Synthesis of 1-amino-4-hydroxycyclohexane-1-carboxylic acids

Abstract

The synthesis of both stereoisomers of 1-amino-4-hydroxycyclohexane-1-carboxylic acid (1 and 2), a new family of constrained hydroxy-α,α-disubstituted-α-amino acids, is achieved through selective transformations of the functional groups of the corresponding enone cycloadduct provided by the Diels–Alder cycloaddition of Danishefsky’s diene to methyl 2-acetamidoacrylate. The stereochemistry of intermediates 8 and 9 in the synthesis of hydroxy-α-amino acids 1 and 2 was unambiguously confirmed by X-ray structure determination.