High diastereoselective amine-catalyzed Knoevenagel–Michael-cyclization–ring-opening cascade between aldehydes, 3-arylisoxazol-5(4H)-ones and 3-aminocyclohex-2-en-1-ones

Abstract

A highly diastereoselective three-component cascade reaction among aromatic aldehydes, 3-arylisoxazol-5(4H)-ones and 3-aminocyclohex-2-en-1-ones takes place under the catalysis of triethylamine, providing (3SR,4SR)-4-aryl-3-[(E)-(hydroxyimino)(aryl)methyl]-4,6,7,8-tetrahydroquinoline-2,5(1H,3H)-diones in 45-85% yields. The transformation presumably proceeds through a sequential cascade of Knoevenagel/Michael-addition/cyclization/ring-opening reactions. This process was carried out in green media (EtOH/water, 1:1-1:3) at reflux. Products are crystallized directly from the reaction mixture and their isolation includes only filtration. The structure of (3SR,4SR)-3-[(E)-(hydroxyimino)(phenyl)methyl]-7,7-dimethyl-4-phenyl-4,6,7,8-tetrahydroquinoline-2,5(1H,3H)-dione was confirmed by X-ray diffraction analysis.

Phase-transfer catalyzed Michael/ammonolysis cascade reactions of enaminones and olefinic azlactones: a new approach to structurally diverse quinoline-2,5-diones

“…N- (7,2,3,4,5,6,7,benzamide (3a) Purified via silica gel column chromatography ( petroleum ether/EtOAc = 2/1); white solid; 44.5 mg, 93% yield; >99 : 1 dr; M.P. : 267.3-268.1 °C; 1 H NMR (400 MHz, CDCl 3 ): δ ( ppm) 7.68-7.61 (m, 2H), 7.48-7.41 (m, 1H), 7.39-7.33 (m, 2H), 7.33-7.29 (m, 2H), 7.29-7.25 (m, 2H), 7.23 (dd, J = 7.0, 4.2 Hz, 3H), 7.11 (d, J = 8.2 Hz, 2H), 6.55 (d, J = 6.7 Hz, 1H), 5.41-5.34 (m, 1H), 4.90 (d, J = 7.6 Hz, 1H), 2.42 (s, 3H), 2.30 (t, J = 9.5 Hz, 2H), 2.26-2.19 (m, 1H), 2.11 (d, J = 17.6 Hz, 1H), 1.07 (s, 3H), 1.00 (s, 3H); 13 C NMR{ 1 H} (101 MHz, CDCl 3 ): δ ( ppm) 195.1, 169.5, 167.3, 152.3, 139.4, 136.4, 134.0, 134.0, 131.8, 130.6, 130.5, 129.0, 128.9, 128.6, 128.2, 127.8, 127.5, 127.1, 117.5, 54.0, 50.2, 41.6, 38.6, 33.1, 28.7, 27.9, 21.3; FTIR (cm −1 ): 3439,2968,2917,1714,1665,1650,1612,1514,1487,1369,1310,1274,1237,695; HRMS (ESI-TOF) m/z: [M + H] + calcd for C 31 H 31 N 2 O 3 : 479.2329, found: 479.2338.…”

“…N- (7, 1, 169.4, 167.4, 152.4, 150.2, 144.5, 139.5, 137.2, 135.6, 133.9, 133.9, 132.5, 131.8, 130.7, 130.6, 129.0, 128.7, 128.6, 127.5, 127.4, 127.1, 126.2, 120.8, 117.3, 54.1, 50.2, 41.6, 38.4, 33.1, 28.7, 28.0, 21.3; FTIR (cm −1 ): 3278,2955,2926,1714,1646,1592,1544,1515,1373,1277,1243,1186,1143,814,717 Procedure for the synthesis of compound 9…”

“…N 2,3,4,5,6,7,8- 7,132.3,131.7,131.6,130.9,130.8,129.8,128.7,128.2,127.4,126.5,126.1,121.4,118.9 (d,J = 17.2 Hz),118.3,117.09 (d,J = 17.2 Hz),64.04,50.15,43.31,41.80,38.62,33.36,28.87,27.83,21.28;19 F NMR (377 MHz, CDCl 3 ): δ ( ppm) −137.7 (d, J = 22.6 Hz), −139.4 (d, J = 22.6 Hz); FTIR (cm −1 ): 3412,2958,2932,1683,1666,1640,1515,1484,1365,1251,1211,1121,811,715 Procedure for the synthesis of compound 13…”

“…Widespread and invigorating developments in the area of organic synthesis and its related sciences over the past several decades have resulted in the explosive growth of interdisciplinary research. 7 Organic chemists have established an arsenal stuffed with many kinds of elaborate tools for the synthesis of biologically relevant molecules and pharmacophore hybrids to date; 8 among these, phase-transfer catalysis (PTC) is considered as a robust and versatile tactic in light of its salient features—it is environmentally benign, has high selectivity, shows speed and operational simplicity, requires mild reaction conditions, and is safe. 9 Since its original disclosure fifty years ago, 10 PTC has played indispensable roles in the chemical industry, the reduction of environmental pollution, decreases in production costs, and increases in operational efficiency.…”

Multicomponent synthesis of 1,4-dihydropyridine-3,5-dicarbonitriles

“…16,17,18 We previously carried out different types of multicomponent processes leading to substituted piperidines and tetrahydropyridines. [19][20][21][22] These processes are three-and four-component reactions occurring under mild conditions. Now, we wish to report our results on the efficient autocatalytic four-component transformation of benzaldehydes 1, malononitrile and cyclic amines 2 into the previously unknown 1,4-dihydropyridine-3,5dicarbonitriles 3 in EtOH at 78 °C, as shown in Scheme 1.…”