Merging the Isonitrile‐Tetrazine (4+1) Cycloaddition and the Ugi Four‐Component Reaction into a Single Multicomponent Process
Yanira Méndez, Aldrin V. Vasco, Galway Ivey, Ana Laura Dias, Peter Gierth, Bárbara B. Sousa, Claudio D. Navo, Ángel Torres-Mozas, Tiago Rodrigues, Gonzalo Jiménez‐Osés, Gonçalo J. L. Bernardes
Abstract
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 4H-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.