アルキル亜鉛ハライドとアルファ-クロロケトンとの触媒的交互結合
Chrysa F Malosh1, Joseph M Ready
1Department of Biochemistry, The University of Texas Southwestern Medical Center at Dallas, 5323 Harry Hines Boulevard, Dallas, TX 75390-9038, USA.
Journal of the American Chemical Society
|August 19, 2004
まとめ
この研究では,ケトンカルボニルに隣接するアルキル基を導入するために,銅触媒化されたクロスカップリング反応を導入しています. この方法は,高収量とステレオ特異性を持つ多様なアルファ-アルキル化ケトンを効率的に合成します.
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
- 合成方法論 合成方法論
背景:
- C−C結合形成の効率的な方法は,有機合成において極めて重要です.
- ケトンのアルファ・アルキレーションは,複雑な分子を作るための重要な変換です.
- 銅で触媒化された反応は,有機変換においてユニークな反応性と選択性を提供します.
研究 の 目的:
- 新しい銅触媒クロスカップリング反応を開発する.
- ケトンカルボニルに隣接する一次および二次アルキル基を導入する.
- 反応の範囲とステレオ化学的結果を調査する.
主な方法:
- アルキル亜鉛ハライドとアルファクロロケトンとの交互結合.
- 銅 ((II) アセチラケトネート (Cu ((acac) 2) を使用した触媒処理.
- 循環性,非循環性,芳香性,およびアリファ性アルファ-クロロケトンを含む基板の範囲の分析.
主要な成果:
- ケトンに隣接する一次および二次アルキル基の導入に成功した.
- 軽度な反応条件下で得られた良い収穫量.
- 立体化学の逆転による光学活性アルファ-クロロケトンから光学活性製品への立体特異的変換.
結論:
- 開発された銅触媒法により,アルファアルキル化ケトンへの効率的な経路が提供されています.
- この反応は,広範囲の基質範囲と優れたステレオ化学的制御を示しています.
- 提案されたメカニズムは,有機金属中間物質による直接の置換を伴う.
関連する概念動画
01:21Acid-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...
00:51Base-Promoted α-Halogenation of Aldehydes and Ketones
α-Halogenation of aldehydes and ketones is a reaction involving the substitution of α hydrogens with halogens in the presence of a base. The reaction begins with the abstraction of α hydrogen by the base to produce a nucleophilic enolate ion. This intermediate undergoes a subsequent nucleophilic substitution with the halogen to produce a monohalogenated carbonyl compound. If the starting substrate has more than one α hydrogen, it is difficult to stop the reaction at the stage of...
01:14Crossed Aldol Reaction Using Weak Bases
This lesson deals with the crossed aldol reaction using weak bases. The self-condensation of an aldehyde having α hydrogen is prevented by adding it slowly to a mixture of formaldehyde and weak bases like hydroxide and alkoxide. Upon slow addition of the aldehyde, the base deprotonates the α carbon of the aldehyde to form the corresponding enolate. The enolate subsequently attacks the formaldehyde to form a single crossed product. Figure 1 depicts the aforementioned reaction.
00:56Crossed Aldol Reaction Using Strong Bases: Directed Aldol Reaction
The reaction between two different carbonyl compounds comprising α hydrogen in the presence of a strong base like lithium diisopropylamide (LDA) to form a crossed aldol product is known as a directed aldol reaction. The directed aldol reaction is depicted in Figure 1.
01:18β-Dicarbonyl Compounds via Crossed Claisen Condensations
Crossed Claisen condensations are base-promoted reactions between two different ester molecules producing β-dicarbonyl compounds. The reaction involving esters, with both containing α hydrogen, results in a mixture of four different products that are difficult to isolate. This reduces the synthetic utility of the reaction.
01:10Factors 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...