Name: acyloin condensation: ester coupling pathway
Uploaded: 2023-04-30T11:23:12.000Z
Duration: 1 min 19 s
Channel: JoVE

ピナコール反応とマクマリー反応に加えて、アシロイン縮合はエステルが関与する別の還元的カップリング反応です。
この反応では、エステルは非プロトン性溶媒中の金属電子源の存在下で反応し、アシロインとも呼ばれるα-ヒドロキシケトンを形成します。
反応はケチルの形成を通じて進行し、ケチルはラジカル二量体化を受けて不安定な四面体中間体を形成し、さらに崩壊して1,2-ジケトンを生成します。
1,2-ジケトンは、求電子剤や還元剤に対してケトンよりも比較的反応性が高いため、2つの電子を移動させることで、1,2-ジケトンを容易に老化に還元します。
最後に、エニディオレートの酸性化により、良好な収率のα-ヒドロキシケトンが得られます。しかし、求核性エンディオレートの反応性は、しばしば副生成物の形成につながります。
望ましくない副反応を防ぐために、塩化トリメチルシリルを添加してエンディオレートをシリル化し、ビスシリルエーテルを生成し、これをさらに水酸で加水分解して最終生成物としてα-ヒドロキシケトンを生成します。

エステルの還元カップリングによるα-ヒドロキシケトン: アシロイン縮合の概要

&alpha;-Hydroxy Ketones via Reductive Coupling of Esters: Acyloin Condensation Overview

ピナコール反応とマクマリー反応には、ケトンまたはアルデヒドの還元カップリングが含まれます。 同様に、非プロトン性溶媒中で金属ナトリウムの存在下で 2 つのエステル分子を二分子還元カップリングすると、α-ヒドロキシ ケトン生成物が得られます。 α-ヒドロキシケトンはアシロインとも呼ばれるため、この反応は「アシロイン縮合」と呼ばれます。



<img alt="Figure1" src="/files/ftp_upload/12908/12908_PT_Figure_1.svg" style="text-align: center; height: 65px;">



アシロイン縮合反応では、エステルがケチルに変換され、ラジカル二量化が起こって不安定な四面体中間体が形成されます。 さらに、この中間体は崩壊して 1,2-ジケトン中間体を生成します。 1,2-ジケトンは、π * エネルギーが低いため、求電子剤や還元剤に対してケトンよりも比較的反応性が高くなります。 その結果、2 つの電子が順番に 1,2-ジケトンに移動し、エンジオラートが形成されます。 最後に、エンジオラート中間体を酸でクエンチすると、α-ヒドロキシケトンが高収率で得られます。

求核性エンジオラートの反応性により、主生成物と一緒に副生成物が得られることがよくあります。 副反応を克服してアシロインの収率を向上させるために、塩化トリメチルシリルを使用してエンジオラートをシリル化します。 これによりビスシリルエーテルが生成され、さらに酸水溶液で加水分解されてα-ヒドロキシケトンが得られます。

ピナコール反応とマクマリー反応には、ケトンまたはアルデヒドの還元的カップリングが含まれます。同様に、2つのエステルの二分子還元結合...

hydroxy-ketones-via-reductive-coupling-esters-acyloin-condensation

Education

JoVE Core

Organic Chemistry

有機化学

Unit 1

ユニット1

Radical Chemistry

ラジカル化学

KEY TERMS AND CONCEPTS

主要用語と概念

acyloin condensation: ester coupling pathway

Acyloin condensation is a reaction that joins two ester molecules to form an alpha-hydroxy ketone. The product is also called an acyloin. In this reaction, sodium metal is used in an aprotic solvent, which supports the reductive coupling step.

The reaction is related to the pinacol and McMurry reactions, which also involve reductive coupling of ketones or aldehydes. Here, the ester first becomes a ketyl. These ketyl species undergo radical dimerization and form an unstable tetrahedral intermediate. That intermediate then collapses to give a 1,2-diketone intermediate.

The 1,2-diketone is more reactive than a ketone toward electrophiles and reducing agents because it has lower pi-star energy. Two electrons then transfer in sequence to form an enediolate. The enediolate is finally quenched with acid to produce the alpha-hydroxy ketone. This reaction can give a good yield, but side products may also form because the enediolate is nucleophilic.

Trimethylsilyl chloride can be used to reduce those side reactions and improve the acyloin yield. It silylates the enediolate to form a bis-silyl ether. Aqueous acid then hydrolyzes this intermediate to give the alpha-hydroxy ketone.

Acyloin Condensation: Ester Coupling Pathway

acyloin-condensation-ester-coupling-pathway

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Radical Geometry: Planarity and Inversion

Radical geometry depends on the electronic structure around the radical center. An unpaired electron, like a lone pair, affects the shape of the molecule. For a trivalent radical, the structure falls between the geometries of carbocations and carbanions. A carbocation with sp2 hybridization is trigonal planar. A carbanion with sp3 hybridization is trigonal pyramidal. The difference comes from the number of nonbonding electrons. The carbocation has none, while the carbanion has two. A carbon...

electron paramagnetic resonance (epr) spectroscopy: organic radicals

electron-paramagnetic-resonance-epr-spectroscopy-organic-radicals

EPR Hyperfine Splitting in Organic Radicals

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radical formation: overview

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Radicals are generated when bonds break in specific ways or when one radical leads to another. In homolytic bond cleavage, a bond splits evenly and forms radicals. In heterolytic bond cleavage, the bond breaks to form ions instead. A fishhook arrow shows the movement of a single electron during homolytic cleavage. Radicals can come from spin-paired molecules by homolysis or by electron transfer. Homolysis forms two radicals. Electron transfer adds an electron to the molecule, and this process...

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Homolysis and Radical Bonds

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Radical Abstraction in Chain Reactions

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Radical Addition and Spin Conservation

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Radicals from Elimination Reactions

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radical reactivity: overview

Radical Reaction Pathways and Stability

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radical-reactivity-electrophilic-radicals

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Nucleophilic Radicals and Alkene Traps

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radical-reactivity-intramolecular-vs-intermolecular

Radical Cyclization in One Molecule

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radical-oxidation-of-allylic-and-benzylic-alcohols

Selective MnO2 Oxidation of Alcohols

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radical-substitution-halogenation-of-alkanes-and-alkyl-substituents

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Alkane Halogenation: Stability and Reaction Rates

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radical substitution: allylic chlorination

radical-substitution-allylic-chlorination

Allylic Chlorination by Radical Chain Reaction

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radical substitution: allylic bromination

Allylic Bromination with NBS

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radical-substitution-hydrogenolysis-alkyl-halides-with-tributyltin

Alkyl Halide Reduction with Tributyltin Hydride

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radical-anti-markovnikov-addition-to-alkenes-overview

Peroxide Effect in HBr Addition to Alkenes

Hydrogen bromide can add to alkenes through a peroxide-driven radical pathway. In this reaction, hydroperoxides or peroxides change the usual addition pattern and lead to alkyl bromides with anti-Markovnikov regiochemistry, which means bromine ends up on the less substituted carbon. This regioselectivity can be explained by radical stability. When the bromine radical adds to the alkene at the less substituted carbon, the reaction forms a more stable tertiary radical intermediate. The same...

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radical-anti-markovnikov-addition-to-alkenes-mechanism

Hydrogen Bromide Addition to Alkenes by Radicals

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radical-anti-markovnikov-addition-to-alkenes-thermodynamics

HBr Selectivity in Alkene Addition Thermodynamics

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vicinal-diols-via-reductive-coupling-aldehydes-or-ketones-pinacol

Pinacol Coupling and Solvent Effects

Pinacol coupling is a radical dimerization reaction that joins aldehydes or ketones to form vicinal diols. Wilhelm Rudolph Fittig first discovered this reaction in 1859. It is a reductive coupling, which means the molecules are joined after they gain electrons. The reaction begins with a single electron transfer from metals such as sodium or magnesium to an aldehyde or ketone. This forms a ketyl, a radical anion. In a ketyl, the carbon atom can carry radical character while the oxygen atom...

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Titanium-Coupled Alkenes from Carbonyls

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&alpha;-hydroxy ketones via reductive coupling of esters: acyloin condensation overview

Acyloin condensation is a reaction that joins two ester molecules to form an alpha-hydroxy ketone. The product is also called an acyloin. In this reaction, sodium metal is used in an aprotic solvent, which supports the reductive coupling step. The reaction is related to the pinacol and McMurry reactions, which also involve reductive coupling of ketones or aldehydes. Here, the ester first becomes a ketyl. These ketyl species undergo radical dimerization and form an unstable tetrahedral...

key terms and concepts

Learn how acyloin condensation couples two esters with sodium metal to form alpha-hydroxy ketones, including ketyls, enediolates, and yield improvement.

Acyloin Condensation: Ester Coupling Pathway | JoVE K12

organic chemistry

JoVE Core 有機化学では、立体化学、反応、メカニズムの基本概念を、簡潔でわかりやすいアニメーション ビデオ レッスンを使用して説明します。さらに、科学者の実際のビデオでは、世界中の今日の研究室で行われている古典的および独自の研究実験における関連概念の適用を示しています。

Acyloin Condensation: Ester Coupling Pathway

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