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

A simple one-pot, two-step strategy for the synthesis of tetrahydro-1-azepino[4,3,2-]indoles via Lewis acid-catalyzed S2-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-1-azepino[4,3,2-]indoles were obtained by starting from enantiopure azetidine.