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

Abstract

Copper-catalysed reaction of the serine-derived zinc reagent 1 with allylic electrophiles gives products arising formally from both S_N2 and S_N2′ pathways. These constitutional isomers can be separated, either directly, or in the case of (2S)-2-tert-butoxycarbonylamino-6-methylhept-5-enoic acid methyl ester (11) and (2S)-2-tert-butoxycarbonylamino-4,4-dimethylhex-5-enoic acid methyl ester (12) by selective epoxidation of 11. Hydrogenation of the double bond, followed by protecting group manipulation, allows the synthesis of the Fmoc-protected amino acids 3–7 ready for automated peptide synthesis.