Palladium(II)-Catalyzed Cyclizative Cross-Coupling of ortho-Alkynylanilines with ortho-Alkynylbenzamides under Aerobic Conditions

摘要

In light of the importance of heterocycles in medicinal chemistry and from the viewpoint of synthetic efficiency, cyclizative dimerization is of particular interest as it allows the preparation of cyclic dimers from linear starting materials and indeed a few successful examples have recently been reported wherein heteronucleometallation is used as a key initiation step (Scheme 1 a). Concurrently, palladium(0)-catalyzed co-cyclization of two internal alkynes, one bearing an electro-phile and the other a nucleophile, by a sequence of carbopalladation and reductive elimination has been developed by the group of Wu. An even more challenging but synthetically powerful transformation would be cyclizative cross-coupling reaction of two different nucleophile-bearing internal alkynes for the one-step construction of heterodimers (Scheme 1 b). To the best of our knowledge, there are only few examples developed by Ma and Yu wherein allenes are used as cyclization partners. We report herein that the cyclizative cross-coupling reaction between o-alkynylanilines (1) and o-alkynylbenzamides (2) takes place efficiently to afford the bis(heterocycle)s 3 (Scheme 2). In this reaction, three chemical bonds are created, thus leading to the formation of two heterocycles, an indole and an iminoiso-benzofuranone, which are tethered by a geometrically defined tetrasubstituted double bond.