誘導C−H結合活性化による芳香イミンの高効率でエナチオセレクティブなサイクリング
Reema K Thalji1, Jonathan A Ellman, Robert G Bergman
1Center for New Directions in Organic Synthesis, Department of Chemistry, University of California-Berkeley, Berkeley, California 94720, USA.
Journal of the American Chemical Society
|June 10, 2004
まとめ
この研究は,芳香C−H結合活性化のための最初の高度なエナチオセレクティブの触媒反応を導入します. この画期的な発見により,より穏やかな条件下で,アロマティックケチミンの効率的かつ選択的なサイクリングが可能になりました.
科学分野:
- 有機化学 オーガニック・ケミストリー
- カタリシス カタリシス カタリシス
- アシンメトリック・シンセシス
背景:
- 芳香C-H結合の活性化は,有機合成における重要な変換である.
- C-H活性化のためのエナチオセレクティブ・メソッドの開発は,依然として大きな課題です.
- 以前の分子内アルキル化の方法は,より高い温度を必要としていました.
研究 の 目的:
- アロマティックC-H結合の活性化を含む最初の高度なエナンチオセレクティブの触媒反応を報告する.
- メタテザードアロマティックケチミンのエナチオセレクティブサイクリングのための効率的な触媒システムを開発する.
- 既存のアキラルシステムと比較して,より穏やかな反応条件を達成するために.
主な方法:
- ロージウム触媒,特に5モル% [RhCl(coe) ]2.2を使用しました.
- エナチオ選択性のために (S) - ビノール由来のフォスフォラミドイトリガンドの15モル%を使用した.
- アロマティックケチミンのアルケニル基によるエナンチオセレクティブサイクリングを研究した.
主要な成果:
- 高いエナチオセレクティビティを達成し,最大96%のEEを達成しました.
- サイクライゼーション反応の定量的収量まで得られる.
- アキラルシステムと比較して反応温度 (最大75°C低) が著しく低下したことを実証した.
結論:
- 開発された触媒システムは,エナチオセレクティブのアロマティックC-H活性化における重要な進歩を表しています.
- 反応は穏やかな条件下で効率的に進行し,特定の基板では室温でも進行します.
- この方法論は,複雑な有機分子の非対称合成のための強力なツールを提供します.
関連する概念動画
Acid-Catalyzed α-Halogenation of Aldehydes and Ketones
By replacing an α-hydrogen with a halogen, acid-catalyzed α-halogenation of aldehydes or ketones yields a monohalogenated product
In the first step of the mechanism, the acid protonates the carbonyl oxygen resulting in a resonance-stabilized cation, which subsequently loses an α-hydrogen to form an enol tautomer. The C=C bond in an enol is highly nucleophilic because of the electron-donating nature of the –OH group. Consequently, the double bond attacks an electrophilic halogen to form a...
In the first step of the mechanism, the acid protonates the carbonyl oxygen resulting in a resonance-stabilized cation, which subsequently loses an α-hydrogen to form an enol tautomer. The C=C bond in an enol is highly nucleophilic because of the electron-donating nature of the –OH group. Consequently, the double bond attacks an electrophilic halogen to form a...
Photochemical Electrocyclic Reactions: Stereochemistry
The absorption of UV–visible light by conjugated systems causes the promotion of an electron from the ground state to the excited state. Consequently, photochemical electrocyclic reactions proceed via the excited-state HOMO rather than the ground-state HOMO. Since the ground- and excited-state HOMOs have different symmetries, the stereochemical outcome of electrocyclic reactions depends on the mode of activation; i.e., thermal or photochemical.
Selection Rules: Photochemical Activation
Selection Rules: Photochemical Activation
ortho–para-Directing Activators: –CH3, –OH, –⁠NH2, –OCH3
All ortho–para directors, excluding halogens, are activating groups. These groups donate electrons to the ring, making the ring carbons electron-rich. Consequently, the reactivity of the aromatic ring towards electrophilic substitution increases. For instance, the nitration of anisole is about 10,000 times faster than the nitration of benzene. The electron-donating effect of the methoxy group in anisole activates the ortho and para positions on the ring and stabilizes the corresponding...
ortho–para-Directing Deactivators: Halogens
Halogens are ortho–para directors. They are more electronegative than carbon. Therefore, as ring substituents, they can withdraw electrons through the inductive effect and deactivate the aromatic ring towards electrophilic substitution. Halogens also have an electron-donating resonance effect on the ring, which influences the orientation of the incoming electrophile. If an electrophile attacks at the ortho or the para position, the halogen donates electrons and stabilizes the intermediate...
meta-Directing Deactivators: –NO2, –CN, –CHO, –⁠CO2R, –COR, –CO2H
All meta-directing substituents are deactivating groups. These substituents withdraw electrons from the aromatic ring, making the ring less reactive toward electrophilic substitution. For example, the nitration of nitrobenzene is 100,000 times slower than that of benzene because of the deactivating effect of the nitro group. The first step in an electrophilic aromatic substitution is the addition of an electrophile to form a resonance-stabilized carbocation. The energy diagrams for the...
Double Resonance Techniques: Overview
Double resonance techniques in Nuclear Magnetic Resonance (NMR) spectroscopy involve the simultaneous application of two different frequencies or radiofrequency pulses to manipulate and observe two distinct nuclear spins. One important application of double resonance is spin decoupling, which selectively suppresses coupling with one type of nucleus while observing the NMR signal from another nucleus, simplifying the spectrum and enhancing resolution.
Spin decoupling is usually achieved by...
Spin decoupling is usually achieved by...


