Stereochemical consequences of the use of chiral N-phosphoryl oxazolidinones in the attempted kinetic resolution of bromomagnesium alkoxides

A number of chiral N-phosphoryl oxazolidinones have been prepared and evaluated as asymmetric phosphoryl transfer agents with the magnesium alkoxide of 1-phenyl ethanol. The reaction proceeded with little stereoselection, which was shown to be a consequence of the reaction mechanism that occurs with inversion of configuration at phosphorus consistent with in-line attack opposite the leaving group.

Figure optionsDownload as PowerPoint slide

(1S)-Phenylethanol diethyl phosphateC12H19O4P[α]D = −20.2 (c 1, CHCl3)Source of chirality = asymmetric synthesis

[(4R)-4-Benzyl-2-oxo-oxazolidin-3-yl]-phosphonic acid diphenyl esterC22H20NO5P[α]D = +58.1 (c 1, CHCl3)Source of chirality = (4R)-4-benzyl-oxazolidin-2-one

[(4R)-4-Benzyl-2-oxo-oxazolidin-3-yl]-phosphonic acid diethyl esterC14H20NO5P[α]D = −33.7 (c 1, CHCl3)Source of chirality = (4R)-benzyl-oxazolidin-2-one

[(4S)-4-Phenyl-2-oxo-oxazolidin-3-yl]-phosphonic acid diethyl esterC13H18NO5P[α]D = −45.3 (c 1, CHCl3)Source of chirality = (4S)-Phenyl-oxazolidin-2-one

[(4R,5S)-Indano[1,2-d]-2-oxo-oxazolidin-3-yl]-phosphonic acid diethyl esterC14H18NO5P[α]D = −13.5 (c 1, CHCl3)Source of chirality = (4R,5S)-indano[1,2-d]oxazolidin-2-one

[(4S)-4-Isopropyl-5,5-dimethyl-2-oxo-oxazolidin-3-yl]-phosphonic acid diethyl esterC12H24NO5P[α]D = −29.4 (c 1, CHCl3)Source of chirality = 5,5-dimethyl-4-isopropyl oxazolidin-2-one

[(4S)-4-Benzyl-2-oxo-5,5-diphenyl-oxazolidin-3-yl]-phosphonic acid diethyl esterC26H28NO5P[α]D = −35.0(c 1, CHCl3)Source of chirality = 5,5-diphenyl-4-benzyl oxazolidin-2-one

[(SP,4S)-4-Isopropyl-5,5-dimethyl-2-oxo-oxazolidin-3-yl]-phosphonic acid ethyl methyl esterC11H22NO5P[α]D = −7.0 (c 1, CHCl3)Source of chirality = 5,5-dimethyl-4-isopropyl oxazolidin-2-one

[(RP,4S)-4-Isopropyl-5,5-dimethyl-2-oxo-oxazolidin-3-yl]-phosphonic acid ethyl methyl esterC11H22NO5P[α]D = −33.7 (c 1, CHCl3)Source of chirality = 5,5-dimethyl-4-isopropyl oxazolidin-2-one