ASYMMETRIC SYNTHESES VIA HETEROCYCLIC INTERMEDIATES-XXII; ENANTIOSELECTIVE SYNTHESIS OF α-ALKENYL GLYCINE METHYL ESTERS AND α-ALKENYL GLYCINES (β,γ-UNSATURATED AMINO ACIDS)

Article abstract of DOI:10.1016/S0040-4020(01)82426-1

Enantioselective syntheses of α-alkenyl glycines of type 10 and of type 23 are described that provide these uncommon amino acids with predictable configuration and with ee-values of >95percent.Both approaches are based on the bislactim ether method developed by Schoellkopf et al.As for 10: The lithiated bis-lactim ether 6 of cyclo(L-val-gly) is reacted with 2<(dimethyl t-butyl)silyl>alkanals 2 to give the addition products 7 with de>95percent.These on acid hydrolysis afford L-valinate 8 and the methyl (2R)-2-amino-4-(dimethyl t-butyl)silyl-3-hydroxyalkanoates 9 which are convertible into the (R)-α-alkenyl glycines of type 10.The scope of this synthesis is limited by the fact that the compounds 9 are thermolabile when disubstituted at C-4.As for 23: The lithiated bis-lactim ether 6 is reacted with thioketones 14 to give the addition products 15 with de>95percent.The S-methyl compounds 16 undergo elimination to give regioselectively the olefins 18 when treated with Raney-Ni.Alternatively, the olefins 18 are obtained from the sulfonium salts 24 by dimethyl sulfide elimination, although this route is less regiospecific.The compounds 18 are cleaved by dilute hydrochloric acid, liberating L-valinate 8 and (R)-α-alkenyl glycine methyl esters 21, which on further hydrolysis yield (R)-α-alkenyl glycines 23.This synthesis is limited only by the availability of thioketones 14.