Supporting Information

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1 Supporting Information Enantioselective Synthesis of 3-Alkynyl-3-Hydroxyindolin-2-ones by Copper-Catalyzed Asymmetric Addition of Terminal Alkynes to Isatins Ning Xu, Da-Wei Gu, Jing Zi, Xin-Yan Wu, and Xun-Xiang Guo* 1

2 Table of Contents 1. General Information Experimental Details and Analytical Data.3 3. Transformation of Product 3aa into Transformation of Product 3aa into X-ray Structure of Product 3qa References and Notes H and 13 C NMR Spectra HPLC Spectra

3 1. General Information. Toluene was distilled over benzophenone ketyl under N 2. MTBE was distilled over CaSO 4 under N 2. Other solvents were purified by usual methods before used. All commercial reagents were used without further purification. NMR spectra were recorded on a 400 spectrometer (400 MHz for 1 H, 100 MHz for 13 C) with deuterated chloroform (CDCl 3 ) as a solvent at 298K. Chemical shifts are reported in δ ppm referenced to an internal SiMe 4 standard for 1 H NMR, chloroform-d (δ 77.16) for 13 C NMR: the following abbreviations are used; s: singlet, d: doublet, t: triplet, q: quartet, m: multiplet. HRMS were obtained on an ESI-TOF mass spectrometer. Falsh column chromatography was performed on silica gel ( mesh). 2. Experimental Details and Analytical Data 2.1 General Procedure for the Synthesis of Substituted Isatins. [1] O NaH, RBr O N DMF, o C H CF 3 CF 3 O N R O To a mixture of 7-CF 3 substituted isatin (1.08 g, 5.0 mmol) and DMF (5.0 ml), NaH (132 mg, 5.5 mmol) was added slowly under N 2 atmosphere and the mixture was stirred at room temperature for 0.5 h. Then the mixture was cooled to 0 o C, and 4-nitrile benzyl bromide (1.08 g, 5.5 mmol) was added dropwise. The mixture was stirred at 0 C until the reaction completed by TLC. The mixture was heated to room temperature and 0.2 M HCl (10 ml) was added, extracted with ethyl acetate, and dried over MgSO 4. After evaporation of the solvent, the residue was purified by recrystallization with EtOH to give the product 1g. 3

4 N O O Compound 1g (72% yield): White solid, mp: o C; 1 H NMR (400 MHz, CDCl 3 ): δ (m, 2H), 7.62 (d, J = 8.4 Hz, 2H), CF 3 1g CN (m, 3H), 5.26 (s, 2H). 13 C NMR (100 MHz, CDCl 3 ): δ 46.2 (q, J = 5.1 Hz), 111.7, (q, J = 32.3 Hz), 118.6, 120.3, (q, J = Hz), 124.3, 126.7, 129.4, 132.6, (q, J = 6.0 Hz), 140.7, , , 159.3, HRMS (ESI) calcd for C 17 H 10 N 2 O 2 F 3 (M + H) +, , found O N CF 3 1h O Compound 1h (58% yield): White solid, mp: o C; 1 H NMR (400 MHz, CDCl 3 ): δ (m, 3H), 7.84 (d, J = 8.1 Hz, 1H), 7.75 (d, J = 8.2 Hz, 1H), (m, 2H), (m, 2H), 7.02 (d, J = 7.2 Hz, 1H), 5.69 (s, 2H). 13 C NMR (100 MHz, CDCl 3 ): δ 44.3 (q, J = 5.2 Hz), (q, J = 32.3 Hz), 120.3, 120.9, 122.1, (q, J = Hz), 123.9, 125.3, 126.2, 126.6, 128.0, 129.1, 129.2, (d, J = 0.9 Hz), 130.4, 133.9, (q, J = 5.7 Hz), (d, J = 1.4 Hz), 159.2, HRMS (ESI) calcd for C 20 H 13 NO 2 F 3 (M + H) +, , found O N CF Et 3 1j O Compound 1j (65% yield): White solid, mp: o C; 1 H NMR (400 MHz, CDCl 3 ): δ 7.90 (d, J = 8.1 Hz, 1H), 7.82 (d, J = 7.3 Hz, 1H), 7.25 (t, J = 7.7 Hz, 1H), 4.01 (q, J = 7.1 Hz, 2H), 1.30 (t, J = 7.0 Hz, 3H). 13 C NMR (100 MHz, CDCl 3 ): δ 13.0 (d, J = 2.8 Hz), 38.1 (q, J = 5.0 Hz), (q, J = 33.3 Hz), 120.2, (q, J = Hz), 123.4, 128.9, (q, J = 6.1 Hz), (d, J = 1.4 Hz), 159.0, HRMS (ESI) calcd for C 11 H 9 NO 2 F 3 (M + H) +, , found O N CF Bu 3 1k O Compound 1k (61% yield): White solid, mp: o C; 1 H NMR (400 MHz, CDCl 3 ): δ 7.88 (d, J = 8.1 Hz, 1H), 7.81 (d, J = 7.3 Hz, 1H), 7.22 (t, J = 7.7 Hz, 1H), (m, 2H), 1.64 (dd, J = 15.7, 8.0 Hz, 2H), 1.40 (dd, J = 15.0, 7.5 4

5 Hz, 2H), 0.96 (t, J = 7.4 Hz, 3H). 13 C NMR (100 MHz, CDCl 3 ): δ 13.7, 20.1, 29.9, 43.0 (q, J = 4.6 Hz), (q, J = 33.3 Hz), 120.3, (q, J = Hz), 123.4, 128.9, (q, J = 6.2 Hz), (d, J = 1.3 Hz), 159.2, HRMS (ESI) calcd for C 13 H 13 NO 2 F 3 (M + H) +, , found O Compound 1l (74% yield): White solid, mp: o C; 1 H NMR (400 F 3 C N Bn O MHz, CDCl 3 ): δ 7.73 (d, J = 7.7 Hz, 1H), (m, 6H), 7.01 (s, 1H), 1l 4.97 (s, 2H). 13 C NMR (100 MHz, CDCl 3 ): δ 44.5, (q, J = 3.8 Hz), 110.9, (q, J = 3.7 Hz), (q, J = Hz), 125.9, 127.7, 128.7, 129.4, 133.9, (q, J = 32.3 Hz), 151.0, 157.6, HRMS (ESI) calcd for C 16 H 11 NO 2 F 3 (M + H) +, , found General Procedure for Cu-Catalyzed Asymmetric Addition of Terminal Alkynes to Isatins. To a mixture of CuI (1.9 mg, 0.01 mmol) and L6 [2] (7.1 mg, mmol), MTBE (0.5 ml) was added under N 2 atmosphere and the mixture was stirred at room temperature for 30 mins. Then isatin 1a (61.0 mg, 0.20 mmol), phenylacetylene (21.4 mg, 0.21 mmol), Et 3 N (40.5 mg, 0.4 mmol), and MTBE (0.5 ml) were added to the mixture. The mixture was stirred at 40 C for 72 h. After completion, the mixture was cooled to room temperature and was passed through a short column of Celite with ethyl acetate as an eluent. After evaporation of the solvent, the residue was subjected to a column chromatography on silica gel with DCM as an eluent to give the product 3aa. 5

6 HO Ph Compound 3aa (94% yield, 92% ee (S)): White solid, mp: o C; The ee CF 3 N Bn O was measured by HPLC (Chiralcel AD-H column, λ = 254 nm, eluent: n-hexane/i-proh = 90/10, flow rate: 0.9 ml/min, t 1 = min (R), t 2 = 3aa min (S)); [α] D (c 0.55, CH 2 Cl 2 ); 1 H NMR (400 MHz, CDCl 3 ): δ 7.85 (d, J = 6.6 Hz, 1H), 7.60 (d, J = 7.4 Hz, 1H), (m, 2H), (m, 9H), 5.22 (s, 2H), 4.40 (brs, 1H). 13 C NMR (100 MHz, CDCl 3 ): δ 45.8 (q, J = 5.2 Hz), 68.0, 85.0, 87.3, (q, J = 33.3 Hz), 121.3, (q, J = Hz), 125.6, 127.1, 128.4, (q, J = 6.1 Hz), 128.6, 128.9, 129.3, 131.9, 132.2, 135.6, , , HRMS (ESI) calcd for C 24 H 17 NO 2 F 3 (M + H) +, , found HO N CF 3 3ba O Ph Me Compound 3ba (90% yield, 91% ee (S)): White solid, mp: o C; The ee was measured by HPLC (Chiralcel AD-H column, λ = 254 nm, eluent: n-hexane/i-proh = 90/10, flow rate: 0.9 ml/min, t 1 = min (R), t 2 = min (S)); [α] D (c 0.59, CH 2 Cl 2 ); 1 H NMR (400 MHz, CDCl 3 ): δ 7.84 (d, J = 7.3 Hz, 1H), 7.61 (d, J = 7.7 Hz, 1H), (m, 2H), (m, 4H), (m, 4H), 5.17 (s, 2H), 4.40 (brs, 1H), 2.27 (s, 3H). 13 C NMR (100 MHz, CDCl 3 ): δ 21.1, 45.6 (q, J = 5.0 Hz), 67.9, 85.0, 87.2, (q, J = 33.3 Hz), 121.4, (q, J = Hz), 123.5, 125.6, 128.4, (q, J = 6.1 Hz), 128.9, 129.3, 129.4, 131.9, 132.2, 132.6, 136.7, 140.5, HRMS (ESI) calcd for C 25 H 19 NO 2 F 3 (M + H) +, , found HO N CF 3 O Ph t Bu Compound 3ca (92% yield, 92% ee (S)): White solid, mp: o C; The ee was measured by HPLC (Chiralcel AD-H column, λ = 254 nm, eluent: n-hexane/i-proh = 90/10, flow rate: 0.9 ml/min, t 1 = ca min (R), t 2 = min (S)); [α] D (c 0.57, CH 2 Cl 2 ); 1 H NMR 6

7 (400 MHz, CDCl 3 ): δ 7.85 (d, J = 7.4 Hz, 1H), 7.62 (d, J = 8.0 Hz, 1H), (m, 2H), (m, 6H), 7.08 (d, J = 8.3 Hz, 2H), 5.19 (s, 2H), 3.98 (brs, 1H), 1.26 (s, 9H). 13 C NMR (100 MHz, CDCl 3 ): δ 31.4, 34.5, 45.6 (q, J = 5.1 Hz), 67.9, 85.0, 87.2, (q, J = 33.3 Hz), 121.4, 123.5, (q, J = Hz), 125.4, 125.5, 128.4, (q, J = 6.1 Hz), 128.9, 129.4, 131.3, 131.8, 132.2, , , 140.7, 150.0, HRMS (ESI) calcd for C 28 H 25 NO 2 F 3 (M + H) +, , found HO N CF 3 3da O Ph F Compound 3da (97% yield, 92% ee (S)): White solid, mp: o C; The ee was measured by HPLC (Chiralcel AD-H column, λ = 254 nm, eluent: n-hexane/i-proh = 90/10, flow rate: 0.9 ml/min, t 1 = min (R), t 2 = min (S)); [α] D (c 0.61, CH 2 Cl 2 ); 1 H NMR (400 MHz, CDCl 3 ): δ 7.86 (d, J = 7.3 Hz, 1H), 7.63 (d, J = 8.0 Hz, 1H), (m, 2H), (m, 4H), 7.12 (dd, J = 8.5, 5.2 Hz, 2H), (m, 2H), 5.17 (d, J = 2.2 Hz, 2H), 4.19 (brs, 1H). 13 C NMR (100 MHz, CDCl 3 ): δ 45.3 (q, J = 5.1 Hz), 67.9, 84.8, 87.4, (q, J = 33.3 Hz), (d, J = 22.2 Hz), 121.2, (q, J = Hz), 123.8, (d, J = 8.0 Hz), 128.5, (q, J = 6.1 Hz), 129.0, 129.5, 131.4, 131.8, 132.2, 140.2, 140.3, (d, J = Hz), HRMS (ESI) calcd for C 24 H 16 NO 2 F 4 (M + H) +, , found HO N CF 3 3ea O Ph Cl Compound 3ea (96% yield, 92% ee (S)): White solid, mp: o C; The ee was measured by HPLC (Chiralcel AD-H column, λ = 254 nm, eluent: n-hexane/i-proh = 90/10, flow rate: 0.9 ml/min, t 1 = min (R), t 2 = min (S)); [α] D (c 0.45, CH 2 Cl 2 ); 1 H NMR (400 MHz, CDCl 3 ): δ 7.87 (d, J = 7.3 Hz, 1H), 7.62 (d, J = 8.1 Hz, 1H), 7.40 (d, J = 7.1 Hz, 2H), 7.33 (t, J = 7.3 Hz, 1H), 7.26 (d, J = 6.9 Hz, 3H), 7.19 (d, J = 8.4 Hz, 2H), 7.07 (d, J = 8.3 Hz, 2H), 7

8 5.17 (q, J = 3.7 Hz, 2H), 4.55 (brs, 1H). 13 C NMR (100 MHz, CDCl 3 ): δ 45.3 (q, J = 5.2 Hz), 67.9, 84.7, 87.4, (q, J = 33.3 Hz), 121.2, (q, J = Hz), 123.8, 127.1, 128.5, (q, J = 6.1 Hz), 128.8, 129.0, 129.5, 131.9, 132.2, 133.0, 134.2, 140.1, HRMS (ESI) calcd for C 24 H 16 NO 2 ClF 3 (M + H) +, , found Ph Compound 3fa (88% yield, 90% ee (S)): White solid, mp: o C; HO N CF 3 3fa O Br The ee was measured by HPLC (Chiralcel AD-H column, λ = 254 nm, eluent: n-hexane/i-proh = 90/10, flow rate: 0.9 ml/min, t 1 = min (R), t 2 = min (S)); [α] D (c 0.38, CH 2 Cl 2 ); 1 H NMR (400 MHz, CDCl 3 ): δ 7.86 (d, J = 7.2 Hz, 1H), 7.64 (d, J = 8.0 Hz, 1H), (m, 8H), 7.02 (d, J = 8.4 Hz, 2H), 5.15 (d, J = 6.2 Hz, 2H), 4.07 (brs, 1H). 13 C NMR (100 MHz, CDCl 3 ): δ 45.4 (q, J = 5.1 Hz), 67.9, 84.7, 87.5, (q, J = 33.3 Hz), 121.1, 121.2, (q, J = Hz), 123.8, 127.5, 128.5, (q, J = 6.1 Hz), 129.1, 129.5, , , 132.2, 134.8, , , HRMS (ESI) calcd for C 24 H 16 NO 2 F 3 Br (M + H) +, , found HO N CF 3 3ga O Ph CN Compound 3ga (92% yield, 90% ee (S)): White solid, mp: o C; The ee was measured by HPLC (Chiralcel AD-H column, λ = 254 nm, eluent: n-hexane/i-proh = 90/10, flow rate: 0.9 ml/min, t 1 = min (R), t 2 = min (S)); [α] D (c 0.58, CH 2 Cl 2 ); 1 H NMR (400 MHz, CDCl 3 ): δ 7.88 (d, J = 7.2 Hz, 1H), 7.64 (d, J = 8.0 Hz, 1H), 7.54 (d, J = 8.3 Hz, 2H), (m, 8H), 5.24 (d, J = 2.3 Hz, 2H), 4.46 (brs, 1H). 13 C NMR (100 MHz, CDCl 3 ): δ 45.6 (q, J = 5.0 Hz), 67.8, 84.5, 87.6, 111.2, (q, J = 33.3 Hz), 118.7, 121.1, (q, J = Hz), 124.0, 126.4, 128.5, (q, J = 6.1 Hz), 129.1, 129.6, 131.8, 132.1, 132.5, 139.7, 141.4, HRMS (ESI) calcd for C 25 H 16 N 2 O 2 F 3 (M + H) +, , found

9 HO Ph Compound 3ha (91% yield, 90% ee (S)): White solid, mp: o C; The N O ee was measured by HPLC (Chiralcel AD-H column, λ = 254 nm, eluent: CF 3 n-hexane/i-proh = 90/10, flow rate: 0.9 ml/min, t 1 = min (R), t 2 = 3ha min (S)); [α] D (c 0.62, CH 2 Cl 2 ); 1 H NMR (400 MHz, CDCl 3 ): δ 7.97 (d, J = 8.3 Hz, 1H), 7.89 (t, J = 8.1 Hz, 2H), 7.71 (d, J = 8.2 Hz, 1H), (m, 3H), (m, 2H), (m, 5H), 7.04 (d, J = 7.2 Hz, 1H), 5.68 (s, 2H), 4.22 (brs, 1H). 13 C NMR (100 MHz, CDCl 3 ): δ 43.8 (q, J = 5.0 Hz), 68.0, 85.0, 87.4, (q, J = 33.3 Hz), 120.8, 121.3, 122.2, (q, J = Hz), 123.7, 125.5, 126.0, 126.4, 127.6, 128.5, (q, J = 6.1 Hz), , , 129.4, 130.5, 130.6, 131.8, 132.2, 133.8, 140.6, HRMS (ESI) calcd for C 28 H 19 NO 2 F 3 (M + H) +, , found HO Ph Compound 3ia (96% yield, 92% ee (S)): White solid, mp: o C; The CF 3 N Me O ee was measured by HPLC (Chiralcel OD-H column, λ = 254 nm, eluent: n-hexane/i-proh = 90/10, flow rate: 0.9 ml/min, t 1 = 7.64 min (S), t 2 = 3ia min (R)); [α] D (c 0.53, CH 2 Cl 2 ); 1 H NMR (400 MHz, CDCl 3 ): δ 7.80 (d, J = 7.2 Hz, 1H), 7.66 (d, J = 8.0 Hz, 1H), (m, 2H), (m, 4H), 4.12 (brs, 1H), 3.44 (q, J = 2.2 Hz, 3H). 13 C NMR (100 MHz, CDCl 3 ): δ 29.5 (q, J = 6.5 Hz), 67.9, 84.9, 87.0, (q, J = 33.3 Hz), 121.4, (q, J = Hz), 123.4, (q, J = 6.1 Hz), , 128.5, 129.3, 131.7, 140.0, 140.1, HRMS (ESI) calcd for C 18 H 13 NO 2 F 3 (M + H) +, , found HO N CF Et 3 3ja O Ph Compound 3ja (98% yield, 93% ee (S)): White solid, mp: o C; The ee was measured by HPLC (Chiralcel OD-H column, λ = 254 nm, eluent: n-hexane/i-proh = 90/10, flow rate: 0.9 ml/min, t 1 = 6.68 min (S), t 2 = 9

10 15.96 min (R)); [α] D (c 0.56, CH 2 Cl 2 ); 1 H NMR (400 MHz, CDCl 3 ): δ 7.81 (d, J = 6.8 Hz, 1H), 7.64 (d, J = 8.1 Hz, 1H), (m, 2H), (m, 4H), 4.61 (brs, 1H), (m, 2H), 1.26 (t, J = 7.0 Hz, 3H). 13 C NMR (100 MHz, CDCl 3 ): δ 12.9 (q, J = 2.0 Hz), 38.1 (q, J = 5.0 Hz), 67.9, 85.0, 86.9, (q, J = 33.3 Hz), 121.5, 123.2, (q, J = Hz), 128.3, (q, J = 6.1 Hz), 128.8, 129.2, 132.2, , , HRMS (ESI) calcd for C 19 H 15 NO 2 F 3 (M + H) +, , found HO N CF Bu 3 3ka O Ph Compound 3ka (97% yield, 93% ee (S)): White solid, mp: o C; The ee was measured by HPLC (Chiralcel OD-H column, λ = 254 nm, eluent: n-hexane/i-proh = 90/10, flow rate: 0.9 ml/min, t 1 = 6.04 min (S), t 2 = min (R)); [α] D (c 0.60, CH 2 Cl 2 ); 1 H NMR (400 MHz, CDCl 3 ): δ 7.80 (d, J = 7.2 Hz, 1H), 7.65 (d, J = 7.6 Hz, 1H), (m, 2H), (m, 4H), 4.40 (brs, 1H), (m, 2H), (m, 2H), (m, 2H), 0.93 (t, J = 7.4 Hz, 3H). 13 C NMR (100 MHz, CDCl 3 ): δ 13.8, 20.1, 29.7 (q, J = 2.1 Hz), 42.9 (q, J = 4.4 Hz), 67.9, 85.1, 86.9, (q, J = 33.3 Hz), 121.5, 123.2, (q, J = Hz), 128.3, (q, J = 6.1 Hz), 128.8, 129.2, 132.1, 132.2, , , HRMS (ESI) calcd for C 21 H 19 NO 2 F 3 (M + H) +, , found HO Ph Compound 3la (91% yield, 89% ee (S)): White solid, mp: o C; F 3 C N Bn O The ee was measured by HPLC (Chiralcel AD-H column, λ = 254 nm, eluent: n-hexane/i-proh = 90/10, flow rate: 0.9 ml/min, t 1 = la min (R), t 2 = min (S)); [α] D (c 0.53, CH 2 Cl 2 ); 1 H NMR (400 MHz, CDCl 3 ): δ 7.72 (d, J = 7.7 Hz, 1H), (m, 11H), 6.93 (s, 1H), 4.94 (q, J = 15.8 Hz, 2H), 4.27 (brs, 1H). 13 C NMR (100 MHz, CDCl 3 ): δ 44.4, 69.4, 84.7, 87.4, (q, J =

11 Hz), (q, J = 4.0 Hz), 121.3, (q, J = Hz), 125.3, 127.3, 128.3, 128.4, 129.2, 129.4, 132.2, (q, J = 33.3 Hz), , 134.4, 142.9, HRMS (ESI) calcd for C 24 H 17 NO 2 F 3 (M + H) +, , found F 3 C HO N Bn O Ph Compound 3ma (90% yield, 93% ee (S)): White solid, mp: o C; The ee was measured by HPLC (Chiralcel OD-H column, λ = 254 nm, eluent: n-hexane/i-proh = 90/10, flow rate: 0.9 ml/min, t 1 = 3ma min (R), t 2 = min (S)); [α] D (c 0.56, CH 2 Cl 2 ); 1 H NMR (400 MHz, CDCl 3 ): δ 7.87 (s, 1H), 7.51 (d, J = 8.2 Hz, 1H), 7.44 (d, J = 6.9 Hz, 2H), (m, 8H), 6.78 (d, J = 8.3 Hz, 1H), 4.94 (d, J = 4.0 Hz, 2H), 4.35 (brs, 1H). 13 C NMR (100 MHz, CDCl 3 ): δ 44.4, 69.4, 84.7, 87.5, 110.0, 121.3, (q, J = 3.7 Hz), (q, J = Hz), (q, J = 33.3 Hz), 127.3, (q, J = 4.0 Hz), 128.2, 128.4, 129.2, 129.4, 129.7, 132.3, 134.5, 145.2, HRMS (ESI) calcd for C 24 H 17 NO 2 F 3 (M + H) +, , found MeO 2 C HO N Bn O Ph Compound 3na (78% yield, 80% ee (S)): White solid, mp: o C; The ee was measured by HPLC (Chiralcel AD-H column, λ = 254 nm, eluent: n-hexane/i-proh = 80/20, flow rate: 3na 0.9 ml/min, t 1 = min (R), t 2 = min (S)); [α] D (c 0.48, CH 2 Cl 2 ); 1 H NMR (400 MHz, CDCl 3 ): δ 8.30 (d, J = 1.4 Hz, 1H), 7.98 (dd, J = 8.3, 1.7 Hz, 1H), 7.45 (d, J = 7.0 Hz, 2H), (m, 8H), 6.76 (d, J = 8.3 Hz, 1H), 4.95 (s, 2H), 4.10 (s, 1H), 3.89 (s, 3H). 13 C NMR (100 MHz, CDCl 3 ): δ 44.4, 52.3, 69.3, 84.9, 87.1, 109.7, 121.4, 125.8, 126.3, 127.2, 128.1, 128.3, 129.1, 129.3, 132.2, 132.9, 134.6, 146.2, 166.5, HRMS (ESI) calcd for C 25 H 20 NO 4 (M + H) +, , found

12 O 2 N HO N Bn O Ph Compound 3oa (93% yield, 84% ee (S)): White solid, mp: o C; The ee was measured by HPLC (Chiralcel AD-H column, λ = 254 nm, eluent: n-hexane/i-proh = 70/30, flow rate: 0.9 ml/min, t 1 = oa min (S), t 2 = min (R)); [α] D (c 0.99, CH 2 Cl 2 ); 1 H NMR (400 MHz, CDCl 3 ): δ 8.50 (d, J = 2.3 Hz, 1H), 8.20 (dd, J = 8.7, 2.3 Hz, 1H), (m, 2H), (m, 8H), 6.80 (d, J = 8.7 Hz, 1H), 4.98 (s, 2H), 4.41 (brs, 1H). 13 C NMR (100 MHz, CDCl 3 ): δ 44.7, 69.1, 84.0, 88.0, 109.9, 121.0, 127.3, 128.4, 128.5, 129.3, 129.6, 130.0, 132.3, 134.0, 134.4, 147.6, HRMS (ESI) calcd for C 23 H 17 N 2 O 4 (M + H) +, , found F HO N Bn O Ph Compound 3pa (87% yield, 82% ee (S)): White solid, mp: o C; The ee was measured by HPLC (Chiralcel OD-H column, λ = 254 nm, eluent: n-hexane/i-proh = 90/10, flow rate: 0.9 ml/min, t 1 = min (S), t 2 = 3pa min (R)); [α] D (c 0.52, CH 2 Cl 2 ); 1 H NMR (400 MHz, CDCl 3 ): δ (m, 2H), 7.37 (dd, J = 7.4, 2.6 Hz, 1H), (m, 8H), 6.92 (td, J = 8.8, 2.6 Hz, 1H), 6.61 (dd, J = 8.6, 4.0 Hz, 1H), 4.90 (s, 2H), 4.64 (brs, 1H). 13 C NMR (100 MHz, CDCl 3 ): δ 44.4, 69.8 (d, J = 1.3 Hz), 85.1, 87.1, (d, J = 7.9 Hz), 113.0, 113.2, 116.7, 116.9, 121.5, 127.3, 128.0, 128.4, (d, J = 19.6 Hz), (d, J = 8.2 Hz), 132.2, 134.8, (d, J = 2.1 Hz), (d, J = Hz), Br HO N Bn O Ph Compound 3qa (78% yield, 86% ee (S)): White solid, mp: o C; The ee was measured by HPLC (Chiralcel OD-H column, λ = 254 nm, eluent: n-hexane/i-proh = 90/10, flow rate: 0.9 ml/min, t 1 = min 3qa (R), t 2 = min (S)); [α] D (c 0.54, CH 2 Cl 2 ); 1 H NMR (400 12

13 MHz, CDCl 3 ): δ 7.73 (d, J = 1.9 Hz, 1H), (m, 2H), (m, 9H), 6.57 (d, J = 8.4 Hz, 1H), 4.90 (s, 2H), 4.24 (brs, 1H). 13 C NMR (100 MHz, CDCl 3 ): δ 44.3, 69.6, 84.9, 87.3, 111.6, 116.6, 121.4, 127.2, 128.1, 128.2, 128.4, 129.1, 129.3, 130.9, 132.3, 133.3, 134.6, 141.2, HO Ph Compound 3ra [3] (16% yield, 85% ee (S)): White solid, mp: o C; N Bn 3ra O The ee was measured by HPLC (Chiralcel AD-H column, λ = 254 nm, eluent: n-hexane/i-proh = 70/30, flow rate: 0.9 ml/min, t 1 = min (R), t 2 = min (S)); [α] D (c 0.49, CH 2 Cl 2 ); 1 H NMR (400 MHz, CDCl 3 ): δ 7.62 (d, J = 7.2 Hz, 1H), 7.43 (d, J = 7.2 Hz, 2H), (m, 9H), 7.10 (d, J = 7.6 Hz, 1H), 6.71 (d, J = 7.8 Hz, 1H), 4.91 (d, J = 2.0 Hz, 2H), 4.17 (brs, 1H). 13 C NMR (100 MHz, CDCl 3 ): δ 44.2, 69.8, 85.6, 86.6, 110.0, 121.7, 123.9, 124.9, 127.3, 127.9, 128.3, 129.0, 129.1, 130.5, 132.2, 135.1, 142.2, MeO HO N Bn O Ph Compound 3sa [3] (33% yield, 87% ee (S)): White solid, mp: o C; The ee was measured by HPLC (Chiralcel AD-H column, λ = 254 nm, eluent: n-hexane/i-proh = 70/30, flow rate: 0.9 ml/min, t 1 = 3sa min (R), t 2 = min (S)); [α] D (c 1.02, CH 2 Cl 2 ); 1 H NMR (400 MHz, CDCl 3 ): δ 7.45 (dd, J = 8.0, 1.4 Hz, 2H), (m, 9H), 6.76 (dd, J = 8.6, 2.6 Hz, 1H), 6.60 (d, J = 8.6 Hz, 1H), 4.90 (s, 2H), 4.14 (brs, 1H), 3.78 (s, 3H). 13 C NMR (100 MHz, CDCl 3 ): δ 44.3, 56.0, 70.1, 85.7, 86.8, 110.7, 111.5, 115.5, 121.8, 127.3, 127.9, 128.4, 129.0, 129.1, 130.1, 132.2, 135.2, 135.5, 156.9, Compound 3ab (99% yield, 93% ee (S)): White solid, mp: o C; HO OMe The ee was measured by HPLC (Chiralcel AD-H column, λ = 254 nm, CF 3 N Bn 3ab O eluent: n-hexane/i-proh = 90/10, flow rate: 0.9 ml/min, t 1 =

14 min (R), t 2 = min (S)); [α] D (c 0.62, CH 2 Cl 2 ); 1 H NMR (400 MHz, CDCl 3 ): δ 7.88 (d, J = 7.1 Hz, 1H), 7.61 (d, J = 8.0 Hz, 1H), 7.37 (dd, J = 7.6, 1.6 Hz, 1H), (m, 7H), (m, 2H), 5.22 (s, 2H), 4.29 (brs, 1H), 3.84 (s, 3H). 13 C NMR (100 MHz, CDCl 3 ): δ 45.7 (q, J = 5.2 Hz), 56.0, 68.0, 84.0, 88.9, 110.6, 110.9, (q, J = 32.3 Hz), 120.6, (q, J = Hz) 123.5, 125.6, 127.1, (q, J = 6.1 Hz), 128.6, 129.1, 131.0, 131.9, 134.0, , , 140.5, 160.7, HRMS (ESI) calcd for C 25 H 19 NO 3 F 3 (M + H) +, , found Compound 3ac (82% yield, 85% ee (S)): White solid, mp: o C; HO Me The ee was measured by HPLC (Chiralcel AD-H column, λ = 254 nm, CF 3 N Bn O eluent: n-hexane/i-proh = 90/10, flow rate: 0.9 ml/min, t 1 = min (R), t 2 = min (S)); [α] D (c 0.54, CH 2 Cl 2 ); 1 H NMR (400 3ac MHz, CDCl 3 ): δ 7.86 (d, J = 7.3 Hz, 1H), 7.63 (d, J = 7.9 Hz, 1H), 7.40 (d, J = 7.5 Hz, 1H), (m, 9H), 5.22 (s, 2H), 3.98 (brs, 1H), 2.37 (s, 3H). 13 C NMR (100 MHz, CDCl 3 ): δ 20.7, 45.8 (q, J = 5.2 Hz), 68.0, 86.3, 88.8, (q, J = 33.3 Hz), 121.1, (q, J = Hz), 123.6, 125.6, 125.7, 127.2, (q, J = 6.1 Hz), 128.6, 128.8, 129.5, 129.7, 131.9, 132.5, 135.7, 140.5, 141.2, HRMS (ESI) calcd for C 25 H 19 NO 2 F 3 (M + H) +, , found HO Me Compound 3ad (95% yield, 94% ee (S)): White solid, mp: o C; The ee was measured by HPLC (Chiralcel AD-H column, λ = CF 3 N Bn O 254 nm, eluent: n-hexane/i-proh = 90/10, flow rate: 0.9 ml/min, t 1 = min (R), t 2 = min (S)); [α] D (c 0.61, 3ad CH 2 Cl 2 ); 1 H NMR (400 MHz, CDCl 3 ): δ 7.85 (d, J = 7.3 Hz, 1H), 14

15 7.59 (d, J = 8.0 Hz, 1H), (m, 10H), 5.21 (s, 2H), 4.56 (brs, 1H), 2.25 (s, 3H). 13 C NMR (100 MHz, CDCl 3 ): δ 21.2, 45.7 (q, J = 5.2 Hz), 67.9, 84.6, 87.4, (q, J = 33.3 Hz), 121.1, (q, J = Hz), 123.6, 125.6, 127.1, 128.3, (q, J = 6.1 Hz), 128.6, 128.9, 129.2, 130.2, 132.0, 132.7, 135.7, 138.1, , , HRMS (ESI) calcd for C 25 H 19 NO 2 F 3 (M + H) +, , found Me Compound 3ae (93% yield, 93% ee (S)): White solid, mp: HO o C; The ee was measured by HPLC (Chiralcel AD-H column, λ = CF 3 N Bn O 254 nm, eluent: n-hexane/i-proh = 90/10, flow rate: 0.9 ml/min, t 1 = min (R), t 2 = min (S)); [α] D (c 0.65, CH 2 Cl 2 ); 3ae 1 H NMR (400 MHz, CDCl 3 ): δ 7.85 (d, J = 7.3 Hz, 1H), 7.59 (dd, J = 8.1 Hz, 1H), 7.30 (d, J = 7.9 Hz, 2H), (m, 4H), 7.14 (d, J = 7.4 Hz, 2H), 7.05 (d, J = 7.9 Hz, 2H), 5.21 (s, 2H), 4.29 (brs, 1H), 2.31 (s, 3H). 13 C NMR (100 MHz, CDCl 3 ): δ 21.6, 45.7 (q, J = 5.2 Hz), 68.0, 84.3, 87.5, (q, J = 33.3 Hz), 118.2, (q, J = Hz), 123.6, 125.6, (q, J = 6.1 Hz), 128.6, 128.9, 129.1, 132.0, 132.1, 135.7, 139.6, , , HRMS (ESI) calcd for C 25 H 19 NO 2 F 3 (M + H) +, , found OMe Compound 3af (78% yield, 89% ee (S)): White solid, mp: HO o C; The ee was measured by HPLC (Chiralcel AD-H column, λ = CF 3 N Bn O 254 nm, eluent: n-hexane/i-proh = 90/10, flow rate: 0.9 ml/min, t 1 = min (R), t 2 = min (S)); [α] D (c 0.55, 3af CH 2 Cl 2 ); 1 H NMR (400 MHz, CDCl 3 ): δ 7.85 (d, J = 7.3 Hz, 1H), 7.59 (d, J = 8.1 Hz, 1H), 7.33 (d, J = 8.6 Hz, 2H), (m, 6H), 6.76 (d, J = 8.6 Hz, 2H), 5.21 (s, 2H), 4.54 (brs, 1H), 3.76 (s, 3H). 13 C NMR (100 MHz, CDCl 3 ): δ 45.7 (q, J = 5.0 Hz), 55.4, 15

16 68.0, 83.8, 87.4, 113.3, (q, J = 33.3 Hz), 114.0, (q, J = Hz), 123.6, 125.6, 127.1, (q, J = 6.1 Hz), 128.6, 128.8, 132.1, 133.8, 135.7, , , 160.4, HRMS (ESI) calcd for C 25 H 19 NO 3 F 3 (M + H) +, , found Et Compound 3ag (96% yield, 92% ee (S)): White solid, mp: o C; HO The ee was measured by HPLC (Chiralcel AD-H column, λ = 254 nm, CF 3 N Bn O eluent: n-hexane/i-proh = 90/10, flow rate: 0.9 ml/min, t 1 = min (R), t 2 = min (S)); [α] D (c 0.59, CH 2 Cl 2 ); 1 H NMR 3ag (400 MHz, CDCl 3 ): δ 7.85 (d, J = 7.1 Hz, 1H), 7.61 (d, J = 7.8 Hz, 1H), 7.35 (d, J = 8.1 Hz, 2H), (m, 4H), 7.14 (d, J = 7.3 Hz, 2H), 7.11 (d, J = 8.2 Hz, 2H), 5.22 (s, 2H), 4.01 (brs, 1H), 2.62 (q, J = 7.6 Hz, 2H), 2.31 (t, J = 7.6 Hz, 3H). 13 C NMR (100 MHz, CDCl 3 ): δ 15.4, 29.0, 45.7 (q, J = 5.2 Hz), 67.9, 84.3, 87.6, (q, J = 33.3 Hz), 118.5, (q, J = Hz), 123.6, 125.6, 127.2, 128.0, (q, J = 6.1 Hz), 128.6, 128.9, 131.9, 132.2, 135.7, , , 146.0, HRMS (ESI) calcd for C 26 H 21 NO 2 F 3 (M + H) +, , found t Bu Compound 3ah (82% yield, 91% ee (S)): White solid, mp: o C; The ee was measured by HPLC (Chiralcel AD-H column, λ = HO CF 3 N Bn O 254 nm, eluent: n-hexane/i-proh = 90/10, flow rate: 0.9 ml/min, t 1 = 6.96 min (R), t 2 = min (S)); [α] D (c 0.61, CH 2 Cl 2 ); 1 H 3ah NMR (400 MHz, CDCl 3 ): δ 7.85 (d, J = 7.1 Hz, 1H), 7.59 (d, J = 8.0 Hz, 1H), 7.35 (d, J = 8.4 Hz, 2H), (m, 8H), 5.22 (s, 2H), 4.59 (brs, 1H), 1.28 (s, 9H). 13 C NMR (100 MHz, CDCl 3 ): δ 31.2, 35.0, 45.7 (q, J = 5.2 Hz), 68.0, 84.4, 87.5, (q, J = 33.3 Hz), 118.3, (q, J = Hz), 123.6, 125.4, 125.6, 127.1, (q, J = 6.1 Hz), 128.6, 128.9, 16

17 132.0, 132.1, 135.7, 140.4, 152.8, HRMS (ESI) calcd for C 28 H 25 NO 2 F 3 (M + H) +, , found F Compound 3ai (81% yield, 88% ee (S)): White solid, mp: o C; HO The ee was measured by HPLC (Chiralcel AD-H column, λ = 254 nm, CF 3 N Bn O eluent: n-hexane/i-proh = 90/10, flow rate: 0.9 ml/min, t 1 = min (R), t 2 = min (S)); [α] D (c 0.55, CH 2 Cl 2 ); 1 H NMR 3ai (400 MHz, CDCl 3 ): δ 7.84 (d, J = 6.6 Hz, 1H), 7.62 (d, J = 8.1 Hz, 1H), (m, 2H), (m, 4H), 7.14 (d, J = 7.1 Hz, 2H), (m, 2H), 5.22 (s, 2H), 4.26 (brs, 1H). 13 C NMR (100 MHz, CDCl 3 ): δ 45.8 (q, J = 5.0 Hz), 67.9, 84.8, 86.2, (q, J = 33.3 Hz), (d, J = 22.2 Hz), (d, J = 3.3 Hz), (q, J = Hz), 123.7, 125.6, 127.2, (q, J = 6.1 Hz), , 128.9, 131.7, (d, J = 8.6 Hz), 135.6, , , (d, J = Hz), HRMS (ESI) calcd for C 24 H 16 NO 2 F 4 (M + H) +, , found Compound 3aj (95% yield, 89% ee (S)): White solid, mp: HO o C; The ee was measured by HPLC (Chiralcel AD-H column, λ = CF 3 N Bn 3aj O 254 nm, eluent: n-hexane/i-proh = 90/10, flow rate: 0.9 ml/min, t 1 = min (R), t 2 = min (S)); [α] D (c 0.52, CH 2 Cl 2 ); 1 H NMR (400 MHz, CDCl 3 ): δ (m, 1H), 7.95 (d, J = 7.3 Hz, 1H), 7.83 (dd, J = 9.0, 4.5 Hz, 2H), 7.65 (t, J = 8.1 Hz, 2H), 7.50 (dd, J = 9.2, 5.2 Hz, 2H), 7.37 (t, J = 7.7 Hz, 1H), (m, 6H), 5.25 (d, J = 2.9 Hz, 2H), 4.17 (brs, 1H). 13 C NMR (100 MHz, CDCl 3 ): δ 45.8 (q, J = 5.1 Hz), 68.2, 85.7, 89.7, (q, J = 32.3 Hz), 118.9, (q, J = Hz), 123.7, 125.1, 125.6, 125.9, 126.7, 127.2, 127.4, 128.5, 128.7, (q, J = 6.1 Hz), 17

18 129.0, 130.0, 131.6, 131.8, 133.2, 133.5, 135.7, 140.5, 140.6, HRMS (ESI) calcd for C 28 H 19 NO 2 F 3 (M + H) +, , found HO S Compound 3ak (93% yield, 85% ee (S)): White solid, mp: o C; The ee was measured by HPLC (Chiralcel AD-H column, λ = 254 nm, eluent: CF 3 N Bn 3ak O n-hexane/i-proh = 90/10, flow rate: 0.9 ml/min, t 1 = min (R), t 2 = min (S)); [α] D (c 0.54, CH 2 Cl 2 ); 1 H NMR (400 MHz, CDCl 3 ): δ 7.84 (d, J = 6.9 Hz, 1H), 7.61 (d, J = 7.7 Hz, 1H), (m, 8H), 6.93 (dd, J = 5.1, 3.7 Hz, 1H), 5.21 (s, 2H), 4.21 (brs, 1H). 13 C NMR (100 MHz, CDCl 3 ): δ 45.8 (q, J = 5.0 Hz), 68.1, 80.8, 88.7, (q, J = 33.3 Hz), 121.1, (q, J = Hz), 123.7, 125.6, 127.2, (q, J = 6.1 Hz), , 128.7, 129.0, , 133.9, 135.6, , , HRMS (ESI) calcd for C 22 H 15 NO 2 F 3 S (M + H) +, , found Compound 3al (96% yield, 91% ee (S)): White solid, mp: o C; The HO ee was measured by HPLC (Chiralcel AD-H column, λ = 254 nm, eluent: CF 3 N Bn O n-hexane/i-proh = 90/10, flow rate: 0.9 ml/min, t 1 = min (R), t 2 = min (S)); [α] D (c 0.58, CH 2 Cl 2 ); 1 H NMR (400 MHz, 3al CDCl 3 ): δ 7.78 (d, J = 6.7 Hz, 1H), 7.59 (d, J = 8.1 Hz, 1H), (m, 4H), 7.12 (d, J = 7.2 Hz, 2H), (m, 1H), 5.20 (s, 2H), 3.81 (brs, 1H), (m, 4H), (m, 4H). 13 C NMR (100 MHz, CDCl 3 ): δ 21.4, 22.2, 25.8, 28.7, 45.6 (q, J = 5.0 Hz), 67.8, 82.4, 89.2, (q, J = 33.3 Hz), 119.4, (q, J = Hz), 123.5, 125.6, 127.1, (q, J = 6.1 Hz), 128.6, 128.8, 132.1, 132.2, 135.7, 137.8, 137.9, 140.3, HRMS (ESI) calcd for C 24 H 21 NO 2 F 3 (M + H) +, , found

19 HO C 4 H 9 Compound 3am (28% yield, 84% ee (S)): White solid, mp: o C; The CF 3 N Bn O ee was measured by HPLC (Chiralcel AD-H column, λ = 254 nm, eluent: n-hexane/i-proh = 70/30, flow rate: 0.9 ml/min, t 1 = 6.07 min (R), t 2 = 3am 6.96 min (S)); [α] D (c 0.42, CH 2 Cl 2 ); 1 H NMR (400 MHz, CDCl 3 ): δ 7.76 (d, J = 7.2 Hz, 1H), 7.59 (d, J = 8.0 Hz, 1H), (m, 4H), 7.11 (d, J = 7.2 Hz, 2H), 5.19 (s, 2H), 3.80 (brs, 1H), 2.23 (t, J = 7.1 Hz, 2H), (m, 2H), (m, 2H), 0.88 (t, J = 7.2 Hz, 3H),. 13 C NMR (100 MHz, CDCl 3 ): δ 13.7, 18.7, 22.0, 30.3, 45.7 (q, J = 5.0 Hz), 67.5, 76.5, 89.1, (q, J = 33.3 Hz), (q, J = Hz), 123.4, 125.6, 127.1, (q, J = 6.1 Hz), 128.6, 128.7, 132.2, 135.8, 140.4, HRMS (ESI) calcd for C 22 H 21 NO 2 F 3 (M + H) +, , found Transformation of product 3aa into 4 [4] To a solution of 10% Pd/C (5.3 mg) in EtOAc (1 ml) under H 2 atmosphere (balloon) at room temperature was added compound 3aa (40.7 mg, 0.1 mmol, 92% ee) and the mixture was stirred at room temperature for 1 h. Then the mixture was passed through a short column of Celite with ethyl acetate as an eluent. After evaporation of the solvent, the residue was subjected to a column chromatography on silica gel with PE/EtOAc (5/1) as an eluent to give the product 4. Compound 4 (97% yield, 90% ee (S)): White solid, mp: o C; The ee was measured by HPLC (Chiralcel AD-H column, λ = 254 nm, eluent: n-hexane/i-proh = 90/10, flow rate: 0.9 ml/min, t 1 = min (R), t 2 = min (S)); [α] D (c 1.12, CHCl 3 ); 1 H NMR (400 MHz, CDCl 3 ): δ 7.62 (d, J = 7.4 Hz, 1H), 7.59 (d, J = 8.2 Hz, 1H), (m, 9H), 7.01 (d, J = 6.9 Hz, 2H), 5.11 (q, J = 17.0 Hz, 2H), 3.58 (brs, 1H), (m, 2H), (m, 2H). 13 C NMR (100 MHz, CDCl 3 ): δ 29.6, 19

20 40.7, 45.7 (q, J = 4.8 Hz), 74.5, (q, J = 33.3 Hz), 123.1, (q, J = Hz), 125.9, 126.3, , (q, J = 6.1 Hz), 128.4, 128.6, 132.9, 136.0, 140.4, 141.0, HRMS (ESI) calcd for C 24 H 21 NO 2 F 3 (M + H) +, , found Transformation of product 3aa into 5 [5] To a solution of 3aa (20.4 mg, 0.05 mmol, 92% ee) in EtOAc (1 ml) under H 2 atmosphere (balloon) at room temperature, quinoline (2.6 μl) and (Lindlar catalyst) Pd/CaCO 3 (2.0 mg) was added compound and the mixture was stirred at room temperature for 24 h. Then the mixture was passed through a short column of Celite with ethyl acetate as an eluent. After evaporation of the solvent, the residue was subjected to a column chromatography on silica gel with PE/EtOAc (5/1) as an eluent to give the product 5. Compound 5 (68% yield, 92% ee (S)): White solid, mp: o C; The ee was measured by HPLC (Chiralcel AD-H column, λ = 254 nm, eluent: n-hexane/i-proh = 90/10, flow rate: 0.9 ml/min, t 1 = min (R), t 2 = min (S)); [α] D (c 0.55, CHCl 3 ); 1 H NMR (400 MHz, CDCl 3 ): δ 7.57 (d, J = 7.3 Hz, 1H), 7.52 (d, J = 8.1 Hz, 1H), (m, 7H), 7.04 (d, J = 7.2 Hz, 2H), (m, 2H), 6.82 (d, J = 12.1 Hz, 1H), 6.00 (d, J = 12.1 Hz, 1H), 4.94 (d, J = 17.2 Hz, 1H), 4.75 (d, J = 17.2 Hz, 1H), 3.32 (brs, 1H). 13 C NMR (100 MHz, CDCl 3 ): δ 45.4 (q, J = 4.8 Hz), 74.7, (q, J = 33.3 Hz), 123.1, (q, J = Hz), 125.7, 127.0, 127.8, (q, J = 6.1 Hz), 128.0, 128.5, 131.0, 133.8, 133.9, 135.9, , , HRMS (ESI) calcd for C 24 H 19 NO 2 F 3 (M + H) +, , found

21 5. X-ray Structure of Product 3qa Table S-1 Crystal data and structure refinement for product 3qa Chemical formula C 23 H 16 BrNO 2 Formula Mass Crystal system monoclinic Space group C 2/c Temperature/K 180(2) Wavelength/Å a/å (8) b/å (5) c/å (8) α/ᵒ 90 β/ᵒ (10) γ/ᵒ 90 Volume/Å (3) Z 8 Calculated density Mg/m Radiation type CuK\a Absorption coefficient/mm F(000) 1696 Crystal size/mm 0.1 x 0.08 x 0.06 Theta range for data collection/ᵒ 4.51 to Reflections collected/unique 18484/3380 Completeness to theta = % Absorption correction None Refinement method Full-matrix least-squares on F 2 Data/restraints/parameters 3380/0/244 Goodness-of-fit on F R int Final R I values (I > 2σ(I)) Final wr(f 2 ) values (I > 2σ(I)) Final R I values (all data) Final wr(f 2 ) values (all data) Largest diff. peak and hole/e.å and

22 6. References and Notes 1. Li, C.; Guo, F.; Xu, K.; Zhang, S.; Hu, Y.; Zha, Z.; Wang, Z. Org. Lett. 2014, 16, Wang, G.; Rexiti, R.; Sha, F.; Wu, X.-Y. Tetrahedron 2015, 71, Chen, Q.; Tang, Y.; Huang, T.; Liu, X.; Lin, L.; Feng, X. Angew. Chem. Int. Ed. 2016, 55, Sanz-Marco, A.; Garcίa-Ortiz, A.; Blay, G.; Fernández, I.; Pedro, J. R. Chem. Eur. J. 2014, 20, Bisai, V.; Suneja, A.; Singh, V. K. Angew. Chem. Int. Ed. 2014, 53,

23 7. 1 H and 13 C NMR Spectra Figure 1. 1 H and 13 C NMR spectra of compound 1g in CDCl 3 23

24 Figure 2. 1 H and 13 C NMR spectra of compound 1h in CDCl 3 24

25 Figure 3. 1 H and 13 C NMR spectra of compound 1j in CDCl 3 25

26 Figure 4. 1 H and 13 C NMR spectra of compound 1k in CDCl 3 26

27 Figure 5. 1 H and 13 C NMR spectra of compound 1l in CDCl 3 27

28 Figure 6. 1 H and 13 C NMR spectra of compound 3aa in CDCl 3 28

29 Figure 7. 1 H and 13 C NMR spectra of compound 3ba in CDCl 3 29

30 Figure 8. 1 H and 13 C NMR spectra of compound 3ca in CDCl 3 30

31 Figure 9. 1 H and 13 C NMR spectra of compound 3da in CDCl 3 31

32 Figure H and 13 C NMR spectra of compound 3ea in CDCl 3 32

33 Figure H and 13 C NMR spectra of compound 3fa in CDCl 3 33

34 Figure H and 13 C NMR spectra of compound 3ga in CDCl 3 34

35 Figure H and 13 C NMR spectra of compound 3ha in CDCl 3 35

36 Figure H and 13 C NMR spectra of compound 3ia in CDCl 3 36

37 Figure H and 13 C NMR spectra of compound 3ja in CDCl 3 37

38 Figure H and 13 C NMR spectra of compound 3ka in CDCl 3 38

39 Figure H and 13 C NMR spectra of compound 3la in CDCl 3 39

40 Figure H and 13 C NMR spectra of compound 3ma in CDCl 3 40

41 Figure H and 13 C NMR spectra of compound 3na in CDCl 3 41

42 Figure H and 13 C NMR spectra of compound 3oa in CDCl 3 42

43 Figure H and 13 C NMR spectra of compound 3pa in CDCl 3 43

44 Figure H and 13 C NMR spectra of compound 3qa in CDCl 3 44

45 Figure H and 13 C NMR spectra of compound 3ab in CDCl 3 45

46 Figure H and 13 C NMR spectra of compound 3ac in CDCl 3 46

47 Figure H and 13 C NMR spectra of compound 3ad in CDCl 3 47

48 Figure H and 13 C NMR spectra of compound 3ae in CDCl 3 48

49 Figure H and 13 C NMR spectra of compound 3af in CDCl 3 49

50 Figure H and 13 C NMR spectra of compound 3ag in CDCl 3 50

51 Figure H and 13 C NMR spectra of compound 3ah in CDCl 3 51

52 Figure H and 13 C NMR spectra of compound 3ai in CDCl 3 52

53 Figure H and 13 C NMR spectra of compound 3aj in CDCl 3 53

54 Figure H and 13 C NMR spectra of compound 3ak in CDCl 3 54

55 Figure H and 13 C NMR spectra of compound 3al in CDCl 3 55

56 Figure H and 13 C NMR spectra of compound 3am in CDCl 3 56

57 Figure H and 13 C NMR spectra of compound 4 in CDCl 3 57

58 Figure H and 13 C NMR spectra of compound 5 in CDCl 3 58

59 8. HPLC Spectra 1. HPLC of 3aa 59

60 2. HPLC of 3ba 60

61 3. HPLC of 3ca 61

62 4. HPLC of 3da 62

63 5. HPLC of 3ea 63

64 6. HPLC of 3fa 64

65 7. HPLC of 3ga 65

66 8. HPLC of 3ha 66

67 9. HPLC of 3ia 67

68 10. HPLC of 3ja 68

69 11. HPLC of 3ka 69

70 12. HPLC of 3la 70

71 13. HPLC of 3ma 71

72 14. HPLC of 3na 72

73 15. HPLC of 3oa 73

74 16. HPLC of 3pa 74

75 17. HPLC of 3qa 75

76 18. HPLC of 3ra 76

77 19. HPLC of 3sa 77

78 20. HPLC of 3ab 78

79 21. HPLC of 3ac 79

80 22. HPLC of 3ad 80

81 23. HPLC of 3ae 81

82 24. HPLC of 3af 82

83 25. HPLC of 3ag 83

84 26. HPLC of 3ah 84

85 27. HPLC of 3ai 85

86 28. HPLC of 3aj 86

87 29. HPLC of 3ak 87

88 30. HPLC of 3al 88

89 31. HPLC of 3am 89

90 32. HPLC of 4 90

91 33. HPLC of 5 91