REMOTE ASYMMETRIC INDUCTION USING AXIALLY CHIRAL TWISTED AMIDES

使用轴向手性扭曲酰胺的远程不对称感应

• 批准号: 10640574
• 负责人: YAMADA Shinji
• 金额: $ 1.79万
• 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: 1998
• 资助国家: 日本
• 起止时间: 1998 至 1999
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10640574/
• 关键词: twisted amide; asymmetric addition; 1,4-dihydropyridine; face-selective addition; neighboring group effect; nicotinic amide; orbital interaction; pyridinium cation

Chiral 1,4-dihydropyridines have received considerable attention as NAD models and synthetic intermediates for various natural products. In general, chiral 1,4-dihydropyridines are synthesized by the addition of nucleophiles to pyridinium salts under chelation control. However, we synthesized them based on a new concept. Thus, axial chirality of an amide bond was employed for discrimination of pyridinium faces. Addition of various nucleophiles to the pyridinium salts of nicotinic amides bearing chiral 1,3-thiazolidine-2-thiones gave (R)-1,4-dihydropyridines, of which stereochemistry was determined by X-ray analysis. To clarify the mechanism of this reaction, 1H and 13C NMR measurements and ab initio 3-21G* calculations were performed. These studies suggest that C4-C3-CO-N-C=S moiety makes helical structure with twisted amide linkage, moreover, the unusual structure was stabilized by intramolecular HOMO-LUMO interaction.

手性1，4-二氢吡啶类化合物作为NAD模型化合物和天然产物的合成中间体受到了广泛的关注。一般来说，手性1，4-二氢吡啶是通过在螯合控制下将亲核试剂加成到吡啶鎓盐上来合成的。然而，我们基于一个新的概念合成了它们。因此，酰胺键的轴向手性用于区分吡啶鎓面。将不同的亲核试剂加成到带有手性1，3-噻唑烷-2-硫酮的烟酰胺吡啶盐上，得到（R）-1，4-二氢吡啶类化合物，其立体化学结构经X-射线分析确定。为了阐明该反应的机理，进行了1H和13 C NMR测量和ab initio 3- 21 G * 计算。这些研究表明，C4-C3-CO-N-C=S部分与扭曲的酰胺键形成螺旋结构，并且这种不寻常的结构是通过分子内HOMO-LUMO相互作用稳定的。

项目成果

S. Yamada, N. Nunami: "A Nonresonated Orthogonally Twisted Amide"Chem. Lett.. 451-452 (1998)

S. Yamada，N. Nunami：“非共振正交扭曲酰胺”化学。

S. Yamada and M. Ichikawa: "Synthesis of Chiral 1,4-Dihydropyridines by Diastereoface-selective Asymmetric Addition to Nicotinic Amides"Tetrahedron Lett.. 40. 4231-4234 (1999)

S. Yamada 和 M. Ichikawa：“通过非对映面选择性不对称加成烟酰胺合成手性 1,4-二氢吡啶”Tetrahedron Lett.. 40. 4231-4234 (1999)

S.Yamada and H.Katsumata: "Asymmetric Acylation of sec-Alcohols with Twisted Amides Possessing Axial Chirality Induced by the Adjacent Chiral Center"J. Org. Chem.. 64. 9365-9323 (1999)

S.Yamada 和 H.Katsumata：“仲醇与具有由相邻手性中心诱导的轴向手性的扭曲酰胺的不对称酰化”J。

S. Yamada, In: "The Amide Linkage : Selected Structural Aspects in Chemistry Biochemistry and Materials" Ed. A. Greenberg, J. F. Liebman"John Wiley & Sons. Inc. : New York. (chapter 8). 215-246 (2000)

S. Yamada，见：“酰胺联结：化学、生物化学和材料中的选定结构方面”Ed。

S. Yamada and N. Nunami: "A Nonresonated Orthogonally Twisted Amide"Chem. Lett.. 451-452 (1998)

S. Yamada 和 N. Nunami：“非共振正交扭曲酰胺”化学。