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.合成了具有扭曲酰胺键的手性扭曲amides4-alkyl-3-pivaloyl-1，3-thiazolidine-2-thiones。通过~(13)C核磁共振和红外光谱确证了其结构和几何构型。反式仲醇的动力学拆分扭曲的酰胺类化合物用于仲醇在中性条件下的不对称酰化反应。仲醇与4位含t-Bu基团的酰胺进行酰化反应，得到具有(S)构型的50-84%ee的相应酯类化合物。以甲基溴化镁为碱时，产物构型颠倒。(S)-4-叔丁基-1，3-噻唑烷-2-硫酮与介孔二醇的不对称单酰化反应高产率地合成了单酯。对顺式-1，4-二羟基四胺有很高的对映选择性(90%ee)。吡喃氧基上碳原子的立体化学为(S)构型。以市售的[15N]甘氨酸和[15N]亮氨酸为原料，经几步反应合成了一系列~(15)C-~(15)N偶联常数与扭转角的关系。用~(13)C核磁共振波谱测定了C-N偶合常数。结果表明，随着扭角的增大，1JC(O)，N值减小。这一结果表明，~(13)C-~(15)N偶合常数是研究酰胺键扭曲的有用参数。

项目成果

S.Yamada: "A Nonresonated Orthogonally Twisted Amides" Chem.Lett.(in press). (1998)

S.Yamada：“非共振正交扭曲酰胺”Chem.Lett.（印刷中）。

山田 眞二: "ねじれ型アミドの合成、構造、反応" 有機合成協会誌. (印刷中). (1998)

Shinji Yamada：“扭曲酰胺的合成、结构和反应”日本有机合成学会杂志（1998 年出版）。

S.Yamada: "Structure Dynamics and Functions of Amides in Molecules" Chapman & Hall,London, 300 (1998)

S.Yamada：“分子中酰胺的结构动力学和功能”查普曼

S.Yamada: "13C-15N Coupling Constants in a Series of Twisted Amides : Relationships with C(O)-N Twist Angles" J.Chem.Soc.Chem.Commun.(in press). (1997)

S.Yamada：“一系列扭曲酰胺中的 13C-15N 耦合常数：与 C(O)-N 扭曲角的关系”J.Chem.Soc.Chem.Commun.（出版中）。

S.Yamada: "13C-15N Coupling Constants in a Series of Twisted Amides : Relationships with C(O)-N Twist Angles" Chem.Commun.885-886 (1997)

S.Yamada：“一系列扭曲酰胺中的 13C-15N 耦合常数：与 C(O)-N 扭曲角的关系” Chem.Commun.885-886 (1997)