Synthesis of N-protected amino acids, especially N-tert-butoxycarbonyl-L-propargylglycine, via zinc-mediated addition of organic halides to glycine cation equivalents.

Abstract

(Un)natural amino acids are prepd. by reaction of PNHCH(OR1)CO2R2 with R3X to give racemic PNHCHR3CO2R2 [P = protecting group; R1 = H, alkyl, cycloalkyl, alkoxyalkyl, acyl, aralkyl, aryl, aroyl; R2 = alkyl, cycloalkyl, alkoxyalkyl, aralkyl, aryl; X = Cl, Br, iodo; R3 = alkyl, cycloalkyl, alkoxyalkyl, alkoxycarbonylalkyl, allyl, PhCH2, (substituted) propargyl]. The method involves reaction of an org. halide with a glycine cation equiv., such as N-BOC-2-acetoxyglycine Me ester, in the presence of Zn dust to give BOC-protected amino acid derivs. in high yield. Typically useful org. halides are allylic, benzylic and propargylic halides. Kinetic resoln. of N-BOC-propargylglycine Me ester with -chymotrypsin provides N-BOC-L-propargylglycine in 92% yield at 88% enantiomeric excess.