Phosphine-Catalyzed Annulations of Azomethine Imines: Allene-Dependent 3 + 2, 3 + 3, 4 + 3, and 3 + 2 + 3 Pathways

In this paper we describe the phosphine-catalyzed 3 + 2, 3 + 3, 4 + 3, and 3 + 2 + 3 annulations of azomethine imines and allenoates. These processes mark the first use of azomethine imines in nucleophilic phosphine catalysis, producing dinitrogen-fused heterocycles, including tetrahydropyrazolo-pyrazolones, -pyridazinones, -diazepinones, and -diazocinones. Counting the two different reaction modes in the 3 + 3 cyclizations, there are five distinct reaction pathways-the choice of which depends on the structure and chemical properties of the allenoate. All reactions are operationally simple and proceed smoothly under mild reaction conditions, affording a broad range of 1,2-dinitrogen-containing heterocycles in moderate to excellent yields. A zwitterionic intermediate formed from a phosphine and two molecules of ethyl 2,3-butadienoate acted as a 1,5-dipole in the annulations of azomethine imines, leading to the 3 + 2 + 3 tetrahydropyrazolo-diazocinone products. The incorporation of two molecules of an allenoate into an eight-membered-ring product represents a new application of this versatile class of molecules in nucleophilic phosphine catalysis. The salient features of this protocol--the facile access to a diverse range of nitrogen-containing heterocycles and the simple preparation of azomethine imine substrates--suggest that it might find extensive applications in heterocycle synthesis.