エナミド指向戦略による非活性化アルケーンによる分岐選択型分子間ケトンα-アルキレーション
1Department of Chemistry, University of Chicago , Chicago, Illinois 60637, United States.
Journal of the American Chemical Society
|September 19, 2017
まとめ
研究者はアルケンを用いたケトンアルキル化の新しい方法を開発した. この戦略は,高分岐選択性を達成し,有機合成に新しいアプローチを提供します.
科学分野:
- 有機化学
- カタリシス
- 合成方法論
背景:
- ケトンアルファアルキレーションは有機合成における基本的な変換である.
- 分子間アルキル化において,高い選択性,特に分岐選択性を達成することは,依然として課題である.
- 特定のポジションでの反応性と選択性を制御するために,グループの戦略を指示することは極めて重要です.
研究 の 目的:
- ケトンの分岐選択型分子間アルファアルキル化のための新しい戦略を開発する.
- ケトン機能化のためのアルキル化剤として単純なアルケンを利用する.
- 望ましい枝分かれした製品に対して高い地域選択性を提供する触媒システムを確立する.
主な方法:
- イソインドリン-1-オンから派生したエナミドを指示テンプレートとして使用する.
- アルキル化反応にカチオンイリジウム触媒を使用する.
- 様々なアリファティックおよびアロマティックアルケンの反応範囲を調査する.
主要な成果:
- ケトンの分子間分岐選択アルファアルキル化に成功した.
- 単純なアルケンをアルキル化剤として使用して高分岐選択性を達成した.
- イソインドリン-1-オン系エナミドの有効性を示した.
- この変換に非常に効率的なカチオンイリジウム触媒を特定した.
結論:
- 説明された戦略は,枝分かれ選択的なケトンアルキル化のための効果的な経路を提供します.
- エナミドとイリジウムの触媒は 複雑な分子を作るための強力なツールです
- 初期メカニズムの調査は,IR-C移動の挿入経路が有効であることを示唆しています.
関連する概念動画
01:10α-Alkylation of Ketones via Enolate Ions
4.0K
Ketones with α protons are deprotonated by strong bases like lithium diisopropylamide (LDA) to form enolate ions. The anion is stabilized by resonance, and its hybrid structure exhibits negative charges on the carbonyl oxygen and the α carbon. This ambident nucleophile can attack an electrophile via two possible sites: the carbonyl oxygen, known as O-attack, or the α carbon, known as C-attack. The nucleophilic attack via the carbanionic site is preferred. This is due to the...
4.0K
01:10Factors Affecting α-Alkylation of Ketones: Choice of Base
3.6K
α-Alkylation of ketones is achieved in the presence of alkyl halides and a base. The reaction proceeds via the formation of an enolate ion followed by nucleophilic substitution. The choice of base employed is essential as it is the key factor in determining the reaction outcome.
The reaction involving bases like EtO− whose conjugate acid EtOH (pKa = 15.9) is stronger than the ketone (pKa = 19.2) results in an equilibrium mixture with higher ketone concentration. As a consequence,...
The reaction involving bases like EtO− whose conjugate acid EtOH (pKa = 15.9) is stronger than the ketone (pKa = 19.2) results in an equilibrium mixture with higher ketone concentration. As a consequence,...
3.6K
01:07Alkylation of β-Ketoester Enolates: Acetoacetic Ester Synthesis
4.7K
Acetoacetic ester synthesis is a method to obtain ketones from alkyl halides and β-keto esters. The reaction occurs in the presence of an alkoxide base that abstracts the acidic proton of the β-keto esters. The step results in an enolate ion which is doubly stabilized. The enolate then reacts with an alkyl halide via the SN2 process to produce an alkylated ester intermediate with a new C–C bond. The hydrolysis of the intermediate, followed by acidification, results in an...
4.7K
01:26Synthesis of α-Substituted Carbonyl Compounds: The Stork Enamine Reaction
4.2K
α-Substituted ketones or aldehydes can be synthesized from enamines by the Stork enamine reaction, named after its pioneer Gilbert Stork. Enamines are useful synthetic intermediates where the lone pair on nitrogen is in conjugation with the C=C bond. They resemble enolate ions, as the resonance forms of both species have a nucleophilic α carbon.
4.2K
01:27Aldol Condensation with β-Diesters: Knoevenagel Condensation
3.9K
The Knoevenagel condensation is an aldol-type reaction involving the condensation of aldehydes or ketones with active methylene compounds such as β-diesters to produce substituted olefins.
3.9K
01:21Acid-Catalyzed α-Halogenation of Aldehydes and Ketones
5.0K
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...
5.0K