Regiodivergent Asymmetric Pyridinium Additions: Mechanistic Insight and Synthetic Applications
Regiodivergent Asymmetric Pyridinium Additions: Mechanistic Insight and Synthetic Applications
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DOI：
10.1002/chem.202202813
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发表时间：
2022-10-19
影响因子：
4.3
通讯作者：
Smith, Joel M.
中科院分区：
文献类型：
--
作者：
Grigolo, Thiago A.;Smith, Joel M.
介绍了芳基和烯基有机金属试剂在取代的n -烷基吡啶杂环上的首次区域发散不对称加成的实用方案。该偶联反应具有较高的区域化学和立体化学选择性，并可通过合理选择氮活化剂获得手性1,2,3-和1,3,4-三取代二氢吡啶产物。为此，我们发现了活化基团的参数化大小与偶联中C2/C4区域选择性之间的相关性。在(+)- n -甲基aspidosperine和(-)-paroxetine的两个简洁的不对称合成中证明了所描述化学的效用。
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.