Ytterbium Acetate Promoted Asymmetric Reductive Amination: Significantly Enhanced Stereoselectivity

Abstract
Reductive amination of prochiral unhindered 2-alkanones 1 with (R)- or (S)-α-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)-α-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.