Abstract
Geometrical cis- and trans- isomers of 2-chloro-, 2-bromo- and 2-fluoro-4-methyl-1,3,2-dioxaphosphorinan-2-thiones were obtained in a diastereoselective way by (a) sulfurization of corresponding cyclic PIII-halogenides, (b) reaction of cyclic phosphorothioic acids with phosphorus pentachloride and (c) halogen–halogen exchange at PIV-halogenide. Their conformation and configuration at the C4-ring carbon and phosphorus stereocentres were studied by NMR (1H, 31P) methods, X-ray analysis and density functional (DFT) calculations. The stereochemistry of displacement reactions (alkaline hydrolysis, methanolysis, aminolysis) at phosphorus and its mechanism were shown to depend on the nature of halogen. Cyclic cis- and trans-isomers of chlorides and bromides react with nucleophiles (HO−, CH3O−, Me2NH) with inversion of configuration at phosphorus. DFT calculations provided evidence that alkaline hydrolysis of cyclic thiophosphoryl chlorides proceeds according to the SN2-P mechanism with a single transition state according to the potential energy surface (PES) observed. The alkaline hydrolysis reaction of cis- and trans-fluorides afforded the same mixture of the corresponding cyclic thiophosphoric acids with the thermodynamically more stable major product. Similar DFT calculations revealed that substitution at phosphorus in fluorides proceeds stepwise according to the A–E mechanism with formation of a pentacoordinate intermediate since a PES with two transition states was observed.
Highlights
In the present paper we report the complete results of our studies on this class of compounds, including their stereospecific synthesis, stereochemical course of displacement reactions at phosphorus in 6 and the density functional (DFT) calculations aimed at determination of the mechanisms of the substitution reactions
Our initial investigations were focused on the efficient preparation and assignment of stereochemistry to 2-chloro, 2-bromo- and 2-fluoro-4-methyl-1,3,2-dioxaphosphorinan-2-thiones 6, which were intended to use as model compounds in subsequent studies of the stereochemistry of nucleophilic substitution at phosphorus
Having in hand the diastereomeric pairs of thiophosphoryl chloride 6(Cl) and fluoride 6(F), we could start with investigation of the stereochemical course of nucleophilic displacement processes occurring at phosphorus
Summary
The stereochemistry and mechanisms of nucleophilic substitution reactions at the phosphorus atom have been the major points of interest of many research groups since the middle of the last century [1]. The stereochemical course of nucleophilic displacement reactions at phosphorus has been a subject of our early systematic studies, which have employed, in the first stage, optically active acyclic thiophosphonic acids 1 and their derivatives, as for example the enantiomeric thiophosphonyl chlorides 2 (Figure 1). Figure optically active acyclic thiophosphonic acidacid (1) and Figure 1
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
