Merging the Isonitrile‐Tetrazine (4+1) Cycloaddition and the Ugi Four‐Component Reaction into a Single Multicomponent Process

Multicomponent reactions are of utmost importance at generating a unique, wide, and complex chemical space. Herein we describe a novel multicomponent approach based on the combination of the isonitrile‐tetrazine (4+1) cycloaddition and the Ugi four‐component reaction to generate pyrazole amide derivatives. The scope of the reaction as well as mechanistic insights governing the 4 H ‐pyrazol‐4‐imine tautomerization are provided. This multicomponent process provides access to a new chemical space of pyrazole amide derivatives and offers a tool for peptide modification and stapling.