Deoxyfluorination of acyl fluorides to trifluoromethyl compounds by FLUOLEAD®/Olah's reagent under solvent-free conditions

Yumeng Liang; Akihito Taya; Zhengyu Zhao; Norimichi Saito; Norio Shibata

doi:10.3762/bjoc.16.254

Deoxyfluorination of acyl fluorides to trifluoromethyl compounds by FLUOLEAD^®/Olah's reagent under solvent-free conditions

Beilstein J Org Chem. 2020 Dec 14:16:3052-3058. doi: 10.3762/bjoc.16.254. eCollection 2020.

Authors

Yumeng Liang¹, Akihito Taya², Zhengyu Zhao², Norimichi Saito³, Norio Shibata^{1

2

4}

Affiliations

¹ Department of Nanopharmaceutical Sciences, Nagoya Institute of Technology, Gokiso, Showa-ku, Nagoya 466-5888, Japan.
² Department of Life Science and Applied Chemistry, Nagoya Institute of Technology, Gokiso, Showa-ku, Nagoya 466-5888, Japan.
³ Pharmaceutical Division, Ube Industries, Ltd., Seavans North Bldg, 1-2-1 Shibaura, Minato-ku, Tokyo 105-8449, Japan.
⁴ Institute of Advanced Fluorine-Containing Materials, Zhejiang Normal University, 688 Yingbin Avenue, 321004 Jinhua, China.

Abstract

A new protocol enabling the formation of trifluoromethyl compounds from acyl fluorides has been developed. The combination of FLUOLEAD^® and Olah's reagent in solvent-free conditions at 70 °C initiated the significant deoxyfluorination of the acyl fluorides and resulted in the corresponding trifluoromethyl products with high yields (up to 99%). This strategy showed a great tolerance for various acyl fluorides containing aryloyl, (heteroaryl)oyl, or aliphatic acyl moieties, providing good to excellent yields of the trifluoromethyl products. Synthetic drug-like molecules were also transformed into the corresponding trifluoromethyl compounds under the same reaction conditions. A reaction mechanism is proposed.

Keywords: acyl fluorides; deoxyfluorination; fluorine; solvent-free; trifluoromethyl group.

Grants and funding

This work was supported by JSPS KAKENHI grants JP 18H02553 (KIBAN B, NS).