Ortho-selective C–H arylation of phenols with N-carboxyindoles under Brønsted acid- or Cu(i)-catalysis

Abstract

Control over chemo- and regioselectivity is a critical issue in the heterobiaryl synthesis via C–H oxidative coupling. To address this challenge, a strategy to invert the normal polarity of indoles in the heterobiaryl coupling was developed. With N-carboxyindoles as umpoled indoles, an exclusively ortho-selective coupling with phenols has been realized, employing a Brønsted acid- or Cu(I)-catalyst (as low as 0.01 mol%). A range of phenols and N-carboxyindoles coupled with exceptional efficiency and selectivity at ambient temperature and the substrates bearing redox-active aryl halides (–Br and –I) smoothly coupled in an orthogonal manner. Notably, preliminary examples of atropselective heterobiaryl coupling have been demonstrated, based on a chiral disulfonimide or a Cu(I)/chiral bisphosphine catalytic system. The reaction was proposed to occur through S_N2′ substitution or a Cu(I)–Cu(III) cycle, with Brønsted acid or Cu(I) catalysts, respectively.