A Novel Approach toward Asymmetric Synthesis of Alcohol Functionalized C-Chiral Diphosphines via Two-Stage Hydrophosphination of Terminal Alkynols

Abstract

Alcohol functionalized diphosphine ligands with chirality residing on the carbon backbone were prepared using a novel two-stage asymmetric synthetic methodology from the corresponding terminal alkynols. Under mild conditions, the alkynols, 3-butyn-1-ol and 2-propyn-1-ol, were subjected to direct hydrophosphination to give the corresponding Markovnikov addition products. The phosphine functionalized alkenols thus obtained were subsequently subjected to a second-stage asymmetric hydrophosphination employing an organopalladium complex containing the ortho-metalated (R)-(1-(dimethylamino)ethyl)naphthalene as a chiral auxiliary and reaction promoter. In the reaction that involved 3-diphenylphosphanyl-but-3-en-1-ol, all four possible stereoisomeric products were generated stereoselectively in the ratio of 1:2:4:18. The major isomer was subsequently isolated in appreciable yield in its configurationally pure form and characterized by means of single-crystal X-ray crystallography. The naphthylamine auxiliary could be removed chemoselectively from the template product by treatment with concentrated hydrochloric acid to form the corresponding optically pure neutral complex. Subsequent ligand displacement from the palladium achieved using aqueous potassium cyanide generated the optically pure diphosphine ligand with chirality residing on the carbon backbone in appreciable yield. However, the similar asymmetric hydrophosphination reaction involving 2-diphenylphosphanyl-prop-2-en-1-ol did not exhibit appreciable selectivity.