β-ディケトンの直接的および高度に地域選択的およびエナチオ選択的アリレーションである
Wesley A Chalifoux1, Samuel K Reznik, James L Leighton
1Department of Chemistry, Columbia University, New York, New York 10027, USA.
Nature
|July 6, 2012
まとめ
複雑な分子の合成に不可欠なケトンのエナチオセレクティブ・アリレーションは,β-ダイケトンの場合も実現可能になった. この新しい方法は,反応性の課題を克服し,貴重なキラル三次カルビノールへのアクセスを拡大します.
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
背景:
- ケトンのエナチオセレクティブ・アリレーションは,キラル三次カルビノールの生成に不可欠である.
- 既存の方法は単純なケトンに限られており,複雑な分子の合成を妨げています.
- 機能的に複雑なケトンに適用できる方法が必要である.
研究 の 目的:
- β-ジケトンのエナンチオセレクティブアリレーションのための方法を開発する.
- 難しい基板から複雑な三次カルビノールの合成を可能にするために.
- 非対称合成におけるβ-ディケトンの固有反応性を克服するために.
主な方法:
- ブロンステッド酸の活性化のためにβ-ダイキトンのエノール形式を使用した.
- 操作的にシンプルで直接的,地域選択的,およびエナチオ選択的アリレーションプロトコルを開発しました.
- 特定の活性化戦略を通じてβ-ダイケトンの核愛性の性質を克服しました.
主要な成果:
- β-ディケトンのエナンチオセレクティブ・アリレーションが成功しました.
- より広い範囲のエナティオメリックに濃縮された,機能的に複雑な三次カルビノールを生成した.
- β-ダイケトンに対する新しい反応経路が示され,既定の化学原理に異議を唱えた.
結論:
- 開発された方法は,ケトンアライレーションの範囲を大幅に拡大します.
- 複雑な合成のための貴重なキラル構成要素に簡単にアクセスできます.
- β-ディケトン反応性の理解と利用における画期的な進歩を表しています.
関連する概念動画
02:36Regioselectivity and Stereochemistry of Hydroboration
A significant aspect of hydroboration–oxidation is the regio- and stereochemical outcome of the reaction.
Hydroboration proceeds in a concerted fashion with the attack of borane on the π bond, giving a cyclic four-centered transition state. The –BH2 group is bonded to the less substituted carbon and –H to the more substituted carbon. The concerted nature requires the simultaneous addition of –H and –BH2 across the same face of the alkene giving syn stereochemistry.
Hydroboration proceeds in a concerted fashion with the attack of borane on the π bond, giving a cyclic four-centered transition state. The –BH2 group is bonded to the less substituted carbon and –H to the more substituted carbon. The concerted nature requires the simultaneous addition of –H and –BH2 across the same face of the alkene giving syn stereochemistry.
01:33Regioselective 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.
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...
01:10α-Alkylation of Ketones via Enolate Ions
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 strong interaction...
01:27Aldol Condensation with β-Diesters: Knoevenagel Condensation
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.
01:14Alkylation 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.