Diastereoselective vinyl phosphate/β-keto phosphonate rearrangements

Abstract

Several nonracemic diols and amino alcohols have been tested for their utility as chiral auxiliaries in vinyl phosphate/β-keto phosphonate rearrangements. When (2R,4R)- or (2S,4S)-pentane-2,4-diol were employed, the diastereomeric β-keto phosphonates obtained from three prochiral cyclohexanones gave separate resonances in their respective 31P NMR spectra, allowing estimation of diastereomeric excess (de) via straightforward integration. A crystalline enol form of the β-keto phosphonate was obtained from one ketone (4-(1,1-(ethylenedioxy)ethyl)-4-methylcyclohexanone, 10), which allowed determination of its absolute stereochemistry by X-ray diffraction analysis. When LTMP was used to induce rearrangement of vinyl phosphates derived from ketone 10 and (2R,4R)-or (2S,4S)-pentane-2,4-diol, a de of 2.5:1 was obtained. In addition, de values of 2.0:1 and 1.4:1 were obtained with parallel rearrangements of 4-isopropyl- and 4-methylcyclohexanone, suggesting that this sequence may be more generally applicable to preparation of nonracemic materials from prochiral cyclohexanones.