Enantio- and Diastereoselective Synthesis of Highly Substituted Benzazepines by a Multicomponent Strategy Coupled with Organocatalytic and Enzymatic Procedures

Enantiomerically pure 4,5-dihydro-1H-benzo[c]azepines with three contiguous stereogenic centers have been assembled by convergent strategy with a good control of diastereoselectivity. The two steps are as follows: an asymmetric organocatalytic Mannich reaction performed on Boc-imines of o-(azidomethyl)benzaldehydes, followed by a one-pot Staudinger/ aza-Wittig/Ugi−Joullié sequence. The latter reaction represents one of the first examples of diastereoselective Ugi threecomponent reaction on a seven-membered cyclic imine. The o-azidomethylbenzaldehydes have been synthesized employing a simple and efficient chemoenzymatic strategy from commercially available building blocks.