Radical-chain reductive alkylation of electron-rich alkenes mediated by silanes in the presence of thiols as polarity-reversal catalysts

Abstract

In the presence of a thiol catalyst, triphenylsilane mediates the reductive alkylation of electron-rich terminal alkenes R¹R²CCH₂ by organic halides R³Hal via electrophilic carbon-centred radicals R³˙. Reactions were carried out in benzene or dioxane solvent using di-tert-butyl hyponitrite (at 60 °C) or dilauroyl peroxide (at 80 °C) as initiators and good yields of the adducts R¹R²CHCH₂R³ were obtained with either methyl thioglycolate or triphenylsilanethiol as catalysts (5–10 mol% based on alkene). In the presence of the thiol, the slow direct abstraction of hydrogen from the silane by the nucleophilic adduct radical R¹R²ĊCH₂R³ is replaced by a cycle of more rapid polarity-matched reactions in which hydrogen-atom transfer to the adduct radical from the thiol is followed by abstraction of hydrogen from the silane by the derived thiyl radical, to regenerate the catalyst. In the absence of thiol, negligible yields of reductive alkylation products were obtained. The homochiral thiols, 1-thio-β-D-mannopyranose tetraacetate and 1-thio-β-D-glucopyranose tetraacetate, and the tetrapivalate and tetrabenzoate analogues of the latter were effective catalysts and reductive carboxyalkylation products with enantiomeric excesses up to 72% were obtained from prochiral alkenes. Homochiral samples of two of these adducts were obtained by recrystallisation and their absolute configurations were determined by X-ray diffraction.