Singapore, #05 01, 28 Medical Drive, Singapore. PR China,

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1 Electronic Supplementary Material (ESI) for Chemical Science. This journal is The Royal Society of Chemistry 2017 Catalyst controlled Regioselectivity in Phosphine Catalysis: Synthesis of Spirocyclic Benzofuranones via Regiodivergent [3+2] Annulations of Aurones and an Allenoate Huanzhen Ni, [a][b] Zhaoyuan Yu, [b][c] Weijun Yao, [d] Yu Lan,* [c] Nisar Ullah,* [e] and Yixin Lu* [a][b][f] [a] Graduate School for Integrative Sciences & Engineering (NGS), Centre for Life Sciences (CeLS), National University of Singapore, #05 01, 28 Medical Drive, Singapore [b] Department of Chemistry, National University of Singapore, 3 Science Drive 3, Singapore. [c] School of Chemistry and Chemical Engineering, Chongqing University, Chongqing , P. R. China. [d] Department of chemistry, Zhejiang Sci Tech University, , P. R. China. [e] Chemistry Department, King Fahd University of Petroleum and Materials, Dhahran 31261, Saudi Arabia. [f] National University of Singapore (Suzhou) Research Institute, 377 Lin Quan Street, Suzhou Industrial Park, Suzhou, Jiangsu, PR China, chmlyx@nus.edu.sg; lanyu@cqu.edu.cn; nullah@kfupm.edu.sa Supporting Information A. General information S2 B. Representative Procedure S2 C. Synthesis of dipeptide phosphine catalysts S3 D. Analytical data and HPLC Chromatogram of the Products S4 E. Synthesis of product 8 S45 F. Determination of stereochemistry of product 8 by 2D NMR S48 G. Computational methods S49 H. Proposed Reaction Cycle and DFT studies S50 I. Calculated Gibbs free energy profiles for the phosphine catalyzed [3+2] S51 annulation of aurone 1a and allene 2a J. B3LYP and M11 absolute calculation energies, enthalpies, and free energies. S55 K. B3LYP geometries for all the optimized compounds and transition states. S57 L. References S114 M. NMR Spectra of the Products S116 S1

2 A. General Information Unless otherwise specified, all reactions were carried out under a nitrogen atmosphere in anhydrous conditions. All the solvents were purified according to the standard procedures. All chemicals which are commercially available were used without further purification unless otherwise noted. Thin layer chromatography (TLC) was performed on silica gel plates (60F 254) using UV light (254 and 365 nm). Flash chromatography was conducted on silica gel ( mesh). 1 H and 13 C NMR spectra were recorded at ambient temperature in CDCl 3 on a Bruker AMX500 (500 MHz) spectrometer. Chemical shifts were reported in parts per million (ppm). All high resolution mass spectra were obtained on a Finnigan/MAT 95XL T spectrometer. ptical rotations were measured using a Jasco DIP 1000 polarimeter. Enantiomeric excesses were determined by HPLC analysis on a chiral stationary phase. Catalyst 3 and 4 were synthesized by following our previously reported procedures. 1 Aurones 1 were synthesized according to literature reported procedures. 2 B. Representative Procedure To a dried round bottle flask with a magnetic stirring bar under N 2 at room temperature were added aurones 1 (0.1 mmol) and allenoate 2a (0.12 mmol), followed by the addition of anhydrous ether (0.5 ml, for selective reaction) or CH 2 Cl 2 (0.5 ml, for selective reaction). Catalyst 4g (0.01 mmol, 10 mg, for selective reaction) or 4b (0.01 mmol, 10 mg, for selective reaction) was then introduced, and the reaction mixture was stirred for 12 hours. The solvent was then removed under reduced pressure and crude product was dissolved in CDCl 3 to for 1 H NMR to analyze the ratio for product 5 and 6. The crude product was then purified by column chromatography (Hexane: ether = 10:1) on silica gel to afford the major annulation adducts 5 or 6. S2

3 C. Synthesis of dipeptide phosphine catalysts Dipeptide catalysts were synthesized according to the previous reported procedure. 1 Catalyst 4c: a white solid; 1 H NMR (500 MHz, acetone d 6 ) δ 8.56 (s, 2H), 8.21 (s, 1H), 7.69 (ddd, J = 7.1 Hz, 5.8 Hz, 1.3 Hz, 4H), (m, 7H), (m, 10H), (m, 1H), 4.14 (qd, J = 6.2 Hz, 2.8 Hz, 1H), 4.07 (ddd, J = 11.6 Hz, 8.9 Hz, 4.5 Hz, 1H), 2.57 (ddd, J = 13.7 Hz, 4.1 Hz, 2.9 Hz, 1H), 2.40 (ddd, J = 13.6 Hz, 10.5Hz, 3.0 Hz, 1H), 2.31 (dq, J = 13.7 Hz, 6.8 Hz, 1H), 1.08 (d, J = 6.7 Hz, 3H), 1.05 (d, J = 6.8 Hz, 3H), 1.02 (s, 9H), 0.94 (d, J = 6.2 Hz, 3H); 13 C NMR (125 MHz, acetone d 6 ) δ , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , 71.00, 70.93, 59.69, 51.97, 51.84, 30.54, 26.61, 19.44, 19.42, 18.98, 18.46, 18.02; 31 P NMR (202 MHz, acetone d 6 ) δ 22.24; HRMS (ESI) m/z calcd for C 46 H 50 F 6 N 2 3 PSi [M + H] + = , found = Catalyst 4e: a white solid; 1 H NMR (500 MHz, acetone d 6 ) δ 8.60 (s, 2H), (m, 2H), 7.72 (dt, J = 8.0 Hz, 1.2 Hz, 4H), 7.46 (ddd, J = 9.9 Hz, 7.3 Hz, 5.8 Hz, 2H), 7.40 (dd, J = 11.2 Hz, 4.3 Hz, 5H), (m, 10H), 4.59 (dd, J = 8.5 Hz, 7.2 Hz, 1H), 4.16 (qd, J = 6.2 Hz, 2.3 Hz, 1H), (m, 1H), 2.49 (ddd, J = 13.7 Hz, 4.8 Hz, 1.9 Hz, 1H), (m, 2H), 1.01 (m, J = 10.6 Hz, 5.0 Hz, 18H); 13 C NMR (125 MHz, acetone d 6 ) δ , , , , , , , , , , , , , , , , , , , , , , , , , , , , 71.16, 71.10, 59.52, 51.88, 51.75, 30.98, 30.87, 30.57, 26.59, 19.15, 19.13, 18.98, 17.81; 31 P NMR (202 MHz, acetone d 6 ) δ 22.68; HRMS (ESI) m/z calcd for C 46 H 50 F 6 N 2 3 PSi [M + H] + = , found = Catalyst 4g: a white solid; 1 H NMR (500 MHz, acetone d 6 ) δ 8.55 (s, 2H), 8.25 (s, 1H), 8.07 (d, J = 7.6 Hz, 1H), (m, 4H), (m, 2H), (m, 8H), (m, 6H), 7.19 (d, J = 9.1 Hz, 1H), 4.64 (dd, J = 7.6 Hz, 4.2 Hz, 1H), (m, 1H), 4.21 (qd, J = 6.2 Hz, 2.7 Hz, 1H), (m, 1H), 2.59 (dd, J = 13.8 Hz, 4.2 Hz, 1H), 2.30 (ddd, J = 13.7 Hz, 9.8 Hz, 1.8 Hz, 1H), 1.22 (d, J = 6.3 Hz, 3H), (m, 12H), 0.91 (s, 9H), 0.17 (d, J = 7.1 Hz, 6H); 13 C NMR (125 MHz, acetone d 6 ) δ , , , , , , , S3

4 133.97, , , , , , , , , , , , , , , , , , , , 70.66, 70.60, 68.47, 59.09, 52.10, 51.98, 30.21, 30.10, 26.64, 25.46, 19.14, 18.96, 18.74, 17.72, 5.23, 5.36; 31 P NMR (202 MHz, Acetone d 6 ) δ 22.60; HRMS (ESI) m/z calcd for C 51 H 62 F 6 N 2 4 PSi 2 [M + H] + = , found = D. Analytical Data and HPLC Chromatogram of the Products tert Butyl (2R,2'S) 3 oxo 2' phenyl 3H spiro[benzofuran 2,1' cyclopentan] 3' ene 3' carboxylate 5a C 2 tbu A white solid; [α] 25 D = (c 1.0, CHCl 3 ); 1H NMR (500 MHz, CDCl 3 ) δ (m, 1H), (m, 1H), (m, 3H), 7.01 (dd, J = 7.4 Hz, 1.7 Hz, 2H), 6.97 (t, J = 7.4 Hz, 1H), 6.93 (q, J = 2.5 Hz, 1H), 6.69 (d, J = 8.4 Hz, 1H), 4.54 (d, J = 1.9 Hz, 1H), 3.16 (dt, J = 18.9 Hz, 2.0 Hz, 1H), 2.90 (ddd, J = 18.9 Hz, 2.5 Hz, 1.5 Hz, 1H), 1.22 (s, 9H). ; 13 C NMR (125 MHz, CDCl 3 ) δ , , , , , , , , , , , , , , 95.44, 80.75, 59.82, 41.90, 27.71; HRMS (ESI) m/z calcd for C 23 H 22 Na 4 [M + Na] + = , found = ; The ee value was 94%, t R (major) = min, t R (minor) = min (Chiralpak IC, λ = 254 nm, 10% i PrH/hexane, flow rate = 1.0 ml/min). racemic 5a S4

5 enantiomeric enriched 5a tert Butyl (2R,2'S) 2' (4 chlorophenyl) 3 oxo 3H spiro[benzofuran 2,1' cyclopentan] 3' ene 3' carboxylate 5b C 2 tbu Cl A white solid; [α] 25 D = (c 1.0, CHCl 3 ); 1 H NMR (500 MHz, CDCl 3 ) δ 7.61 (d, J = 7.7 Hz, 1H), (m, 1H), 7.12 (d, J = 8.4 Hz, 2H), 7.00 (t, J = 7.4 Hz, 1H), 6.96 (d, J = 8.3 Hz, 2H), 6.93 (q, J = 2.5 Hz, 1H), 6.73 (d, J = 8.4 Hz, 1H), 4.51 (d, J = 1.5 Hz, 1H), 3.15 (dt, J = 18.9 Hz, 2.0 Hz, 1H), 2.89 (ddd, J = 18.9 Hz, 2.5 Hz, 1.5 Hz, 1H); 13 C NMR (125 MHz, Acetone d 6 ) δ , , , , , , , , , , , , , , , , , , , , , 88.79, 38.93, 31.46, 13.12; HRMS (ESI) m/z calcd for C 23 H 21 ClNa 4 [M + Na] + = , found = ; The ee value was 93%, t R (major) = min, t R (minor) = min (Chiralpak IC, λ = 254 nm, 1% i PrH/hexane, flow rate = 1.0 ml/min). S5

6 Racemic 5b Enantioenriched 5b tert Butyl (2R,2'S) 2' (3 chlorophenyl) 3 oxo 3H spiro[benzofuran 2,1' cyclopentan] 3' ene 3' carboxylate 5c C 2 tbu Cl A white solid; [α] 25 D = (c 1.0, CHCl 3 ); 1 H NMR (500 MHz, CDCl 3 ) δ (m, 1H), (m, 1H), (m, 1H), 7.05 (t, J = 7.7 Hz, 2H), 7.00 (t, J = 7.5 Hz, 1H), 6.95 (q, J = 2.5 Hz, 1H), 6.88 (d, J = 7.6 Hz, 1H), 6.74 (dd, J = 8.5 Hz, 0.5 Hz, 1H), 4.50 (d, J = 1.7 Hz, 1H), 3.16 (dt, J = 18.9 Hz, 2.0 Hz, 1H), (m, 1H), 1.25 S6

7 (s, 9H); 13 C NMR (125 MHz, CDCl 3 ) δ , , , , , , , , , , , , , , , , 95.12, 81.05, 59.22, 41.98, 27.74; HRMS (ESI) m/z calcd for C 23 H 21 ClNa 4 [M + Na] + = , found = ; The ee value was 91%, t R (major) = min, t R (minor) = min (Chiralpak IC, λ = 254 nm, 10% i PrH/hexane, flow rate = 1.0 ml/min). Racemic 5c Enantioenriched 5c S7

8 tert Butyl (2R,2'S) 2' (2 chlorophenyl) 3 oxo 3H spiro[benzofuran 2,1' cyclopentan] 3' ene 3' carboxylate 5d Cl C 2 tbu Yellow oil; [α] 25 D = (c 1.0, CHCl 3 ); 1 H NMR (500 MHz, CDCl 3 ) δ 7.67 (dd, J = 7.7, 0.7 Hz, 1H), 7.46 (ddd, J = 8.5 Hz, 7.3 Hz, 1.4 Hz, 1H), 7.25 (dd, J = 7.7 Hz, 1.6 Hz, 1H), (m, 1H), 7.14 (dd, J = 7.9 Hz, 1.3 Hz, 1H), (m, 1H), (m, 1H), 6.99 (q, J = 2.5 Hz, 1H), 6.70 (d, J = 8.4 Hz, 1H), 5.15 (d, J = 2.2 Hz, 1H), (m, 1H), (m, 1H), 1.22 (s, 9H); 13 C NMR (125 MHz, CDCl 3 ) δ , , , , , , , , , , , , , , , , 94.08, 80.87, 55.21, 42.30, 27.67; HRMS (ESI) m/z calcd for C 23 H 21 ClNa 4 [M + Na] + = , found = ; The ee value was 91%, t R (major) = min, t R (minor) = min (Chiralpak IC, λ = 254 nm, 5% i PrH/hexane, flow rate = 1.0 ml/min). Racemic 5d S8

9 Enantioenriched 5d tert Butyl (2R,2'S) 2' (4 fluorophenyl) 3 oxo 3H spiro[benzofuran 2,1' cyclopentan] 3' ene 3' carboxylate 5e C 2 tbu F A white solid; [α] 25 D = (c 1, CHCl 3 ); 1 H NMR (500 MHz, CDCl 3 ) δ 7.60 (dd, J = 7.7, 0.6 Hz, 1H), 7.45 (dd, J = 11.5, 4.0 Hz, 1H), (m, 3H), 6.92 (q, J = 2.4 Hz, 1H), 6.83 (t, J = 8.6 Hz, 2H), 6.71 (d, J = 8.5 Hz, 1H), 4.53 (d, J = 1.7 Hz, 1H), 3.15 (dt, J = 18.9, 1.9 Hz, 1H), 2.89 (dd, J = 18.9, 1.7 Hz, 1H), 1.24 (s, 11H); 13 C NMR (125 MHz, CDCl 3 ) δ , , , (d, J = Hz), , , , (d, J = 3.2 Hz), (d, J = 8.1 Hz), , , , , (d, J = 21.3 Hz), , 95.30, 80.89, 59.10, 41.80, 27.76; HRMS (ESI) m/z calcd for C 23 H 21 FNa 4 [M + Na] + = , found = ; The ee value was 94%, t R (major) = min, t R (minor) = min (Chiralpak IC, λ = 254 nm, 10% i PrH/hexane, flow rate = 1.0 ml/min). S9

10 Racemic 5e Enantioenriched 5e tert Butyl (2R,2'S) 2' (4 methoxyphenyl) 3 oxo 3H spiro[benzofuran 2,1' cyclopentan] 3' ene 3' carboxylate 5f C 2 tbu Me A white solid; [α] 25 D = (c 1, CHCl 3 ); 1 H NMR (500 MHz, CDCl 3 ) δ (m, 1H), 7.44 (t, J = 7.8 Hz, 1H), 6.98 (t, J = 7.5 Hz, 1H), 6.93 (d, J = 8.4 Hz, 2H), 6.90 (q, J = 2.2 Hz, 1H), 6.73 (d, J = 8.4 Hz, 1H), 6.68 (d, J = 8.4 Hz, 2H), 4.50 (d, J = 1.4 Hz, 1H), 3.72 (s, 3H), 3.14 (d, J = 18.9 Hz, 1H), 2.88 (d, J = 18.9 Hz, 1H), 1.25 (s, 10H); 13 C NMR S10

11 (125 MHz, CDCl 3 ) δ , , , , , , , , , , , , , , 95.54, 80.71, 59.10, 55.12, 41.78, 27.78; HRMS (ESI) m/z calcd for C 24 H 24 Na 5 [M + Na] + = , found = ; The ee value was 96%, t R (major) = min, t R (minor) = min (Chiralpak IC, λ = 254 nm, 5% i PrH/hexane, flow rate = 1.0 ml/min). Racemic 5f Enantioenriched 5f S11

12 tert Butyl (2R,2'S) 3 oxo 2' (p tolyl) 3H spiro[benzofuran 2,1' cyclopentan] 3' ene 3' carboxylate 5g C 2 tbu A white solid; [α] 25 D = (c 1, CHCl 3 ); 1 H NMR (500 MHz, CDCl 3 ) δ (m, 1H), 7.44 (ddd, J = 8.5 Hz, 7.3 Hz, 1.4 Hz, 1H), 6.98 (t, J = 7.4 Hz, 1H), 6.94 (d, J = 8.0 Hz, 2H), (m, 3H), 6.73 (d, J = 8.4 Hz, 1H), 4.51 (d, J = 2.0 Hz, 1H), 3.14 (dt, J = 18.9, 2.0 Hz, 1H), 2.89 (ddd, J = 18.8, 2.6, 1.6 Hz, 1H), 2.23 (s, 3H), 1.25 (s, 9H); 13 C NMR (125 MHz, CDCl 3 ) δ , , , , , , , , , , , , , , 95.46, 80.70, 59.29, 41.89, 27.75, 21.07; HRMS (APCI) m/z calcd for C 24 H 24 Na 4 [M + Na] + = , found = ; The ee value was 95%, t R (major) = min, t R (minor) = min (Chiralpak IC, λ = 254 nm, 5% i PrH/hexane, flow rate = 1.0 ml/min). Racemic 5g S12

13 Enantioenriched 5g tert Butyl (2R,2'S) 3 oxo 2' (o tolyl) 3H spiro[benzofuran 2,1' cyclopentan] 3' ene 3' carboxylate 5h C 2 tbu A white solid; [α] 25 D = (c 1, CHCl 3 ); 1 H NMR (500 MHz, CDCl 3 ) δ 7.62 (d, J = 7.7 Hz, 1H), (m, 1H), (m, 1H), 7.10 (t, J = 7.4 Hz, 1H), (m, 2H), 6.91 (dt, J = 5.8 Hz, 2.8 Hz, 2H), 6.72 (d, J = 8.4 Hz, 1H), 4.84 (d, J = 2.1 Hz, 1H), (m, 1H), (m, 1H), 2.02 (s, 3H), 1.17 (s, 9H); 13 C NMR (125 MHz, CDCl 3 ) δ , , , , , , , , , , , , , , , , 95.02, 80.61, 54.85, 42.19, 27.62, 19.49; HRMS (ESI) m/z calcd for C 24 H 24 Na 4 [M + Na] + = , found = ; The ee value was 97%, t R (major) = min, t R (minor) = min (Chiralpak IC, λ = 254 nm, 10% i PrH/hexane, flow rate = 1.0 ml/min). S13

14 Racemic 5h Enantioenriched 5h tert Butyl (2R,2'S) 2' (4 cyanophenyl) 3 oxo 3H spiro[benzofuran 2,1' cyclopentan] 3' ene 3' carboxylate 5i C 2 tbu NC A white solid; [α] 25 D = (c 1, CHCl 3 ); 1 H NMR (500 MHz, CDCl 3 ) δ 7.62 (d, J = 7.6 Hz, 1H), (m, 3H), 7.15 (d, J = 8.1 Hz, 2H), (m, 2H), 6.69 (d, J = 8.4 Hz, 1H), 4.59 (s, 1H), 3.19 (dt, J = 19.0 Hz, 1.9 Hz, 1H), (m, 1H), 1.25 (s, 9H); 13 C NMR (125 MHz, CDCl 3 ) δ , , , , , , S14

15 137.23, , , , , , , , , 94.96, 81.30, 59.52, 42.12, 27.77; HRMS (ESI) m/z calcd for C 24 H 21 NNa 4 [M + Na] + = , found = ; The ee value was 93%, t R (major) = min, t R (minor) = min (Chiralpak IC, λ = 254 nm, 5% i PrH/hexane, flow rate = 1.0 ml/min). Racemic 5i Enantioenriched 5i tert Butyl (2R,2'S) 2' (naphthalen 2 yl) 3 oxo 3H spiro[benzofuran 2,1' cyclopentan] 3' ene 3' carboxylate 5j C 2 tbu S15

16 A white solid; [α] 25 D = (c 1, CHCl 3 ); 1 H NMR (500 MHz, CDCl 3 ) δ (m, 1H), 7.66 (m, 2H), 7.61 (dd, J = 7.8 Hz, 0.6 Hz, 1H), 7.47 (s, 1H), (m, 2H), (m, 1H), 7.21 (dd, J = 8.4 Hz, 1.1 Hz, 1H), 6.99 (q, J = 2.5 Hz, 1H), 6.92 (t, J = 7.5 Hz, 1H), 6.62 (d, J = 8.5 Hz, 1H), 4.74 (d, J = 1.7 Hz, 1H), 3.20 (dt, J = 18.8, 1.9 Hz, 1H), (m, 1H), 1.15 (s, 9H); 13 C NMR (125 MHz, CDCl 3 ) δ , , , , , , , , , , , , , , , , , , , , 95.65, 80.81, 59.65, 42.21, 27.69; HRMS (ESI) m/z calcd for C 27 H 24 Na 4 [M + Na] + = , found = ; The ee value was 94%, t R (major) = min, t R (minor) = min (Chiralpak IC, λ = 254 nm, 5% i PrH/hexane, flow rate = 1.0 ml/min). Racemic 5j S16

17 Enantioenriched 5j tert Butyl (2R,2'S) 2' (3,4 dimethoxyphenyl) 3 oxo 3H spiro[benzofuran 2,1' cyclopentan] 3' ene 3' carboxylate 5k C 2 tbu Me Me A white solid; [α] 25 D = 99.8 (c 1, CHCl 3 ); 1 H NMR (500 MHz, CDCl 3 ) δ 7.60 (d, J = 7.6 Hz, 1H), (m, 1H), 6.98 (t, J = 7.5 Hz, 1H), (m, 1H), 6.71 (d, J = 8.4 Hz, 1H), 6.62 (d, J = 8.2 Hz, 1H), 6.54 (dd, J = 8.2 Hz, 1.6 Hz, 1H), 6.51 (s, 1H), 4.50 (s, 1H), 3.78 (s, 3H), 3.71 (s, 3H), 3.14 (d, J = 18.9 Hz, 1H), (m, 1H), 1.26 (s, 9H); 13 C NMR (125 MHz, CDCl 3 ) δ , , , , , , , , , , , , , , , , 95.62, 80.79, 59.55, 55.79, 55.72, 41.75, 27.81; HRMS (ESI) m/z calcd for C 25 H 26 Na 6 [M + Na] + = , found = ; The ee value was 96%, t R (minor) = min, t R (major) = min (Chiralpak IC, λ = 254 nm, 20% i PrH/hexane, flow rate = 1.0 ml/min). Racemic 5k S17

18 Enantioenriched 5k tert Butyl (2R,2'S) 3 oxo 2' (thiophen 2 yl) 3H spiro[benzofuran 2,1' cyclopentan] 3' ene 3' carboxylate 5l C 2 tbu S A yellow solid; [α] 25 D = (c 1, CHCl 3 ); 1 H NMR (500 MHz, CDCl 3 ) δ (m, 1H), (m, 1H), 7.11 (d, J = 5.1 Hz, 1H), 7.02 (t, J = 7.5 Hz, 1H), (m, 1H), 6.87 (d, J = 8.5 Hz, 1H), 6.80 (dd, J = 5.0 Hz, 3.6 Hz, 1H), 6.72 (d, J = 3.4 Hz, 1H), 4.84 (d, J = 1.7 Hz, 1H), 3.13 (dt, J = 18.8 Hz, 1.9 Hz, 1H), (m, 1H), 1.29 (s, 9H); 13 C NMR (125 MHz, CDCl 3 ) δ , , , , , , , , , , , , , , , 94.85, 80.96, 54.29, 41.39, 27.78; HRMS (ESI) m/z calcd for C 21 H 20 Na 4 S [M + Na] + = , found = ; The ee value was 95%, t R (major) = min, t R (minor) = min (Chiralpak IC, λ = 254 nm, 5% i PrH/hexane, flow rate = 1.0 ml/min). S18

19 Racemic 5l Enantioenriched 5l tert Butyl (2R,2'S) 2' cyclohexyl 3 oxo 3H spiro[benzofuran 2,1' cyclopentan] 3' ene 3' carboxylate 5m C 2 tbu Colorless oil; [α] 25 D = 52.3 (c 1, CHCl 3 ); 1 H NMR (500 MHz, CDCl 3 ) δ 7.70 (d, J = 7.7 Hz, 1H), (m, 1H), 7.11 (dd, J = 7.9 Hz, 5.1 Hz, 2H), 6.67 (q, J = 2.4 Hz, 1H), 3.33 (d, J = 1.6 Hz, 1H), 2.83 (dd, J = 18.6 Hz, 1.4 Hz, 1H), (m, 1H), (m, 1H), (m, 6H), 1.53 (s, 9H), (m, 2H), (m, 1H), 0.88 (qd, J = 12.4 Hz, 3.3 Hz, 1H); 13 C NMR (125 MHz, CDCl 3 ) δ , , , , , , , S19

20 122.02, , , 96.41, 80.78, 56.05, 43.00, 38.62, 30.47, 30.41, 28.14, 27.20, 27.09, 26.53; HRMS (ESI) m/z calcd for C 23 H 28 Na 4 [M + Na] + = , found = ; The ee value was 95%, t R (major) = min, t R (minor) = min (Chiralpak IC, λ = 254 nm, 1% i PrH/hexane, flow rate = 1.0 ml/min). Racemic 5m Enantioenriched 5m tert Butyl (2R,2'S) 2' isopropyl 3 oxo 3H spiro[benzofuran 2,1' cyclopentan] 3' ene 3' carboxylate 5n C 2tBu S20

21 A white solid; [α] 25 D = 31.7 (c 1, CHCl 3 ); 1 H NMR (500 MHz, CDCl 3 ) δ 7.71 (dd, J = 7.9 Hz, 1.1 Hz, 1H), (m, 1H), 7.11 (dd, J = 8.2 Hz, 6.2 Hz, 2H), 6.70 (q, J = 2.4 Hz, 1H), 3.37 (dd, J = 3.5 Hz, 1.8 Hz, 1H), (m, 1H), (m, 1H), 2.36 (dtd, J = 14.2 Hz, 7.1 Hz, 4.0 Hz, 1H), 1.52 (s, 9H), 1.05 (d, J = 7.1 Hz, 3H), 0.81 (d, J = 7.1 Hz, 3H); 13 C NMR (125 MHz, CDCl 3 ) δ , , , , , , , , , 96.55, 80.76, 56.47, 43.05, 28.13, 27.99, 19.96, 19.64; HRMS (ESI) m/z calcd for C 20 H 24 Na 4 [M + Na] + = , found = ; The ee value was 94%, t R (major) = min, t R (minor) = min (Chiralpak IC, λ = 254 nm, 5% i PrH/hexane, flow rate = 1.0 ml/min). Racemic 5n Enantioenriched 5n S21

22 tert Butyl (2R,2'S) 2' butyl 3 oxo 3H spiro[benzofuran 2,1' cyclopentan] 3' ene 3' carboxylate 5o C 2 tbu Colorless oil; [α] 25 D = 21 (c 1, CHCl 3 ); 1 H NMR (500 MHz, CDCl 3 ) δ 7.70 (dd, J = 7.9 Hz, 1.1 Hz, 1H), 7.64 (ddd, J = 8.5 Hz, 7.3 Hz, 1.4 Hz, 1H), (m, 2H), 6.66 (q, J = 2.5 Hz, 1H), (m, 1H), 2.94 (ddd, J = 18.9 Hz, 2.3 Hz, 1.6 Hz, 1H), (m, 1H), (m, 1H), 1.71 (ddd, J = 18.6 Hz, 9.5Hz, 4.7 Hz, 1H), 1.52 (s, 9H), (m, 4H), (m, 1H), 0.74 (t, J = 7.2 Hz, 3H); 13 C NMR (125 MHz, CDCl 3 ) δ , , , , , , , , , , 95.82, 80.76, 52.31, 43.18, 29.76, 28.16, 26.55, 22.68, 13.74; HRMS (ESI) m/z calcd for C 21 H 26 Na 4 [M + Na] + = , found = ; The ee value was 94%, t R (major) = min, t R (minor) = min (Chiralpak IC, λ = 254 nm, 0.5% i PrH/hexane, flow rate = 1.0 ml/min). Racemic 5o S22

23 Enantioenriched 5o tert Butyl (2R,2'S) 2' ethyl 3 oxo 3H spiro[benzofuran 2,1' cyclopentan] 3' ene 3' carboxylate 5p C 2 tbu Colorless oil; [α] 25 D = 4.8 (c 1, CHCl 3 ); 1 H NMR (500 MHz, CDCl 3 ) δ 7.71 (d, J = 7.6 Hz, 1H), 7.65 (dd, J = 12.0 Hz, 4.7 Hz, 1H), 7.12 (dd, J = 11.9 Hz, 5.2 Hz, 2H), 6.68 (q, J = 2.3 Hz, 1H), (m, 1H), 2.94 (dd, J = 18.9 Hz, 1.5 Hz, 1H), 2.76 (dd, J = 18.9 Hz, 1.8 Hz, 1H), 1.86 (dqd, J = 15.0 Hz, 7.5 Hz, 3.2 Hz, 1H), (m, 1H), 1.66 (t, J = 5.0 Hz, 1H), 0.71 (t, J = 7.4 Hz, 3H); 13 C NMR (125 MHz, CDCl 3 ) δ , , , , , , , , , , 95.82, 80.77, 53.63, 43.21, 28.15, 20.13, 12.14; HRMS (ESI) m/z calcd for C 19 H 22 Na 4 [M + Na] + = , found = ; The ee value was 96%, t R (major) = min, t R (minor) = min (Chiralpak IC, λ = 254 nm, 1% i PrH/hexane, flow rate = 1.0 ml/min). S23

24 Racemic 5p Enantioenriched 5p tert Butyl (2R,5'S) 3 oxo 5' phenyl 3H spiro[benzofuran 2,1' cyclopentan] 2' ene 2' carboxylate 6a C 2 tbu A white solid; [α] 25 D = (c 1, CHCl 3 ); 1 H NMR (500 MHz, CDCl 3 ) δ 7.57 (dd, J = 7.7 Hz, 0.8 Hz, 1H), 7.44 (t, J = 2.4 Hz, 1H), 7.40 (ddd, J = 8.5 Hz, 7.3 HZ, 1.4 Hz, 1H), (m, 5H), 6.92 (t, J = 7.5 Hz, 1H), 6.78 (d, J = 8.3 Hz, 1H), 3.99 (t, J = 8.0 Hz, 1H), 3.08 (qdd, J = 18.8 Hz, 8.1 Hz, 2.5 Hz, 2H), 1.17 (s, 9H); 13 C NMR (125 MHz, CDCl 3 ) δ , , , , , , , , , , , , , , S24

25 96.87, 81.58, 54.23, 37.96, 27.61; HRMS (ESI) m/z calcd for C 23 H 22 Na 4 [M + Na] + = , found = ; The ee value was 98%, t R (minor) = min, t R (major) = min (Chiralpak IC, λ = 254 nm, 10% i PrH/hexane, flow rate = 1.0 ml/min). Racemic 6a Enantioenriched 5q tert Butyl (2R,5'S) 5' (4 chlorophenyl) 3 oxo 3H spiro[benzofuran 2,1' cyclopentan] 2' ene 2' carboxylate 6b C 2 tbu Cl S25

26 A white solid; [α] 25 D = (c 0.5, CHCl 3 ); 1 H NMR (500 MHz, CDCl 3 ) δ 7.58 (d, J = 7.6 Hz, 1H), (m, 1H), 7.42 (t, J = 2.4 Hz, 1H), (m, 4H), 6.96 (t, J = 7.4 Hz, 1H), 6.81 (d, J = 8.3 Hz, 1H), 3.95 (t, J = 8.1 Hz, 1H), (m, 2H), 1.16 (s, 9H); 13 C NMR (125 MHz, CDCl 3 ) δ , , , , , , , , , , , , , , 96.59, 81.72, 53.48, 38.16, 27.60; HRMS (ESI) m/z calcd for C 23 H 21 ClNa 4 [M + Na] + = , found = ; The ee value was 98%, t R (minor) = min, t R (major) = min (Chiralpak IC, λ = 254 nm, 10% i PrH/hexane, flow rate = 1.0 ml/min). Racemic 6b Enantioenriched 6b S26

27 tert Butyl (2R,5'S) 5' (3 chlorophenyl) 3 oxo 3H spiro[benzofuran 2,1' cyclopentan] 2' ene 2' carboxylate 6c C 2 tbu Cl A white solid; [α] 25 D = (c 1, CHCl 3 ); 1 H NMR (500 MHz, CDCl 3 ) δ 7.60 (d, J = 7.6 Hz, 1H), (m, 1H), 7.42 (t, J = 2.4 Hz, 1H), 7.24 (s, 1H), (m, 3H), 6.96 (t, J = 7.5 Hz, 1H), 6.84 (d, J = 8.3 Hz, 1H), 3.95 (t, J = 8.0 Hz, 1H), (m, 2H), 1.18 (s, 9H); 13 C NMR (125 MHz, CDCl 3 ) δ , , , , , , , , , , , , , , , , 96.54, 81.72, 53.66, 38.06, 27.61; HRMS (ESI) m/z calcd for C 27 H 24 Na 4 [M + Na] + = , found = ; The ee value was 98%, t R (minor) = min, t R (minor) = min (Chiralpak IC, λ = 254 nm, 10% i PrH/hexane, flow rate = 1.0 ml/min). Racemic 6c S27

28 Enantioenriched 6c tert Butyl (2R,5'S) 3 oxo 5' (o tolyl) 3H spiro[benzofuran 2,1' cyclopentan] 2' ene 2' carboxylate 6d C 2 tbu A white solid; [α] 25 D = (c 1, CHCl 3 ); 1 H NMR (500 MHz, CDCl 3 ) δ 7.58 (d, J = 7.6 Hz, 1H), 7.45 (t, J = 2.4 Hz, 1H), (m, 2H), 7.13 (t, J = 7.4 Hz, 1H), 7.01 (t, J = 7.4 Hz, 1H), 6.93 (t, J = 7.4 Hz, 2H), 6.81 (d, J = 8.4 Hz, 1H), 4.35 (t, J = 7.8 Hz, 1H), 3.06 (dddd, J = 19.1 Hz, 9.9 Hz, 7.8 Hz, 2.5 Hz, 2H), 2.16 (s, 3H), 1.17 (s, 9H); 13 C NMR (125 MHz, CDCl 3 ) δ , , , , , , , , , , , , , , , , 96.72, 81.55, 48.56, 39.54, 27.61, 19.88; HRMS (ESI) m/z calcd for C 24 H 24 Na 4 [M + Na] + = , found = ; The ee value was 99%, t R (minor) = min, t R (major) = min (Chiralpak IC, λ = 254 nm, 5% i PrH/hexane, flow rate = 1.0 ml/min). S28

29 Racemic 6d Enantioenriched 6d tert Butyl (2R,5'S) 5' (4 bromophenyl) 3 oxo 3H spiro[benzofuran 2,1' cyclopentan] 2' ene 2' carboxylate 6e C 2tBu Br A white solid; [α] 25 D = (c 1, CHCl 3 ); 1 H NMR (500 MHz, CDCl 3 ) δ 7.58 (d, J = 7.6 Hz, 1H), (m, 1H), 7.41 (t, J = 2.4 Hz, 1H), 7.29 (d, J = 8.3 Hz, 3H), 7.07 (d, J = 8.4 Hz, 2H), 6.96 (t, J = 7.4 Hz, 1H), 6.82 (d, J = 8.2 Hz, 1H), 3.94 (t, J = 8.0 Hz, 1H), (m, 2H), 1.17 (s, 9H); 13 C NMR (125 MHz, CDCl 3 ) δ , , , S29

30 151.31, , , , , , , , , , , 96.53, 81.72, 53.51, 38.14, 27.60; HRMS (ESI) m/z calcd for C 23 H 21 BrNa 4 [M + Na] + = , found = ; The ee value was 98%, t R (minor) = min, t R (major) = min (Chiralpak IC, λ = 254 nm, 20% i PrH/hexane, flow rate = 1.0 ml/min). Racemic 6e Enantioenriched 6e S30

31 tert Butyl (2R,5'S) 5' (4 methoxyphenyl) 3 oxo 3H spiro[benzofuran 2,1' cyclopentan] 2' ene 2' carboxylate 6f C 2 tbu Me A white solid; [α] 25 D = (c 1, CHCl 3 ); 1 H NMR (500 MHz, CDCl 3 ) δ 7.56 (dd, J = 7.7 Hz, 0.8 Hz, 1H), 7.41 (ddd, J = 9.9 Hz, 6.0 Hz, 1.4 Hz, 2H), (m, 2H), 6.92 (dd, J = 11.4 Hz, 4.1 Hz, 1H), 6.81 (d, J = 8.3 Hz, 1H), (m, 2H), 3.94 (t, J = 8.1 Hz, 1H), 3.69 (s, 3H), 3.02 (dd, J = 8.1 Hz, 2.5 Hz, 2H), 1.16 (s, 9H); 13 C NMR (125 MHz, CDCl 3 ) δ , , , , , , , , , , , , , , 96.90, 81.56, 55.10, 53.63, 38.33, 27.60; HRMS (ESI) m/z calcd for C 24 H 24 Na 5 [M + Na] + = , found = ; The ee value was 99%, t R (minor) = min, t R (major) = min (Chiralpak IC, λ = 254 nm, 5% i PrH/hexane, flow rate = 1.0 ml/min). Racemic 6f S31

32 Enantioenriched 6f tert Butyl (2R,5'S) 3 oxo 5' (p tolyl) 3H spiro[benzofuran 2,1' cyclopentan] 2' ene 2' carboxylate 6g C 2 tbu A white solid; [α] 25 D = (c 1, CHCl 3 ); 1 H NMR (500 MHz, CDCl 3 ) δ (m, 1H), (m, 2H), 7.07 (d, J = 8.0 Hz, 2H), 6.96 (d, J = 8.0 Hz, 2H), 6.93 (t, J = 7.5 Hz, 1H), 6.81 (d, J = 8.2 Hz, 1H), 3.96 (t, J = 8.0 Hz, 1H), (m, 2H), 2.21 (s, 3H), 1.17 (s, 9H); 13 C NMR (125 MHz, CDCl 3 ) δ , , , , , , , , , , , , , , 96.91, 81.53, 53.90, 38.20, 27.61, 20.99; HRMS (ESI) m/z calcd for C 24 H 24 Na 4 [M + Na] + = , found = ; The ee value was 99%, t R (minor) = min, t R (major) = min (Chiralpak IC, λ = 254 nm, 10% i PrH/hexane, flow rate = 1.0 ml/min). S32

33 Racemic 6g Enantioenriched 6g tert Butyl (2R,5'S) 3 oxo 5' (m tolyl) 3H spiro[benzofuran 2,1' cyclopentan] 2' ene 2' carboxylate 6h C 2 tbu A white solid; [α] 25 D = (c 1, CHCl 3 ); 1 H NMR (500 MHz, CDCl 3 ) δ 7.58 (d, J = 7.4 Hz, 1H), 7.42 (dd, J = 8.3 Hz, 7.3 Hz, 2H), 7.04 (t, J = 7.7 Hz, 1H), 6.99 (d, J = 2.9 Hz, 2H), 6.93 (t, J = 7.2 Hz, 2H), 6.79 (d, J = 8.3 Hz, 1H), 3.95 (t, J = 8.0 Hz, 1H), (m, 2H), 2.22 (s, 3H), 1.17 (s, 9H); 13 C NMR (125 MHz, CDCl 3 ) δ , , , S33

34 151.73, , , , , , , , , , , , , 96.91, 81.56, 54.17, 38.02, 27.62, 21.23; HRMS (ESI) m/z calcd for C 24 H 24 Na 4 [M + Na] + = , found = ; The ee value was 98%, t R (minor) = min, t R (major) = min (Chiralpak IC, λ = 254 nm, 10% i PrH/hexane, flow rate = 1.0 ml/min). Racemic 6h Enantioenriched 6h S34

35 tert Butyl (2R,5'S) 5' (4 fluorophenyl) 3 oxo 3H spiro[benzofuran 2,1' cyclopentan] 2' ene 2' carboxylate 6i C 2 tbu F A white solid; [α] 25 D = (c 1, CHCl 3 ); 1 H NMR (500 MHz, CDCl 3 ) δ 7.57 (dd, J = 7.7 Hz, 0.9 Hz, 1H), 7.43 (ddd, J = 9.0 Hz, 6.0 Hz, 1.9 Hz, 2H), (m, 2H), (m, 1H), (m, 3H), 3.96 (t, J = 8.1 Hz, 1H), (m, 2H), 1.17 (s, 9H); 13 C NMR (125 MHz, CDCl 3 ) δ , , (d, J = Hz), , , , , (d, J = 3.2 Hz), (d, J = 8.0 Hz), , , , (d, J = 21.3 Hz), , 96.67, 81.66, 78.41, 53.48, 38.23, 27.61; HRMS (ESI) m/z calcd for C 23 H 21 FNa 4 [M + Na] + = , found = ; The ee value was 96%, t R (minor) = min, t R (major) = min (Chiralpak IC, λ = 254 nm, 20% i PrH/hexane, flow rate = 1.0 ml/min). Racemic 6i S35

36 Enantioenriched 6i tert Butyl (2R,5'S) 5' (naphthalen 2 yl) 3 oxo 3H spiro[benzofuran 2,1' cyclopentan] 2' ene 2' carboxylate 6j C 2 tbu A white solid; [α] 25 D = (c 1, CHCl 3 ); 1 H NMR (500 MHz, CDCl 3 ) δ 7.72 (dd, J = 9.0 Hz, 4.8 Hz, 2H), (m, 2H), (m, 1H), 7.48 (t, J = 2.4 Hz, 1H), 7.39 (ddd, J = 10.1 Hz, 8.1 Hz, 3.1 Hz, 3H), (m, 1H), 6.87 (t, J = 7.4 Hz, 1H), 6.75 (d, J = 8.3 Hz, 1H), 4.18 (t, J = 8.0 Hz, 1H), 3.17 (dddd, J = 21.7 Hz, 18.8 Hz, 8.0 Hz, 2.5 Hz, 2H), 1.18 (s, 9H); 13 C NMR (125 MHz, CDCl 3 ) δ , , , , , , , , , , , , , , , , , , , 97.09, 81.64, 54.27, 38.38, 27.62; HRMS (ESI) m/z calcd for C 27 H 24 Na 4 [M + Na] + = , found = ; The ee value was 98%, t R (minor) = min, t R (major) = min (Chiralpak IC, λ = 254 nm, 5% i PrH/hexane, flow rate = 1.0 ml/min). S36

37 Racemic 6j Enantioenriched 6j tert Butyl (2R,5'S) 5' (3,4 dimethoxyphenyl) 3 oxo 3H spiro[benzofuran 2,1' cyclopentan] 2' ene 2' carboxylate 6k C 2 tbu Me Me A white solid; [α] 25 D = (c 1, CHCl 3 ); 1 H NMR (500 MHz, CDCl 3 ) δ 7.57 (d, J = 7.8 Hz, 1H), 7.42 (ddd, J = 6.0 Hz, 4.9 Hz, 1.4 Hz, 2H), 6.94 (t, J = 7.4 Hz, 1H), 6.80 (d, J = 8.3 Hz, 1H), 6.73 (dd, J = 8.2 Hz, 1.8 Hz, 1H), 6.68 (d, J = S37

38 1.7 Hz, 1H), 6.65 (d, J = 8.3 Hz, 1H), 3.94 (t, J = 8.1 Hz, 1H), 3.77 (s, 3H), 3.73 (s, 3H), (m, 2H), 1.16 (s, 9H); 13 C NMR (125 MHz, CDCl 3 ) δ , , , , , , , , , , , , , , , , 96.96, 81.62, 55.81, 55.71, 53.94, 38.08, 27.60; HRMS (ESI) m/z calcd for C 25 H 26 Na 6 [M + Na] + = , found = ; The ee value was 99%, t R (minor) = min, t R (major) = min (Chiralpak IC, λ = 254 nm, 20% i PrH/hexane, flow rate = 1.0 ml/min). Racemic 6k Enantioenriched 6k S38

39 tert Butyl (2R,5'R) 3 oxo 5' (thiophen 2 yl) 3H spiro[benzofuran 2,1' cyclopentan] 2' ene 2' carboxylate 6l C 2 tbu S A yellow solid; [α] 25 D = (c 1, CHCl 3 ); 1 H NMR (500 MHz, CDCl 3 ) δ (m, 1H), (m, 1H), 7.39 (t, J = 2.4 Hz, 1H), (m, 1H), 6.99 (t, J = 7.4 Hz, 1H), 6.92 (d, J = 8.4 Hz, 1H), 6.78 (d, J = 3.4 Hz, 2H), 4.31 (t, J = 8.1 Hz, 1H), 3.09 (dddd, J = 20.6 Hz, 18.6 Hz, 8.1Hz, 2.5 Hz, 2H), 1.18 (s, 9H); 13 C NMR (125 MHz, CDCl 3 ) δ , , , , , , , , , , , , , , 96.17, 81.72, 49.25, 39.92, 27.62; HRMS (ESI) m/z calcd for C 21 H 20 Na 4 S [M + Na] + = , found = ; The ee value was 99%, t R (minor) = min, t R (major) = min (Chiralpak IC, λ = 254 nm, 10% i PrH/hexane, flow rate = 1.0 ml/min). Racemic 6l S39

40 Enantioenriched 6l tert Butyl (2R,5'S) 5' cyclohexyl 3 oxo 3H spiro[benzofuran 2,1' cyclopentan] 2' ene 2' carboxylate 6m C 2 tbu Colorless oil; [α] 25 D = 32.1 (c 1, CHCl 3 ); 1 H NMR (500 MHz, CDCl 3 ) δ 7.70 (dd, J = 7.8 Hz, 1.2 Hz, 1H), 7.60 (ddd, J = 8.6 Hz, 7.3 Hz, 1.4 Hz, 1H), (m, 1H), (m, 2H), 2.72 (ddd, J = 17.8 Hz, 7.0 Hz, 3.0 Hz, 1H), (m, 1H), 2.54 (ddd, J = 17.8 Hz, 7.9 Hz, 2.1 Hz, 1H), 1.77 (d, J = 12.8 Hz, 1H), (m, 1H), (m, 2H), (m, 1H), (m, 1H), 1.12 (s, 9H), (m, 4H), (m, 1H); 13 C NMR (125 MHz, CDCl 3 ) δ , , , , , , , , , , 97.30, 81.39, 54.29, 37.18, 35.39, 32.48, 31.29, 27.59, 26.14, 26.11, 25.79; HRMS (ESI) m/z calcd for C 23 H 28 Na 4 [M + Na] + = , found = ; The ee value was 98%, t R (minor) = min, t R (major) = min (Chiralpak IC, λ = 254 nm, 3% i PrH/hexane, flow rate = 1.0 ml/min). S40

41 Racemic 6m Enantioenriched 6m tert Butyl (2R,5'S) 5' isopropyl 3 oxo 3H spiro[benzofuran 2,1' cyclopentan] 2' ene 2' carboxylate 6n C 2 tbu A while solid; [α] 25 D = 47.4 (c 1, CHCl 3 ); 1 H NMR (500 MHz, CDCl 3 ) δ 7.70 (dd, J = 7.9, 1.1 Hz, 1H), (m, 1H), (m, 1H), (m, 2H), (m, 1H), (m, 2H), (m, 1H), 1.12 (s, 9H), 0.94 (d, J = 6.7 Hz, 3H), 0.60 (d, J = 6.6 Hz, 3H); 13 C NMR (125 MHz, CDCl 3 ) δ , , , , , , , , , , 97.40, 81.40, 55.52, 35.76, 27.85, 27.58, 22.19, 21.17; HRMS S41

42 (ESI) m/z calcd for C 20 H 24 Na 4 [M + Na] + = , found = ; The ee value was 98%, t R (minor) = min, t R (major) = min (Chiralpak IC, λ = 254 nm, 5% i PrH/hexane, flow rate = 1.0 ml/min). Racemic 6n Enantioenriched 6n tert Butyl (2R,5'R) 5' butyl 3 oxo 3H spiro[benzofuran 2,1' cyclopentan] 2' ene 2' carboxylate 6o C 2 tbu S42

43 Colorless oil; [α] 25 D = (c 0.5, CHCl 3 ); 1 H NMR (500 MHz, CDCl 3 ) δ 7.70 (d, J = 7.6 Hz, 1H), (m, 1H), 7.29 (t, J = 2.4 Hz, 1H), (m, 2H), 2.83 (ddd, J = 18.4 Hz, 7.5 Hz, 3.0 Hz, 1H), 2.73 (dtd, J = 9.8 Hz, 7.5 Hz, 5.1 Hz, 1H), 2.42 (ddd, J = 18.4 Hz, 7.5, 2.0 Hz, 1H), (m, 2H), (m, 3H), 1.15 (s, 9H), (m, 1H), 0.79 (t, J = 7.1 Hz, 3H); 13 C NMR (125 MHz, CDCl 3 ) δ , , , , , , , , , , 97.73, 81.38, 48.48, 37.63, 30.05, 27.88, 27.59, 22.63, 13.86; HRMS (ESI) m/z calcd for C 21 H 26 Na 4 [M + Na] + = , found = ; The ee value was 97%, t R (minor) = min, t R (major) = min (Chiralpak IC, λ = 254 nm, 5% i PrH/hexane, flow rate = 1.0 ml/min). Racemic 6o Enantioenriched 6o S43

44 tert Butyl (2R,5'R) 5' ethyl 3 oxo 3H spiro[benzofuran 2,1' cyclopentan] 2' ene 2' carboxylate 6p C 2 tbu Colorless oil; [α] 25 D = 98.2 (c 1, CHCl 3 ); 1 H NMR (500 MHz, CDCl 3 ) δ (m, 1H), (m, 1H), 7.30 (t, J = 2.4 Hz, 1H), (m, 2H), 2.85 (ddd, J = 18.5 Hz, 7.5 Hz, 3.0 Hz, 1H), (m, 1H), 2.42 (ddd, J = 18.6 Hz, 7.6 Hz, 2.0 Hz, 1H), (m, 1H), (m, 1H), 1.15 (s, 9H), 0.80 (t, J = 7.4 Hz, 3H); 13 C NMR (125 MHz, CDCl 3 ) δ , , , , , , , , , , 97.65, 81.39, 50.21, 37.33, 27.59, 21.43, 12.35; HRMS (ESI) m/z calcd for C 19 H 22 Na 4 [M + Na] + = , found = ; The ee value was 98%, t R (minor) = min, t R (major) = min (Chiralpak IC, λ = 254 nm, 5% i PrH/hexane, flow rate = 1.0 ml/min). Racemic 6p S44

45 Enantioenriched 6p E. Synthesis of product 8 C 2 tbu H 2 C 2 tbu 30% TFA CH Pd/C DCM 6n (98% ee) 7 8 dr > 19:1 90% yield 97 % ee dr > 19:1 94% yield 98 % ee To 6n (65.7 mg, 0.2 mmol) in methanol (2 ml) was added Pd/C (6.6 mg, 10%), and H 2 was introduced to the system. After 12 hour, Pd/C was removed by filtration. The mixture was concentrated, and the residue was purified by flash column chromatography (hexane/ether = 10 : 1) to afford 7 as a colorless oil (59.5 mg, >19:1 dr, 90% yield). 7: [α] 25 D = 50.8 (c 1, CHCl 3 ); 1 H NMR (500 MHz, CDCl 3 ) δ 7.70 (d, J = 7.5 Hz, 1H), (m, 1H), 7.09 (t, J = 7.8 Hz, 2H), 3.38 (dd, J = 10.3 Hz, 8.2 Hz, 1H), (m, 1H), 2.21 (dt, J = 11.9 Hz, 8.0 Hz, 1H), (m, 2H), 1.86 (ddd, J = 18.4 Hz, 11.6 Hz, 7.2 Hz, 1H), 1.61 (dq, J = 13.5, 6.7 Hz, 1H), 0.97 (s, 9H), 0.84 (d, J = 6.7 Hz, 3H), 0.58 (d, J = 6.7 Hz, 3H); 13 C NMR (125 MHz, CDCl 3 ) δ , , , , , , , , 97.90, 81.01, 57.14, 54.79, 28.33, 27.60, 27.39, 23.83, 23.00, 21.31; HRMS (ESI) m/z calcd for C 20 H 26 Na 4 S45

46 [M + Na] + = , found = ; The ee value was 97%, t R (minor) = min, t R (major) = min (Chiralpak IC, λ = 254 nm, 5% i PrH/hexane, flow rate = 1.0 ml/min). Racemic 7 Enantioenriched 7 To a CH 2 Cl 2 (1.5 ml) solution of 7 (59.5 mg, 0.18 mmol) at 0 o C was added trifluoroacetic acid (0.75 ml, 30%) dropwise. The mixture was stirred at room temperature for 2 h, and the solvent was removed. The crude product was then purified by flash column chromatography (hexane/ethyl acetate = 1 : 2) to afford 8 as a colorless oil (46.4 mg, >19:1 dr, 94% yield). S46

47 8: [α] 25 D = 54.2 (c 1, CHCl 3 ); 1 H NMR (500 MHz, CDCl 3 ) δ (m, 1H), (m, 1H), (m, 2H), 3.41 (t, J = 9.0 Hz, 1H), (m, 1H), 2.16 (dt, J = 11.7 Hz, 8.0 Hz, 1H), (m, 2H), (m, 1H), 1.58 (tt, J = 13.5 Hz, 6.7 Hz, 1H), 0.82 (d, J = 6.7 Hz, 3H), 0.54 (d, J = 6.7 Hz, 3H); 13 C NMR (125 MHz, CDCl 3 ) δ , , , , , , , 97.16, 56.83, 53.80, 28.40, 27.58, 24.23, 22.87, 21.30; HRMS (ESI) m/z calcd for C 16 H 18 Na 4 [M + Na] + = , found = ; The ee value was 98%, t R (major) = min, t R (minor) = min (Chiralpak IC, λ = 254 nm, 30% i PrH/hexane, flow rate = 1.0 ml/min). Racemic 8 Enantioenriched 8 S47

48 F. Determination of stereochemistry of product 8 by 2D NMR H a H b Figure S1. CSY spectrum for product 8 S48

49 H a H b Figure S2. NSEY spectrum of product 8 Proton H a and H b were identified using CSY. NSEY showed the two protons had correlations, which suggested they were on the same side of the cyclopentane ring. Therefore, the stereochemistry of the newly installed chiral center in product 8 could be determined as shown in the structure. G. Computational methods Density functional theory (DFT) methods, as implemented in the Gaussian 09 program 3, have been employed to study the phosphine catalyzed [3+2] annulation. Molecular geometries of the complexes were optimized via DFT calculations using the B3LYP 4 /6 31G(d) 5 level of theory. The vibrational frequencies were computed at the same S49

50 level of theory to determine whether the optimized structure was at an energy minimun. Solvent effects were determined within SMD 6 model (toluene) at the M11 7 /6 311+G(d) 8 level of theory using gas phase optimized geometries. H. Proposed Reaction Cycle and DFT studies The plausible mechanism for the phosphine catalyzed [3+2] annulation of aurone with allene is shown in Scheme S1. Based on the previous exploration of phosphine catalyzed [3+2] annulation reactions, we proposed that the reaction is initially undergoes the nucleophilic attack of the phosphine catalyst A on allene 2a to give a zwitterionic species B. The allenoate moiety of intermediate B exists two resonance structures (C or G), in which the negative charge could be attributed to the α or γ position, respectively. The followed nucleophilic addition could take place with either α or γ position with aurone 1 to yield zwitterionic intermediate D or H, respectively. Subsequently, the stepwise [3+2] annulation yields phosphorus ylide E or I. Then the proton transfer affords α annulation product 5 or γ annulation product 6, respectively, and regenerates the active catalyst A. C 2 tbu E PR 3 C 2 tbu F PR 3 R C 2 tbu 5 R 6 R C 2 tbu -annulation pathway PR 3 A C 2 tbu 2a tbu 2 C R R R PR 3 C 2 tbu PR 3 C 2 tbu B 1 1 PR3 PR 3 R C 2 tbu tbu 2 C D C G R J -annulation pathway PR 3 tbu 2 C tbu 2 C R H I R PR 3 PR 3 Scheme S1. Proposed mechanism for the phosphine catalyzed [3+2] annulation of aurones with allenes. S50

51 Figure S3. The B3LYP calculated NPA charge distributions for intermediate 12 int and 25 int. Figure S4. ptimized transition states 14 ts re (indicated as TS 1 in the main article), 18 ts si (TS 2), 27 ts re (TS 3) and 31 ts si (TS 4). The relative free energies are given in kilocalories per mole. S51

52 I. Calculated Gibbs free energy profiles for the phosphine catalyzed [3+2] annulation of aurone 1a and allene 2a. Figure S5. The DFT computed energy surfaces of the catalyst 4e catalyzed [3+2] annulation of aurone 1a and allene 2a. S52

53 G (kcal/mol) H (kcal/mol)) TBDPS Ph P Ph N H H ipr N H tbu F 3 C tbu 2a 0.0 (0.0) 4c 23-ts CF (-9.1) 22-int TBDPS Ph P Ph N H ipr H N H tbu CF 3 F 3 C 22-int 16.3 (1.3) 23-ts 2.4 (-13.4) 24-int nucleophilic attack 1a 6.0 (-8.6) 25-int TBDPS Ph P Ph tbu N H ipr H N H CF 3 F 3 C 27-ts-re 5.1 (-26.0) 26-int 9.4 (-23.8) 27-ts-re TBDPS TBDPS TBDPS TBDPS Ph Ph Ph Ph P Ph P Ph P Ph P Ph N N tbu N tbu H N H H H ipr H ipr H ipr H N H N H ipr H tbu NH N H CF 3 CF 3 CF 3 CF 3 F 3 C F 3 C F 3 C F 3 C 4c 24-int 25-int 26-int TBDPS Ph tbu P Ph N H H CF ipr N 3 H CF 3 31-ts-si TBDPS Ph P Ph tbu N H ipr H N H F 3 C (-45.2) 28-int-re CF 3 28-int-re 5.1 (-28.1) 29-ts-re C 2 tbu Ph 6-re -2.6 (-34.5) 30-int-re TBDPS Ph tbu P Ph N H H ipr N CF 3 H CF 3 32-int-si TBDPS F 3 C 16.3 (-14.6) 31-ts-re 7.5 (-25.0) 31-ts-si C 2 tbu Ph 6-si tbu N H ipr H NH CF 3 Ph P Ph 29-ts-re -7.1 (-39.8) 32-int-re (-45.6) 32-int-si 5-re (49.6) 4c 3.2 (-29.7) 33-ts-si TBDPS Ph P Ph tbu N H H ipr CF 3 N H 33-ts-si 6.7 (-26.5) 33-ts-re CF 3 TBDPS F 3 C tbu N H ipr H NH CF (-38.1) 34-int-si Ph P Ph 30-int-re -6.7 (-37.3) 34-int-re C 2 tbu Ph 5-re TBDPS Ph P Ph tbu N H H ipr CF 3 N H 34-int-si (50.8) 4c (50.8) 4c TBDPS TBDPS TBDPS TBDPS Ph Ph Ph Ph P Ph P Ph P Ph N N N tbu P Ph N tbu H tbu H tbu H H ipr H ipr H ipr H H ipr N H N H N H N H CF 3 CF 3 CF 3 CF 3 F 3 C F 3 C F 3 C F 3 C 31-ts-re 32-int-re 33-ts-re 34-int-re annulation (si-face attack) annulation (re-face attack) annulation (re-face attack) 6-re 6-si CF 3 Figure S6. The DFT computed energy surfaces of the catalyst 4c catalyzed [3+2] annulation of aurone 1a and allene 2a. S53

54 Figure S7. ptimized transition states 14 ts re, 14 ts si, 31 ts re and 31 ts si. The relative free energies are given in kilocalories per mole. S54

55 J. B3LYP and M11 absolute calculation energies, enthalpies, and free energies. Geometry E B3LYP(elec) 1 E M11(toluene) 2 Correction of Correction of IF H (gas phase) G (gas phase) 4e c a a re si re si int ts int int int ts re(ts 1) int re ts re int re ts si int si ts si int si ts si(ts 2) int si ts si int si int ts S55

56 24 int int int ts re(ts 3) int re ts re int re ts re int re ts re int re ts si(ts 4) int si ts si int si The electronic energy calculated by B3LYP in gas phase. 2 The electronic energy calculated by M11 in toluene. 3 The thermal correction to enthalpy calculated by B3LYP in gas phase. 4 The thermal correction to Gibbs free energy calculated by B3LYP in gas phase. 5 The B3LYP calculated imaginary frequencies for the transition states in gas phase. S56

57 K. B3LYP geometries for all the optimized compounds and transition states. 4e P C H H C H C H C H H H C C C C H C H C H H H C C C C H C H C H H H Si C C C C H C H C H H H C C C C H C H C H H H C C H H H C H H H C H H H N H C C H C C H H H C H H H N H C H C C S57

58 C C H C H C H C C F F F F F F c P C H H C H C H C H H H C C C C H C H C H H H C C C C H C H C H H H Si C C C C H C H C H H H C C C C H C H C H H H C C H H H C H H H C H H H N H C C C C H H H C H S58

59 H H N H C H C C C C H C H C H C C F F F F F F H a C C H H C H C C C H H H C H H H C H H H a C C C C C C C C H H H H C H C C C C H C H C H H H re C C C C C C C C H H H H C H C C C C S59

60 H C H C H H H C C H H C C C C H H H C H H H C H H H H si C C C C C C C C H H H H C H C C C C H C H C H H H C C H H C C C C H H H C H H H C H H H H re C C C C C C C C H H H H C H C C S60

61 C C H C H C H H H C C H H C C C C H H H C H H H C H H H H si C C C C C C C C H H H H C H C C C C H C H C H H H C C H H C C C C H H H C H H H C H H H H int P C H H C H C H C H H H C C C C S61

62 H C H C H H H C C C C H C H C H H H Si C C C C H C H C H H H C C C C H C H C H H H C C H H H C H H H C H H H N H C C H C C H H H C H H H N H C C C H H C H C C H C H H H C H H H C H H H C C C S62

63 C H C H C H C C F F F F F F ts P C H H C H C H C H H H C C C C H C H C H H H C C C C H C H C H H H Si C C C C H C H C H H H C C C C H C H C H H H C C H H H C H H H C H H H N H C C H C C H H H C H S63

64 H H N H C C C H H C H C C H C H H H C H H H C H H H C C C C H C H C H C C F F F F F F int P C H H C H C H C H H H C C C C H C H C H H H C C C C H C H C H H H Si C C C C H C H C H H H C C C C H S64

65 C H C H H H C C H H H C H H H C H H H N H C C H C C H H H C H H H N H C C C H H C H C C H C H H H C H H H C H H H C C C C H C H C H C C F F F F F F int P C H H C H C H C H H H C C C C H C H C S65

66 H H H C C C C H C H C H H H Si C C C C H C H C H H H C C C C H C H C H H H C C H H H C H H H C H H H N H C C H C C H H H C H H H N H C C C H H C H C C H C H H H C H H H C H H H C C C C H C H S66

67 C H C C F F F F F F int P C H H C H C H C H H H C C C C H C H C H H H C C C C H C H C H H H Si C C C C H C H C H H H C C C C H C H C H H H C C H H H C H H H C H H H N H C C H C C H H H C H H H N H S67

68 C C C H H C H C C H C H H H C H H H C H H H C C C C H C H C H C C F F F F F F C C C C C C C C H H H H C H C C C C H C H C H H H ts-re P C H H C H C H C H H H C C C C H C H C H H H C C C C H C S68

69 H C H H H Si C C C C H C H C H H H C C C C H C H C H H H C C H H H C H H H C H H H N H C C H C C H H H C H H H N H C C C H H C H C C H C H H H C H H H C H H H C C C C H C H C H C C F F F F F S69

70 F C C C C C C C C H H H H C H C C C C H C H C H H H ts-si P C H H C H C H C H H H C C C C H C H C H H H C C C C H C H C H H H Si C C C C H C H C H H H C C C C H C H C H H H C C H H H C H H H C H H S70

71 H N H C C H C C H H H C H H H N H C C C H H C H C C H C H H H C H H H C H H H C C C C H C H C H C C F F F F F F C C C C C C C C H H H H C H C C C C H C H C H H H int-re P C H H C H C H C H H S71

72 H C C C C H C H C H H H C C C C H C H C H H H Si C C C C H C H C H H H C C C C H C H C H H H C C H H H C H H H C H H H N H C C H C C H H H C H H H N H C C C H H C H C C H C H H H C H H H C H S72

73 H H C C C C H C H C H C C F F F F F F C C C C C C C C H H H H C H C C C C H C H C H H H int-si P C H H C H C H C H H H C C C C H C H C H H H C C C C H C H C H H H Si C C C C H C H C H H H C C C C H S73

74 C H C H H H C C H H H C H H H C H H H N H C C H C C H H H C H H H N H C C C H H C H C C H C H H H C H H H C H H H C C C C H C H C H C C F F F F F F C C C C C C C C H H H H C H C C C C H C S74

75 H C H H H ts-re P C H H C H C H C H H H C C C C H C H C H H H C C C C H C H C H H H Si C C C C H C H C H H H C C C C H C H C H H H C C H H H C H H H C H H H N H C C H C C H H H C H H H N H C C C H S75

76 H C H C C H C H H H C H H H C H H H C C C C H C H C H C C F F F F F F C C C C C C C C H H H H C H C C C C H C H C H H H ts-si P C H H C H C H C H H H C C C C H C H C H H H C C C C H C H C H H H S76

77 Si C C C C H C H C H H H C C C C H C H C H H H C C H H H C H H H C H H H N H C C H C C H H H C H H H N H C C C H H C H C C H C H H H C H H H C H H H C C C C H C H C H C C F F F F F F C C C C S77

78 C C C C H H H H C H C C C C H C H C H H H int-re P C H H C H C H C H H H C C C C H C H C H H H C C C C H C H C H H H Si C C C C H C H C H H H C C C C H C H C H H H C C H H H C H H H C H H H N H C S78

79 C H C C H H H C H H H N H C C C H H C H C C H C H H H C H H H C H H H C C C C H C H C H C C F F F F F F C C C C C C C C H H H H C H C C C C H C H C H H H int-si P C H H C H C H C H H H C C C C S79

80 H C H C H H H C C C C H C H C H H H Si C C C C H C H C H H H C C C C H C H C H H H C C H H H C H H H C H H H N H C C H C C H H H C H H H N H C C C H H C H C C H C H H H C H H H C H H H C C C S80

81 C H C H C H C C F F F F F F C C C C C C C C H H H H C H C C C C H C H C H H H ts-si P C H H C H C H C H H H C C C C H C H C H H H C C C C H C H C H H H Si C C C C H C H C H H H C C C C H C H C H H S81

82 H C C H H H C H H H C H H H N H C C H C C H H H C H H H N H C C C H H C H C C H C H H H C H H H C H H H C C C C H C H C H C C F F F F F F C C C C C C C C H H H H C H C C C C H C H C H H H S82

83 19-int-si P C H H C H C H C H H H C C C C H C H C H H H C C C C H C H C H H H Si C C C C H C H C H H H C C C C H C H C H H H C C H H H C H H H C H H H N H C C H C C H H H C H H H N H C C C H H C H C S83

84 C H C H H H C H H H C H H H C C C C H C H C H C C F F F F F F C C C C C C C C H H H H C H C C C C H C H C H H H ts-si P C H H C H C H C H H H C C C C H C H C H H H C C C C H C H C H H H Si C C C S84

85 C H C H C H H H C C C C H C H C H H H C C H H H C H H H C H H H N H C C H C C H H H C H H H N H C C C H H C H C C H C H H H C H H H C H H H C C C C H C H C H C C F F F F F F C C C C C C C C H S85

86 H H H C H C C C C H C H C H H H int-si P C H H C H C H C H H H C C C C H C H C H H H C C C C H C H C H H H Si C C C C H C H C H H H C C C C H C H C H H H C C H H H C H H H C H H H N H C C H C C H S86

87 H H C H H H N H C C C H H C H C C H C H H H C H H H C H H H C C C C H C H C H C C F F F F F F C C C C C C C C H H H H C H C C C C H C H C H H H int P C H H C H C H C H H H C C C C H C H C H S87

88 H H C C C C H C H C H H H Si C C C C H C H C H H H C C C C H C H C H H H C C H H H C H H H C H H H N H C C H C C H H H C H H H N H C C C H H C H C C H C H H H C H H H C H H H C C C C H C H C S88

89 H C C F F F F F F ts P C H H C H C H C H H H C C C C H C H C H H H C C C C H C H C H H H Si C C C C H C H C H H H C C C C H C H C H H H C C H H H C H H H C H H H N H C C H C C H H H C H H H N H C S89

90 C C H H C H C C H C H H H C H H H C H H H C C C C H C H C H C C F F F F F F int P C H H C H C H C H H H C C C C H C H C H H H C C C C H C H C H H H Si C C C C H C H C H H H C C C C H C H C H H S90

91 H C C H H H C H H H C H H H N H C C H C C H H H C H H H N H C C C H H C H C C H C H H H C H H H C H H H C C C C H C H C H C C F F F F F F int P C H H C H C H C H H H C C C C H C H C H H H C C S91

92 C C H C H C H H H Si C C C C H C H C H H H C C C C H C H C H H H C C H H H C H H H C H H H N H C C H C C H H H C H H H N H C C C H H C H C C H C H H H C H H H C H H H C C C C H C H C H C C F S92

93 F F F F F int P C H H C H C H C H H H C C C C H C H C H H H C C C C H C H C H H H Si C C C C H C H C H H H C C C C H C H C H H H C C H H H C H H H C H H H N H C C H C C H H H C H H H N H C C C H S93

94 H C H C C H C H H H C H H H C H H H C C C C H C H C H C C F F F F F F C C C C C C C C H H H H C H C C C C H C H C H H H ts-re P C H H C H C H C H H H C C C C H C H C H H H C C C C H C H C H H H S94

95 Si C C C C H C H C H H H C C C C H C H C H H H C C H H H C H H H C H H H N H C C H C C H H H C H H H N H C C C H H C H C C H C H H H C H H H C H H H C C C C H C H C H C C F F F F F F C C C C S95

96 C C C C H H H H C H C C C C H C H C H H H int-re P C H H C H C H C H H H C C C C H C H C H H H C C C C H C H C H H H Si C C C C H C H C H H H C C C C H C H C H H H C C H H H C H H H C H H H N H C S96

97 C H C C H H H C H H H N H C C C H H C H C C H C H H H C H H H C H H H C C C C H C H C H C C F F F F F F C C C C C C C C H H H H C H C C C C H C H C H H H ts-re P C H H C H C H C H H H C C C C S97

98 H C H C H H H C C C C H C H C H H H Si C C C C H C H C H H H C C C C H C H C H H H C C H H H C H H H C H H H N H C C H C C H H H C H H H N H C C C H H C H C C H C H H H C H H H C H H H C C C S98

99 C H C H C H C C F F F F F F C C C C C C C C H H H H C H C C C C H C H C H H H int-re P C H H C H C H C H H H C C C C H C H C H H H C C C C H C H C H H H Si C C C C H C H C H H H C C C C H C H C H H S99

100 H C C H H H C H H H C H H H N H C C H C C H H H C H H H N H C C C H H C H C C H C H H H C H H H C H H H C C C C H C H C H C C F F F F F F C C C C C C C C H H H H C H C C C C H C H C H H H S100

101 31-ts-re P C H H C H C H C H H H C C C C H C H C H H H C C C C H C H C H H H Si C C C C H C H C H H H C C C C H C H C H H H C C H H H C H H H C H H H N H C C H C C H H H C H H H N H C C C H H C H C S101

102 C H C H H H C H H H C H H H C C C C H C H C H C C F F F F F F C C C C C C C C H H H H C H C C C C H C H C H H H ts-si P C H H C H C H C H H H C C C C H C H C H H H C C C C H C H C H H H Si C C C S102

103 C H C H C H H H C C C C H C H C H H H C C H H H C H H H C H H H N H C C H C C H H H C H H H N H C C C H H C H C C H C H H H C H H H C H H H C C C C H C H C H C C F F F F F F C C C C C C C C H S103

104 H H H C H C C C C H C H C H H H int-re P C H H C H C H C H H H C C C C H C H C H H H C C C C H C H C H H H Si C C C C H C H C H H H C C C C H C H C H H H C C H H H C H H H C H H H N H C C H C C H S104

105 H H C H H H N H C C C H H C H C C H C H H H C H H H C H H H C C C C H C H C H C C F F F F F F C C C C C C C C H H H H C H C C C C H C H C H H H int-si P C H H C H C H C H H H C C C C H C H C H S105

106 H H C C C C H C H C H H H Si C C C C H C H C H H H C C C C H C H C H H H C C H H H C H H H C H H H N H C C H C C H H H C H H H N H C C C H H C H C C H C H H H C H H H C H H H C C C C H C H C S106

107 H C C F F F F F F C C C C C C C C H H H H C H C C C C H C H C H H H ts-re P C H H C H C H C H H H C C C C H C H C H H H C C C C H C H C H H H Si C C C C H C H C H H H C C C C H C H C H H H C C H H S107

108 H C H H H C H H H N H C C H C C H H H C H H H N H C C C H H C H C C H C H H H C H H H C H H H C C C C H C H C H C C F F F F F F C C C C C C C C H H H H C H C C C C H C H C H H H ts-si P C H S108

109 H C H C H C H H H C C C C H C H C H H H C C C C H C H C H H H Si C C C C H C H C H H H C C C C H C H C H H H C C H H H C H H H C H H H N H C C H C C H H H C H H H N H C C C H H C H C C H C H S109

110 H H C H H H C H H H C C C C H C H C H C C F F F F F F C C C C C C C C H H H H C H C C C C H C H C H H H int-re P C H H C H C H C H H H C C C C H C H C H H H C C C C H C H C H H H Si C C C C H C H C S110

111 H H H C C C C H C H C H H H C C H H H C H H H C H H H N H C C H C C H H H C H H H N H C C C H H C H C C H C H H H C H H H C H H H C C C C H C H C H C C F F F F F F C C C C C C C C H H H H S111

112 C H C C C C H C H C H H H int-si P C H H C H C H C H H H C C C C H C H C H H H C C C C H C H C H H H Si C C C C H C H C H H H C C C C H C H C H H H C C H H H C H H H C H H H N H C C H C C H H H C H H S112

113 H N H C C C H H C H C C H C H H H C H H H C H H H C C C C H C H C H C C F F F F F F C C C C C C C C H H H H C H C C C C H C H C H H H S113

114 L. References [1] a) X. Han, Y. Wang, F. Zhong, Y. Lu, J. Am. Chem. Soc. 2011, 133, b) X. Han, F. Zhong, Y. Wang, Y. Lu, Angew. Chem. Int. Ed. 2012, 51, 767 c) F. Zhong, X. Han, Y. Wang, Y. Lu, Chem. Sci. 2012, 3, 1231 d) F. Zhong, X. Han, Y. Wang, Y. Lu, Angew. Chem. Int. Ed. 2011, 50, 7837 e) F. Zhong, J. Luo, G. Y. Chen, X. Dou, Y. Lu, J. Am. Chem. Soc. 2012, 134, f) F. Zhong, X. Dou, X. Han, W. Yao, Q. Zhu, Y. Meng, Y. Lu, Angew. Chem. Int. Ed. 2013, 52, 943 g) W. Yao, X. Dou, Y. Lu, J. Am. Chem. Soc. 2015, 137, 54. [2] H. M. Sim, K. Y. Loh, W. K. Yeo, C. Y. Lee, M. L. Go ChemMedChem 2011, 6, 713. [3] M. J. Frisch, G. W. Trucks, H. B. Schlegel, G. E. Scuseria, M. A. Robb, J. R. Cheeseman, G. Scalmani, V. Barone, B. Mennucci, G. A. Petersson, H. Nakatsuji, M. Caricato, X. Li, H. P. Hratchian, A. F. Izmaylov, J. Bloino, G. Zheng, J. L. Sonnenberg, M. Hada, M. Ehara, K. Toyota, R. Fukuda, J. Hasegawa, M. Ishida, T. Nakajima, Y. Honda,. Kitao, H. Nakai, T. Vreven, J. J. A. Montgomery, J. E. Peralta, F. gliaro, M. Bearpark, J. J. Heyd, E. Brothers, K. N. Kudin, V. N. Staroverov, T. Keith, R. Kobayashi, J. Normand, K. Raghavachari, A. Rendell, J. C. Burant, S. S. Iyengar, J. Tomasi, M. Cossi, N. Rega, J. M. Millam, M. Klene, J. E. Knox, J. B. Cross, V. Bakken, C. Adamo, J. Jaramillo, R. Gomperts, R. E. Stratmann,. Yazyev, A. J. Austin, R. Cammi, C. Pomelli, J. W. chterski, R. L. Martin, K. Morokuma, V. G. Zakrzewski, G. A. Voth, P. Salvador, J. J. Dannenberg, S. Dapprich, A. D. Daniels,. Farkas, J. B. Foresman, J. V. rtiz, J. Cioslowski, D. J. Fox, Gaussian 09, revision D.01, Gaussian, Inc.: Wallingford, CT, [4] (a) A. D. Becke, J. Chem. Phys. 1993, 98, (b) C. Lee, W. Yang, R. G. Parr, Phys. Rev. B: Condens. Matter Mater. Phys. 1988, 37, 785. (c) P. J. Stephens, F. J. Devlin, C. F. Chabalowski, M. J. Frisch, J. Phys. Chem. 1994, 98, S114

115 [5] (a) W. J. Hehre, R. Ditchfield, J. A. Pople, J. Chem. Phys. 1972, 56, (b) J. D. Dill, J. A. Pople, J. Chem. Phys. 1975, 62, (c) M. M. Francl, W. J. Pietro, W. J. Hehre, J. S. Binkley, M. S. Gordon, D. J. DeFrees, J. A. Pople, J. Chem. Phys. 1982, 77, 3654 [6] A. V. Marenich, C. J. Cramer, D. G. Truhlar, J. Phys. Chem. B 2009, 113, [7] R. Peverati, D. G. Truhlar. J. Phys. Chem. Lett. 2011, 2, [8] (a) R. Krishnan, J. S. Binkley, R. Seeger, J. A. Pople, J. Chem. Phys. 1980, 72, 650. (b) A. D. McLean, G. S. Chandler, J. Chem. Phys. 1980, 72, S115

116 M. NMR Spectra of the Products S116

117 f1 (ppm) S117

118 S118

119 Cl 5d C 2 tbu Cl 5d C 2 tbu f1 (ppm) S119

120 f1 (ppm) S120

121 f1 (ppm) S121

122 f1 (ppm) S122

123 f1 (ppm) S123

124 S124

125 S125

126 Me Me C 2 tbu 5k Me Me C 2 tbu 5k S126

127 S127

128 S128

129 C 2 tbu 5n C 2 tbu 5n S129

130 S130

131 S131

132 S132

133 S133

134 S134

135 S135