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Organocatalytic Synthesis of Tetrahydroquinolines from α,β-Unsaturated Ketones via 1,5-Hydride Transfer/Cyclization
Organocatalytic Synthesis of Tetrahydroquinolines from α,β-Unsaturated Ketones via 1,5-Hydride Transfer/Cyclization
Bulletin of the Korean Chemical Society. 2013. Nov, 34(11): 3463-3466
Copyright © 2013, Korea Chemical Society
  • Received : July 28, 2013
  • Accepted : August 05, 2013
  • Published : November 20, 2013
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Dae Young Kim

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Experimental Section
General. All commercial reagents and solvents were used without purification. TLC analyses were carried out on precoated silica gel plates with F 254 indicator. Visualization was accomplished by UV light (254 nm), I 2 , p -anisaldehyde, ninhydrin, and phosphomolybdic acid solution as an indicator. Purification of reaction products was carried out by flash chromatography using E. Merck silica gel 60 (230-400 mesh). 1 H NMR and 13 C NMR spectra were recorded on a Bruker DRX 400 (400 MHz for 1 H, 100 MHz for 13 C) and AC 200 (200 MHz for 1 H, 50 MHz for 13 C). Chemical shift values (δ) are reported in ppm relative to Me4Si (0.0 ppm).
General Procedure for the Catalytic Enantioselective 1,5-Hydride Transfer/Cyclization of β-(o-(Dialkylamino)-aryl)-α,β-unsaturated Ketones 1: To a stirred solution of β-( o -(dialkylamino)aryl)-α,β-unsaturated ketone 1 (0.3 mmol) and HOTf (16 μL, 0.18 mmol) in THF (0.3 mL) was added benzyl amine (9.8 μL, 0.09 mmol). The mixture was refluxed for 10-48 h, diluted with saturated NaHCO 3 solution (10 mL) and extracted with ethyl acetate (2 × 10 mL). The combined organic layers were dried over MgSO 4 , filtered, concentrated, and purified by flash chromatography to afford tetrahydroquinoline derivatives 2 .
1-(1,2,3,3a,4,5-Hexahydropyrrolo[1,2-a]quinolin-4-yl)-ethanone (2a): Major diastereomer. 1 H NMR (400 MHz, CDCl 3 ) δ 7.11 (td, J = 8.0 Hz, 1.6 Hz, 1 H), 7.03-7.02 (m, 1H), 6.58 (td, J = 7.2 Hz, 0.8 Hz, 1H), 6.45-6.43 (m, 1H), 3.49 (ddd, J = 15.2 Hz, 10.8 Hz, 5.2 Hz, 1H), 3.40 (ddd, J = 10.8 Hz, 9.2 Hz, 1.6 Hz, 1H), 3.19 (ddd, J = 18.8 Hz, 9.6 Hz, 7.6 Hz, 1H), 2.90-2.87 (m, 2H), 2.49 (ddd, J = 16.4 Hz, 9.6 Hz, 6.4 Hz, 1H), 2.29 (s, 3H), 2.25-1.87 (m, 3H), 1.50-1.37 (m, 1H); 13 C NMR (100 MHz, CDCl 3 ) δ 208.21, 143.52, 128.45, 127.70, 119.83, 115.04, 110.14, 59.23, 50.37, 46.88, 31.96, 31.75, 30.53, 23.99.
1-(2,3,4,4a,5,6-Hexahydro-1H-pyrido[1,2-a]quinolin-5-yl)ethanone (2b): Major diastereomer. 1 H NMR (200 MHz, CDCl 3 ) δ 7.10-7.00 (m, 2H), 6.61-6.40 (m, 2H), 3.45-3.38 (m, 2H), 3.19-3.10 (m, 1H), 2.90-2.80 (m, 2H), 2.50-2,45 (m, 1H), 2.29 (s, 3H), 2.25-1.30 (m, 6H); 13 C NMR (50 MHz, CDCl 3 ) δ 208.4, 143.3, 128.3, 127.5, 119.7, 115.1, 110.5, 59.3, 50.37, 49.8, 35.5, 31.9, 28.4, 26.5, 23.7.
1-(5,6,6a,7,8,9,10,11-Octahydroazepino[1,2-a]quinolin-6-yl)ethanone (2c): Major diastereomer. 1 H NMR (400 MHz, CDCl 3 ) δ 7.06-7.00 (m, 2H), 6.58-6.53 (m, 2H), 3.80-3.74 (m, 2H), 3.15 (ddd, J = 15.2 Hz, 10.4 Hz, 4.8 Hz, 1H), 3.07-2.96 (m, 2H), 2.66-2.62 (m, 1H), 2.13 (s, 3H), 2.10-1.95 (m,1 H), 1.80-1.37 (m, 7H); 13 C NMR (100 MHz, CDCl 3 ) δ 209.57, 144.01, 128.96, 127.47, 118.56, 115.32, 110.20, 58.92, 49.56, 49.23, 35.43, 28.17, 26.95, 26.69, 26.47, 25.59.
1-(3-Bromo-5,6,6a,7,8,9,10,11-octahydroazepino[1,2-a]-quinolin-6-yl)ethanone (2d): Major diastereomer. 1 H NMR (400 MHz, CDCl 3 ) δ 7.11-7.09 (m, 2H), 6.40-6.38 (m, 2H), 3.81-3.71 (m, 2H), 3.14 (ddd, J = 15.6 Hz, 11.6 Hz, 5.2 Hz, 1H), 3.04 (dd, J = 16.8 Hz, 3.6 Hz, 1H), 2.96 (dd, J = 16.8 Hz, 5.6 Hz, 1H), 2.65-2.62 (m, 1H), 2.13 (s, 3H), 2.07-1.95 (m, 1H), 1.80-1.30 (m, 7H); 13 C NMR (100 MHz, CDCl 3 ) δ 208.87, 142.85, 131.35, 130.02, 120.60, 111.79, 106.90, 58.96, 49.41, 49.14, 35.39, 37.92, 26.56, 26.39, 25.72, 25.65.
1-(6,6a,7,8,9,10,11,12-Octahydro-5H-azocino[1,2-a]quinolin-6-yl)ethanone (2e): Major diastereomer. 1 H NMR (400 MHz, CDCl 3 ) δ 7.08-7.04 (m, 1H), 7.01-6.99 (m, 1H), 6.59-6.53 (m, 2H), 3.79-3.70 (m, 2H), 3.24 (ddd, J = 14.8 Hz, 10.8 Hz, 3.6 Hz, 1H), 3.03 (d, J = 4.8 Hz, 2H), 2.66-2.63 (m, 1H), 2.10 (s, 3H), 2.00-1.40 (m, 10H); 13 C NMR (100 MHz, CDCl 3 ) δ 209.57, 144.12, 128.98, 127.47, 118.53, 115.26, 111.11, 59.29, 52.60, 49.57, 33.67, 28.07, 27.70, 27.28, 26.72, 26.21, 25.94.
1-(5,6,6a,7,8,9,10,11,12,13-Decahydroazonino[1,2-a]-quinolin-6-yl)ethanone (2f): Major diastereomer. 1 H NMR (400 MHz, CDCl 3 ) δ 7.13-7.09 (m, 1H), 7.07-7.05 (m, 1H), 6.77-6.75 (m, 1H), 6.68 (td, J = 7.2 Hz, 0.8 Hz, 1H), 3.71-3.65 (m, 2H), 3.23 (ddd, J = 15.2 Hz, 7.2 Hz, 4.0 Hz, 1H), 3.07 (dd, J = 18.0 Hz, 14.8 Hz, 1H), 2.77-2.69 (m, 2H), 2.26 (s, 3H), 1.92-1.41 (m, 10H), 1.35-0.80 (m, 2H), 13 C NMR (100 MHz, CDCl 3 ) δ 209.13, 144.65, 129.71, 127.16, 121.09, 116.87, 114.93, 60.44, 56.92, 48.58, 28.74, 28.04, 27.70, 27.30, 25.51, 25.11, 24.94, 24.70.
1-(3-Bromo-5,6,6a,7,8,9,10,11,12,13-decahydroazonino-[1,2-a]quinolin-6-yl)ethanone (2g): Major diastereomer. 1 H NMR (400 MHz, CDCl 3 ) δ 7.18-7.16 (m, 2H), 6.32-6.61 (m, 1H), 3.72-3.68 (m, 1H), 3.63 (ddd, J = 14.8 Hz, 7.6 Hz, 3.6 Hz, 1H), 3.23 (ddd, J = 15.2 Hz, 3.6 Hz, 7.2 Hz, 1H), 3.04 (dd, J = 18.0 Hz, 14.4 Hz, 1H), 2.73-2.66 (m, 2H), 2.26 (s, 3H), 1.92-1.40 (m, 10H), 1.30-1.20 (m, 1H), 1.17-0.80 (m, 1H); 13 C NMR (100 MHz, CDCl 3 ) δ 208.49, 143.61, 131.99, 129.90, 123.19, 116.26, 108.62, 60.51, 56.89, 48.37, 28.75, 27.98, 27.53, 27.14, 25.57, 25.16, 24.92, 24.51.
1-(3-(Trifluoromethyl)-5,6,6a,7,8,9,10,11,12,13-decahydroazonino[1,2-a]quinolin-6-yl)ethanone (2h): Major diastereomer. 1 H NMR (400 MHz, CDCl 3 ) δ 7.33-7.26 (m, 2H), 6.75-6.73 (m, 1H), 3.80-3.74 (m, 2H), 3.28 (ddd, J = 15.2 Hz, 7.2 Hz, 4.0 Hz, 1H), 3.09 (dd, J = 16.8 Hz, 13.6 Hz, 1H), 2.79 (dd, J = 16.8 Hz, 4.8 Hz, 1H), 2.71 (ddd, J = 13.2 Hz, 4.8 Hz, 3.2 Hz, 1H), 2.27 (s, 3H), 1.95-1.15 (m, 12H) ); 13C NMR (100 MHz, CDCl 3 ) δ 208.23, 141.93, 126.67 (q, J = 4.0 Hz), 125.03 (q, J = 267.0 Hz), 124.35 (q, J = 4.0 Hz), 120.50, 118.02 (q, J = 32.0 Hz), 113.38, 61.06, 56.52, 48.76, 28.74, 28.47, 27.47, 26.83, 26.04, 25.62, 25.33, 24.74.
1-(5,6,6a,7,8,9,10,11,12,13-Decahydroazonino[1,2-a]-quinolin-6-yl)propan-1-one (2i): 2.3:1 Diastereomeric mixture. 1 H NMR (400 MHz, CDCl 3 ) δ 7.05-7.01 (m, 1H), 7.00-6.92 (m, 2H), 6.70-6.68 (m, 1H), 6.62-6.50 (m, 2H), 3.72-3.51 (m, 3H), 2.69-2.63 (m, 2H), 2.58-2.57 (m, 0.5H), 2.50-2.35 (m, 3H), 1.85-0.5 (m, 18H), 1.03 (t, J = 7.2 Hz, 3H), 0.87 (t, J = 7.2 Hz, 1.5H); 13 C NMR (100 MHz, CDCl3) δ 210.89, 210.61, 143.98, 143.64, 128.64, 127.90, 126.22, 126.07, 120.17, 118.33, 115.76, 114.90, 113.85, 112.09, 59.94, 59.53, 55.85, 55.58, 53.12, 53.05, 47.82, 46.59, 33.34, 32.27, 32.13, 27.33, 26.96, 26.67, 26.28, 25.93, 25.15, 25.12, 24.47, 24.07, 23.88, 23.68, 6.84, 6.69.
1-(5,6,6a,7,8,9,10,11,12,13-decahydroazonino[1,2-a]quinolin-6-yl)-3-phenylpropan-1-one (2j): Major diastereomer. 1 H NMR (400 MHz, CDCl 3 ) δ 7.31-7.18 (m, 5H), 7.11-7.07 (m, 1H), 7.06-7.03 (m, 1H), 6.75-6.73 (m, 1H), 6.67 (td, J = 7.2 Hz, 1.2 Hz, 1H), 3.67-3.58 (m, 2H), 3.21-3.14 (m, 1H), 3.13-3.06 (m, 1H), 3.05-3.00 (m, 1H), 2.99-2.93 (m, 2H), 2.87 (t, J = 7.2 Hz, 2H), 2.75-2.65 (m, 2H), 1.90-1.19 (m, 11H), 1.03-0.97 (m, 1H); 13 C NMR (100 MHz, CDCl 3 ) δ 210.11, 144.64, 141.10, 129.69, 128.59, 128.42, 127.13, 126.25, 121.11, 116.87, 114.96, 60.39, 56.89, 40.08, 43.02, 29.74, 27.93, 27.68, 27.29, 25.48, 25.10, 24.84, 24.58.
(5,6,6a,7,8,9,10,11,12,13-Decahydroazonino[1,2-a]quinolin-6-yl)(3-nitrophenyl)methanone (2k): Major diastereomer. 1 H NMR (400 MHz, CDCl 3 ) δ 8.71-8.70 (m, 1H), 8.43-8.41 (m, 1H), 8.20-8.17 (m, 1H), 7.70-7.16 (m, 1H), 7.12-7.07 (m, 1H), 6.98-6.97 (m, 1H), 6.70-6.68 (m, 1H), 6.62 (td, J = 7.2 Hz, 0.8 Hz, 1H), 3.77-3.73 (m, 1H), 3.71-3.67 (m, 1H), 3.66-3.59 (m, 1H), 3.14 (dd, J = 16.8 Hz, 6.4 Hz, 1H), 3.06-2.97 (m, 2H), 1.90-1.40 (m, 12H); 13 C NMR (100 MHz, CDCl 3 ) δ 198.53, 148.67, 144.79, 133.77, 130.09, 128.81, 127.32, 122.87, 119.46, 116.52, 113.46 (two aromatic carbons missing), 61.24, 56.57, 44.35, 32.89, 28.48, 27.18, 26.84, 25.90, 25.73, 24.93.
Acknowledgements
This research was supported by Soonchunhyang University Research Fund.
References