Chemo- and regio-selective amidation of indoles with isocyanates using borane Lewis acids. Issue 19 (1st September 2022)

• Record Type: Journal Article
• Authors: Dasgupta, Ayan; Guerzoni, Michael G.; Alotaibi, Nusaybah; van Ingen, Yara; Farshadfar, Kaveh; Richards, Emma; Ariafard, Alireza; Melen, Rebecca L.
• Is Part Of: Catalysis science & technology. Volume 12:Issue 19(2022)
• Page Start: 5982
• Page End: 5990
• Publication Date: 2022-09-01
• Subjects: Catalysis -- Periodicals; 541.395
• DOI: 10.1039/d2cy01441f
• Languages: English
• ISSNs: 2044-4753

Abstract

Abstract : A metal-free synthetic route using boranes has been developed for the amidation of indoles. A detailed mechanistic study was carried out to understand the reaction mechanism. Abstract : The efficacy of boron-based catalysts has drawn considerable attention from the scientific community due to their relatively low toxicities and high selectivities. Formation of a new carbon–carbon or carbon–nitrogen bond to generate an amide/urea functionality using mild, catalytic reaction protocols has always been an important challenge, as functionalised amides and urea derivatives are important scaffolds in medicinal chemistry. Herein we report a facile and mild catalytic reaction protocol towards the amidation of N -methyl indoles/pyrroles (17 examples, yields up to 58%) using B(C6 F5 )3 (30 mol%). Moreover, our investigation revealed that although catalytic amounts of B(C6 F5 )3 (10 mol%) are efficient towards the N -carboxamidation of unprotected indoles, catalytic BCl3 (5 mol%) is capable of producing near quantitative yields of the N -carboxamidation products (21 examples, yields up to 95%). In contrast with previous literature reports, the reaction between 2-(alkynyl)anilines and aryl isocyanates using catalytic BCl3 (5 mol%) afforded N–H inserted products (9 examples, yields up to 71%) chemo-selectively as opposed to the intramolecular hydroamination product. Comprehensive DFT studies have been undertaken to understand the mechanistic details of the N–H functionalisation of indoles.