One-Pot Synthesis of Fused N,O-Heterocycles through Rh(III)-Catalyzed Cascade Reactions of Aromatic/Vinylic N-Alkoxy-Amides with 4-Hydroxy-2-Alkynoates

A highly efficient and regioselective synthesis of furo[3,4-c]isoquinoline-1,5(3H,4H)-diones and furo[3,4-b]pyridine-2,5(1H,7H)-diones via Rh(III)-catalyzed one-pot cascade reactions of aromatic/vinylic N-alkoxyamides with 4-hydroxy-2-alkynoates is presented. Mechanistically, the formation of the title compounds is triggered by a Rh(III)-catalyzed inert C(sp(2))-H bond activation of the amide substrate followed by its [4+2] annulation and lactonization with 4-hydroxy-2-alkynoate featuring with an oxidizing and partially traceless directing group. To the best of our knowledge, this is the first example in which both the furan-2(5H)-one and the pyridin-2(1H)-one scaffolds are constructed in one pot under one set of reaction conditions. Compared with literature methods, notable features of this new protocol include facile formation of bis-heterocyclic scaffolds from readily available acyclic substrates, broad substrate scope with good tolerance of a wide range of functional groups, excellent regioselectivity and high efficiency.