Asymmetric syntheses of α-methyl γ-amino acid derivatives

This project was undertaken to demonstrate the potential of asymmetric hydrogenations mediated by the chiral, carbene-oxazoline analogue of Crabtree's catalyst "cat" in asymmetric hydrogenations of allylic amine derivatives of amino acids. Peripheral features of the substrates (protecting groups, functional groups related by redox processes, and alkene geometries) were varied to optimize the stereochemical vectors exerted by the substrate and align them with the catalyst vector. N-Acetyl-protected, O-TBDPS-protected allylic substrates 9a-e emerged as the best for this reaction; syn-products were formed from the E-alkenes, while the Z-isomers gave anti-target materials, both with high diastereoselectivities. This study featured asymmetric catalysis to elaborate optically active substrates into more stereochemically complex chirons; we suggest that the approach used, optimization of stereocontrol by varying peripheral aspects of the substrate, tends to be easier than de novo catalyst design for each substrate type. In other words, optimization of the substrate vector is likely to be more facile than enhancement of the catalyst vector via ligand modifications.