ABSTRACT
Dynamic kinetic resolution (deracemization) of various alpha-alkyl-substituted beta-ketoamides 1 via asymmetric transfer hydrogenation proceeded efficiently to give the corresponding syn-beta-hydroxy amides 3 in high diastereo- and enantioselectivities. Specifically, subjection of 1 to HCO(2)H and Et(3)N in the presence of 0.5-1 mol % of pentafluorobenzenesulfonyl-DPEN-Ru catalyst 2b at 30-40 degrees C in either PhCH(3) or CH(2)Cl(2) generated the syn-hydroxy product 3 selectively in 15-33:1 dr, 93-97% ee, and 75-88% isolated yields.
Subject(s)
Amides/chemical synthesis , beta-Lactams/chemical synthesis , Amides/chemistry , Catalysis , Combinatorial Chemistry Techniques , Hydrogenation , Kinetics , Molecular Structure , Stereoisomerism , beta-Lactams/chemistryABSTRACT
Asymmetric hydrogenation of allylic dimethylcarbinamide 2 with 1 mol % of cationic Rh(I)-Josiphos complex in THF under 500 psi of H2 generated the corresponding tertiary carbinamide 1 in 98.5% assay yield and a 94:6 enantiomeric ratio. Upon crystallization, the product was isolated in 91% isolated yield and 95:5 enantiomeric ratio.