Regiocontrolled Direct C−H Arylation of Indoles at the C4 and C5 Positions

• Published in: Angewandte Chemie International Edition Vol. 56; no. 14; pp. 3966 - 3971
• Main Authors: Yang, Youqing, Gao, Pan, Zhao, Yue, Shi, Zhuangzhi
• Format: Journal Article
• Language: English
• Published: WEINHEIM Wiley 27.03.2017; Wiley Subscription Services, Inc
• Edition: International ed. in English
• Subjects: arylation; Chemistry; Chemistry, Multidisciplinary; copper; Hydrogen bonds; Indoles; palladium; Physical Sciences; regioselectivity; Science & Technology; regioselectivity; ROOM-TEMPERATURE; DIAZONAMIDE-A; DIARYLIODONIUM SALTS; 2ND TOTAL-SYNTHESIS; arylation; FUNCTIONALIZATION; indoles; MILD CONDITIONS; BOND ARYLATION; REGIOSELECTIVE SYNTHESIS; copper; palladium; N-PIVALOYLINDOLES; CATALYZED DIRECT ARYLATION
• ISSN: 1433-7851; 1521-3773
• DOI: 10.1002/anie.201612599

An effective and practical strategy has been established for the direct and site‐selective arylation of indoles at the C4 and C5 positions with the aid of a readily accessible, cheap, and removable pivaloyl directing group at the C3 position. This transformation shows good functional‐group tolerance and could serve as a powerful synthetic tool for the synthesis of medicinally relevant compounds. This method and those developed in previous research together enable the regiocontrolled direct arylation of indole at each C−H bond without prefunctionalization of the reactive sites. Grand Slam: An effective and practical strategy has been established for the direct site‐selective arylation of indoles at the C4 or C5 position (see scheme) by the use of a readily available and removable pivaloyl directing group (DG) at the indole C3 position. Now the direct site‐selective arylation of indoles at any given C−H bond is possible by the appropriate choice of this or a previously developed complementary method.