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，当在0℃下将醛（2当量）添加到酮和NaH（1.1当量）在THF中的混合物中时，发生多米诺醇醛-Tishchenko反应，得到带有C(2)-取代基的1,3-二醇作为单一非对映异构体。应当指出的是，当在该温度下搅拌酮和NaH在THF中的混合物时，没有观察到氢气的放出，并且醛的滴加引发了氢气的放出，有趣的是，氢气的放出与醛的添加同步。羟醛-Tishchenko 产品被证明具有异常的抗羟醛和抗 Tishchenko 立体化学结果。此外，当醛（2当量）被两种不同的醛A（1当量）和B（1当量）取代时，空间要求较低，或者如果A和B的要求性质相似，则将更具反应性的醛纳入羟醛工艺中，剩余的醛用作Tishchenko工艺中的氢化物供体。此外，三甲基氯硅烷不会以任何方式影响反应。所有这些发现可能表明，涉及酮、两个醛和NaH的四种组分通过它们之间的弱相互作用组装在一起，并保持组装的微妙平衡：没有明显的烯醇中间体不能介入。受到这种化学的强烈启发，我们关注了其他传统碱，例如叔丁醇钾，并发现了从简单的酮生成的热力学控制的烯醇的隐藏方面。 在生成环己烷-1,3-二酮的多米诺迈克尔-克莱森反应中起重要作用。我们还发现炔烃在DMSO中用氢氧化铵碱处理可以产生相应的乙炔阴离子。该化学强烈激励人们关注炔烃作为双向扩链工具，并开发了几种使用炔丙基-烯丙基杂化阳离子的合成有机反应，该阳离子可以通过路易斯酸的作用由1-烯丙基炔丙基三甲基甲硅烷基醚制备。较少的

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*

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。

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, 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