title: An investigation of the observed, but counter-intuitive, stereoselectivity noted during chiral amine synthesis via N-chiral-ketimines.
abstract: The default explanation for good to high diastereomeric excess when reducing N-chiral imines possessing only mediocre cis/trans-imine ratios (>15% cis-imine) has invariably been in situ cis-to-trans isomerization before reduction; but until now no study unequivocally supported this conclusion. The present study co-examines an alternative hypothesis, namely that some classes of cis-imines may hold conformations that erode the inherent facial bias of the chiral auxiliary, providing more of the trans-imine reduction product than would otherwise be expected. The ensuing experimental and computational (DFT) results favor the former, pre-existing, explanation.
authors.affiliation: Department of Chemistry, School of Engineering and Science, Jacobs University Bremen, Campus Ring 1, 28759 Bremen, Germany.
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Nugent
authors.forename: Richard Vaughan
authors.initials: RV
authors.lastname: Williams
authors.forename: Andrei
authors.initials: A
authors.lastname: Dragan
authors.forename: Alejandro Alvarado
authors.initials: AA
authors.lastname: Méndez
authors.forename: Andrei V
authors.initials: AV
authors.lastname: Iosub
keywords: chiral amines; cis/trans isomerization; imine isomerization; imine reduction; reductive amination