Rhodium/Lewis Acid Catalyzed Regioselective Addition of 1,3-Dicarbonyl Compounds to Internal Alkynes

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1 Supporting Information for: Rhodium/Lewis Acid Catalyzed Regioselective Addition of 1,3-Dicarbonyl Compounds to Internal Alkynes Wei-Feng Zheng, Qiu-Jing Xu and Qiang Kang* College of Materials Science and Engineering, Fujian Normal University, 8 Shangsan Road, Fuzhou, , China. Key Laboratory of Coal to Ethylene Glycol and Its Related Technology, Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences, 155 Yangqiao Road West, Fuzhou, , China

2 Table of Contents: 1 General Information S2 2 Optimization conditions S3 3 Synthesis of the substrates S6 4 1 H NMR monitoring experiments S9 5 Mechanistic Experiments S13 6 Control Experiments S15 7 Characterizations S18 8 Copies of 1 H NMR and 13 C NMR spectra of the compounds S43 S1

3 1. General Information All non-aqueous reactions were performed in oven-dried glassware and standard Schlenk tubes under an atmosphere of nitrogen. 1,2-dichloroethane (DCE), 1,2- dichlorobenzene (ODCB), acetonitrile (CH3CN) were distilled from CaH2 under inert atmosphere. Tetrahydrofuran (THF), dioxane and toluene (PhMe) were distilled from sodium and benzophenone under inert atmosphere. All other solvents and reagents were used as received unless otherwise noted. Thin layer chromatography was performed using silica gel 60 F-254 precoated plates (0.2~0.3 mm) and visualized by short-wave UV (254 nm) irradiation, potassium permanganate, CAM or iodine stain. The 1 H and 13 C NMR spectra were obtained in CDCl3 using a Bruker Avance III spectrometer at 400 and 100 MHz for 1 H and 13 C NMR, respectively. Chemical shifts (δ) for 1 H NMR spectra are recorded in parts per million from tetramethylsilane with the solvent resonance as the internal standard (chloroform, δ 7.26 ppm). Data are reported as follows: chemical shift, multiplicity (s = singlet, d = doublet, t = triplet, q = quartet, qn = quintet, m = multiplet and br = broad), coupling constant in Hz, and integration. Chemical shifts for 13 C NMR spectra are recorded in parts per million from tetramethylsilane using the central peak of deuterochloroform (δ ppm) as the internal standard. The infrared spectra were recorded on a VERTEX 70 IR spectrometer as KBr pellets, with absorption reported in cm -1. HRMS data were obtained on a Bruker Impact II UHR-TOF system. Melting points were measured on SGW X-4 apparatus. S2

4 2. Optimization Conditions Table S1: Investigation of the Effect of Solvents. a entry solvent yield of 3a (%) [b] 1 DCE 99 2 Dioxane 14 3 ODCB 43 4 Toluene 18 5 THF 99 6 CH3CN 11 a Reaction conditions: 0.1 mmol 1a, 0.2 mmol 2a, 5 mol% [Rh(COD)Cl]2, 12 mol% DPEphos and 6 mol% Yb(OTf)3 in solvent (0.1 M) at 70 o C, 24 hours. b Determined by GC with n-dodecane as internal standard. Table S2: Optimization of the Temperature. a entry T ( o C) yield of 3a (%) [b] 1 r.t. 6 [c] [c] S3

5 a Reaction conditions: 0.1 mmol 1a, 0.2 mmol 2a, 5 mol% [Rh(COD)Cl]2, 12 mol% DPEphos and 6 mol% Yb(OTf)3 in DCE (0.1 M) at T o C, 24 hours. b Isolated yield. c Incomplete conversion. Table S3: Screening the Loading of Catalyst, Ligand and Lewis Acid. a entry x,y,z (mol %) yield of 3a (%) [b] 1 2,4, ,6, ,5, ,10, ,12,6 99 a Reaction conditions: 0.1 mmol 1a, 0.2 mmol 2a, x mol% [Rh(COD)Cl]2, y mol% DPEphos and z mol% Yb(OTf)3 in DCE (0.1 M) at 70 o C, 24 hours. b Isolated yield. Table S4: Investigation of the Effect of Solvent. a entry solvent yield of 3b (%) [b] 1 DCE 90 2 Dioxane 17 3 ODCB 68 S4

6 4 Toluene 29 5 THF 72 6 CH3CN 42 a Reaction conditions: 0.1 mmol 1a, 0.1 mmol 2a, 5 mol% [Rh(COD)Cl]2, 12 mol% BINAP and 6 mol% Sc(OTf)3 in solvent (0.1 M) at 70 o C, 48 hours. b Isolated yield. Table S5: Screening the Loading of Catalyst, Ligand and Lewis Acid. a entry x,y,z (mol %) yield of 3b (%) [b] 1 3,6, ,10, ,12,6 90 a Reaction conditions: 0.1 mmol 1a, 0.1 mmol 2a, x mol % [Rh(COD)Cl]2, y mol % BINAP and x mol % Sc(OTf)3 in DCE (0.1 M) at 70 o C, 48 hours. b Isolated yield. S5

7 3. Synthesis of the Substrates Figure S1: Synthesis of 1,3-dicarbonyl substrates. 1,3-dicarbonyl substrates 1g-1l were prepared according to literature. [1] 1b-1f were commercial reagents. Figure S2: Synthesis of the alkyne substrates. Alkynes 2b, 2c and 2l were prepared according to literature procedure. [2] Alkynes 2g- 2j were prepared from 2k, and 2k were prepared according to literature procedure from 5-hexyn-1-ol. [3] Alkynes 2m [4], 2n [5], 2o [6], and 2p [7] were prepared according to literature procedure. Alkyne 2q was prepared from estrone and 3-pentyn-1-ol. [8] Alkynes 2d was prepared from 4-Ethynylbenzonitrile with 3.0 equiv n-buli and 1.2 S6

8 equiv CH3I according to literature procedure. [2] 1-Phenylallene 4 was prepared from styrene according to literature procedure. [9] Deuterated 1-Phenyl-1-propyne 2a-d3 was prepared from phenylacetylene according to literature procedure. [10] Alkynes 2a, 2f and 2r were commercial reagents. General Procedure for the Addition of 1,3-Dicarbonyl Compounds to Internal Alkynes General procedure A: In a 10 ml flame dried schlenk tube fitted with a rubber septum and magnetic bar, [Rh(COD)Cl]2 (2.5 mg, mmol or 5.0 mg, 0.01 mmol), DPEphos (6.5 mg, mmol or 13.0 mg, mmol), Yb(OTf)3 (3.8 mg, mmol or 7.6 mg, mmol) were added in the glove box and then 1,3-dicarbonyl 1 (0.1 mmol or 0.2 mmol), internal alkyne 2 (0.2 mmol or 0.4 mmol) were added by syringe with 1mL or 2 ml anhydrous dichloroethane (DCE). The tube was sealed and heated to 70 o C for hours. After the reaction was complete (monitored by TLC), the reaction mixture was directly purified by flash chromatography on silica gel. General procedure B: In a 10 ml flame dried schlenk tube fitted with a rubber septum and magnetic bar, [Rh(COD)Cl]2 (2.5 mg, mmol or 5.0 mg, 0.01 mmol), BINAP (7.5 mg, mmol or 15.0 mg, mmol), Sc(OTf)3 (3.0 mg, 0.006mmol S7

9 or 6.0 mg, mmol) were added in the glove box and then 1,3-dicarbonyl 1 (0.1 mmol or 0.2 mmol), internal alkyne 2 (0.1 mmol or 0.2 mmol) were added by syringe with 1mL or 2 ml anhydrous dichloroethane (DCE). The tube was sealed and heated to 70 o C for hours. After the reaction was complete (monitored by TLC), the reaction mixture was directly purified by flash chromatography on silica gel. Procedure for Rhodium/Lewis Acid Catalyzed the Addition of Acetylacetone (1a) to 1-Phenyl-1-Propyne (2a) on Gram Scale. In a 100 ml flame dried schlenk flask fitted with a rubber septum and magnetic bar, [Rh(COD)Cl]2 (123.3 mg, 0.25 mmol), DPEphos (322.8 mg, 0.6 mmol), Yb(OTf)3 (191.4 mg, 0.3 mmol) were added in the glove box and then 1a (0.5 g, 5 mmol), 2a (1.16 g, 10 mmol) were added by syringe with 50 ml anhydrous dichloroethane (DCE). The flask was sealed and heated to 70 o C for 48 hours. After the reaction was complete (monitored by TLC), the solvent was removed under vacuum and the reaction mixture was purified by flash chromatography on silica gel to provide 3a as a colorless oil, 0.99 g, 92% yield (eluting with 2-5% EtOAc in PE (elution gradient)). S8

10 4. 1 H NMR Monitoring Experiments Figure S3: 1 H NMR monitoring experiment of branched product 3a. S9

11 Figure S4: Reaction profile of 1 equivalent 1a with 2 equivalent 2a under the reaction condition A. Figure S5: 1 H NMR monitoring experiment of branched product 3a and linear product 4a. S10

12 Figure S6: Reaction profile of 1 equivalent 1a with 1 equivalent 2a under the reaction condition A. S11

13 Figure S7: 1 H NMR monitoring experiment of branched product 3a and linear product 4a. Figure S8: Reaction profile of 2 equivelent 1a with 1 equivelent 2a under the reaction condition A. S12

14 Figure S9: 1 H NMR monitoring experiment of branched product 5k and linear product 6k. Figure S10: Reaction profile of 1k under the reaction condition B. S13

15 5. Mechanistic Experiments Procedure for the Coupling of Pentane-2,4-dione 1a and 1-Phenylallene 7 The reaction was carried out according to the general procedure A to achieve product 2a as a colorless oil (39.4 mg, 91% yield). Procedure for the Coupling of Pentane-2,4-dione (1a) Deuterated 1-Phenyl-1- propyne (2a-d3) The reaction was carried out according to the general procedure A to achieve product 3a-dn as a pale yellow oil (35.4 mg, 82% yield). S14

16 ppm Figure S11: 1 H NMR of 3a-dn ppm Figure S12: 1 H NMR of 3a-dn. S15

17 6. Control Experiments Figure S13: Crossover experiment. In a 10 ml flame dried schlenk tube fitted with a rubber septum and magnetic bar, [Rh(COD)Cl]2 (8.6 mg, mmol), BINAP (26.1 mg, mmol), Sc(OTf)3 (10.3 mg, mmol) were added in the glove box and then 5f/6f (119.0mg, 0.35 mmol, Branched : Linear = 73:27), pentane-2,4-dione 1a (105 mg, 1.05 mmol, 3 equiv) were added by syringe with 3.5 ml anhydrous dichloroethane (DCE). The tube was sealed and heated to 70 o C for 48 hours. The ratio of 6f and 3a were determined by 1 H NMR analysis of the crude mixture. Figure S14: Investigation of the effect of rhodium catalyst and Lewis acid in retroallylic alkylation. S16

18 In a 10 ml flame dried schlenk tube fitted with a rubber septum and magnetic bar, [Rh(COD)Cl]2 (4.9 mg, 0.01 mmol), BINAP (14.8 mg, mmol), Sc(OTf)3 (5.9 mg, mmol) were added in the glove box and then 5f/6f (68 mg, 0.2 mmol, Branched : Linear = 90:10) was added by syringe with 2 ml anhydrous dichloroethane (DCE). The tube was sealed and heated to 70 o C for 24 hours. The ratio of 5f and 6f were determined by 1 H NMR analysis of the crude reaction mixture. Figure S15: Control experiment in the absence of Lewis acid. In a 10 ml flame dried schlenk tube fitted with a rubber septum and magnetic bar, [Rh(COD)Cl]2 (6.4 mg, mmol), BINAP (19.3 mg, mmol) were added in the glove box and then 5f/6f (88.4 mg, 0.26 mmol, Branched : Linear = 88:12) was added by syringe with 2.6 ml anhydrous dichloroethane (DCE). The tube was sealed and heated to 70 o C for 24 hours. The ratio of 5f/6f was determined by 1 H NMR analysis of crude reaction mixture. S17

19 Figure S16: Control experiment in the absence of rhodium complex. In a 10 ml flame dried schlenk tube fitted with a rubber septum and magnetic bar, Sc(OTf)3 (5.9 mg, mmol) was added in the glove box and then 5f/6f (68 mg, 0.2 mmol, Branched : Linear = 71:29) was added by syringe with 2 ml anhydrous dichloroethane (DCE). The tube was sealed and heated to 70 o C for 24 hours. The ratio of 5f/6f was determined by 1 H NMR analysis of crude reaction mixture. Figure S17: Control experiment in the absence of rhodium complex and Lewis acid. In a 10 ml flame dried schlenk tube fitted with a rubber septum and magnetic bar, 5f/6f (68 mg, 0.2 mmol, Branched : Linear = 71:29) was added followed by 2 ml anhydrous dichloroethane (DCE). The tube was sealed and heated to 70 o C for 24 hours. The ratio of 5f/6f was determined by 1 H NMR analysis of crude reaction mixture. S18

20 7. Characterizations 1,3-Bis(4-fluorophenyl)propane-1,3-dion Analytical data for 1g: pale yellow solid. 1 H NMR (400 MHz, CDCl3) δ (m, 2H), 7.92 (d, J = 8.6 Hz, 2H), 7.47 (d, J = 8.6 Hz, 2H), 7.17 (t, J = 8.6 Hz, 2H), 6.76 (s, 1H). 1,3-Bis(4-chlorophenyl)propane-1,3-dione Analytical data for 1h: pale yellow solid. 1 H NMR (400 MHz, CDCl3) δ 7.92 (d, J = 8.6 Hz, 4H), 7.47 (d, J = 8.6 Hz, 4H), 6.77 (s, 1H). 1,3-Bis(4-bromophenyl)propane-1,3-dione Analytical data for 1i: pale brown solid. 1 H NMR (400 MHz, CDCl3) δ 7.85 (d, J = 8.6 Hz, 4H), 7.63 (d, J = 8.5 Hz, 4H), 6.77 (s, 1H). 1,3-Di-p-tolylpropane-1,3-dione S19

21 Analytical data for 1j: pale yellow solid. 1 H NMR (400 MHz, CDCl3) δ 7.89 (d, J = 8.2 Hz, 4H), 7.29 (d, J = 8.1 Hz, 4H), 6.81 (s, 1H), 2.43 (s, 6H). 1,3-Bis(4-methoxyphenyl)propane-1,3-dione Analytical data for 1k: pale yellow solid. 1 H NMR (400 MHz, CDCl3) δ 7.97 (d, J = 8.9 Hz, 1H), 6.97 (d, J = 8.9 Hz, 1H), 6.72 (s, 1H), 3.87 (s, 1H). 1,3-Di(naphthalen-2-yl)propane-1,3-dione Analytical data for 1l: pale yellow solid. 1 H NMR (400 MHz, CDCl3) δ 8.60 (s, 2H), 8.08 (dd, J = 8.6, 1.7 Hz, 2H), 8.02 (d, J = 7.5 Hz, 2H), 7.96 (d, J = 8.6 Hz, 2H), 7.91 (d, J = 7.6 Hz, 2H), 7.60 (dq, J = 6.7, 5.4 Hz, 4H), 7.16 (s, 1H). 1-Methyl-4-(prop-1-yn-1-yl)benzene Analytical data for 2b: colorless oil. 1 H NMR (400 MHz, CDCl3) δ 7.28 (d, J = 8.2 Hz, 2H), 7.08 (d, J = 8.1 Hz, 2H), 2.32 (s, 3H), 2.03 (s, 3H). Ethyl 4-(prop-1-yn-1-yl)benzoate S20

22 Analytical data for 2c: colorless oil. 1 H NMR (400 MHz, CDCl3) δ 7.97 (d, J = 8.4 Hz, 2H), 7.44 (d, J = 8.4 Hz, 2H), 4.39 (q, J = 7.2 Hz, 2H), 2.08 (s, 3H), 1.40 (t, J = 7.1 Hz, 3H). 1-(4-(Prop-1-yn-1-yl)phenyl)pentan-1-one Analytical data for 2d: yellow oil. 1 H NMR (400 MHz, CDCl3) δ 7.88 (d, J = 8.4 Hz, 2H), 7.46 (d, J = 8.4 Hz, 2H), 2.95 (t, J = 7.4 Hz, 2H), 2.08 (s, 3H), 1.75 (p, J = 7.2 Hz, 2H), 1.45 (dt, J = 15.0, 7.5 Hz, 2H), 0.97 (t, J = 7.2 Hz, 3H). IR (KBr) 1178, 1206, 1508, 1541, 1558, 1602, 1636, 1717, 1734, 2344, 2363, HRMS (ESI + ) calcd for [C14H16O+Na] + : Found: Pent-3-yn-1-ylbenzene Analytical data for 2e: colorless oil. 1 H NMR (400 MHz, CDCl3) δ (m, 2H), 7.21 (d, 3H), 2.82 (t, J = 7.7 Hz, 2H), (m, 2H), 1.78 (t, J = 2.5 Hz, 3H). ((Hex-4-yn-1-yloxy)methyl)benzene Analytical data for 2g: colorless oil. 1 H NMR (400 MHz, CDCl3) δ 7.34 (d, J = 4.4 Hz, 4H), (m, 1H), 4.51 (s, 2H), 3.56 (t, J = 6.3 Hz, 2H), (m, 2H), (m, 5H). 13 C NMR (100 MHz, CDCl3) δ 138.6, 128.3, 127.6, 127.5, 78.5, 75.7, 72.9, 68.9, 29.1, 15.5, 3.4. IR (KBr) 697, 736, 1027, 1105, 1364, 1454, 2366, 2856, 2919, HRMS (ESI + ) calcd for [C 13H 16O+Na] + : Found: S21

23 Hex-4-yn-1-yl benzoate Analytical data for 2h: colorless oil. 1 H NMR (400 MHz, CDCl3) δ 8.05 (dd, J = 7.1 Hz, J = 1.4 Hz, 2H), 7.55 (t, J = 7.4 Hz, 1H), 7.43 (t, J = 7.6 Hz, 2H), 4.41 (t, J = 6.3 Hz, 2H), (m, 2H), 1.95 (p, J = 6.7 Hz, 2H), 1.77 (t, J = 2.5 Hz, 3H). 13 C NMR (100 MHz, CDCl3) δ 166.5, 132.8, 130.3, 129.5, 128.3, 77.7, 76.3, 63.8, 28.1, 15.6, 3.4. IR (KBr) 710, 1026, 1115, 1272, 1450, 1719, 2364, HRMS (ESI + ) calcd for [C13H14O2+Na] + : Found: tert-butyl(hex-4-yn-1-yloxy)dimethylsilane Analytical data for 2i: colorless oil. 1 H NMR (400 MHz, CDCl3) δ 3.68 (t, J = 6.1 Hz, 2H), (m, 2H), 1.77 (t, J = 2.6 Hz, 3H), 1.67 (p, J = 6.7 Hz, 2H), 0.89 (s, 9H), 0.05 (s, 6H). Hex-4-yn-1-yl 4-methylbenzenesulfonate Analytical data for 2j: colorless oil. 1 H NMR (400 MHz, CDCl3) δ 7.81 (d, J = 8.4 Hz, 2H), 7.35 (d, J = 8.2 Hz, 2H), 4.14 (t, J = 6.5 Hz, 2H), 2.45 (s, 3H), (m, 2H), 1.80 (p, J = 6.8 Hz, 2H), 1.69 (t, J = 2.5 Hz, 3H). Hex-4-yn-1-ol S22

24 Analytical data for 2k: pale yellow oil. 1 H NMR (400 MHz, CDCl3) δ 3.75 (t, J = 6.1 Hz, 2H), (m, 2H), 1.78 (t, J = 2.6 Hz, 3H), 1.76 (m, J = 6.6 Hz,2H), 1.70 (s, 1H). 6-Chlorohex-2-yne Analytical data for 2l: pale yellow oil. 1 H NMR (400 MHz, CDCl3) δ 3.65 (t, J = 6.4 Hz, 2H), (m, 2H), 1.93 (td, J = 20.2, 13.4, 6.7 Hz, 2H), 1.78 (t, J = 2.5 Hz, 3H). 2,2-Dimethyl-1-phenylhex-4-yn-1-one Analytical data for 2m: colorless oil. 1 H NMR (400 MHz, CDCl3) δ 7.63 (d, J = 7.0 Hz, 2H), 7.46 (t, J = 7.2 Hz, 1H), 7.40 (t, J = 7.6 Hz, 2H), 2.51 (dd, J = 4.9, 2.4 Hz, 2H), 1.77 (t, J = 2.5 Hz, 3H), 1.39 (s, 6H). N-benzyl-N-(but-2-yn-1-yl)-4-methylbenzenesulfonamide Analytical data for 2n: white solid. 1 H NMR (400 MHz, CDCl3) δ 7.81 (d, J = 8.3 Hz, 2H), (m, 7H), 4.32 (s, 2H), 3.88 (q, J = 2.4 Hz, 2H), 2.45 (s, 3H), 1.55 (t, J = 2.4 Hz, 3H). S23

25 2,2,2-Trifluoro-N-(hex-4-yn-1-yl)acetamide Analytical data for 2o: colorless oil. 1 H NMR (400 MHz, CDCl3) δ 6.89 (s, 1H), 3.51 (q, J = 6.5 Hz, 2H), (m, 2H), (m, 5H). (8R,9S,13S,14S)-13-methyl-3-(pent-3-yn-1-yloxy)-7,8,9,11,12,13,15,16-octahydro- 6H-cyclopenta[a]phenanthren-17(14H)-one Analytical data for 2q: white solid. 1 H NMR (400 MHz, CDCl3) δ 7.20 (d, J = 8.9 Hz, 1H), 6.73 (dd, J = 8.6, 2.7 Hz, 1H), 6.66 (d, J = 2.6 Hz, 1H), 4.04 (t, J = 7.2 Hz, 2H), 2.91 (dd, J = 11.5, 5.0 Hz, 2H), (m, 2H), 2.54 (dd, J = 18.9, 8.7 Hz, 1H), (m, 1H), (m, 1H), (m, 4H), 1.80 (t, J = 2.5 Hz, 3H), (m, 6H), 0.91 (s, 3H). 13 C NMR (100 MHz, CDCl3) δ 220.9, 156.5, 137.7, 132.2, 126.3, 114.6, 112.2, 75.0, 66.5, 50.3, 47.9, 43.9, 38.3, 35.8, 31.5, 29.6, 26.5, 25.8, 21.5, 19.7, 13.8, 3.5, 0.9. IR (KBr) 817, 1007, 1055, 1160, 1254, 1499, 1609, 1738, 2861, HRMS (ESI + ) calcd for [C23H28O2+H] + : Found: S24

26 3-(1-Phenylallyl)pentane-2,4-dione (3a) Prepared according to the general procedure A to provide 3a as a colorless oil, 42.8 mg, 99% yield after purification by silica gel column chromatography, eluting with 2-5% EtOAc in PE (elution gradient). The analytical data of 3a was in agreement with those reported [1]. 1 H NMR (400 MHz, CDCl3) δ (m, 2H), (m, 3H), (m, 1H), (m, 2H), 4.26 (d, J = 11.7 Hz, 1H), 4.19 (dd, J = 11.7, 7.7 Hz, 1H), 2.25 (s, 3H), 1.88 (s, 3H). 3-(1-(p-Tolyl)allyl)pentane-2,4-dione (3b) Prepared according to the general procedure A to provide 3b as a yellow oil, 45.5 mg, 99% yield after purification by silica gel column chromatography, eluting with 5-7% EtOAc in PE (elution gradient). 1 H NMR (400 MHz, CDCl3) δ (m, 4H), 5.85 (ddd, J = 17.3, 10.2, 7.7 Hz, 1H), 5.08 (m, 2H), 4.24 (d, J = 11.7 Hz, 1H), 4.13 (dd, J = 11.7, 7.8 Hz, 1H), 2.29 (s, 3H), 2.24 (s, 3H), 1.89 (s, 3H). 13 C NMR (100 MHz, CDCl3) δ 202.9, 202.8, 138.2, 136.8, 136.7, 129.5, 127.7, 116.1, 74.2, 49.4, 29.9, 29.5, IR (KBr) 525, 819, 923, 1154, 1356, 1513, 1699, 2364, 2924, HRMS (ESI + ) calcd for [C15H18O2+Na] + : Found: Ethyl 4-(4-acetyl-5-oxohex-1-en-3-yl)benzoate (3c) S25

27 Prepared according to the general procedure A to provide 3c as a yellow oil, 57.0 mg, 99% yield after purification by silica gel column chromatography, eluting with 5-7% EtOAc in PE (elution gradient). 1 H NMR (400 MHz, CDCl3) δ 7.99 (d, J = 8.4 Hz, 2H), 7.29 (d, J = 8.3 Hz, 2H), (m, 1H), 5.12 (dd, J = 13.8, 3.3 Hz, 2H), 4.36 (q, J = 7.1 Hz, 2H), (m, 2H), 2.25 (s, 3H), 1.91 (s, 3H), 1.39 (t, J = 7.1 Hz, 3H). 13 C NMR (100 MHz, CDCl3) δ 202.2, 202.0, 166.1, 149.9, 137.1, 130.0, 129.4, 127.9, 117.1, 73.9, 60.8, 49.4, 29.9, 29.4, IR (KBr) 768, 857, 927, 1020, 1106, 1182, 1278, 1359, 1609, 1716, 2366, HRMS (ESI + ) calcd for [C17H20O4+Na] + : Found: (1-(4-Pentanoylphenyl)allyl)pentane-2,4-dione (3d) Prepared according to the general procedure A to provide 3d as a yellow oil, 57.1 mg, 95% yield after purification by silica gel column chromatography, eluting with 5-7% EtOAc in PE (elution gradient). 1 H NMR (400 MHz, CDCl3) δ 7.91 (d, J = 8.4 Hz, 2H), 7.30 (d, J = 8.4 Hz, 2H), (m, 1H), (m, 2H), (m, 2H), 2.94 (t, J = 7.4 Hz, 2H), 2.25 (s, 3H), 1.92 (s, 3H), 1.74 (p, J = 7.6 Hz, 2H), 1.45 (td, J = 15.0, 7.5 Hz, 2H), 0.96 (t, J = 7.4 Hz, 3H). 13 C NMR (100 MHz, CDCl3) δ 202.2, 202.1, 199.9, 145.1, 137.1, 136.0, 128.6, 128.1, 117.3, 73.9, 49.4, 38.23, 30.0, S26

28 29.4, 26.4, 22.4, IR (KBr) 926, 1010, 1183, 1267, 1358, 1605, 1699, 2366, HRMS (ESI + ) calcd for [C19H24O3+Na] + : Found: (5-Phenylpent-1-en-3-yl)pentane-2,4-dione (3e) Prepared according to the general procedure A to provide 3e as a colorless oil, 30.7 mg, 63% yield after purification by silica gel column chromatography, eluting with 9-12% DCM in PE (elution gradient). 1 H NMR (400 MHz, CDCl3) δ (m, 2H), 7.18 (d, J = 7.2 Hz, 1H), 7.14 (d, J = 7.2 Hz, 2H), (m, 1H), (m, 2H), 3.70 (d, J = 10.4 Hz, 1H), 2.91 (qd, J = 10.4, 3.0 Hz, 1H), (m, 1H), (m, 1H), 2.11 (s, 3H), 2.09 (s, 3H), (m, 1H), (m, 1H). 13 C NMR (100 MHz, CDCl3) δ 203.5, 203.3, 141.5, 137.5, 128.4, 128.3, 125.9, 118.4, 74.6, 43.9, 34.2, 33.0, 29.9, IR (KBr) 700, 47, 923, 1149, 1357, 1455, 1698, 2367, HRMS (ESI + ) calcd for [C16H20O2+Na] + : Found: (Non-1-en-3-yl)pentane-2,4-dione (3f) Prepared according to the general procedure A to provide 3f as a colorless oil, 18.4 mg, 82% yield after purification by silica gel column chromatography, eluting with 33-35% DCM in PE (elution gradient). 1 H NMR (400 MHz, CDCl3) δ (m, 1H), (m, 2H), 3.68 (d, J = 10.6 Hz, 1H), 2.86 (dd, J = 19.4, 9.6 Hz, 1H), 2.20 (s, 3H), 2.10 (s, 3H), (m, 10H), 0.87 (t, J = 6.4 Hz, 3H). 13 C NMR (100 S27

29 MHz, CDCl3) δ 203.7, 203.6, 137.9, 117.6, 74.8, 44.8, 32.5, 31.6, 30.2, 29.5, 28.9, 26.7, 22.5, IR (KBr) 1360, 1457, 1541, 1558, 1699, 2364, 2857, HRMS (ESI + ) calcd for [C14H24O2+Na] + : Found: (6-(Benzyloxy)hex-1-en-3-yl)pentane-2,4-dione (3g) Prepared according to the general procedure A to provide 3g as a colorless oil, 55.1 mg, 95% yield after purification by silica gel column chromatography, eluting with 5-7% EtOAc in PE (elution gradient). 1 H NMR (400 MHz, CDCl3) δ (m, 5H), (m, 1H), (m, 2H), 4.47 (s, 2H), 3.69 (t, J = 10.6 Hz, 1H), (m, 2H), 2.92 (qd, J = 10.4, 3.4 Hz, 1H), 2.18 (s, 3H), 2.09 (s, 3H), (m, 1H), (m, 1H), (m, 1H), (m, 1H). 13 C NMR (100 MHz, CDCl3) δ 203.5, 203.4, 138.4, 137.6, 128.3, 127.5, , 74.6, 72.8, 69.7, 44.1, 30.1, 29.5, 28.9, IR (KBr) 698, 739, 923, 1102, 1274, 1358, 1698, 2365, 2858, HRMS (ESI + ) calcd for [C18H24O3+Na] + : Found: Acetyl-6-oxo-4-vinylheptyl benzoate (3h) Prepared according to the general procedure A to provide 3h as a colorless oil, 54.4 mg, 90% yield after purification by silica gel column chromatography, eluting with 5-7% EtOAc in PE (elution gradient). 1 H NMR (400 MHz, CDCl3) δ (m, 2H), (m, 1H), 7.46 (t, J = 7.6 Hz, 2H), (m, 1H), (m, 2H), S28

30 (m, 2H), 3.72 (t, J = 10.4 Hz, 1H), 2.98 (qd, J = 10.3, 3.1 Hz, 1H), 2.19 (s, 3H), 2.11 (s, 3H), (m, 1H), (m, 1H), (m, 1H), (m, 1H). 13 C NMR (100 MHz, CDCl3) δ 203.3, 203.2, 166.5, 137.3, 132.9, 130.2, 129.5, 128.3, 118.3, 74.5, 64.4, 43.9, 30.1, 29.4, 28.8, IR (KBr) 714, 925, 1070, 1116, 1275, 1358, 1452, 1717, 2368, HRMS (ESI + ) calcd for [C18H22O4+Na] + : Found: (6-((tert-Butyldimethylsilyl)oxy)hex-1-en-3-yl)pentane-2,4-dione (3i) Prepared according to the general procedure A to provide 3i as a colorless oil, 47.4 mg, 76% yield after purification by silica gel column chromatography, eluting with 2-5% EtOAc in PE (elution gradient). 1 H NMR (400 MHz, CDCl3) δ 5.47 (ddd, J = 18.3, 13.5, 9.4 Hz, 1H), (m, 2H), 3.66 (d, J = 10.6 Hz, 1H), 3.55 (t, J = 6.0 Hz, 2H), 2.89 (qd, J = 10.4, 2.7 Hz, 1H), 2.16 (s, 3H), 2.07 (s, 3H), (m, 1H), (m, 2H), (m, 1H), 0.85 (s, 9H), 0.03 (s, 6H). 13 C NMR (100 MHz, CDCl3) δ 203.6, 203.5, 137.8, 117.8, 74.7, 62.6, 44.2, 30.0, 29.9, 29.6, 28.7, 25.9, 18.2, IR (KBr) 775, 835, 1099, 1255, 1358, 1472, 1700, 2366, 2857, HRMS (ESI + ) calcd for [C17H32O3Si+Na] + : Found: Acetyl-6-oxo-4-vinylheptyl 4-methylbenzenesulfonate (3j) S29

31 Prepared according to the general procedure A to provide 3j as a colorless oil, 56.3 mg, 80% yield after purification by silica gel column chromatography, eluting with 17-20% EtOAc in PE (elution gradient). 1 H NMR (400 MHz, CDCl3) δ 7.77 (d, J = 8.2 Hz, 2H), 7.35 (d, J = 8.0 Hz, 2H), (m, 1H), (m, 2H), (m, 2H), 3.65 (d, J = 10.4 Hz, 1H), 2.84 (qd, J = 10.3, 2.9 Hz, 1H), 2.45 (s, 3H), 2.17 (s, 3H), 2.08 (s, 3H), (m, 1H), (m, 1H), (m, 1H), (m, 1H). 13 C NMR (100 MHz, CDCl3) δ 203.0, 202.9, 144.7, 136.9, 132.9, 129.8, 127.8, 118.5, 74.2, 69.9, 43.6, 30.2, 29.4, 28.1, 26.3, IR (KBr) 555, 664, 816, 927, 1176, 1358, 1699, 2366, HRMS (ESI + ) calcd for [C18H24O5S+Na] + : Found: (6-Hydroxyhex-1-en-3-yl)pentane-2,4-dione (3k) Prepared according to the general procedure A to provide 3k as a colorless oil, 22.6 mg, 57% yield after purification by silica gel column chromatography, eluting with 33-35% EtOAc in PE (elution gradient). 1 H NMR (400 MHz, CDCl3) δ (m, 1H), (m, 2H), 3.70 (d, J = 10.4 Hz, 1H), 3.64 (t, J = 6.0 Hz, 2H), 2.93 (qd, J = 10.3, 2.8 Hz, 1H), 2.21 (s, 3H), 2.11 (s, 3H), 1.72 (s, 1H), (m, 1H), (m, 2H), (m, 1H). 13 C NMR (100 MHz, CDCl3) δ 203.7, 203.4, 137.5, 118.1, 74.6, 62.2, 43.8, 30.3, 29.7, 29.4, IR (KBr) 923, 1153, 1359, 1419, 1541, 1697, 2363, HRMS (ESI + ) calcd for [C11H18O3+Na] + : Found: (6-Chlorohex-1-en-3-yl)pentane-2,4-dione (3l) S30

32 Prepared according to the general procedure A to provide 3l as a yellow oil, 42.2 mg, 97% yield after purification by silica gel column chromatography, eluting with 5-7% EtOAc in PE (elution gradient). 1 H NMR (400 MHz, CDCl3) δ (m, 1H), (m, 2H), 3.70 (d, J = 10.5 Hz, 1H), (m, 2H), (qd, J = 10.4, 3.1 Hz, 1H), 2.21 (s, 3H), 2.11 (s, 3H), (m, 1H), (m, 1H), (m, 1H), (m, 1H). 13 C NMR (100 MHz, CDCl3) δ 203.3, 203.1, 137.2, 118.3, 74.5, 44.5, 43.6, 30.0, 29.8, IR (KBr) 925, 1147, 1358, 1420, 1699, 2367, HRMS (ESI + ) calcd for [C11H17O2Cl+Na] + : Found: Acetyl-2,2-dimethyl-1-phenyl-4-vinylheptane-1,6-dione (3m) Prepared according to the general procedure A to provide 3m as a colorless oil, 28.3 mg, 47% yield after purification by silica gel column chromatography, eluting with 5-7% EtOAc in PE (elution gradient). 1 H NMR (400 MHz, CDCl3) δ 7.63 (d, J = 7.6 Hz, 2H), 7.49 (t, J = 7.0 Hz, 1H), 7.42 (d, J = 7.4 Hz, 2H), (m, 1H), (m, 2H), 3.71 (d, J = 10.0 Hz, 1H), 3.12 (qd, J = 10.4, 2.7 Hz, 1H), 2.21 (s, 3H), 2.18 (dd, J = 12.0, 3.0 Hz, 1H), 2.08 (s, 3H), 1.53 (dd, J = 13.8, 2.5 Hz, 1H) 1.36 (d, J = 2.7 Hz, 6H). 13 C NMR (100 MHz, CDCl3) δ 208.6, 203.4, 203.2, 138.9, 138.2, 130.8, 128.0, 127.9, 118.2, 74.8, 47.0, 42.6, 42.1, 30.2, 29.9, 28.9, IR (KBr) 1361, 1419, 1473, 1558, 1698, 1733, , HRMS (ESI + ) calcd for [C19H24O3+Na] + : Found: S31

33 N-(3-acetyl-4-oxo-2-vinylpentyl)-N-benzyl-4-methylbenzenesulfonamide (3n) Prepared according to the general procedure A to provide 3n as a colorless oil, 50.4 mg, 61% yield after purification by silica gel column chromatography, eluting with 9-12% EtOAc in PE (elution gradient). 1 H NMR (400 MHz, CDCl3) δ 7.67 (d, J = 8.6 Hz, 2H), (m, 7H), 5.68 (dt, J = 17.2, 9.9 Hz, 1H), 4.95 (dd, J = 10.2, 1.2 Hz, 1H), 4.76 (d, J = 17.2 Hz, 1H), 4.50 (d, J = 14.6 Hz, 1H), 4.10 (d, J = 14.6 Hz, 1H), 3.86 (d, J = 7.0 Hz, 1H), 3.31 (dd, J = 14.2, 7.7 Hz, 1H), 2.94 (dd, J = 14.2, 6.8 Hz, 1H), 2.72 (m, 1H), 2.44 (s, 3H), 2.06 (s, 3H), 1.94 (s, 3H). 13 C NMR (100 MHz, CDCl3) δ 203.9, 203.5, 143.5, 136.2, 136.0, 135.3, 129.7, 128.9, 128.6, 128.1, 127.2, 118.9, 68.6, 54.0, 51.7, 43.3, 30.2, 29.4, IR (KBr) 549, 656, 699, 928, 1159, 1339, 1496, 1699, 2364, HRMS (ESI + ) calcd for [C23H27NO4S+H] + : Found: N-(5-acetyl-6-oxo-4-vinylheptyl)-2,2,2-trifluoroacetamide (3o) Prepared according to the general procedure A to provide 3o as a colorless oil, 45.2 mg, 77% yield after purification by silica gel column chromatography, eluting with 17-20% EtOAc in PE (elution gradient). 1 H NMR (400 MHz, CDCl3) δ 6.72 (s, 1H), (m, 1H), (m, 2H), 3.71 (d, J = 10.8 Hz, 1H), 3.47 (td, J = 13.4, 6.3 Hz, 1H), 3.36 (td, J = 12.4, 5.5 Hz,1H), 2.90 (qd, J = 10.4, 2.9 Hz, 1H), 2.20 (s, S32

34 3H), 2.11 (s, 3H), (m, 1H), (m, 1H), (m, 1H), (m, 1H). 13 C NMR (100 MHz, CDCl3) δ 203.6, 203.0, (q, J = 36.6 Hz), 137.0, 118.6, (q, J = Hz), 74.1, 43.0, 39.1, 30.5, 29.4, 29.1, F NMR (376 MHz, CDCl3) δ IR (KBr) 1156, 1361, 1419, 1457, 1508, 1699, 2365, HRMS (ESI + ) calcd for [C13H18NO3F3+Na] + : Found: (5-(((8R,9S,13S,14S)-13-methyl-17-oxo-7,8,9,11,12,13,14,15,16,17-decahydro- 6H-cyclopenta[a]phenanthren-3-yl)oxy)pent-1-en-3-yl)pentane-2,4-dione (3q) Prepared according to the general procedure A to provide 3q as a yellow oil, 76.1 mg, 87% yield after purification by silica gel column chromatography, eluting with 9-12% EtOAc in PE (elution gradient). 1 H NMR (400 MHz, CDCl3) δ 7.19 (d, J = 8.6 Hz, 1H), 6.69 (dd, J = 8.6, 2.6 Hz, 1H), 6.61 (d, J = 2.5 Hz, 1H), (m, 1H), (m, 2H), (m, 2H), 3.81 (d, J = 10.4 Hz, 1H), 3.22 (qd, J = 10.0, 3.3 Hz, 1H), (m, 2H), 2.53 (dd, J = 18.7, 8.6 Hz, 1H), (m, 1H), 2.23 (s, 3H), (m, 1H), 2.13 (s, 3H), (m, 4H), (m, 1H), (m, 4H), (m, 2H), 1.25 (s, 1H), 0.91 (s, 3H). 13 C NMR (100 MHz, CDCl3) δ 220.9, 203.4, 203.4, 156.6, 137.7, 136.9, 132.1, 126.2, 118.5, 114.4, 112.0, 73.9, 64.7, 50.3, 47.9, 43.9, 41.0, 38.3, 35.8, 31.8, 31.5, 29.8, 29.7, 29.6, 26.5, 25.8, 21.5, IR (KBr) 1055, 1159, 1253, 1358, 1499, 1698, 1737, 2366, HRMS (ESI + ) calcd for [C28H36O4+Na] + : Found: S33

35 (E)-3-(1-Phenylbut-2-en-1-yl)pentane-2,4-dione (3r) Prepared according to the general procedure A to provide 3r as a colorless oil, 39.6 mg, 43% yield after purification by silica gel column chromatography, eluting with 1-3% EtOAc in PE (elution gradient). 1 H NMR (400 MHz, CDCl3) δ 7.29 (t, J = 7.3 Hz, 2H), 7.19 (t, J = 9.6 Hz, 3H), (m, 2H), 4.23 (d, J = 11.7 Hz, 1H), 4.12(dd, J = 11.6, 7.1 Hz, 1H), 2.23 (s, 3H), 1.87 (s, 3H), 1.61 (d, J = 5.2 Hz, 3H). 13 C NMR (100 MHz, CDCl3) δ 203.0, 202.9, , 130.7, 128.8, 127.7, 127.4, 126.9, 74.6, 49.1, 30.0, 29.5, IR (KBr) 700, 755, 967, 1153, 1356, 1453, 1699, 2363, 2919, HRMS (ESI + ) calcd for [C15H18O2+Na] + : Found: (E)-3-(4-Phenylbut-3-en-2-yl)pentane-2,4-dione (3r ) Prepared according to the general procedure A to provide 3r as a colorless oil, 41.4 mg, 45% yield after purification by silica gel column chromatography, eluting with 1-3% EtOAc in PE (elution gradient). 1 H NMR (400 MHz, CDCl3) δ (m, 4H), (m, 1H), 6.44 (d, J = 15.9 Hz, 1H), 5.99 (dd, J = 15.9, 8.5 Hz, 1H), 3.70 (d, J = 10.3 Hz, 1H), (m, 1H), 2.22 (s, 3H), 2.13 (s, 3H), 1.08 (d, J = 6.7 Hz, 3H). 13 C NMR (100 MHz, CDCl3) δ 203.5, 203.4, 136.7, 130.9, 130.9, 128.5, 127.5, 126.2, 75.5, 37.8, 29.9, 29.6, IR (KBr) 694, 749, 969, 1155, 1357, 1492, 1698, 2362, 2926, 2966, HRMS (ESI + ) calcd for [C15H18O2+Na] + : Found: S34

36 4-(1-Phenylallyl)heptane-3,5-dione (5a) Prepared according to the general procedure A to provide 5a as a colorless oil, 24.1 mg, 99% yield after purification by silica gel column chromatography, eluting with 17-20% DCM in PE (elution gradient). 1 H NMR (400 MHz, CDCl3) of 5a: δ 7.28 (d, J = 7.4 Hz, 2H), (m, 3H), 5.86 (ddd, J = 17.1, 10.5, 7.2 Hz, 1H), (m, 2H), (m, 2H), 2.61 (qd, J = 7.5, 1.9 Hz, 2H), 2.26 (dq, J = 18.4, 7.4 Hz, 1H), 2.08 (dq, J = 18.4, 7.2 Hz, 1H), 1.03 (t, J = 7.1 Hz, 3H), 0.72 (t, J = 7.2 Hz, 3H). 1 H NMR (400 MHz, CDCl3) of 6a: δ 7.30 (m, 5H), 6.45 (d, J = 15.6 Hz, 1H), (m, 1H), 3.84 (t, J = 7.0 Hz, 1H), 2.76 (m, 2H), (m, 4H), 1.05 (t, J = 6.8 Hz, 6H). 13 C NMR (100 MHz, CDCl3) of 5a: δ 205.3, 140.1, 138.2, 128.8, 127.9, 127.1, 116.4, 72.9, 49.8, 36.3, 35.6, 7.3, 7.1. IR (KBr) 702, 922, 1101, 1347, 1456, 1699, 1733, 2939, HRMS (ESI + ) calcd for [C16H20O2+Na] + : Found: ,6-Dimethyl-4-(1-phenylallyl)heptane-3,5-dione (5b) Prepared according to the general procedure A to provide 5b as a colorless oil, 19.1 mg, 70% yield after purification by silica gel column chromatography, eluting with 17-20% DCM in PE (elution gradient). 1 H NMR (400 MHz, CDCl3) of 5b: δ 7.29 (m, 2H), 7.20 (m, 3H), 5.89 (ddd, J = 17.2, 10.2, 8.2 Hz, 1H), 5.08 (m, 2H), 4.46 (d, J = 11.8 Hz, 1H), 4.29 (dd, J = 11.2, 8.2 Hz, 1H), (m, 1H), (m, 1H), S35

37 1.09 (dd, J = 15.8, 6.8 Hz, 6H), 0.73 (d, J = 6.8 Hz, 3H), 0.63 (d, J = 6.9 Hz, 3H). 1 H NMR (400 MHz, CDCl3) of 6b: δ 7.29 (m, 5H), 6.45 (d, J = 15.8 Hz, 1H), 6.09 (m, 1H), 4.11 (t, J = 7.0 Hz, 1H), (m, 4H), 1.12 (dd, J = 15.6, 6.8 Hz, 12H). 13 C NMR (100 MHz, CDCl3) of 5b: δ 208.4, 208.3, 140.4, 138.4, 128.7, 128.3, 127.0, 116.7, 71.5, 50.2, 40.6, 40.3, 18.8, 18.2, 18.1, IR (KBr) 701, 758, 921, 1058, 1465, 1696, 1728, 2934, HRMS (ESI + ) calcd for [C18H24O2+Na] + : Found: (6-(Benzyloxy)hex-1-en-3-yl)heptane-3,5-dione (5c) Prepared according to the general procedure A to provide 5c as a colorless oil, 49.6 mg, 77% yield after purification by silica gel column chromatography, eluting with 5-7% EtOAc in PE (elution gradient). 1 H NMR (400 MHz, CDCl3) δ (m, 4H), (m, 1H), (m, 1H), (m, 2H), 4.47 (s, 2H), 3.70 (d, J = 10.9 Hz, 1H), (m, 2H), 2.95 (qd, J = 10.4, 3.1 Hz, 1H), (m, 4H), (m, 1H), (m, 1H), (m, 1H), (m, 1H), 1.01 (t, J = 7.4 Hz, 3H), 0.97 (t, J = 7.4 Hz, 3H). 13 C NMR (100 MHz, CDCl3) δ 206.0, 205.9, 138.4, 137.8, 128.2, 127.5, 127.4, 117.7, 73.1, 72.8, 69.7, 44.3, 36.1, 35.7, 29.0, 26.9, 7.4, 7.2. IR (KBr) 698, 737, 921, 1102, 1352, 1456, 1698, 2857, HRMS (ESI + ) calcd for [C20H28O3+Na] + : Found: Methyl 2-acetyl-3-phenylpent-4-enoate (5d) S36

38 Prepared according to the general procedure A to provide 5d as a colorless oil, 21.6 mg, 93% yield after purification by silica gel column chromatography, eluting with 33-35% DCM in PE (elution gradient). Major diastereomer: 1 H NMR (400 MHz, CDCl3): δ (m, 2H), (m, 3H), (m, 1H), (m, 2H), (m, 1H), (m, 1H), 3.73 (s, 3H), 1.98 (s, 3H). 13 C NMR (100 MHz, CDCl3): δ 201.4, 168.4, 139.8, 138.1, 128.8, 127.9, 127.2, 116.3, 64.8, 52.5, 49.5, Minor diastereomer: 1 H NMR (400 MHz, CDCl3): δ (m, 2H), (m, 3H), (m, 1H), (m, 2H), (m, 1H), (m, 1H), 3.46 (s, 3H), 2.29 (s, 3H). 13 C NMR (100 MHz, CDCl3): δ 201.6, 168.1, 140.1, 137.8, 128.6, 127.8, 127.1, 116.7, 65.2, 52.3, 49.4, IR (KBr) 700, 1157, 1419, 1490, 1541, 1717, 2367, HRMS (ESI + ) calcd for [C14H16O3+Na] + : Found: Acetyl-3-(1-phenylallyl)dihydrofuran-2(3H)-one (5e) Prepared according to the general procedure A to provide 5e as a colorless oil, 24.2 mg, 98% yield after purification by silica gel column chromatography, eluting with 33-35% DCM in PE (elution gradient). Major diastereomer: 1 H NMR (400 MHz, CDCl3): δ (m, 3H), 7.15 (d, J = 7.6 Hz, 2H), (m, 1H), (m, 1H), 5.02 (dd, J = 16.9, 0.6 Hz, 1H), 4.42 (d, J = 7.0 Hz, 1H), (m, 2H), (m, 1H), (m, 1H), 2.22 (s, 3H). 13 C NMR (100 MHz, CDCl3): δ 201.1, 174.7, 137.9, 136.1, 128.9, 128.5, 127.6, 119.4, 66.2, 53.0, 26.5, Minor diastereomer: 1 H NMR (400 MHz, CDCl3): δ (m, 5H), (m, 1H), (m, 2H), 4.49 (d, J = 8.8 Hz, 1H), 4.00 (q, J = 8.0 Hz, 1H), 3.54 (td, J = 8.6, S37

39 4.8 Hz, 0.1H), (m, 1H), 2.45 (s, 3H), (m, 1H). 13 C NMR (100 MHz, CDCl3): δ 201.4, 174.4, 137.5, 134.7, 129.1, 128.7, 127.7, 119.0, 66.4, 51.8, 26.2, IR (KBr) 703, 931, 1028, 1162, 1375, 1491, 1712, 1760, 2363, HRMS (ESI + ) calcd for [C15H16O3+Na] + : Found: Cinnamyl-1,3-diphenylpropane-1,3-dione (6f) Prepared according to the general procedure B to provide 6f as a colorless oil, 29.2 mg, 90% yield after purification by silica gel column chromatography, eluting with 2-5% EtOAc in PE (elution gradient). 1 H NMR (400 MHz, CDCl3) δ 7.98 (d, J = 7.8 Hz, 4H), 7.58 (t, J = 7.2 Hz, 2H), 7.47 (t, J = 7.2 Hz, 4H), 7.26 (d, J = 3.6 Hz, 4H), (m, 1H), 6.48 (d, J = 15.8 Hz, 1H), (m, 1H), 5.37 (t, J = 6.6 Hz, 1H), 3.04 (t, J = 6.9 Hz, 2H). 13 C NMR (100 MHz, CDCl3) δ 195.5, 136.9, 135.9, 133.5, 132.5, 128.9, 128.6, 128.4, 127.3, 126.7, 126.1, 57.2, IR (KBr) 692, 746, 966, 1263, 1448, 1559, 1696, 2345, 2926, 3026, HRMS (ESI + ) calcd for [C24H20O2+Na] + : Found: Cinnamyl-1,3-bis(4-fluorophenyl)propane-1,3-dione (6g) Prepared according to the general procedure B to provide 6g as a colorless oil, 23.7 mg, 63% yield after purification by silica gel column chromatography, eluting with 2- S38

40 5% EtOAc in PE (elution gradient). 1 H NMR (400 MHz, CDCl3) δ (m, 2H), 7.90 (d, J = 8.6 Hz, 2H), 7.44 (d, J = 8.5 Hz, 2H), 7.26 (d, J = 4.2 Hz, 4H), (m, 1H), 7.15 (t, J = 8.5 Hz, 2H), 6.47 (d, J = 15.8 Hz, 1H), (m, 1H), 5.23 (t, J = 6.7 Hz, 1H), 3.01 (t, J = 6.6 Hz, 2H). 13 C NMR (100 MHz, CDCl3) δ 194.2, 193.8, (d, J = Hz), 140.3, 136.8, 134.2, 132.8, (d, J = 2.8 Hz), (d, J = 9.4 Hz), 129.9, 129.3, 128.5, 127.5, 126.2, 126.1, (d, J = 22.0 Hz), 57.6, F NMR (376 MHz, CDCl3) δ (tt, J = 8.2, 5.3 Hz). IR (KBr) 741, 847, 965, 1156, 1234, 1399, 1507, 1595, 1697, 2364, HRMS (ESI + ) calcd for [C24H18O2F2+Na] + : Found: ,3-Bis(4-chlorophenyl)-2-cinnamylpropane-1,3-dione (6h) Prepared according to the general procedure B to provide 6h as a colorless oil, 30.7 mg, 75% yield after purification by silica gel column chromatography, eluting with 2-5% EtOAc in PE (elution gradient). 1 H NMR (400 MHz, CDCl3) δ 7.89 (d, J = 8.6 Hz, 4H), 7.42 (d, J = 8.6 Hz, 4H), (m, 4H), (m, 1H), 6.46 (d, J = 15.8 Hz, 1H), (m, 1H), 5.21 (t, J = 6.4 Hz, 1H), 3.00 (t, J = 6.7 Hz, 2H). 13 C NMR (100 MHz, CDCl3) δ 194.2, 140.3, 136.7, 134.2, 132.8, 129.9, 129.3, 128.5, 127.5, 126.1, 126.1, 57.5, IR (KBr) 741, 1093, 1263, 1399, 1588, 1697, 2362, HRMS (ESI + ) calcd for [C24H18O2Cl2+Na] + : Found: ,3-Bis(4-bromophenyl)-2-cinnamylpropane-1,3-dione (6i) S39

41 Prepared according to the general procedure B to provide 6i as a colorless oil, 32.9 mg, 66% yield after purification by silica gel column chromatography, eluting with 2-5% EtOAc in PE (elution gradient). 1 H NMR (400 MHz, CDCl3) δ 7.80 (d, J = 8.6 Hz, 4H), 7.60 (d, J = 8.6 Hz, 4H), (m, 4H), (m, 1H), 6.46 (d, J = 15.6 Hz, 1H), (m, 1H), 5.21 (t, J = 6.7 Hz, 1H), 3.00 (t, J = 6.6 Hz, 2H). 13 C NMR (100 MHz, CDCl3) δ 194.4, 136.7, 134.6, 132.9, 132.3, 130.0, 129.1, 128.5, 127.5, 126.2, 126.0, 57.5, IR (KBr) 737, 840, 1008, 1071, 1262, 1396, 1583, 1697, 2363, HRMS (ESI + ) calcd for [C24H18O2Br2+Na] + : Found: Cinnamyl-1,3-di-p-tolylpropane-1,3-dione (6j) Prepared according to the general procedure B to provide 6j as a colorless oil, 27.9 mg, 76% yield after purification by silica gel column chromatography, eluting with 2-5% EtOAc in PE (elution gradient). 1 H NMR (400 MHz, CDCl3) δ 7.88 (d, J = 8.2 Hz, 4H), (m, 8H), (m, 1H), 6.47 (d, J = 15.8 Hz, 1H), (m, 1H), 5.30 (t, J = 6.8 Hz, 1H), 3.00 (t, J = 6.8 Hz, 2H), 2.38 (s, 6H). 13 C NMR (100 MHz, CDCl3) δ 195.2, 144.4, 137.1, 133.5, 132.2, 129.6, 128.7, 128.4, 127.2, 127.0, 126.1, 57.2, 33.0, IR (KBr) 741, 818, 964, 1179, 1265, 1559, 1691, 2365, 2920, HRMS (ESI + ) calcd for [C26H24O2+Na] + : Found: S40

42 2-Cinnamyl-1,3-bis(4-methoxyphenyl)propane-1,3-dione (6k) Prepared according to the general procedure B to provide 6k as a colorless oil, 36.0 mg, 90% yield after purification by silica gel column chromatography, eluting with 9-12% EtOAc in PE (elution gradient). 1 H NMR (400 MHz, CDCl3) δ 7.97 (d, J = 8.9 Hz, 4H), (m, 4H), (m, 1H), 6.91 (d, J = 8.9 Hz, 4H), 6.47 (d, J = 15.8 Hz, 1H), (m, 1H), 5.23 (t, J = 6.5 Hz, 1H), 3.83 (s, 6H), 3.00 (t, J = 6.8 Hz, 2H). 13 C NMR (100 MHz, CDCl3) δ 194.1, 163.8, 137.1, 132.2, 130.9, 129.0, 128.4, 127.2, 127.1, 126.1, 114.0, 57.2, 55.5, IR (KBr) 745, 842, 1027, 1168, 1261, 1599, 1685, 2365, 2839, HRMS (ESI + ) calcd for [C26H24O4+Na] + : Found: Cinnamyl-1,3-di(naphthalen-2-yl)propane-1,3-dione (6l) Prepared according to the general procedure B to provide 6l as a colorless oil, 35.3 mg, 80% yield after purification by silica gel column chromatography, eluting with 5-7% EtOAc in PE (elution gradient). 1 H NMR (400 MHz, CDCl3) δ 8.55 (s, 2H), 8.06 (dd, J = 8.6, 1.4 Hz, 2H), (m, 6H), 7.60 (t, J = 7.6 Hz, 2H), 7.52 (t, J = 7.6 Hz, 2H), 7.24 (dt, J = 14.8, 6.7 Hz, 4H), (m, 1H), 6.54 (d, J = 15.8 Hz, 1H), (m, 1H), 5.66 (t, J = 6.7 Hz, 1H), 3.18 (t, J = 6.8 Hz, 2H). 13 C NMR (100 MHz, CDCl3) δ 195.5, 136.9, 135.7, 133.4, 132.5, 132.4, 130.5, 129.7, 128.9, 128.8, S41

43 128.4, 127.7, 127.3, 126.9, 126.8, 126.1, 124.1, 57.7, IR (KBr) 745, 820, 1123, 1176, 1278, 1466, 1689, 2366, HRMS (ESI + ) calcd for [C32H24O2+Na] + : Found: References: [1] T. M. Beck, B. Breit, Org. Lett. 2016, 18, [2] T. Fujihara, Y. Tani, K. Semba, J. Terao, Y. Tsuji, Angew. Chem. Int. Ed. 2012, 51, [3] F. A. Cruz, Z. Chen, S. I. Kurtoic, V. M. Dong, Chem. Commun. 2016, 52, [4] H. Kusama, K. Ishida, H. Funami, N. Iwasawa, Angew. Chem. Int. Ed. 2008, 47, [5] S. Arai, T. Sato, A. Nishida, Adv. Synth. Catal. 2009, 351, [6] J. M. Carney, P. J. Donoghue, W. M. Wuest, O. Wiest, P. Helquist, Org. Lett. 2008, 10, [7] S. Holing, B. Haberlag, M. Tamm, J. Collatz, P. Mack, J. L. M. Steidle, M. Vences, S. Schulz, Chem. Eur. J. 2014, 20, [8] Z. Xu, H. Chen, Z. Wang, A. Ying, L. Zhang, J. Am. Chem. Soc. 2016, 138, [9] T. Kippo, T. Fukuyama, I. Ryu, Org. Lett. 2011, 13, [10] T. Jiang, X. Quan, C. Zhu, P. G. Andersson, J.-E. Beckvall, Angew. Chem. Int. Ed. 2016, 55, S42

44 8. Copies of 1 H NMR and 13 C NMR Spectra of the Compounds ppm Figure S18: 1 H NMR of 1g ppm Figure S19: 1 H NMR of 1h S43

45 ppm Figure S20: 1 H NMR of 1i ppm Figure S21: 1 H NMR of 1j S44

46 ppm Figure S22: 1 H NMR of 1k ppm Figure S23: 1 H NMR of 1l S45

47 ppm Figure S24: 1 H NMR of 2b ppm Figure S25: 1 H NMR of 2c S46

48 ppm Figure S26: 1 H NMR of 2d ppm Figure S27: 13 C NMR of 2d S47

49 ppm Figure S28: 1 H NMR of 2e ppm Figure S29: 1 H NMR of 2g S48

50 ppm Figure S30: 13 C NMR of 2g ppm Figure S31: 1 H NMR of 2h S49

51 ppm Figure S32: 13 C NMR of 2h ppm Figure S33: 1 H NMR of 2i S50

52 ppm Figure S34: 1 H NMR of 2j ppm Figure S35: 1 H NMR of 2k S51

53 ppm Figure S36: 1 H NMR of 2l ppm Figure S37: 1 H NMR of 2m S52

54 ppm Figure S38: 1 H NMR of 2n ppm Figure S39: 1 H NMR of 2o S53

55 ppm Figure S40: 1 H NMR of 2q ppm Figure S41: 13 C NMR of 2q S54

56 ppm Figure S42: 1 H NMR of 3a S55

57 ppm Figure S43: 1 H NMR of 3b ppm Figure S44: 13 C NMR of 3b S56

58 ppm Figure S45: 1 H NMR of 3c ppm Figure S46: 13 C NMR of 3c S57

59 ppm Figure S47: 1 H NMR of 3d ppm Figure S48: 13 C NMR of 3d S58

60 ppm Figure S49: 1 H NMR of 3e ppm Figure S50: 13 C NMR of 3e S59

61 ppm Figure S51: 1 H NMR of 3f ppm Figure S52: 13 C NMR of 3f S60