KINETIC RESOLUTION OF sec-ALCOHOLS WITH TWISTED AMIDES

仲醇与扭曲酰胺的动力学解析

• 批准号: 08640755
• 负责人: YAMADA Shinji
• 金额: $ 1.34万
• 依托单位: OCHANOMIZU UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1996
• 资助国家: 日本
• 起止时间: 1996 至 1997
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08640755/
• 关键词: twisted amides; asymmetric acylation; kinetic resolution; hydroxy group; ester; sec-alcohol; diol; amide; ヒドロキシル基

1. Synthesis of chiral twisted amides4-alkyl-3-pivaloyl-1,3-thiazolidine-2-thiones possessing twisted amide bonds were synthesized. The structure and geometry were confirmed by 13C NMR and IR spectroscopies.2. Kinetic resolution of recemic sec-alcoholsThe twisted amides were used for the enantioselective acylation of sec-alcohols under neutral conditions. Acylations of the sec-alcohols with an amide having t-Bu group at 4-position gave the corresponding esters in 50-84% ee with (S) configuration. When methyl magnesium bromide was used as a base, the configuration of the products werereversed.3. Desymmetrization of meso-diolsEnantioselective monoacylation of meso-diols with (S)-4-t-butyl-1,3-thiazolidine-2-thione were performed to give monoesters in high yields. Very high enantioselectivity (90%ee) was obtained for cis-1,4-dihydroxytetraline. The stereochemistry at the carbon attached to the pivaloyloxy group is (S) configuration.4. Relationships between 13C-15N coupling constants and twist anglesA series of twisted amides enliched to 99% with 15N was synthesized via several steps from commercially available [15N] glycine and [15N] leucine. The C-N coupling constants were measured using 13C NMR spectroscopy. It was found that as the twist angle increase, the 1JC (O), N value decreases. This result suggests that the 13C-15N coupling constant is a useful parameter for the study of amide bond twisting.

1.手性扭曲酰胺的合成合成了具有扭曲酰胺键的4-烷基-3-新戊酰基-1,3-噻唑烷-2-硫酮。其结构和几何形状经13C NMR和IR光谱证实。 2．仲醇的动力学拆分扭曲酰胺用于在中性条件下对仲醇进行对映选择性酰化。仲醇用4位具有t-Bu基团的酰胺酰化，得到具有(S)构型的50-84％ee的相应酯。当甲基溴化镁为碱时，产物构型发生逆转。 3．内消旋二醇的去对称化用(S)-4-叔丁基-1,3-噻唑烷-2-硫酮对内消旋二醇进行对映选择性单酰化，以高产率得到单酯。顺式 1,4-二羟基四氢化萘获得了非常高的对映选择性 (90%ee)。连接到新戊酰氧基的碳的立体化学是(S)构型。4． 13C-15N 偶联常数与扭转角之间的关系通过几个步骤从市售的[15N]甘氨酸和[15N]亮氨酸合成了一系列用15N富集至99%的扭转酰胺。使用 13C NMR 光谱测量 C-N 耦合常数。发现随着扭转角增大，1JC(O)、N值减小。该结果表明 13C-15N 耦合常数是研究酰胺键扭曲的有用参数。