Grigolo Thiago A, Smith Joel M
Department of Chemistry and Biochemistry, Florida State University, 95 Chieftan Way, Tallahassee, 32306 Florida, USA.
Chemistry. 2022 Dec 9;28(69):e202202813. doi: 10.1002/chem.202202813. Epub 2022 Oct 19.
A practical protocol for the first regiodivergent asymmetric addition of aryl and alkenyl organometallic reagents to substituted N-alkyl pyridinium heterocycles is described. The couplings proceed with high regiochemical and stereochemical selectivities, and provide access to chiral 1,2,3- and 1,3,4-trisubstituted dihydropyridine products, controlled by judicious choice of nitrogen activating agent. To this end, a correlation was found between the parameterized size of the activating group and the C2/C4 regioselectivity in the couplings. The utility of the described chemistry was demonstrated in two concise asymmetric syntheses of (+)-N-methylaspidospermidine and (-)-paroxetine.
本文描述了一种实用的方法，用于将芳基和烯基有机金属试剂首次区域发散性不对称加成到取代的N-烷基吡啶杂环上。该偶联反应具有高区域化学和立体化学选择性，通过明智地选择氮活化剂，可得到手性1,2,3-和1,3,4-三取代二氢吡啶产物。为此，发现了活化基团的参数化大小与偶联反应中C2/C4区域选择性之间的相关性。在(+)-N-甲基阿朴菲啶和(-)-帕罗西汀的两个简洁不对称合成中证明了所描述化学方法的实用性。
