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Epoxides, as a prominent small ring O-heterocyclic and the privileged pharmacophores for medicinal chemistry, have recently represented an ideal substrate for the development of single-atom replacements. The previous O-to-C replacement strategy for epoxides to date typically requires high temperatures to achieve low yields and lacks substrate range and functional group tolerance, so achieving this oxygen-carbon exchange remains a formidable challenge. Here, we report a silver-catalyzed direct conversion of epoxides into trifluoromethylcyclopropanes in a single step using trifluoromethyl N-triftosylhydrazones as carbene precursors, thereby achieving oxygen-carbon exchange via a tandem deoxygenation/[2 + 1] cycloaddition. The reaction shows broad tolerance of functional groups, allowing routine cheletropic olefin synthesis in a strategy for the net oxygen-carbon exchange reaction. The utility of this method is further showcased with the late-stage diversification of epoxides derived from bioactive natural products and drugs. Mechanistic experiments and DFT calculations elucidate the reaction mechanism and the origin of the chemo- and stereoselectivity. Epoxides are prominent small-ring O-heterocycles found in a variety of bioactive natural products and pharmaceuticals. Here, the authors report a silver carbene strategy to achieve O-to-C atom exchange of epoxides in a single step, affording diverse fluoroalkylcyclopropanes. [ABSTRACT FROM AUTHOR]

The construction of allylic quaternary sp3‐carbon centers has long been a formidable challenge in transition‐metal‐catalyzed alkyl‐allyl coupling reactions due to the severe steric hindrance. Herein, we report an effective carbene strategy that employs well‐defined vinyl‐N‐triftosylhydrazones as a versatile allylating reagent to enable direct assembly of these medicinally desirable structural elements from low‐cost alkane feedstocks. The reaction exhibited excellent site selectivity for tertiary C−H bonds, broad scope (>60 examples and >20 : 1:0 r. r.) and good efficiency, even on a gram‐scale, making it a convenient alternative to the well‐known Trost–Tsuji allylation reaction for the formation of alkyl–allyl bonds. Combined experimental and computational studies were employed to unravel the mechanism and origin of site‐ and chemoselectivity of the reaction. [ABSTRACT FROM AUTHOR]

The C–F bond cleavage and C–C bond formation (i.e., carbodefluorination) of readily accessible (per)fluoroalkyl groups constitutes an atom-economical and efficient route to partially fluorinated compounds. However, the selective mono-carbodefluorination of trifluoromethyl (CF3) groups remains a challenge, due to the notorious inertness of C–F bond and the risk of over-defluorination arising from C–F bond strength decrease as the defluorination proceeds. Herein, we report a carbene-initiated rearrangement strategy for the carbodefluorination of fluoroalkyl ketones with β,γ-unsaturated alcohols to provide skeletally and functionally diverse α-mono- and α,α-difluoro-γ,δ-unsaturated ketones. The reaction starts with the formation of silver carbenes from fluoroalkyl N-triftosylhydrazones, followed by nucleophilic attack of a β,γ-unsaturated alcohol to form key silver-coordinated oxonium ylide intermediates, which triggers selective C–F bond cleavage by HF elimination and C–C bond formation through Claisen rearrangement of in situ generated difluorovinyl ether. The origin of chemoselectivity and the reaction mechanism are determined by experimental and DFT calculations. Collectively, this strategy by an intramolecular cascade process offers significant advances over existing stepwise strategies in terms of selectivity, efficiency, functional group tolerance, etc. The selective functionalization of trifluoromethyl groups is challenging due to the inertness of the C–F bonds. Here the authors report a method for the carbodefluorination of C–F bonds of fluoroalkyl ketones via a carbene-initiated rearrangement strategy. [ABSTRACT FROM AUTHOR]

Abstract: A catalyst‐dependent chemoselective one‐carbon insertion of diazo compounds into the C−C or C−H bonds of 1,3‐dicarbonyl species is reported. In the presence of silver(I) triflate, diazo insertion into the C(=O)−C bond of the 1,3‐dicarbonyl substrate leads to a 1,4‐dicarbonyl product containing an all‐carbon α‐quaternary center. This reaction constitutes the first example of an insertion of diazo‐derived carbenoids into acyclic C−C bonds. When instead scandium(III) triflate was applied as the catalyst, the reaction pathway switched to formal C−H insertion, affording 2‐alkylated 1,3‐dicarbonyl products. Different reaction pathways are proposed to account for this powerful catalyst‐dependent chemoselectivity. [ABSTRACT FROM AUTHOR]