Regioselective Synthesis of 2,3-Disubstituted Indoles via Interrupted Heyns Rearrangement Involving C-C Bond Cleavage

A novel metal free, Br & oslash;nsted acid mediated and operationally simple strategy has been developed for regioselective synthesis of 2,3-disubstituted indoles from alpha-hydroxyketones and o-aminoaryl ketones in excellent yields. The reaction proceeds via interrupted Heyns rearrangement through the generation of aminoenol intermediate followed by intramolecular trapping and aromatization with C-C bond cleavage and release of corresponding ester. The mechanism was further supported by the identification of ester in GCMS and reaction of cyclic alpha-hydroxydimethylketal, which afforded ester tethered indole derivative. The regioselective synthesis of 2,3-disubstituted indoles have been achieved from alpha-hydroxyketones and o-aminoaryl ketones in the presence of Br & oslash;nsted acid. The reaction is operationally simple and involves generation of aminoenol intermediate followed by intramolecular trapping, viz. interrupted Heyns rearrangement, and aromatization with C-C bond cleavage and release of corresponding ester. image