Stereoselective synthesis of functionalised cycloalkene α-quaternary α-amino acid derivatives

A route for the preparation of unsaturated cyclic alpha-quaternary a-amino acid derivatives is described. Stepwise and stereocontrolled alkylations of the chiron (R)-2-isopropyl-3,6-dimethoxy-2,5-dihydropyrazine provided gem-disubstituted derivatives with an alkene and an alkoxo substituent. The Wacker oxidation was compatible for chemoselective oxidation of the alkene function. Formation of a methyl ketone or an aldehyde was substrate dependent. Spironnulation in the dioxo substrates was effected with caesium carbonate in acetonitrile by intramolecular aldol condensations. The regiochemistry was substrate dependent. Cleavage of the heterospiranes under mild acidic conditions provided cyclic alpha-quaternary alpha-amino acid derivatives. (C) 2003 Elsevier Ltd. All rights reserved.