以色列理工学院Ilan Marek小组报道了在非环体系中通过亲核取代在四元立体中心进行立体定向分子重排。相关论文于2025年3月19日发表于国际顶尖学术期刊《自然-化学》杂志上。

在这里，课题组研究人员提出了一个策略，以制备复杂的分子骨架通过立体定向S_N1在一个第四立体中心在无环体系。通过利用邻近基团的参与，该课题组人员促进了独特的环丙基碳基阳离子中间体的选择性形成，该中间体经过选择性亲核取代，具有高非对映选择性，并通过分子重排在远离原始碳正离子的远处完全反转构型。这种方法已被应用于生成均烯丙基叔氟化物、溴化物、氯化物、醚、硫氰酸酯和叠氮化物，证明了它在获得具有特殊非对映选择性的各种官能团方面的适用性。这一转变为构建复杂的分子结构开辟了新的途径，通过精确立体控制在非环体系的第四立体中心的C-C键裂解。

研究人员表示，在四价（sp³）碳上亲核取代是有机合成中的一个基本转变，对于形成碳碳和碳杂原子键至关重要。虽然S_N2反应的机理已经被很好地理解，但由于连续碳正离子中间体的复杂性，在S_N1型反应中实现立体化学控制仍然极具挑战性。

附：英文原文

Title: Stereospecific molecular rearrangement via nucleophilic substitution at quaternary stereocentres in acyclic systems

Author: Patel, Kaushalendra, Marek, Ilan

Issue&Volume: 2025-03-19

Abstract: Nucleophilic substitution at tetravalent (sp3) carbon is a fundamental transformation in organic synthesis, essential for creating carbon–carbon and carbon–heteroatom bonds. While the mechanism of the SN2 reaction is well understood, achieving stereochemical control in SN1-type reactions remains extremely challenging due to the complexity of successive carbocation intermediates. Here we present a strategy for preparing complex molecular skeletons via stereospecific SN1 at a quaternary stereocentre in acyclic systems. By leveraging neighbouring group participation, we facilitate the selective formation of a unique cyclopropylcarbinyl cation intermediate that undergoes selective nucleophilic substitution with high diastereoselectivity and complete inversion of configuration at a distant position from the original carbocation via molecular rearrangement. This methodology has been applied to generate homoallylic tertiary fluorides, bromides, chlorides, ethers, thiocyanates and azides, demonstrating its applicability in accessing diverse functional groups with exceptional diastereoselectivities. This transformation opens new avenues for constructing complex molecular architectures through precise stereocontrol of C–C bond cleavage at a quaternary stereocentre in acyclic systems.

DOI: 10.1038/s41557-025-01783-2

Source: https://www.nature.com/articles/s41557-025-01783-2