Han Kehui, Wang Yanyan, Zhao Pei, You Xiaohui, Wang Jun, Guo Yanchun, Zhao Yufen, Cao Shuxia
Green Catalysis Center, College of Chemistry, Zhengzhou University, Kexue Road No. 100, Zhengzhou 450001, China.
Institute Drug Discovery Technology, Ningbo University, Ningbo, Zhejiang 315211, China.
J Org Chem. 2021 Mar 19;86(6):4512-4531. doi: 10.1021/acs.joc.0c02953. Epub 2021 Feb 17.
The stereochemical mechanism of the nucleophilic substitution reaction at pentacoordinate phosphorus (P-V) atom is rarely studied. Here, we report the Atherton-Todd-type reaction of pentacoordinate hydrospirophosphorane with phenolic compounds in detail. The stereochemical mechanism of nucleophilic substitution at P-V atom was proposed by P NMR tracing experiment, X-ray diffraction analysis, and density functional theory calculations. The first step of the Atherton-Todd-type reaction is the formation of halogenated spirophosphorane intermediate with retention of configuration at phosphorus definitely. The second step is a nucleophilic substitution reaction at P-V atom of halogenated spirophosphorane. When using CCl as a halogenating agent, the reaction of chlorinated spirophosphorane proceeds via S2(P-V) mechanism, and the backside attack of P-Cl bond is the main pathway. For chlorinated spirophosphorane with Δ configuration, the completely P-inverted product is normally obtained. As for chlorinated spirophosphorane with Λ configuration, which has larger steric hindrance behind P-Cl bond, the proportion of P-retained products apparently increases and a pair of diastereoisomers is acquired. Furthermore, if CBr is used as a halogenating agent, the nucleophilic substitution reaction of brominated spirophosphorane may go through a S1(P-V) mechanism to afford a pair of diastereoisomers.
关于五配位磷（P-V）原子上亲核取代反应的立体化学机理鲜有研究。在此，我们详细报道了五配位氢螺磷烷与酚类化合物的阿特金森-托德型反应。通过磷核磁共振追踪实验、X射线衍射分析以及密度泛函理论计算，提出了P-V原子上亲核取代反应的立体化学机理。阿特金森-托德型反应的第一步是明确形成在磷原子处构型保持的卤代螺磷烷中间体。第二步是卤代螺磷烷的P-V原子上的亲核取代反应。当使用四氯化碳作为卤化剂时，氯化螺磷烷的反应通过S2(P-V)机理进行，P-Cl键的背面进攻是主要途径。对于具有Δ构型的氯化螺磷烷，通常会得到完全P构型翻转的产物。至于具有Λ构型的氯化螺磷烷，其P-Cl键后方的空间位阻较大，P构型保持产物的比例明显增加，并且会得到一对非对映异构体。此外，如果使用四溴化碳作为卤化剂，溴化螺磷烷的亲核取代反应可能通过S1(P-V)机理进行，从而得到一对非对映异构体。
