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.

这项研究开发了新型的 Reppe 反应，它可以从三种不同的不对称乙炔中得到钛化形式的单一芳香族化合物。另外，我们还开发了一种氮杂-Reppe 反应，用腈代替上述一种或两种乙炔。此外，通过这些新反应制备了一些生物活性化合物或医学上重要的化合物。 1)由乙炔酯、末端乙炔、二价钛醇盐试剂(Ti(O-i-Pr)_4/2 i-PrMgCl (1))和炔丙基溴得到单一异构体形式的苄基钛化合物。首次合成alcyopterosin A，并有效合成抗癌剂的芳香族部分， 2) α-吡啶基钛化合物是由乙炔酰胺、末端乙炔、钛试剂 1 和磺酰腈得到的，该反应被应用于抗过敏物质苯并环庚吡啶的合成。乙炔酰胺的单一异构体，末端乙炔、钛试剂 1 和腈 4)α-吡啶基钛化合物是从乙炔、腈、钛试剂 1 和磺酰乙炔开始反应而得到的，我们成功地制备了 。环噻唑霉素的光学活性吡啶单元 5) 氨基吡啶。 6)由不对称乙炔、(磺酰氨基)乙炔、钛试剂1和两种不同的腈得到单一异构体形式的吡咯甲醛。

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