AgNTf2-catalyzed formal [3 + 2] cycloaddition of ynamides with unprotected isoxazol-5-amines: efficient access to functionalized 5-amino-1H-pyrrole-3-carboxamide derivatives.

Ziping Cao,Yuanling Pang,Laijin Tian,Xin Meng,Xuejun Sun,Jiekun Zhu,Li Liu

doi:10.3762/bjoc.15.255

Ziping Cao, Yuanling Pang + Show 5 more

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https://doi.org/10.3762/bjoc.15.255

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Abstract

A formal [3 + 2] cycloaddition between ynamides and unprotected isoxazol-5-amines has been developed in the presence of catalytic AgNTf2 in an open flask. By the protocol, a variety of functionalized 5-amino-1H-pyrrole-3-carboxamide derivatives can be obtained in up to 99% yield. The reaction mechanism might involve the generation of an unusual α-imino silver carbene intermediate (or a silver-stabilized carbocation) and subsequent cyclization/isomerization to build the significant pyrrole-3-carboxamide motif. The reaction features the use of an inexpensive catalyst, simple reaction conditions, simple work-up without column chromatographic purification for most of products and high yields.

Highlights

Silver-catalyzed transformations of alkynes have attracted much attention over the past decade [1,2]
Following our ongoing interest in the alkyne chemistry [36,37,38], we recently envisaged that the reaction of ynamides with isoxazoles could proceed under silver catalysis conditions, involving the generation of α-imino silver carbene and subsequent cyclization to pyrroles (Scheme 2b)
We have developed a reaction of ynamides with unprotected isoxazol-5-amines that can achieve the synthesis of Scheme 6: Possible reaction routes of intermediate C

Summary

Introduction

Silver-catalyzed transformations of alkynes have attracted much attention over the past decade [1,2]. In 2015, Ye and co-workers, as pioneers, developed this chemistry with the employment of isoxazole nucleophiles in gold-catalyzed formal [3 + 2] cycloaddition reaction of ynamides [31,32], and zinc-catalyzed the reaction of ynol ethers [33], giving the respective multi-substituted pyrrole derivatives efficiently (Scheme 2a) [34,35]. Following our ongoing interest in the alkyne chemistry [36,37,38], we recently envisaged that the reaction of ynamides with isoxazoles could proceed under silver catalysis conditions, involving the generation of α-imino silver carbene and subsequent cyclization to pyrroles (Scheme 2b).

Results

Conclusion