Origin of Regio and Stereoselectivity in Conjugate Addition Reactions

共轭加成反应中区域和立体选择性的起源

• 批准号: 07457520
• 负责人: TOMIOKA Kiyoshi
• 金额: $ 4.86万
• 依托单位: KYOTO UNIVERSITY (1996-1997)Osaka University (1995)
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 1995
• 资助国家: 日本
• 起止时间: 1995 至 1997
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07457520/
• 关键词: enantioselective reaction; conjugate addition; imine; lithium enolate; LUMO coefficients; ligand; catalytic reaction; beta-lactam; 有機銅; 錯体; ホスフィン; 立体選択性; 配座変換; 反応面; 求核付加反応; 不斉補助剤

We have reported the successful chiral ligand-mediated asymmetric 1,2- and 1,4-addition reactions of organolithiums to various imines of aryl and alpha, beta-unsaturated aldehydes Thus, organo-lithiums add to the cyclohexylimines 1,2 (R=c-C6Hll) in 1,4-fashion to give, after hydrolysis, the corresponding aldehydes in up to 99% ee and in high to good yields. On the other hand, the reactions with arylimines exclusively afford 1,2-adducts in up to 90% ee and in nearly quantitative yields, giving us a good method for the preparation of chiral amines. It is also interesting in that the reactions with both cyclohexyl- and arylimines of 1-fluoronaphthalene-2-carbaldehyde exclusively proceed in 1,4-fashion to provide nucleophilic aromatic substitution products in high yields. Since deep understanding of the factors governing regioselectivity is a long-standing problem and essential for further development of the much more effective catalytic asymmetric reactions of the ene-imines. we carried out molecular orbital calculations and revealed that the experimentally observed regioselectivity is rationalized by the relative magnitude of the LUMO coefficients.

我们已经报道了手性配体介导的有机锂与各种芳基和α， β -不饱和醛的不对称1,2和1,4加成反应的成功，因此，有机锂以1,4方式与环己基1,2 （R=c-C6Hll）加成，在水解后，相应的醛的ee高达99%，收率很高。另一方面，与芳基胺的反应只产生1,2-加合物，ee达90%，产率接近定量，为制备手性胺提供了一种很好的方法。同样有趣的是，与1-氟萘-2-乙醛的环己基和芳基的反应完全以1,4方式进行，以高收率提供亲核芳香取代产物。因为深入了解控制区域选择性的因素是一个长期存在的问题，并且对于进一步开发更有效的催化不对称反应至关重要。我们进行了分子轨道计算，并揭示了实验观察到的区域选择性是由LUMO系数的相对大小合理化的。

项目成果

Masashi Mizuno, Kunihiko Fujii, and Kiyoshi Tomioka: "The Asymmetric Horner-Wadsworth-Emmons Reaction Mediated by An External Chiral Ligand." Angew.Chem.Int.Ed.Engl. 37(4). 515-517 (1998)

Masashi Mizuno、Kunihiko Fujii 和 Kiyoshi Tomioka：“外部手性配体介导的不对称霍纳-沃兹沃斯-埃蒙斯反应”。

Katsumi Nishimura, Takashi Ono, Yasuo Nagaoka, and Kiyoshi Tomioka: "Steric Tuning of Reactivity and Enantioselectivity in Addition of Thiophenol to alpha, beta-Unsaturated Esters Mediated by a Chiral Ligand." J.Am.Chem.Soc.119(52). 12974-12975 (1997)

Katsumi Nishimura、Takashi Ono、Yasuo Nagaoka 和 Kiyoshi Tomioka：“在手性配体介导的 α、β-不饱和酯中添加苯硫酚，对反应性和对映选择性进行空间调节。”

A.Iida: "Trichothecinols A,B and C,Potent Anti‐Tumor Promoting Sesquiterpenoids from the Fungus Trichothecium roseum." Tetrahedroon Letters. 37・51. 9219‐9220 (1996)

A.Iida：“单端孢菌素 A、B 和 C，来自真菌单端孢菌的倍半萜类化合物的有效抗肿瘤作用”，《四面体快报》9219-9220。

N.Nishimura: "Steric Tuning of Reactivity and Enantioselectivity in Addition of Thiophenol to α.β-Unsaturated Esters Mediated by a Chiral Ligand" J.Am.Chem.Soc.119・52. 12974-12975 (1997)

N. Nishimura：“手性配体介导的苯硫酚与 α.β-不饱和酯的反应性和对映选择性的空间调节”J.Am.Chem.Soc.119·52 (1997)。

Kiyoshi Tomioka: "Diastereoselective Thiophenol Addition to (S)-N-α,β-Unsaturated Carbonyl-γ-trityloxymethyl-γ-butyrolactams" J.Org.Chem.60(19). 6188-6190 (1995)

Kiyoshi Tomioka：“非对映选择性苯硫酚加成到 (S)-N-α,β-不饱和羰基-γ-三苯甲氧基甲基-γ-丁内酰胺”J.Org.Chem.60(19) (1995)。