Development of reactions based on addition of electrophiles to methylenebisphosphonates

基于向亚甲基二膦酸酯添加亲电子试剂的反应的发展

基本信息

批准号：
12672053
负责人：
NAGAOKA Yasuo
金额：
$ 1.86万
依托单位：
Kansai University (2001-2002)Kyoto University (2000)
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2000
资助国家：
日本
起止时间：
2000 至 2002
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12672053/
关键词：
alkenylphosphonate allene chiral phosphine ligand conjugate addition conjugate reduction vinyl anion Michael reaction ヒストン脱アセチル化酵素 HDAC ホスホナート環化反応

项目摘要

Allenes are recent focus of versatile class of intermediates in a variety of organic synthetic processes. We developed a novel method to synthesize allenes by successive Horner-Wadsworth-Emmons olefination starting from methylene-bisphosphonate and two carbonyl compounds. The key to success is KH or KH-18-crown-6 as a base for second HWE olefination of hydroxyalkenylphosphonates. Asymmetric allene synthesis based on this method is now in progress.As our continuing studies of efficient synthetic application of lithium phosphonates, we have developed cyclization reaction of bis-alkenylphosphonate 1. Although the reaction of 1 with organolithium reagents afforded both tandem Michael cyclization products and α-deprotonation-cyclization products, the latter was selectively formed in high yield by simply treating 1 with LDA. Application of chiral bis-alkenylphosphonate 2 opens a simple synthetic way to chiral phosphine ligand 5. Treatment of 2 with LDA followed by electrophilic trapping of intermediate cyclic lithium phosphonate 3 with benzaldehyde afforded aldol-type adduct 4 in 54%. The alcohol 4 was transformed to 5 by 6 steps in 16% yield.

艾伦（Allens）是各种有机合成过程中的中间体，由连续的horner-wadsworth-emmons烯烃从甲基 - 双膦键和两个羰基甲基磷酸化合物开始我们继续使用磷酸锂的效率施用1.尽管1与有组织岩的反应，后者通过简单地用LDA处理1的方法，以高收率形成了率。磷酸锂3 withalde hyde在54％中获得了预期的加合物4。

项目成果

期刊论文数量（40）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Masashi Ono, Katsumi Nishimura, Hiroshi Tsubouchi, Yasuo Nagaoka, Kiyoshi Tomioka: "Total Synthesis of (-)-Neplanocin A by Using Lithium Thiolate-Initiated Michael-Aldol Tandem Cyclization Reaction"J.Org.Chem.. 66(24). 8199-8203 (2001)

Masashi Ono、Katsumi Nishimura、Hiroshi Tsubouchi、Yasuo Nagaoka、Kiyoshi Tomioka：“利用硫醇锂引发的 Michael-Aldol 串联环化反应全合成 (-)-Neplanocin A”J.Org.Chem.. 66(24)。

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Hideki Inoue, Hiroshi Tsubouchi, Yasuo Nagaoka, Kiyoshi Tomioka: "Synthesis of Allenes by Double Horner-Wadsworth-Emmons Reaction"Tetrahedron. 58(1). 83-90 (2002)

Hideki Inoue、Hiroshi Tsubouchi、Yasuo Nagaoka、Kiyoshi Tomioka：“通过双霍纳-沃兹沃斯-埃蒙斯反应合成艾伦烯”四面体。

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Shinichi Uesato, Manabu Kitagawa, Yasuo Nagaoka, Taishi Maeda, Hiroshi Kuwajima, Takao Yamori: "Novel Histone Deacetylase Inhibitors : N-Hydroxy-carboxamids Possessing a Terminal Bicyclic Aryl Group"Bioorg.Med.Chem.Lett.. 12(10). 1347-1349 (2002)

Shinichi Uesato、Manabu Kitakawa、Yasuo Nagaoka、Taishi Maeda、Hiroshi Kuwajima、Takao Yamori：“新型组蛋白脱乙酰酶抑制剂：具有末端双环芳基的 N-羟基-羧酰胺”Bioorg.Med.Chem.Lett.. 12(10)。