Iridium‐Catalyzed Direct C4‐ and C7‐Selective Alkynylation of Indoles Using Sulfur‐Directing Groups

• Published in: Angewandte Chemie International Edition Vol. 58; no. 29; pp. 9856 - 9860
• Main Authors: Kona, Chandrababu Naidu, Nishii, Yuji, Miura, Masahiro
• Format: Journal Article
• Language: English
• Published: WEINHEIM Wiley 15.07.2019; Wiley Subscription Services, Inc
• Edition: International ed. in English
• Subjects: Alkaloids; Alkynes; Catalysis; Chemistry; Chemistry, Multidisciplinary; C−H activation; heterocycles; Indoles; Iridium; Physical Sciences; Science & Technology; Selectivity; Sulfur; C7-FUNCTIONALIZATION; ALKYL; alkynes; ARYLATION; AMIDATION; C-H ALKYNYLATION; iridium; FUNCTIONALIZATION; C-H activation; OLEFINATION; heterocycles; sulfur; DERIVATIVES; C−H activation
• DOI: 10.1002/anie.201904709
• ISSN: 1433-7851

Indoles and their analogues have been one of the most ubiquitous heterocycles during the past century, and extensive studies have been conducted to establish practical synthetic methods for their derivatives. In particular, selective functionalization of the poorly reactive benzenoid core over the pyrrole ring has been a great challenge. Reported herein is an iridium‐catalyzed direct alkynylation of the indole C4‐ and C7‐positions with the assistance of sulfur directing groups. This transformation shows a wide range of functional‐group tolerance with exceptional site selectivity. The directing group can be either easily removed or transformed after catalysis. The synthetic utility of the alkyne fragment is demonstrated by the derivatization into the core structure of natural indole alkaloids. S‐directed: An iridium‐catalyzed direct alkynylation for the indole C4‐ and C7‐positions was achieved with the assistance of sulfur directing groups. The transformation shows broad functional‐group tolerance with complete site selectivity, and the directing group can be either easily removed or transformed after the reaction.