Copper-Catalyzed Three-Component Spiroannulation: Modular Access to 1,3,7,8-Tetraazaspiro[4.4]nona-3,6-dienes via a Metal-Free and Subsequent Cu(II) Relay Strategy

Abstract

A continuous one-pot protocol involving a metal-free oxidative 5-exo-trig cyclization of β, γ-unsaturated hydrazones, followed by Cu(II)-catalyzed intermolecular [3+2] cycloaddition with oximes and nitriles, has been established. Over 90 examples of 1,3,7,8-tetraazaspiro[4.4]nona-3,6-dienes were obtained via this spirocyclization under air. This protocol features excellent functional group tolerance, a wide range of aryl, heteroaryl, alkyl, ketone, ester, ether, thiol ether, silane, alkene, allene, and alkyne groups are all well tolerated.