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

Research paper by Luis C LC Misal Castro, Ibrahim I Sultan, Kohei K Nishi, Hayato H Tsurugi, Kazushi K Mashima

Indexed on: 10 Feb '21Published on: 09 Feb '21Published in: Journal of Organic Chemistry


Multifunctionalized indole derivatives were prepared by reducing azoarenes in the presence of ketones and bis(neopentylglycolato)diboron (Bnep) 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 Bnep and form ,'-diboryl-1,2-diarylhydrazines as key intermediates. Further reaction of ,'-diboryl-1,2-diarylhydrazines with ketones afforded -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 - and -protecting functional groups.