Development of an efficient method for synthesizing N-heterocyclic compounds based on a divalent titanium complex

开发基于二价钛配合物的高效合成N-杂环化合物的方法

• 批准号: 09555284
• 负责人: SATO Fumie
• 金额: $ 3.01万
• 依托单位: Tokyo Institute of Technology
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 1997
• 资助国家: 日本
• 起止时间: 1997 至 1999
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09555284/
• 关键词: divalent titanium; Allyltitanium; imine; asymmetric synthesis; homoenolate; acetal; aminocarbonyl compounds; stereoselective; アミノ酸; 光学活性; ヘテロ環化合物; 1-デオキシアミノ糖; セリン; シクロプロパノール; アリルアルコール; ピペリジン; キノロン; ピロール; インドール; チタン; 求核アシル置換; ビシクロ環

A new titanium complex (ηィイD12ィエD1-propene)Ti(O-i-Pr)ィイD22ィエD2 (1), generated in situ by treatment of Ti(O-i-Pr)ィイD24ィエD2 with 2 equiv of i-PrMgX (X = Cl or Br), nicely acts as a versatile titanium(II) equivalent to effect the following unique transformations. Thus, alkynes react with 1 to afford the alkyne-titanium complexes of type (ηィイD12ィエD1-alkyne)Ti(O-i-Pr)ィイD22ィエD2, which could be utilized as a vicinal vinylic dianion equivalent in the reactions with various kinds of electrophiles. Allyl- and allenyltitaniums could readily be prepared from allylic or propargylic alcohol derivatives by the reaction with 1 through an oxidative addition pathway. While acetylenic esters resulted in an intramolecular nucleophilic acyl substitution (INAS) reaction to afford α,β-unsaturated carbonyl compounds, olefinic esters undergo tandem INAS and intramolecular carbonyl addition reactions to give cyclopropanols. Ene-ene, ene-yne, and yne-yne coupling reactions proceed in an intra- or intermolecular way via a cyclometallation reaction, and the generated titanacyclic complexes react with a variety of electrophiles in a chemo-, regio-, stereoselective way.By utilizing these reactions, we have now succeeded in synthesizing N-heterocycles and/or their precursors, which include quinolones, pyrroles, indoles, optically active N-heterocycles, 2,6-disubstituted piperodines, β-lactams, azasugars and γ-amino carbonyl compounds.

一种新的钛络合物 (ηィイD12ィエD1-丙烯)Ti(O-i-Pr)ィイD22ィエD2 (1)，通过用 2 当量的 i-PrMgX（X = Cl 或 Br）处理 Ti(O-i-Pr)ィイD24ィエD2 原位生成，可以很好地充当多功能钛 (II) 等效物实现以下独特的转变。因此，炔烃与1反应得到(ηィイD12ィエD1-炔)Ti(O-i-Pr)ィイD22ィエD2类型的炔-钛配合物，其可以在与各种亲电试剂的反应中用作邻乙烯基双阴离子等价物。烯丙基钛和烯丙基钛可以很容易地由烯丙醇或炔丙醇衍生物通过氧化加成途径与1反应来制备。炔酯通过分子内亲核酰基取代 (INAS) 反应生成 α,β-不饱和羰基化合物，而烯酯则通过串联 INAS 和分子内羰基加成反应生成环丙醇。烯-烯、烯-炔和炔-炔偶联反应通过环金属化反应以分子内或分子间的方式进行，生成的钛环配合物以化学、区域、立体选择性的方式与多种亲电子试剂反应。通过利用这些反应，我们现在已经成功合成了N-杂环和/或其前体，其中包括 喹诺酮类、吡咯类、吲哚类、光学活性N-杂环类、2,6-二取代哌啶类、β-内酰胺类、氮杂糖类和γ-氨基羰基化合物。

项目成果

Hirokazu Urabe: "A Titanacycle-to-Carbocycle Relay Leading to an Expedient Synthesis of Cycleopentadienols"Angew. Chem. Int. Ed. Engl. 39, 23. 3516-3518 (1999)

Hirokazu Urabe：“钛环到碳环的中继导致环戊二烯醇的便捷合成”Angew。

Hirokazu Urabe: "A Titanacycle-to-Carbocycle Relay Leading to an Expedient Synthesis of Cyclopentadienols"Angew. Chem. Int. Ed. Engl.. 39, 23. 3516-3518 (1999)

Hirokazu Urabe：“钛环到碳环的中继导致环戊二烯醇的便捷合成”Angew。

Hirokazu Urabe: "Stereocontrolled Cyclization of Enynols and Allenynols with (η^2-Propene)Ti(O-i-Pr)_2 Important Role of Unprotected Hydroxy Group at a Remote Position" Tetrahedron Letters:. 39,40. 7329-7332 (1998)

Hirokazu Urabe：“烯醇和烯醇与 (η^2-丙烯)Ti(O-i-Pr)_2 远程位置上未受保护的羟基的重要作用”四面体快报：39,40 (1998)。

Xin Teng: "Synthesis of Chiral Allyltitaniums Having an Amino Group at the C-4 Position and Their diastereoslective Addition Reaction with Aldehydes"Tetrahedron Letters. 38, 52. 8977-8980 (1997)

滕鑫：“C-4位氨基手性烯丙基钛的合成及其与醛的非对映加成反应”四面体快报。

Hirokazu Urabe: "A Titanacycle-to-Carbocycle Relay Leading to an Expedient Synthesis of Cyclopentadienols"Angew. Chem. Int. Ed. Engl. 39,23. 3516-3518 (1999)

Hirokazu Urabe：“钛环到碳环的中继导致环戊二烯醇的便捷合成”Angew。