A broadly applicable Diels-Alder based Synthesis of Ketamine related Arylcyclohexylamines

Abstract

Herein we report the synthesis of both aryl derivatives of ketamine and aryl derivatives of ketamine’s major metabolites hydroxynorketamine (HNK), norketamine (NK) and dehydronorketamine (DHNK) via a microwave-assisted Diels-Alder reaction to form the substituted cyclohexane core structure. Starting with aryl acrylic esters as dienophiles and siloxybutadienes as diene counterparts, a wide range of substituted arylcyclohexylamines was obtained after several modification steps of the initial Diels-Alder products.