Fluoroalkyl N-sulfonyl hydrazones: An efficient reagent for the synthesis of fluoroalkylated compounds

Abstract

Fluoroalkyl N-sulfonyl hydrazones are versatile reagents that can be used to synthesize a wide range of diverse fluoroalkylated organic molecules. Although it has been known since 1975, the chemistry of fluoroalkyl N-sulfonyl hydrazones has recently only received great attention from the scientific community. Generally, they are used as either safe and bench-stable diazo precursors in carbene transfer reactions or as 1,3-dipoles in cycloaddition and cyclization reactions. Notably, fluoroalkyl N-sulfonyl hydrazones to replace toxic fluoroalkyl diazo compounds in carbene transfer reactions reduce the risk of rapid accumulation of explosive diazo compounds and improve functional group compatibility and substrate scope. Given the growing importance of fluoroalkyl N-sulfonyl hydrazones in chemical synthesis, a comprehensive review of this topic in the literature is essential to demonstrate their synthetic potential. In this review, we critically summarize and comprehensively analyze the publications in various literatures on the chemistry of fluoroalkyl N-sulfonyl hydrazones starting from 1990 to date. The classification of the different reactivity profiles of fluoroalkyl N-sulfonyl hydrazones and the efficiencies of similar types of reactions or substrates with fluoroalkyl diazo compounds are compared.

Direct gem‐Difluoroalkenylation of X−H Bonds with Trifluoromethyl Ketone N‐Triftosylhydrazones for Synthesis of Tetrasubstituted Heteroatomic gem‐Difluoroalkenes

“…We next set out to assess the generality of trifluoromethyl ketone N ‐triftosylhydrazones (Figure 3a) [15] . The N ‐triftosylhydrazones derived from ubiquitous trifluoromethyl ketones proved to be equally applicable.…”

“…For example, N-methylarylamine with different functional groups on the phenyl ring was well tolerated under the standard conditions and provided the desired gem-difluorovinylamines in 75 %-90 % yield (4-13). Linear, branched, and cyclic alkyl substituted secondary arylamines all underwent smooth reactions with N-triftosylhydrazone (1 a) (14)(15)(16)(17)(18)(19)(20)(21). In addition, the alkyl chain containing different functionalities, such as ether, pyranyl, cyano, alkenyl, and alkynyl group, proved to be compatible (22)(23)(24)(25)(26).…”

“…We next set out to assess the generality of trifluoromethyl ketone N-triftosylhydrazones (Figure 3a). [15] The N-triftosylhydrazones derived from ubiquitous trifluoromethyl ketones proved to be equally applicable. For instance, the hydrazones bearing alkyl, methoxy, trifluoromethoxy, halogen, phenyl, trifluoromethyl, ester, and piperonyl groups worked well, and the electronic effect of the substituents on the phenyl ring had no obvious influence on the outcome of the reaction (81-92).…”

Dearomative [4 + 3] cycloaddition of furans with vinyl-N-triftosylhydrazones by silver catalysis: stereoselective access to oxa-bridged seven-membered bicycles

“…As part of our continued efforts in the design and application of functionalized N -triftosylhydrazones, 16,17 we were intrigued by the possibility of applying this approach to solve the aforementioned issues in the [4 + 3] cycloaddition methodology. Here we report a silver-catalyzed dearomative [4 + 3] cycloaddition of furans using the easily decomposable vinyl- N -triftosylhydrazones as donor and donor–acceptor vinylcarbene precursors (Fig.…”

Catalytic Asymmetric C(sp3)–H Carbene Insertion Approach to Access Enantioenriched 3-Fluoroalkyl 2,3-Dihydrobenzofurans

“…Even though fluoroalkyl metal carbenes were widely explored in asymmetric cycloaddition, − X–H insertion, − and cross-coupling reactions, , the chemistry of such carbene insertion in asymmetric C–H bond functionalization remains an underdeveloped area, which is probably due to the intrinsic inertness of C­(sp 3 )–H bonds and the lack of an efficient fluoroalkyl carbene source (Figure b). − So far, there has been only one example, reported by the Arnold group, of the successful use of a fluoroalkyl carbene in an enantioselective C­(sp 3 )–H functionalization reaction using enzyme catalysis, which employed a potentially explosive, toxic, and pre-prepared trifluoromethyl diazomethane solution. Building on our continuous interest in the design and applications of fluoroalkyl N -sulfonylhydrazones, − we herein report a rhodium-catalyzed asymmetric carbene insertion into ether α-C–H bonds that uses easily decomposable fluoroalkyl N -triftosylhydrazones (triftosyl = 2-(trifluoromethyl)­benzenesulfonyl, Tfs) as operationally simple and bench-stable carbene precursors under mild conditions (Figure c). Such a powerful method enables the enantioenriched synthesis of fluoroalkyl 2,3-dihydrobenzofuran derivatives in good to excellent yields with high stereoselectivities.…”