Ytterbium acetate promoted asymmetric reductive amination: significantly enhanced stereoselectivity.
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.
Nugent
Thomas C
TC
Department of Chemistry, School of Engineering and Science, Jacobs University Bremen, Campus Ring 1, 28759 Bremen, Germany. t.nugent@jacobs-university.de
El-Shazly
Mohamed
M
Wakchaure
Vijay N
VN
D000588:Amines / Q000737:chemistry*; D002384:Catalysis; D013237:Stereoisomerism; D015018:Ytterbium / Q000737:chemistry*
D000588:Amines; D015018:Ytterbium