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

Munira Taj Muhammad, Yihang Jiao, Changqing Ye, Mong‐Feng Chiou, Muhammad Israr, Xiaotao Zhu, Yajun Li, Zhenhai Wen, Armido Studer, Hongli Bao

2020Nature Communications63 citationsDOIOpen Access PDF

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 two-step pathway is involved. DFT calculations revealed an unusual dibenzenesulfonimide-assisted 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.

Topics & Concepts

AlleneRegioselectivityChemistryCombinatorial chemistryFluorineOrganic chemistryCatalysisFluorine in Organic Chemistry