Metal-free directed sp2-C-H borylation

Jiahang Lv; Xiangyang Chen; Xiao-Song Xue; Binlin Zhao; Yong Liang; Minyan Wang; Liqun Jin; Yu Yuan; Ying Han; Yue Zhao; Yi Lu; Jing Zhao; Wei-Yin Sun; Kendall N Houk; Zhuangzhi Shi

doi:10.1038/s41586-019-1640-2

Metal-free directed sp²-C-H borylation

Nature. 2019 Nov;575(7782):336-340. doi: 10.1038/s41586-019-1640-2. Epub 2019 Sep 30.

Authors

Jiahang Lv^#^{1

2}, Xiangyang Chen^#³, Xiao-Song Xue^{3

4}, Binlin Zhao¹, Yong Liang¹, Minyan Wang¹, Liqun Jin⁵, Yu Yuan², Ying Han², Yue Zhao¹, Yi Lu¹, Jing Zhao¹, Wei-Yin Sun¹, Kendall N Houk⁶, Zhuangzhi Shi^{7

8

9}

Affiliations

¹ State Key Laboratory of Coordination Chemistry, Chemistry and Biomedicine Innovation Center (ChemBIC), School of Chemistry and Chemical Engineering, Nanjing University, Nanjing, China.
² College of Chemistry and Chemical Engineering, Yangzhou University, Yangzhou, China.
³ Department of Chemistry and Biochemistry, University of California, Los Angeles, Los Angeles, CA, USA.
⁴ State Key Laboratory of Elemento-organic Chemistry, College of Chemistry, Nankai University, Tianjin, China.
⁵ College of Chemical Engineering, Zhejiang University of Technology, Hangzhou, China.
⁶ Department of Chemistry and Biochemistry, University of California, Los Angeles, Los Angeles, CA, USA. houk@chem.ucla.edu.
⁷ State Key Laboratory of Coordination Chemistry, Chemistry and Biomedicine Innovation Center (ChemBIC), School of Chemistry and Chemical Engineering, Nanjing University, Nanjing, China. shiz@nju.edu.cn.
⁸ College of Chemistry and Chemical Engineering, Yangzhou University, Yangzhou, China. shiz@nju.edu.cn.
⁹ State Key Laboratory of Elemento-organic Chemistry, College of Chemistry, Nankai University, Tianjin, China. shiz@nju.edu.cn.

^# Contributed equally.

PMID: 31723273
DOI: 10.1038/s41586-019-1640-2

Abstract

Organoboron reagents are important synthetic intermediates that have a key role in the construction of natural products, pharmaceuticals and organic materials¹. The discovery of simpler, milder and more efficient approaches to organoborons can open additional routes to diverse substances^2-5. Here we show a general method for the directed C-H borylation of arenes and heteroarenes without the use of metal catalysts. C7- and C4-borylated indoles are produced by a mild approach that is compatible with a broad range of functional groups. The mechanism, which is established by density functional theory calculations, involves BBr₃ acting as both a reagent and a catalyst. The potential utility of this strategy is highlighted by the downstream transformation of the formed boron species into natural products and drug scaffolds.

Publication types

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

MeSH terms

Biological Products / chemical synthesis
Biological Products / chemistry
Boron / chemistry*
Boron Compounds / chemical synthesis*
Boron Compounds / chemistry*
Density Functional Theory
Drug Discovery
Indoles / chemistry
Organometallic Compounds / chemistry
Pharmaceutical Preparations / chemical synthesis
Pharmaceutical Preparations / chemistry

Substances

Biological Products
Boron Compounds
Indoles
Organometallic Compounds
Pharmaceutical Preparations
Boron