Author:

Keywords:

c-c coupling, cyclization, nitrogen heterocycles, medium-ring compounds, microwave chemistry, highly enantioselective synthesis, c-h activation, efficient synthesis, asymmetric-synthesis, lactam precursors, domino reactions, propargylamines, (-)-aphanorphine, alkyne, Science & Technology, Physical Sciences, Chemistry, Organic, Chemistry, C-C coupling, Cyclization, Nitrogen heterocycles, Medium-ring compounds, Microwave chemistry, HIGHLY ENANTIOSELECTIVE SYNTHESIS, C-H ACTIVATION, EFFICIENT SYNTHESIS, ASYMMETRIC-SYNTHESIS, LACTAM PRECURSORS, DOMINO REACTIONS, PROPARGYLAMINES, ALKYNE, ALDEHYDE, 0304 Medicinal and Biomolecular Chemistry, 0305 Organic Chemistry, Organic Chemistry, 3404 Medicinal and biomolecular chemistry, 3405 Organic chemistry

Abstract:

An efficient diversity-oriented procedure for the two-step synthesis of 3-benzazepines is described. The Cu-I-catalyzed three-component coupling of an aldehyde, an alkyne and an amine (A(3)-coupling) provides the required propargylamines and assures the generation of diversity. The Pd-catalyzed intramolecular acetylene hydroarylation reaction selectively creates the seven-membered 3-benzazepine framework with full control over the ring size and the geometry around the double bond. Microwave irradiation is demonstrated to be highly efficient in promoting both steps.