Highly Diastereoselective Synthesis of Oxindole-Bearing Pyrroloindoline via Gold Catalyzed Carbophilic Carbene Transfer Reaction

A new type of gold catalyzed intermolecular dearomative cyclization reaction between diazo oxindole and tryptamine has been developed by utilizing the combination of L₃AuCl/Ag₃PO₄ (L₃=hexamethyl phosphane triamine) as the catalyst. This method allows for the facile preparation of a series of C-3-oxindole fused pyrroloindoline products in moderate to good yields with high diastereoselectivities. A plausible reaction mechanism, involving a cascade process of regioselective nucleophilic addition of the carbophilic gold carbenoid intermediate onto tryptamine, followed by an intramolecular cyclization, has been proposed, in which, the high diastereoselectivity is attributed to a preferred transition state. Moreover, three oxindole-bearing indolo[2,3-b] quinoline derivatives were synthesized through dearomative cyclization of homotryptamine derivative 4a with the respective 3-diazoindolin-2-one substrates using a similar strategy. A gram-scale experiment successfully yielded 1.95 g of 3 aa in 85 % yield with a diastereomeric ratio (dr) of 10.4/1, ultimately enabling a five-step synthesis of the natural product (±)-folicanthine.