Direct chemical synthesis of chiral methanol of 98% ee and its conversion to [(2)H1,(3)H]methyl tosylate and [(2)H1,(3)H-methyl]methionine.

This paper describes the synthesis of chiral methanols [(R)- and (S)-CHDTOH] in a total of 12 steps starting from (chloromethyl)dimethylphenylsilane. The metalated carbamates derived from (dimethylphenylsilyl)methanol and secondary amines were borylated at low temperatures (-78 or -94 degrees C) using borates derived from tert-butyl alcohol and (+)-pinane-2,3-diol or (R,R)-1,2-dicyclohexylethane-1,2-diol to give diastereomeric boronates (dr 1:1 to 5:1). The carbamoyloxy group could be replaced smoothly with inversion of configuration by an isotope of hydrogen using LiAlH(D)4 [or LiBEt3H(D,T)]. If the individual diastereomeric boronates were reduced with LiAlD4 and oxidized with H2O2/NaHCO3, monodeuterated (dimethylphenylsilyl)methanols of ee > 98% resulted. The absolute configurations of the boronates were based on a single-crystal X-ray structure analysis. Brook rearrangement of the enantiomers of (dimethylphenylsilyl)-[(2)H1,(3)H]methanol prepared similarly furnished the chiral methanols which were isolated as 3,5-dinitrobenzoates in 81% and 90% yield, respectively. For determination of the enantiomeric excesses (98%), the methyl groups were transferred to the nitrogen of (S)-2-methylpiperidine and (3)H{(1)H} NMR spectra were recorded. The Brook rearrangement is a stereospecific process following a retentive course. The chiral methanols were also transformed into methyl tosylates used to prepare [(2)H1,(3)H-methyl]methionines in high overall yields (>80%).