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Catalyst-Controlled Divergent Reactions of 2,3-Disubstituted Indoles with Propargylic Alcohols: Synthesis of 3<i>H</i>-Benzo[<i>b</i>]azepines and Axially Chiral Tetrasubstituted Allenes

Chenxiao Qian, Tingting Huang, Jianwei Sun, Pengfei Li

2022Organic Letters40 citationsDOI

Abstract

Catalyst-controlled divergent reactions of 2,3-disubstituted indoles with propargylic alcohols were developed for the first time. In the presence of TsOH or B(C6F5)3 as catalyst, 2,3-disubstituted indoles reacted smoothly with 3-alkynyl-3-hydroxyisoindolinones to afford 3H-benzo[b]azepines by selective C2(sp2)–C3(sp2) ring expansion of indoles. In contrast, decreasing the catalyst strength (e.g., with chiral phosphoric acid) interrupted the cascade reactions, affording axially chiral tetrasubstituted allenes bearing an adjacent chiral quaternary carbon stereocenter. Control experiments provided insights into the reaction mechanism.

Topics & Concepts

StereocenterChemistryCatalysisPhosphoric acidCombinatorial chemistryMedicinal chemistryOrganic chemistryEnantioselective synthesisAxial and Atropisomeric Chirality SynthesisAsymmetric Synthesis and CatalysisChemical synthesis and alkaloids
Catalyst-Controlled Divergent Reactions of 2,3-Disubstituted Indoles with Propargylic Alcohols: Synthesis of 3<i>H</i>-Benzo[<i>b</i>]azepines and Axially Chiral Tetrasubstituted Allenes | Litcius