School of Chemistry and Materials Science, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, 1 Sub-lane Xiangshan, Hangzhou, 310024, China.
State Key Laboratory of Bio-Organic and Natural Products Chemistry, Center for Excellence in Molecular Synthesis, Shanghai Institute of Organic Chemistry, University of Chinese Academy of Sciences, 345 Lingling Road, Shanghai, 200032, China.
Angew Chem Int Ed Engl. 2022 Sep 19;61(38):e202209087. doi: 10.1002/anie.202209087. Epub 2022 Aug 16.
The Heck reaction between N-heteroaryl halides and heterocyclic alkenes provides a convenient approach to biologically relevant α-heteroaryl functionalized heterocycles, yet reactions of this type have been challenging due to strong N-heteroaryl coordination to palladium metal, which causes catalyst poisoning. In this report, an efficient palladium-catalyzed Heck reaction between N-heteroaryl halides and heterocyclic olefins is established, leading to a variety of α-heteroaryl substituted heterocycles. The method features an unprecedented broad substrate scope and excellent functional group compatibility. The employment of a sterically bulky P, P=O ligand containing an anthryl moiety is crucial for this transformation due to the coordinative unsaturation facilitated by its steric bulkiness. The asymmetric variant of the Heck reaction is achieved with (S)-DTBM-SEGPHOS via a cationic palladium pathway, which has enabled an efficient asymmetric synthesis of (S)-nicotine and its analogues.
N-杂芳基卤化物与杂环烯烃的 Heck 反应为生物相关的α-杂芳基功能化杂环化合物提供了一种便捷的方法，但由于 N-杂芳基与钯金属的强配位作用导致催化剂中毒，此类反应一直具有挑战性。在本报告中，建立了一种高效的钯催化 N-杂芳基卤化物与杂环烯烃的 Heck 反应，得到了多种α-杂芳基取代的杂环化合物。该方法具有前所未有的广泛底物范围和优异的官能团兼容性。使用含有蒽基部分的空间位阻大的 P，P=O 配体对于这种转化至关重要，因为其空间位阻促进了配位不饱和性。通过阳离子钯途径实现了 Heck 反应的不对称变体，该变体通过（S）-DTBM-SEGPHOS 实现，从而能够高效地不对称合成（S）-尼古丁及其类似物。
