Unlocking the reactivity of difluoroketene and its synthetic applications

Discovery and application of reactive intermediates has prominently expedited the development of organic chemistry. In this respect, while ketene has been well recognized as a versatile intermediate for a wide range of transformations, practical application of difluoroketene remained virtually unrealized because of its highly reactive nature. Herein, we present a transition-metal-free approach for in situ generation of difluoroketene using difluorobromoacetylsilane as a precursor. The controlled release of chemically labile difluoroketene under mild conditions, achieved through desilylative β-elimination, establishes a foundation for successful development of its Belluš-Claisen rearrangement with allylic amines, Staudinger [2 + 2] cycloaddition with imines, [4 + 2] cycloaddition, as well as insertion into alcohols, amines, and thiols for their difluoroacetylation. A series of mechanistic experiments provide concrete support for the involvement of difluoroketene in these transformations. Although ketenes are important intermediates in chemical synthesis, the high reactivity of difluoroketene has impeded its controlled generation and practical application. Here, the authors report a transition-metal-free strategy for its mild, in situ production from difluorobromoacetylsilane, enabling cycloadditions, rearrangements and difluoroacetylations.