Amino fluorination : transition-metal-free N–F bond insertion into Diazocarbonyl Compounds

Abstract

Diazoacetate derivatives play an important role in the synthetic community. Over the past century, signi?cant advances have been made towards the generation of carbenoid intermediates triggered by transition-metals. The resulting reactive species can undergo valuable transformations, such as threemembered ring (cyclopropane, cyclopropene) formation, X–H bond insertion (X ¼ C, N, O, S, etc.) and ylide generation (Scheme 1a–c).1 van Vranken, Barluenga, Wang, and others have developed palladium- or copper-catalysed multiple component reactions of diazo compounds, which allow the installation of two separated functional moieties on the carbenic carbon via a single operation (Scheme 1d).2 Despite these important advances, the direct introduction of two functional groups to the same carbon center, namely gem-difunctionalization of donor/acceptor (D/A) carbenes, is still far from well developed.3,4 It is of note that these processes at least involve one C–C bond formation.5 Thus the studies on the gem-difunctionalization of D/A carbenes, which involves two distinct carbon heteroatom bond formations, would greatly enhance the synthetic applications of diazo compounds. Single substitution of hydrogen with ?uorine may alter the chemical and physical properties of a potential drug candidate by blocking undesired metabolism at a speci?c site.6 In contrast to the relatively large number of reports on the catalytic insertion of N–H bonds to a-diazocarbonyl compounds,7 a simple yet appealing concept for the transition-metal catalysed N–F bond insertion has not been realized thus far. N-Fluorobenzenesulfonimide (NFSI) is inexpensive and shelf stable, and is o?en employed as a mild electrophilic uorinating or aminating reagent.8,9 Recently, Liu10 and Zhang11 demonstrated that NFSI could serve as both an amino and ‘uorine source for the transition-metal-catalysed amino?uorination of alkenes (Scheme 2a). Inspired by these seminal works, we envisioned that NFSI might be an ideal candidate for the transition-metal catalysed N–F bond insertion into D/A carbenes (Scheme 2b). Although procedures for the amination7,12 or ?uorination13,14 of diazo compounds are known, to our knowledge, direct amino- ?uorination of diazo compounds remains unexplored. Herein, we present our primary results on gem-amino?uorination of diazocarbonyl compounds under mild conditions. Kinetic studies and DFT calculations shed light on the mechanism of the current N–F bond insertion.