美国匹兹堡大学Dong, Guangbin团队报道了S_NV反应合成有机硼酸酯的立体特异性亚烯基同系物。相关研究成果发表在2024年5月23日出版的《自然》。

协同亲核取代，即S_N2反应，是合成中用于引入新官能团并构建碳-碳和碳-杂原子键的一种基本有机转化。S_N2反应通常涉及亲核试剂对C（sp³）X键（X=卤素或其他离去基团）的σ*轨道的背面攻击，导致立体中心的完全反转。相反，电子无偏的sp²乙烯基亲电试剂上相应的立体反转亲核取代，即协同S_NV（σ）反应，要少得多，而且到目前为止，仅限于主要在成环过程中精心设计的底物。

该文中，研究表明，在金属化复合物中，所提出的应变释放机制可以加速协同S_NV反应，从而发展出各种有机硼酸盐的通用和立体特异性亚烯基同系物。这种方法能够迭代引入多个亚烯基单元，得到交叉共轭的多烯，否则难以制备。还展示了在合成含有多取代烯烃的生物活性化合物方面的进一步应用。计算研究表明，在正方形平面过渡态中，通过减少空间应变促进了一种不寻常的类S_N2协同途径，这解释了这种金属化S_NV反应的高效率和立体反转特征。

附：英文原文

Title: Stereospecific alkenylidene homologation of organoboronates by SNV reaction

Author: Chen, Miao, Knox, Christian D., Madhusudhanan, Mithun C., Tugwell, Thomas H., Liu, Coco, Liu, Peng, Dong, Guangbin

Issue&Volume: 2024-05-23

Abstract: Concerted nucleophilic substitution, known as SN2 reaction, is a fundamental organic transformation used in synthesis to introduce new functional groups and construct carboncarbon and carbonheteroatom bonds1. SN2 reactions typically involve backside attack of a nucleophile to the σ* orbital of a C(sp3)X bond (X= halogen or other leaving group), resulting in complete inversion of a stereocenter 2. In contrast, the corresponding stereoinvertive nucleophilic substitution on electronically unbiased sp2 vinyl electrophiles, namely concerted SNV(σ) reaction, is much rarer and so far, limited to carefully designed substrates mostly in ring-forming processes3,4. Here we show that concerted SNV reactions can be accelerated by a proposed strain-release mechanism in metallated complexes, leading to the development of a general and stereospecific alkenylidene homologation of diverse organoboronates. This method enables the iterative incorporation of multiple alkenylidene units, giving cross-conjugated polyenes that are challenging to prepare otherwise. Further application to the synthesis of bioactive compounds containing multi-substituted alkenes is also demonstrated. Computational studies suggest an unusual SN2-like concerted pathway promoted by diminishing steric strain in the square planar transition state, which explains the high efficiency and stereoinversive feature of this metallate SNV reaction.

DOI: 10.1038/s41586-024-07579-7

Source: https://www.nature.com/articles/s41586-024-07579-7