Palladium-catalysed enantiodivergent synthesis of cis- and trans-4-aminocyclohex-2-enols

Abstract

Enantiomerically pure cis- and trans-4-aminocyclohex-2-enols are prepared from cyclohexa-1,3-diene via (-)-cis-(1R,4S )-4-acetoxycyclohex-2-enol (-)-2a using palladium(0) chemistry. Benzylamine and diethylamine are tested in the Pd⁰-catalysed allylic amination reactions. Since acetate is too slow as a leaving group and gave considerable amounts of side products, a number of leaving groups have been investigated. Of these phosphinate and 2,4-dichlorobenzoate are excellent leaving groups and result in efficient and highly stereoselective reactions; chloride as allylic leaving group also gives good results. By variation of the leaving group and proper choice of the protecting group it is possible to synthesise all four stereoisomers of 4-aminocyclohex-2-enol in good yield and high enantiomeric excess.