Tf2O-mediated multistate reactivity to access N-acyl and N-aryl azacycles: late-stage modification of bioactive
Zoya Shafeeq1,2, Mohammad Yaqoob Bhat1,2, Ashiq Hussain Padder1
1Natural Product and Medicinal Chemistry Division, CSIR Indian Institute of Integrative Medicine, Jammu 180001, India. naqazi@iiim.ac.in.
Abstract:
N-Acyl and N-aryl azacycles are widely recognized pharmacophores, recurring in heterocyclic frameworks that drive biological activity and drug-like properties. Herein, we report an operationally simple, efficient, Tf2O-driven activation of THF and cyclic amines to afford reactive triflate intermediates that assemble with nitriles or arylamines, followed by cyclization-elimination to furnish N-acyl and N-aryl azacycles. This methodology enables the construction of both five- and six-membered heterocyclic frameworks and accommodates deconstructive fluorination to afford mono-fluorinated derivatives, enamides, and late-stage functionalization of bioactive scaffolds.
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