Direct Synthesis of Indoles from Azoarenes and Ketones with Bis(neopentylglycolato)diboron Using 4,4′-Bipyridyl as an Organocatalyst

Multifunctionalized indole derivatives were prepared by reducing azoarenes in the presence of ketones and bis(neopentylglycolato)diboron (B(2)nep(2)) with a catalytic amount of 4,4'-bipyridyl under neutral reaction conditions, where 4,4'bipyridyl acted as an organocatalyst to activate the B-B bond of B(2)nep(2), and form N,N'-diboryl-1,2-diarylhydrazines as key intermediates. Further reaction of NN'-diboryl-1,2-diarylhydrazines with ketones afforded N-vinyl-1,2-diarylhydrazines, which rearranged to the corresponding indoles via the Fischer indole mechanism. This organocatalytic system was applied to diverse alkyl cyclic ketones, dialkyl, and alkyl/aryl ketones, including heteroatoms. Methyl alkyl ketones gave the corresponding 2-methyl-3-substituted indoles in a regioselective manner. This protocol allowed us to expand the preparation of indoles having high compatibility with not only electron-donating and electron-withdrawing groups but also N- and O-protecting functional groups.

Automated summary

A new method for preparing multifunctionalized indole derivatives under neutral conditions was developed using an organocatalytic system involving 4,4'-bipyridyl to activate the B-B bond of B(2)nep(2). This protocol allows for a wide range of indole synthesis and shows high compatibility with different functional groups.