Studies Toward Improved Enantiocontrol in the Asymmetric Cu-Catalyzed Reductive Coupling of Ketones and Allenamides: 1,2-Aminoalcohol Synthesis

Herein, we report the development of an improved system for the Cu-catalyzed enantioselective reductive coupling of ketones and allenamides through the optimization of the allenamide to avoid an on-cycle rearrangement. High enantioselectivities could be obtained for a variety of ketones. Use of the acyclic allenamides described herein selectively generated anti-diastereomers in contrast to cyclic allenamides that were previously shown to favor the syn-form. A rationale for this change in diastereoselectivity is also presented.

Automated summary

In this study, we present an improved system for the Cu-catalyzed enantioselective reductive coupling of ketones and allenamides by optimizing the allenamide to prevent on-cycle rearrangement. High enantioselectivities were achieved for various ketones. Unlike cyclic allenamides, which favor the syn-form, the acyclic allenamides described in this work selectively generated anti-diastereomers. A rationalization for this change in diastereoselectivity is also provided.