Yamada Takahiro, Hashimoto Yoshimitsu, Tanaka Kosaku, Morita Nobuyoshi, Tamura Osamu
Showa Pharmaceutical University, Machida, Tokyo 194-8543, Japan.
Org Lett. 2021 Mar 5;23(5):1659-1663. doi: 10.1021/acs.orglett.1c00061. Epub 2021 Feb 10.
An efficient synthetic method for multisubstituted pyridines from β-aryl-substituted α,β-unsaturated oxime ethers and alkenes via Pd-catalyzed C-H activation has been developed. Systematic optimization of catalyst ligands revealed that sterically hindered pyridines increased the reactivity. Mechanistic studies suggested that the products are formed by Pd-catalyzed β-alkenylation of α,β-unsaturated oxime followed by aza-6π-electrocyclization. Various oximes and alkenes could be utilized to afford multisubstituted pyridines with complete regioselectivity. The usefulness of this methodology was showcased by the synthesis of 4-aryl-substituted pyridine derivatives, which are difficult to access with previously reported Rh-catalyzed approaches with alkenes.
已开发出一种通过钯催化的C-H活化，由β-芳基取代的α,β-不饱和肟醚和烯烃高效合成多取代吡啶的方法。对催化剂配体的系统优化表明，空间位阻吡啶可提高反应活性。机理研究表明，产物是通过钯催化的α,β-不饱和肟的β-烯基化反应，随后进行氮杂-6π-电环化反应形成的。各种肟和烯烃可用于以完全的区域选择性提供多取代吡啶。该方法的实用性通过4-芳基取代吡啶衍生物的合成得到了展示，而这些衍生物难以通过先前报道的与烯烃的铑催化方法获得。
