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

发现在0 ℃下，将醛（2eq）加入到酮和NaH（1.1eq）的THF混合物中，发生多米诺羟醛-Tishchenko反应，得到一个单一的非对映异构体，即具有C（2）-取代基的1，3-二醇。应当注意，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，并且醛的滴加引发氢气的放出，这有趣地与醛的加入同步。aldol-Tishchenko产品被证明无一例外地具有抗aldol和抗Tishchenko立体化学结果。此外，当用两种不同的醛A（1当量）和B（1当量）代替醛（2当量）时，在空间上要求较低，或者如果A和B的要求性质相似，则将更具反应性的醛引入羟醛缩合法，剩余的醛用作Tishchenko法中的氢化物供体。三甲基氯硅烷对反应B没有影响 ...更多信息 无论如何。所有这些发现可能表明，包括酮、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，保持组装的微妙平衡：没有明显的烯醇化物中间体不能介入。受到这种化学的强烈启发，我们关注了其他传统碱，例如叔丁氧钾，并发现了热力学上隐藏的方面-由简单酮生成的可控烯醇化物在多米诺Michael-Claisen反应中起重要作用，导致环己烷-1，3-二酮。我们还发现，炔可以导致相应的乙炔阴离子处理氢氧化铵碱在DMSO中。这一化学反应强烈地促进了人们对炔作为双向扩链工具的关注，并发展了几种利用炔丙基-烯丙基杂化阳离子的有机合成反应，这些杂化阳离子可以由1-烯丙基炔丙基三甲基硅醚通过刘易斯酸的作用制备。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