Asymmetric synthesis of alpha-amino acids: preparation and alkylation of monocyclic iminolactones derived from alpha-methyl trans-cinnamaldehyde.
Two novel chiral monocyclic iminolactones 14a and 14b have been prepared. The chiral auxiliary 12 was obtained from alpha-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 alpha-methyl-alpha,alpha-disubstituted products 15 and 16 in good yields (78-99%) and excellent diastereoselectivity (de >98%). Alkylations of the iminolactone 14b furnished the alpha-benzyl-alpha,alpha-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 alpha,alpha-disubstituted alpha-amino acids in good yields (80-98%) and high enantiomeric excesses (98-99%) with good recovery of compound 12 (83-92%).
Lu
Ta-Jung
TJ
Department of Chemistry, National Chung-Hsing University, Taichung, Taiwan 40227, Republic of China. tjlu@dragon.nchu.edu.tw
Lin
Cheng-Kun
CK
D000171:Acrolein / Q000031:analogs & derivatives* / Q000737:chemistry; D000478:Alkylation; D000596:Amino Acids / Q000138:chemical synthesis*; D018360:Crystallography, X-Ray; D003500:Cyclization; D007202:Indicators and Reagents; D007783:Lactones / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D013237:Stereoisomerism
D000596:Amino Acids; D007202:Indicators and Reagents; D007783:Lactones; D000171:Acrolein; C012843:cinnamaldehyde