定义Definition
狄尔斯-阿尔德反应是共轭双烯与亲双烯体（烯烃或炔烃）发生 [4+2] 环加成，一步生成六元环（环己烯衍生物）的反应。它同时形成两个新的 C–C σ 键，立体专一性强，是构建六元环最重要的方法之一。
The Diels–Alder reaction is a [4+2] cycloaddition between a conjugated diene and a dienophile (an alkene or alkyne) that forms a six-membered ring, a cyclohexene derivative, in a single step. It makes two new C–C σ bonds at once with high stereospecificity, and is one of the most important ways to build six-membered rings.
机理Mechanism
反应是协同的周环过程：双烯的 HOMO 与亲双烯体的 LUMO 同面-同面重叠，三对 π 电子经环状过渡态重排为两个 σ 键和一个新 π 键。按伍德沃德-霍夫曼规则，热条件下 [4s+2s] 是对称性允许的。双烯必须采取 s-顺式构象才能反应。
The reaction is a concerted pericyclic process: the diene's HOMO overlaps suprafacially with the dienophile's LUMO, and three pairs of π electrons reorganise through a cyclic transition state into two σ bonds and one new π bond. Under the Woodward–Hoffmann rules the thermal [4s+2s] process is symmetry-allowed. The diene must adopt the s-cis conformation to react.
发现与由来Discovery
1928 年德国化学家奥托·狄尔斯和他的学生库尔特·阿尔德报道了环戊二烯与对苯醌、马来酸酐的加成，并认识到这是一类普遍的“双烯合成”。两人因此获得 1950 年诺贝尔化学奖。此前已有人观察到类似产物，但没有正确解释其结构。
In 1928 the German chemist Otto Diels and his student Kurt Alder reported the addition of cyclopentadiene to p-benzoquinone and maleic anhydride and recognised it as a general diene synthesis. They shared the 1950 Nobel Prize in Chemistry for it. Others had seen similar products earlier but had not explained their structures correctly.
选择性规律Selectivity rules
反应保持双烯和亲双烯体原有的立体关系（顺式取代基在产物中仍为顺式）。环状双烯反应时以内型（endo）产物为主，即阿尔德内型规则，常归因于次级轨道作用。双烯带给电子基、亲双烯体带吸电子基时反应最快（正常电子需求）；区域选择性服从“邻对位”规律。
The reaction preserves the original stereochemistry of diene and dienophile: cis substituents stay cis in the product. With cyclic dienes the endo product usually dominates (Alder's endo rule), often attributed to secondary orbital interactions. It is fastest when the diene carries donor groups and the dienophile acceptor groups (normal electron demand), and its regiochemistry follows the ortho–para rule.
发展与应用Developments and applications
路易斯酸催化可显著加速反应并提高选择性；1989 年起科里等发展了手性催化剂实现不对称狄尔斯-阿尔德反应。反电子需求、杂狄尔斯-阿尔德（含 N、O 的双烯或亲双烯体）反应扩展了适用范围。该反应广泛用于甾体、利血平、紫杉醇等天然产物的全合成。
Lewis-acid catalysis speeds the reaction greatly and sharpens selectivity; from 1989 Corey and others developed chiral catalysts for asymmetric Diels–Alder reactions. Inverse-electron-demand and hetero-Diels–Alder variants, with N or O in the diene or dienophile, widen its scope. It is used throughout the total synthesis of natural products such as steroids, reserpine and taxol.
反应Reactions
通常加热即可；亲双烯体带吸电子基（C=O、CN、NO₂）时反应快，可用 AlCl₃、BF₃ 等路易斯酸催化。
Usually just heat; dienophiles bearing acceptor groups (C=O, CN, NO₂) react fastest, and Lewis acids such as AlCl₃ or BF₃ catalyse it.
双烯旋转为 s-顺式构象，与亲双烯体平行靠近。
The diene rotates to the s-cis conformation and approaches the dienophile face to face.
经六元环状过渡态，两端同时形成两个新的 σ 键。
Through a six-membered cyclic transition state, two new σ bonds form at both ends simultaneously.
原双烯中间的单键变为新的 C=C 双键，得到环己烯骨架。
The central single bond of the diene becomes the new C=C double bond, giving the cyclohexene skeleton.
经典的内型选择性实例
The classic example of endo selectivity
构建取代环己烯
Building a substituted cyclohexene
可逆的狄尔斯-阿尔德反应（逆反应称逆狄尔斯-阿尔德）
A reversible case; the reverse is the retro-Diels–Alder reaction
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.
六个 π 电子环状协同移动，两根新 σ 键同时形成
Six π electrons move in a ring; both new σ bonds form at once
环己烯
Cyclohexene
年表Timeline
- 1928
狄尔斯与阿尔德发表双烯合成
Diels and Alder publish the diene synthesis
- 1950
两人获诺贝尔化学奖
Both receive the Nobel Prize in Chemistry
- 1951
伍德沃德在甾体全合成中运用该反应
Woodward uses it in steroid total synthesis
- 1965
伍德沃德与霍夫曼提出轨道对称守恒规则
Woodward and Hoffmann formulate orbital-symmetry rules
- 1989
科里报道高对映选择性的催化不对称版本
Corey reports a highly enantioselective catalytic version