Development and Synthetic Application of Metalative Reppe Reaction

金属化Reppe反应的进展及合成应用

• 批准号: 14350472
• 负责人: URABE Hirokazu
• 金额: $ 4.03万
• 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: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2004
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14350472/
• 关键词: acetylene; azatitanacyclopentadiene; nitrile; pyridine; pyrrole; Reppe reaction; titanacyclopentadiene; titanium alkoxide; 抗アレルギー薬剤; 光学活性ピリジン; シクロチアゾマイシン; チタンアルコキシド; ベンゾシクロヘプタピリジン; ピリジルチタン; アミノピリジン; レッペ反応; アルシオプテロシン; ピリジンアルデヒド; プラジミシン

This research has developed new styles of the Reppe reaction, which afford single aromatic compounds as a titanated form from three different, unsymmetrical acetylenes. Alternatively, replacing one or two acetylene(s) above with nitriles, we also developed an aza-Reppe reaction, producing metalated pyridines or pyrroles as a single isomer. Moreover, some biologically active compounds or medicinally important compounds were prepared by these new reactions. Thus, 1)benzyltitanium compounds were obtained as a single isomer from acetylenic esters, terminal acetylenes, a divalent titanium alkoxide reagent (Ti(O-i-Pr)_4/2 i-PrMgCl (1)), and propargyl bromides. This reaction was applied to the first synthesis of alcyopterosin A and an efficient synthesis of an aromatic moiety of an anti-cancer agent, pradimicin. 2)α-Pyridyltitanium compounds were obtained as a single isomer from acetylenic amides, terminal acetylenes, the titanium reagent 1, and a sulfonylnitrile. This reaction was applied to the synthesis of an antiallergic substance, benzocycloheptapyridine. 3)Pyridinecarbaldehydes were obtained as a single isomer from acetylenic amides, terminal acetylenes, the titanium reagent 1, and nitriles. 4)α-Pyridyltitanium compounds were obtained as a single isomer from acetylenes, nitriles, the titanium reagent 1, and a sulfonylacetylene. Starting this reaction with optically active nitriles, we attained an efficient preparation of an optically active pyridine unit of cyclothiazomycin. 5)Aminopyridines were obtained as a single isomer from acetylenes, (sulfonylamino)acetylenes, the titanium reagent 1, and nitriles. 6)Pyrrolecarbaldehydes were obtained as a single isomer from unsymmetrical acetylenes, the titanium reagent 1, and two different nitriles.

这项研究开发了REPPE反应的新样式，该反应提供了单个芳族化合物，作为来自三种不同的，不对称的乙酰乙烯的滴定形式。或者，我们还用硝酸盐代替一个或两个乙炔，我们还开发了一种Aza-reppe反应，从而产生金属的吡啶或吡咯，作为单个异构体。此外，这些新反应制备了一些具有生物活性化合物或药物重要的化合物。 1）从乙酰基因酯，末端乙酰基烯，二价钛醛钛合剂（Ti（O-I-I-PR）_4/2 I-PrmGCl（1））和丙藻bromiess获得苯基坦原化合物作为单个异构体。该反应应用于Alcyopterosin a的第一个合成，并有效合成抗癌剂Pradimicin的芳族部分。 2）从乙酰基酰胺，末端乙酰烯，钛试剂1和磺酰硝基的单个异构体获得α-吡啶基坦烷化合物。该反应应用于抗抗细胞苯并糖蛋白酶的合成。 3）从乙酰基酰胺，末端乙酰烯，钛试剂1和硝酸盐中获得吡啶甲醛作为单个异构体。 4）α-吡啶基坦烷化合物是从乙炔，硝酸盐，钛试剂1和亚磺酰胺乙烯的单个异构体获得的。从光学活跃的硝酸酯开始此反应，我们获得了旋风的静脉霉素的光学活性吡啶单元的有效制备。 5）氨基吡啶作为来自乙酰基烯，（硫基氨基氨基）乙酰烯，钛试剂1和硝酸盐的单一异构体获得。 6）从不对称的乙炔，钛试剂1和两种不同的硝酸酯中获得吡foLOCARBALDEDYES作为单个异构体。

项目成果

H.Urabe, D.Suzuki, F.Sato: "Generation of an Acetylene-titanium Alkoxide Complex. Preparation of (Z)-1,2-Dideuterio-1-(trimethylsilyl)-1-hexene"Org.Synth.. 80. 120-128 (2003)

H.Urabe、D.Suzuki、F.Sato：“乙炔-钛醇盐络合物的生成。(Z)-1,2-Dideuterio-1-(三甲基甲硅烷基)-1-己烯的制备”Org.Synth.. 80

Preparation of Heterocyclic Compounds via Group 4(Ti or Zr) Metallacycles. Cyclization of, Acetylenes, Olefins, and Hetero-unsaturated Compounds

通过第 4 族（Ti 或 Zr）金属环制备杂环化合物。

• 发表时间: 2005
• 期刊: J.Synth.Org.Chem.Jpn. 63
• 作者: H.Urabe

Selective preparation of benzyltitanium compounds by the metalative Reppe reaction. Its application to the first synthesis of alcyopterosin A

• DOI: 10.1021/ja027008o
• 发表时间: 2002-08-21
• 期刊: JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
• 影响因子: 15
• 作者: Tanaka, R;Nakano, Y;Sato, F
• 通讯作者: Sato, F

4族(Ti,Zr)メタラサイクルを経るヘテロ環化合物の合成法-アセチレン、オレフィン、およびヘテロ不飽和化合物の環化反応

通过第 4 族 (Ti,Zr) 金属环合成杂环化合物 - 乙炔、烯烃和杂不饱和化合物的环化反应

• 发表时间: 2005
• 期刊: 有機合成化学協会誌 63
• 作者: A.Matsumoto;D.Furukawa;Y.Mori;T.Tanaka;K.Oka;占部弘和
• 通讯作者: 占部弘和

Practical preparation of N-(1-alkynyl)sulfonamides and their remote diastereoselective addition to aldehydes via titanation

• DOI: 10.1021/ol036396b
• 发表时间: 2004-03-04
• 期刊: ORGANIC LETTERS
• 影响因子: 5.2
• 作者: Hirano, S;Tanaka, R;Sato, F
• 通讯作者: Sato, F