Asymmetric Synthesis of α-Amino Acids: Preparation and Alkylation of Monocyclic Iminolactones Derived from α-Methyl <i>trans</i>-Cinnamaldehyde

Two novel chiral monocyclic iminolactones 14a and 14b have been prepared. The chiral auxiliary 12 was obtained from α-methyl-trans-cinnamaldehyde through reduction, methylation, Sharpless asymmetric dihydroxylation, and oxidation in 87% overall yield. Esterification of compound 12 with the respective protected amino acids followed by deprotection and cyclization provided the corresponding iminolactones, each in 82% overall yield. Alkylation of the iminolactone 14a afforded the α-methyl-α,α-disubstituted products 15 and 16 in good yields (78−99%) and excellent diastereoselectivity (de >98%). Alkylations of the iminolactone 14b furnished the α-benzyl-α,α-disubstituted products 15a, 16b, 17, and 18 in good yields (51−86%) but moderate diastereoselectivities (43−56%). When HMPA or DMPU was used as a cosolvent, the rate of alkylation of the iminolactone 14b was accelerated with improved yields (56−99%) and diastereoselectivities (50−83%). Hydrolysis of the dialkylated iminolactones yielded the α,α-disubstituted α-amino acids in good yields (80−98%) and high enantiomeric excesses (98−99%) with good recovery of compound 12 (83−92%).