Enantioselective Parallel Kinetic Resolution of Aziridine-Containing Quinoxalines via Chiral Phosphoric Acid Catalyzed Transfer Hydrogenation

This manuscript describes asymmetric synthesis of novel chiral aziridinoquinoxaline scaffolds using chiral phosphor-ic acid-catalyzed parallel kinetic and kinetic resolutions under transfer hydrogenation conditions with Hantzsch es-ters. While the achiral phosphoric acids such as BPPA were found to promote diastereoselective substrate-controlled reductions from the more sterically accessible face with excellent diastereoselectivities, (R)-TRIP catalyst was unique in dictating the catalyst-controlled Si-face selectivity for both enantiomers of the starting materials. The parallel kinet-ic resolution was successfully accomplished for 16 different substrates and led to highly enantioenriched and readily separable diasteromers with (S)-configuration of the newly formed stereocenter (32-61% yield, 64-99% ee, for the (S,S,R)-diastereomers and 7-45% yield, 97-99% ee for the (R,R,S)-diastereomers). This process could be coupled with ring-opening of the (S,S,R)-diastereomer with thiophenol to produce chiral tetrahydroquinoxalines with three con-tiguous stereocenters.