Atmospheric Oxygen Mediated Radical Hydrothiolation of Alkenes

Abstract

Am ild, metal-free, atmospheric oxygen-mediated radical hydrothiolation of alkenes (and alkyne) is reported. Av ariety of sulfur containingm otifs including alkanethiols,t hiophenols and thioacidsu ndergo an atmospheric oxygen-mediated radicalh ydrothiolation reaction with ap lethora of alkenes in good yield with excellent functional group compatibility,t ypically with short reaction times to furnisharange of functionalized products. Biomoleculesp rovedt olerant to the conditions and the procedure is robust and easily executable requiring no specialized equipment. Concise mechanistic studies confirm the process proceeds throughr adical intermediates in at hiol-ene reaction manifold. Them ethodology offers an efficient "green" approach for thiol-ene mediated "click" ligation and am ilder alternative to thermally initiated hydrothiolation processes.

Role of thiol oxidation by air in the mechanism of the self-initiated thermal thiol–ene polymerization

“…54 Recently, this mechanism was also postulated to explain the atmospheric oxygen-promoted addition of thiol to alkene. 55 In agreement with our study, Hbonding influenced the extent and efficiency of coupling. More generally, our data support that the driving force for thiol oxidation is the polarization of the S-H bond.…”

Radical-mediated thiol–ene ‘click’ reactions in deep eutectic solvents for bioconjugation

“…Olefin-based radical syntheses in DESs in the presence of air have recently been reported in the form of Cu-catalysed polymerisation 36 and Meyer-Schuster rearrangement. 29 Having recently reported atmospheric oxygen mediated TEC and ATE reactions, 37 we next investigated these conditions and their scope within the context of the DES solvent system (Scheme 1). Due to lack of requirement for an initiator or sensitiser, these initiation conditions further strengthen the 'green' chemistry characteristics of this methodology, with high atom economy and use of non-volatile, recyclable solvents.…”

“…The success of the Cys examples in the O 2 initiated conditions gives an important mechanistic insight, as the postulated mechanism involves generation of H 2 O 2 , 37 which has been shown to react with thiols to generate disulfides via the sulfenic acid, 40 and also to oxidise thioethers to sulfones, including in DESs. 41,42 The lack of side products of these types that are observed in this reaction implies that any H 2 O 2 generated is only present in small quantities insufficient to cause side reactions.…”

“…To further examine the potential for application of this methodology to large-scale synthesis of modified Cys residues, the O 2 initiated synthesis of 11 was performed at a 6.5 mmol scale, providing the target in 47% yield. As the mechanism previously proposed for this reaction hypothesises the presence of peroxides, 37 a potential hazard at larger scale, the peroxide concentration was monitored using MQuant peroxide strips. Throughout the reaction time, no peroxides were detected by this method.…”

n-Butyllithium-Induced Tandem [3,3]-Sigmatropic Rearrangement and Carbonyl Olefination of Allyl-1,1-dichlorovinyl Ethers

“…Distilled water was used in all experiments. Organic extracts were dried over anhydrous Na 2 SO 4 , filtered, and concentrated in vacuo (20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30). Chromatography refers to silica gel chromatography (silica gel 60, 230−400 mesh).…”