Enantioselective Rhodium-Catalyzed Synthesis of Branched Allylic Amines by Intermolecular Hydroamination of Terminal Allenes

摘要

α-Chiral allylic amines are an important, versatile class of building blocks for organic synthesis that can be employed in the formation of a diverse array of nitrogen-containing molecules, and many strategies for their enantioselective synthesis have been developed. Several of the most general methods (for example, allylic substitution, the Overman rearrangement, or imine vinylation) require either activated substrates and/or stoichiometric amounts of either a leaving group or an organometallic reagent, which makes them less attractive in terms of atom and/or step economy. Catalytic enantioselective intermolecular hydroamination is a highly attractive, atom economical approach for the synthesis of non-racemic amines and their derivatives, and has been the subject of much attention. Despite extensive effort, efficient methods for catalytic enantioselective intermolecular hydroamination are rare. Although the enantioselective intermolecular hydroamination of allenes would be an efficient method for the synthesis of a-chiral allylic amines, only one example has been reported, which requires internal allenes, has a limited scope, and provides only moderate levels of enantioselectivity (Scheme la). To date, the enantioselective intermolecular hydroamination of mono-substituted allenes has not been reported, owing to the propensity of many hydroamination catalysts to form achiral products (either imines or linear allylic amines) from such substrates (Scheme 1 b). Herein, we report the first example of the enantioselective intermolecular hydroamination of mono-substituted allenes, producing versatile branched allylic amines with perfect regioselectivity, high yield and good enantioselectivity (Scheme 1 c).