Catalytic asymmetric addition of Grignard reagents to alkenyl-substituted aromatic N-heterocycles

• Autores: Ravindra P. Jumde, Francesco Lanza, Marieke J. Veenstra
• Localización: Science, ISSN 0036-8075, Vol. 352, Nº 6284, 2016, págs. 433-437
• Idioma: inglés
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• Resumen

  • Catalytic asymmetric conjugate addition reactions represent a powerful strategy to access chiral molecules in contemporary organic synthesis. However, their applicability to conjugated alkenyl-N-heteroaromatic compounds, of particular interest in medicinal chemistry, has lagged behind applications to other substrates. We report a highly enantioselective and chemoselective catalytic transformation of a wide range of β-substituted conjugated alkenyl-N-heteroaromatics to their corresponding chiral alkylated products. This operationally simple methodology can introduce linear, branched, and cyclic alkyl chains, as well as a phenyl group, at the β-carbon position. The key to this success was enhancement of the reactivity of alkenyl-heteroaromatic substrates via Lewis acid activation, in combination with the use of readily available and highly reactive Grignard reagents and a copper catalyst coordinated by a chiral chelating diphosphine ligand.