Department of Chemistry, University of Rochester , Rochester, New York 14627, United States.
J Org Chem. 2013 Oct 4;78(19):9541-52. doi: 10.1021/jo4007514. Epub 2013 Jun 10.
A study of the reactivity and diastereoselectivity of the Lewis acid promoted cascade cyclizations of both acyclic and macrocyclic alkynones is described. In these reactions, a β-iodoallenolate intermediate is generated via conjugate addition of iodide to an alkynone followed by an intramolecular aldol reaction with a tethered aldehyde to afford a cyclohexenyl alcohol. The Lewis acid magnesium iodide (MgI2) was found to promote irreversible ring closure, while cyclizations using BF3·OEt2 as promoter occurred reversibly. For both acyclic and macrocyclic alkynones, high diastereoselectivity was observed in the intramolecular aldol reaction. The MgI2 protocol for cyclization was applied to the synthesis of advanced intermediates relevant to the synthesis of phomactin natural products, during which a novel transannular cation-olefin cyclization was observed. DFT calculations were conducted to analyze the mechanism of this unusual MgI2-promoted process.
描述了路易斯酸促进的非环状和大环炔酮级联环化的反应性和非对映选择性研究。在这些反应中，通过碘化物与炔酮的共轭加成生成β-碘代烯醇盐中间体，然后与连接的醛进行分子内Aldol 反应，得到环己烯醇。发现路易斯酸碘化镁（MgI2）促进不可逆的闭环，而使用 BF3·OEt2 作为促进剂的环化反应是可逆的。对于非环状和环状炔酮，在分子内Aldol 反应中观察到高非对映选择性。MgI2 环化方案被应用于与 phomactin 天然产物合成相关的高级中间体的合成中，在此期间观察到了一种新的中环阳离子-烯烃环化。进行了 DFT 计算来分析这种不寻常的 MgI2 促进过程的机制。
