Generation of Alkyl Radicals from Thiols via Zinc Thiolates: Application for the Synthesis ofgem‐Difluorostyrenes

Abstract

Reaction of thiols with α‐(trifluoromethyl)styrenes under photocatalytic conditions leading to desulfurative allylic fluorine substitution is described. The reaction is performed by treatment of thiols with benzyl zinc chloride to generate zinc thiolates followed by visible light induced desulfurization by means of triphenylphosphine. Radicals formed after the C−S bond cleavage react with the double bond affording gem‐difluorostyrenes.

Recent Advances in C-F Bond Cleavage Enabled by Visible Light Photoredox Catalysis

“…As described above, phosphinyl radical cations have been employed for the deoxygenative activation of sodium sulfinates (Scheme 16), carboxylic acids (Scheme 25), and oximes (Scheme 31). Recently, Dilman disclosed a novel approach to generate alkyl radicals via phosphine-mediated C-S bond cleavage of thiols, which react with α-CF 3 styrenes to give gem-difluorostyrenes (Scheme 35) [84]. Thiol is known as a good hydrogen donor in radical reactions.…”

“…and oximes (Scheme 31). Recently, Dilman disclosed a novel approach to generate alkyl radicals via phosphine-mediated C-S bond cleavage of thiols, which react with α-CF3 styrenes to give gem-difluorostyrenes (Scheme 35) [84]. Thiol is known as a good hydrogen donor in radical reactions.…”

Photocatalytic Alkylation of α-(Trifluoromethyl)Styrenes with Potassium Xanthogenates

“…1 H NMR (300 MHz, CDCl 3 ) δ: 7.45-7.27 (m, 5H), 2.47 (dt, J = 7.4, 2.5 Hz, 2H), 1.97-1.79 (m, 1H), 1.76-0.62 (m, 4H), 1.60-1.47 (m, 2H), 1.29-1.19 (m, 2H). 13 (3-Cyclohexyl-1,1-difluoroprop-1-en-2-yl)benzene (3f) [5]. Yield 88 mg (75%).…”

“…The advent of photocatalysis has offered novel opportunities in radical chemistry, primarily associated with methods for the generation of radical intermediates [2][3][4]. Recently, we described an approach for the direct generation of free radicals from aliphatic thiols via their in situ conversion into zinc thiolates with subsequent abstraction of the sulfur by triphenylphosphine [5] (Scheme 1) The key idea of this method is that a combination of a thiolate and a phosphorus (III) reagent upon photoredox oxidation leads to a free radical and the strong phosphorus-sulfur double bond. This reaction may proceed via initial oxidation of either the thiolate anion or the phosphorus atom.…”

Photocatalyzed Decarboxylative Thiolation of Carboxylic Acids Enabled by Fluorinated Disulfide

“…Indeed, hydrogen atom transfer (HAT) between thiols and alkyl radicals is facile, 8 and minimization of the concentration of species with the S−H bond is needed. 9 This problem can be overcome by an auxiliary group such as Nhydroxyphthalimide ester to exclude hydrogen atom donors from the reaction mixture (Scheme 1B, top pathway). 4a,b Another method is the direct photoinduced reduction of N-(acyloxy)phthalimides with a thiolate anion.…”