双语化学辞典Chem Lexicon
反应 · 有机化学 · 周环反应 Organic chemistry · Pericyclic reactions

克莱森重排Claisen rearrangement

拼音Pinyin kè lái sēn chóng pái 别名Also [3,3]-σ 迁移(烯丙基乙烯基醚);[3,3]- sigmatropic rearrangement of allyl vinyl ethers

定义Definition

克莱森重排是烯丙基乙烯基醚或烯丙基芳基醚在加热下发生 [3,3]-σ 迁移,生成 γ,δ-不饱和羰基化合物或邻烯丙基苯酚的协同周环反应。

The Claisen rearrangement is a concerted [3,3]-sigmatropic shift of an allyl vinyl ether or allyl aryl ether on heating, giving a γ,δ-unsaturated carbonyl compound or an o-allylphenol.

机理与立体化学Mechanism and stereochemistry

六个原子经椅式(优先)环状过渡态重组:断裂 C–O σ 键,形成新的 C–C σ 键,π 键迁移。立体化学可由椅式过渡态准确预测,手性能高效传递。芳基烯丙基醚先得到二烯酮中间体,再互变异构为酚;若两个邻位都被占据,则进一步发生科普重排到对位。

Six atoms reorganise through a (preferably chair) cyclic transition state: a C–O σ bond breaks, a C–C σ bond forms and the π bonds shift. The chair TS predicts stereochemistry and transfers chirality efficiently. Aryl allyl ethers give a dienone that tautomerises to the phenol; if both ortho positions are blocked a further Cope shift moves the allyl to para.

由来Origin

路德维希·克莱森于 1912 年报道(芳基烯丙基醚重排为邻烯丙基苯酚)。

Reported by Ludwig Claisen in 1912 (aryl allyl ethers to o-allylphenols).

重要变体Important variants

约翰逊–克莱森(原酸酯)、埃申莫瑟–克莱森(酰胺缩醛)、爱尔兰–克莱森(烯醇硅醚酯,低温即可)等变体在天然产物合成中广泛用于立体选择性构建 C–C 键。生物体内分支酸 → 预苯酸是酶催化的克莱森重排(分支酸变位酶)。

Johnson (orthoester), Eschenmoser (amide acetal) and Ireland (silyl ketene acetal, low temperature) variants build C–C bonds stereoselectively in natural-product synthesis. Chorismate → prephenate is an enzyme-catalysed Claisen (chorismate mutase).

反应Reactions

CH2=CH–O–CH2–CH=CH2 △⟶ CH2=CH–CH2–CH2–CHO

150–250 °C 加热(芳基醚约 200 °C);爱尔兰变体可在室温

Heat at 150–250 °C (aryl ethers ~200 °C); the Ireland variant runs near room temperature

  1. 形成椅式六元环过渡态。

    A chair-like six-membered transition state forms.

  2. C–O 键断裂与 C–C 键形成协同发生。

    C–O cleavage and C–C formation occur together.

  3. 芳基醚的二烯酮互变异构为酚。

    For aryl ethers the dienone tautomerises to the phenol.

烯丙基苯基醚 200 °C⟶ 2-烯丙基苯酚Phenyl group 200 °C⟶ 2-Phenol

芳香克莱森重排。

Aromatic Claisen rearrangement.

反应机理图Mechanism

红色弯箭头表示一对电子的移动方向:从电子来源(孤对电子或化学键)指向电子去向。Red curly arrows show where an electron pair moves: from its source (lone pair or bond) to its destination.

1

椅式六元环过渡态,[3,3] σ 迁移

Chair-like six-membered transition state, a [3,3] sigmatropic shift

△
2

γ,δ-不饱和醛(4-戊烯醛)

γ,δ-Unsaturated aldehyde (pent-4-enal)

年表Timeline

  • 1912

    克莱森报道该重排

    Claisen reports the rearrangement

  • 1940

    科普报道全碳 [3,3] 重排

    Cope reports the all-carbon [3,3] shift

  • 1972

    爱尔兰报道烯醇硅醚酯版本

    Ireland reports the ester-enolate variant