New routes to β-cycloalkylalanine derivatives using serine-derived organozinc reagents

Organic & Biomolecular Chemistry Pub Date: 2005-10-03 DOI: 10.1039/B512784J

Abstract

Two distinct routes to β-cycloalkylalanine derivatives have been developed. The first route employs the reaction of the iodoalanine-derived zinc–copper reagent 2 with cycloalk-1-en-3-yl phosphates, and the second uses the palladium-catalysed coupling of the iodoalanine-derived zinc reagent 1 with cycloalkenyl triflates; in each case, catalytic hydrogenation of the unsaturated product leads to the protected β-cycloalkylalanine. The latter route allows access to a range of cycloalkyl derivatives, with ring sizes of 5–8. β-(1-Methyl-1-cyclohexyl)alanine may be prepared using reaction of the zinc–copper reagent 2 with 3-methyl-2-cyclohexenyl chloride, followed by hydrogenation. The corresponding cyclopentyl derivative may be prepared by reaction of the same zinc–copper reagent 2 with diethyl geranylphosphate, followed by ring-closing metathesis and hydrogenation.

Graphical abstract: New routes to β-cycloalkylalanine derivatives using serine-derived organozinc reagents
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