OPPOSITE STEREOCHEMICAL EFFECTS EXERTED BY CECL3 AND TICL4 ON THE LEWIS ACID-MEDIATED REDUCTION OF ALPHA-ALKYL-BETA-KETOPHOSPHINE OXIDES WITH METALLIC HYDRIDES - A HIGHLY STEREOSELECTIVE PROTOCOL FOR THE SYNTHESIS OF SYN AND ANTI ALPHA-ALKYL-BETA-HYDROXYPHOSPHINE OXIDES

A general, highly efficient methodology for obtaining both syn and ant i beta-hydroxyphosphine oxides by reduction of the corresponding beta- ketophosphine oxides is described. The nature of the Lewis acid was fo und to be pivotal in determining the outcome of these reactions. Stron gly chelating TiCl4 led to the anti isomer in high diastereoisomeric e xcess in noncoordinating solvents (CH2Cl2) at -78 degrees C with BH3/p y as reducing agent, while nonchelating CeCl3 gave a high excess of th e syn isomer in coordinating solvents (THF) at the same temperature wi th LiBH4 as reducing agent. In the latter case, CeCl3 is essential in achieving high yields and stereoselectivity, since it allows the react ion to be performed at low temperatures. Otherwise, higher temperature s (0 degrees C) are required, which lower both yields and selectivitie s. Moreover, each step of the protocol for the synthesis of stereodefi ned disubstituted olefins from alkylphosphine oxides (Warren's modific ation of the Horner procedure) has been optimized, and the optimized p rocedure has been applied to the synthesis of muscalure, the pheromone of the domestic fly.