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Organocatalytic Oxidative Enamine Catalysis and 1,5-Hydride Transfer/Cyclization: Synthesis of Tetrahydroquinoline Derivatives
Organocatalytic Oxidative Enamine Catalysis and 1,5-Hydride Transfer/Cyclization: Synthesis of Tetrahydroquinoline Derivatives
Bulletin of the Korean Chemical Society. 2013. Dec, 34(12): 3891-3894
Copyright © 2013, Korea Chemical Society
  • Received : August 05, 2013
  • Accepted : September 20, 2013
  • Published : December 20, 2013
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Mi Hyun Kim
Dae Young Kim

Abstract
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Experimental
General Procedure for the Synthesis of Tetrahydroquinoline Derivatives 2: To a stirred solution of 3-( o -(dialkylamino) aryl)propanals 1 (0.3 mmol) in CH 2 Cl 2 (1.0 mL) was added DDQ (68.1 mg, 0.3 mmol), racemic diarylprolinol silylether catalyst III (35.9 mg, 0.06 mmol), and DNBS (14.9 mg, 0.06 mmol). The mixture was refluxed for 0.5-7 d, diluted with saturated NaHCO 3 solution (10 mL) and extracted with ethyl acetate (2 × 15 mL). The combined organic layers were dried over MgSO 4 , filtered, concentrated, and purified by flash chromatography (EtOAc/hexane = 1:10) to afford tetrahydroquinoline derivatives 2 .
6R,6aS)-5,6,6a,7,8,9,10,11,12,13-Decahydroazonino[1,2- a]quinoline-6-carbaldehyde (2a): Major diastereomer; 1 H NMR (400 MHz, CDCl 3 ) δ 9.83 (d, J = 0.8 Hz, 1H), 7.14- 7.07 (m, 2H), 6.80-6.77 (m, 1H), 6.70 (td, J = 7.2 Hz, 1.2 Hz, 1H), 3.76 (dt, J = 10.8 Hz, 2.4 Hz, 1H), 3.67 (ddd, J = 14.8 Hz, 8.0 Hz, 3.6 Hz, 1H), 3.22 (ddd, J = 14.8 Hz, 6.8 Hz, 3.6 Hz, 1H), 3.05-2.98 (m, 1H), 2.87 (dd, J = 16.8 Hz, 5.6 Hz, 1H), 2.70-2.65 (m, 1H), 1.84-1.10 (m, 12H); 13 C NMR (100 MHz, CDCl 3 ) δ 203.21, 144.97, 129.77, 127.35, 120.33, 117.04, 115.24, 58.88, 56.79, 48.00, 28.87, 27.62, 27.25, 25.44, 25.09, 24.74, 23.33; EI-MS: m/z 258.1 [M+H] + ; ESIHRMS: m/z calcd for C 17 H 24 NO [M+H] + : 258.1861; found 258.1858.
(6R,6aR)-6,6a,7,8,9,10,11,12-Octahydro-5H-azocino[1,2- a]quinoline-6-carbaldehyde (2b): Major diastereomer; 1 H NMR (400 MHz, CDCl 3 ) δ 9.50 (d, J = 0.4 Hz, 1H), 7.08- 7.03 (m, 2H, 6.61-6.54 (m, 2H), 3.84-3.79 (m, 2H), 3.24- 3.21 (m, 1H), 3.20-3.06 (m, 2H), 2.54-2.51 (m, 1H), 2.01- 1.32 (m, 10H); 13 C NMR (100 MHz, CDCl 3 ) δ 203.32, 143.98, 129.52, 127.54, 117.37, 115.53, 111.33, 55.45, 53.15, 48.65, 33.90, 27.82, 26.91, 26.26, 26.09, 24.17; EI-MS: m/z 244.1 [M+H] + ; ESI-HRMS: m/z calcd for C 16 H 22 NO [M+H] + : 244.1701; found 244.1697.
(6R,6aS)-5,6,6a,7,8,9,10,11-Octahydroazepino[1,2-a]quinoline- 6-carbaldehyde (2c): Major diastereomer; 1 H NMR (400 MHz, CDCl 3 ) δ 9.55 (s, 1H), 7.06-7.01 (m, 2H), 6.52- 6.54 (m, 1H), 6.40-6.48 (m, 1H), 3.85 (dd, J = 6.0 Hz, 3.0 Hz, 1H), 3.82-3.79 (m, 1H), 3.22-3.09 (m, 2H), 3.02 (dd, J = 8.0 Hz, 6.5 Hz, 1 H), 2.54-2.52 (m, 1H), 1.81-1.95 (m, 1H), 1.67-1.57 (m, 6H), 1.37-1.34 (m, 1H) ; 13 C NMR (100 MHz, CDCl 3 ) δ 203.17, 144.90, 129.50, 127.53, 117.15, 115.67, 110.39, 58.26, 49.58, 47.95, 35.02, 26.63, 26.13, 25.94, 23.80; EI-MS: m/z 230.1 [M+H] + ; ESI-HRMS: m/z calcd for C 15 H 20 NO [M+H] + : 230.1545; found 230.1541.
(4aS,5R)-2,3,4,4a,5,6-Hexahydro-1H-pyrido[1,2-a]quinoline- 5-carbaldehyde (2d): Major diastereomer; 1 H NMR (400 MHz, CDCl 3 ) δ 9.63 (d, J = 1.6 Hz, 1H), 7.10 (td, J = 8.4 Hz, 1.6 Hz, 1H), 7.03-7.01 (m, 1H), 6.78-6.76 (m, 1H), 6.67 (td, J = 7.2 Hz, 0.8 Hz, 1H), 3.95-3.91 (m, 1H), 3.45 (ddd, J = 10.8 Hz, 5.2 Hz, 2.0 Hz, 1H), 2.99 (dd, J = 15.2 Hz, 6.4 Hz, 1H), 2.90-2.84 (m, 2H), 2.63-2.58 (m, 1H), 1.90- 1.50 (m, 6H); 13 C NMR (100 MHz, CDCl 3 ) δ 202.72, 145.73, 128.89, 127.65, 122.10, 117.62, 112.60, 56.53, 52.01, 48.39, 31.26, 25.99, 24.98, 24.06; EI-MS: m/z 216.1 [M+H] + .
(3aS,4R)-1,2,3,3a,4,5-Hexahydropyrrolo[1,2-a]quinoline- 4-carbaldehyde (2e): Major diastereoisomer; 1 H NMR (400 MHz, CDCl 3 ) δ 9.91 (d, J = 2.0 Hz, 1H), 7.11-7.08 (m, 1H), 7.35 (d, J = 7.0 Hz, 1H), 6.60-6.57 (m, 1H), 6.44 (d, J = 8.0 Hz, 1H) 3.49 (ddd, J = 10.4 Hz, 10.1 Hz, 4.9 Hz, 1H), 3.38 (ddd, J = 11.1 Hz, 8.9 Hz, 2.1 Hz, 1H), 3.22-3.17 (m, 1H), 2.93-2.91 (m, 2H), 2.50-2.41 (m, 1H), 2.32-2.28 (m, 1H), 2.13-2.10 (m, 1H), 1.97-1.95 (m, 1H), 1.58-1.54 (m, 1H); 13 C NMR (100 MHz, CDCl 3 ) δ 202.99, 143.89, 128.70, 127.76, 119.06, 115.48, 110.45, 57.75, 50.35, 46.64, 31.62, 28.59, 24.02; EI-MS: m/z 202.1 [M+H] + ; ESI-HRMS: m/z calcd for C 13 H 16 NO [M+H] + : 202.1232; found 202.1238.
(6R,6aS)-3-Bromo-5,6,6a,7,8,9,10,11,12,13-decahydroazonino[ 1,2-a]quinoline-6-carbaldehyde (2f): Major diastereomer; 1 H NMR (400 MHz, CDCl 3 ) δ 9.81 (d, J = 0.8 Hz, 1H), 7.19-7.17 (m, 2H), 6.65-6.62 (m, 1H), 3.76 (dt, J = 10.4 Hz, 2.8 Hz, 1H), 3.61 (ddd, J = 14.8 Hz, 7.6 Hz, 3.2 Hz, 1H), 3.21 (ddd, J = 14.8 Hz, 6.8 Hz, 3.2 Hz, 1H), 3.01 (dd, J = 16.8 Hz, 13.6 Hz, 1H), 2.82 (dd, J = 17.2 Hz, 5.6 Hz, 1H), 2.67-2.61 (m, 1H), 1.90-1.10 (m, 12H); 13 C NMR (100 MHz, CDCl 3 ) δ 202.46, 143.95, 132.07, 130.11, 122.40, 116.58, 108.80, 58.92, 56.75, 47.82, 28.81, 27.46, 27.10, 25.51, 25.16, 24.74, 23.15; EI-MS: m/z 336.0 [M+H] + .
(6R,6aS)-3-Fluoro-5,6,6a,7,8,9,10,11,12,13-decahydroazonino[ 1,2-a]quinoline-6-carbaldehyde (2g): Major diastereomer; 1 H NMR (400 MHz, CDCl 3 ) δ 9.82 (d, J = 0.4 Hz, 1H), 6.86-6.77 (m, 2H), 6.71 (dd, J = 8.8 Hz, 4.8 Hz, 1H), 3.75 (dt, J = 11.2 Hz, 2.8 Hz, 1H), 3.54 (ddd, J = 14.8 Hz, 8.4 Hz, 3.6 Hz, 1H), 3.21 (ddd, J = 14.8 Hz, 6.4 Hz, 3.2 Hz, 1H), 3.03 (dd, J = 16.4 Hz, 13.6 Hz, 1H), 2.82 (dd, J = 16.8 Hz, 5.2 Hz, 1H), 2.70-2.64 (m, 1H), 1.90-1.25 (m, 11H), 1.15-1.05 (m, 1H); 13 C NMR (100 MHz, CDCl 3 ) δ 202.77, 155.38 (d, J = 234.7 Hz), 141.38, 121.78 (d, J = 7.1 Hz), 116.55 (d, J = 8.4 Hz), 115.62 (d, J = 21.7 Hz), 114.08 (d, J = 22.0 Hz), 58.20, 57.21, 47.47, 28.52, 27.53, 27.44, 24.89, 24.55, 24.31, 23.38; EI-MS: m/z 276.1 [M+H] + .
(6R,6aS)-3-(Trifluoromethyl)-5,6,6a,7,8,9,10,11,12,13- decahydroazonino[1,2-a]quinoline-6-carbaldehyde (2h): Major diastereomer; 1 H NMR (400 MHz, CDCl 3 ) δ 9.50 (s, 1H), 7.30-7.28 (m, 2H), 6.66-6.64 (m, 1H), 3.92-3.88 (m, 1H), 3.72 (ddd, J = 12.4 Hz, 6.4 Hz, 3.2 Hz, 1H), 3.27 (ddd, J = 15.2 Hz, 7.6 Hz, 3.2 Hz, 1H), 3.18-3.14 (m, 1H), 3.12- 3.10 (m, 1H), 2.61 (dt, J = 6.4 Hz, 2.4 Hz, 1H), 1.90-1.30 (m, 12H); 13 C NMR (100 MHz, CDCl 3 ) δ 202.31, 147.19, 126.57 (q, J = 3.6 Hz), 124.60 (q, J = 4.1 Hz), 123.81 (q, J = 265.2), 117.19, 116.99 (q, J = 32.2 Hz), 110.71, 59.84, 56.65, 48.75, 33.22, 30.92, 27.69, 26.57, 26.39, 25.35, 23.75; EI-MS: m/z 326.1 [M+H] + .
(6R,6aS)-2-Chloro-5,6,6a,7,8,9,10,11,12,13-decahydroazonino[ 1,2-a]quinoline-6-carbaldehyde (2i): Major diastereomer; 1 H NMR (400 MHz, CDCl 3 ) δ 9.81 (d, J = 0.4 Hz, 1H), 6.98-6.96 (m, 1H), 6.72-6.70 (m, 1H), 6.64 (dd, J = 8.0 Hz, 2.0 Hz, 1H), 3.77 (dt, J = 10.8 Hz, 2.4 Hz, 1H), 3.64 (ddd, J = 15.2 Hz, 7.2 Hz, 3.6 Hz, 1H), 3.22 (ddd, J = 14.8 Hz, 7.2 Hz, 3.6 Hz, 1H), 3.02-2.94 (m, 1H), 2.82 (dd, J = 17.2 Hz, 5.6 Hz, 1H), 2.64 (ddd, J = 13.6 Hz, 5.2 Hz, 4 Hz, 1H), 1.90-1.10 (m, 12H); 13 C NMR (100 MHz, CDCl 3 ) δ 202.53, 145.92, 132.75, 130.66, 118.62, 116.85, 114.40, 58.98, 56.75, 48.11, 29.06, 27.40, 17.10, 25.60, 25.24, 24.77, 22.87; EI-MS: m/z 292.1 [M+H] + .
(6R,6aS)-2-Methoxy-5,6,6a,7,8,9,10,11,12,13-decahydroazonino[ 1,2-a]quinoline-6-carbaldehyde (2j): Major diastereomer; 1 H NMR (400 MHz, CDCl 3 ) δ 9.81 (d, J = 0.8 Hz, 1H), 7.00-6.98 (m, 1H), 6.31-6.29 (m, 2H), 3.78 (s, 3H), 3.73-3.64 (m, 2H), 3.22 (ddd, J = 15.2 Hz, 7.2 Hz, 3.6 Hz, 1H), 3.00-2.94 (m, 2H), 2.82 (dd, J = 16.0 Hz, 5.2 Hz, 2.68- 2.63 (m, 1H), 1.90-1.10 (m, 12H); 13 C NMR (100 MHz, CDCl 3 ) δ 203.26, 159.20, 145.91, 130.24, 113.04, 102.10, 100.95, 59.19, 56.80, 55.19, 48.52, 29.02 27.63, 27.16, 25.62, 25.30, 24.86, 22.69; EI-MS: m/z 288.1 [M+H] + .
(12bR,13R)-6,7,8,12b,13,14-Hexahydrobenzo[3,4]azepino[ 1,2-a]quinoline-13-carbaldehyde (2k): Major diastereomer. 1 H NMR (400 MHz, CDCl 3 ) δ 9.64 (d, J = 1.6 HZ, 1H), 7.18-7.02 (m, 6H), 6.67-6.58 (m, 2H), 5.05 (d, J = 6.4 Hz, 1H), 2.99-2.90 (m, 2H), 2.65 (dt, J = 14 Hz, 4.8 Hz, 1H), 2.27-2.19 (m, 1H), 1.68-1.61 (m, 1H); 13 C NMR (100 MHz, CDCl 3 ) δ 203.02, 143.42, 139.63, 139.28, 130.80, 129.28, 127.86, 127.65, 127.16, 126.54, 119.34, 116.07, 110.66, 63.26, 49.49, 46.33, 31.88, 26.72, 24.73; EI-MS: m/z 278.1 [M+H] + .
(11bR,12R)-7,11b,12,13-Tetrahydro-6H-isoquinolino[2,1- a]quinoline-12-carbaldehyde (2l): Major diastereomer. 1 H NMR (400 MHz, CDCl 3 ) δ 9.39 (s, 1H), 7.33-7.28 (m, 2H), 7.24-7.19 (m, 2H), 7.14-7.10 (m, 2H), 6.85-6.83 (m, 1H), 6.79 (td, J = 7.2 Hz, 0.8 Hz, 1H), 4.66-4.67 (m, 1H), 4.01- 3.97 (m, 1H), 3.41 (d, J = 16.8 Hz, 1H), 3.29 (dt, J = 7.2 Hz, 1.6 Hz, 1H), 3.17 (dd, J = 16.4 Hz, 6.8 Hz, 1H), 3.08-3.04 (m, 1H), 3.02-2.99 (m, 1H), 2.93-2.89 (m, 1H); 13 C NMR (100 MHz, CDCl 3 ) δ 202.02, 146.38, 135.36, 134.98, 129.86, 128.81, 126.95, 126.83, 126.24, 121.32, 118.87, 112.11 (one aromatic carbon missing), 57.61, 51.21, 42.06, 29.89, 27.67; EI-MS: m/z 264.1 [M+H] + .
Acknowledgements
This research was supported by Soonchunhyang University Research Fund and Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (2013-052688).
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