title: Metal-free Cross-Dehydrogenative Coupling of HN-azoles with α-C(sp3)-H Amides via C-H Activation and Its Mechanistic and Application Studies.
abstract: A metal-free one step coupling reaction between various N-azole rings and diverse α-C(sp3)-H containing amides has been developed under oxidative reaction conditions. Commercially available tetrabutyl ammonium iodide (TBAI) in the presence of terbutylhydroperoxide (TBHP), under neat reaction condition, efficiently catalyzed the coupling. Various azole types, such as 1H-benzotriazoles, 1H-1,2,3-triazoles, 1H-1,2,4-triazoles, 1H-tetrazoles, 1H-pyrazoles, and 1H-benzimidazoles, and α-C(sp3)-H containing amides, such as N,N-dimethylacetamide, N,N-dimethylbenzamide, N-methylacetamide, N,N-diethylacetamide, N-methylpyrrolidine, and pyrrolidine-2-one, were successfully employed for the coupling. A series of designed and controlled experiments were also performed in order to study the involvement of the different intermediates. Based on the evidence, a plausible mechanism is also proposed. These novel, simple, rapid, attractive, and straightforward transformations open the way of the construction of novel highly functionalized N-azoles via direct covalent N-H bond transformations onto N-C bonds. This approach allows to the synthesis of complex molecules requiring number of steps using classical synthetic ways. In addition, the range of α-C(sp3)-H containing amide substrates is virtually unlimited highlighting the potential value of this simple system for the construction of complex heterocyclic molecules, such as fused azoles derivatives.
authors.affiliation: Medicinal Chemistry Division, CSIR-Indian Institute of Integrative Medicine, Academy of Scientific and Innovative Research , Canal Road, Jammu 180001, India.
authors.forename: Hariprasad
authors.initials: H
authors.lastname: Aruri
authors.affiliation: Medicinal Chemistry Division, CSIR-Indian Institute of Integrative Medicine, Academy of Scientific and Innovative Research , Canal Road, Jammu 180001, India.
authors.forename: Umed
authors.initials: U
authors.lastname: Singh
authors.affiliation: Medicinal Chemistry Division, CSIR-Indian Institute of Integrative Medicine, Academy of Scientific and Innovative Research , Canal Road, Jammu 180001, India.
authors.forename: Mukesh
authors.initials: M
authors.lastname: Kumar
authors.affiliation: Medicinal Chemistry Division, CSIR-Indian Institute of Integrative Medicine, Academy of Scientific and Innovative Research , Canal Road, Jammu 180001, India.
authors.forename: Sumit
authors.initials: S
authors.lastname: Sharma
authors.affiliation: Medicinal Chemistry Division, CSIR-Indian Institute of Integrative Medicine, Academy of Scientific and Innovative Research , Canal Road, Jammu 180001, India.
authors.forename: Sravan Kumar
authors.initials: SK
authors.lastname: Aithagani
authors.affiliation: X-ray Crystallography Laboratory, University of Jammu , Jammu Tawi 180006, India.
authors.forename: Vivek K
authors.initials: VK
authors.lastname: Gupta
authors.affiliation: PRES Sorbonne Paris Cité, CNRS UMR 860, Laboratoire de Chimie et de Biochimie Pharmacologiques et Toxicologique, Université Paris Descartes , 45, rue des Saints Pères, 75006 Paris, France.
authors.forename: Serge
authors.initials: S
authors.lastname: Mignani
authors.affiliation: Medicinal Chemistry Division, CSIR-Indian Institute of Integrative Medicine, Academy of Scientific and Innovative Research , Canal Road, Jammu 180001, India.
authors.forename: Ram A
authors.identifier: 0000-0002-0752-6238
authors.initials: RA
authors.lastname: Vishwakarma
authors.affiliation: Medicinal Chemistry Division, CSIR-Indian Institute of Integrative Medicine, Academy of Scientific and Innovative Research , Canal Road, Jammu 180001, India.
authors.forename: Parvinder Pal
authors.identifier: 0000-0001-8824-7945
authors.initials: PP
authors.lastname: Singh