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

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 17-25 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

(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 842.2 ppm, [α] 28 D -177.0 (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. 1 77 Se NMR 842.7 ppm, [α] 28 D 177.0 (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, 129.76, 129.65, 128.7, 127.9, 127.8, 127.2, 126.2, 124.8, 123.5, 123.4, 120.5, 111.4, 56.2, 49.4, 29.7. 77 Se NMR 825.2 ppm HRMS-ES + m/z: 384.0503 (Calculated for C 20 H 17 NO 80 2 Se + H + : 384.0498). [α] 30 D -92.7 (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 155-157 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), 7.60-7.50 (m, 3H). 7.45 (t, J = 7.7. Hz, 1H), 7.40 (t, J = 7.9 Hz, 1H), 6.21-6.15 (m, 1H), 6.14-6.08 (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, 128.93, 128.87, 128.78, 127.8, 126.8, 126.6, 126.1, 125.2, 123.5, 123.3, 122.8, 45.5, 20.4. HRMS-ES + m/z 355.0856 (calculated for C 19 H 15 ClN 2 O 3 + H + 355.0844). [α] 29 D -84.0 (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 62-64 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

1H), 7.90 (d, J = 8.1 Hz, 1H), 7.80 (d, J = 7.0 Hz, 1H), 7.42-7.63 (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, 128.95, 128.94, 127.3, 127.2, 126.98, 126.3, 125.0, 123.7, 123.1, 48.9, 18.9. 77 Se NMR 839.5 ppm. HRMS-ES + m/z: 399.0230 (Calculated for C 19 H 14 N 2 O 80 3 Se + H + : 399.0243). [α] 29 D +25.5 (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), 7.63-7.47 (m, 8H), 7.42-7.38 (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, 127.8., 126.7, 126.1, 125.95, 125.90, 123.7, 123.2, 116.6, 45.4, 22.2. HRMS-ES + m/z: 551.1314 (Calculated for C 32 H 27 BrN 2 O 2 + H + : 551.1329). [α] 29 D -122.2 (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 94-96 o C. 1 H NMR (400 MHz, CDCl 3 ) 8.06-8.12 (m, 2H), 7.72-7.93 (m, 8H), 7.47-7.55 (m, 2H), 7.35-7.44 (m, 4H), 7.27-7.33 (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 ) 165.52, 165.21, 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, 126.8., 126.7, 126.1, 125.92, 125.88, 125.4, 125.1, 125.05, 123.5, 123.4, 122.95, 122.88, 48.2, 46.0, 36.3, 22.8. 77 Se NMR 836.2 ppm HRMS-ES + m/z: 549.1078 (Calculated for C 32 H 26 N 2 O 80 2 Se - H + : 549.1091). [α] 30 D +130.5 (c = 0.5, CHCl 3 ). S3

(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, 26.0. HRMS-ES + m/z: 324.2078 (Calculated for C 20 H 25 N 3 O + H + : 324.2070). [α] 27 D +52.6 (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 94-96 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, 131.04, 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, 26.3. HRMS-ES + m/z: 554.1300 (Calculated for C 27 H 28 IN 3 O 2 + H + : 554.1299). [α] 28 D +24.4 (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), 7.97-7.93 (m, 1H), 7.47 (t, J = 7.6 Hz, 1H), 7.42-7.22 (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), 3.63-3.53 (m, 1H), 3.28-3.16 (m, 1H), 2.84-2.69 (m, 2H), 2.38-2.27 (m, 1H), 2.0-1.93 (m, 1H), 1.75 (s, 1H), 1.69-1.43 (m, 3H) 13 C S4

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, 27.6. HRMS-ES + m/z: 458.1914 (Calculated for C 27 H 27 N 3 O 2 S + H + : 458.1897). [α] 26 D +76.3 (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 194-196 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, 114.6., 101.8, 58.6, 56.2, 56.0, 53.8, 41.5, 39.5, 29.7, 27.7, 27.6. 77 Se NMR 858.1 ppm. HRMS-ES + m/z: 506.1352 (Calculated for C 27 H 27 N 3 O 80 2 Se + H + : 506.1343). [α] 30 D +49.2 (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, 26.0. HRMS-ES + m/z: 294.1917 (Calculated for C 19 H 23 N 3 + H + : 294.1965). [α] 29 D +87.0 (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 88-90 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

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, 129.03, 129.0, 128.4, 128.0, 126.7, 126.5, 123.6 114.6, 114.4, 92.7, 55.8, 53.6, 46.1, 41.1, 39.5, 27.8, 27.3. HRMS-ES + m/z: 524.1191 (Calculated for C 26 H 26 IN 3 O + H + : 524.1193). [α] 29 D +37.4 (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 56-58 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), 7.96-7.86 (m, 1H), 7.72-7.67 (m, 1H), 7.66-7.59 (m, 1H), 7.49-7.45 (m, 1H), 7.44-7.41 (m, 1H), 7.40-7.36 (m, 1H), 7.29-7.25 (m, 1H), 6.36 (bs, 1H), 5.93-5.75 (m, 1H), 5.07-4.98 (m, 2H), 3.55-3.39 (m, 2H), 3.24 (t, J = 12.0Hz, 1H), 2.84-2.69 (m, 2H), 2,35-2.24 (m, 1H), 1.68 (bs, 2H), 1.25-1.17 (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, 27.6. 77 Se NMR 872.5 ppm. HRMS-ES + m/z: 476.1241 (Calculated for C 26 H 25 N 3 O 80 Se + H + : 476.1237). [α] 30 D +93.4 (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, 24.9. HRMS-ES + m/z: 324.2080 (Calculated for C 20 H 25 N 3 O + H + : 324.2070). [α] 30 D +71.7 (c = 0.5, CHCl 3 ). S6

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 78-80 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), 7.21-7.35 (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), 2.79-3.06 (m, 6H), 2.20-2.30 (m, 1H), 1.38-1.53 (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, 122.02, 121.8, 114.8, 101.7, 92.3, 55.7, 55.5, 49.1, 47.2, 39.0, 29.6, 27.3, 26.6. HRMS-ES + m/z: 554.1298 (Calculated for C 27 H 28 IN 3 O 2 + H + : 554.1299). [α] 26 D +70.0 (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 60-62 o C. 1 H NMR (400 MHz, CDCl 3 ) 8.74 (d, J = 4.6 Hz, 1H), 7.99-7.96 (m, 1H), 7.95 (s, 1H), 7.54-7.49 (m, 1H), 7.45 (t, J = 7.2 Hz, 1H), 7.38 (bs, 1H), 7.34-7.27 (m, 2H), 7.24 (s, 1H), 6.56-6.20 (m, 1H), 5.93-5.77 (m, 1H), 5.18 (d, J = 17.5 Hz, 1H), 5.08 (d, J = 10.9 Hz, 1H), 3.98 (s, 3H), 3.62-3.48 (m, 1H), 3.43-3.30 (m, 1H), 3.01-2.94 (m, 2H), 2.34-2.22 (m, 1H), 1.72 (s, 1H), 1.68-1.55 (m, 3H), 1.51-1.36 (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, 27.2. 77 Se NMR 861.4 ppm. HRMS-ES + m/z: 506.1358 (Calculated for C 27 H 27 N 3 O 80 2 Se + H + : 506.1343). [α] 30 D -11.8 (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

3.30 (bs, 3H), 3.07 (bs, 3H), 2.54 (bs, 3H), 1.94-1.77 (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, 24.6. HRMS-ES + m/z: 913.3839 (Calculated for C 52 H 59 BrN 6 O 4 + H + : 913.3837). [α] 30 D +42.7 (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 160-162 o C. 1 H NMR (400 MHz, CDCl 3 ) 8.73 (d, J = 4.2 Hz, 2H), 8.06-7.90 (m, 5H), 7.71 (bs, 2H), 7.46 (d, J = 4.4 Hz, 2H), 7.37 (dd, J = 9.2, 2.3 Hz, 2H), 5.71-5.63 (m, 2H), 5.0-4.90 (m, 4H), 3.93 (s, 6H), 3.45-3.21 (m, 7H), 2.90 (s, 2H), 2.83 (s, 2H), 2.34 (bs, 3H), 1.76-1.52 (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, 128.7., 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, 14.1. 77 Se NMR 700.6 ppm. HRMS-ES + m/z: 911.3758 (Calculated for C 52 H 58 N 6 O 80 4 Se + H + : 911.3764). [α] 30 D -39.6 (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), 7.20-7.07 (m, 3H), 6.97 (bs, 1H), 5.71-5.60 (m, 1H), 5.05-4.75 (m, 3H), 3.90 (s, 3H), 3.20 (t, J = 12.0 Hz, 2H), 2.80-2.60 (m, 4H), 2.40 (s, 3H), 2.28-2.22 (m, 1H), 1.70-1.50 (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

56.0, 55.8, 53.4, 46.1, 41.3, 39.5, 29.1, 27.9, 27.4, 10.5. HRMS-ES + m/z: 568.1468 (Calculated for C 28 H 30 IN 3 O 2 + H + : 568.1455). [α] 28 D +64.4 (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), 8.0-7.85 (m, 3H), 7.80-7.73 (m, 1H), 7.37-7.31 (m, 1H), 7.30-7.26 (m, 1H), 7.23-7.20 (m, 1H), 6.48 6.26 (m, 1H), 6.03-5.81 (m, 1H), 5.12-4.99 (m, 2H), 3.95 (s, 3H), 3.70--3.49 (m, 2H), 3.24 (t, J = 11.8 Hz, 1H), 2.88 (s, 2H), 2.30 (bs, 1H), 2.14 (s, 3H), 1.74-1.68 (m, 1H), 1.62-1.52 (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, 20.2. 77 Se NMR 835.1 ppm. HRMS-ES + m/z: 520.1484 (Calculated for C 28 H 29 N 3 O 2 Se + H + : 520.1499). [α] 30 D +124.6 (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), 7.50-7.30 (m, 4H), 7.0 (s, 1H), 6.80 (dd, J = 8.7, 2.5 Hz, 1H), 5.80-5.60 (m, 1H), 5.10-4.80 (m, 3H), 3.90 (s, 3H), 3.70 (s, 3H), 3.27-3.19 (m, 2H), 2.70 (m, 3H), 2.30 (s, 1H), 1.68-1..58 (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, 27.4. HRMS-ES + m/z: 536.1538 (Calculated for C 28 H 30 BrN 3 O 3 + H + : 536.1543). [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 190-192 o C. 1 H S9

NMR (400 MHz, CDCl 3 ) 8.77 (s, 1H), 8.05-7.85 (m, 2H), 7.45-7.30 (m, 4H), 7.15-7.02 (s, 1H), 6.50-6.20 (m, 1H), 6.05-5.80 (m, 1H), 5.20-5.0 (m, 2H), 4.0 (s, 3H), 3.80 (s, 3H), 3.60 (s, 2H), 3.27 (t, J = 12.0 Hz, 1H), 2.85-2.70 (m, 2H), 2.35 (s, 1H), 1.90 (s, 1H), 1.80-1.50 (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, 27.6. 77 Se NMR 867.6 ppm. HRMS-ES + m/z: 536.1451 (Calculated for C 28 H 29 N 3 O 3 Se + H + : 536.1449). [α] 29 D +120.7 (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 94-96 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), 5.05-4.80 (m, 3H), 3.94 (s, 3H), 3.82 (s, 3H), 3.74 (s, 3H), 3.28-3.18 (m, 2H), 2.80-2.56 (m, 4H), 2.30 (bs, 1H), 1.70-1.50 (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, 26.1. HRMS-ES + m/z: 568.1703 (Calculated for C 29 H 32 BrN 3 O 4 + H + : 568.1630). [α] 30 D -34.2 (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 182-184 o C. 1 H NMR (400 MHz, CDCl 3 ) 8.80 (d, J = 4.3 Hz, 1H), 8.0-7.90 (m, 2H), 7.40-7.27 (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), 3.62-3.50 (m, 2H), 3.27 (t, J = 12.0 Hz, 1H), 2.80-2.70 (m, 2H), 2.33 (bs, 1H), 1.90 (bs, 1H), 1.74 (s, 1H), 1.70-1.45 (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

58.7, 56.2, 56.1, 55.9, 41.5, 39.5, 36.4, 31.4, 29.6, 27.7, 27.6. 77 Se NMR 859.0 ppm. HRMS- ES + m/z: 566.1532 (Calculated for C 29 H 31 N 3 O 4 Se + H + : 566.1554). [α] 29 D +50.3 (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 84-86 o C. 1 H NMR (400 MHz, CDCl 3 ) 8.66 (d, J = 4.5 Hz, 1H), 8.03-7.95 (m, 1H), 7.75 (bs, 1H), 7.66 (s, 1H), 7.38-7.25 (m, 4H), 5.68 (quintet, J = 8.7 Hz, 1H), 5.06-4.80 (m, 3H), 3.94 (s, 3H), 3.35-3.30 (m, 4H), 2.75-2.65 (m, 2H), 2.25 (s, 1H), 1.70-1..57 (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, 26.2. HRMS-ES + m/z: 544.1334 (Calculated for C 27 H 26 BrF 2 N 3 O 2 + H + : 544.1230). [α] 28 D -23.3 (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 196-198 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), 7.90-7.76 (m, 1H), 7.75-7.65 (m, 1H), 7.52-7.27 (m, 3H), 6.25 (s, 1H), 6.0--5.80 (m, 1H), 5.15-4.95 (m, 2H), 3.98 (bs, 3H), 3.62-3.35 (m, 2H), 3.26 (t, J = 11.4 Hz, 1H), 2.84-2.65 (m, 2H), 2.40-2.28 (m, 1H), 2.05-1.92 (m, 1H), 1.90-1..77 (m, 1H), 1.70-1.42 (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, 131.99, 131.97, 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, 22.6. HRMS-ES + m/z: 542.1156 (Calculated for C 27 H 25 F 2 N 3 O 2 Se + H + : 542.1154). S11

(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, 27.9. HRMS-ES + m/z: 175.0773 (Calculated for C 11 H 12 O - 2 H + : 175.0754). (E)-5-(4-Fluorophenyl)pent-4-enoic acid (Substrate for 18): 5 1 H NMR (400 MHz, CDCl 3 ) 10.20 (bs, 1H), 7.32-7.25 (m, 2H), 6.97 (t, J = 8.7 Hz, 2H), 6.39 (d, J = 15.8 Hz, 1H), 6.16-6.05 (m, 1H), 2.55-2.49 (m, 4H) 13 C NMR (100 MHz, CDCl 3 ) 179.1, 163.1, 160.1, 133.5, 133.4, 130.1, 127.8, 127.75, 127.6, 127.5, 115.5, 115.3, 33.8, 27.8. HRMS-ES + m/z: 193.0674 (Calculated for C 11 H 11 FO - 2 H + : 193.0659). (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), 6.22-6.12 (m, 1H), 2.57-2.50 (m, 4H) 13 C NMR (100 MHz, CDCl 3 ) 179.1, 135.7, 132.8, 130.1, 128.71, 128.67, 127.3, 33.6, 27.8. HRMS-ES + m/z: 209.0380 (Calculated for C 11 H 11 ClO - 2 H + : 209.0364). (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), 6.25-6.13 (m, 1H),, 2.56-2.49 (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, 27.9. HRMS-ES + m/z: 252.9853 (Calculated for C 11 H 11 BrO 2 - H + : 252.9859). (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), 6.20-6.10 (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, 21.2. HRMS-ES + m/z: 189.0905 (Calculated for C 12 H 14 O - 2 H + : 189.0910). S12

(E)-5-(4-(tert-Butyl)phenyl)pent-4-enoic acid (Substrate for 22): 5 1 H NMR (400 MHz, CDCl 3 ) 7.33-7.24 (m, 4H), 6.42 (d, J = 15.9 Hz, 1H), 6.20-6.10 (m, 1H), 2.57-2.48 (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, 27.9. LRMS-ES + m/z: 231.1431 (Calculated for C 15 H 20 O - 2 H + : 231.1380). (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), 6.10-6.0 (m, 1H), 3.78 (s, 3H), 2.53-2.49 (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, 27.8. HRMS-ES + m/z: 205.0884 (Calculated for C 12 H 14 O 3 - H + : 205.0859). (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), 6.77-6.70 (m, 2H), 6.34 (d, J = 15.7 Hz, 1H), 6.06-5.98 (m, 1H), 5.92 (s, 2H), 2.53-2.47 (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, 27.8. HRMS-ES + m/z: 219.0669 (Calculated for C 12 H 12 O - 4 H + : 219.0652). (5R,6S)-5-Bromo-6-phenyltetrahydro-2H-pyran-2-one (17): 5 White solid, mp 114-116 C; 1 H NMR (400 MHz, CDCl 3 ) 7.42-7.35 (m, 3H), 7.33-7.28 (m, 2H), 5.54 (d, J = 6.4 Hz, 1H), 4.36 (q, J = 5.7 Hz, 1H), 3.0-2.90 (m, 1H), 2.76-2.65 (m, 1H), 2.46-2.35 (m, 1H), 2.30-2.20 (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] 276.9835, found 276.9836. 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 105-107 C; 1 H NMR (400 MHz, CDCl 3 ) 7.34-7.27 (m, 2H), 7.08 (t, J = 8.6 Hz, 2H), 5.46 (d, J = S13

7.4 Hz, 1H), 4.31-4.23 (m, 1H), 2.98-2.84 (m, 1H), 2.75-2.63 (m, 1H), 2.50-2.39 (m, 1H), 2.37-2.24 (m, 1H) 13 C NMR (100 MHz, CDCl 3 ) 168.9, 164.2, 161.8, 133.04, 133.01, 128.6, 128.5, 115.9, 115.7, 84.9, 46.9, 28.8, 28.4; GCMS (ESI) m/z: 271.9 (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 110-112 C; 1 H NMR (400 MHz, CDCl 3 ) 7.39-7.35 (m, 2H), 7.27-7.23 (m, 2H), 5.46 (d, J = 7.2 Hz, 1H), 4.30-4.23 (m, 1H), 2.98-2.86 (m, 1H), 2.75-2.64 (m, 1H), 2.48-2.38 (m, 1H), 2.35-2.25 (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: 287.9 (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 116-118 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), 4.30-4.22 (m, 1H), 2.97-2.87 (m, 1H), 2.75-2.65 (m, 1H), 2.48-2.38 (m, 1H), 2.35-2.26 (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: 333.9 (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), 4.39-4.32 (m, 1H), 2.97-2.87 (m, 1H), 2.73-2.64 (m, 1H), 2.46-2.37 (m, 1H), 2.35 (s, 3H), 2.29-2.21 (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

21.0; GCMS (ESI) m/z: 267.9 (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 ) 7.42-7.37 (m, 2H), 7.24-7.20 (m, 2H), 5.55 (d, J = 6.0 Hz, 1H), 4.43-4.36 (m, 1H), 2.99-2.87 (m, 1H), 2.74-2.63 (m, 1H), 2.45-2.34 (m, 1H), 2.28-2.18 (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: 295.0 (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 84-86 C; 1 H NMR (400 MHz, CDCl 3 ) 7.26-7.21 (m, 2H), 6.93-6.84 (m, 2H), 5.46 (d, J = 6.9 Hz, 1H), 4.35-4.28 (m, 1H), 3.80 (s, 3H), 2.97-2.86 (m, 1H), 2.74-2.63 (m, 1H), 2.49-2.38 (m, 1H), 2.32-2.23 (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: 285.9 (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 ) 6.81-6.76 (m, 3H), 5.98 (s, 2H), 5.40 (d, J = 7.0 Hz, 1H), 4.28 (q, J = 6.3 Hz, 1H), 2.96-2.84 (m, 1H), 2.73-2.62 (m, 1H), 2.50-2.40 (m, 1H), 2.33-2.22 (m, 1H) 13 C NMR (100 MHz, CDCl 3 ) 169.05, 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: 298.9902 (calculated for C 12 H 11 BrO 4 [M + H] 298.9913). 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

(R)-6-((R)-1-Bromoheptyl)tetrahydro-2H-pyran-2-one (25): Colorless oil. 1 H NMR (400 MHz, CDCl 3 ) 4.42-4.34 (m, 1H), 4.03-3.96 (m, 1H), 2.65-2.56 (m, 1H), 2.50-2.39 (m,1h), 2.05-1.80 (m, 7H), 1.63-1.50 (m, 1H), 1.31-1.21 (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: 277.0804 (calculated for C 12 H 21 BrO 2 [M + H] 277.0798). 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 - 82 6% 2 Toluene - 65 15% 3 Tetrahydrofuran - 72-13% 4 Diethyl ether - 85 4% 5 Dichloro ethane - 81 30% 6 DCM : Toluene (1:1) - 72 26% 7 DCM : Hexane (1:1) - 67 33% 8 DCM : Acetone (1:1) - 53 13% 9 Trifluoro ethanol - 43-10 Hexafluoro isopropanol - 70-11 c DCM - 82 28% 12 d DCM - 84 32% 13 e DCM - 76 34% 14 f DCM - 82 20% 15 DCM quininamine (100 mol %) 57-25% 16 DCM quinidinamine (100 mol %) 51 8% 17 DCM Benzoic acid (100 mol %) 74 44 18 DCM NsNH 2 (50 mol %) 45 29 S16

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

Figure S1 77 Se NMR of 1 S18

Figure S2 77 Se NMR of 2 S19

Figure S3 1 H NMR of 3 S20

Figure S4 13 C NMR of 3 S21

Figure S5 77 Se NMR of 3 S22

Figure S6 HRMS (ESI) of 3 (m/z 384.0503, calcd for C 20 H 17 NO 2 Se + H + : 384.0498) S23

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

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

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

Figure S10 1 H NMR of 4 S27

Figure S11 13 C NMR of 4 S28

Figure S12 77 Se NMR of 4 S29

Figure S13 HRMS (ESI) of 4 (m/z 399.0230, calcd for C 19 H 14 N 2 O 3 Se + H + : 399.0243) S30

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

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

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

Figure S17 1 H NMR of 5 S34

Figure S18 13 C NMR of 5 S35

Figure S19 77 Se NMR 5 S36

Figure S20 HRMS (ESI) of 5 (m/z 549.1091, calcd for C 32 H 26 N 2 O 2 Se - H + : 549.1078) S37

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

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

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

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

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

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

Figure S27 1 H NMR of 6 S44

Figure S28 13 C NMR of 6 S45

Figure S29 HRMS (ESI) of 6 (m/z: 458.1914 calculated for C 27 H 27 N 3 O 2 S + H + : 458.1897) S46

Figure S30 1 H NMR of 7 S47

Figure S31 13 C NMR of 7 S48

Figure S32 77 Se NMR of 7 S49

Figure S33 HRMS (ESI) of 7 (m/z: 506.1352 calculated for C 27 H 27 N 3 O 2 80 Se + H + : 506.1343) S50

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

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

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

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

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

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

Figure S40 1 H NMR of 8 S57

Figure S41 13 C NMR of 8 S58

Figure S42 77 Se NMR of 8 S59

Figure S43 HRMS (ESI) of 8 (m/z: 476.1241 calculated for C 26 H 25 N 3 O 80 Se + H + : 476.1237) S60

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

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

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

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

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

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

Figure S50 1 H NMR of 9 S67

Figure S51 13 C NMR of 9 S68

Figure S52 77 Se NMR 9 S69

Figure S53 HRMS (ESI) of 9 (m/z: 506.1358 calculated for C 27 H 27 N 3 O 2 80 Se + H + : 506.1343) S70

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

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

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

Figure S57 1 H NMR of 10 S74

Figure S58 13 C NMR of 10 S75

Figure S59 77 Se NMR of 10 S76

Figure S60 HRMS (ESI) of 10 S77

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

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

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

Figure S64 1 H NMR of 11 S81

Figure S65 13 C NMR of 11 S82

Figure S66 77 Se NMR 11 S83

Figure S67 HRMS (ESI) of 11 (m/z: 520.1484 calculated for C 28 H 29 N 3 O 2 Se + H + : 520.1499) S84

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

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

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

Figure S71 1 H NMR of 12 S88

Figure S72 13 C NMR of 12 S89

Figure S73 HRMS (ESI) of 12 (m/z: 536.1451 calculated for C 28 H 29 N 3 O 3 Se + H + : 536.1449). S90

Figure S74 77 Se NMR of 12 S91

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

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

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

Figure S78 1 H NMR of 13 S95

Figure S79 13 C NMR of 13 S96

Figure S80 77 Se NMR 13 S97

Figure S81 HRMS (ESI) of 13 S98

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

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

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

Figure S85 1 H NMR of 14 S102

Figure S86 13 C NMR of 14 S103

Figure S87 HRMS (ESI) of 14 (m/z: 542.1156 calculated for C 27 H 25 F 2 N 3 O 2 Se + H + : 542.1154) S104

Figure S88 1 H NMR of 15 S105

Figure S89 13 C NMR of 15 S106

Figure S90 77 Se NMR of 15 S107

Figure S91 HRMS (ESI) of 15 (m/z: 522.1658 calculated for C 28 H 31 N 3 O 2 80 Se + H + : 522.1656) S108

Figure S92 1 H NMR of 16 S109

Figure S93 13 C NMR of 16 S110

Figure S94 HRMS (ESI) of 16 (m/z: 1013.2789 calculated for C 54 H 56 N 6 O 4 80 Se 2 + H + : 1013.2780) S111

Figure 95 1 H NMR spectrum for substrate of 17 S112

Figure 96 13 C NMR spectrum for substrate of 17 S113

Figure S97 HRMS (ESI) substrate of 17 (m/z: 175.0773 calculated for C 11 H 12 O 2 - H + : 175.0754) S114

Figure 98 1 H NMR spectrum for substrate of 18 S115

Figure S99 13 C NMR spectrum for substrate of 18 S116

Figure S100 HRMS (ESI) of substrate for 18 (m/z: 193.0674 calculated for C 11 H 11 FO 2 - H + : 193.0659) S117

Figure 101 1 H NMR spectrum of substrate for 19 S118

Figure S102 13 C NMR spectrum of substrate for 19 S119

Figure S103 DEPT-135 spectrum of substrate for 19 S120

Figure S104 HRMS (ESI) of substrate for 19 (m/z: 209.0380 calculated for C 11 H 11 ClO 2 - H + : 209.0364) S121

Figure 105 1 H NMR spectrum of substrate for 20 S122

Figure S106 13 C NMR spectrum of substrate for 20 S123

Figure S107 DEPT-135 spectrum of substrate for 20 S124

Figure S108 HRMS (ESI) of substrate for 20 (m/z: 252.9853 calculated for C 11 H 11 BrO 2 - H + : 252.9859) S125

Figure 109 1 H NMR spectrum of substrate for 21 S126

Figure 110 13 C NMR spectrum of substrate for 21 S127

Figure 111 HRMS (ESI) of substrate for 21 (m/z: 189.0905 calculated for C 12 H 14 O 2 - H + : 189.0910) S128

Figure 112 1 H NMR spectrum of substrate for 22 S129

Figure S113 13 C NMR spectrum of substrate for 22 S130

Figure S114 DEPT-135 spectrum of substrate for 22 S131

Figure S115 LRMS (ESI) of substrate for 22 (m/z: 231.1431 calculated for C 15 H 20 O 2 - H + : 231.1380) S132

Figure 116 1 H NMR spectrum of substrate for 23 S133

Figure S117 13 C NMR spectrum of substrate for 23 S134

Figure S118 HRMS (ESI) substrate of 23 (m/z: 205.0884 calculated for C 12 H 14 O 3 - H + : 205.0859) S135

Figure S119 DEPT-135 spectrum of substrate for 23 S136

Figure 120 1 H NMR spectrum of substrate for 24 S137

Figure S121 13 C NMR spectrum of substrate for 24 S138

Figure S122 DEPT-135 spectrum of substrate for 24 S139

Figure S123 HRMS (ESI) of substrate for 24 (m/z: 219.0669 calculated for C 12 H 12 O 4 - H + : 219.0652) S140

Figure S124 1 H NMR of 17 S141

Figure S125 13 C NMR of 17 S142

Figure S126 HRMS (ESI) of 17 (calculated for C 11 H 11 BrO 2 [M + Na] 276.9835, found 276.9836) S143

Figure S127 Chiral HPLC chromatogram of 17 S144

Figure S128 1 H NMR of 18 S145

Figure S129 13 C NMR of 18 S146

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

Figure S131 Chiral HPLC chromatogram of 18 S148

Figure S132 1 H NMR of 19 S149

Figure S133 13 C NMR of 19 S150

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

Figure S135 Chiral HPLC chromatogram of 19 S152

Figure S136 1 H NMR of 20 S153

Figure S137 1 H NMR of 20 S154

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

Figure S139 Chiral HPLC chromatogram of 20 S156

Figure S140 1 H NMR of 21 S157

Figure S141 1 H NMR of 21 S158

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

Figure S143 Chiral HPLC chromatogram of 21 S160

Figure S144 1 H NMR of 22 S161

Figure S145 13 C NMR of 22 S162

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

Figure S147 Chiral HPLC chromatogram of 22 S164

Figure S148 1 H NMR of 23 S165

Figure S149 13 C NMR of 23 S166

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

Figure S151 Chiral HPLC chromatogram of 23 S168

Figure S152 1 H NMR of 24 S169

Figure S153 13 C NMR of 24 S170

Figure S154 HRMS (ESI) of 24 (Calculated for C 12 H 11 BrO 4 [M + H] 298.9913, found 298.9902) S171

Figure S155 Chiral HPLC chromatogram of 24 S172

Figure S156 1 H NMR of 25 S173

Figure S157 13 C NMR of 25 S174

Figure S158 HRMS (ESI) of 25 (Calculated for C 12 H 21 BrO 2 [M + H] 277.0798, found 277.0804) S175

Figure S159 Chiral HPLC chromatogram of 25 S176

Figure S160 Mass spectrometric analysis of intermediate I between isoselenazolone 7 and NBS m/z: 681.9652 calculated for C 31 H 31 BrN 4 O 4 80 Se : 682.0684) S177

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

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 474.45 334.01 Wavelength 0.71073 0.71073 CCDC No. 930743 930740 Solvent system Ethanol Dichloromethane Crystal System Orthorhombic Monoclinic Space Group P2 1 2 1 2 1 P2 1 /a a (Å) 6.7354(3) 5.6772(2) b (Å) 9.8135(4) 18.4085(8) c (Å) 33.7695(13) 11.1037(5) α (⁰) 90 90 β (⁰) 90 94.925(2) γ (⁰) 90 90 Volume (Å 3 ) 2232.09(16) 1156.15(8) Z 4 4 ρ (g/cm 3 ) 1.412 1.919 μ (mm -1 ) 1.705 6.988 F (000) 976 648 θ min, max 2.40, 26.50 2.21, 25.00 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. 33402 18599 No. unique/ observed 4587/4025 2034/1772 reflections. No. of parameters 281 136 R_all, R_obs 0.0482, 0.0388 0.1005, 0.0911 wr 2 _all, wr 2 _obs 0.0907, 0.0875 0.1838, 0.1803 Δρ min,max (eå -3 ) -0.236, 0.677-0.897, 0.996 GooF 1.108 1.229 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 (P2 1 2 1 2 1 ) C21-H21 O1 0.93 3.197(4) 2.45 137 x+1, y, z C12-H12A N1 0.97 3.438(5) 2.68 135 x-1/2, -y+3/2, -z Se1 O1 3.000(2) x+1, y, z S179

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 N3 1.865(3) Se1 C20 1.882(3) O1 C18 1.228(4) N1 C4 1.293(5) N1 C5 1.357(5) N2 C15 1.428(6) N2 C11 1.461(4) N2 C16 1.475(5) N3 C18 1.363(4) N3 C1 1.460(4) C1 C11 1.532(5) C1 C2 1.535(4) C2 C3 1.365(4) C2 C6 1.414(4) C3 C4 1.416(5) C5 C10 1.398(5) C5 C6 1.426(4) C6 C7 1.416(4) C7 C8 1.355(5) C8 C9 1.396(6) C9 C10 1.337(6) C11 C12 1.539(5) C12 C13 1.507(6) C13 C17 1.528(6) C13 C14 1.534(8) C14 C15 1.518(9) C16 C17 1.518(6) C17 C25A 1.495(12) C18 C19 1.464(4) C19 C20 1.380(4) C19 C24 1.395(5) C20 C21 1.386(5) C21 C22 1.375(5) C22 C23 1.382(5) C23 C24 1.369(5) C25A C26A 1.269(16) TS 5: List of Bond angles in 8 N3 Se1 C20 85.5(1) C4 N1 C5 117.3(3) C15 N2 C11 111.7(3) C15 N2 C16 107.5(4) C11 N2 C16 107.1(3) C18 N3 C1 122.6(3) C18 N3 Se1 115.9(2) C1 N3 Se1 121.4(2) N2 C11 C12 111.2(3) C1 C11 C12 111.3(3) C13 C12 C11 108.6(3) C12 C13 C17 110.2(4) C12 C13 C14 107.7(4) C17 C13 C14 108.1(4) C15 C14 C13 107.4(4) N2 C15 C14 113.4(4) S180

N3 C1 C11 112.7(2) N3 C1 C2 109.9(3) C11 C1 C2 112.9(2) C3 C2 C6 118.5(3) C3 C2 C1 121.3(3) C6 C2 C1 120.2(3) C2 C3 C4 118.8(3) N1 C4 C3 125.0(3) N1 C5 C10 117.7(3) N1 C5 C6 122.7(3) C10 C5 C6 119.5(3) C2 C6 C7 125.7(3) C2 C6 C5 117.7(3) C7 C6 C5 116.6(3) C8 C7 C6 121.4(4) C7 C8 C9 121.0(4) C10 C9 C8 119.4(4) C9 C10 C5 122.0(4) N2 C11 C1 110.8(3) N2 C16 C17 112.9(4) C25A C17 C16 126.1(7) C25A C17 C13 105.5(9) C16 C17 C13 107.4(3) O1 C18 N3 123.9(3) O1 C18 C19 125.2(3) N3 C18 C19 111.0(3) C20 C19 C24 119.2(3) C20 C19 C18 115.4(3) C24 C19 C18 125.4(3) C19 C20 C21 121.3(3) C19 C20 Se1 112.1(2) C21 C20 Se1 126.6(3) C22 C21 C20 118.4(3) C21 C22 C23 121.1(3) C24 C23 C22 120.2(4) C23 C24 C19 119.8(3) C26A C25A C17 121.5(15) TS 6: List of Torsion angles in 8 C20 Se1 N3 C18 0.1(3) C20 Se1 N3 C1-176.0(3) C18 N3 C1 C11-112.6(3) Se1 N3 C1 C11 63.3(3) C18 N3 C1 C2 120.6(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 C6 143.5(3) C6 C2 C3 C4-0.2(5) C1 C2 C3 C4-179.8(3) C5 N1 C4 C3 0.5(6) C2 C3 C4 N1-0.8(6) C4 N1 C5 C10-179.2(4) C4 N1 C5 C6 0.9(5) C3 C2 C6 C7-179.1(3) C1 C2 C6 C7 0.5(5) C3 C2 C6 C5 1.3(4) C1 C2 C6 C5-179.1(3) N1 C5 C6 C2-1.8(5) C10 C5 C6 C2 178.3(3) N1 C5 C6 C7 178.7(3) C10 C5 C6 C7-1.3(5) C2 C6 C7 C8-179.2(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 C15 61.4(6) C17 C13 C14 C15 57.7(6) C11 N2 C15 C14 55.6(6) C16 N2 C15 C14-61.6(5) C13 C14 C15 N2 3.6(7) C15 N2 C16 C17 58.3(5) C11 N2 C16 C17-61.9(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 -176.5(9) C12 C13 C17 C25A -79.5(8) C14 C13 C17 C25A 162.9(8) C12 C13 C17 C16 57.1(5) C14 C13 C17 C16-60.4(5) C1 N3 C18 O1-4.3(5) Se1 N3 C18 O1 179.7(3) C1 N3 C18 C19 176.6(3) Se1 N3 C18 C19 0.5(4) O1 C18 C19 C20 179.7(4) N3 C18 C19 C20-1.2(5) O1 C18 C19 C24-0.6(6) N3 C18 C19 C24 178.5(3) C24 C19 C20 C21-0.4(6) C18 C19 C20 C21 179.3(3) C24 C19 C20 Se1-178.4(3) C18 C19 C20 Se1 1.3(4) S181

C8 C9 C10 C5 1.6(7) N1 C5 C10 C9-179.6(4) C6 C5 C10 C9 0.3(6) C15 N2 C11 C1 68.6(5) C16 N2 C11 C1-173.9(3) C15 N2 C11 C12-55.7(5) C16 N2 C11 C12 61.7(4) N3 C1 C11 N2 51.5(4) C2 C1 C11 N2 176.7(3) N3 C1 C11 C12 175.8(3) C2 C1 C11 C12-59.0(4) N2 C11 C12 C13-3.3(5) C1 C11 C12 C13-127.3(4) C11 C12 C13 C17-57.0(5) C11 C12 C13 C14 60.7(5) N3 Se1 C20 C19-0.8(3) N3 Se1 C20 C21-178.7(4) C19 C20 C21 C22 0.5(6) Se1 C20 C21 C22 178.2(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 C23-179.9(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

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

TS 7: List of selected bond lengths in 20 Br1 C8 1.942(14) Br2 C4 1.889(11) O2 C11 1.351(14) O2 C7 1.439(15) O1 C11 1.212(14) C11 C10 1.472(17) C3 C4 1.356(16) C3 C2 1.376(17) C1 C2 1.368(17) C1 C6 1.373(17) C1 C7 1.485(17) C6 C5 1.367(16) C4 C5 1.383(16) C8 C7 1.40(2) C8 C9 1.54(2) C9 C10 1.49(2) TS 8: List of selected bond angles in 20 C11 O2 C7 119.4(9) O1 C11 O2 117.0(11) O1 C11 C10 125.8(12) O2 C11 C10 117.3(11) C4 C3 C2 120.8(11) C2 C1 C6 119.8(11) C2 C1 C7 117.4(13) C6 C1 C7 122.8(14) C1 C2 C3 119.6(11) C5 C6 C1 120.3(11) C3 C4 C5 119.5(11) C3 C4 Br2 119.8(9) C5 C4 Br2 120.7(9) C7 C8 C9 117.0(15) C7 C8 Br1 116.7(11) C9 C8 Br1 110.2(11) C6 C5 C4 119.8(11) C10 C9 C8 111.0(12) C11 C10 C9 115.9(13) C8 C7 O2 110.0(14) C8 C7 C1 118.5(15) O2 C7 C1 109.3(10) TS 9: List of selected torsion angles in 20 C7 O2 C11 O1-174.3(14) C7 O2 C11 C10 4.2(19) C6 C1 C2 C3 2.2(18) C7 C1 C2 C3-179.5(12) C4 C3 C2 C1-4.1(19) C2 C1 C6 C5-0.5(19) C7 C1 C6 C5-178.7(12) C2 C3 C4 C5 4.2(18) C2 C3 C4 Br2-177.6(9) C1 C6 C5 C4 0.6(18) C3 C4 C5 C6-2.5(17) Br2 C4 C5 C6 179.3(9) C7 C8 C9 C10-15(3) Br1 C8 C9 C10-151.3(13) O1 C11 C10 C9-146.3(15) O2 C11 C10 C9 35(2) C8 C9 C10 C11-29(2) C9 C8 C7 O2 52(2) Br1 C8 C7 O2-174.4(12) C9 C8 C7 C1 178.8(15) Br1 C8 C7 C1-48(2) C11 O2 C7 C8-48(2) C11 O2 C7 C1-179.6(12) C2 C1 C7 C8 106(2) C6 C1 C7 C8-76(2) C2 C1 C7 O2-127.1(14) C6 C1 C7 O2 51(2) S184

References (1) Balkrishna S J, Bhakuni B S, Chopra D and Kumar S 2010 Org. Lett. 12 5394. (2) Balkrishna S J, Bhakuni B S and Kumar S 2011 Tetrahedron 67 9565. (3) Cassani C, Rapún R M, Arceo E, Bravo F and Melchiorre P 2013 Nature Protocols 8 325. (4) Wang W, Ma X, Wan J, Cao J and Tang Q 2012 Dalton Trans. 41 5715. (5) Tan C K, Zhou L and Yeung Y Y 2011 Org. Lett.13 2738. S185