Enhancement of the carbamate activation rate enabled syntheses of tetracyclic benzolactams: 8-oxoberbines and their 5- and 7-membered C-ring homologues

Abstract

A route to the direct amidation of aromatic-ring-tethered N-carbamoyl tetrahydroisoquinoline substrates was developed. This route enabled general access to 8-oxoberberines and their 5- and 7- membered C-ring homologues. It overcomes the undesired tandem side-reactions that result in the destruction of the isoquinoline backbone, which inevitably occurred under our previously reported superacidic carbamate activation method.