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

被引：0

作者：

Gesmundo, Nathan J. ^{[1
]}

Shi, Lei ^{[2
]}

Smith, Russell C. ^{[3
]}

机构：

[1] AbbVie Inc, Adv Chem Technol, Small Mol Therapeut & Platform Technol, 1 North Waukegan Rd, N Chicago, IL 60064 USA

[2] AbbVie Inc, Small Mol Therapeut & Platform Technol, Global Med Chem, 1 North Waukegan Rd, N Chicago, IL 60064 USA

[3] AbbVie Inc, Centralized Organ Synth Grp, Small Mol Therapeut & Platform Technol, N Chicago, IL 60064 USA

来源：

HELVETICA CHIMICA ACTA | 2023年 / 106卷 / 12期

关键词：

bicyclo[1.1.1]pentane; bioisosteres; copper; copper-catalysis; high-throughput experimentation; non-photonic coupling; synthetic methods; ANALOGS;

D O I：

10.1002/hlca.202300158

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

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. image

引用

页数：8