Opposite stereochemical effects exerted by CeCl3 and TiCl4 on the Lewis acid mediated reduction of α-alkyl-β-ketophosphine oxides with metallic hydrides: A highly stereoselective protocol for the synthesis of syn and anti α-alkyl-β-hydroxyphosphine oxides

Article abstract of DOI:10.1002/chem.19970031209

A general, highly efficient methodology for obtaining both syn and anti α-hydroxyphosphine oxides by reduction of the corresponding α-ketophosphine oxides is described. The nature of the Lewis acid was found to be pivotal in determining the outcome of these reactions. Strongly chelating TiCl₄ led to the anti isomer in high diastereoisomeric excess in noncoordinating solvents (CH₂Cl₂) at -78°C with BH₃/py as reducing agent, while nonchelating CeCl₃ gave a high excess of the syn isomer in coordinating solvents (THF) at the same temperature with LiBH₄ as reducing agent. In the latter case, CeCl₃ is essential in achieving high yields and stereoselectivity, since it allows the reaction to be performed at low temperatures. Otherwise, higher temperatures (0 °C) are required, which lower both yields and selectivities. Moreover, each step of the protocol for the synthesis of stereodefined disubstituted olefins from alkylphosphine oxides (Warren's modification of the Homer procedure) has been optimized, and the optimized procedure has been applied to the synthesis of muscalure, the pheromone of the domestic fly.