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1,4-二氢吡啶已作为各种天然产物的NAD模型和合成中间体受到了很大的关注。通常，手性1,4-二氢吡啶是通过在螯合控制下向吡啶季盐中添加到吡啶盐中合成的。但是，我们根据新概念合成它们。因此，采用酰胺键的轴向手性来歧视吡啶丁族面。将各种亲核试剂添加到带有手性1,3-噻唑烷-2-硫代基因的烟碱酰胺的吡啶丁盐中得到（R）-1,4-二氢吡啶，其中立体化学由X射线分析确定。为了阐明该反应的机制，进行了1H和13C NMR的测量以及从头算3-21G*的计算。这些研究表明，C4-C3-CO-N-C = S部分具有旋转酰胺连接的螺旋结构，此外，异常结构通过分子内同性恋相互作用稳定。

项目成果

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, 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 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。