TUrning Regioselectivity into Stereoselectivity: Efficient Dual Resolution of P-Stereogenic Phosphine Oxides through Bifurcation of the Reaction Pathway of a Common Intermediate

摘要

Synthetic routes that provide facile access to either enantiomeric form of a target compound are particularly valuable. The crystallization-free dual resolution of phosphine oxides that gives highly enantioenriched materials (up to 94 % ee) in excellent yields is reported. Both enantiomeric oxides have been prepared from a single intermediate, (R_p)-alkoxy-phosphonium chloride, which is formed in the course of a selective dynamic kinetic resolution using a single enantiomer of menthol as the chiral auxiliary. The origin of the dual stereoselectivity lies in bifurcation of the reaction pathway of this intermediate, which works as a stereochemical railroad switch. Under controlled conditions, Arbuzov-type collapse of this intermediate proceeds through C—O bond fission with retention of the configuration at the phosphorus center. Conversely, alkaline hydrolysis of the P-0 bond leads to the opposite S_p enantiomer.