Enantioselective synthesis of polysubstituted prolines by Binap-silver-catalyzed 1,3-dipolar cycloadditions

The enantioselective 1,3-dipolar cycloaddition reaction of stabilized azomethine ylides, generated from iminoesters, with maleimides was efficiently achieved by intermediacy of an equimolar mixture of chiral (R)- or (S)-Binap and AgClO4. The high stability of the titled catalytic metal-complex to light exposure and its insolubility in toluene made possible its recovery and reutilization in other new process. In order to get a better understanding of the behavior of these chiral catalysts, we have carried out DFT1 calculations demonstrating the experimentally observed high enantio- and endo-selectivity through a very asynchronous transition state.

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Ethyl (1S,3R,3aS,6aR)-5-methyl-3-phenyl-4,6-dioxooctahydropyrrolo[3,4-c]pyrrole-1-carboxylateC16H18N2O4[α]D=+74[α]D=+74 (c 1, CHCl3, 90% ee from HPLC)Source of chirality: (S)-BinapAbsolute configuration: (1S,3R,3aS,6aR)

Isopropyl (1S,3R,3aS,6aR)-5-methyl-3-phenyl-4,6-dioxooctahydropyrrolo[3,4-c]pyrrole-1-carboxylateC17H20N2O4[α]D=+63[α]D=+63 (c 0.7, CHCl3, 99% ee from HPLC)Source of chirality: (S)-BinapAbsolute configuration: (1S,3R,3aS,6aR)

tert-Butyl (1S,3R,3aS,6aR)-5-methyl-3-phenyl-4,6-dioxooctahydropyrrolo[3,4-c]pyrrole-1-carboxylateC18H22N2O4[α]D=+33.9[α]D=+33.9 (c 0.8, CHCl3, 92% ee from HPLC)Source of chirality: (S)-BinapAbsolute configuration: (1S,3R,3aS,6aR)

tert-Butyl (1S,3R,3aS,6aR)-5-methyl-3-(2-naphthyl)-4,6-dioxooctahydropyrrolo[3,4-c]pyrrole-1-carboxylateC22H24N2O4[α]D=+39.8[α]D=+39.8c 1, CHCl3, 92% ee from HPLC, 75:25 endo/exo)Source of chirality: (S)-BinapAbsolute configuration: (1S,3R,3aS,6aR)

(1S,3R,3aS,6aR)-Methyl 5-methyl-4,6-dioxo-3-(o-tolyl)octahydropyrrolo[3,4-c]pyrrole-1-carboxylateC16H18N2O4[α]D=+50.8[α]D=+50.8 (c 0.6, CHCl3, 75% ee from HPLC)Source of chirality: (S)-BinapAbsolute configuration: (1S,3R,3aS,6aR)

tert-Butyl (1S,3R,3aS,6aR)-3-(4-methoxyphenyl)-5-methyl-4,6-dioxooctahydropyrrolo[3,4-c]pyrrole-1-carboxylateC19H24N2O5[α]D=+93[α]D=+93 (c 0.5,CHCl3, 84% ee from HPLC)Source of chirality: (S)-BinapAbsolute configuration: (1S,3R,3aS,6aR)

tert-Butyl (1S,3R,3aS,6aR)-3-(4-chlorophenyl)-5-methyl-4,6-dioxooctahydropyrrolo[3,4-c]pyrrole-1-carboxylateC18H21ClN2O4[α]D=+16[α]D=+16 (c 0.5, CHCl3, 82% ee from HPLC)Source of chirality: (S)-BinapAbsolute configuration: (1S,3R,3aS,6aR)

(2S,3S,4S,5R)-3,4-Diisopropyl 2-methyl 5-phenylpyrrolidine-2,3,4-tricarboxylateC20H27NO6[α]D=+32.1[α]D=+32.1 (c 0.5, CHCl3, 82% ee from HPLC)Source of chirality: (S)-BinapAbsolute configuration: (2S,3S,4S,5R)

(2S,3S,4S,5R)-3,4-Diisobutyl 2-methyl 5-phenylpyrrolidine-2,3,4-tricarboxylateC22H31NO6[α]D=+47.1[α]D=+47.1 (c 0.5, CHCl3. 82% ee from HPLC)Source of chirality: (S)-BinapAbsolute configuration: (2S,3S,4S,5R)