Direct Chemical Synthesis of Chiral Methanol of 98% ee and Its Conversion to [2H1,3H]Methyl Tosylate and [2H1,3H-Methyl]Methionine
详细信息 查看全文
- 作者：Biljana Peric Simov ; Frank Wuggenig ; Kurt Mereiter ; Hendrik Andres ; Julien France ; Peter Schnelli ; and Friedrich Hammerschmidt
- 刊名：Journal of the American Chemical Society
- 出版年：2005
- 出版时间：October 12, 2005
- 年：2005
- 卷：127
- 期：40
- 页码：13934 - 13940
- 全文大小：167K
- 年卷期：v.127,no.40(October 12, 2005)
- ISSN：1520-5126
文摘
This paper describes the synthesis of chiral methanols [(R)- and (S)-CHDTOH] in a total of 12steps starting from (chloromethyl)dimethylphenylsilane. The metalated carbamates derived from (dimethylphenylsilyl)methanol and secondary amines were borylated at low temperatures (-78 or -94 
C) usingborates derived from tert-butyl alcohol and (+)-pinane-2,3-diol or (R,R)-1,2-dicyclohexylethane-1,2-diol togive diastereomeric boronates (dr 1:1 to 5:1). The carbamoyloxy group could be replaced smoothly withinversion of configuration by an isotope of hydrogen using LiAlH(D)4 [or LiBEt3H(D,T)]. If the individualdiastereomeric boronates were reduced with LiAlD4 and oxidized with H2O2/NaHCO3, monodeuterated(dimethylphenylsilyl)methanols of ee > 98% resulted. The absolute configurations of the boronates werebased on a single-crystal X-ray structure analysis. Brook rearrangement of the enantiomers of (dimethylphenylsilyl)-[2H1,3H]methanol prepared similarly furnished the chiral methanols which were isolated as3,5-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 3H{1H} NMR spectrawere recorded. The Brook rearrangement is a stereospecific process following a retentive course. Thechiral methanols were also transformed into methyl tosylates used to prepare [2H1,3H-methyl]methioninesin high overall yields (>80%).
C) usingborates derived from tert-butyl alcohol and (+)-pinane-2,3-diol or (R,R)-1,2-dicyclohexylethane-1,2-diol togive diastereomeric boronates (dr 1:1 to 5:1). The carbamoyloxy group could be replaced smoothly withinversion of configuration by an isotope of hydrogen using LiAlH(D)4 [or LiBEt3H(D,T)]. If the individualdiastereomeric boronates were reduced with LiAlD4 and oxidized with H2O2/NaHCO3, monodeuterated(dimethylphenylsilyl)methanols of ee > 98% resulted. The absolute configurations of the boronates werebased on a single-crystal X-ray structure analysis. Brook rearrangement of the enantiomers of (dimethylphenylsilyl)-[2H1,3H]methanol prepared similarly furnished the chiral methanols which were isolated as3,5-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 3H{1H} NMR spectrawere recorded. The Brook rearrangement is a stereospecific process following a retentive course. Thechiral methanols were also transformed into methyl tosylates used to prepare [2H1,3H-methyl]methioninesin high overall yields (>80%).