Sequential [3,3]-Sigmatropic Rearrangement/Nucleophilic Aryl­ation of N-(Benzoyloxy)enamides towards the Preparation of Cyclic β-Aryl-β-amino Alcohols

Abstract

A new method has been developed for the efficient synthesis of cyclic β-aryl-β-amino alcohol derivatives bearing a tetrasubstituted carbon center via the [3,3]-sigmatropic rearrangement of N-(benzoyloxy)enamides followed by nucleophilic arylation reaction with a range of triarylaluminum reagents. The resulting products were converted into the corresponding sterically congested cyclic β-amino alcohols, as well as the dissociative anesthetic agent Tiletamine.

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

“…A universal synthesis method covering a wide substrate range is advantageous for building a broad substance library. A number of methods for the synthesis of aryl derivatives of ketamine, norketamine, and hydroxynorketamine has been reported in the literature. ,− In addition, some asymmetric approaches for the synthesis of aryl-substituted analogues of ketamine and ketamine metabolites have been published . We opted for a racemic synthesis because it is assumed that both enantiomers contribute to the pro-neuroplastic effects in different ways. , Since hydroxynorketamine derivatives are usually generated from norketamine derivatives by a Rubottom oxidation, we first focused on the preparation of norketamine analogues.…”