A Broadly Applicable Diels-Alder-Based Synthesis of Ketamine-Related Arylcyclohexylamines

Herein, we report the synthesis of aryl derivatives of ketamine and 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 [El Sheikh, S.; Weber, H.; Kortenbrede, L.; Drouvé, N. A broadly applicable Diels–Alder based Synthesis of Ketamine related Arylcyclohexylamines.