(Difluoromethyl)trimethylsilane (TMSCHF2): A Useful Difluoromethylating Nucleophilic Source
Margherita Miele, Vittorio Pace
Abstract
Significant advancements have been achieved due to the excellent versatility of the commercially available (difluoromethyl)trimethylsilane (TMSCHF2) as a competent donor of the CHF2 group under nucleophilic regime.[2] It is a commercially or easily accessible liquid documenting excellent experimental manipulability due to its relatively high boiling point. Researchers have used TMSCHF2 for the delivery of the CHF2 unit to Weinreb amides en route to difluoromethyl-ketones. The activation of TMSCHF2 with potassium tertamylate (t-AmOK) ensured higher yields compared with different Lewis bases, enabling an efficient synthesis of these ketones under full chemocontrol, as evidenced in the case of variously functionalized acylating linchpins. Taking advantage of the versatility of using isocyanates and isothiocyanates in forging (thio)-amidic linkages, researchers used TMSCHF2 activated with t-AmOK for preparing in a single synthetic operation difluoromethyl analogues with very high chemoselectivity.