达布科
烯酮
催化作用
芳基
化学
贝利斯-希尔曼反应
组合化学
有机化学
烷基
作者
Victoria Dimakos,Daniel P. Canterbury,Sébastien Monfette,Philipp C. Roosen,Stephen G. Newman
标识
DOI:10.1021/acscatal.2c03448
摘要
Cyclic enone derivatives are important scaffolds in medicinal chemistry; methods that enable direct and selective C-arylations of these compounds have the potential to enable the rapid evaluation of pharmaceutically relevant molecules. Herein, a method for the direct, selective Pd-catalyzed α-arylation of cyclic enones with (hetero)aryl triflates is described. High-throughput screening identified the biaryl phosphines JohnPhos and CPhos as optimal ligands and DABCO as an essential additive, allowing for the formation of the regioisomer opposite to that obtained under traditional Mizoroki–Heck protocols. Preliminary mechanistic investigations suggest that the reaction proceeds by enone activation analogous to a Morita–Baylis–Hillman reaction followed by Pd-catalyzed enolate arylation. The palladium catalyst is hypothesized to serve a dual role: as a Lewis acid catalyst to facilitate 1,4-addition of the DABCO to the enone substrate and as a cross-coupling catalyst to enable C–C bond formation.
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