Highly Diastereo‐ and Enantioselective Synthesis of Tetrahydro‐5H‐Indolo[2,3‐b]quinolines through Copper‐Catalyzed Propargylic Dearomatization of Indoles

• Published in: Chemistry : a European journal Vol. 23; no. 51; pp. 12489 - 12493
• Main Authors: Shao, Wen, You, Shu‐Li
• Format: Journal Article
• Language: English
• Published: WEINHEIM Wiley 12.09.2017; Wiley Subscription Services, Inc
• Subjects: Alkaloids; asymmetric catalysis; Chemical reactions; Chemical synthesis; Chemistry; Chemistry, Multidisciplinary; Copper; dearomatization; Enantiomers; indole; Indoles; Organic chemistry; Organic compounds; Physical Sciences; propargylation; Quinolines; Science & Technology; ASYMMETRIC DEAROMATIZATION; ARYLATIVE DEAROMATIZATION; indole; PENICILLIUM-EXPANSUM; dearomatization; propargylation; asymmetric catalysis; SUBSTITUTION-REACTIONS; 3+2 CYCLOADDITION; PYRROLOINDOLINES; CONSTRUCTION; ESTERS; copper; ALLYLIC DEAROMATIZATION; DERIVATIVES
• ISSN: 0947-6539; 1521-3765
• DOI: 10.1002/chem.201703443

The first copper‐catalyzed intermolecular asymmetric propargylic dearomatization/annulation cascade sequence of indoles via a copper‐allenylidene amphiphilic intermediate has been achieved. This protocol provides a direct asymmetric synthetic method for the preparation of tetrahydro‐5H‐indolo[2,3‐b]quinolines, the core structure of indole alkaloids communesins A–H and perophoramidine. This method features excellent yields, high diastereoselectivity (up to >19:1 d.r.) and enantioselectivity (up to 94 % ee), mild conditions and wide substrate scope. Reaching great heights: The first copper‐catalyzed intermolecular asymmetric propargylic dearomatization/annulation cascade sequence of indoles via a copper‐allenylidene amphiphilic intermediate has been achieved. This protocol provides a direct asymmetric synthetic method for the preparation of tetrahydro‐5H‐indolo[2,3‐b]quinolines, the core structure of indole alkaloids communesins A–H and perophoramidine. This method features excellent yields, high diastereoselectivity (up to >19:1 d.r.) and enantioselectivity (up to 94 % ee), mild conditions and wide substrate scope.