Efficient Difluoromethylation of Alcohols Using TMSCF2Br as a Unique and Practical Difluorocarbene Reagent under Mild Conditions

A general method for the efficient difluoromethylation of alcohols using commercially available TMSCF₂Br (TMS=trimethylsilyl) as a unique and practical difluorocarbene source is developed. This method allows primary, secondary, and even tertiary alkyl difluoromethyl ethers to be synthesized under weakly basic or acidic conditions. The reaction mainly proceeds through the direct interaction between a neutral alcohol and difluorocarbene, which is different from the difluoromethylation of phenols. Moreover, alcohols containing other moieties that are also reactive toward difluorocarbene can be transformed divergently by using TMSCF₂Br. This research not only solves the synthetic problem of difluorocarbene‐mediated difluoromethylation of alcohols, it also provides new insights into the different reaction mechanisms of alcohol difluoromethylation and phenol difluoromethylation with difluorocarbene species.     

Enantioselective Propargylation of Polyols and Desymmetrization of meso 1,2‐Diols by Copper/Borinic Acid Dual Catalysis

A copper/borinic acid dual catalytic reaction enabled the enantioselective propargylation of aliphatic polyols. Readily available reagents and catalysts were used in this transformation, which displayed good to excellent chemo‐ and stereoselectivity for a broad array of substrates. The method was also applicable to the desymmetrization of meso 1,2‐diols to furnish products with three stereogenic centers and a terminal alkyne group in one operation.