Myrtenal and Myrtanal as Auxiliaries in the Synthesis of Some C,P-Stereogenic Hydroxyphosphine Oxides and Hydroxyphosphine-Boranes Possessing up to Four Contiguous Centers of Chirality

1,4- and 1,2-additons of secondary phosphine oxides to (1R)-myrtenal and (1S)-myrtanal were evaluated as potential routes to P,C-stereogenic phosphine oxides bearing additional hydroxyl or aldehyde functions. 1,4-Additions of racemic secondary phosphine oxides to (1R)-myrtenal were found to offer moderate to good stereoselectivity which shows some promise for utility in kinetic resolution processes, especially at lower conversions. In case of 1,2-additions making the process doubly asymmetric by using an enantiomerically pure secondary phosphine oxide as substrate turned out to be practical. The stereochemical course of the addition reactions under study is presented. The P-resolved 1,2-addition products were demonstrated to undergo facile reduction by BH3 at room temperature leading to the formation of the corresponding α-hydroxyphosphine-boranes with clean inversion of configuration at the P-centre. All P,C-stereogenic phosphine oxides and boranes that were isolated in the form of a single diastereoisomer were assigned their absolute configurations by means of X-ray crystallography and/or 2D NMR spectral techniques

Resolution of P-Sterogenic 1-Phenylphosphin-2-en-4-one 1-Oxide into Two Enantiomers by (<i>R</i>,<i>R</i>)-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 (2), was achieved through the fractional crystallization of its diastereomeric complexes with (4R,5R)-(−)-2,2-dimethyl -α,α,α′,α′-tetraphenyl-dioxolan-4,5-dimethanol (R,R-TADDOL) followed by the liberation of the individual enantiomers of 2 by flash chromatography on silica gel columns. The resolution process furnished the two enantiomers of 2 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., (R)-2•R,R)-TADDOL and (S)-2•(R,R)-TADDOL. The structural analysis revealed that in the (R)-2•(R,R)-TADDOL complex, the P-phenyl substituent occupied a pseudoequatorial position, whereas in (S)-2•(R,R)-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 (R,R)-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 (R)-2 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 (R)-2 by PhSiH3 at 60 °C revealed an unexpectedly low barrier for P-inversion in 1-phenylphosphin-2-en-4-one