A new route to hydrophobic amino acids using copper-promoted reactions of serine-derived organozinc reagents

Copper-catalysed reaction of the serine-derived zinc reagent 1 with allylic electrophiles gives products arising formally from both S(N)2 and S(N)2' p athways. These constitutional isomers can be separated, either directly, or in the case of (2S)-2-tert-butoxycarbonylamino-6-methylhept-5-enoic acid m ethyl ester (11) and (2S)-2-tert-butoxycarbonylamino-4,4-dimethylhex-5-enoi c acid methyl ester (12) by selective epoxidation of 11. Hydrogenation of t he double bond, followed by protecting group manipulation, allows the synth esis of the Fmoc-protected amino acids 3-7 ready for automated peptide synt hesis.