Synthesis of 3-(2-Indolinyl)indoles via Intermolecular Aza-Friedel–Crafts Reaction between 3,3-Disubstituted Indolenines and Indoles

Abstract An intermolecular aza-Friedel–Crafts (FC) reaction between indoles and 3,3-disubstituted indolenines─readily prepared via NaOtBu/Et3B-promoted 3,3-dialkylation of 1H-indoles─has been developed for the synthesis of structurally diverse 2,3,3-trisubstituted indolines. Using catalytic TsOH·H2O under mild conditions, the aza-FC reaction provides direct access to biologically relevant 3-(3,3-dialkylindolin-2-yl)indoles bearing an all-carbon quaternary center at the C3 position of the indoline ring. Despite the propensity of 3,3-disubstituted indolenines to undergo the competing Plancher rearrangement leading to the formation of the corresponding 2,3-disubstituted indoles, the desired aza-FC products were obtained with excellent chemoselectivity in most cases. The protocol accommodates a broad range of C3-unsubstituted indoles and both 3,3-diallyl- and 3,3-dibenzyl-substituted indolenines, affording the products in good to excellent yields (up to 85% over two steps) with good functional-group tolerance.