Overcoming Electron Bias in Hydroarylation of Phenylpropiolic Acid Derivatives To Enable Highly Reversed Regio- and Stereoselectivity via Steric and Transient Post Addition Coordination

作者：Hui Li, Xu Tian, Qin-Qin Dang, Jing Zhang, Zhen‐Kang Wen · 发表于：ACS Catalysis · 年份：2024 · DOI：10.1021/acscatal.4c01944 · 被引用次数：9 · 研究领域：Asymmetric Synthesis and Catalysis、Catalytic Cross-Coupling Reactions、Synthetic Organic Chemistry Methods

The regio- and stereoselective hydroarylation of internal alkynes via transition-metal catalysis offers a direct approach for designing highly stereodefined multifunctionalized olefins. Through recognition of electronic bias, β- syn -hydroarylation of electronic poor alkynes with arylboronic acids has been well studied. However, from the same starting materials, achieving the opposite α-selective and highly anti -stereoselective hydroarylation remains a significant challenge due to these inherent biases. Therefore, an alternative synthetic pathway to trisubstituted alkenes with reversed positioning and configuration of substituents is highly desirable. Based on steric repulsion-induced regioselectivity and transient post-addition coordination-directed stereoselectivity, we report herein an α-hydroarylation method for phenylpropiolic esters using a nickel catalyst that promotes a formal anti -addition pathway. A broad range of organoboronic acids and phenylpropiolic acid derivatives are compatible with this hydroarylation protocol, offering an alternative selectivity to traditional β- syn -hydroarylation reactions. The distinct advantages of our method include precise control over selectivity, reduced catalyst loading, and broad tolerance toward functional groups. These features highlight the potential of our approach in the synthesis of multifunctionalized alkenes and in the late-stage modification of alkyne-based drug intermediates, showcasing its versatility and applicabili...