Transition-Metal-Free Controllable Single and Double Difluoromethylene Formal Insertions into C-H Bonds of Aldehydes with TMSCF₂Br

We have developed a new strategy for controllable single and double difluoromethylene (CF2) formal insertions into C-H bonds of aldehydes with nearly full selectivity under transition-metal-free conditions. The key to the success of controllable CF2 insertions lies in the well-defined formation of 2,2-difluoroenolsilyl ether and 2,2,3,3-tetrafluorocyclopropanolsilyl ether intermediates using difluorocarbene reagent TMSCF2Br (TMS=trimethylsilyl). These two intermediates can react with various electrophiles including proton sources and various halogenation reagents, allowing for the access to diverse arrays of ketones containing difluoromethylene (CF2) and tetrafluoroethylene (CF2CF2) units. The first synthesis of relatively stable 2,2,3,3-tetrafluorocyclopropanolsilyl ethers has been achieved, which offers a new platform to explore other unknown chemical space.