was then added dropwise over 1 h via the addition funnel, during which time a significant exotherm was observed. The reaction was then placed in an oil bath and heated at reflux for 2 h. After cooling to rt, cyclobutanone (1.47 g, 21 mmol) was added. After stirring for 12 h, saturated NH 4 Cl (aq) was added. The organic layer was extracted with ethyl acetate and washed with brine, separated, dried over MgSO 4, filtered and then concentrated. The residue was purified by silica gel column chromatography to afford the product. Synthesis of 1g, 1h To a solution of cyclobutanone (10 mmol) in THF (8 ml) and H 2 O (2 ml) at room temperature was added substituted allyl bromide (10 mmol), followed by indium powder (10 mmol). The resulting mixture was then stirred at room temperature for 12h. The resulting mixture was filtered through a pad of celite, rinsed with EtOAc, the layers separated, the aqueous layer extracted with EtOAc, dried over MgSO 4, filtered and then concentrated. The residue was purified by silica gel column chromatography to afford the product. S 3

4 (2) General Procedure B: Synthesis of 1,5-diketone products 2a 2ao, 7, 8 To an over-dried sealed tube equipped with a stirrer bar was added [Rh(COD)Cl] 2 (2.5 mg, mmol), PPh 3 (5.2 mg, 0.02 mmol) and K 2 CO 3 (1.4 mg, 0.01 mmol) in glove box. Then, a solution of alkenyl cyclobutanol 1 (0.30 mmol, 1.5 equiv.) and aldehyde (0.20 mmol, 1.0 equiv.) in dry xylene (1.0ml) was added. The tube was sealed and removed from the glove box. After stirred at 140 C for 6 h, the reaction mixture was cooled to room temperature. The resulting mixture was passed through a pad of silica gel and eluted with ethyl acetate. The filtrate was concentrated under reduced pressure. The residue was purified by silica gel flash chromatography (hexane/etoac = 5:1) to give pure product. The detailed ligands screening. Entry Catalyst Ligand Base Solvent Temp.( C) Time (h) Yield(%) 1 [Rh(COD)Cl] 2 PPh 3 K 3 PO 4 Toluene [Rh(COD)Cl] 2 PCy 3 K 3 PO 4 Toluene [Rh(COD)Cl] 2 (4-FPh) 3 P K 3 PO 4 Toluene [Rh(COD)Cl] 2 (4-MeOPh) 3 P K 3 PO 4 Toluene [Rh(COD)Cl] 2 (2-MeOPh) 3 P K 3 PO 4 Toluene [Rh(COD)Cl] 2 (4-MePh) 3 P K 3 PO 4 Toluene [Rh(COD)Cl] 2 (3-MePh) 3 P K 3 PO 4 Toluene [Rh(COD)Cl] 2 (2-MePh) 3 P K 3 PO 4 Toluene [Rh(COD)Cl] 2 dppm K 3 PO 4 Toluene [Rh(COD)Cl] 2 dppe K 3 PO 4 Toluene [Rh(COD)Cl] 2 dppp K 3 PO 4 Toluene [Rh(COD)Cl] 2 dppb K 3 PO 4 Toluene [Rh(COD)Cl] 2 dppf K 3 PO 4 Toluene S 4

5 3. Synthesis and Characterization of Materials 1-vinylcyclobutanol (1a) Compound 1a is a known compound. According to General Procedure A, product 1a (2.2 g, 22.5 mmol, 63%) was obtained from cyclobutanone (2.5 g, 35.7 mmol) and vinylmagnesium bromide (43ml, 1.0 M in THF) as light yellow oil with spectral properties identical to the reported in the literature. [1] 1 H NMR (400 MHz, CDCl 3 ): δ 6.10 (dd, J = 17.3, 10.7 Hz, 1H), 5.23 (d, J = 17.3 Hz, 1H), 5.04 (dd, J = 10.7, 1.2 Hz, 1H), 2.37 (s, 1H), (m, 4H), (m, 1H), (m, 1H). 1-(prop-1-en-2-yl)cyclobutanol (1b) Compound 1b is a known compound. According to General Procedure A, product 1b (550 mg, 4.9 mmol, 69%) was obtained from cyclobutanone (0.5 g, 7.1 mmol) and isopropenylmagnesium bromide (17.2ml, 0.5 M in THF) as light yellow oil with spectral properties identical to the reported in the literature. [2] 1 H NMR (400 MHz, CDCl 3 ): δ 4.94 (s, 1H), 4.81 (s, 1H), (m, 2H), 2.15 (s, 1H), (m, 2H), (m, 1H), 1.78 (s, 3H), (m, 1H). (E)-1-(but-2-en-2-yl)cyclobutanol (1c) Compound 1c is a known compound. According to General Procedure A, product 1c ( 1.02 g, 8.1 mmol, 81%) was obtained from cyclobutanone (700 mg, 10.0 mmol) and 1-Methyl-1-propenylmagnesium bromide (22ml, 0.5 M in THF) as light yellow oil with spectral properties identical to the reported in the literature. [3] 1 H NMR (400 MHz, CDCl 3 ): δ 5.22 (qd, J = 7.1, 1.4 Hz, 1H), (m, 3H), (m, 2H), (m, 2H), 1.63 (s, 3H), 1.57 (d, J = 1.4 Hz, 3H). 1-(1-phenylvinyl)cyclobutanol (1d) S 5

6 Compound 1d is a known compound. According to General Procedure A, product 1d (320 mg, 1.5 mmol, 61%) was obtained from cyclobutanone (210 mg, 3.0 mmol) and α-bromostyrene (458 mg, 2.5 mmol) as light yellow oil with spectral properties identical to the reported in the literature. [4] 1 H NMR (400 MHz, CDCl 3 ): δ (m, 2H), (m, 3H), (m, 2H), (m, 2H), (m, 2H), 2.08 (s, 1H), (m, 1H), (m, 1H). 13 C NMR (101 MHz, CDCl 3 ): δ 152.3, 139.0, 128.1, 127.5, 127.4, 112.8, 78.0, 77.4, 35.6, (Z)-1-styrylcyclobutanol (1e) Compound 1e is a known compound. According to General Procedure A, product 1e (365 mg, 2.1 mmol, 42%) was obtained from cyclobutanone (420 mg, 6.0 mmol) and β-bromostyrene (915 mg, 5.0 mmol) as light yellow oil with spectral properties identical to the reported in the literature. [5] 1 H NMR (400 MHz, CDCl 3 ): δ 7.35 (d, J = 7.5 Hz, 2H), 7.22 (t, J = 7.5 Hz, 2H), 7.14 (t, J = 7.3 Hz, 1H), 6.42 (d, J = 12.2 Hz, 1H), 5.86 (d, J = 12.2 Hz, 1H), 2.27 (s, 1H), 2.14 (t, J = 7.7 Hz, 4H), (m, 1H), (m, 1H). 13 C NMR (101 MHz, CDCl 3 ): δ 136.2, 131.5, 129.3, 128.0, 127.3, 74.0, 38.0, allylcyclobutanol (1f) Compound 1f is a known compound. According to General Procedure A, product 1f (1.2 g, 10.9 mmol, 76%) was obtained from cyclobutanone (1.0 g, 14.3 mmol) and allylmagnesium bromide (17.2ml, 1.0 M in THF) as light yellow oil with spectral properties identical to the reported in the literature. [6] 1 H NMR (300 MHz, CDCl 3 ): δ 5.82 (ddt, J = 12.5, 7.9, 7.3 Hz, 1H), (m, 2H), 2.55 (s, 1H), 2.31 (d, J = 7.2 Hz, 2H), 2.01 (dd, J = 16.4, 9.5 Hz, 4H), (m, 1H), (m, 1H). 13 C NMR (75 MHz, CDCl 3 ): δ 133.6, 118.5, 73.8, 43.8, 35.2, (2-methylallyl)cyclobutanol (1g) S 6

7 Compound 1g is a known compound. According to General Procedure A, product 1g (422 mg, 3.4 mmol, 67%) was obtained from cyclobutanone (350 mg, 5.0 mmol) and 3-bromo-2-methylpropene (1.35 g, 10 mmol) as light yellow oil with spectral properties identical to the reported in the literature. [7] 1 H NMR (400 MHz, CDCl 3 ): δ 4.90 (s, 1H), 4.76 (s, 1H), (m, 3H), (m, 4H), (m, 4H), (m, 1H). 13 C NMR (101 MHz, CDCl 3 ): δ 142.6, 114.2, 74.0, 47.4, 36.2, 24.0, (2-phenylallyl)cyclobutanol (1h) According to General Procedure A, product 1h (1.54 g, 8.2 mmol, 82%) was obtained from cyclobutanone (700 mg, 10.0 mmol) and 3-bromo-2-phenylpropene (1.96 g, 10.0 mmol) as light yellow oil. 1 H NMR (400 MHz, CDCl 3 ): δ (m, 2H), (m, 2H), (m, 1H), 5.36 (d, J = 1.6 Hz, 1H), 5.16 (s, 1H), 2.83 (s, 2H), 2.21 (s, 1H), (m, 4H), (m, 1H), (m, 1H). 13 C NMR (101 MHz, CDCl 3 ):δ 145.1, 142.1, 128.2, 127.4, 126.2, 116.1, 74.4, 44.6, 35.4, IR (neat) cm -1 ṽ: 3391, 2980, 2933, 1623, 1492, 1443, 1264, 1120, 1069, 963, 898, 778, 699; HRMS (EI(+), 70 ev) : C 13 H 16 O [M] + : calcd , found: (but-3-en-1-yl)cyclobutanol (1i) Compound 1i is a known compound. According to General Procedure A, product 1i (1.02 g, 8.1 mmol, 81%) was obtained from cyclobutanone (700 mg, 10.0 mmol) and 3-butenylmagnesium bromide (24 ml, 0.5 M in THF) as light yellow oil with spectral properties identical to the reported in the literature. [8] 1 H NMR (400 MHz, CDCl 3 ): δ (m, 1H), (m, 1H), (m, 1H), 2.29 (s, 1H), (m, 2H), (m, 4H), (m, 3H), (m, 1H). 13 C NMR (101 MHz, CDCl 3 ):δ 139.0, 114.3, 75.1, 38.4, 35.8, 27.9, ((benzyloxy)methyl)-1-vinylcyclobutanol (1j) S 7

8 Compound 1j is a known compound. According to General Procedure A, product 1j (245 mg, 1.1 mmol, 86%, dr = 6/1) was obtained from 3-((benzyloxy)methyl)cyclobutanone (250 mg, 1.31 mmol) and vinylmagnesium bromide (1.5 ml, 1.0 M in THF) as light yellow oil with spectral properties identical to the reported in the literature. [9] 1 H NMR (400 MHz, CDCl 3 ): δ (m, 4H), (m, 1H), 6.08 (ddd, J = 17.3, 10.7, 1.3 Hz, 1H), 5.26 (d, J = 17.3 Hz, 1H), 5.07 (d, J = 10.7 Hz, 1H), 4.55 (s, 2H), 3.50 (d, J = 5.3 Hz, 2H), 2.73 (s, 1H), (m, 2H), (m, 1H), (m, 2H). 13 C NMR (101 MHz, CDCl 3 ): δ 142.5, 138.1, 128.4, 127.7, 127.6, 111.4, 74.0, 73.1, 72.0, 39.1, phenyl-1-vinylcyclobutanol (1k) Compound 1k is a known compound. According to General Procedure A, product 1k (277 mg, 1.6 mmol, 93%, dr = 5/1) was obtained from 3-phenylcyclobutanone (250 mg, 1.71 mmol) and vinylmagnesium bromide (2.1 ml, 1.0 M in THF) as light yellow oil with spectral properties identical to the reported in the literature. [10] 1 H NMR (400 MHz, CDCl 3 )δ 7.29 (t, J = 7.6 Hz, 2H), 7.23 (d, J = 7.2 Hz, 2H), 7.18 (t, J = 7.2 Hz, 1H), 6.21 (dd, J = 17.3, 10.6 Hz, 1H), 5.36 (d, J = 17.3 Hz, 1H), 5.16 (d, J = 10.7 Hz, 1H), (m, 1H), (m, 2H), 2.49 (br, 1H), (m, 2H). 2-benzyl-1-vinylcyclobutanol (1l) Compound 1l is a known compound. According to General Procedure A, product 1l (264 mg, 1.4 mmol, 90%, dr > 20/1) was obtained from 3-phenylcyclobutanone (250 mg, 1.56 mmol) and vinylmagnesium bromide (1.9 ml, 1.0 M in THF) as light yellow oil with spectral properties identical to the reported in the literature. [11] 1 H NMR (400 MHz, CDCl 3 ) δ 7.26 (t, J = 7.5 Hz, 2H), (m, 3H), 6.02 (dd, J = 17.3, 10.6 Hz, 1H), 5.07 (dd, J = 61.8, 14.0 Hz, 2H), 2.92 (dd, J = 13.8, 6.4 Hz, 1H), 2.74 (dd, J = 13.7, S 8

9 9.5 Hz, 1H), (m, 1H), (m, 1H), (m, 1H), (m, 2H), 1.57 (br, 1H). 4. Synthesis and Characterization of Products 1-phenylheptane-1,5-dione (2a) Compound 2a is a known compound. According to General Procedure B, product 2a (40.0 mg, mmol, 98%) was obtained from 1a (30.0 mg, 0.30 mmol) and benzaldehyde (21.2 mg, 0.20 mmol) as yellow solid with spectral properties identical to the reported in the literature. [12] 1 H NMR (400 MHz, CDCl 3 ) δ (m, 2H), 7.47 (t, J = 7.4 Hz, 1H), 7.37 (t, J = 7.6 Hz, 2H), 2.93 (t, J = 7.1 Hz, 2H), 2.46 (t, J = 7.1 Hz, 2H), 2.35 (q, J = 7.3 Hz, 2H), (m, 2H), 0.97 (t, J = 7.3 Hz, 3H). 13 C NMR (101 MHz, CDCl 3 ) δ 210.8, 199.5, 136.5, 132.8, 128.3, 127.7, 40.9, 37.2, 35.6, 18.0, (4-fluorophenyl)heptane-1,5-dione (2b) According to General Procedure B, product 2b (42.6 mg, mmol, 96%) was obtained from 1a (30.0 mg, 0.30 mmol) and 4-fluorobenzaldehyde (24.8 mg, 0.20 mmol) as yellow solid, mp = o C. 1 H NMR (400 MHz, CDCl 3 ) δ 7.97 (dd, J = 8.4, 5.6 Hz, 2H), 7.10 (t, J = 8.5 Hz, 2H), 2.96 (t, J = 7.1 Hz, 2H), 2.53 (t, J = 6.9 Hz, 2H), 2.42 (q, J = 7.3 Hz, 2H), (m, 2H), 1.04 (t, J = 7.3 Hz, 3H). 13 C NMR (101 MHz, CDCl 3 ) δ 211.1, 198.2, (d, J C-F = Hz), 133.1, (d, J C-F = 9.4 Hz), (d, J C-F = 21.9 Hz), 41.0, 37.4, 35.9, 18.2, 7.7. IR (neat) cm -1 ṽ: 2891, 1707, 1671, 1595, 1508, 1452, 1375, 1264, 1202, 1160, 985, 867, 768; HRMS (EI(+), 70 ev) : C 13 H 15 FO 2 [M] + : calcd , found: (4-chlorophenyl)heptane-1,5-dione (2c) According to General Procedure B, product 2c (35.2 mg, mmol, 74%) was obtained from 1a (30.0 mg, 0.30 mmol) and 4-chlorobenzaldehyde (28.0 mg, 0.20 mmol) as yellow solid, mp = o C. 1 H NMR (400 MHz, CDCl 3 ) δ 7.88 (d, J = 8.4 Hz, 2H), 7.41 (d, J = 8.4 Hz, 2H), 2.96 (t, J = 7.0 Hz, 2H), 2.52 (t, J = 6.9 Hz, 2H), 2.42 (q, J = 7.3 Hz, 2H), (m, 2H), 1.04 (t, J = 7.3 Hz, 3H). S 9

10 13 C NMR (101 MHz, CDCl 3 ) δ 211.1, 198.5, 139.4, 135.0, 129.4, 128.8, 41.0, 37.5, 35.9, 18.2, 7.8. IR (neat) cm -1 ṽ: 2959, 2897, 1707, 1671, 1587, 1451, 1406, 1375, 1262, 1204, 1091, 1015, 864, 797, 767; HRMS (EI(+), 70 ev) : C 13 H 15 ClO 2 [M] + : calcd , found: (4-bromophenyl)heptane-1,5-dione (2d) According to General Procedure B, product 2d (25.4 mg, 0.09 mmol, 45%) was obtained from 1a (30.0 mg, 0.30 mmol) and 4-bromobenzaldehyde (37.0 mg, 0.20 mmol) as yellow solid, mp = o C. 1 H NMR (400 MHz, CDCl 3 ) δ 7.82 (d, J = 8.5 Hz, 2H), 7.59 (d, J = 8.4 Hz, 2H), 2.97 (t, J = 7.0 Hz, 2H), 2.54 (t, J = 6.9 Hz, 2H), 2.43 (q, J = 7.3 Hz, 2H), (m, 2H), 1.05 (t, J = 7.3 Hz, 3H). 13 C NMR (101 MHz, CDCl 3 ) δ 211.1, 198.8, 135.4, 131.9, 129.6, 128.2, 41.0, 37.5, 35.9, 18.2, 7.8. IR (neat) cm -1 ṽ: 2920, 2850, 1706, 1670, 1645, 1582, 1465, 1416, 1260, 1094, 1015, 799; HRMS (EI(+), 70 ev) :C 13 H 15 BrO 2 [M] + : calcd , found: (o-tolyl)heptane-1,5-dione (2e) According to General Procedure B, product 2e (31.8 mg, mmol, 73%) was obtained from 1a (30.0 mg, 0.30 mmol) and 2-methylbenzaldehyde (24.0 mg, 0.20 mmol) as yellow solid, mp = o C. 1 H NMR (400 MHz, CDCl 3 ) δ 7.64 (d, J = 7.7 Hz, 1H), 7.36 (t, J = 7.5 Hz, 1H), 7.25 (t, J = 7.8 Hz, 2H), 2.93 (t, J = 7.1 Hz, 2H), 2.53 (t, J = 7.1 Hz, 2H), 2.49 (s, 3H), 2.44 (q, J = 7.3 Hz, 2H), (m, 2H), 1.06 (t, J = 7.3 Hz, 3H). 13 C NMR (101 MHz, CDCl 3 ) δ 211.1, 203.8, 138.0, 137.7, 131.9, 131.2, 128.4, 125.6, 41.2, 40.3, 35.9, 21.3, 18.4, 7.8. IR (neat) cm -1 ṽ: 1710, 1682, 1454, 1410, 1373, 1289, 1258, 1223, 1113, 974, 755; HRMS (EI(+), 70 ev) : C 14 H 18 O 2 [M] + : calcd , found: mesitylheptane-1,5-dione (2f) According to General Procedure B, product 2f (20.7 mg, mmol, 42%) was obtained from 1a (30.0 mg, 0.30 mmol) and mesitaldehyde (29.6 mg, 0.20 mmol) as yellow solid, mp = o C. 1 H NMR (400 MHz, CDCl 3 ) δ 6.82 (s, 2H), 2.72 (t, J = 7.1 Hz, 2H), 2.55 (dd, J = 14.0, 7.0 Hz, 2H), 2.43 (q, J = 7.2 Hz, 2H), 2.26 (s, 3H), 2.17 (s, 6H), (m, 2H), 1.05 (t, J = 7.3 Hz, 3H). 13 C NMR (101 MHz, CDCl 3 ) δ 211.0, 210.3, 139.5, 138.3, 132.4, 128.4, 43.6, 41.1, 35.9, 21.0, 19.0, 17.5, 7.8. IR (neat) cm -1 ṽ: 2963, 2933, 1699, 1610, 1451, 1410, 1375, 1260, 1091, 1019, 853, 798; S 10

11 HRMS (EI(+), 70 ev) : C 16 H 22 O 2 [M] + : calcd , found: (2-methoxyphenyl)heptane-1,5-dione (2g) According to General Procedure B, product 2g (30.9 mg, mmol, 66%) was obtained from 1a (30.0 mg, 0.30 mmol) and 2-methoxybenzaldehyde (27.2 mg, 0.20 mmol) as yellow solid, mp = o C. 1 H NMR (400 MHz, CDCl 3 ) δ 7.65 (dd, J = 7.7, 1.8 Hz, 1H), (m, 1H), (m, 2H), 3.87 (s, 3H), 2.99 (t, J = 7.0 Hz, 2H), 2.48 (t, J = 7.3 Hz, 2H), 2.41 (q, J = 7.3 Hz, 2H), (m, 2H), 1.03 (t, J = 7.3 Hz, 3H). 13 C NMR (101 MHz, CDCl 3 ) δ 211.4, 202.1, 158.4, 133.3, 130.1, 128.2, 120.6, 111.4, 55.4, 42.6, 41.4, 35.8, 18.4, 7.8. IR (neat) cm -1 ṽ: 2970, 2938, 2840, 1709, 1670, 1596, 1484, 1461, 1371, 1285, 1243, 1163, 1112, 1021, 982, 756; HRMS (EI(+), 70 ev) : C 14 H 18 O 3 [M] + : calcd , found: (4-methoxyphenyl)heptane-1,5-dione (2h) Compound 2h is a known compound. According to General Procedure B, product 2h (40.7 mg, mmol, 87%) was obtained from 1a (30.0 mg, 0.30 mmol) and 4-methoxybenzaldehyde (27.2 mg, 0.20 mmol) as yellow solid with spectral properties identical to the reported in the literature. [13] 1 H NMR (400 MHz, CDCl 3 ) δ 7.93 (d, J = 8.8 Hz, 2H), 6.91 (d, J = 8.8 Hz, 2H), 3.85 (s, 3H), 2.94 (t, J = 7.1 Hz, 2H), 2.52 (t, J = 7.0 Hz, 2H), 2.42 (q, J = 7.3 Hz, 2H), (m, 2H), 1.04 (t, J = 7.3 Hz, 3H). 13 C NMR (101 MHz, CDCl 3 ) δ 211.3, 198.4, 163.4, 130.3, 129.8, 113.6, 55.4, 41.2, 37.1, 35.8, 18.5, (5-oxoheptanoyl)benzonitrile (2i) According to General Procedure B, product 2i (36.6 mg, 0.16 mmol, 80%) was obtained from 1a (30.0 mg, 0.30 mmol) and 4-cyanobenzaldehyde (26.2 mg, 0.20 mmol) as yellow solid, mp = o C. 1 H NMR (400 MHz, CDCl 3 ) δ 8.04 (d, J = 8.0 Hz, 2H), 7.76 (d, J = 8.1 Hz, 2H), 3.02 (t, J = 7.0 Hz, 2H), 2.55 (t, J = 6.8 Hz, 2H), 2.43 (q, J = 7.3 Hz, 2H), (m, 2H), 1.05 (t, J = 7.3 Hz, 3H). 13 C NMR (101 MHz, CDCl 3 ) δ 211.0, 198.4, 139.6, 132.4, 128.4, 117.9, 116.2, 40.8, 37.8, 35.9, 17.9, 7.7.IR (neat) cm -1 ṽ: 2958, 2228, 1709, 1688, 1603, 1453, 1405, 1373, 1262, 1200, 1110, 1016, 981, 800, 767; HRMS (EI(+), 70 ev) : C 14 H 15 NO 2 [M] + : calcd , found: S 11

12 methyl 4-(5-oxoheptanoyl)benzoate (2j) According to General Procedure B, product 2j (47.7 mg, mmol, 91%) was obtained from 1a (30.0 mg, 0.30 mmol) and methyl 4-formylbenzoate (32.8 mg, 0.20 mmol) as yellow solid, mp = o C. 1 H NMR (400 MHz, CDCl 3 ) δ 8.10 (d, J = 8.3 Hz, 2H), 7.99 (d, J = 8.4 Hz, 2H), 3.93 (s, 3H), 3.03 (t, J = 7.0 Hz, 2H), 2.54 (t, J = 7.0 Hz, 2H), 2.43 (q, J = 7.3 Hz, 2H), (m, 2H), 1.05 (t, J = 7.3 Hz, 3H). 13 C NMR (101 MHz, CDCl 3 ) δ 211.1, 199.2, 166.2, 139.9, 133.8, 129.8, 127.9, 52.4, 41.0, 37.8, 35.9, 18.0, 7.8. IR (neat) cm -1 ṽ: 1719, 1674, 1435, 1373, 1280, 1193, 1107, 1014, 986, 956, 875, 754, 701; HRMS (EI(+), 70 ev) : C 15 H 18 O 4.[M] + : calcd , found: (4-(trifluoromethyl)phenyl)heptane-1,5-dione (2k) According to General Procedure B, product 2k (50.6 mg, mmol, 93%) was obtained from 1a (30.0 mg, 0.30 mmol) and 4-(trifluoromethyl)benzaldehyde (34.8 mg, 0.20 mmol) as yellow solid, mp = o C. 1 H NMR (400 MHz, CDCl 3 ) δ 8.05 (d, J = 7.9 Hz, 2H), 7.71 (d, J = 7.9 Hz, 2H), 3.03 (t, J = 7.0 Hz, 2H), 2.55 (t, J = 6.8 Hz, 2H), 2.43 (q, J = 7.3 Hz, 2H), (m, 2H), 1.05 (t, J = 7.3 Hz, 3H). 13 C NMR (101 MHz, CDCl 3 ) δ 211.0, 198.8, 139.3, (q, J C-F = 32.7 Hz), 128.4, (q, J C-F = 3.7 Hz), (q, J C-F = Hz), 40.9, 37.8, 35.9, 18.0, 7.8. IR (neat) cm -1 ṽ: 1707, 1675, 1410, 1376, 1323, 1261, 1176, 1112, 1064, 1012, 985, 866, 834, 602, 501; HRMS (EI(+), 70 ev) : C 14 H 15 F 3 O 2 [M] + : calcd , found: (4-(dimethylamino)phenyl)heptane-1,5-dione (2l) According to General Procedure B, product 2l (38.5 mg, mmol, 78%) was obtained from 1a (30.0 mg, 0.30mmol) and 4-dimethylaminobenzaldehyde (29.8 mg, 0.20 mmol) as yellow solid, mp = o C. 1 H NMR (400 MHz, CDCl 3 ) δ 7.88 (d, J = 8.9 Hz, 2H), 6.64 (d, J = 8.9 Hz, 2H), 3.05 (s, 6H), 2.90 (t, J = 7.1 Hz, 2H), 2.52 (t, J = 7.1 Hz, 2H), 2.42 (q, J = 7.4 Hz, 2H), (m, 2H), 1.04 (t, J = 7.3 Hz, 3H). 13 C NMR (101 MHz, CDCl 3 ) δ 211.5, 198.0, 153.3, 130.2, 124.8, 110.6, 41.5, 40.0, 36.8, 35.9, 18.9, 7.8. IR (neat) cm -1 ṽ: 2920, 2849, 1710, 1647, 1600, 1417, 1369, 1261, 1184, 1092, 1020, 799; HRMS (EI(+), 70 ev) : C 15 H 21 NO 2 [M] + : calcd , found: S 12

13 4-(5-oxoheptanoyl)benzaldehyde (2m) According to General Procedure B, product 2m (20.0 mg, mmol, 43%) was obtained from 1a (30.0 mg, 0.30 mmol) and terephthalaldehyde (26.8 mg, 0.20 mmol) as yellow solid, mp = o C. 1 H NMR (400 MHz, CDCl 3 ) δ (s, 1H), 8.10 (d, J = 8.1 Hz, 2H), 7.97 (d, J = 8.1 Hz, 2H), 3.06 (t, J = 7.0 Hz, 2H), 2.56 (t, J = 6.8 Hz, 2H), 2.44 (q, J = 7.3 Hz, 2H), (m, 2H), 1.06 (t, J = 7.3 Hz, 3H). 13 C NMR (101 MHz, CDCl 3 ) δ 211.1, 199.2, 191.6, 140.9, 139.0, 129.8, 128.6, 41.0, 38.0, 35.9, 18.0, 7.8. IR (neat) cm -1 ṽ: 2919, 2849, 1704, 1677, 1645, 1417, 1374, 1264, 1205, 1112, 1015, 985, 817, 773; HRMS (EI(+), 70 ev) : C 14 H 16 O 3 [M] + : calcd , found: , 1'-(1,4-phenylene)bis(heptane-1,5-dione) (2n) According to General Procedure B, product 2n (45.0 mg, mmol, 68%) was obtained from 1a (60.0 mg, 0.60 mmol) and diphenylacetylene (26.8mg, 0.20 mmol) as yellow solid, mp = o C. 1 H NMR (400 MHz, CDCl 3 ) δ 8.03 (s, 4H), 3.04 (t, J = 7.0 Hz, 4H), 2.56 (t, J = 6.9 Hz, 4H), 2.44 (q, J = 7.3 Hz, 4H), (m, 4H), 1.06 (t, J = 7.3 Hz, 6H). 13 C NMR (101 MHz, CDCl 3 ) δ 211.0, 199.2, 139.8, 128.2, 41.0, 37.9, 35.9, 18.09, 7.8. IR (neat) cm -1 ṽ: 2935, 2877, 1704, 1674, 1603, 1405, 1371, 1263, 1111, 1014, 982, 816, 762; HRMS (EI(+), 70 ev) : C 20 H 26 O 4 [M] + : calcd , found: (naphthalen-1-yl)heptane-1,5-dione (2o) According to General Procedure B, product 2o (41.2 mg, mmol, 81%) was obtained from 1a (30.0 mg, 0.30 mmol) and 1-naphthaldehyde (31.2 mg, 0.20 mmol) as yellow solid, mp = o C. 1 H NMR (400 MHz, CDCl 3 ) δ 8.59 (d, J = 8.6 Hz, 1H), 7.98 (d, J = 8.2 Hz, 1H), 7.88 (d, J = 7.3 Hz, 2H), 7.54 (ddd, J = 22.6, 15.2, 7.8 Hz, 3H), 3.09 (t, J = 7.1 Hz, 2H), 2.57 (t, J = 7.1 Hz, 2H), 2.44 (q, J = 7.3 Hz, 2H), (m, 2H), 1.06 (t, J = 7.3 Hz, 3H). 13 C NMR (101 MHz, CDCl 3 ) δ 211.1, 204.1, 135.7, 133.9, 132.6, 130.0, 128.4, 127.9, 127.6, 126.4, 125.6, 124.4, 41.2, 40.9, 35.9, S 13

14 18.7, 7.8. IR (neat) cm -1 ṽ: 1708, 1676, 1506, 1408, 1369, 1234, 1172, 1104, 1070, 942, 799, 775; HRMS (EI(+), 70 ev) : C 17 H 18 O 2 [M] + : calcd , found: (naphthalen-2-yl)heptane-1,5-dione (2p) According to General Procedure B, product 2p (44.7 mg, mmol, 88%) was obtained from 1a (30.0 mg, 0.30 mmol) and 2-naphthaldehyde (31.2 mg, 0.20 mmol) as yellow solid. mp = o C. 1 H NMR (400 MHz, CDCl 3 ) δ 8.47 (s, 1H), 8.02 (d, J = 8.6 Hz, 1H), 7.95 (d, J = 8.0 Hz, 1H), (m, 2H), 7.56 (dt, J = 14.8, 6.9 Hz, 2H), 3.14 (t, J = 7.0 Hz, 2H), 2.58 (t, J = 7.0 Hz, 2H), 2.44 (q, J = 7.3 Hz, 2H), (m, 2H), 1.06 (t, J = 7.3 Hz, 3H). 13 C NMR (101 MHz, CDCl 3 ) δ 211.2, 199.7, 135.5, 134.0, 132.4, 129.7, 129.5, 128.4, 127.7, 126.7, 123.7, 41.2, 37.5, 35.9, 18.4, 7.8. IR (neat) cm -1 ṽ: 2971, 2932, 1708, 1677, 1625, 1413, 1370, 1265, 1178, 1110, 1024, 916, 872, 827, 771, 746; HRMS (EI(+), 70 ev) : C 17 H 18 O 2 [M] + : calcd , found: (furan-2-yl)heptane-1,5-dione (2q) Compound 2q is a known compound. According to General Procedure B, product 2q (33.0 mg, 0.17 mmol, 85%) was obtained from 1a (30.0 mg, 0.30 mmol) and 2-furaldehyde (19.2 mg, 0.20 mmol) as yellow oil with spectral properties identical to the reported in the literature. [14] 1 H NMR (400 MHz, CDCl 3 ): δ 7.55 (s, 1H), 7.18 (d, J = 3.2 Hz, 1H), 6.51 (d, J = 1.6 Hz, 1H), 2.84 (t, J = 7.1 Hz, 2H), 2.50 (t, J = 7.0 Hz, 2H), 2.40 (q, J = 7.3 Hz, 2H), (m, 2H), 1.03 (t, J = 7.3 Hz, 3H). 13 C NMR (101 MHz, CDCl 3 ): δ 211.0, 188.9, 152.5, 146.3, 117.1, 112.1, 41.0, 37.3, 35.9, 18.2, (thiophen-2-yl)heptane-1,5-dione (2r) According to General Procedure B, product 2r (35.3 mg, mmol, 84%) was obtained from 1a (30.0 mg, 0.30 mmol) and 2-thenaldehyde (22.4 mg, 0.20 mmol) as yellow solid, mp = o C. 1 H NMR (400 MHz, CDCl 3 ): δ 7.72 (d, J = 2.7 Hz, 1H), 7.61 (d, J = 4.5 Hz, 1H), 7.11 (t, J = 4.1 Hz, 1H), 2.93 (t, J = 7.0 Hz, 2H), 2.53 (t, J = 6.9 Hz, 2H), 2.41 (dd, J = 14.6, 7.3 Hz, 2H), (m, 2H), 1.04 (t, J = 7.3 Hz, 3H). 13 C NMR (101 MHz, CDCl 3 ): δ 211.1, 192.8, 144.1, 133.5, 132.0, 128.1, 41.0, 38.2, 35.9, 18.6, 7.8. IR (neat) cm -1 ṽ: 1704, 1653, 1516, 1452, 1412, 1376, 1265, 1202, 1062, 935, 856, 725; HRMS (EI(+), 70 ev) : C 11 H 14 O 2 S [M] + : calcd , found: S 14

15 1-(1-methyl-1H-pyrrol-2-yl)heptane-1,5-dione (2s) According to General Procedure B, product 2s (30.2 mg, mmol, 73%) was obtained from 1a (30.0 mg, 0.30 mmol) and N-methylpyrrole-2-carboxaldehyde (21.8 mg, 0.20 mmol) as yellow solid, mp = o C. 1 H NMR (400 MHz, CDCl 3 ): δ 6.96 (d, J = 2.8 Hz, 1H), 6.79 (s, 1H), (m, 1H), 3.93 (s, 3H), 2.79 (t, J = 7.2 Hz, 2H), 2.50 (t, J = 7.1 Hz, 2H), 2.42 (q, J = 7.3 Hz, 2H), (m, 2H), 1.04 (t, J = 7.3 Hz, 3H). 13 C NMR (101 MHz, CDCl 3 ): δ 211.2, 190.8, 130.9, 130.6, 119.2, 107.9, 77.3, 77.0, 76.7, 41.4, 37.9, 37.7, 35.8, 19.2, 7.8. IR (neat) cm -1 ṽ: 2971, 2937, 1709, 1643, 1526, 1407, 1380, 1311, 1244, 1095, 1062, 958, 740; HRMS (EI(+), 70 ev) : C 12 H 17 NO 2 [M] + : calcd , found: (1-methyl-1H-indol-2-yl)heptane-1,5-dione (2t) According to General Procedure B, product 2t (35.0 mg, mmol, 68%) was obtained from 1a (30.0 mg, 0.30 mmol) and 1-methylindole-2-carboxaldehyde (31.8 mg, 0.20 mmol) as yellow solid, mp = o C. 1 H NMR (400 MHz, CDCl 3 ): δ (m, 1H), 7.77 (s, 1H), (m, 3H), 3.83 (s, 3H), 2.85 (t, J = 7.2 Hz, 2H), 2.55 (t, J = 6.9 Hz, 2H), 2.43 (q, J = 7.3 Hz, 2H), (m, 2H), 1.05 (t, J = 7.3 Hz, 3H). 13 C NMR (101 MHz, CDCl 3 ): δ 211.6, 195.2, 137.4, 135.6, 126.2, 123.3, , , 116.2, 109.6, 41.4, 38.7, 35.9, 33.5, 19.4, 7.8. IR (neat) cm -1 ṽ: 2963, 2917, 1709, 1646, 1529, 1463, 1373, 1260, 1091, 1019, 865, 798; HRMS (EI(+), 70 ev) : C 16 H 19 NO 2 [M] + : calcd , found: (E)-1-phenylnon-1-ene-3,7-dione (2u) According to General Procedure B, product 2u (27.1 mg, mmol, 59%) was obtained from 1a (30.0 mg, 0.30 mmol) and cinnamaldehyde (26.4 mg, 0.20 mmol) as yellow oil. 1 H NMR (400 MHz, CDCl 3 ): δ (m, 3H), (m, 3H), 6.72 (d, J = 16.3 Hz, 1H), 2.72 (t, J = 7.1 Hz, 2H), 2.51 (t, J = 7.1 Hz, 2H), 2.43 (q, J = 7.3 Hz, 2H), (m, 2H), 1.06 (t, J = 7.3 Hz, 3H). 13 C NMR (101 MHz, CDCl 3 ): δ 211.2, 199.9, 142.7, 134.4, 130.4, 128.9, 128.2, 126.0, 41.1, 39.6, 35.9, 18.2, 7.8. IR (neat) cm -1 ṽ: 2972, 2934, 1711, 1661, 1606, 1451, 1377, 1260, S 15

16 1187, 1129, 1070, 798, 751, 699; HRMS (EI(+), 70 ev) : C 15 H 18 O 2 [M] + : calcd , found: (E)-2-methyl-1-phenylnon-1-ene-3,7-dione (2v) According to General Procedure B, product 2v (40.0 mg, mmol, 82%) was obtained from 1a (30.0 mg, 0.30 mmol) and α-methylcinnamaldehyde (29.2 mg, 0.20 mmol) as yellow oil. 1 H NMR (400 MHz, CDCl 3 ): δ 7.53 (s, 1H), 7.40 (t, J = 6.6 Hz, 4H), (m, 1H), 2.85 (t, J = 7.1 Hz, 2H), 2.51 (t, J = 7.0 Hz, 2H), 2.44 (q, J = 7.3 Hz, 2H), 2.05 (s, 3H), (m, 2H), 1.06 (t, J = 7.3 Hz, 3H). 13 C NMR (101 MHz, CDCl 3 ): δ 211.3, 201.8, 138.8, 137.1, 135.8, 129.7, 128.5, 128.4, 41.3, 36.5, 35.9, 18.8, 13.1, 7.8. IR (neat) cm -1 ṽ: 1710, 1663, 1624, 1447, 1411, 1369, 1211, 1114, 1052, 751, 698; HRMS (EI(+), 70 ev) : C 16 H 20 O 2 [M] + : calcd , found: (E)-1-(4-methoxyphenyl)non-1-ene-3,7-dione (2w) According to General Procedure B, product 2w (24.0 mg, mmol, 46%) was obtained from 1a (30.0 mg, 0.30 mmol) and 4-methoxycinnamaldehyde (32.4 mg, 0.20 mmol) as yellow oil. 1 H NMR (400 MHz, CDCl 3 ): δ 7.54 (s, 1H), 7.50 (s, 1H), 7.49 (s, 1H), 6.91 (d, J = 8.6 Hz, 2H), 6.60 (d, J = 16.2 Hz, 1H), 3.84 (s, 3H), 2.68 (t, J = 7.1 Hz, 2H), 2.50 (t, J = 7.1 Hz, 2H), 2.43 (q, J = 7.4 Hz, 2H), (m, 2H), 1.05 (t, J = 7.3 Hz, 3H). 13 C NMR (101 MHz, CDCl 3 ): δ 211.3, 199.9, 161.5, 142.5, 130.0, 127.0, 123.9, 114.4, 55.4, 41.2, 39.5, 35.9, 18.4, 7.8.IR (neat) cm -1 ṽ: 2928, 1708, 1649, 1602, 1511, 1457, 1249, 1177, 1105, 1029, 807; HRMS (EI(+), 70 ev) : C 16 H 20 O 3 [M] + : calcd , found: methyldec-8-ene-3,7-dione (2x) According to General Procedure B, product 2x (27.3 mg, mmol, 75%) was obtained from 1a (30.0 mg, 0.30 mmol) and 3-methyl-2-butenal (16.8 mg, 0.20 mmol) as yellow oil. 1 H NMR (400 MHz, CDCl 3 ): δ 6.05 (s, 1H), (m, 6H), 2.13 (s, 3H), (m, 5H), 1.04 (t, J = 7.3 Hz, 3H). 13 C NMR (101 MHz, CDCl 3 ): δ 211.3, 200.4, 155.4, 123.5, 43.0, 41.3, 35.8, 27.7, 20.7, 18.2, 7.8. IR (neat) cm -1 ṽ: 2972, 2935, 1711, 1686, 1620, 1445, 1412, 1376, 1211, 1112, 1028, 813; HRMS (EI(+), 70 ev) : C 11 H 18 O 2 [M] + : calcd , found: (S)-1-(4-(prop-1-en-2-yl)cyclohex-1-en-1-yl)heptane-1,5-dione (2y) S 16

17 According to General Procedure B, product 2y (37.7 mg, mmol, 76%) was obtained from 1a (30.0 mg, 0.30 mmol) and (-)-perillaldehyde (30.0 mg, 0.20 mmol) as yellow oil. 1 H NMR (400 MHz, CDCl 3 ): δ 6.92 (s, 1H), 4.73 (d, J = 17.1 Hz, 2H), 2.66 (t, J = 7.1 Hz, 2H), (m, 6H), 2.15 (d, J = 11.2 Hz, 3H), (m, 3H), 1.74 (s, 3H), (m, 1H), 1.04 (t, J = 7.3 Hz, 3H). 13 C NMR (101 MHz, CDCl 3 ):δ 211.4, 200.6, 148.8, 139.4, 138.6, 109.2, 41.4, 40.1, 36.0, 35.8, 31.3, 26.9, 23.5, 20.7, 18.7, 7.8. IR (neat) cm -1 ṽ: 2933, 1711, 1663, 1641, 1450, 1415, 1375, 1221, 1181, 1113, 951, 888; HRMS (EI(+), 70 ev) : C 16 H 24 O 2 [M] + : calcd , found: phenylnonane-3,7-dione (2z) According to General Procedure B, product 2z (40.0 mg, mmol, 86%) was obtained from 1a (30.0 mg, 0.30 mmol) and phenylpropyl aldehyde (26.8 mg, 0.20 mmol) as yellow oil. 1 H NMR (400 MHz, CDCl 3 ):δ (m, 2H), (m, 3H), 2.89 (t, J = 7.6 Hz, 2H), 2.71 (t, J = 7.6 Hz, 2H), (m, 6H), (m, 2H), 1.03 (t, J = 7.3 Hz, 3H). 13 C NMR (101 MHz, CDCl 3 ):δ 211.0, 209.6, 140.9, 128.4, 128.3, 126.0, 44.1, 41.8, 41.0, 35.8, 29.7, 17.7, 7.7. IR (neat) cm -1 ṽ: 2934, 2896, 1707, 1603, 1494, 1451, 1409, 1374, 1101, 1067, 987, 749, 699, 540, 510; HRMS (EI(+), 70 ev) : C 15 H 20 O 2 [M] + : calcd , found: tridecane-3,7-dione (2aa) According to General Procedure B, product 2aa (33.5 mg, mmol, 79%) was obtained from 1a (30.0 mg, 0.30 mmol) and heptaldehyde (22.8 mg, 0.20 mmol) as yellow oil. 1 H NMR (400 MHz, CDCl 3 ): δ (m, 8H), (m, 2H), (m, 2H), (m, 6H), 1.03 (t, J = 7.3 Hz, 3H), 0.86 (t, J = 6.5 Hz, 3H). 13 C NMR (101 MHz, CDCl 3 ): δ 211.2, 210.9, 42.8, 41.5, 41.1, 35.8, 31.6, 28.9, 23.8, 22.5, 17.8, 14.0, 7.8. IR (neat) cm -1 ṽ: 2927, 2855, 1705, 1456, 1412, 1377, 1251, 1095, 1061, 1017, 991, 795; HRMS (EI(+), 70 ev) : C 13 H 24 O 2 [M] + : calcd , found: chloroundecane-3,7-dione (2ab) S 17

18 According to General Procedure B, product 2ab (35.7 mg, mmol, 82%) was obtained from 1a (30.0 mg, 0.30 mmol) and 5-chloropentanal (20.4 mg, 0.20 mmol) as yellow oil. 1 H NMR (400 MHz, CDCl 3 ): δ 3.52 (t, J = 6.2 Hz, 2H), (m, 8H), (m, 2H), (m, 4H), 1.03 (t, J = 7.3 Hz, 3H). 13 C NMR (101 MHz, CDCl 3 ): δ 211.1, 209.9, 44.6, 41.7, 41.6, 41.1, 35.9, 31.9, 21.0, 17.7, 7.8. IR (neat) cm -1 ṽ: 2936, 2874, 1708, 1610, 1452, 1412, 1376, 1253, 1102, 1021, 991, 756, 724, 646; HRMS (EI(+), 70 ev) : C 11 H 19 ClO 2 [M] + : calcd , found: cyclohexylheptane-1,5-dione (2ac) According to General Procedure B, product 2ac (31.5 mg, mmol, 75%) was obtained from 1a (30.0 mg, 0.30 mmol) and cyclohexanecarboxaldehyde (22.4 mg, 0.20 mmol) as yellow oil. 1 H NMR (400 MHz, CDCl 3 ): δ (m, 6H), (m, 1H), (m, 6H), (m, 1H), (m, 5H), 1.02 (t, J = 7.3 Hz, 3H). 13 C NMR (101 MHz, CDCl 3 ): δ 213.7, 211.2, 50.7, 41.2, 39.4, 35.8, 28.4, 25.8, 25.6, 17.7, 7.8. IR (neat) cm -1 ṽ: 2963, 2931, 2854, 1710, 1449, 1411, 1260, 1019, 866, 798, 698; HRMS (EI(+), 70 ev) : C 13 H 22 O 2 [M] + : calcd , found: (S)-9, 13-dimethyltetradec-12-ene-3,7-dione (2ad) According to General Procedure B, product 2ad (35.8 mg, mmol, 71%) was obtained from 1a (30.0 mg, 0.30 mmol) and citronellal (30.8 mg, 0.20 mmol) as yellow oil. 1 H NMR (400 MHz, CDCl 3 ): δ 5.07 (t, J = 7.0 Hz, 1H), (m, 7H), (m, 1H), (m, 3H), (m, 2H), 1.67 (s, 3H), 1.58 (s, 3H), (m, 1H), (m, 1H), 1.04 (t, J = 7.3 Hz, 3H), 0.87 (d, J = 6.6 Hz, 3H). 13 C NMR (101 MHz, CDCl 3 ): δ 211.1, 210.6, 131.5, 124.2, 50.2, 42.1, 41.1, 37.0, 35.8, 28.9, 25.7, 25.4, 19.7, 17.7, 17.6, 7.8. IR (neat) cm -1 ṽ: 2962, 2930, 1709, 1455, 1410, 1375, 1260, 1111, 1028, 976, 799; HRMS (EI(+), 70 ev) : C 16 H 28 O 2 [M] + : calcd , found: methyl-1-phenylheptane-1,5-dione (2ae) According to General Procedure B, product 2ae (31.4 mg, mmol, 72%) was obtained from 1b (33.6 mg, 0.30 mmol) and benzaldehyde (21.2mg, 0.20 mmol) as yellow solid, mp = o C. 1 H NMR (400 MHz, CDCl 3 ) δ (m, 2H), (m, 1H), (m, 2H), 3.00 S 18

19 (t, J = 7.0 Hz, 2H), (m, 3H), (m, 2H), 1.08 (d, J = 6.9 Hz, 6H). 13 C NMR (101 MHz, CDCl 3 ) δ 214.4, 199.9, 136.7, 133.0, 128.5, 128.0, 40.8, 39.1, 37.5, 18.24, IR (neat) cm -1 ṽ: 2968, 2932, 1707, 1682, 1597, 1448, 1369, 1226, 1086, 998, 753, 691; HRMS (EI(+), 70 ev): C 14 H 18 O 2 [M] + : calcd , found: methyl-1-phenyloctane-1,5-dione (2af) According to General Procedure B, product 2af (17.2 mg, mmol, 37%) was obtained from 1c (37.8 mg, 0.30 mmol) and benzaldehyde (21.2mg, 0.20 mmol) as yellow solid, mp = o C. 1 H NMR (400 MHz, CDCl 3 ) δ (m, 2H), 7.56 (t, J = 7.3 Hz, 1H), 7.46 (t, J = 7.6 Hz, 2H), (m, 1H), (m, 1H), 2.66 (dq, J = 14.2, 7.0 Hz, 1H), (m, 2H), (m, 1H), (m, 1H), (m, 2H), 1.13 (d, J = 7.0 Hz, 3H), 0.91 (t, J = 7.4 Hz, 3H). 13 C NMR (101 MHz, CDCl 3 ) δ 214.3, 199.8, 136.7, 133.1, 128.6, 128.0, 45.4, 43.0, 35.9, 27.0, 17.1, 16.6, IR (neat) cm -1 ṽ: 2964, 2932, 1684, 1597, 1452, 1372, 1265, 1211, 1020, 972, 745, 692; HRMS (EI(+), 70 ev) : C 15 H 20 O 2 [M] + : calcd , found: , 6-diphenylheptane-1,5-dione (2ag) According to General Procedure B, product 2ag (28.6 mg, mmol, 51%) was obtained from 1d (52.2 mg, 0.30 mmol) and benzaldehyde (21.2mg, 0.20 mmol) as yellow solid, mp = o C. 1 H NMR (400 MHz, CDCl 3 ) δ 7.88 (d, J = 7.4 Hz, 2H), 7.54 (t, J = 7.4 Hz, 1H), 7.43 (t, J = 7.6 Hz, 2H), 7.30 (t, J = 7.3 Hz, 2H), 7.21 (t, J = 8.2 Hz, 3H), (m, 1H), (m, 2H), 2.49 (t, J = 6.9 Hz, 2H), 2, (m, 2H), 1.40 (d, J = 7.0 Hz, 3H). 13 C NMR (101 MHz, CDCl 3 ) δ 210.5, 199.7, 140.4, 136.7, 133.0, 128.9, 128.5, 128.0, 127.8, 127.1, 53.0, 39.9, 37.3, 18.3, IR (neat) cm -1 ṽ: 2921, 2851, 1712, 1679, 1633, 1492, 1450, 1375, 1262, 1071, 1008, 799, 760, 732, 699; HRMS (DART): C 19 H 20 O 2 [M+H] + : calcd , found: (E)-2-phenylhex-4-en-3-one (2ag ) Compound 2ag is a known compound. According to General Procedure B (without benzaldehyde), product 2ag (23.7 mg, mmol, 68%) was obtained from 1d (34.8 mg, 0.20 mmol) as yellow oil with spectral properties identical to the reported in the literature. [23] 1 H NMR (400 MHz, CDCl 3 ) δ 7.32 (t, J = 7.4 Hz, 2H), (m, 3H), 6.90 (dq, J = 15.5, 6.9 Hz, 1H), 6.10 (dq, J = 15.5, 1.6 Hz, 1H), 3.91 (q, J = 6.9 Hz, 1H), 1.79 (dd, J = 6.9, 1.7 Hz, 3H), 1.41 (d, J = 6.9 Hz, 3H). 13 C NMR (101 MHz, CDCl 3 ) δ 199.4, 142.8, 140.8, 130.0, 128.8, 128.0, S 19

20 127.0, 51.0, 18.2, , 7-diphenylheptane-1,5-dione (2ah) According to General Procedure B, product 2ah (37.5 mg, mmol, 67%) was obtained from 1e (52.2 mg, 0.30 mmol) and benzaldehyde (21.2mg, 0.20 mmol) as yellow solid, mp = o C. 1 H NMR (400 MHz, CDCl 3 ) δ 7.94 (d, J = 7.8 Hz, 2H), 7.55 (t, J = 7.3 Hz, 1H), 7.45 (t, J = 7.7 Hz, 2H), (m, 2H), 7.18 (d, J = 6.6 Hz, 3H), 2.97 (t, J = 7.0 Hz, 2H), 2.90 (t, J = 7.6 Hz, 2H), 2.74 (t, J = 7.6 Hz, 2H), 2.52 (t, J = 7.0 Hz, 2H), (m, 2H). 13 C NMR (101 MHz, CDCl 3 ) δ 209.6, 199.6, 140.9, 136.7, 133.0, 128.5,128.4, 128.2, 128.0, 126.0, 44.2, 41.8, 37.3, 29.7, IR (neat) cm -1 ṽ: 2957, 2922, 1710, 1681, 1599, 1494, 1449, 1409, 1372, 1260, 1096, 1023, 798, 745, 696; HRMS (EI(+), 70 ev) : C 19 H 20 O 2 [M] + : calcd , found: phenyloctane-1,5-dione (2ai) According to General Procedure B, product 2ai (28.0 mg, mmol, 64%) was obtained from 1f (33.6 mg, 0.30 mmol) and benzaldehyde (21.2mg, 0.20 mmol) as yellow solid, mp = o C. 1 H NMR (400 MHz, CDCl 3 ) δ (m, 2H), (m, 1H), (m, 2H), 3.01 (t, J = 7.0 Hz, 2H), 2.53 (t, J = 7.0 Hz, 2H), 2.38 (t, J = 7.4 Hz, 2H), (m, 2H), (m, 2H), 0.91 (t, J = 7.4 Hz, 3H). 13 C NMR (101 MHz, CDCl 3 ) δ 210.8, 199.8, 136.7, 133.0, 128.6, 128.0, 44.7, 41.6, 37.5, 18.2, 17.3, IR (neat) cm -1 ṽ: 2960, 2926, 1706, 1675, 1596, 1448, 1407, 1375, 1261, 1203, 1091, 1011, 799, 744, 691; HRMS (EI(+), 70 ev) : C 14 H 18 O 2 [M] + : calcd , found: methyl-1-phenyloctane-1,5-dione (2aj) According to General Procedure B, product 2aj (36.2 mg, mmol, 78%) was obtained from 1g (37.8 mg, 0.30 mmol) and benzaldehyde (21.2mg, 0.20 mmol) as yellow solid, mp = o C. 1 H NMR (400 MHz, CDCl 3 ) δ 7.97 (d, J = 7.5 Hz, 2H), 7.55 (t, J = 7.3 Hz, 1H), 7.45 (t, J = 7.5 Hz, 2H), 3.05 (dd, J = 15.8, 6.0 Hz, 1H), 2.77 (dd, J = 15.7, 7.3 Hz, 1H), 2.67 (td, J = 13.2, 6.6 Hz, 1H), 2.53 (dd, J = 16.4, 6.3 Hz, 1H), (m, 3H), (m, 2H), 0.99 (d, J = 6.6 Hz, 3H), 0.90 (t, J = 7.4 Hz, 3H). 13 C NMR (101 MHz, CDCl 3 ) δ 210.5, 199.6, 136.9, 133.0, 128.6, 128.1, 49.4, 45.1, 45.0, 26.0, 20.2, 17.2, S 20

21 IR (neat) cm -1 ṽ: 2961, 2932, 1708, 1681, 1597, 1450, 1367, 1280, 1215, 1004, 752, 692; HRMS (EI(+), 70 ev) : C 15 H 20 O 2 [M] + : calcd , found: , 3-diphenyloctane-1,5-dione (2ak) According to General Procedure B, product 2ak (23.0 mg, mmol, 39%) was obtained from 1h (56.4 mg, 0.30 mmol) and benzaldehyde (21.2 mg, 0.20 mmol) as yellow solid, mp = o C. 1 H NMR (400 MHz, CDCl 3 ) δ (m, 2H), 7.54 (t, J = 7.3 Hz, 1H), 7.44 (t, J = 7.7 Hz, 2H), (m, 4H), 7.18 (t, J = 6.9 Hz, 1H), (m, 1H), 3.32 (ddd, J = 34.9, 16.4, 7.0 Hz, 2H), 2.85 (qd, J = 16.6, 7.1 Hz, 2H), 2.31 (td, J = 7.2, 1.7 Hz, 2H), (m, 2H), 0.83 (t, J = 7.4 Hz, 3H). 13 C NMR (101 MHz, CDCl 3 ) δ 209.5, 198.5, 143.7, 136.8, 133.1, , , 128.1, 127.4, 126.6, 48.7, 45.1, 44.8, 36.8, 17.0, IR (neat) cm -1 ṽ: 2960, 2922, 2851, 1681, 1646, 1597, 1450, 1368, 1261, 1207, 1094, 1024, 978, 801, 747, 700; HRMS (EI(+), 70 ev) : C 20 H 22 O 2 [M] + : calcd , found: methyl-1-phenyloctane-1,5-dione (2al) According to General Procedure B, product 2al (21.4 mg, mmol, 46%) was obtained from 1i (37.8 mg, 0.30 mmol) and benzaldehyde (21.2 mg, 0.20 mmol) as yellow solid, mp = o C. 1 H NMR (400 MHz, CDCl 3 ) δ (m, 2H), 7.57 (t, J = 7.3 Hz, 1H), 7.47 (t, J = 7.5 Hz, 2H), (m, 1H), (m, 1H), (m, 3H), 2.08 (td, J = 14.1, 7.6 Hz, 1H), 1.75 (dt, J = 14.1, 6.3 Hz, 1H), (m, 2H), 1.19 (d, J = 6.9 Hz, 3H), 0.88 (t, J = 7.4 Hz, 3H). 13 C NMR (101 MHz, CDCl 3 ) δ 210.8, 203.9, 136.4, 133.0, 128.7, 128.3, 44.8, 39.8, 39.5, 27.2, 17.4, 17.3, IR (neat) cm -1 ṽ: 2963, 2933, 1711, 1680, 1596, 1451, 1373, 1260, 1230, 1094, 1021, 972, 797, 705; HRMS (EI(+), 70 ev) : C 15 H 20 O 2 [M] + : calcd , found: ((benzyloxy)methyl)-1-phenylheptane-1,5-dione (2am) According to General Procedure B, product 2am (44.7 mg, mmol, 69%) was obtained from 1j (65.4 mg, 0.30 mmol) and benzaldehyde (21.2 mg, 0.20 mmol) as yellow solid, mp = o C. 1 H NMR (400 MHz, CDCl 3 ) δ (m, 2H), 7.55 (t, J = 7.4 Hz, 1H), 7.45 (t, J = 7.6 Hz, 2H), (m, 5H), 4.46 (s, 2H), 3.48 (d, J = 5.5 Hz, 2H), 3.07 (ddd, J = 38.3, 16.6, 6.6 Hz, 2H), (m, 1H), 2.60 (qd, J = 17.0, 6.6 Hz, 2H), 2.43 (q, J = 7.3 Hz, 2H), 1.02 (t, J = 7.3 Hz, 3H). 13 C NMR (101 MHz, CDCl 3 ) δ 210.7, 199.4, 138.2, 136.9, 133.0, 128.5, 128.3, 128.1, S 21

22 127.6, 127.5, 73.0, 72.3, 43.8, 40.0, 36.2, 31.2, 7.7. IR (neat) cm -1 ṽ: 2964, 2917, 2854, 1711, 1683, 1597, 1450, 1411, 1366, 1261, 1212, 1099, 1022, 799, 750, 695; HRMS (DART): C 21 H 24 O 3 [M+H] + : calcd , found: , 3-diphenylheptane-1,5-dione (2an) According to General Procedure B, product 2an (32.0 mg, mmol, 57%) was obtained from 1k (52.2 mg, 0.30 mmol) and benzaldehyde (21.2 mg, 0.20 mmol) as yellow solid, mp = o C. 1 H NMR (400 MHz, CDCl 3 ) δ 7.91 (d, J = 7.7 Hz, 2H), 7.54 (t, J = 7.3 Hz, 1H), 7.43 (t, J = 7.6 Hz, 2H), (m, 4H), 7.18 (t, J = 6.7 Hz, 1H), (m, 1H), 3.32 (ddd, J = 36.9, 16.4, 7.0 Hz, 2H), 2.85 (qd, J = 16.4, 7.1 Hz, 2H), (m, 2H), 0.97 (t, J = 7.3 Hz, 3H). 13 C NMR (101 MHz, CDCl 3 ) δ 210.0, 198.6, 143.7, 136.8, 133.1, , , 128.1, 127.3, 126.7, 48.4, 44.8, 36.8, 36.3, 7.6. IR (neat) cm -1 ṽ: 2921, 1701, 1677, 1593, 1450, 1404, 1353, 1264, 1207, 1135, 975, 814, 745, 700, 681, 589, 570; HRMS (EI(+), 70 ev) : C 19 H 20 O 2 [M] + : calcd , found: benzyl-1-phenylheptane-1,5-dione (2ao) According to General Procedure B, product 2ao (18.8 mg, mmol, 32%) was obtained from 1l (56.4 mg, 0.30 mmol) and benzaldehyde (21.2 mg, 0.20 mmol) as yellow solid, mp = o C. 1 H NMR (400 MHz, CDCl 3 ) δ 7.91 (d, J = 7.6 Hz, 2H), 7.55 (t, J = 7.2 Hz, 1H), 7.45 (t, J = 7.5 Hz, 2H), 7.26 (t, J = 7.4 Hz, 2H), (m, 1H), 7.14 (d, J = 7.4 Hz, 2H), (m, 4H), (m, 1H), (m, 1H), (m, 2H), (m, 1H), 0.92 (t, J = 7.2 Hz, 3H). 13 C NMR (101 MHz, CDCl 3 ) δ 214.5, 199.4, 139.2, 136.7, 133.1, 128.8, 128.6, 128.5, 128.0, 126.4, 52.7, 38.4, 36.7, 35.8, 25.9, 7.4. IR (neat) cm -1 ṽ: 2932, 1709, 1684, 1598, 1495, 1451, 1372, 1261, 1213, 1112, 1027, 972, 741, 698; HRMS (EI(+), 70 ev) : C 20 H 22 O 2 [M] + : calcd , found: ethyl-6-phenyltetrahydro-2H-pyran (3) According to a procedure reported by G. A. Olah et al. [15] To a solution of compound 1a (50 mg, 0.25 mmol) in CH 2 Cl 2 (0.8 ml) was added Et 3 SiH (116 mg, 1.0 mmol), followed by TMSOTf (0.9 mg, mmol) at 0 o C. The mixture was stirred at 0 o C for 4 h and then allowed to stand 12 h at room temperature. The reaction was quenched with saturated NaHCO 3 solution. The mixture was S 22

23 extracted three times with CH 2 Cl 2. The combined organic phases were dried over MgSO 4, concentrated in vacuo and the residue was purified by silica gel flash chromatography (hexane/etoac = 5:1) to give product 3 (42 mg, 88% yield) as colorless oil. 1 H NMR (400 MHz, CDCl 3 ) δ (m, 4H), 7.25 (t, J = 7.1 Hz, 1H), 4.38 (dd, J = 11.2, 1.8 Hz, 1H), (m, 1H), (m, 1H), 1.86 (d, J = 12.2 Hz, 1H), (m, 3H), (m, 2H), 1.30 (qd, J = 13.4, 3.7 Hz, 1H), 0.99 (t, J = 7.5 Hz, 3H). 13 C NMR (101 MHz, CDCl 3 ) δ 143.7, 128.1, 127.0, 125.8, 79.52, 79.48, 33.7, 30.6, 29.4, 24.1, 9.9. IR (neat) cm -1 ṽ: 2933, 2851, 1453, 1381, 1206, 1084, 1044, 1004, 911, 806, 745, 696; HRMS (EI(+), 70 ev) : C 13 H 18 O [M] + : calcd , found: ethyl-6-phenylpiperidine (4) Compound 4 is a known compound. According to a procedure reported by K. Abe et al. [16] To a solution of compound 1a (40 mg, 0.20 mmol) in dry methanol (4.0 ml) was added sodium cyanoborohydride (12.6 mg, 0.20 mmol) and ammonium bromide (40 mg, 0.40 mmol). The mixture was stirred for 4 days at room temperature and then acidified to ph=3 with conc. hydrochloric acid. Stirring was continued for 3 h at room temperature and the mixture evaporated to dryness. The residue was washed with ether (3 20 ml), made alkaline to ph=11 with aqueous 10% sodium hydroxide, and extracted with ether (10 20 ml). The combined organic phases were dried over Na 2 SO 4, concentrated in vacuo and the residue was purified by silica gel flash chromatography (hexane/etoac = 1:1) to give product 4 (34 mg, 90% yield) as yellow oil with spectral properties identical to the reported in the literature. [17] 1 H NMR (400 MHz, CDCl 3 ) δ 7.40 (d, J = 7.5 Hz, 1H), 7.32 (t, J = 7.4 Hz, 2H), 7.23 (d, J = 7.3 Hz, 1H), 3.65 (d, J = 10.8 Hz, 1H), (m, 1H), (m, 2H), (m, 1H), (m, 2H), (m, 4H), 0.91 (t, J = 7.5 Hz, 3H). 13 C NMR (101 MHz, CDCl 3 ) δ 138.5, 128.6, 128.5, 127.7, 62.4, 60.4, 31.0, 27.7, 27.0, 23.6, ethyl-2-phenylcyclopentane-1,2-diol (5) According to a procedure reported by N. Kise et al. [18] Rigorously deoxygenated THF (4.0 ml) was added to a mixture of compound 1a (80 mg, 0.40 mmol) and Zn dust (78 mg, 1.2 mmol) under Ar atmosphere at 0 o C. A solution of TiCl 4 (114 mg, 0.6 mmol) in THF (2 ml) was then added. The mixture was stirred for 1 h at 0 o C and then allowed to stand 12h at room temperature. The reaction was quenched with saturated NaHCO 3 solution and extracted three times with EtOAc. The combined organic phases were dried over MgSO 4, concentrated in vacuo and the residue was purified by silica gel flash chromatography (hexane/etoac = 5:1) to give product 5 (67 mg, 81% yield) as white solid, mp = o C. S 23

24 1 H NMR (400 MHz, CDCl 3 ) δ (m, 2H), (m, 2H), (m, 1H), 3.23 (s, 1H), 2.47 (s, 1H), (m, 1H), (m, 2H), (m, 2H), (m, 1H), (m, 2H), 0.82 (t, J = 7.4 Hz, 3H). 13 C NMR (101 MHz, CDCl 3 )δ 143.4, 127.8, 127.0, 126.2, 84.3, 84.2, 36.6, 33.5, 28.7, 19.0, 8.0. IR (neat) cm -1 ṽ: 3425, 3339, 2964, 2878, 1492, 1447, 1388, 1279, 1199, 1133, 1100, 1021, 877, 799, 760, 696, 620, 557; HRMS (EI(+), 70 ev) : C 13 H 18 O 2 [M] + : calcd , found: methyl-5,6-dihydro-[1,1'-biphenyl]-3(4H)-one (6) Compound 6 is a known compound. To a solution of compound 1a (40 mg, 0.20 mmol) in EtOH (0.5 ml) and H 2 O (0.5 ml) was added KOH (22 mg, 0.40 mmol). The mixture was stirred at 80 o C for 3h and then extracted three times with CH 2 Cl 2. The combined organic phases were dried over MgSO 4, concentrated in vacuo and the residue was purified by silica gel flash chromatography (hexane/etoac = 5:1) to give product 6 (21 mg, 95% yield) as colorless oil with spectral properties identical to the reported in the literature. [19] 1 H NMR (400 MHz, CDCl 3 ) δ 7.39 (t, J = 7.5 Hz, 2H), (m, 1H), 7.20 (dd, J = 8.1, 1.0 Hz, 2H), 2.63 (td, J = 6.1, 1.8 Hz, 2H), (m, 2H), (m, 2H), 1.72 (s, 3H). 13 C NMR (101 MHz, CDCl 3 ) δ 200. (s), 156.6, 141.3, 131.8, 128.3, 127.8, 127.0, 37.7, 32.9, 22.8, ,9-diphenylnonane-3,7-dione (7) According to General Procedure B, product 7 (956 mg, 3.10 mmol, 54%) was obtained from 1e (1.50 g, 8.61 mmol) and phenylpropyl aldehyde (770 mg, 5.74 mmol) as yellow oil. 1 H NMR (400 MHz, CDCl 3 ) δ (m, 4H), 7.22 (dd, J = 10.6, 4.6 Hz, 6H), 2.90 (dd, J = 9.5, 5.7 Hz, 4H), 2.72 (dd, J = 9.6, 5.6 Hz, 4H), 2.39 (t, J = 7.1 Hz, 4H), (m, 2H). 13 C NMR (101 MHz, CDCl 3 ) δ 209.3, 140.8, 128.3, 128.1, 125.9, 43.9, 41.5, 29.5, IR (neat) cm -1 ṽ: 3026, 2932, 1705, 1604, 1495, 1451, 1409, 1261, 1074, 1028, 799, 747, 699; HRMS (EI(+), 70 ev) : C 21 H 24 O 2 [M] + : calcd , found: Norlobelane According to a procedure reported by K. Abe et al. [20] To a solution of compound 3n (85 mg, 0.28 mmol) in dry methanol (6.0 ml) was added sodium cyanoborohydride (18 mg, 0.28 mmol) and S 24

25 ammonium bromide (55 mg, 0.56 mmol). The mixture was stirred for 4 days at room temperature and then acidified to ph = 3 with conc. hydrochloric acid. Stirring was continued for 3 h at room temperature and the mixture evaporated to dryness. The residue was washed with ether (3 20 ml), made alkaline to ph = 11 with aqueous 10% sodium hydroxide, and extracted with ether (10 20 ml). The combined organic phases were dried over Na 2 SO 4, concentrated in vacuo and the residue was purified by silica gel flash chromatography (hexane/etoac = 1:1) to give product Norlobelane (75 mg, 92% yield) as yellow solid with spectral properties identical to the reported in the literature. [21] 1 H NMR (400 MHz, CDCl 3 ) δ (m, 4H), (m, 6H), (m, 4H), (m, 2H), (m, 7H), (m, 2H), 1.13 (ddd, J = 24.2, 13.0, 3.8 Hz, 2H). 13 C NMR (101 MHz, CDCl 3 ) δ 142.1, , , 125.6, 56.5, 38.8, 32.5, 32.3, (R)-10-((5R, 8R, 9S, 10S, 13R, 14S, 17R)-10, 13-dimethyl-3-oxohexadecahydro-1H-cyclopenta[a]phenanthren-17-yl)undecane-3,7-dione (8) According to General Procedure B, product 8 (180 mg, 0.40 mmol, 66%) was obtained from (R)-4-((5R, 8R, 9S, 10S, 13R, 14S, 17R)-10, 13-dimethyl-3-oxohexadecahydro -1H-cyclopenta[a]phenanthren-17-yl) pentanal [22] (215 mg, 0.60 mmol) and 1a (88.0 mg, 0.90 mmol) as white solid, mp = o C. 1 H NMR (400 MHz, CDCl 3 ) δ 2.68 (t, J = 14.3 Hz, 1H), (m, 6H), (m, 2H), 2.15 (d, J = 14.9 Hz, 1H), (m, 3H), (m, 5H), (m, 4H), (m, 7H), (m, 4H), (m, 9H), 0.89 (d, J = 6.2 Hz, 3H), 0.66 (s, 3H). 13 C NMR (101 MHz, CDCl 3 ) δ 213.4, , , 56.4, 56.0, 44.3, 42.8, 42.4, 41.6, 41.2, 40.7, 40.0, 39.6, 37.2, 37.0, 35.9, 35.5, 35.3, 34.9, 29.8, 28.2, 26.6, 25.8, 24.1, 22.6, 21.2, 18.4, 17.8, 12.1, 7.8. IR (neat) cm -1 ṽ: 2932, 2865, 1709, 1448, 1422, 1378, 1335, 1254, 1099, 1062, 1023, 802, 769, 532; HRMS (DART) : C 30 H 48 O 3 [M+H] + : calcd , found: S 25

26 5. Deuterium-labeling Experiments HNMR D-NMR impurity in CDCl 3 S 26

27 HNMR DNMR impurity in CDCl 3 S 27

28 To identify the turn-over-limiting step, we measured kinetic isotope effects (KIE) via intermolecular competitions experiments of deuterated aldehydes with their protio analogue. With 1a as the coupling partner, a KIE of 2.3 was observed for the reaction which suggested the oxidative addition of the rhodium to the aldehyde is the rate-limiting step. HNMR DNMR impurity in CDCl 3 S 28

29 6. In-Situ IR Experiments 17 min 24 min 90 min S 29

30 In a Hammett study with different para-substituted benzaldehydes, a positive ρ value of 0.87 was measured, indicating a negative charge facilitates the reaction turn-over which is in agreement with that the oxidative addition is the rate-limiting step. S 30