Tandem Inter-/intramolecular Coupling Mediated by a Ti(II) Reagent : One-step Multibond-forming Reactions

Ti(II) 试剂介导的串联分子间/分子内偶联：一步多键形成反应

• 批准号: 14550819
• 负责人: OKAMOTO Sentaro
• 金额: $ 2.24万
• 依托单位: Kanagawa University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-14550819/
• 关键词: low valent; titanium; tandem reactions; cyclization; bicyclic compounds; alkaroids; steroids; vitamin D_3; アルカロイド

We have developed efficient inter-and intramolecular cyclization reactions of unsaturated compounds mediated by a divalent titanium reagent. Based on these reactions, in this project we developed Ti(II)-mediated tandem or domino inter-and intramolecular coupling reactions of unsaturated compounds which enable multiple bond-forming in one-pot.Thus, 1,4-diynes reacted with the Ti(II)-reagent and allylic compounds to provide allyltitanated intermediate and this was further reacted with one more equivalent of the Ti(II)-reagentin situto provide cyclic bistitanated organic molecule in good yield, which was reacted with a various kind of electrophiles such as H+, D+, I+ and aldehydes to afford the corresponding hydrolysis, deuteriolysis, iodolysis and carbonyl addition compounds. The reactions involved maximum five-bond forming in a single vessel.Extensively, the method was applied to intra-/intramolecular domino reactions such as bicyclization of functionalized 2,7-enynes to bicyclo[3.3.0]-, [4.3.0]-carbo-and heterocyclic compounds.Considering efficiency, economical advantage and/or high stereoselectivity of the reactions developed here and also non-toxity and inexpensiveness of the Ti(II)-reagent, we believe that the methods might be useful as a powerful tool in organic synthesis.

我们已经开发了有效的二价钛试剂介导的不饱和化合物的分子间和分子内环化反应。基于这些反应，在本项目中，我们开发了Ti（II）介导的串联或多米诺不饱和化合物的分子间和分子内偶联反应，其能够在一锅中形成多个键。4-二炔与Ti（II）-试剂和烯丙基化合物反应以提供烯丙基钛酸酯化的中间体，并且将其进一步与再一当量的Ti（II）-二炔反应。反应物原位生成环状双钛酸酯有机分子，与各种亲电试剂如H+、D+、I+和醛反应，得到相应的水解、氘解、碘解和羰基加成化合物。该方法可用于2，7-烯炔化合物的分子内/分子内多米诺反应，如双环[3.3.0]-、[4.3.0]-碳环和杂环化合物的合成，考虑到反应的效率、经济性和高立体选择性，以及Ti（II）试剂的无毒和廉价，我们相信，这些方法可能是有用的，作为一个强有力的工具，在有机合成。

项目成果

Kohki Fukuhara, Sentaro Okamoto, Fumie Sato: "Asymmetric Synthesis of Allyl-and α-Allenylamines from Chiral Imines and Alkynes via (η^2-Imine)Ti(O-i-Pr)_2 Complexes"Organic Letters. 5. 2145-2149 (2003)

Kohki Fukuhara、Sentaro Okamoto、Fumie Sato：“通过 (η^2-Imine)Ti(O-i-Pr)_2 配合物从手性亚胺和炔烃不对称合成烯丙基和 α-烯胺”有机快报 5。2145-2149（ 2003）

Yongcheng Song, Sentaro Okamoto, Fumie Sato: "An efficient synthesis of optically active (2R,3R)-2-methyl-3-[(1R)-1 -methylprop-2-enyl]cyclopentanone, a useful chiral building block for synthesis of vitamin D and steroids"Tetrahedron Letters. 44. 2113-211

Yong Cheng Song、Sentaro Okamoto、Fumie Sato：“光学活性 (2R,3R)-2-甲基-3-[(1R)-1-甲基丙-2-烯基]环戊酮的有效合成，这是一种有用的手性合成结构单元

Subburaj Kandasamy, Sentaro Okamoto, Fumie Sato: "Development of New Chiral Building Blocks for Synthesis of Bicyclo[3.3.0]octane Compounds"J.Org.Chem.. 67. 1024-1026 (2002)

Subburaj Kandasamy、Sentaro Okamoto、Fumie Sato：“用于合成双环[3.3.0]辛烷化合物的新型手性结构单元的开发”J.Org.Chem.. 67. 1024-1026 (2002)

Yongcheng Song, Sentaro Okamoto, Fumie Sato: "An efficient synthesis of optically active (2 R,3R)-2-methyl-3-[(1 R)]-1-methylprop-2-enyl]cyclopentanone, a useful chiral building block for synthesis of vitamin D and steroids"Tetrahedron Letters. Vol.44. 21

Yong Cheng Song、Sentaro Okamoto、Fumie Sato：“光学活性 (2 R,3R)-2-甲基-3-[(1 R)]-1-甲基丙-2-烯基]环戊酮的有效合成，这是一种有用的手性结构

Takeshi Hanazawa, Akiko Koyama, Kunio Nakata, Sentaro Okamoto: "New Convergent Synthesis of 1α,25-Dihydroxyvitamin D_3 and Its Analogues by Suzuki-Miyaura Coupling between A-ring and C, D-ring Parts"J.Org.Chem.. 68. 9767-9772 (2003)

Takeshi Hanazawa、Akiko Koyama、Kunio Nakata、Sentaro Okamoto：“通过 A 环和 C、D 环部分之间的 Suzuki-Miyaura 偶联，新合成 1α,25-二羟基维生素 D_3 及其类似物”J.Org.Chem.. 68.9767-9772 (2003)