Origins of Stereoselectivity in Mannich Reactions Catalyzed by Chiral Vicinal Diamines

J Org Chem. 2018 Mar 16;83(6):3171-3176. doi: 10.1021/acs.joc.8b00037. Epub 2018 Feb 26.

Abstract

The origins of the enantio- and diastereoselectivities in the Mannich reactions between aldehydes and ketimines catalyzed by chiral vicinal diamines have been determined by density functional theory calculations and distortion-interaction analysis. Computational results indicate a strong energetic preference for hydrogen-bonded nine-membered cyclic transition states. The favored transition states involve eight heavy atoms in the crown (chair-chair) conformation using the nomenclature of the analogous cyclic hydrocarbons. Energetic discrimination in the chirality-imparting step arises from pseudogauche-butane-type interactions in the disfavored transition states, as well as steric clashes between the N-Boc protecting group and the ammonium N-substituents.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.