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.

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 [A broadly applicable Diels–Alder based Synthesis of Ketamine related Arylcyclohexylamines10.26434/chemrxiv- 2022-xf1l9ChemRxiv2022].