Metal-Free Directed C-H Borylation of Pyrroles

Zheng-Jun Wang; Xiangyang Chen; Lei Wu; Jonathan J Wong; Yong Liang; Yue Zhao; Kendall N Houk; Zhuangzhi Shi

doi:10.1002/anie.202016573

Metal-Free Directed C-H Borylation of Pyrroles

Angew Chem Int Ed Engl. 2021 Apr 6;60(15):8500-8504. doi: 10.1002/anie.202016573. Epub 2021 Mar 5.

Authors

Zheng-Jun Wang¹, Xiangyang Chen², Lei Wu¹, Jonathan J Wong², Yong Liang¹, Yue Zhao¹, Kendall N Houk², Zhuangzhi Shi¹

Affiliations

¹ State Key Laboratory of Coordination Chemistry, Chemistry and Biomedicine Innovation Center (ChemBIC), School of Chemistry and Chemical Engineering, Nanjing University, Nanjing, 210093, China.
² Department of Chemistry and Biochemistry, University of California, Los Angeles, CA, 90095, USA.

PMID: 33449421
DOI: 10.1002/anie.202016573

Abstract

Robust strategies to enable the rapid construction of complex organoboronates in selective, practical, low-cost, and environmentally friendly modes remain conspicuously underdeveloped. Here, we develop a general strategy for the site-selective C-H borylation of pyrroles by using only BBr₃ directed by pivaloyl groups, avoiding the use of any metal. The site-selectivity is generally dominated by chelation and electronic effects, thus forming diverse C2-borylated pyrroles against the steric effect. The formed products can readily engage in downstream transformations, enabling a step-economic process to access drugs such as Lipitor. DFT calculations (wB97X-D) demonstrate the preferred positional selectivity of this reaction.

Keywords: C−H borylation; DFT calculations; metal-free reactions; pyrroles; site-selectivity.

Publication types

Research Support, Non-U.S. Gov't