STEREOELECTIVE REACTION BY USING AN INTRAMOLECULAR CATION-π INTERACTION

利用分子内阳离子-π 相互作用的立体选择性反应

• 批准号: 13650901
• 负责人: YAMADA Shinji
• 金额: $ 2.24万
• 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: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13650901/
• 关键词: cation-π interaction; asymmetric addition; 1,4-dihydropyridine; face-selective addition; intermolecular interaction; nicotinic amide; X-ray structures; pyridinium salt; meroquinen; ピペリジン誘導体; 立体選択的反応; 求核付加反心; オキサゾリジン; CDスペクトル; カチオンーπ相互作用; 1,

Chiral 1,4-dihydropyridines are continue to be of great interest in relation with calcium agonists, NADH models, and intermediates for alkaloid syntheses, the stereoselective synthesis of these compounds has attracted the attention of researchers. Here we report a new synthetic method of chiral 1,4-dihydropyridines by way of a face-selective addition to a cation-π complex.Our strategy of a nicotinic amide derivative into a pyridinium salt gives rise to an attractive force between the two entities to form a cation-π complex ; (b) The selective shielding of one side of the pyridinium face by the phenyl ring enables nucleophiles to attack the complex only from the non-shielded side, which will result in 1,4-dihydropyridine stereoselectively.The reaction of nicotinic amide derivatives 1a (R=benzyl) and 1b (R=phenyl) with ketene silyl acetals in presence of methyl chloroformate gave corresponding 1,2-dihydroyridines 2a (99%de) and 2b (12%de), respectively. Significant difference in the stereoselectivities would be attributable to the geometrical differences between the intermediary pyridinium salts ; the benzyl group much more effectively shields one side of the pyridinium face than the phenyl group.^1H NMR studies and X-ray crystallographic analysis clarified the existence of a cation-π interaction during the reactions.

手性1,4-二氢吡啶在钙激动剂、NADH模型和生物碱合成中间体方面继续引起人们的极大兴趣，这些化合物的立体选择性合成引起了研究人员的关注，在这里我们报道了一种新的手性合成方法。 1,4-二氢吡啶通过面选择性加成到阳离子-π复合物上。我们将烟酰胺衍生物转化为吡啶鎓的策略盐在两个实体之间产生吸引力，形成阳离子-π络合物；(b)苯环选择性屏蔽吡啶鎓表面的一侧，使得亲核试剂只能从非屏蔽侧攻击络合物，立体选择性地生成1,4-二氢吡啶。烟酰胺衍生物1a（R=苄基）和1b（R=苯基）与乙烯酮甲硅烷基缩醛在氯甲酸甲酯存在下分别生成相应的 1,2-二氢吡啶 2a (99%de) 和 2b (12%de)。立体选择性的显着差异可归因于中间吡啶鎓盐之间的几何差异。苄基比苯基更有效地保护吡啶鎓表面的一侧。^1H NMR 研究和 X 射线晶体学分析阐明了反应过程中阳离子-π 相互作用的存在。

项目成果

S.Yamada, A.Homma: "N-Substituent Effect on the cis-trans Geometry of Nine-Membered Lactams."Chem.Commun.. 2656-2657 (2002)

S.Yamada, A.Homma：“N-取代基对九元内酰胺顺反几何结构的影响。”Chem.Commun. 2656-2657 (2002)

S.Yamada, K.Matsuda: "Remarkable Thiocarbonyl and Ring-Size Effects on the Amide Bond Twisting"Chem. Lett.. 750-751 (2001)

S.Yamada、K.Matsuda：“显着的硫代羰基和环尺寸对酰胺键扭曲的影响”Chem。

山田眞二: "分子内相互作用による有機分子の立体配座制御と合成的利用"日本結晶学会誌. 44. 240-245 (2002)

Shinji Yamada：“通过分子内相互作用实现有机分子的构象控制和合成利用”日本晶体学会杂志 44. 240-245 (2002)。

M.Matsumoto, S.Yamada: "Asakura Inc."Series of Chemistry of 21th Century "Chemistry of Organic Reaction"(in press). (2004)

M.Matsumoto、S.Yamada：《Asakura Inc.》21世纪化学丛书《有机反应化学》（出版中）。

S.Yamada, C.Morita: "Face-selective Addition to a Cation-π Complex of Pyridinium Salt : Synthesis of Chiral 1,4-Dihydropyridines"J.Am.Chem.Soc.. 124. 8184-8185 (2002)

S.Yamada、C.Morita：“吡啶鎓盐的阳离子 π 络合物的面选择性加成：手性 1,4-二氢吡啶的合成” J.Am.Chem.Soc.. 124. 8184-8185 (2002)