Photoredox Defluorinative Silylation of α-Trifluoromethyl Arylalkenes Using Silacarboxylic Acids as Silyl Radical Precursors

Abstract

A photoredox defluorinative silylation of α-trifluoromethyl arylalkenes for rapid access to useful gem-difluoroalkenes is disclosed. Stable and easily prepared silacarboxylic acids are used as silyl radical precursors in a photocatalytic decarboxylative process. The mild conditions and operational simplicity make our method a straightforward strategy to construct gem-difluoroalkenes bearing various functional groups, and a powerful strategy for incorporating a gem-difluoroalkene moiety into natural products and drug molecules.

Key words

photoredox reaction - defluorination - silylation - difluoroalkenes - silyl radicals - late-stage modification

Publication History

Received: 26 May 2023

Accepted after revision: 04 July 2023

Accepted Manuscript online:
04 July 2023

Article published online:
21 August 2023

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• 16 Silylated gem-Difluoroalkenes 3a–z; General Procedure A screw-capped vial equipped with a stirrer bar was charged with the appropriate silanecarboxylic acid 1 (0.1 mmol, 1.0 equiv), difluoroalkene 2 (0.11 mmol, 1.1 equiv), 4CzIPN (PC₁ ; 2 mol%), and K₂CO₃ (0.15 mmol, 1.5 equiv) under N₂ in a glove box. EtOAc (1.5 mL) was added the vial from a syringe, and the vial was sealed with a cap containing a PTFE septum and removed from the glove box. The stirred mixture was then irradiated by a 20 W blue LED under a N₂ balloon for 12 h. When the reaction was complete, the crude mixture was purified by flash chromatography (silica gel, PE). (3,3-Difluoro-2-phenylprop-2-en-1-yl)(dimethyl)phenylsilane (3a)¹⁷ Colourless oil; yield: 27 mg (93%). ¹H NMR (400 MHz, CDCl₃): δ = 7.41–7.44 (m, 2 H), 7.20–7.35 (m, 8 H,), 1.98 (dd, J = 2.1 Hz, J= 3.1 Hz, 2 H), 0.15 (s, 6 H). ¹³C NMR (101 MHz, CDCl₃): δ = 152.7 (dd, J = 284.3 Hz, J = 288.1 Hz), 138.2, 134.9 (dd, J = 3.7 Hz, J = 5.1 Hz), 133.4, 129.1, 128.3 (t, J = 2.9 Hz), 128.2, 127.7, 127.1, 90.0 (dd, J = 14.6 Hz, 23.4 Hz), 16.5, –3.0. ¹⁹F NMR (377 MHz, CDCl₃): δ = –91.7 (d, J = 48.6 Hz), –94.3 (d, J = 48.5 Hz).
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