One-Pot Synthesis of 1,2-Disubstituted 4-, 5-, 6-, and 7-Azaindoles from Amino-o-halopyridines via N-Arylation/Sonogashira/Cyclization Reaction.

A direct synthesis of several 1,2-disubstituted 4-, 5-, 6-, and 7-azaindoles from available amino-o-halopyridines is described. This procedure involves a palladium-catalyzed N-arylation followed by a Sonogashira reaction and subsequent cyclization in a one-pot manner, exhibiting a wide scope and compatibility with electron-withdrawing and electron-donating groups. The strategy represents an advancement in azaindole chemistry with a straightforward approach toward 1,2-disubstituted azaindoles, while avoiding complex N-arylations of hindered 2-substituted azaindoles and difficult purification steps of intermediates.

Synthesis of Substituted 4-, 5-, 6-, and 7-Azaindoles from Aminopyridines via a Cascade C-N Cross-Coupling/Heck Reaction.

A practical palladium-catalyzed cascade C-N cross-coupling/Heck reaction of alkenyl bromides with amino-o-bromopyridines is described for a straightforward synthesis of substituted 4-, 5-, 6-, and 7-azaindoles using a Pd2(dba)3/XPhos/t-BuONa system. This procedure consists of the first cascade C-N cross-coupling/Heck approach toward all four azaindole isomers from available aminopyridines. The scope of the reaction was investigated and several alkenyl bromides were used, allowing access to different substituted azaindoles.