通过C-H烯基化/扭矩选择性6π电环化串联反应合成内消旋酮洛芬。
Synthesis of ent-ketorfanol via a C-H alkenylation/torquoselective 6π electrocyclization cascade.
作者信息
Phillips Eric M, Mesganaw Tehetena, Patel Ashay, Duttwyler Simon, Mercado Brandon Q, Houk Kendall N, Ellman Jonathan A
机构信息
Department of Chemistry, Yale University, 225 Prospect St., New Haven, CT 06520 (USA).
Department of Chemistry and Biochemistry, University of California, Los Angeles, Los Angeles, CA 90095-1569 (USA).
出版信息
Angew Chem Int Ed Engl. 2015 Oct 5;54(41):12044-8. doi: 10.1002/anie.201505604. Epub 2015 Aug 17.
Abstract
The asymmetric synthesis of ent-ketorfanol from simple and commercially available precursors is reported. A Rh(I) -catalyzed intramolecular CH alkenylation/torquoselective 6π electrocyclization cascade provides a fused bicyclic 1,2-dihydropyridine as a key intermediate. Computational studies were performed to understand the high torquoselectivity of the key 6π electrocyclization. The computational results demonstrate that a conformational effect is responsible for the observed selectivity. The ketone functionality and final ring are introduced in a single step by a redox-neutral acid-catalyzed rearrangement of a vicinal diol to give the requisite carbonyl, followed by intramolecular Friedel-Crafts alkylation.
摘要
报道了从简单且市售的前体不对称合成对映-酮洛芬。铑（I）催化的分子内C-H烯基化/扭矩选择性6π电环化级联反应提供了一种稠合双环1,2-二氢吡啶作为关键中间体。进行了计算研究以理解关键6π电环化的高扭矩选择性。计算结果表明，构象效应是观察到的选择性的原因。酮官能团和最终环通过邻二醇的氧化还原中性酸催化重排一步引入，以得到所需的羰基，随后进行分子内傅克烷基化反应。
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