アルファ,β-非置換β-アミノ酸のエナンチオセレクティブ合成
Mukund P Sibi1, Prabagaran Narayanasamy, Sandeep G Ghorpade
1Department of Chemistry, North Dakota State University, Fargo, North Dakota 58105, USA.
Journal of the American Chemical Society
|September 25, 2003
まとめ
この研究は,マグネシウム触媒を用いたイミドからキラルイソキシゾリジノンを合成するための新しい方法を導入しています. その結果生成する化合物は,価値あるベータアミノ酸に変換できます.
科学分野:
- 有機化学 オーガニック・ケミストリー
- アシンメトリック・シンセシス
- カタリシス カタリシス カタリシス
背景:
- チラルベータアミノ酸は,医薬品における重要な構成要素である.
- それらの合成のための効率的な方法の開発は極めて重要です.
研究 の 目的:
- アルファ,ベータ-トランス-変位されたN-ベンジリソキサゾリジノンを合成するための高度にダイアステロセレクティブおよびエナチオセレクティブの方法を開発する.
- これらのイソクサゾリジノンの直接変換を貴重なベータアミノ酸に探索する.
主な方法:
- Mg(NTf2) 2とリガンド18によって触媒化されたイミドにN-ベンジルヒドロキシラミンを添加する.
- 結果となるイソキサゾリジノンの水素分解.
主要な成果:
- 高いダイアステロ選択性 (93-99% de) とエナチオ選択性 (60-96% ee) を達成した.
- アルファ,β-トランス-非置換されたN-ベンジリソキサゾリジノンを成功して合成しました.
- アルファ,β-非置換β-アミノ酸への直接変換が実証されています.
結論:
- 開発された触媒システムは,キラル型イソクサゾリジノーンへの効率的な経路を提供します.
- この方法は,価値あるキラルベータアミノ酸誘導体への直接的な経路を提供します.
関連する概念動画
Reactions of Aldehydes and Ketones: Baeyer–Villiger Oxidation
Baeyer–Villiger oxidation converts aldehydes to carboxylic acids and ketones to esters. The reaction uses peroxy acids or peracids and is often catalyzed by acid. The reaction is named after its pioneers, Adolf von Baeyer and Victor Villiger. The reaction is achieved by a wide range of peracids such as m-chloroperoxybenzoic acid (mCPBA), perbenzoic acid (C6H5COOOH), peracetic acid (CH3COOOH), hydrogen peroxide (H2O2), and tert-butyl hydroperoxide (t-BuOOH).
The carbonyl center is activated by...
The carbonyl center is activated by...
Regioselective Formation of Enolates
As depicted in the figure below, the unsymmetrical ketones can form two possible enolates: less substituted or more substituted enolates. Usually, the thermodynamic enolates are formed from the more substituted α-carbon atom, while the kinetic enolates are formed faster by deprotonation from the less substituted position. The thermodynamic enolates have lower energy, so they are more stable. But the energy required to form kinetic enolates is less.
Conjugate Addition to α,β-Unsaturated Carbonyl Compounds
α,β-Unsaturated carbonyl compounds are molecules bearing a carbonyl and alkene functionality in conjugation with each other. The conjugation in the molecule leads to three resonance structures. The hybrid form exhibits two probable electrophilic sites: the carbonyl carbon and the β carbon.
Factors Affecting α-Alkylation of Ketones: Choice of Base
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, side reactions...
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, side reactions...
Alkylation of β-Ketoester Enolates: Acetoacetic Ester Synthesis
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 alkylated β-keto acid.
Alkylation of β-Diester Enolates: Malonic Ester Synthesis
Malonic ester synthesis is a method to obtain α substituted carboxylic acids from ꞵ-diesters such as diethyl malonate and alkyl halides.


