A Practical and Scalable Non‐Photonic Decarboxylative C‒N Coupling of Bicyclo[1.1.1]Pentane Carboxylate by Leveraging High Throughput Experimentation

Research towards the development of novel synthetic methods to access substituted bicyclo[1.1.1]pentane (BCP) structural motifs has been conducted by both academic groups and industrial organizations. Recent developments have been strongly focused on the utility of visible light catalysis to promote a cornucopia of radical‐based transformations, including incorporation of BCP motifs. While these methods have proven powerful in accessing various substitution patterns, some scalability challenges remain. Herein we describe a focused effort on the high‐throughput experimentation (HTE) guided optimization of a decarboxylative non‐photonic coupling that can be conducted using traditional batch reactors. Employing an unanticipated mixture of copper(I) chloride and cyclopentyl methyl ether (CPME) results in the formation of a N‐substituted bicyclo[1.1.1]pentyl pyrazole product while limiting the overall equivalency of the hypervalent iodonium precursor.