Transition-Metal-Free Synthesis of Trifluoromethylated Furans via a Bu₃P-Mediated Tandem Acylation–Wittig Reaction

Abstract

A highly efficient nucleophilic addition–O-acylation–intramolecular Wittig reaction of β-trifluoromethyl α,β-enones is disclosed. This strategy features mild reaction conditions and provides a practical transition-metal-free method to a set of biologically significant trifluoromethylated furans in high yields with diverse functional groups.

Key words

β-trifluoromethyl α,β-enones - Wittig reaction - nucleophilic addition - furans - trifluoromethylated furans

Publication History

Received: 07 July 2020

Accepted after revision: 03 August 2020

Article published online:
02 September 2020

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• 9 Typical Procedure for the Bu₃P-Mediated Tandem Acylation–Wittig Reaction In a 25 mL dry Schlenk tube equipped with a stirring bar, a solution of acyl chloride 2 (1.1 equiv) and Bu₃P (1.1 equiv) in dry THF (1.0 mL) and a solution of β-trifluoromethyl α,β-enone 1 (0.2 mmol) in dry THF (1.0 mL) was added. Subsequently, Et₃N (1.5 equiv) was added to the above reaction solution. The reaction mixture was stirred for 0.5 h at room temperature, the reaction was monitored by TLC (hexane). Thereafter, the solvent was removed by evaporation in vacuo, and the residue was purified by flash chromatography on silica gel (hexane/EtOAc = 100:0 to 40:1) to furnished the desired trifluoromethyl-functionalized multisubstituted furans 3. Analytical Data for Compound 3aa White solid. ¹H NMR (500 MHz, CDCl₃): δ = 7.79−7.72 (m, 4 H), 7.49−7.41 (m, 5 H), 7.34−7.32 (m, 1 H), 6.89 (s, 1 H). ¹³C NMR (125 MHz, CDCl₃): δ = 153.03, 151.90 (q, J = 5.00 Hz), 129.46, 129.31, 128.90, 128.67, 128.41, 127.15 (q, J = 1.25 Hz), 124.06, 122.91 (q, J = 266.25 Hz), 114.29 (q, J = 37.50 Hz), 105.27 (q, J = 3.75 Hz). ¹⁹F NMR (376 MHz, CDCl₃): δ = –56.41 ppm. HRMS (EI): m/z calcd for C₁₇H₁₁F₃O [M]⁺: 288.0757; found: 288.0753.

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