Catalytic Ring Expansion of Indole toward Dibenzoazepine Analogues Enabled by Cationic Palladium(II) Complexes
datasetposted 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.
Read the peer-reviewed publication
widely prescribed drugsshift process aroundindole heteroaromatic corefused cyclic backbonebifunctional quinolinyl groupactive organometallic species>- containing heterocyclesn elimination cascadecatalytic ring expansionn catalytic ringwide rangevia thereby givingstrategy simplifiessitu significant portionsignificant importancering openingregioselective recyclizationredox neutralrapid accessproduct freeprepare otherwisepowerful toolnucleophilic additionmolecular complexitymechanistic studiesfunctional groupsexpanding productsdibenzoazepine analoguesconcise accesscommercially availablecationic palladiumcarbon unit