A Synthetic Route to Tetrahydro-1H-azepino[4,3,2-cd]indoles via Ring-Opening Cyclization of Activated Azetidines with 4-Bromoindole: Toward a Vasopressin V2 Receptor Antagonist

Abstract

A simple one-pot, two-step strategy for the synthesis of tetrahydro-1H-azepino[4,3,2-cd]indoles via Lewis acidcatalyzed S N 2-type ring opening of activated azetidines with 4-bromoindole, followed by a Pd-catalyzed intramolecular C−N cyclization reaction, with good to excellent yields is described. Utilizing this protocol, the vasopressin V2 receptor antagonist precursor has been synthesized easily. Enantioenriched tetrahydro-1H-azepino[4,3,2-cd]indoles were obtained by starting from enantiopure azetidine.