| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 1347117 | Tetrahedron: Asymmetry | 2014 | 7 Pages |
An asymmetric two-step approach toward the synthesis of chiral cyclopropane-fused tetrahydroquinolines is described. In this synthesis, an asymmetric organocatalytic Michael/alkylation domino reaction of dialkyl bromomalonates with o-N-protected aminophenyl α,β-unsaturated aldehydes allows the process to proceed efficiently to afford the corresponding 2-formylcyclopropane products in good yields and with high enantioselectivities (up to 97% ee). In addition, a one-pot procedure for the DBU-mediated aza-cyclization of the 2-formylcyclopropane adducts was applied for the formation of chiral cyclopropane-fused tetrahydroquinolines.
Graphical abstractFigure optionsDownload full-size imageDownload as PowerPoint slide
(1aS,2S,7bS)-3-Benzyl 1,1-dimethyl 1a,2-dihydro-2-hydroxy-7bH-cyclopropa[c]quinoline-1,1,3-tricarboxylateEe = 96%[α]D26 = −53.5 (c 0.9, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (1aS,2S,7bS)
(1aS,2S,7bS)-3-tert-Butyl 1,1-dimethyl 1a,2-dihydro-2-hydroxy-7bH-cyclopropa[c]quinoline-1,1,3-tricarboxylateEe = 96%[α]D26 = −60.6 (c 1.50, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (1aS,2S,7bS)
(1aS,2S,7bS)-3-Benzyl 1,1-diethyl 1a,2-dihydro-2-hydroxy-7bH-cyclopropa[c]quinoline-1,1,3-tricarboxylateEe = 92%[α]D24 = −54.8 (c 2.2, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (1aS,2S,7bS)
Benzyl 2-((1S,3R)-2,2-di((benzyloxy)carbonyl)-3-formylcyclopropyl)phenylcarbamateEe = 95%[α]D28 = +15.44 (c 0.87, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (1S,3R)
Benzyl 2-((1S,3R)-2,2-di(methoxycarbonyl)-3-formylcyclopropyl)-4-methylphenylcarbamateEe = 94%[α]D25 = −16.7 (c 1.84, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (1S,3R)
Benzyl 2-((1S,3R)-2,2-di(methoxycarbonyl)-3-formylcyclopropyl)-6-methylphenylcarbamateEe = 92%[α]D27 = +2.4 (c 1.58, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (1S,3R)
Benzyl 2-((1S,3R)-2,2-di(methoxycarbonyl)-3-formylcyclopropyl)-4-chlorophenylcarbamateEe = 94%[α]D24 = −26.21 (c 0.91, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (1S,3R)
Benzyl 2-((1S,3R)-2,2-di(methoxycarbonyl)-3-formylcyclopropyl)-5-chlorophenylcarbamateEe = 97%[α]D27 = +5.45 (c 1.38, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (1S,3R)
Benzyl 2-((1S,3R)-2,2di(methoxycarbonyl)-3-formylcyclopropyl)-4-bromophenylcarbamateEe = 93%[α]D26 = −33.74 (c 0.96, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (1S,3R)
tert-Butyl 2-((1S,3R)-2,2-di(methoxycarbonyl)-3-formylcyclopropyl)-4-bromophenylcarbamateEe = 95%[α]D26 = −31.6 (c 0.81, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (1S,3R)
(1aS,2S,7bS)-3-Benzyl 1,1-dimethyl 1a,2-dihydro-2-hydroxy-7bH-cyclopropa[c]quinoline-1,1,3-tricarboxylateEe = 96%[α]D26 = −53.5 (c 0.9, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (1aS,2S,7bS)
(1aS,2S,7bS)-3-tert-Butyl 1,1-dimethyl 1a,2-dihydro-2-hydroxy-7bH-cyclopropa[c]quinoline-1,1,3-tricarboxylateEe = 96%[α]D26 = −60.6 (c 1.50, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (1aS,2S,7bS)
(1aS,2S,7bS)-3-Benzyl 1,1-diethyl 1a,2-dihydro-2-hydroxy-7bH-cyclopropa[c]quinoline-1,1,3-tricarboxylateEe = 92%[α]D24 = −54.8 (c 2.2, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (1aS,2S,7bS)
(1aS,2S,7bS)-Tribenzyl 1a,2-dihydro-2-hydroxy-7bH-cyclopropa[c]quinoline-1,1,3-tricarboxylateEe = 95%[α]D23 = −81.7 (c 1.2, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (1aS,2S,7bS)
(1aS,2S,7bS)-3-Benzyl 1,1-dimethyl 1a,2-dihydro-2-hydroxy-6-methyl-7bH-cyclopropa[c]quinoline-1,1,3-tricarboxylateEe = 94%[α]D24 = −0.4 (c 1.2, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (1aS,2S,7bS)
(1aS,2S,7bS)-3-Benzyl 1,1-dimethyl 1a,2-dihydro-2-hydroxy-4-methyl-7bH-cyclopropa[c]quinoline-1,1,3-tricarboxylateEe = 92%[α]D23 = −81.7 (c 1.2, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (1aS,2S,7bS)
(1aS,2S,7bS)-3-Benzyl 1,1-dimethyl 6-chloro-1a,2-dihydro-2-hydroxy-7bH-cyclopropa[c]quinoline-1,1,3-tricarboxylateEe = 94%[α]D24 = −11.8 (c 1.0, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (1aS,2S,7bS)
(1aS,2S,7bS)-3-Benzyl 1,1-dimethyl 5-chloro-1a,2-dihydro-2-hydroxy-7bH-cyclopropa[c]quinoline-1,1,3-tricarboxylateEe = 97%[α]D23 = −81.7 (c 1.2, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (1aS,2S,7bS)
(1aS,2S,7bS)-3-Benzyl 1,1-dimethyl 6-bromo-1a,2-dihydro-2-hydroxy-7bH-cyclopropa[c]quinoline-1,1,3-tricarboxylateEe = 93%[α]D25 = −53.5 (c 0.9, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (1aS,2S,7bS)
(1aS,2S,7bS)-3-tert-Butyl 1,1-dimethyl 6-bromo-1a,2-dihydro-2-hydroxy-7bH-cyclopropa[c]quinoline-1,1,3-tricarboxylateEe = 95%[α]D22 = −3.65 (c 0.8, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (1aS,2S,7bS)
