DEVELOPMENT AND SYNTHETIC APPLICATION FOR STEREOSELECTIVE MICHAEL/ALDOL TANDEM REACTION TRIGGERED BY THIOLATE ANION

硫醇阴离子引发的立体选择性迈克尔/醛醇串联反应的开发及合成应用

• 批准号: 11640536
• 负责人: KAMIMURA Akio
• 金额: $ 2.62万
• 依托单位: YAMAGUCHI UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11640536/
• 关键词: Michael addition; aldol reaction; tandem reaction; stereoselecivity; radical cyclization; radical elimination; β-lactams; regioselectivity; ホフマン脱離; テトラヒドロフラン; 反応機構; NMR; 立体選択的反応; α,β-不飽和アミド; チオラート; セレノラート; Baylis-Hillman反応

The titled reaction, the Michael/aldol tandem reaction, was investigated and found the following developments.1) We found this reaction can be applied to not only unsaturated esters but also unsaturated amides. Use of the procedure makes it easy to prepare amide-Baylis-Hillman adducts, which was difficult to synthesize under classical Baylis-Hillman reaction conditions. It should be mentioned that our reaction condition requires no special protection for the acidic amide NH proton for the progress of aldol reaction.2) Use of magnesium ion as a counter cation of thiolate opens the new aspect of the reaction that shows opposite diastereoselectivity for the aldol reaction. Under these conditions, anti-aldols, the preparation of which are recognized to be limited. We have also attempted to catch the reaction intermediate to understand the reaction mechanism, and found that a-thioalkoxide is the intermediate of the reaction.3) We have developed a new ready method to prepare multi-substituted tetrahydrofurans through the present method.4) Regiochemistry of radical elimination reaction was investigated. The regioselective transformation of the tandem adducts to α, β-unsaturated or β, γ-unsaturated ester was accomplished. This result is the first example of the regiocontrol in the radical elimination reaction.5) We have accomplished the first regiocontrol of the tandem or the Michael reaction of thiol to unsymmetrically substituted fumaric ester.

对Michael/Aldol串联反应进行了研究，发现了以下几个新的进展：1）发现该反应不仅适用于不饱和酯，而且适用于不饱和酰胺。使用该方法可以容易地制备酰胺-Baylis-Hillman加合物，这在经典的Baylis-Hillman反应条件下难以合成。2）使用镁离子作为硫醇盐的抗衡阳离子为反应开辟了一个新的方面，即对羟醛缩合反应表现出相反的非对映选择性。在这些条件下，抗醛醇的制备被认为是有限的。我们还尝试捕捉反应中间体来理解反应机理，发现α-硫代醇盐是反应的中间体; 3）通过本方法发展了一种制备多取代四氢呋喃的简便方法; 4）研究了自由基消除反应的区域化学。实现了串联加合物向α，β-不饱和酯或β，γ-不饱和酯的区域选择性转化。这一结果是在自由基消除反应中区域控制的第一个例子。5）我们完成了硫醇到不对称取代的富马酸酯的串联或Michael反应的第一个区域控制。

项目成果

Akio Kamimura: "Regioselective Conjugate Addition of Thiols to Unsymmetric Fumaric Esters in the Presence of Lithium Cation"Tetrahedron Lett.. 42・48. 8497-8500 (2001)

Akio Kamimura：“在锂阳离子存在下，硫醇与不对称富马酸酯的区域选择性共轭加成”Tetrahedron Lett.. 8497-8500 (2001)

Hiromasa Mitsudera: "anti-Aldol Selective Tandem Michael/Aldol Reaction with Magnesium Selenolate and Stereoselective Preparation of Tetrasubstituted Tetrahydrofuran"Tetrahedron Lett. Vol.40. 7389-7392 (1999)

光寺宏正：“硒酸镁的抗羟醛选择性串联迈克尔/羟醛反应和四取代四氢呋喃的立体选择性制备”四面体莱特。

Hiromasa Mitsudera: "anti-Aldol Selective Tandem Michael/Aldol Reaction with Magnesium Selenolate and Stereoselective Preparation of Tetrasubstituted Tetrahydrofuran"Tetrahedron Lett.. 40・41. 7389-7392 (1999)

光寺宏正：“硒酸镁的抗羟醛选择性串联迈克尔/羟醛反应和四取代四氢呋喃的立体选择性制备”Tetrahedron Lett.. 7389-7392 (1999)

Akio Kamimura: "Stereoselective construction of multi-substituted tetrahydrofurans via three components-condensation reaction"Tetrahedron. 58. 2605-2611 (2002)

Akio Kamimura：“通过三组分缩合反应立体选择性构建多取代四氢呋喃”四面体。

Akio Kamimura: "Regioselective Conjugate Addition of Thiols to Unsymmetric Fumaric Esters in the Presence of Lithium Cation"Tetrahedron Lett. Vol.42. 8497-8500 (2001)

Akio Kamimura：“在锂阳离子存在下，硫醇与不对称富马酸酯的区域选择性共轭加成”四面体快报。