Novel Domino Cross-aldol/Tishchenko Reaction Promoted by NaH

NaH 促进的新型多米诺交叉羟醛/Tishchenko 反应

• 批准号: 13450373
• 负责人: SAITO Seiki
• 金额: $ 9.47万
• 依托单位: Okayama University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-13450373/
• 关键词: cross aldol-Tishchenko reaction; three-contiguous stereocenters; sodium hydride base; ammonium hydroxide base; acetylide addition; cyclohexene-1,3-diones; propargyl-allyl hybrid cation; 連続二重マイケル・クライゼン反応; 4,4-ジ置換シクロヘキサン-1,3-ジオン; 6,6-ジ置換-3-メトキシ-2-シ

We have found that when an aldehyde (2 eq) was added to a mixture of a ketone and NaH (1.1 eq) in THF at 0℃, domino aldol-Tishchenko reaction took place to afford a 1,3-diol with C(2)-substituent as a single diastereoisomer. It should be noted that no evolution of hydrogen gas was observed when the mixture of the ketone and NaH in THF was stirred at that temperature, and the dropwise addition of the aldehyde triggered the evolution of hydrogen gas which interestingly synchronized to the addition of aldehyde. The aldol-Tishchenko product was proven to have unexceptionally anti-aldol and anti-Tishchenko stereochemical outcome. Furthermore, when the aldehyde (2 eq) was replaced with two different aldehydes A (1 eq) and B (1 eq), Sterically less demanding or, if demanding nature of A and B was similar, more reactive one was incorporated into the aldol process, remaining aldehyde being used as a hydride donor in the Tishchenko process. Also chlorotrimethylsilane didn't affect the reaction b … More y any means. All these findings might indicate that the four component involving the ketone, two of aldehydes, and NaH assemble together through weak interaction among them by keeping delicate balance of the assembly : no distinct enolate intermediate could not intervened.Being strongly inspired by such chemistry, we paid attention to other traditional bases such as potassium tert-butoxide and found hidden aspects of thermodynamically-controlled enolate generated from simple ketone which plays an important role in domino Michael-Claisen reaction leading to cyclohexane-1,3-dione. We have also found that alkynes can lead to the corresponding acetylide anions on treatment with ammonium hydroxide base in DMSO. This chemistry gave strong incentive to be concerned with alkynes as two directional chain extension tool, and developed several synthetic organic reactions using propargyl-allyl hybrid cation which can be prepared from 1-allylpropargyl ssitrimethylsilyl ether by the action of Lewis acid. Less

我们发现，当一个醛（2当量）加入到酮和萘（1.1当量）的混合物中，在0℃的THF中，发生了domino aldoll - tishchenko反应，生成了一个具有C(2)取代基的1,3-二醇作为单一的非对映异构体。需要注意的是，在该温度下搅拌四氢呋喃中酮和钠的混合物时，没有观察到氢气的析出，而乙醛的逐渐加入引发了氢气的析出，有趣的是，氢气的析出与乙醛的加入同步。aldol-Tishchenko产品被证明具有抗aldol和抗tishchenko立体化学效果。此外，当醛（2 eq）被两种不同的醛A （1 eq）和B （1 eq）取代时，空间要求较低，或者如果A和B的要求性质相似，则将更活泼的醛加入醛醇过程，剩余的醛在Tishchenko过程中用作氢化物供体。氯三甲基硅烷对反应没有影响。所有这些发现可能表明，酮类、两种醛类和钠等四种成分通过弱相互作用组装在一起，保持了组装的微妙平衡，没有不同的烯醇酸中间体不能干预。受到这种化学反应的强烈启发，我们关注了叔丁酸钾等其他传统碱，并发现了由简单酮生成的热力学控制烯醇酯的隐藏方面，它在多米诺michael - clisen反应中起重要作用，从而得到环己烷-1,3-二酮。我们还发现，在DMSO中，氢氧化铵碱处理后，炔烃可以生成相应的乙酰基阴离子。这一化学反应强烈地激发了人们对炔烃作为双向延伸链工具的关注，并发展了几种以1-烯丙基丙炔基三甲基硅基醚为原料，在路易斯酸作用下制备丙炔烯基杂化阳离子的合成有机反应。少

项目成果

Lewis acid-catalyzed nucleophilic substitutions of propargylic and allylic silyl ethers with enol silyl ethers.

• DOI: 10.1021/ol0271537
• 发表时间: 2003-01
• 期刊: Organic letters
• 影响因子: 5.2
• 作者: T. Ishikawa*;T. Aikawa;Yumiko Mori;S. Saito*

Diastereoselective Allylationa of Allyl-Propargyl Hybrid Cations : Synthesis of Conjugated 1,5-Dien-7-yne Frameworks Bearing C(4)-Stereogenic Centers

烯丙基-炔丙基杂化阳离子的非对映选择性烯丙基化: 带有 C(4)-立体中心的共轭 1,5-Dien-7-yne 框架的合成

• 发表时间: 2004
• 期刊: Organic Letters 6
• 作者: Teruhiko Ishikawa;Toshiaki Aikawa;Yumiko Mori;Seiki Saito
• 通讯作者: Seiki Saito

T.Ishikawa, T.Mizuta, K.Hagiwara, T.Aikawa, T.Kudoh, S.Saito (T.Ishikawa): "Catalytic Alkynylation of Ketones and Aldehydes Using Quaternary Ammonium Hydroxide Base"The Journal of Organic Chemistry. 67(in press). (2003)

T.Ishikawa、T.Mizuta、K.Hagiwara、T.Aikawa、T.Kudoh、S.Saito (T.Ishikawa)：“使用季铵氢氧化物催化酮和醛的炔基化”有机化学杂志。

T.Ishikawa, R.Kadaya, M.Arai, H.Takahashi, Y.Kaisi, T.Mizuta, K.Yoshikai, S.Saito (T.Ishikawa): "Revisiting the Michael-Claisen [3+3] Route to 1, 3-Cyclohexanedione Frameworks : Hidden Aspects of Thermodynamically Controlled Enolates"The Journal of Organi

T.Ishikawa、R.Kadaya、M.Arai、H.Takahashi、Y.Kaisi、T.Mizuta、K.Yoshikai、S.Saito (T.Ishikawa)：“重访 Michael-Claisen [3 3] 通往 1 的路线

Novel carbon-carbon bond-forming reactions using carbocations produced from substituted propargyl silyl ethers by the action of TMSOTf

• DOI: 10.1021/jo010157p
• 发表时间: 2001-06-29
• 期刊: JOURNAL OF ORGANIC CHEMISTRY
• 影响因子: 3.6
• 作者: Ishikawa, T;Okano, M;Saito, S
• 通讯作者: Saito, S