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

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-1<i>H</i>-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.