Solvent‐Switched Oxidation Selectivities with O2: Controlled Synthesis of α‐Difluoro(thio)methylated Alcohols and Ketones

Abstract The solvent‐switched hydroxylation and oxygenation of α‐difluoro(thio)methylated carbanions with molecular oxygen under mild conditions are reported. This strategy tames the redox reactions of the in situ generated hydroperoxy difluoromethylsulfides, in which solvent‐bonding can alter their reactivity and switch the oxidation selectivities. These controllable three‐component reactions of gem ‐difluoroalkenes, thiols and molecular oxygen afford various useful α‐difluoro(thio)methylated alcohols and ketones in high yields. Significantly, this protocol has been applied in the synthesis different bioactive molecules. Mechanism studies enable the detection of the hydroperoxy difluoromethylsulfide intermediates and exclude the thiol‐based radical pathway.