Synthesis of difluoromethylated allenes through trifunctionalization of 1,3-enynes

Abstract

Organofluorine compounds have shown their great value in many aspects. Moreover, allenes are also a class of important compounds. Fluorinated or fluoroalkylated allenes might provide an option as candidates for drug and material developments, as allenes allow a great number of valuable transformations. Herein, we report a metal-free synthesis of difluoromethylated allenes via regioselective trifunctionalization of 1,3-enynes. This method proceeds through double C-F bond formation with concomitant introduction of an amino group to the allene. Synthetic applications are conducted and preliminary mechanistic studies suggest that a twostep pathway is involved. DFT calculations revealed an unusual dibenzenesulfonimideassisted fluorination/fluoroamination with NFSI. In addition, kinetic reaction study revealed the induction period of both major and side products to support the proposed reaction mechanism. This work offers a convenient approach for the synthesis of a range of difluoromethylated allenes and is also a rare example of trifunctionalization of 1,3-enynes.

Cobalt-Catalyzed Divergent Aminofluorination and Diamination of Styrenes with N-Fluorosulfonamides

“…Note that N -fluorobenzenesulfonimide (NFSI) has been widely investigated as the versatile amination agent, fluorination agent, and also atom-economical aminofluorination agent . For instance, both Markovnikov and anti-Markovnikov aminofluorination reactions of alkenes with NFSI have been developed in palladium catalysis and copper catalysis, respectively (Scheme A) . The implementation of a catalytic amount of 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO), serving as the fluorine shuttle toward the formation of the strong F–Si bond, facilitated the copper-catalyzed diamination reaction of alkenes instead (Scheme B) .…”

HFIP-Catalyzed Difluoroalkylation of Propargylic Alcohols to Access Tetrasubstituted Difluoroalkyl Allenes

“…4 In 2020, Bao and coworkers reported a metal-free synthesis of tetrasubstituted difluoromethyl allenes via the 1,1,4-trifunctionalization of 1,3enynes with N-fluorobenzenesulfonimide (NFSI) as the fluorination source (Scheme 1b). 5 Thus the development of new efficient strategies for the synthesis of multiply function- alized tetrasubstituted difluoroalkyl allenes using easily available reaction partners is highly desirable. Among the established methods to construct allenes, the direct transformation of propargylic alcohols or their derivatives represents one of the most efficient approaches with great successes achieved.…”

“…In 2019, Wang and coworkers developed a Ni-catalyzed 1,4-carbofluoroalkylation of 1,3-enynes to access tetrasubstituted difluoroalkyl allenes using difluoroalkyl halides (Scheme a) . In 2020, Bao and coworkers reported a metal-free synthesis of tetrasubstituted difluoromethyl allenes via the 1,1,4-trifunctionalization of 1,3-enynes with N -fluorobenzenesulfonimide (NFSI) as the fluorination source (Scheme b) . Thus the development of new efficient strategies for the synthesis of multiply functionalized tetrasubstituted difluoroalkyl allenes using easily available reaction partners is highly desirable.…”

Palladium-catalyzed allene synthesis enabled by β-hydrogen elimination from sp2-carbon

“…Therefore, it is highly desirable to develop new approaches via new mechanistic pathways, which may deliver the allenes e ciently from easily accessible starting materials and complement the current methodologies. [25][26][27][28][29][30][31][32][33] Therefore, β-hydrogen elimination of allylic palladium from sp 2 -carbon represents an attractive new strategy for allene synthesis.…”