Cobalt-Catalyzed Enantioselective C-H Arylation of Indoles
Nicolas Jacob1, Yassir Zaid1, João C A Oliveira2
1Laboratoire d'Innovation Moléculaire et Applications (UMR CNRS 7042), Université de Strasbourg/Université de Haute-Alsace, ECPM, 67087 Strasbourg, France.
Abstract:
Atropoisomeric (hetero)biaryls are scaffolds with increasing importance in the pharmaceutical and agrochemical industries. Although it is the most obvious disconnection to construct such compounds, the direct enantioselective C-H arylation through the concomitant induction of the chiral information remains extremely challenging and uncommon. Herein, the unprecedented earth-abundant 3d-metal-catalyzed atroposelective direct arylation is reported, furnishing rare atropoisomeric C2-arylated indoles. Kinetic studies and DFT computation revealed an uncommon mechanism for this asymmetric transformation, with the oxidative addition being the rate- and enantio-determining step. Excellent stereoselectivities were reached (up to 96% ee), while using an unusual N-heterocyclic carbene ligand bearing an essential remote substituent. Attractive dispersion interactions along with positive C-H---π interactions exerted by the ligand were identified as key factors to guarantee the excellent enantioselection.
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