American Chemical Society
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Catalytic Ring Expansion of Indole toward Dibenzoazepine Analogues Enabled by Cationic Palladium(II) Complexes

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posted on 2022-05-10, 14:13 authored by Jiaping Wu, Yanfei Liu, Baiyang Qian, Haitao Yang, Lili Lu, Jitan Zhang, Yongjia Shang
Catalytic ring expansion serves as a powerful tool for the rapid access to molecular complexity and is of significant importance for chemical synthesis. Herein, we report a catalytic ring-expanding reaction of indoles via a C–N bond cleavage by in situ generated cationic palladium­(II) complexes, which provides a concise access to a seven-membered azaheterocycle. The reaction is enabled by a bifunctional quinolinyl group through stabilizing the generated active organometallic species and offering a two-carbon unit for the fused cyclic backbone of the ring-expanding products. As indoles are commercially available and the reaction is by-product free, redox neutral, and tolerant of a wide range of functional groups, this strategy simplifies the synthesis of dibenzoazepine analogues that account for a significant portion of widely prescribed drugs but are challenging to prepare otherwise. The mechanistic studies of the reaction indicate a nucleophilic addition/β-N elimination cascade to accomplish the ring opening of the indole heteroaromatic core and a metal-shift process around the active organometallic species to enable the regioselective recyclization, thereby giving the seven-membered N-containing heterocycles.