An unexpected tandem enantioselective Michael addition/oxa-nucleophilic rearrangement reaction of β,γ-unsaturated α-keto esters catalyzed by cinchona alkaloids

Cinchona alkaloids were found to catalyze an enantioselective Michael addition/oxa-nucleophilic rearrangement reaction of β,γ-unsaturated α-keto esters 1 and malonates 2. Using the optimum catalyst quinine 4a, a series of the rearranged products 3 were obtained with up to 98% yield and 82% ee under mild reaction conditions.

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(S,Z)-Trimethyl 4-(cinnamoyloxy)-2-phenylbut-3-ene-1,1,4-tricarboxylateC25H24O8Ee = 80%[α]D25=-156.4 (c 1.5, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (S)

(S,Z)-Trimethyl 4-(cinnamoyloxy)-2-(4-fluorophenyl)but-3-ene-1,1,4-tricarboxylateC25H23FO8Ee = 80%[α]D26=-80.5 (c 1.0, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (S)

(S,Z)-Trimethyl 2-(4-chlorophenyl)-4-(cinnamoyloxy)but-3-ene-1,1,4-tricarboxylateC25H23ClO8Ee = 80%[α]D27=-144.0 (c 1.0, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (S)

(S,Z)-Trimethyl 2-(4-bromophenyl)-4-(cinnamoyloxy)but-3-ene-1,1,4-tricarboxylateC25H23BrO8Ee = 80%[α]D27=-136.0 (c 1.0, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (S)

(S,Z)-Trimethyl 2-(3-chlorophenyl)-4-(cinnamoyloxy)but-3-ene-1,1,4-tricarboxylateC25H23ClO8Ee = 78%[α]D27=-116.8 (c 1.0, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (S)

(S,Z)-Trimethyl 4-(cinnamoyloxy)-2-(4-nitrophenyl)but-3-ene-1,1,4-tricarboxylateC25H23NO10Ee = 72%[α]D27=-145.2 (c 1.0, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (S)

(S,Z)-Trimethyl 4-(cinnamoyloxy)-2-p-tolylbut-3-ene-1,1,4-tricarboxylateC25H26O8Ee = 79%[α]D27=-125.3 (c 1.2, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (S)

(S,Z)-Trimethyl 4-(cinnamoyloxy)-2-(4-ethoxyphenyl)but-3-ene-1,1,4-tricarboxylateC27H28O9Ee = 70%[α]D27=-122.2 (c 1.25, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (S)

(S,Z)-Trimethyl 4-(cinnamoyloxy)-2-(2,4-dichlorophenyl)but-3-ene-1,1,4-tricarboxylateC25H22ClO8Ee = 58%[α]D27=-50.2 (c 0.8, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (S)

(S,Z)-Trimethyl 2-(2-bromophenyl)-4-(cinnamoyloxy)but-3-ene-1,1,4-tricarboxylateC25H23BrO8Ee = 54%[α]D27=-22.9 (c 0.53, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (S)

(S,Z)-4-Ethyl 1,1-dimethyl 4-(cinnamoyloxy)-2-phenylbut-3-ene-1,1,4-tricarboxylateC26H26O8Ee = 79%[α]D27=-95.7 (c 1.7, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (S)

(S,Z)-4-Allyl 1,1-dimethyl 4-(cinnamoyloxy)-2-phenylbut-3-ene-1,1,4-tricarboxylateC27H26O8Ee = 78%[α]D27=-108.7 (c 1.0, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (S)

(S,Z)-4-tert-Butyl 1,1-dimethyl 4-(cinnamoyloxy)-2-phenylbut-3-ene-1,1,4-tricarboxylateC28H30O8Ee = 79%[α]D27=-96.7 (c 0.7, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (S)

(S,Z)-4-Benzyl 1,1-dimethyl 4-(cinnamoyloxy)-2-phenylbut-3-ene-1,1,4-tricarboxylateC31H28O8Ee = 80%[α]D27=-85.9 (c 1.0, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (S)

(S,Z)-4-(4-Bromobenzyl) 1,1-dimethyl 2-phenyl-4-((Z)-3-phenylacryloyloxy)but-3-ene-1,1,4-tricarboxylateC31H27BrO8Ee = 77%[α]D27=-79.7 (c 1.0, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (S)

(S,Z)-4-Isopropyl 1,1-dimethyl 2-phenyl-4-((Z)-3-phenylacryloyloxy)but-3-ene-1,1,4-tricarboxylateC27H28O8Ee = 78%[α]D27=-108.7 (c 1.4, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (S)

(S,Z)-Trimethyl 2-(4-bromophenyl)-4-((E)-but-2-enoyloxy)but-3-ene-1,1,4-tricarboxylateC20H21BrO8Ee = 80%[α]D26=-98.4 (c 1.65, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (S)

(S,Z)-1,1-Diethyl 4-methyl 2-(4-bromophenyl)-4-(cinnamoyloxy)but-3-ene-1,1,4-tricarboxylateC27H273BrO8Ee = 82%[α]D26=-147.4 (c 1.0, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (S)

(S,Z)-1,1-Diisopropyl 4-methyl 2-(4-bromophenyl)-4-(cinnamoyloxy)but-3-ene-1,1,4-tricarboxylateC29H31BrO8Ee = 82%[α]D28=-163.1 (c 1.0, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (S)

(S,Z)-1,1-Dibenzyl 4-methyl 2-(4-bromophenyl)-4-(cinnamoyloxy)but-3-ene-1,1,4-tricarboxylateC37H31BrO8Ee = 82%[α]D27=-115.1 (c 1.0, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (S)