Solvent-Induced Reversal of Enantioselectivity in the Synthesis of Succinimides by the Addition of Aldehydes to Maleimides Catalysed by Carbamate-Monoprotected 1,2-Diamines

• Published in: European journal of organic chemistry Vol. 2015; no. 6; pp. 1218 - 1225
• Main Authors: Flores-Ferrándiz, Jesús, Fiser, Béla, Gómez-Bengoa, Enrique, Chinchilla, Rafael
• Format: Journal Article
• Language: English
• Published: Weinheim WILEY-VCH Verlag 01-02-2015; WILEY‐VCH Verlag; Wiley Subscription Services, Inc
• Subjects: Asymmetric catalysis; Enantioselectivity; Michael addition; Organo­catalysis; Solvent effects; Transition states
• ISSN: 1434-193X; 1099-0690
• DOI: 10.1002/ejoc.201403415

A simple change in the polarity of the solvent allows both enantiomers of substituted succinimides to be obtained in the enantioselective conjugate addition reaction of aldehydes, mainly α,α‐disubstituted, to maleimides catalysed by chiral carbamate‐monoprotected trans‐cyclohexane‐1,2‐diamines. Using a single enantiomer of the organocatalyst, both enantiomers of the resulting Michael adducts are obtained in high yields by simply changing the reaction solvent from aqueous DMF (up to 84 % ee) to chloroform (up to 86 % ee). Theoretical calculations are used to explain this uncommon reversal of the enantioselectivity; two transition state orientations of different polarities are differently favoured in polar or nonpolar solvents.
An inversion of enantioselectivity is achieved by simply changing the solvent in the enantioselective Michael addition reaction of aldehydes to maleimides catalysed by carbamate‐monoprotected trans‐cyclohexane‐1,2‐diamines. The reasons behind this uncommon enantioswitch are explained using theoretical calculations.