Asymmetric syntheses via heterocyclic intermediates-XXII: Enantioselective synthesis of α-alkenyl glycine methyl esters and α-alkenyl glycines (β,γ -unsaturated amino acids)

Abstract

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 >95%. Both approaches are based on the bislactim ether method developed by Schöllkopf . 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>95%. These on acid hydrolysis afford L-valinate 8 and the methyl (2 R)-2-amino-4-(dimethyl t-butyl)silyl-3-hydroxyalkanoate 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 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