Recent Advances in Monofluorinated Carbenes, Carbenoids, Ylides, and Related Species.

The synthesis of monofluorinated compounds is of great interest because of the vast applications of organofluorine compounds. Recently, the introduction of monofluorocarbene synthons has emerged as an important strategy for the synthesis of fluorine-containing products. In contrast to direct fluorination, in which C-F bonds are formed, the use of monofluorinated carbenes and related reactive species involves C-C or C-X bond formation while delivering valuable fluorine atoms into the target structure. Owing to increased knowledge on carbon-carbon and carbon-heteroatom bond formations, monofluorinated carbenes have enormous potential for the synthesis of organofluorine compounds, which, in our opinion, has not yet been fully exploited. This review summarizes the recent advances in the synthetic applications of monofluorinated carbenes, carbenoids, ylides, and related species.

Iron-Catalyzed Fluoromethylene Transfer from a Sulfonium Reagent.

Herein, we report the first example of an iron porphyrin catalyzed fluoromethylene transfer from (2,4-dimethylphenyl)(fluoromethyl)(phenyl)sulfonium tetrafluoroborate to unactivated alkenes. The fluorocarbene or fluoromethylene synthon is the smallest "organic" node in a molecular graph of the organofluorine compounds. In this work, we present alternative solution to unavailable fluorodiazomethane (CHFN2), a missing one-carbon C1 piece in fluorine chemistry, by using a fluoromethylsulfonium reagent.

Monofluorinated 5-membered rings via fluoromethylene transfer: synthesis of monofluorinated isoxazoline N-oxides.

The synthesis of five-membered rings using fluoromethylene transfer chemistry is an attractive method for building fluorinated products of high value. This work demonstrates for the first time that one-fluorine-one-carbon modification of a substrate could be a viable strategy to access monofluorinated five-membered rings. The synthetic methodology was developed to access monofluorinated isoxazoline-N-oxides in one step starting from substituted 2-nitroacrylates using fluoromethylsulfonium reagents.

Optimized Monofluoromethylsulfonium Reagents for Fluoromethylene-Transfer Chemistry.

An investigation of the properties and reactivity of fluoromethylsulfonium salts resulted in the redesign of the reagents for fluoromethylene transfer chemistry. The model reaction, fluorocyclopropanation of nitrostyrene, turned out to be a suitable platform for the discovery of more streamlined fluoromethylene transfer reagents. The incorporation of halides on one aryl ring increased the reactivity, and 2,4-dimethyl substitution on the other aryl ring provided a balance between the reactivity/crystallinity of the reagent as well as the atom economy. The utility of new reagents was demonstrated by the development of an efficient fluorocyclopropanation protocol to access a range of monofluorinated cyclopropane derivatives.

Diastereoselective Monofluorocyclopropanation Using Fluoromethylsulfonium Salts.

Diarylfluoromethylsulfonium salts, alternatives to freons or advanced fluorinated building blocks, are bench stable and easy-to-use sources of direct fluoromethylene (:CHF) transfer to alkenes. These salts enabled development of a trans-selective monofluorinated Johnson-Corey-Chaykovsky reaction with vinyl sulfones or vinyl sulfonamides to access synthetically challenging monofluorocyclopropane scaffolds. The described method offers rapid access to monofluorinated cyclopropane building blocks with further functionalization opportunities to deliver more complex synthetic targets diastereoselectively.