1,2-Metallate Rearrangement Using Indole Boronate Species to Access 2,3-Diarylindoles and Indolines.

Abstract

A transition metal-free multicomponent reaction using lithiated indole, boronic ester, pyridine, and ethyl chloroformate was developed to access C2,C3 bis-arylated indoles, which are present in several marketed drugs and bioactive compounds. One-pot access to unsymmetrical C2,C3-diaryl indole from the parent indole remains a huge synthetic challenge. Our group was able to achieve this goal through a transition metal-free 1,2-metalate rearrangement of the indole boronate complex. The reaction of indole boronate species with activated pyridine allows 1,2-migration to access pyridyl-indoleboronate species, which will convert to the corresponding indole upon oxidation and indoline after deborylation. The reaction tolerates substituted pyridines, quinolone, isoquinoline, and more. Both aryl and alkyl boronic esters were accommodated under optimized reaction conditions. Apart from mechanistic studies using 11B-NMR, this methodology has been applied to the gram-scale synthesis of several bioactive compounds.