Asymmetric syntheses via heterocyclic intermediates. 22. Enantioselective synthesis of alpha-alkenyl glycine methyl esters and alphy-alkenyl glycines (beta,gamma-unsaturated amino acids)

Abstract

Enantioselective syntheses of α-alkenyl glycines of type 10 and of type 23 are described that provide these uncommon ammo acids with predictable conf&uration and with ec-values of >95%. Both approaches are based on the bislactim ether method developed by SchBllkopf et al. As for 10: The lithiated his-lactim ether 6 of cyclo(t-val-gly) is reacted with 2-[(dimethyl t-butyl)silyl]alkanals 2 to give the addition products 7 with de> 95%. These on acid hydrolysis afford L-valinate 8 and the methyl (2R)-2-amino4(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 disubstitued 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>95%. The S-methyl compounds 16 undergo elimination to give regioselectively the olefins 18 when treated with Raney-Ni. Alternatively, the olefms 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 methvl esters 21. which on further hvdrolvsis vield (R)-α-alkenyl glycines 23. This synthesis is limited only by the availability of thioketones 14.