We have now fully developed our original dynamic resolution methodology1 into an efficient process for the synthesis of P-stereogenic phosphorus compounds. The heart of the process is the generation of one diastereomer of an alkoxyphosphonium salt by dynamic resolution of a rapidly racemising chlorophosphonium salt with a chiral alcohol e.g. menthol. The alkoxy salts can be obtained in up to 99:1 dr (98% de) and their configuration confirmed by X-ray crystallography. The configuration is preserved during their thermal Arbusov collapse to the phosphine oxide. Conversely, their base promoted hydrolysis leads to the opposite enantiomer, confirmed by isotopic labelling,2 effectively turning regioselectivity into stereoselectivity. Further applications of this methodology will be presented as well as findings indicating that nucleophilic displacement at tetra-coordinate phosphonium cations [R3PX]+ and [R3POR']+ occurs via an ion-pair mediated associative mechanism. Work is underway to apply the new methodologies and DFT-based selectivity prediction approaches to efficient synthesis of a range of P-stereogenic molecules.Acknowledgement: This work was supported by a Science Foundation Ireland Principal Investigator Grant (09/IN.1/ B2627)References:1. Bergin, E.; O'Connor, C. T.; Robinson, S. B.; McGarrigle, E. M.; O'Mahony, C. P.; Gilheany, D. G. J. Am. Chem. Soc., 2007  , 129, 9566-9567.2. Nikitin, K.; Rajendran. K.; M�ller-Bunz H.; Gilheany, D.G. Ang. Chem. Int. Ed., 2014,  53, 1906-1909.

Dynamic resolution of <i>P</i>-stereogenic phosphine oxides with choice of enantiomer in the work-up

248th National Meeting (2014)

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Dynamic resolution of P-stereogenic phosphine oxides with choice of enantiomer in the work-up