武汉大学王春江团队报道了铱催化的不对称级联烯丙基化/Retro-Claisen反应。相关研究成果发表在2022年10月20日出版的《美国化学会杂志》。

对映体富集的3-羟基甲基戊烯醛单元是许多具有重要生物活性的天然产物和药物候选物的关键结构核心之一。然而，迄今为止，很少有关于相关骨架的合成方法的报道。

该文中，研究人员成功地开发了一种铱催化的不对称级联烯丙基化/Retro-Claisen反应，该反应可使易得的β-二酮与VEC发生反应，并可以良好的产率和优异的对映选择性，制备多种功能化的手性3-羟基甲基戊烯醛衍生物。β-位上含有不同吸电子基团的各种1，3-二酮和官能化酮，作为具有高反应性和优异的区域/化学/对映选择性的优秀伴侣具有良好的耐受性。产物手性3-羟基甲基戊烯醛衍生物的合成效用通过克级转化、氢化、环丙烷化、氢化硼化和烯烃复分解得到了很好的证明。

此外，该方案在有用的手性构建块（S）-谷口内酯的简明合成和天然产物胞苷的正式合成中展示了合成应用。根据实验结果和对照实验，研究人员提出了合理的反应途径。

附：英文原文

Title: Iridium-Catalyzed Asymmetric Cascade Allylation/Retro-Claisen Reaction

Author: Zhi-Yuan Yi, Lu Xiao, Xin Chang, Xiu-Qin Dong, Chun-Jiang Wang

Issue&Volume: October 20, 2022

Abstract: An enantiomerically enriched 3-hydroxymethyl pentenal unit is one of the key structural cores in plenty of natural products and drug candidates with significant biological activities. However, very few synthetic methodologies for the facile construction of the related skeletons have been reported to date. Herein, an elegant iridium-catalyzed asymmetric cascade allylation/retro-Claisen reaction of readily available β-diketones with VEC was successfully developed, and a wide range of functionalized chiral 3-hydroxymethyl pentenal derivatives could be prepared in good yields with excellent enantioselectivities. Various 1,3-diketones and functionalized ketones containing different electron-withdrawing groups on the β-position were well tolerated as outstanding partners with high reactivity and excellent regio-/chemo-/enantioselectivity. The synthetic utility of product chiral 3-hydroxymethyl pentenal derivatives was well shown through gram-scale transformation, hydrogenation, cyclopropanation, hydroboration, and olefin metathesis. Moreover, this elegant protocol demonstrated synthetic applications in the concise synthesis of synthetically useful chiral building block (S)-Taniguchi lactone and the formal synthesis of natural product cytisine. A rational reaction pathway was proposed based on the experimental results and control experiments.

DOI: 10.1021/jacs.2c08811

Source: https://pubs.acs.org/doi/10.1021/jacs.2c08811