Cu(I)-Catalyzed Atropselective Heterobiaryl Coupling Employing Umpoled Indoles

Despite significant advances in the C-H/C-H coupling for the synthesis of axially chiral indolylaryl compounds, control over chemo-, regio-, and atropselectivity remains a significant challenge. We introduce herein N-carboxyindoles as an electrophilic partner that couple with a range of 2-naphthols and phenols in a highly chemo- and enantioselective manner (up to 96:4 er). Deuterium exchange and in-situ 1H NMR spectroscopy supports that the chirality is generated and transferred via dearomatized naphthol intermediates. Experiments with radical clocks, radical inhibitors and DFT computation suggested an outer-sphere attack of N-carboxyindole on Cu-bound naphthols, rather than through ligated naphthoxyl radical intermediates.