Significant Effects of Nonconjugated Remote Substituents in Catalytic Asymmetric Epoxidation

Yang, Dan; Yip, Yiu-chung; Chen, Jian; Cheung, Kung‐Kai

doi:10.1021/ja980435a

Cited by 91 publications

(45 citation statements)

References 26 publications

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“…This relationship suggests that the relative rate of formation of each enantiomer is directly related to the electronic character of the catalyst, rather than any size change caused by substitution of a halogen for a hydrogen atom. While LFERs have been observed between enantiomeric ratio and catalyst electronic structure in other catalytic systems, [21][22][23][24][25] this is the first example of a direct electronic effect on enantioselectivity in a hydrogen-bondcatalyzed reaction. Of additional note, a plot correlating the initial rate of formation for each enantiomer was constructed.…”

Section: Methodsmentioning

confidence: 99%

Systematically Probing the Effect of Catalyst Acidity in a Hydrogen‐Bond‐Catalyzed Enantioselective Reaction

Jensen

Sigman

2007

Angewandte Chemie

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Hydrogen bonding is ubiquitous in nature and is a prevalent mode of substrate activation in enzymes. Recently, chemists have begun to exploit this mode of activation in asymmetric catalysis by designing synthetic catalysts that use hydrogen bonds. [1][2][3] These catalysts feature a variety of structural motifs and hydrogen-bond-donating functional groups. In light of the rapid development of new hydrogen-bond-catalyzed reactions, we felt that a greater understanding of the connection between catalyst activity and structure would aid the advancement of the field. While detailed mechanistic studies have been performed to clarify the role of hydrogen bonding in many enzymatic systems and on general acid catalysis, [4,5] few have been performed on synthetic asymmetric catalysts. [6] Herein, we present a systematic study on the effect of catalyst acidity in a hydrogen-bond-catalyzed reaction, wherein linear free energy relationships are observed between the catalyst acidity and both the reaction rate and enantioselectivity.We have developed a hydrogen-bond catalyst which has a unique design featuring an oxazoline core with a pendant amine and alcohol group. This design provides two sites with hydrogen-bond donating groups which can be independently tuned (Scheme 1).[7] Catalysts of this type have been shown to be effective in the asymmetric hetero-Diels-Alder reaction between Rawals diene (D) and benzaldehyde (A). [7][8][9][10][11] The modular nature of the catalyst makes it well suited for a mechanistic study, as catalyst derivatives can be rapidly synthesized and evaluated to probe the relationship between the catalyst structure and activity.We hypothesized that a more acidic catalyst would be a better hydrogen-bond donor and thus would lead to enhanced substrate activation, as has been previously demonstrated. [12][13][14] To investigate this connection, systematic changes to the acidity of the N-H proton were made by synthesizing halogenated acetamide derivatives of the catalyst (Scheme 1). These variations were selected because of the substantial pK a range that may be studied while avoiding significant structural changes [15,16] and because the catalyst derivatives can be synthesized from a common precursor.[17]Compounds 1-5 were then evaluated as catalysts in the hetero-Diels-Alder reaction. [8][9][10][11] The yields of the isolated products after a 48 h reaction time suggest a relationship between acidity and catalyst activity (Scheme 1).[18] To our surprise, a trend in enantioselectivity was also observed, with the highest enantiomeric excess measured for the most acidic catalyst.To better understand the observed trends corresponding to the electronic nature of the catalyst, kinetic measurements were performed to probe the general mechanistic features of the reaction. Using the optimal catalyst 1, the following rate dependencies were observed: first-order dependence on [1], saturation in [aldehyde] (Figure 1), and first-order dependence on [diene] at high [aldehyde].[17] Based on these findings, a mechanism ...

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Section: Methodsmentioning

confidence: 99%

Systematically Probing the Effect of Catalyst Acidity in a Hydrogen‐Bond‐Catalyzed Enantioselective Reaction

Jensen

Sigman

2007

Angewandte Chemie

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“…In the epoxidation of trans-stilbene, the series of small substituents (F, Cl, OH, OEt and H) give ees of 42-87%, exhibiting a very high correlation with the respective Hammett r values. These results have been rationalized on the basis of stabilization of the favored transition state (307) by field effects [367]. Some interesting immobilized dioxirane precursors have also been reported, such as the novel heterogeneous ketone 308 [368] and the fluoroketone 309, designed for use in fluorous media [369].…”

Section: Using Dioxiranesmentioning

confidence: 96%

Three‐Membered Heterocycles. Structure and Reactivity

Murphree

2011

Modern Heterocyclic Chemistry

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“…Wiskur 等 [15] 在研究手性四咪唑催化的硅化动力图 3 Pauson-Khand 反应中的底物取代基电子效应 [13] 图 4 烯丙基化反应中的非共轭取代基电子效应 [14] 学拆分的机理时, 同样发现了三芳基硅试剂的取代此外, 杨丹等 [16] 、Chan 等 [17~19] 、Garner 等 [20] 、 Mezzetti 等 [21] 、Brown 等 [22] 、Coates 等 [23] 在各自的反应体系研究中均使用过取代基常数与对映选择性的相关来研究反应机理, 在此不再一一列举.…”

Section: Hammett 参数unclassified

“…场效应来自于键的偶极性造成的局部电荷以及形式电荷对分子中远距离位置产生的电场影响, 1998 年, 杨丹等 [16] 系统研究了手性酮催化不对称环氧化反应中远端取代基的电子效应对反应选择性的影响 http://engine.scichina.com/doi/10.1360/N032015-00240 图 8 基于自由能相关的催化剂开发 [27] (图 9), 发现产物的对映选择性与催化剂远端取代基的场效应参数呈线性关系, 这说明催化剂中 C-X 键负电荷聚集端更接近底物并能稳定过渡态中底物部分形成的正电荷, 该研究为非共轭远端取代基电子效应的首例报道.…”

Section: 场效应参数unclassified

“…2013 年, Gilmour 等 [31] 以 MacMillan 催化剂为模型研究了有机小分子催化剂中非共价作用对反应选择性的影响, 发现催化剂芳香取代基四极距与反应图 9 环氧化反应中的取代基场效应-自由能相关 [16] 图 10 多聚环化反应中的取代基极化率-自由能相关 [29,30] ee 值或 es 值呈一定的线性关系, 并由此实现了对催化剂的改进. 然而由于其采用的是与 ee 值的直接相关, 严格来讲并不是线性自由能相关关系, 故在此不多讲述.…”

Section: 极化率及四极矩参数unclassified

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Linear free-energy relationships in asymmetric catalysis

Zhang¹,

Li²,

Luo³

et al. 2016

Sci. Sin.-Chim

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Chiral aldehyde catalysis: a highly promising concept in asymmetric catalysis SCIENCE CHINA Chemistry 62, 3 (2019); Quantum chemical study on asymmetric catalysis reduction of imine Science in China Series B-Chemistry 46, 124 (2003); Chiral covalent organic frameworks for asymmetric catalysis and chiral separation SCIENCE CHINA Chemistry 60, 1015 (2017); Chiral model complexes for methane monooxygenase and their asymmetric catalysis of styrene epoxidation

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Significant Effects of Nonconjugated Remote Substituents in Catalytic Asymmetric Epoxidation

Cited by 91 publications

References 26 publications

Systematically Probing the Effect of Catalyst Acidity in a Hydrogen‐Bond‐Catalyzed Enantioselective Reaction

Systematically Probing the Effect of Catalyst Acidity in a Hydrogen‐Bond‐Catalyzed Enantioselective Reaction

Three‐Membered Heterocycles. Structure and Reactivity

Linear free-energy relationships in asymmetric catalysis

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