Ytterbium acetate promoted asymmetric reductive amination: significantly enhanced stereoselectivity

J Org Chem. 2008 Feb 15;73(4):1297-305. doi: 10.1021/jo7021235. Epub 2008 Jan 17.

Abstract

Reductive amination of prochiral unhindered 2-alkanones 1 with (R)- or (S)-alpha-MBA in the presence of Yb(OAc)3 (50-110 mol %), Raney-Ni, and hydrogen (120 psi) results in increased diastereoselectivity for the amine products 2 (80-89% de) with good yield (80-87%). The increased de is based on comparison with the best previously reported de's when using (R)- or (S)-alpha-MBA, regardless of the strategy employed [stepwise (isolation of ketimines) or one-pot (reductive amination)], reducing agent examined, or achiral Lewis acid or Brønsted acid examined. An in situ cis- to trans-ketimine isomerization mechanism, promoted by Yb(OAc)3, has been proposed to account for the observed increase in diastereoselectivity and suggests a new entry into the control of ketimine geometry.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amines / chemistry*
  • Catalysis
  • Stereoisomerism
  • Ytterbium / chemistry*

Substances

  • Amines
  • Ytterbium