Metal-Free C-H Alkyliminylation and Acylation of Alkenes with Secondary Amides.

Pei-Qiang Huang,Ying-Hong Huang,Hui Geng,Jian-Liang Ye

doi:10.1038/srep28801

Pei-Qiang Huang, Ying-Hong Huang + Show 2 more

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https://doi.org/10.1038/srep28801

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Abstract

Carbon–carbon bond formation by metal-free cross-coupling of two reactants with low reactivity represents a challenge in organic synthesis. Secondary amides and alkenes are two classes of bench-stable compounds. The low electrophilicity of the former and low nucleophilicity of the latter make the direct coupling of these two partners challenging yet highly desirable. We report herein an unprecedented intermolecular reaction of secondary amides with alkenes to afford α,β-unsaturated ketimines or enones, which are versatile intermediates for organic synthesis and are prevalent in bioactive compounds and functional materials. Our strategy relies on the chemoselective activation of the secondary amide with trifluoromethanesulfonic anhydride (Tf2O)/2-fluoropyridine to generate a highly reactive nitrilium intermediate, which reacts efficiently with alkenes. This metal-free synthesis is characterized by its mild reaction conditions, excellent functional group tolerance and chemoselectivity, allowing the preparation of multi-functionalized compounds without using protecting groups.

Highlights

Organic chemistry is the chemistry of carbon compounds
In response to this challenge, we report a metal-free intermolecular coupling reaction of secondary amides with alkenes to afford multi-functionalized α,β-unsaturated ketimines and enones (Fig. 1b)
With the use of trifluoromethanesulfonic anhydride (Tf2O) as a powerful yet chemoselective amide-activating reagent, the reactions are conducted under mild conditions and tolerate a host of sensitive functional groups in both the nucleophilic and electrophilic reaction partners

Summary

Introduction

Organic chemistry is the chemistry of carbon compounds. carbon–carbon (C–C) bond-forming reactions occupy the central position in organic synthesis. An efficient intermolecular cross-coupling reaction of alkenes with secondary amides remains elusive (Fig. 1b) Such a transformation would be highly useful considering the widespread use of secondary amides as intermediates in organic synthesis and the requisite conversion of these species into other classes of compounds[16,17] at lower oxidation states[15,18,19,20,21,22,23,24] as well as the versatility of α,β-unsaturated ketimines (enimines)[25] and α,β-unsaturated ketones (enones) in organic synthesis, medicinal chemistry[26], and molecular switches[27]. (B–N cyclization) and Schnider–Hellerbach’s extended B–N cyclization. (b) Our metal-free Tf2O-mediated C–H functionalization of alkenes with secondary amides

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