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Reinvestigation of the Substitutions Reaction of Stereogenic Phosphoryl Compounds: Stereochemistry, Mechanism, and Applications

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journal contribution
posted on 18.10.2017, 00:00 by Li-Juan Liu, Wei-Min Wang, Lan Yao, Fan-Jie Meng, Yong-Ming Sun, Hao Xu, Zhong-Yuan Xu, Qiang Li, Chang-Qiu Zhao, Li-Biao Han
Nucleophilic substitutions at P centers are of high importance in biological processes and asymmetric synthesis. However, detailed studies on this topic are rare. P-Stereogenic compounds containing P–Cl, P–O, and P–S bonds were diastereoselectively prepared and then used to study the substitution of Cl, O, and S at phosphorus centers with organometallic reagents. It was proposed that with alkynyl metallic reagents an SN2-like mechanism (route A1) and a Berry pseudorotation (BPR) of pentacoordinated phosphorus intermediates (route B1) were involved and afforded P-inverted and P-retained products, respectively. The P-inverted conversion of a P–Cl functionality to a P–C functionality can be controlled by either the temperature or the order of addition of the starting materials. The introduction of a P–Cl bond using an alkyl metallic reagent proceeded through routes A2 and A2′. At higher temperatures, P-inverted products were predominantly afforded via SN2-like route A2. At lower temperatures, bis-substituted products were formed via route A2′ and cleavage of the P–O bond. The P–S bonds were accompanied by the epimerization of the starting materials, triggered by the alkylthio anion, via route C. The epimerization can be suppressed by the use of a poorly soluble magnesium alkylthiolate, and the P-retained compounds will be formed as the major products via route B3 and BPR of the intermediates.