Base-Catalyzed Synthesis of Substituted Indazoles under Mild, Transition-Metal-Free Conditions

摘要

Coupling reactions are among the most versatile and efficient methods for C-C, C-N, and C-O bond formation.''1 They have enriched the toolbox of synthetic chemists with a great number of inter-and intramolecular reactions for the step-economical synthesis of complex and functionalized molecules. For the synthesis of N-heterocyclic compounds, C-N coupling reactions are highly valuable; consequently, they have quite frequently been used in the preparation of specific polymers, dyes, and biologically active molecules to be used as agrochemicals and drugs. They are most often catalyzed by Pd-, Ni-, or Cu-based complexes, often at elevated temperatures. Especially if applied in the synthesis of pharmaceuticals, the use of such transition-metal catalysts is controversial, since they may remain in the products as trace impurities, which have to be removed in tedious additional steps. Hence, reaction protocols that enable the preparation of compounds through inter-or intramolecular C-N coupling reactions in the absence of transition metals are attractive and considered sustainable. In this context, we previously reported various base-mediated N-, O-, and S-arylation reactions, including intramolecular ring-closing reactions to give heterocyclic products. We now wondered about a transition-metal-free synthetic route to indazoles.