Resolution of P-Sterogenic 1-Phenylphosphin-2-en-4-one 1-Oxide into Two Enantiomers by (,)-TADDOL and Conformational Diversity of the Phosphinenone Ring and TADDOL in the Crystal State.

The resolution of racemic 1-phenylphosphin-2-en-4-one 1-oxide (), was achieved through the fractional crystallization of its diastereomeric complexes with (4,5)-(-)-2,2-dimethyl -α,α,α',α'-tetraphenyl-dioxolan-4,5-dimethanol (-TADDOL) followed by the liberation of the individual enantiomers of by flash chromatography on silica gel columns. The resolution process furnished the two enantiomers of of 99.1 and 99.9% e.e. at isolated yields of 62 and 59% (counted for the single enantiomer), respectively. The absolute configurations of the two enantiomers were established by means of X-ray crystallography of their diastereomerically pure complexes, i.e., ()-•,)-TADDOL and ()•(,)-TADDOL. The structural analysis revealed that in the ()-•(,)-TADDOL complex, the P-phenyl substituent occupied a pseudoequatorial position, whereas in ()-•(,)-TADDOL, it appeared in both the pseudoequatorial and the pseudoaxial positions in four symmetrically independent molecules. Concurrent conformational changes of the TADDOL molecules were best described by the observed changes of a pseudo-torsional CO...OC angle that could be considered as a possible measure of TADDOL conformation in its receptor-ligand complexes. The structural analysis of the (,)-TADDOL molecule revealed that efficiency of this compound for use as an effective resolving factor comes from its ability to flexibly fit its structure to both enantiomers of a ligand molecule, producing a rare case of resolution for both pure enantiomers with one chiral separating agent. The resolved ()- was used to assign the absolute configuration of a recently described (-)-1-phenylphosphin-2-en-4-one 1-sulfide by chemical correlation. In addition, an attempted stereoretentive reduction of ()- by PhSiH at 60 °C revealed an unexpectedly low barrier for P-inversion in 1-phenylphosphin-2-en-4-one.