Cinchona-Alkaloids based Isoselenazolones: Synthesis and Their Catalytic Application in Asymmetric Bromolactonization of Alkenoic Acid

Transcript

1 Cinchona-Alkaloids based Isoselenazolones: Synthesis and Their Catalytic Application in Asymmetric Bromolactonization of Alkenoic Acid Contents Analytical data for isoselenazolones 1-14 and their substrates, alkenoic acids and bromolactones Screening of various solvents for bromolactonization (Table 1) Racemization described by bromonium ion-alkene intermediate (Scheme 1) S2-S16 S16 S17 1 H, 13 C, 77 Se NMR and mass spectra for isoselenazolones 1-14, monoselenide 15, diselenide 16 and their substrates S18-S111 1 H and 13 C NMR and mass spectra for alkenoic acids S112-S140 1 H and 13 C NMR, mass spectra and HPLC chromatograms for bromolactones Mass spectra for intermediate between isoselenazolone 7 and NBS Crystallographic details for compounds 8 and 20 S141-S176 S177 S178-S184 S1

2 (S)-2-(1-Phenylethyl)benzo[d][1,2]selenazol-3(2H)-one (1): Yield: 0.20 g (96%). 1 H, 13 C NMR chemical shifts and mass analysis are similar to the racemic compound. 1,2 77 Se NMR ppm, [α] 28 D (c = 0.55, MeOH). (R)-2-(1-Phenylethyl)benzo[d][1,2]selenazol-3(2H)-one (2): Yield: 0.24 g (95%). 1 H, 13 C NMR chemical shifts and mass analysis are similar to the racemic compound Se NMR ppm, [α] 28 D (c = 0.55, MeOH). (S)-7-Methoxy-2-(1-(naphthalen-1-yl)ethyl)benzo[d][1,2]selenazol-3(2H)-one (3): Yield 0.17 g (76%). 1 H NMR (400 MHz, CDCl 3 ) 8.10 (m, 1H), 7.90 (m, 2H), 7.74(m, 2H), 7.50 (m, 3H), 7.40 (t, J = 7.9 Hz, 1H), 6.90 (d, J = 8.0 Hz, 1H), 6.60 (q, J = 6.6 Hz, 1H), 3.80 (s, 3H), 1.90 (d, J = 6.6 Hz, 3H) 13 C NMR (100 MHz, CDCl 3 ) 166.4, 154.5, 137.1, 133.8, 131.7, , , 128.7, 127.9, 127.8, 127.2, 126.2, 124.8, 123.5, 123.4, 120.5, 111.4, 56.2, 49.4, Se NMR ppm HRMS-ES + m/z: (Calculated for C 20 H 17 NO 80 2 Se + H + : ). [α] 30 D (c = 0.3, CHCl 3 ). (S)-2-Chloro-N-(1-(naphthalen-1-yl)ethyl)-3-nitrobenzamide (Substrate for 4): Yield 0.9 g (92%), mp C. 1 H NMR (400 MHz, CDCl 3 ) 8.20 (d, J = 8.5 Hz, 1H), 7.90 (d, J =8.1 Hz, 1H), 7.80 (d, J = 8.2 Hz, 1H), 7.75 (dd, J = 8.0, 1.5 Hz, 1H), 7.62 (dd, J = 7.7, 1.5 Hz, 1H), (m, 3H) (t, J = 7.7. Hz, 1H), 7.40 (t, J = 7.9 Hz, 1H), (m, 1H), (m, 1H), 1.80 (d, J = 6.5 Hz, 3H) 13 C NMR (100 MHz, CDCl 3 ) 164.6, 138.6, 137.0, 134.0, 132.2, 131.0, , , , 127.8, 126.8, 126.6, 126.1, 125.2, 123.5, 123.3, 122.8, 45.5, HRMS-ES + m/z (calculated for C 19 H 15 ClN 2 O 3 + H ). [α] 29 D (c = 0.7, CHCl 3 ). (S)-2-(1-(Naphthalen-1-yl)ethyl)-7-nitrobenzo[d][1,2]selenazol-3(2H)-one (4): Yield 0.32 g (72%), mp o C. 1 H NMR (400 MHz, CDCl 3 ) 8.40 (d, J = 7.3 Hz, 2H), 8.00 (d, J = 7.2 Hz, S2

3 1H), 7.90 (d, J = 8.1 Hz, 1H), 7.80 (d, J = 7.0 Hz, 1H), (m, 5H), 6.50 (q, J = 6.5 Hz, 1H), 1.90 (d, J = 6.5 Hz, 3H) 13 C NMR (100 MHz, CDCl 3 ) 164.4, 142.3, 136.7, 136.3, 134.5, 134.0, 131.5, 130.1, , , 127.3, 127.2, , 126.3, 125.0, 123.7, 123.1, 48.9, Se NMR ppm. HRMS-ES + m/z: (Calculated for C 19 H 14 N 2 O 80 3 Se + H + : ). [α] 29 D (c = 0.5, CHCl 3 ). 2-Bromo-N1-((R)-1-(naphthalen-1-yl)ethyl)-N3-((S)-1-(naphthalen-1- yl)ethyl)isophthalamide (Substrate for 5): Yield 0.69 g (88%), mp above 200 o C. 1 H NMR (400 MHz, CDCl 3 ) 9.10 (d, J = 7.9 Hz, 2H), 8.20 (d, J = 8.4 Hz, 2H), 7.90 (d, J = 8.0 Hz, 2H), 7.80 (d, J = 8.1 Hz, 2H), (m, 8H), (m, 1H), 7.30 (d, 2H), 5.90 (quintet, J = 7.2 Hz, 2H) 1.55 (d, J = 6.9 Hz, 6H) 13 C NMR (100 MHz, CDCl 3 ) 166.7, 140.6, 140.2, 133.8, 130.8, 129.1, 127.9, , 126.7, 126.1, , , 123.7, 123.2, 116.6, 45.4, HRMS-ES + m/z: (Calculated for C 32 H 27 BrN 2 O 2 + H + : ). [α] 29 D (c = 0.05, CHCl 3 ). N-((R)-1-(Naphthalen-1-yl)ethyl)-2-((S)-1-(naphthalen-1-yl)ethyl)-3-oxo-2,3- dihydrobenzo[d][1,2]selenazole-7-carboxamide (5): Yield 0.42 g (71%), mp o C. 1 H NMR (400 MHz, CDCl 3 ) (m, 2H), (m, 8H), (m, 2H), (m, 4H), (m, 1H), 7.20 (t, J = 7.6 Hz, 1H), 6.45 (q, J = 6.6 Hz, 1H), 5.95 (quintet, J = 7.0 Hz, 1H) 1.86 (d, J = 6.7 Hz, 3H), 1.73 (d, J = 6.8 Hz, 3H) 13 C NMR (100 MHz, CDCl 3 ) , , 162.5, 142.0, 137.4, 137.3, 133.9, 133.8, 131.6, 130.9, 130.7, 129.3, 128.8, 128.7, 128.5, 127.5, , 126.7, 126.1, , , 125.4, 125.1, , 123.5, 123.4, , , 48.2, 46.0, 36.3, Se NMR ppm HRMS-ES + m/z: (Calculated for C 32 H 26 N 2 O 80 2 Se - H + : ). [α] 30 D (c = 0.5, CHCl 3 ). S3

4 (1S)-(6-Methoxyquinolin-4-yl)((2S,4S,5R)-5-vinylquinuclidin-2-yl)methanamine (Quininamine): 3 Yield 0.74 g (80%). 1 H NMR (400 MHz, CDCl 3 ) 8.64 (d, J = 4.5 Hz, 1H), 7.94 (d, J = 9.2 Hz, 1H), 7.56 (s, 1H), 7.36 (s, 1H), 7.28 (dd, J = 9.2, 2.5 Hz, 1H), 5.70 (quintet, J = 8.8 Hz, 1H), 4.90 (m, 2H), 4.50 (s, 1H) 3.86 (s, 3H), 3.09 (m, 3H), 2.70 (m, 2H), 2.24 (m, 4H), 1.48 (m, 3H), 1.33 (t, J = 11.8 Hz, 1H) 13 C NMR (100 MHz, CDCl 3 ) 157.6, 147.9, 147.1, 144.0, 141.7, 131.7, 128.8, 121.2, 119.9, 114.3, 101.9, 62.3, 56.3, 55.5, 40.9, 39.8, 29.6, 28.1, 27.5, HRMS-ES + m/z: (Calculated for C 20 H 25 N 3 O + H + : ). [α] 27 D (c = 0.5, CHCl 3 ). 2-Iodo-N-((1S)-(6-methoxyquinolin-4-yl)((2S,4S,5R)-5-vinylquinuclidin-2- yl)methyl)benzamide (Substrate for 6 and 7): Yield 0.65 g (92 %), mp o C. 1 H NMR (400 MHz, CDCl 3 ) 8.77 (s, 1H), 8.06 (d, J = 9.2 Hz, 1H), 7.80 (d, J = 7.5 Hz, 1H), 7.76 (s, 1H), 7.50 (s, 1H), 7.42 (d, J = 9.3 Hz, 1H), 7.33 (s, 2H), 7.20 (s, 1H) 7.09 (t, J = 6.1 Hz, 1H), 5.75 (quintet, J = 8.5 Hz, 1H), 5.0 (m, 2H), 4.01 (s, 3H), 3.25 (m, 3H), 2.74 (m, 3H), 2.74 (m, 3H), 2.32 (s, 2H), 1.70 (m, 3H), 1.52 (t, J = 11.0 Hz, 1H) 13 C NMR (100 MHz, CDCl 3 ) 169.0, 157.8, 147.5, 144.9, 141.9, 141.2, 139.9, 135.3, 131.9, , 128.9, 128.4, 128.0, 121.6,115.0, 114.7, 102.2, 92.3, 56.0, 55.8, 45.97, 41.3, 39.3, 29.7, 27.9, 27.4, HRMS-ES + m/z: (Calculated for C 27 H 28 IN 3 O 2 + H + : ). [α] 28 D (c = 0.4, CHCl 3 ). 2-((1S)-(6-Methoxyquinolin-4-yl)((2S,4S,5R)-5-vinylquinuclidin-2- yl)methyl)benzo[d]isothiazol-3(2h)-one (6): Yield 0.16 g (63 %), mp above 225 o C. 1 H NMR (400 MHz, CDCl 3 ) 8.80 (d, J = 4.6 Hz, 1H), 7.98 (s, 1H), (m, 1H), 7.47 (t, J = 7.6 Hz, 1H), (m, 5H), 6.52 (d, J = 11.2 Hz, 1H), 5.96 (q, J = 8.7 Hz,1H), 5.12 (s, 1H), 5.09 (d, J = 5.5 Hz, 1H), 4.0 (s, 3H), 3.78 (q, J = 8.8 Hz, 1H), (m, 1H), (m, 1H), (m, 2H), (m, 1H), (m, 1H), 1.75 (s, 1H), (m, 3H) 13 C S4

5 NMR (100 MHz, CDCl 3 ) 165.1, 158.7, 147.0, 145.0, 141.7, 140.8, 140.6, 131.7, 131.6, 128.8, 126.8, 125.3, 124.6, 122.8, 120.4, 119.1, 114.6, 101.6, 57.2, 56.4, 56.1, 53.0, 41.6, 39.4, 29.7, 28.3, HRMS-ES + m/z: (Calculated for C 27 H 27 N 3 O 2 S + H + : ). [α] 26 D (c = 0.2, CHCl 3 ). 2-((1S)-(6-Methoxyquinolin-4-yl)((2S,4S,5R)-5-vinylquinuclidin-2- yl)methyl)benzo[d][1,2]selenazol-3(2h)-one (7) (By using potassium tert-butoxide): Yield 0.3 g (84%) mp o C. 1 H NMR (400 MHz, CDCl 3 ) 8.80 (d, J = 4.4 Hz, 1H), 8.0 (m, 3H), 7.48 (m, 2H), 7.35 (m, 3H), 6.40 (m, 1H), 5.96 (s, 1H), 5.11 (m, 2H), 4.02 (m, 3H), 3.62 (m, 2H), 3.30 (t, J = 12 Hz, 1H), 2.80 (m, 2H), 2.36 (s, 1H), 1.95 (s, 1H), 1.77 (s, 1H), 1.62 (m, 3H) 13 C NMR (100 MHz, CDCl 3 ) 171.1, 166.9, 158.5, 147.1, 144.9, 142.9, 141.7, 139.1, 131.8, 131.6, 128.8, 127.6, 126.0, 124.0, 122.8, 118.5, , 101.8, 58.6, 56.2, 56.0, 53.8, 41.5, 39.5, 29.7, 27.7, Se NMR ppm. HRMS-ES + m/z: (Calculated for C 27 H 27 N 3 O 80 2 Se + H + : ). [α] 30 D (c = 0.2, CHCl 3 ). (1S)-Quinolin-4-yl((2S,4S,5R)-5-vinylquinuclidin-2-yl)methanamine (Cinchonidinamine): 4 Yield 0.53 g (72%). 1 H NMR (400 MHz, CDCl 3 ) 8.80 (d, J = 4.1 Hz, 1H), 8.27 (s, 1H), 8.05 (d, J = 8.4 Hz, 1H), 7.60 (t, J = 7.1 Hz, 1H), 7.46 (m, 2H), 5.70 (quintet, J = 8.5 Hz, 1H), 4.88 (m, 2H), 4.60 (s, 1H) 3.07 (m, 3H), 2.70 (m, 2H), 2.23 (m, 4H), 1.46 (m, 3H), 1.30 (t, J = 10.7 Hz, 1H) 13 C NMR (100 MHz, CDCl 3 ) 150.3, 148.7, 148.5, 141.7, 130.3, 128.9, 127.8, 126.4, 123.3, 119.6, 114.3, 61.9, 56.2, 53.5, 40.8, 39.7, 28.0, 27.5, HRMS-ES + m/z: (Calculated for C 19 H 23 N 3 + H + : ). [α] 29 D (c = 0.6, CHCl 3 ). 2-Iodo-N-((1S)-quinolin-4-yl((2S,4S,5R)-5-vinylquinuclidin-2-yl)methyl)benzamide (Substrate for 8): Yield 0.60 g (87%), mp o C. 1 H NMR (400 MHz, CDCl 3 ) 8.84 (m, 1H), 8.46 (d, J = 8.5Hz, 1H), 8.11 (m, 1H), 7.60 (m, 5H), 7.23 (m, 2H), 6.95 (m, 1H), 5.64 (m, S5

6 1H), 5.21 (m, 1H), 4.91 (m, 2H), 3.17 (m, 3H), 2.67 (m, 3H), 2.23 (s, 1H), 1.56 (m, 3H), 1.35 (t, J = 10.5Hz, 1H) 13 C NMR (100 MHz, CDCl 3 ) 169.0, 151.0, 150.0, 148.6, 141.7, 141.3, 139.7, 130.9, 130.5, , 129.0, 128.4, 128.0, 126.7, 126.5, , 114.4, 92.7, 55.8, 53.6, 46.1, 41.1, 39.5, 27.8, HRMS-ES + m/z: (Calculated for C 26 H 26 IN 3 O + H + : ). [α] 29 D (c = 0.2, CHCl 3 ). 2-((1S)-Quinolin-4-yl((2S,4S,5R)-5-vinylquinuclidin-2-yl)methyl)benzo[d][1,2]selenazol- 3(2H)-one (8): Yield 0.3 g (67%), mp o C. 1 H NMR (400 MHz, CDCl 3 ) 8.89 (d, J = 4.5Hz, 1H), 8.61 (bs, 1H), 8.10 (d, J = 8.5Hz, 1H), (m, 1H), (m, 1H), (m, 1H), (m, 1H), (m, 1H), (m, 1H), (m, 1H), 6.36 (bs, 1H), (m, 1H), (m, 2H), (m, 2H), 3.24 (t, J = 12.0Hz, 1H), (m, 2H), 2, (m, 1H), 1.68 (bs, 2H), (m, 3H) 13 C NMR (100 MHz, CDCl 3 ) 167.4, 162.5, 150.2, 149.9, 148.6, 145.3, 141.6, 131.8, 130.2, 129.6, 128.6, 127.6, 127.5, 125.8, 123.8, 118.7, 118.3, 114.6, 101.6, 55.9, 55.9, 53.5, 41.3, 39.5, 36.5, 29.7, 27.7, Se NMR ppm. HRMS-ES + m/z: (Calculated for C 26 H 25 N 3 O 80 Se + H + : ). [α] 30 D (c = 0.2, CHCl 3 ). (1R)-(6-Methoxyquinolin-4-yl)((2R,4S,5R)-5-vinylquinuclidin-2-yl)methanamine (Quinidinamine): 3 Yield 0.8 g (84%). 1 H NMR (400 MHz, CDCl 3 ) 8.60 (d, J = 4.5 Hz, 1H), 7.88 (d, J = 9.2 Hz, 1H), 7.44 (m, 2H), 7.22 (dd, J = 9.2, 2.5 Hz, 1H), 5.74 (quintet, J = 8.7 Hz, 1H), 4.92 (m, 2H), 4.53 (s, 1H) 3.81 (s, 3H), 2.84 (m, 6H), 2.46 (s, 2H), 2.11 (q, J = 7.7 Hz, 1H), 1.40 (m, 3H) 13 C NMR (100 MHz, CDCl 3 ) 157.6, 147.6, 147.5, 144.5, 140.7, 131.6, 128.6, 121.6, 119.8, 114.4, 101.4, 62.3, 55.4, 55.3, 49.4, 47.3, 39.3, 27.5, 26.6, HRMS-ES + m/z: (Calculated for C 20 H 25 N 3 O + H + : ). [α] 30 D (c = 0.5, CHCl 3 ). S6

7 2-Iodo-N-((1R)-(6-methoxyquinolin-4-yl)((2R,4S,5R)-5-vinylquinuclidin-2- yl)methyl)benzamide (Substrate for 9): Yield 0.71 g (86%), mp o C. 1 H NMR (400 MHz, CDCl 3 ) 8.66 (m, 1H), 7.97 (m, 1H), 7.72 (d, J = 8.0 Hz, 1H), 7.67 (s, 1H), 7.44 (d, J = 4.5 Hz, 1H), (m, 3H), 6.95 (t, J = 7.5 Hz, 1H), 5.90 (m, 1H), 5.48 (bs, 1H), 5.10 (m, 2H), 3.93 (s, 3H), 3.27 (bs, 2H), (m, 6H), (m, 1H), (m, 3H) 13 C NMR (100 MHz, CDCl 3 ) 169.1, 157.8, 147.7, 147.4, 144.6, 144.5, 141.9, 140.5, 139.7, 131.5, 130.9, 128.6, 128.4, 128.0, , 121.8, 114.8, 101.7, 92.3, 55.7, 55.5, 49.1, 47.2, 39.0, 29.6, 27.3, HRMS-ES + m/z: (Calculated for C 27 H 28 IN 3 O 2 + H + : ). [α] 26 D (c = 0.2, CHCl 3 ). 2-((1R)-(6-Methoxyquinolin-4-yl)((2R,4S,5R)-5-vinylquinuclidin-2- yl)methyl)benzo[d][1,2]selenazol-3(2h)-one (9): Yield 0.29 g (64%), mp o C. 1 H NMR (400 MHz, CDCl 3 ) 8.74 (d, J = 4.6 Hz, 1H), (m, 1H), 7.95 (s, 1H), (m, 1H), 7.45 (t, J = 7.2 Hz, 1H), 7.38 (bs, 1H), (m, 2H), 7.24 (s, 1H), (m, 1H), (m, 1H), 5.18 (d, J = 17.5 Hz, 1H), 5.08 (d, J = 10.9 Hz, 1H), 3.98 (s, 3H), (m, 1H), (m, 1H), (m, 2H), (m, 1H), 1.72 (s, 1H), (m, 3H), (m, 2H) 13 C NMR (100 MHz, CDCl 3 ) 167.5, 162.5, 158.5, 158.1, 147.1, 144.9, 143.3, 140.3, 131.8, 131.5, 128.6, 127.5, 126.0, 123.9, 122.8, 118.4, 114.8, 101.6, 58.7, 55.9, 55.7, 52.9, 39.1, 36.5, 29.7, 27.6, Se NMR ppm. HRMS-ES + m/z: (Calculated for C 27 H 27 N 3 O 80 2 Se + H + : ). [α] 30 D (c = 0.8, CHCl 3 ). 2-Bromo-5-(tert-butyl)-N1,N3-bis((1S)-(6-methoxyquinolin-4-yl)((2S,4S,5R)-5- vinylquinuclidin-2-yl)methyl)isophthalamide (Substrate for 10): Yield 0.77 g (95%), mp above 200 o C. 1 H NMR (400 MHz, CDCl 3 ) 8.73 (s, 3H), 8.0 (d, J = 9.1 Hz, 3H), 7.76 (s, 3H), 7.65 (bs, 2H), 7.36 (d, J = 9.2 Hz, 3H), 6.0 (bs, 2H), 5.7 (bs, 4H), 3.90 (s, 6H), 3.56 (bs, 4H), S7

8 3.30 (bs, 3H), 3.07 (bs, 3H), 2.54 (bs, 3H), (m, 11H), 1.10 (s, 9H) 13 C NMR (100 MHz, CDCl 3 ) 168.5, 158.6, 151.0, 147.8, 144.8, 137.8,131.7, 128.3, 127.6, 122.5, 120.3, 117.4, 114.0, 102.0, 101.7, 59.0, 55.9, 54.1, 49.4, 41.6, 36.8, 31.0, 30.98, 30.9, 27.0, HRMS-ES + m/z: (Calculated for C 52 H 59 BrN 6 O 4 + H + : ). [α] 30 D (c = 0.2, CHCl 3 ). 5-(tert-Butyl)-N,2-bis((1S)-(6-methoxyquinolin-4-yl)((2S,4S,5R)-5-vinylquinuclidin-2- yl)methyl)-3-oxo-2,3-dihydrobenzo[d][1,2]selenazole-7-carboxamide (10): Yield 0.32 g (65%), mp o C. 1 H NMR (400 MHz, CDCl 3 ) 8.73 (d, J = 4.2 Hz, 2H), (m, 5H), 7.71 (bs, 2H), 7.46 (d, J = 4.4 Hz, 2H), 7.37 (dd, J = 9.2, 2.3 Hz, 2H), (m, 2H), (m, 4H), 3.93 (s, 6H), (m, 7H), 2.90 (s, 2H), 2.83 (s, 2H), 2.34 (bs, 3H), (m, 10H), 1.22 (s, 9H) 13 C NMR (100 MHz, CDCl 3 ) 178.8, 168.0, 162.7, 158.2, 157.7, 154.3, 151.3, 150.7, 147.6, 147.3, 147.0, 144.8, 144.7, 140.3, 139.3, 138.7, 131.8, 131.4, 129.6, , 127.9, 127.3, 125.1, 122.0, 121.9, 120.5, 119.0, 116.3, 115.5, 115.0, 114.1, 101.9, 55.8, 55.3, 50.5, 41.2, 38.8, 36.5, 34.7, 33.8, 31.9, 31.4, 30.8, 29.7, 29.5, 29.4, 29.1, 28.9, 27.2, 25.6, 22.7, Se NMR ppm. HRMS-ES + m/z: (Calculated for C 52 H 58 N 6 O 80 4 Se + H + : ). [α] 30 D (c = 0.2, CHCl 3 ). 2-Iodo-N-((1S)-(6-methoxyquinolin-4-yl)((2S,4S,5R)-5-vinylquinuclidin-2-yl)methyl)-3- methylbenzamide (Substrate for 11): Yield 0.55 g (91%), mp above 225 o C. 1 H NMR (400 MHz, CDCl 3 ) 8.68 (d, J = 4.5 Hz, 1H), 8.0 (d, J = 9.1 Hz, 1H), 7.75 (bs, 1H), 7.42 (d, J = 4.3 Hz, 1H), 7.30 (dd, J = 9.2, 2.6 Hz, 1H), (m, 3H), 6.97 (bs, 1H), (m, 1H), (m, 3H), 3.90 (s, 3H), 3.20 (t, J = 12.0 Hz, 2H), (m, 4H), 2.40 (s, 3H), (m, 1H), (m, 4H) 13 C NMR (100 MHz, CDCl 3 ) 170.1, 157.9, 147.8, 147.5, 144.8, 143.7, 142.7, 141.5, 141.2, 131.8, 130.3, 128.0, 125.2, 121.7, 118.9, 114.7, 102.3, 99.0, S8

9 56.0, 55.8, 53.4, 46.1, 41.3, 39.5, 29.1, 27.9, 27.4, HRMS-ES + m/z: (Calculated for C 28 H 30 IN 3 O 2 + H + : ). [α] 28 D (c = 0.2, CHCl 3 ). 2-((1S)-(6-Methoxyquinolin-4-yl)((2S,4S,5R)-5-vinylquinuclidin-2-yl)methyl)-7- methylbenzo[d][1,2]selenazol-3(2h)-one (11): Yield 0.26 g (71%), mp decomposed after 155 o C. 1 H NMR (400 MHz, CDCl 3 ) 8.76 (d, J = 4.5 Hz, 1H), (m, 3H), (m, 1H), (m, 1H), (m, 1H), (m, 1H), (m, 1H), (m, 1H), (m, 2H), 3.95 (s, 3H), (m, 2H), 3.24 (t, J = 11.8 Hz, 1H), 2.88 (s, 2H), 2.30 (bs, 1H), 2.14 (s, 3H), (m, 1H), (m, 2H), 1.21 (s, 2H) 13 C NMR (100 MHz, CDCl 3 ) 167.6, 162.5, 158.5, 147.1, 144.9, 142.7, 141.6, 132.7, 131.9, 131.6, 127.3, 126.7, 126.1, 122.7, 118.5, 114.6, 101.8, 58.5, 56.0, 53.7, 41.6, 39.5, 36.4, 31.4, 29.7, 28.2, 27.6, Se NMR ppm. HRMS-ES + m/z: (Calculated for C 28 H 29 N 3 O 2 Se + H + : ). [α] 30 D (c = 0.2, CHCl 3 ). 2-Bromo-5-methoxy-N-((1S)-(6-methoxyquinolin-4-yl)((2S,4S,5R)-5-vinylquinuclidin-2- yl)methyl)benzamide (Substrate for 12): Yield 0.77 g (90%), 1 H NMR (400 MHz, CDCl 3 ) 8.70 (d, J = 4.1 Hz, 1H), 8.0 (d, J = 9.1 Hz, 1H), 7.70 (s, 1H), (m, 4H), 7.0 (s, 1H), 6.80 (dd, J = 8.7, 2.5 Hz, 1H), (m, 1H), (m, 3H), 3.90 (s, 3H), 3.70 (s, 3H), (m, 2H), 2.70 (m, 3H), 2.30 (s, 1H), (m, 3H), 1.45 (m, 1H), 1.10 (t, J = 7.2 Hz, 1H) 13 C NMR (100 MHz, CDCl 3 ) 167.1, 158.8, 157.8, 147.8, 147.6, 144.8, 141.5, 141.2, 138.1, 134.1, 131.7, 121.6, 117.7, 115.0, 114.7, 114.5, 109.5, 102.1, 56.0, 55.7, 55.6, 46.0, 41.1, 39.7, 39.5, 27.9, 27.5, HRMS-ES + m/z: (Calculated for C 28 H 30 BrN 3 O 3 + H + : ). [α] 29 D -7.0 (c = 0.2, CHCl 3 ). 5-Methoxy-2-((1S)-(6-methoxyquinolin-4-yl)((2S,4S,5R)-5-vinylquinuclidin-2- yl)methyl)benzo[d][1,2]selenazol-3(2h)-one (12): Yield 0.35 g (70%), mp o C. 1 H S9

10 NMR (400 MHz, CDCl 3 ) 8.77 (s, 1H), (m, 2H), (m, 4H), (s, 1H), (m, 1H), (m, 1H), (m, 2H), 4.0 (s, 3H), 3.80 (s, 3H), 3.60 (s, 2H), 3.27 (t, J = 12.0 Hz, 1H), (m, 2H), 2.35 (s, 1H), 1.90 (s, 1H), (m, 4H) 13 C NMR (100 MHz, CDCl 3 ) 166.9, 158.8, 147.2, 144.9, 142.7, 141.4, 132.2, 132.1, 131.6, 128.6, 128.4, 124.9, 122.7, 121.7, 118.4, 114.8, 110.7, 101.8, 60.4, 58.8, 56.0, 55.6, 53.9, 41.6, 39.4, 31.9, 29.7, Se NMR ppm. HRMS-ES + m/z: (Calculated for C 28 H 29 N 3 O 3 Se + H + : ). [α] 29 D (c = 0.06, CHCl 3 ). 2-Bromo-4,5-dimethoxy-N-((1S)-(6-methoxyquinolin-4-yl)((2S,4S,5R)-5-vinylquinuclidin-2- yl)methyl)benzamide (Substrate for 13): Yield 0.95 g (94%), mp o C. 1 H NMR (400 MHz, CDCl 3 ) 8.70 (d, J = 4.5 Hz, 1H), 8.0 (d, J = 9.3 Hz, 1H), 7.70 (s, 1H), 7.42 (d, J = 4.6 Hz, 1H), 7.34 (dd, J = 9.2, 2.5 Hz, 1H), 7.10 (s, 1H), 6.90 (s, 1H), 5.70 (quintet, J = 8.3 Hz, 1H), (m, 3H), 3.94 (s, 3H), 3.82 (s, 3H), 3.74 (s, 3H), (m, 2H), (m, 4H), 2.30 (bs, 1H), (m, 4H), 1.42 (t, J = 10.7 Hz, 1H) 13 C NMR (100 MHz, CDCl 3 ) 166.4, 157.8, 150.9, 148.3, 147.8, 147.6, 144.8, 141.3, 131.8, 128.5, 121.6, 119.6, 115.8, 114.6, 113.3, 112.0, 110.1, 102.0, 56.3, 56.1, 56.0, 55.7, 46.1, 41.1, 39.6, 27.9, 27.4, 26.9, HRMS-ES + m/z: (Calculated for C 29 H 32 BrN 3 O 4 + H + : ). [α] 30 D (c = 0.9, CHCl 3 ). 5,6-Dimethoxy-2-((1S)-(6-methoxyquinolin-4-yl)((2S,4S,5R)-5-vinylquinuclidin-2- yl)methyl)benzo[d][1,2]selenazol-3(2h)-one (13): Yield 0.27 g (68 %), mp o C. 1 H NMR (400 MHz, CDCl 3 ) 8.80 (d, J = 4.3 Hz, 1H), (m, 2H), (m, 3H), 6.90 (s, 1H), 6.3 (bs, 1H), 5.90 (bs, 1H), 5.07 (d, J = 14.7 Hz, 2H), 3.97 (s, 3H), 3.87 (s, 3H), 3.85 (s, 3H), (m, 2H), 3.27 (t, J = 12.0 Hz, 1H), (m, 2H), 2.33 (bs, 1H), 1.90 (bs, 1H), 1.74 (s, 1H), (m, 3H) 13 C NMR (100 MHz, CDCl 3 ) 162.5, 158.4, 153.2, 148.7, 147.1, 144.8, 143.1, 141.6, 132.0, 131.5, 128.4, 122.5, 120.0, 118.4, 114.6, 109.3, 105.4, 101.9, S10

11 58.7, 56.2, 56.1, 55.9, 41.5, 39.5, 36.4, 31.4, 29.6, 27.7, Se NMR ppm. HRMS- ES + m/z: (Calculated for C 29 H 31 N 3 O 4 Se + H + : ). [α] 29 D (c = 0.3, CHCl 3 ). 2-Bromo-4,5-difluoro-N-((1S)-(6-methoxyquinolin-4-yl)((2S,4S,5R)-5-vinylquinuclidin-2- yl)methyl)benzamide (Substrate for 14): Yield 0.78 g (92%), mp o C. 1 H NMR (400 MHz, CDCl 3 ) 8.66 (d, J = 4.5 Hz, 1H), (m, 1H), 7.75 (bs, 1H), 7.66 (s, 1H), (m, 4H), 5.68 (quintet, J = 8.7 Hz, 1H), (m, 3H), 3.94 (s, 3H), (m, 4H), (m, 2H), 2.25 (s, 1H), (m, 3H), 1.48 (t, J = 12.4 Hz, 1H) 13 C NMR (100 MHz, CDCl 3 ) 165.2, 158.0, 152.1, 151.9, 150.7, 150.6, 149.5, 149.4, 148.2, 148.0, 147.7, 147.5, 144.8, 141.1, 133.9, 132.1, 122.5, 122.3, 121.7, 119.0, 118.8, 114.8, 113.4, 101.9, 55.9, 55.7, 55.6, 41.1, 39.6, 39.4, 27.8, 27.3, HRMS-ES + m/z: (Calculated for C 27 H 26 BrF 2 N 3 O 2 + H + : ). [α] 28 D (c = 0.2, CHCl 3 ). 5,6-Difluoro-2-((1S)-(6-methoxyquinolin-4-yl)((2S,4S,5R)-5-vinylquinuclidin-2- yl)methyl)benzo[d][1,2]selenazol-3(2h)-one (14): Yield 0.21 g (62%), mp o C. 1 H NMR (400 MHz, CDCl 3 ) 8.74 (d, J = 4.3 Hz, 1H), 7.98 (d, J = 9.3 Hz, 1H), (m, 1H), (m, 1H), (m, 3H), 6.25 (s, 1H), (m, 1H), (m, 2H), 3.98 (bs, 3H), (m, 2H), 3.26 (t, J = 11.4 Hz, 1H), (m, 2H), (m, 1H), (m, 1H), (m, 1H), (m, 3H) 13 C NMR (100 MHz, CDCl 3 ) 165.8, 158.7, 157.4, 147.8, 147.2, 144.8, 140.7, 139.3, 132.1, , , 131.6, 128.6, 128.5, 124.3, 122.8, 121.6, 121.0, 118.4, 116.7, 116.5, 115.3, 114.8, 114.4, 114.1, 102.2, 101.5, 59.1, 56.0, 54.1, 47.9, 41.6, 31.6, 29.7, 27.5, HRMS-ES + m/z: (Calculated for C 27 H 25 F 2 N 3 O 2 Se + H + : ). S11

12 (E)-5-Phenylpent-4-enoic acid (Substrate for 17): 5 1 H NMR (400 MHz, CDCl 3 ) 7.88 (d, J = 7.9 Hz, 2H), 7.46 (t, J = 7.4 Hz, 1H), 7.36 (t, J = 7.6 Hz, 2H), 3.60 (s, 3H), 3.21 (t, J = 6.6 Hz, 2H), 2.66 (t, J = 6.6 Hz, 2H) 13 C NMR (100 MHz, CDCl 3 ) 179.0, 137.3, 131.2, 128.5, 128.0, 127.2, 126.1, 33.7, HRMS-ES + m/z: (Calculated for C 11 H 12 O - 2 H + : ). (E)-5-(4-Fluorophenyl)pent-4-enoic acid (Substrate for 18): 5 1 H NMR (400 MHz, CDCl 3 ) (bs, 1H), (m, 2H), 6.97 (t, J = 8.7 Hz, 2H), 6.39 (d, J = 15.8 Hz, 1H), (m, 1H), (m, 4H) 13 C NMR (100 MHz, CDCl 3 ) 179.1, 163.1, 160.1, 133.5, 133.4, 130.1, 127.8, , 127.6, 127.5, 115.5, 115.3, 33.8, HRMS-ES + m/z: (Calculated for C 11 H 11 FO - 2 H + : ). (E)-5-(4-Chlorophenyl)pent-4-enoic acid (Substrate for 19): 5 1 H NMR (400 MHz, CDCl 3 ) 7.24 (s, 4H), 6.38 (d, J = 15.8 Hz, 1H), (m, 1H), (m, 4H) 13 C NMR (100 MHz, CDCl 3 ) 179.1, 135.7, 132.8, 130.1, , , 127.3, 33.6, HRMS-ES + m/z: (Calculated for C 11 H 11 ClO - 2 H + : ). (E)-5-(4-Bromophenyl)pent-4-enoic acid (Substrate for 20): 5 1 H NMR (400 MHz, CDCl 3 ) 7.40 (d, J = 8.5 Hz, 2H), 7.19 (d, J = 8.4 Hz, 2H), 6.37 (d, J = 15.8 Hz, 1H), (m, 1H),, (m, 4H) 13 C NMR (100 MHz, CDCl 3 ) 178.0, 136.2, 131.6, 130.1, 128.9, 127.6, 120.9, 33.4, HRMS-ES + m/z: (Calculated for C 11 H 11 BrO 2 - H + : ). (E)-5-(p-Tolyl)pent-4-enoic acid (Substrate for 21): 5 1 H NMR (400 MHz, CDCl 3 ) 7.24 (d, J = 8.2 Hz, 2H), 7.09 (d, J = 7.9 Hz, 2H), 6.40 (d, J = 15.7 Hz, 1H), (m, 1H), 2.53 (d, J = 2.8 Hz, 4H), 2.30 (s, 3H) 13 C NMR (100 MHz, CDCl 3 ) 179.1, 136.9, 134.5, 131.0, 129.2, 126.9, 126.2, 33.9, 27.9, HRMS-ES + m/z: (Calculated for C 12 H 14 O - 2 H + : ). S12

13 (E)-5-(4-(tert-Butyl)phenyl)pent-4-enoic acid (Substrate for 22): 5 1 H NMR (400 MHz, CDCl 3 ) (m, 4H), 6.42 (d, J = 15.9 Hz, 1H), (m, 1H), (m, 4H), 1.30 (s, 9H) 13 C NMR (100 MHz, CDCl 3 ) 178.5, 150.2, 134.5, 130.9, 127.2, 125.8, 125.4, 34.5, 33.8, 31.3, LRMS-ES + m/z: (Calculated for C 15 H 20 O - 2 H + : ). (E)-5-(4-Methoxyphenyl)pent-4-enoic acid (Substrate for 23): 5 1 H NMR (400 MHz, CDCl 3 ) 7.26 (d, J = 9.0 Hz, 2H), 6.82 (d, J = 8.7 Hz, 2H), 6.38 (d, J = 15.8 Hz, 1H), (m, 1H), 3.78 (s, 3H), (m, 4H) 13 C NMR (100 MHz, CDCl 3 ) 178.8, 159.1, 130.6, 130.1, 127.2, 125.8, 113.7, 55.2, 33.7, HRMS-ES + m/z: (Calculated for C 12 H 14 O 3 - H + : ). (E)-5-(Benzo[d][1,3]dioxol-5-yl)pent-4-enoic acid (Substrate for 24): Light brown solid, Yield 0.14 g (54%), 1 H NMR (400 MHz, CDCl 3 ) 6.87 (s, 1H), (m, 2H), 6.34 (d, J = 15.7 Hz, 1H), (m, 1H), 5.92 (s, 2H), (m, 4H) 13 C NMR (100 MHz, CDCl 3 ) 178.9, 147.9, 146.9, 131.8, 130.8, 126.3, 120.5, 108.2, 105.5, 101.0, 33.8, HRMS-ES + m/z: (Calculated for C 12 H 12 O - 4 H + : ). (5R,6S)-5-Bromo-6-phenyltetrahydro-2H-pyran-2-one (17): 5 White solid, mp C; 1 H NMR (400 MHz, CDCl 3 ) (m, 3H), (m, 2H), 5.54 (d, J = 6.4 Hz, 1H), 4.36 (q, J = 5.7 Hz, 1H), (m, 1H), (m, 1H), (m, 1H), (m, 1H) 13 C NMR (100 MHz, CDCl 3 ) 169.5, 137.0, 129.1, 128.8, 126.4, 85.9, 47.3, 28.4, 27.6; HRMS (ESI) m/z: Calculated for C 11 H 11 BrO 2 [M + Na] , found HPLC (Daicel Chiralpak IC-3, i-proh/hexane = 25/75, 0.6 ml/min, 214 nm) t 1 = 26.6 min (major), t 2 = 28.7 min (minor). (5R,6S)-5-Bromo-6-(4-fluorophenyl)tetrahydro-2H-pyran-2-one (18): 5 White solid, mp C; 1 H NMR (400 MHz, CDCl 3 ) (m, 2H), 7.08 (t, J = 8.6 Hz, 2H), 5.46 (d, J = S13

14 7.4 Hz, 1H), (m, 1H), (m, 1H), (m, 1H), (m, 1H), (m, 1H) 13 C NMR (100 MHz, CDCl 3 ) 168.9, 164.2, 161.8, , , 128.6, 128.5, 115.9, 115.7, 84.9, 46.9, 28.8, 28.4; GCMS (ESI) m/z: (calculated for C 11 H 10 BrFO 2 [M] 271.9). HPLC (Daicel Chiralpak IB, i-proh/hexane = 25/75, 0.6 ml/min, 214 nm) t 1 = 29.3 min (major), t 2 = 31.2 min (minor) (5R,6S)-5-Bromo-6-(4-chlorophenyl)tetrahydro-2H-pyran-2-one (19): 5 White solid, mp C; 1 H NMR (400 MHz, CDCl 3 ) (m, 2H), (m, 2H), 5.46 (d, J = 7.2 Hz, 1H), (m, 1H), (m, 1H), (m, 1H), (m, 1H), (m, 1H) 13 C NMR (100 MHz, CDCl 3 ) 168.7, 135.6, 135.1, 129.0, 128.0, 84.9, 46.7, 28.7, 28.3; GCMS (ESI) m/z: (calculated for C 11 H 10 BrClO 2 [M] 287.9). HPLC (Daicel Chiralpak IB, i-proh/hexane = 25/75, 0.6 ml/min, 214 nm) t 1 = 24.3 min (minor), t 2 = 25.5 min (major). (5R,6S)-5-Bromo-6-(4-bromophenyl)tetrahydro-2H-pyran-2-one (20): 5 White solid, mp C; 1 H NMR (400 MHz, CDCl 3 ) 7.53 (d, J = 8.2 Hz, 2H), 7.21 (d, J = 8.2 Hz, 2H), 5.45 (d, J = 7.2 Hz, 1H), (m, 1H), (m, 1H), (m, 1H), (m, 1H), (m, 1H) 13 C NMR (100 MHz, CDCl 3 ) 168.7, 136.1, 131.9, 128.1, 123.0, 84.6, 46.8, 28.6, 28.3; GCMS (ESI) m/z: (calculated for C 11 H 10 Br 2 O 2 [M] 333.9). HPLC (Daicel Chiralpak IB, i-proh/hexane = 25/75, 0.6 ml/min, 214 nm) t 1 = 25.0 min (minor), t 2 = 27.5 min (major). (5R,6S)-5-Bromo-6-(p-tolyl)tetrahydro-2H-pyran-2-one (21): 5 Semi solid; 1 H NMR (400 MHz, CDCl 3 ) 1 H NMR (400 MHz, CDCl 3 ) 7.19 (s, 4H), 5.51 (d, J = 6.4 Hz, 1H), (m, 1H), (m, 1H), (m, 1H), (m, 1H), 2.35 (s, 3H), (m, 1H) 13 C NMR (100 MHz, CDCl 3 ) 169.1, 139.0, 134.3, 129.5, 126.3, 85.6, 47.5, 28.4, 27.6, S14

15 21.0; GCMS (ESI) m/z: (calculated for C 12 H 13 BrO 2 [M ] 267.9). HPLC (Daicel Chiralpak IA, i-proh/hexane = 10/90, 0.6 ml/min, 214 nm) t 1 = 35.1 min (minor), t 2 = 37.9 min (major). (5R,6S)-5-Bromo-6-(4-(tert-butyl)phenyl)tetrahydro-2H-pyran-2-one (22): 5 Semi solid; 1 H NMR (400 MHz, CDCl 3 ) (m, 2H), (m, 2H), 5.55 (d, J = 6.0 Hz, 1H), (m, 1H), (m, 1H), (m, 1H), (m, 1H), (m, 1H), 1.30 (s, 9H) 13 C NMR (100 MHz, CDCl 3 ) 169.0, 152.2, 134.4, 126.0, 125.8, 85.3, 47.1, 34.7, 31.2, 28.2, 27.3; GCMS (ESI) m/z: (calculated for C 15 H 19 BrO 2 [M CH 3 ] 295.0). HPLC (Daicel Chiralpak IC-3, i-proh/hexane = 25/75, 0.6 ml/min, 214 nm) t 1 = 30.4 min (minor), t 2 = 33.3 min (major). (5R,6S)-5-Bromo-6-(4-methoxyphenyl)tetrahydro-2H-pyran-2-one (23): 5 White solid, mp C; 1 H NMR (400 MHz, CDCl 3 ) (m, 2H), (m, 2H), 5.46 (d, J = 6.9 Hz, 1H), (m, 1H), 3.80 (s, 3H), (m, 1H), (m, 1H), (m, 1H), (m, 1H); 13 C NMR (100 MHz, CDCl 3 ) 169.0, 160.1, 129.3, 127.9, 114.1, 85.4, 55.3, 47.4, 28.6, 28.0; GCMS (ESI) m/z: (calculated for C 12 H 13 BrO 3 [M] 285.9). HPLC (Daicel Chiralpak IC-3, i-proh/hexane = 25/75, 0.6 ml/min, 214 nm) t 1 = 57.3 min (minor), t 2 = 59.9 min (major). (5R,6S)-6-(Benzo[d][1,3]dioxol-5-yl)-5-bromotetrahydro-2H-pyran-2-one (24): Semi solid, 1 H NMR (400 MHz, CDCl 3 ) (m, 3H), 5.98 (s, 2H), 5.40 (d, J = 7.0 Hz, 1H), 4.28 (q, J = 6.3 Hz, 1H), (m, 1H), (m, 1H), (m, 1H), (m, 1H) 13 C NMR (100 MHz, CDCl 3 ) , 148.2, 148.1, 130.9, 120.6, 108.3, 106.8, 101.5, 85.4, 47.2, 28.6, 28.2; HRMS (ESI) m/z: (calculated for C 12 H 11 BrO 4 [M + H] ). HPLC (Daicel Chiralpak IC-3, i-proh/hexane = 25/75, 0.6 ml/min, 214 nm) t 1 = 23.6 min (major), t 2 = 31.2 min (minor). S15

16 (R)-6-((R)-1-Bromoheptyl)tetrahydro-2H-pyran-2-one (25): Colorless oil. 1 H NMR (400 MHz, CDCl 3 ) (m, 1H), (m, 1H), (m, 1H), (m,1h), (m, 7H), (m, 1H), (m, 6H), 0.86 (t, J = 6.8 Hz, 3H) 13 C NMR (100 MHz, CDCl 3 ) 170.7, 81.5, 56.7, 34.1, 31.6, 29.6, 28.6, 27.8, 25.2, 22.5, 18.4, 14.0.; HRMS (ESI) m/z: (calculated for C 12 H 21 BrO 2 [M + H] ). HPLC (Daicel Chiralpak ADH, i-proh/hexane = 10/90, 1.0 ml/min, 210 nm) t 1 = 7.0 min (major), t 2 = 8.0 (minor). TS1. Screening of Various Solvents For Bromolactonization Reaction Entry a Solvent Additive Yield b % ee 1 Chloroform % 2 Toluene % 3 Tetrahydrofuran % 4 Diethyl ether % 5 Dichloro ethane % 6 DCM : Toluene (1:1) % 7 DCM : Hexane (1:1) % 8 DCM : Acetone (1:1) % 9 Trifluoro ethanol Hexafluoro isopropanol c DCM % 12 d DCM % 13 e DCM % 14 f DCM % 15 DCM quininamine (100 mol %) 57-25% 16 DCM quinidinamine (100 mol %) 51 8% 17 DCM Benzoic acid (100 mol %) DCM NsNH 2 (50 mol %) S16

17 Scheme 1. Racemization Described by Bromonium ion-alkene Intermediate S17

18 Figure S1 77 Se NMR of 1 S18

19 Figure S2 77 Se NMR of 2 S19

20 Figure S3 1 H NMR of 3 S20

21 Figure S4 13 C NMR of 3 S21

22 Figure S5 77 Se NMR of 3 S22

23 Figure S6 HRMS (ESI) of 3 (m/z , calcd for C 20 H 17 NO 2 Se + H + : ) S23

24 Figure S7 1 H NMR of (S)-2-chloro-N-(1-(naphthalen-1-yl) ethyl)-3-nitrobenzamide S24

25 Figure S8 13 C NMR of (S)-2-chloro-N-(1-(naphthalen-1-yl) ethyl)-3-nitrobenzamide S25

26 Figure S9 HRMS (ESI) of (S)-2-chloro-N-(1-(naphthalen-1-yl) ethyl)-3-nitrobenzamide S26

27 Figure S10 1 H NMR of 4 S27

28 Figure S11 13 C NMR of 4 S28

29 Figure S12 77 Se NMR of 4 S29

30 Figure S13 HRMS (ESI) of 4 (m/z , calcd for C 19 H 14 N 2 O 3 Se + H + : ) S30

31 Figure S14 1 H NMR of 2-bromo-N1-((R)-1-(naphthalen-1-yl)ethyl)-N3-((S)-1-(naphthalen-1- yl)ethyl)isophthalamide S31

32 Figure S15 13 C NMR of 2-bromo-N1-((R)-1-(naphthalen-1-yl) ethyl)-n3-((s)-1-(naphthalen-1- yl)ethyl)isophthalamide S32

33 Figure S16 HRMS (ESI) of 2-bromo-N1-((R)-1-(naphthalen-1-yl) ethyl)-n3-((s)-1-(naphthalen- 1-yl)ethyl)isophthalamide S33

34 Figure S17 1 H NMR of 5 S34

35 Figure S18 13 C NMR of 5 S35

36 Figure S19 77 Se NMR 5 S36

37 Figure S20 HRMS (ESI) of 5 (m/z , calcd for C 32 H 26 N 2 O 2 Se - H + : ) S37

38 Figure S21 1 H NMR of (1S)-(6-methoxyquinolin-4-yl)((2S,4S,5R)-5-vinylquinuclidin-2- yl)methanamine S38

39 Figure S22 13 C NMR of (1S)-(6-methoxyquinolin-4-yl)((2S,4S,5R)-5-vinylquinuclidin-2- yl)methanamine S39

40 Figure S23 HRMS (ESI) of (1S)-(6-methoxyquinolin-4-yl)((2S,4S,5R)-5-vinylquinuclidin-2- yl)methanamine S40

41 Figure S24 1 H NMR of 2-iodo-N-((1S)-(6-methoxyquinolin-4-yl)((2S,4S,5R)-5- vinylquinuclidin-2-yl)methyl)benzamide S41

42 Figure S25 13 C NMR of 2-iodo-N-((1S)-(6-methoxyquinolin-4-yl)((2S,4S,5R)-5- vinylquinuclidin-2-yl)methyl)benzamide S42

43 Figure S26 HRMS (ESI) of 2-iodo-N-((1S)-(6-methoxyquinolin-4-yl)((2S,4S,5R)-5- vinylquinuclidin-2-yl)methyl)benzamide S43

44 Figure S27 1 H NMR of 6 S44

45 Figure S28 13 C NMR of 6 S45

46 Figure S29 HRMS (ESI) of 6 (m/z: calculated for C 27 H 27 N 3 O 2 S + H + : ) S46

47 Figure S30 1 H NMR of 7 S47

48 Figure S31 13 C NMR of 7 S48

49 Figure S32 77 Se NMR of 7 S49

50 Figure S33 HRMS (ESI) of 7 (m/z: calculated for C 27 H 27 N 3 O 2 80 Se + H + : ) S50

51 Figure S34 1 H NMR of (1S)-quinolin-4-yl((2S,4S,5R)-5-vinylquinuclidin-2-yl)methanamine S51

52 Figure S35 13 C NMR of (1S)-quinolin-4-yl((2S,4S,5R)-5-vinylquinuclidin-2-yl)methanamine S52

53 Figure S36 HRMS (ESI) of (1S)-quinolin-4-yl((2S,4S,5R)-5-vinylquinuclidin-2-yl)methanamine S53

54 Figure S37 1 H NMR of 2-iodo-N-((1S)-quinolin-4-yl((2S,4S,5R)-5-vinylquinuclidin-2- yl)methyl)benzamide S54

55 Figure S38 13 C NMR of 2-iodo-N-((1S)-quinolin-4-yl((2S,4S,5R)-5-vinylquinuclidin-2- yl)methyl)benzamide S55

56 Figure S39 HRMS (ESI) of 2-iodo-N-((1S)-quinolin-4-yl((2S,4S,5R)-5-vinylquinuclidin-2- yl)methyl)benzamide S56

57 Figure S40 1 H NMR of 8 S57

58 Figure S41 13 C NMR of 8 S58

59 Figure S42 77 Se NMR of 8 S59

60 Figure S43 HRMS (ESI) of 8 (m/z: calculated for C 26 H 25 N 3 O 80 Se + H + : ) S60

61 Figure S44 1 H NMR of (1R)-(6-methoxyquinolin-4-yl)((2R,4S,5R)-5-vinylquinuclidin-2- yl)methanamine S61

62 Figure S45 13 C NMR of (1R)-(6-methoxyquinolin-4-yl)((2R,4S,5R)-5-vinylquinuclidin-2- yl)methanamine S62

63 Figure S46 HRMS (ESI) of (1R)-(6-methoxyquinolin-4-yl)((2R,4S,5R)-5-vinylquinuclidin-2- yl)methanamine S63

64 Figure S47 1 H NMR of 2-iodo-N-((1R)-(6-methoxyquinolin-4-yl)((2R,4S,5R)-5- vinylquinuclidin-2-yl)methyl)benzamide S64

65 Figure S48 13 C NMR of 2-iodo-N-((1R)-(6-methoxyquinolin-4-yl)((2R,4S,5R)-5- vinylquinuclidin-2-yl)methyl)benzamide S65

66 Figure S49 HRMS (ESI) of 2-iodo-N-((1R)-(6-methoxyquinolin-4-yl)((2R,4S,5R)-5- vinylquinuclidin-2-yl)methyl)benzamide S66

67 Figure S50 1 H NMR of 9 S67

68 Figure S51 13 C NMR of 9 S68

69 Figure S52 77 Se NMR 9 S69

70 Figure S53 HRMS (ESI) of 9 (m/z: calculated for C 27 H 27 N 3 O 2 80 Se + H + : ) S70

71 Figure S54 1 H NMR of 2-bromo-5-(tert-butyl)-N1,N3-bis((1S)-(6-methoxyquinolin-4- yl)((2s,4s,5r)-5-vinylquinuclidin-2-yl)methyl)isophthalamide S71

72 Figure S55 13 C NMR of 2-bromo-5-(tert-butyl)-N1,N3-bis((1S)-(6-methoxyquinolin-4- yl)((2s,4s,5r)-5-vinylquinuclidin-2-yl)methyl)isophthalamide S72

73 Figure S56 HRMS (ESI) of 2-bromo-5-(tert-butyl)-N1,N3-bis((1S)-(6-methoxyquinolin-4- yl)((2s,4s,5r)-5-vinylquinuclidin-2-yl)methyl)isophthalamide S73

74 Figure S57 1 H NMR of 10 S74

75 Figure S58 13 C NMR of 10 S75

76 Figure S59 77 Se NMR of 10 S76

77 Figure S60 HRMS (ESI) of 10 S77

78 Figure S61 1 H NMR of 2-iodo-N-((1S)-(6-methoxyquinolin-4-yl)((2S,4S,5R)-5- vinylquinuclidin-2-yl)methyl)-3-methylbenzamide S78

79 Figure S62 13 C NMR of 2-iodo-N-((1S)-(6-methoxyquinolin-4-yl)((2S,4S,5R)-5- vinylquinuclidin-2-yl)methyl)-3-methylbenzamide S79

80 Figure S63 HRMS (ESI) of 2-iodo-N-((1S)-(6-methoxyquinolin-4-yl)((2S,4S,5R)-5- vinylquinuclidin-2-yl)methyl)-3-methylbenzamide S80

81 Figure S64 1 H NMR of 11 S81

82 Figure S65 13 C NMR of 11 S82

83 Figure S66 77 Se NMR 11 S83

84 Figure S67 HRMS (ESI) of 11 (m/z: calculated for C 28 H 29 N 3 O 2 Se + H + : ) S84

85 Figure S68 1 H NMR of 2-bromo-5-methoxy-N-((1S)-(6-methoxyquinolin-4-yl)((2S,4S,5R)-5- vinylquinuclidin-2-yl)methyl)benzamide S85

86 Figure S69 13 C NMR of 2-bromo-5-methoxy-N-((1S)-(6-methoxyquinolin-4-yl)((2S,4S,5R)-5- vinylquinuclidin-2-yl)methyl)benzamide S86

87 Figure S70 HRMS (ESI) of 2-bromo-5-methoxy-N-((1S)-(6-methoxyquinolin-4-yl)((2S,4S,5R)- 5-vinylquinuclidin-2-yl)methyl)benzamide S87

88 Figure S71 1 H NMR of 12 S88

89 Figure S72 13 C NMR of 12 S89

90 Figure S73 HRMS (ESI) of 12 (m/z: calculated for C 28 H 29 N 3 O 3 Se + H + : ). S90

91 Figure S74 77 Se NMR of 12 S91

92 Figure S75 1 H NMR of 2-bromo-4,5-dimethoxy-N-((1S)-(6-methoxyquinolin-4-yl)((2S,4S,5R)- 5-vinylquinuclidin-2-yl)methyl)benzamide S92

93 Figure S76 13 C NMR of 2-bromo-4,5-dimethoxy-N-((1S)-(6-methoxyquinolin-4-yl)((2S,4S,5R)- 5-vinylquinuclidin-2-yl)methyl)benzamide S93

94 Figure S77 HRMS (ESI) of 2-bromo-4,5-dimethoxy-N-((1S)-(6-methoxyquinolin-4- yl)((2s,4s,5r)-5-vinylquinuclidin-2-yl)methyl)benzamide S94

95 Figure S78 1 H NMR of 13 S95

96 Figure S79 13 C NMR of 13 S96

97 Figure S80 77 Se NMR 13 S97

98 Figure S81 HRMS (ESI) of 13 S98

99 Figure S82 1 H NMR of 2-bromo-4,5-difluoro-N-((1S)-(6-methoxyquinolin-4-yl)((2S,4S,5R)-5- vinylquinuclidin-2-yl)methyl)benzamide S99

100 Figure S83 13 C NMR of 2-bromo-4,5-difluoro-N-((1S)-(6-methoxyquinolin-4-yl)((2S,4S,5R)-5- vinylquinuclidin-2-yl)methyl)benzamide S100

101 Figure S84 HRMS (ESI) of 2-bromo-4,5-difluoro-N-((1S)-(6-methoxyquinolin-4-yl)((2S,4S,5R)- 5-vinylquinuclidin-2-yl)methyl)benzamide S101

102 Figure S85 1 H NMR of 14 S102

103 Figure S86 13 C NMR of 14 S103

104 Figure S87 HRMS (ESI) of 14 (m/z: calculated for C 27 H 25 F 2 N 3 O 2 Se + H + : ) S104

105 Figure S88 1 H NMR of 15 S105

106 Figure S89 13 C NMR of 15 S106

107 Figure S90 77 Se NMR of 15 S107

108 Figure S91 HRMS (ESI) of 15 (m/z: calculated for C 28 H 31 N 3 O 2 80 Se + H + : ) S108

109 Figure S92 1 H NMR of 16 S109

110 Figure S93 13 C NMR of 16 S110

111 Figure S94 HRMS (ESI) of 16 (m/z: calculated for C 54 H 56 N 6 O 4 80 Se 2 + H + : ) S111

112 Figure 95 1 H NMR spectrum for substrate of 17 S112

113 Figure C NMR spectrum for substrate of 17 S113

114 Figure S97 HRMS (ESI) substrate of 17 (m/z: calculated for C 11 H 12 O 2 - H + : ) S114

115 Figure 98 1 H NMR spectrum for substrate of 18 S115

116 Figure S99 13 C NMR spectrum for substrate of 18 S116

117 Figure S100 HRMS (ESI) of substrate for 18 (m/z: calculated for C 11 H 11 FO 2 - H + : ) S117

118 Figure H NMR spectrum of substrate for 19 S118

119 Figure S C NMR spectrum of substrate for 19 S119

120 Figure S103 DEPT-135 spectrum of substrate for 19 S120

121 Figure S104 HRMS (ESI) of substrate for 19 (m/z: calculated for C 11 H 11 ClO 2 - H + : ) S121

122 Figure H NMR spectrum of substrate for 20 S122

123 Figure S C NMR spectrum of substrate for 20 S123

124 Figure S107 DEPT-135 spectrum of substrate for 20 S124

125 Figure S108 HRMS (ESI) of substrate for 20 (m/z: calculated for C 11 H 11 BrO 2 - H + : ) S125

126 Figure H NMR spectrum of substrate for 21 S126

127 Figure C NMR spectrum of substrate for 21 S127

128 Figure 111 HRMS (ESI) of substrate for 21 (m/z: calculated for C 12 H 14 O 2 - H + : ) S128

129 Figure H NMR spectrum of substrate for 22 S129

130 Figure S C NMR spectrum of substrate for 22 S130

131 Figure S114 DEPT-135 spectrum of substrate for 22 S131

132 Figure S115 LRMS (ESI) of substrate for 22 (m/z: calculated for C 15 H 20 O 2 - H + : ) S132

133 Figure H NMR spectrum of substrate for 23 S133

134 Figure S C NMR spectrum of substrate for 23 S134

135 Figure S118 HRMS (ESI) substrate of 23 (m/z: calculated for C 12 H 14 O 3 - H + : ) S135

136 Figure S119 DEPT-135 spectrum of substrate for 23 S136

137 Figure H NMR spectrum of substrate for 24 S137

138 Figure S C NMR spectrum of substrate for 24 S138

139 Figure S122 DEPT-135 spectrum of substrate for 24 S139

140 Figure S123 HRMS (ESI) of substrate for 24 (m/z: calculated for C 12 H 12 O 4 - H + : ) S140

141 Figure S124 1 H NMR of 17 S141

142 Figure S C NMR of 17 S142

143 Figure S126 HRMS (ESI) of 17 (calculated for C 11 H 11 BrO 2 [M + Na] , found ) S143

144 Figure S127 Chiral HPLC chromatogram of 17 S144

145 Figure S128 1 H NMR of 18 S145

146 Figure S C NMR of 18 S146

147 Figure S130 GCMS of 18 (calculated for C 11 H 10 BrFO 2 [M] 271.9, found 271.9) S147

148 Figure S131 Chiral HPLC chromatogram of 18 S148

149 Figure S132 1 H NMR of 19 S149

150 Figure S C NMR of 19 S150

151 Figure S134 GCMS of 19 (Calculated for C 11 H 10 BrClO 2 [M] 287.9, found 287.9) S151

152 Figure S135 Chiral HPLC chromatogram of 19 S152

153 Figure S136 1 H NMR of 20 S153

154 Figure S137 1 H NMR of 20 S154

155 Figure S138 GCMS of 20 (Calculated for C 11 H 10 Br 2 O 2 [M] 333.9, found 333.9) S155

156 Figure S139 Chiral HPLC chromatogram of 20 S156

157 Figure S140 1 H NMR of 21 S157

158 Figure S141 1 H NMR of 21 S158

159 Figure S142 GCMS of 21 (Calculated for C 12 H 13 BrO 2 [M ] 267.9, found 267.9) S159

160 Figure S143 Chiral HPLC chromatogram of 21 S160

161 Figure S144 1 H NMR of 22 S161

162 Figure S C NMR of 22 S162

163 Figure S146 GCMS of 22 (Calculated for C 15 H 19 BrO 2 [M CH 3 ] 295.0, found 295.0) S163

164 Figure S147 Chiral HPLC chromatogram of 22 S164

165 Figure S148 1 H NMR of 23 S165

166 Figure S C NMR of 23 S166

167 Figure S150 GCMS of 23 (Calculated for C 12 H 13 BrO 3 [M] 285.9, found 285.9) S167

168 Figure S151 Chiral HPLC chromatogram of 23 S168

169 Figure S152 1 H NMR of 24 S169

170 Figure S C NMR of 24 S170

171 Figure S154 HRMS (ESI) of 24 (Calculated for C 12 H 11 BrO 4 [M + H] , found ) S171

172 Figure S155 Chiral HPLC chromatogram of 24 S172

173 Figure S156 1 H NMR of 25 S173

174 Figure S C NMR of 25 S174

175 Figure S158 HRMS (ESI) of 25 (Calculated for C 12 H 21 BrO 2 [M + H] , found ) S175

176 Figure S159 Chiral HPLC chromatogram of 25 S176

177 Figure S160 Mass spectrometric analysis of intermediate I between isoselenazolone 7 and NBS m/z: calculated for C 31 H 31 BrN 4 O 4 80 Se : ) S177

178 Data collection, structure solution and refinement: Single crystal X-ray diffraction data of all the compounds were collected at 25 C on a Bruker Apex II D8 Venture diffractometer equipped with CMOS detector. Data reduction and integration were performed by SAINT V7.685A12 and absorption corrections and scaling was done using SADABS. All the crystal structures were solved by direct methods using SIR 92 and refined by the full matrix least squares method using SHELXL97 present in the program suite WinGX. ORTEP diagrams of all the compounds were generated using ORTEP32 and packing diagrams were generated using Mercury software. Geometrical calculations were done using PARST and PLATON. The non-hydrogen atoms were refined anisotropically and the hydrogen atoms bonded to C and N atoms were positioned geometrically and refined using a riding model. TS 2 lists the crystallographic and refinement data of all the compounds. Involved intermolecular interactions in the crystal packing were presented in TS 3. List of selected bond lengths, bond angles and torsion angles were given in TS 4-TS 6 and TS 7-TS 9 for compounds 8 and 20 respectively. Crystallographic modeling of disorder: The ethenyl group at quinine moiety on compounds 8 displays disorder at two positions (major conformer labeled as A ). The associated disorders were refined using PART command in SHELXL97 with occupancy ratio of 0.52(1): 0.48(1) for compound 8. The thermal parameters of involved atoms were constrained to be equal by EADP command in SHELXL 97. The distance and angle restrain DFIX, DANG or SADI were applied in order to model the associated disorder in the ethenyl group. S178

179 TS 2: Crystallographic and Refinement Data: DATA Compound 8 Compound 20 Molecular Formula C 26 H 25 N 3 OSe C 11 H 10 Br 2 O 2 Molecular weight Wavelength CCDC No Solvent system Ethanol Dichloromethane Crystal System Orthorhombic Monoclinic Space Group P P2 1 /a a (Å) (3) (2) b (Å) (4) (8) c (Å) (13) (5) α (⁰) β (⁰) (2) γ (⁰) Volume (Å 3 ) (16) (8) Z 4 4 ρ (g/cm 3 ) μ (mm -1 ) F (000) θ min, max 2.40, , h min,max ;k min,max ; l min,max -8, 8; -12, 12; - 42,42-6, 6; -21, 21; - 13,13 Treatment of hydrogen Fixed Fixed No. of reflections No. unique/ observed 4587/ /1772 reflections. No. of parameters R_all, R_obs , , wr 2 _all, wr 2 _obs , , Δρ min,max (eå -3 ) , , GooF TS 3: List of Intermolecular Interactions D-H A D-H(Å) D A(Å) H A (Å) D-H A ( ) SYMMETRY CODE Compound 8 (P ) C21-H21 O (4) x+1, y, z C12-H12A N (5) x-1/2, -y+3/2, -z Se1 O (2) x+1, y, z S179

180 1) Compound 8: (a) (b) Figure S161 (a) ORTEP of 8 drawn with 50% ellipsoidal properties. Hydrogen atoms were omitted for clarity. (b) Molecular diagram of 8 displaying atom numbering scheme. TS 4: List of Bond length in 8 Se1 N (3) Se1 C (3) O1 C (4) N1 C (5) N1 C (5) N2 C (6) N2 C (4) N2 C (5) N3 C (4) N3 C (4) C1 C (5) C1 C (4) C2 C (4) C2 C (4) C3 C (5) C5 C (5) C5 C (4) C6 C (4) C7 C (5) C8 C (6) C9 C (6) C11 C (5) C12 C (6) C13 C (6) C13 C (8) C14 C (9) C16 C (6) C17 C25A 1.495(12) C18 C (4) C19 C (4) C19 C (5) C20 C (5) C21 C (5) C22 C (5) C23 C (5) C25A C26A 1.269(16) TS 5: List of Bond angles in 8 N3 Se1 C (1) C4 N1 C (3) C15 N2 C (3) C15 N2 C (4) C11 N2 C (3) C18 N3 C (3) C18 N3 Se (2) C1 N3 Se (2) N2 C11 C (3) C1 C11 C (3) C13 C12 C (3) C12 C13 C (4) C12 C13 C (4) C17 C13 C (4) C15 C14 C (4) N2 C15 C (4) S180

181 N3 C1 C (2) N3 C1 C (3) C11 C1 C (2) C3 C2 C (3) C3 C2 C (3) C6 C2 C (3) C2 C3 C (3) N1 C4 C (3) N1 C5 C (3) N1 C5 C (3) C10 C5 C (3) C2 C6 C (3) C2 C6 C (3) C7 C6 C (3) C8 C7 C (4) C7 C8 C (4) C10 C9 C (4) C9 C10 C (4) N2 C11 C (3) N2 C16 C (4) C25A C17 C (7) C25A C17 C (9) C16 C17 C (3) O1 C18 N (3) O1 C18 C (3) N3 C18 C (3) C20 C19 C (3) C20 C19 C (3) C24 C19 C (3) C19 C20 C (3) C19 C20 Se (2) C21 C20 Se (3) C22 C21 C (3) C21 C22 C (3) C24 C23 C (4) C23 C24 C (3) C26A C25A C (15) TS 6: List of Torsion angles in 8 C20 Se1 N3 C18 0.1(3) C20 Se1 N3 C (3) C18 N3 C1 C (3) Se1 N3 C1 C (3) C18 N3 C1 C (3) Se1 N3 C1 C2-63.6(3) N3 C1 C2 C3 89.8(4) C11 C1 C2 C3-36.9(4) N3 C1 C2 C6-89.8(3) C11 C1 C2 C (3) C6 C2 C3 C4-0.2(5) C1 C2 C3 C (3) C5 N1 C4 C3 0.5(6) C2 C3 C4 N1-0.8(6) C4 N1 C5 C (4) C4 N1 C5 C6 0.9(5) C3 C2 C6 C (3) C1 C2 C6 C7 0.5(5) C3 C2 C6 C5 1.3(4) C1 C2 C6 C (3) N1 C5 C6 C2-1.8(5) C10 C5 C6 C (3) N1 C5 C6 C (3) C10 C5 C6 C7-1.3(5) C2 C6 C7 C (4) C5 C6 C7 C8 0.3(5) C6 C7 C8 C9 1.6(7) C7 C8 C9 C10-2.6(8) C12 C13 C14 C (6) C17 C13 C14 C (6) C11 N2 C15 C (6) C16 N2 C15 C (5) C13 C14 C15 N2 3.6(7) C15 N2 C16 C (5) C11 N2 C16 C (5) N2 C16 C17 C25B 130.6(11) N2 C16 C17 C25A 127.6(11) N2 C16 C17 C13 2.5(5) C12 C13 C17 C25B -59.0(10) C14 C13 C17 C25B (9) C12 C13 C17 C25A -79.5(8) C14 C13 C17 C25A 162.9(8) C12 C13 C17 C (5) C14 C13 C17 C (5) C1 N3 C18 O1-4.3(5) Se1 N3 C18 O (3) C1 N3 C18 C (3) Se1 N3 C18 C19 0.5(4) O1 C18 C19 C (4) N3 C18 C19 C20-1.2(5) O1 C18 C19 C24-0.6(6) N3 C18 C19 C (3) C24 C19 C20 C21-0.4(6) C18 C19 C20 C (3) C24 C19 C20 Se (3) C18 C19 C20 Se1 1.3(4) S181

182 C8 C9 C10 C5 1.6(7) N1 C5 C10 C (4) C6 C5 C10 C9 0.3(6) C15 N2 C11 C1 68.6(5) C16 N2 C11 C (3) C15 N2 C11 C (5) C16 N2 C11 C (4) N3 C1 C11 N2 51.5(4) C2 C1 C11 N (3) N3 C1 C11 C (3) C2 C1 C11 C (4) N2 C11 C12 C13-3.3(5) C1 C11 C12 C (4) C11 C12 C13 C (5) C11 C12 C13 C (5) N3 Se1 C20 C19-0.8(3) N3 Se1 C20 C (4) C19 C20 C21 C22 0.5(6) Se1 C20 C21 C (3) C20 C21 C22 C23 0.1(7) C21 C22 C23 C24-0.7(8) C22 C23 C24 C19 0.8(7) C20 C19 C24 C23-0.2(6) C18 C19 C24 C (4) C25B C17 C25A C26A -5(2) C16 C17 C25A C26A 2(3) C13 C17 C25A C26A 128(2) C25A C17 C25B C26B 14.0(19) C16 C17 C25B C26B -160(3) C13 C17 C25B C26B -41(3) Figure S162. Packing view down the ac plane via Se O and C-H O intermolecular interactions in 8. S182

183 Figure S163. Packing of molecules down the bc plane in 8. 2) Compound 20: Figure S164. ORTEP of 20 drawn with 50% ellipsoidal properties with atom numbering scheme. S183

184 TS 7: List of selected bond lengths in 20 Br1 C (14) Br2 C (11) O2 C (14) O2 C (15) O1 C (14) C11 C (17) C3 C (16) C3 C (17) C1 C (17) C1 C (17) C1 C (17) C6 C (16) C4 C (16) C8 C7 1.40(2) C8 C9 1.54(2) C9 C (2) TS 8: List of selected bond angles in 20 C11 O2 C (9) O1 C11 O (11) O1 C11 C (12) O2 C11 C (11) C4 C3 C (11) C2 C1 C (11) C2 C1 C (13) C6 C1 C (14) C1 C2 C (11) C5 C6 C (11) C3 C4 C (11) C3 C4 Br (9) C5 C4 Br (9) C7 C8 C (15) C7 C8 Br (11) C9 C8 Br (11) C6 C5 C (11) C10 C9 C (12) C11 C10 C (13) C8 C7 O (14) C8 C7 C (15) O2 C7 C (10) TS 9: List of selected torsion angles in 20 C7 O2 C11 O (14) C7 O2 C11 C10 4.2(19) C6 C1 C2 C3 2.2(18) C7 C1 C2 C (12) C4 C3 C2 C1-4.1(19) C2 C1 C6 C5-0.5(19) C7 C1 C6 C (12) C2 C3 C4 C5 4.2(18) C2 C3 C4 Br (9) C1 C6 C5 C4 0.6(18) C3 C4 C5 C6-2.5(17) Br2 C4 C5 C (9) C7 C8 C9 C10-15(3) Br1 C8 C9 C (13) O1 C11 C10 C (15) O2 C11 C10 C9 35(2) C8 C9 C10 C11-29(2) C9 C8 C7 O2 52(2) Br1 C8 C7 O (12) C9 C8 C7 C (15) Br1 C8 C7 C1-48(2) C11 O2 C7 C8-48(2) C11 O2 C7 C (12) C2 C1 C7 C8 106(2) C6 C1 C7 C8-76(2) C2 C1 C7 O (14) C6 C1 C7 O2 51(2) S184

185 References (1) Balkrishna S J, Bhakuni B S, Chopra D and Kumar S 2010 Org. Lett (2) Balkrishna S J, Bhakuni B S and Kumar S 2011 Tetrahedron (3) Cassani C, Rapún R M, Arceo E, Bravo F and Melchiorre P 2013 Nature Protocols (4) Wang W, Ma X, Wan J, Cao J and Tang Q 2012 Dalton Trans (5) Tan C K, Zhou L and Yeung Y Y 2011 Org. Lett S185