Regioselective Synthesis of N-Heteroaromatic Trifluoromethoxy Compounds by Direct O-CF3 Bond Formation

Apeng Liang; Shuaijun Han; Zhenwei Liu; Liang Wang; Jingya Li; Dapeng Zou; Yangjie Wu; Yusheng Wu

doi:10.1002/chem.201505181

Regioselective Synthesis of N-Heteroaromatic Trifluoromethoxy Compounds by Direct O-CF3 Bond Formation

Chemistry. 2016 Apr 4;22(15):5102-6. doi: 10.1002/chem.201505181. Epub 2016 Feb 25.

Authors

Apeng Liang^{1

2}, Shuaijun Han¹, Zhenwei Liu¹, Liang Wang¹, Jingya Li^{1

2}, Dapeng Zou^{3

4}, Yangjie Wu⁵, Yusheng Wu^{6

7

8}

Affiliations

¹ The College of Chemistry and Molecular Engineering, Zhengzhou University, Zhengzhou, 450001, P. R. China.
² Tetranov Biopharm, LLC and Collaborative Innovation Center of New Drug Research and Safety Evaluation, Henan Province, No. 75 Daxue Road, Zhengzhou, 450052, P. R. China.
³ The College of Chemistry and Molecular Engineering, Zhengzhou University, Zhengzhou, 450001, P. R. China. [email protected].
⁴ Tetranov Biopharm, LLC and Collaborative Innovation Center of New Drug Research and Safety Evaluation, Henan Province, No. 75 Daxue Road, Zhengzhou, 450052, P. R. China. [email protected].
⁵ The College of Chemistry and Molecular Engineering, Zhengzhou University, Zhengzhou, 450001, P. R. China. [email protected].
⁶ The College of Chemistry and Molecular Engineering, Zhengzhou University, Zhengzhou, 450001, P. R. China. [email protected].
⁷ Tetranov Biopharm, LLC and Collaborative Innovation Center of New Drug Research and Safety Evaluation, Henan Province, No. 75 Daxue Road, Zhengzhou, 450052, P. R. China. [email protected].
⁸ Tetranov International, Inc., 100 Jersey Avenue, Suite A340, New Brunswick, NJ, 08901, USA. [email protected].

PMID: 26791812
DOI: 10.1002/chem.201505181

Abstract

The first one-step method for the synthesis of ortho-N-heteroaromatic trifluoromethoxy derivatives by site-specific O-CF3 bond formation using hydroxylated N-heterocycles and Togni's reagent is described. The approach enables the unprecedented syntheses of a wide range of six or five-membered N-heteroaromatic trifluoromethoxy compounds containing one or two heteroatoms from most commonly used hydroxylated N-heterocycles. Notable advantages of this method include its simplicity and mild conditions, avoidance of the need for metals or toxic reagents, and compatibility with a variety of functional groups. Furthermore, this method is especially suitable for the larger scale application.

Keywords: C−O bond formation; N-heterocycles; hypervalent iodine reagents; trifluoromethylation.

Publication types

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