Development of Highly Efficient Asymmetric Reactions Based on Construction of Functionalized Multinucleating Chiral Reaction Field

基于功能化多核手性反应场构建高效不对称反应的进展

• 批准号: 13640529
• 负责人: UKAJI Yutaka
• 金额: $ 2.62万
• 依托单位: Kanazawa University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13640529/
• 关键词: multinuclealing; tartaric acid ester; chiral; 1,3-dipolar cycloaddition reaction; nitrile oxide; nitrone; carbonylation; γ-lactam; キラル反応場; 複核化; イソオキサゾリジン; ニトロン; Reformatsky型試薬; β-アミノ酸誘導体

The development of a practical and efficient method for the construction of chiral molecules is essential to explore new medicines and agricultural chemicals. In order to develop more efficient chiral environment, incorporation of multi metal centers should be more effective, because the cooperative action of the metals can efficiently control the stereochemical course of the reactants to produce the corresponding optically active chemicals.A catalytic asymmetric 1,3-dipolar cycloaddition reaction of a nitrone possessing diisopropyl amide moiety to g-substituted allylic alcohols was achieved by using diisopropyl (R,R)-tartrate as a chiral auxiliary to afford the corresponding 3,4,5-trisubstituted isoxazolidines with excellent enantioselectivity up to over 99% ee.The asymmetric 1,3-dipolar cycloaddition of nitrile oxides, generated in situ from aldoximes by direct oxidation with t-butyl hypochlorite, to 2-propen-1-01 was achieved by utilizing diisopropyl (R,R)-tartrate as a chiral auxiliary to afford the corresponding R-2-isoxazolines with high enantioselectivity up to 96% ee.γ-Lactams can be synthesized from the reaction of N-tosyl homoallylamines catalyzed by palladium and copper salts under normal pressure of CO and O2 at rt. Monocarbonylation proceeded by the use of [PdCl_2(CH_3CN)_2] and CuCl to afford 3-methyl-2-pyrrolidinones, while the use of PdCl_2 and CuCl_2] chaneged the reaction course to the dicarbonylation to produce 3-(alkoxycarbonyl)methyl-2-pyrrolidinones in good yield, respectively. In the presence of chiral bioxazoline ligand, the optically active γ-lactams could be obtained.

开发一种实用、高效的手性分子构建方法对于开发新的药物和农药是必不可少的。为了开发更有效的手性环境，需要更有效地引入多金属中心，因为金属中心的协同作用可以有效地控制反应物的立体化学过程，生成相应的光学活性化合物.以二异丙基（R，R）-酒石酸酯作为手性助剂，合成了相应的3，4，5-三取代异恶唑烷，其对映选择性高达99%ee以上。利用二异丙基（R，R）-酒石酸酯为手性助剂，合成了相应的R-2-异恶唑啉，对映选择性高达96%ee。在常压、CO和O_2气氛下，用钯盐和铜盐催化合成了对甲苯磺酰基高烯丙基胺，并在[PdCl_2（CH_3CN）]存在下进行了单羰基化反应PdCl_2和CuCl_2]使反应转向双羰基化反应，分别以较高的收率得到3-（烷氧羰基）甲基-2-吡咯烷酮。在手性双恶唑啉配体的存在下，可以得到光学活性的γ-内酰胺。

项目成果

Y. Ukaji: "Development of New Asymmetric Reactions Utilizing Tartaric Acid Esters as Chiral Auxiliaries. The Design of an Efficient Chiral Multinucleating System"Synlett.. in press.

Y. Ukaji：“利用酒石酸酯作为手性助剂开发新的不对称反应。高效手性多核系统的设计”Synlett.. 已出版。

Y. Ukaji, S. Takenaka, Y. Horita, K. Inomata: "Asymmetric Addition of Reformatsky-Type Reagent to Imines Utilizing Diisopropyl Tartrate as a Chiral Auxiliary"Chem. Lett.. 2001(3). 254-255 (2001)

Y. Ukaji、S. Takenaka、Y. Horita、K. Inomata：“利用酒石酸二异丙酯作为手性助剂将 Reformatsky 型试剂不对称加成到亚胺中”Chem。

M. Tsuji: "Asymmetric 1,3-Dipolar Cycloaddition of Nitrite Oxides Generated in situ by Direct Oxidation of Aldoximes"Chem. Lett.. 1112-1113 (2002)

M. Tsuji：“通过醛肟直接氧化原位生成亚硝酸盐的不对称 1,3-偶极环加成”Chem。

X. Ding: "A Catalytic Asymmetric 1,3-Dipolar Cycloaddition of Nitrones to Allyl Alcohol"Chem. Lett.. 468-469 (2001)

X. Ding：“硝酮与烯丙醇的催化不对称1,3-偶极环加成”Chem.

Y. Ukaji: "Development of New Asymmetric Reactions Utilizing Tartaric Acid Esters"My Favorite Organic Synthesis. 238-239 (2002)

Y. Ukaji：“利用酒石酸酯开发新的不对称反应”我最喜欢的有机合成。