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%).
Peric Simov
Biljana
B
Institut für Organische Chemie der Universität Wien, Währingerstrasse 38, A-1090 Wien, Austria.
Wuggenig
Frank
F
Mereiter
Kurt
K
Andres
Hendrik
H
France
Julien
J
Schnelli
Peter
P
Hammerschmidt
Friedrich
F
D001557:Benzenesulfonates / Q000138:chemical synthesis* / Q000737:chemistry; D018360:Crystallography, X-Ray; D000432:Methanol / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000737:chemistry; D008715:Methionine / Q000138:chemical synthesis* / Q000737:chemistry; D008958:Models, Molecular; D008968:Molecular Conformation; D013237:Stereoisomerism
D001557:Benzenesulfonates; C506825:methyl tosylate; D008715:Methionine; D000432:Methanol