Tollefson Emily J, Dawson David D, Osborne Charlotte A, Jarvo Elizabeth R
Department of Chemistry, University of California , Irvine, California 92697-2025, United States.
J Am Chem Soc. 2014 Oct 22;136(42):14951-8. doi: 10.1021/ja5076426. Epub 2014 Oct 13.
The stereospecific ring-opening of O-heterocycles to provide acyclic alcohols and carboxylic acids with controlled formation of a new C-C bond is reported. These reactions provide new methods for synthesis of acyclic polyketide analogs with complex stereochemical arrays. Stereoselective synthesis of the cyclic template is utilized to control relative configuration; subsequent stereospecific nickel-catalyzed ring-opening affords the acyclic product. Aryl-substituted tetrahydrofurans and tetrahydropyrans undergo nickel-catalyzed Kumada-type coupling with a range of Grignard reagents to furnish acyclic alcohols with high diastereoselectivity. Enantioenriched lactones undergo Negishi-type cross-coupling with dimethylzinc to afford enantioenriched carboxylic acids. Application in a two-step enantioselective synthesis of an anti-dyslipidemia agent is demonstrated.
据报道，O-杂环的立体定向开环可提供具有受控新C-C键形成的无环醇和羧酸。这些反应为合成具有复杂立体化学阵列的无环聚酮类似物提供了新方法。利用环状模板的立体选择性合成来控制相对构型；随后的立体定向镍催化开环得到无环产物。芳基取代的四氢呋喃和四氢吡喃与一系列格氏试剂发生镍催化的熊田型偶联，以高非对映选择性提供无环醇。对映体富集的内酯与二甲基锌发生根岸型交叉偶联，得到对映体富集的羧酸。展示了其在抗血脂异常药物的两步对映选择性合成中的应用。
