Synthesis of Azepines via a [6 + 1] Annulation of Ynenitriles with Reformatsky Reagents

A protocol for the direct synthesis of azepines using a hafnium­(III)-catalyzed [6 + 1] annulation of N-tethered ynenitriles with Reformatsky reagents is reported. A broad range of 3-amino-2,7-dihydro-1H-azepine-4-carboxylates 4aa–4he were obtained in high yields and with excellent functional group tolerance. The copper-mediated reactions of isolable Blaise intermediates (enamino esters 3), uniquely underwent 5-endo cyclization to afford the β-2,5-dihydropyrrolyl α,β-unsaturated esters 5aa–5fc, which exhibit anticancer activity.