Preparation of both diastereomers of enantiomerically pure asymmetric vinylphosphonamidates 4a and 4b, and nucleophilic addition of carbon nucleophiles to them is reported.We have previously reported on the diastereoselective addition of carbon nucleophiles to chiral vinyl phosphonamidates as a means of preparing asymmetric b-substituted phosphoamidates and phosphonates. 1,2 Additions to vinylphosphonamidates such as 3-diphenylmethyl-2-(prop-2-enyl)-2-oxo-1,3,2-oxazaphosphorinane 1 (Figure), where the phosphorus atom is part of a six-membered ring, proceed with good selectivities (typically upto 80% d.e.) and the relative configuration of the major diastereomer is (S P ,S C(b) /R P ,R C(b) ). 1 In order to control the absolute configuration at the b-substituent, we used enantiomeri-This approach presented two challenges. Although both phosphorus epimers of 2 are accessible, the R P epimer was formed in low yields and could not be prepared in large enough quantities to make it a useful reagent for synthesis. More importantly, selectivities were considerably lower in additions to 2 (typically up to 60% de).
FigureHerein, we report an improved method for the control of the absolute configuration in the additions of carbon nucleophiles to asymmetric vinyl phosphonamidates. It has the advantage that both phosphorus epimers of asymmetric vinyl phosphonamidates are synthetically accessible and that the diastereoeselectivities of the additions are considerably improved.Diastereomeric allyl phosphonamidates 3a and 3b were prepared in two steps from N-(R-1-phenylethyl)propanolamine 1,3 (Scheme 1) and were cleanly separated by chromatography. One of the diastereomers 3a was crystalline and its absolute configuration was determined by X-ray diffraction. Both diastereomers were then individually transformed to the corresponding vinylphosphonamidates 4a and 4b (Scheme 1). 4 The separation of the diastereomers prior to the migration of double bond is essential as a mixture of 4a and 4b could not be easily separated by chromatography.
We report on the asymmetric induction by a chiral phosphorus atom contained in a 2-oxo-1,3,2-oxazaphosphorinane ring into an adjacent keto, alkane, or alkene function.
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