定义Definition
罗宾森环化是酮（或其烯醇负离子）与甲基乙烯基酮先发生迈克尔加成，再进行分子内羟醛缩合并脱水，生成环己烯酮（新的六元环）的串联反应。
The Robinson annulation is a tandem Michael addition of a ketone (enolate) to methyl vinyl ketone followed by intramolecular aldol condensation and dehydration, building a new cyclohexenone ring.
机理Mechanism
第一步：碱生成的烯醇负离子对甲基乙烯基酮共轭加成（迈克尔），得到 1,5-二酮。第二步：1,5-二酮甲基酮端的烯醇负离子进攻环上羰基，分子内羟醛加成成六元环，随后脱水得 α,β-不饱和环己烯酮。
First, the enolate adds conjugately to methyl vinyl ketone (Michael), giving a 1,5-diketone. Second, an enolate of the methyl ketone end attacks the ring carbonyl in an intramolecular aldol that closes a six-membered ring, which dehydrates to the cyclohexenone.
由来Origin
英国化学家罗伯特·罗宾森于 1935 年报道，用于甾体和萜类的合成；罗宾森因生物碱等天然产物研究获 1947 年诺贝尔化学奖。
Reported by Robert Robinson in 1935 for steroid and terpene synthesis; he won the 1947 Nobel Prize for natural-product (alkaloid) chemistry.
不对称版本Asymmetric version
1971 年哈约什–帕里什–埃德–绍尔–维歇特反应用 L-脯氨酸催化三酮的分子内羟醛缩合，高对映选择性得到维兰德–米舍尔酮——现代有机催化的先驱。
In 1971 the Hajos–Parrish–Eder–Sauer–Wiechert reaction used L-proline to catalyse the intramolecular aldol of a triketone, giving the Wieland–Miescher ketone enantioselectively — a forerunner of modern organocatalysis.
反应Reactions
KOH 或 NaOEt/EtOH，或先酸催化迈克尔再碱催化羟醛；加热脱水
KOH or NaOEt in EtOH, or acid-catalysed Michael then base-catalysed aldol; heat to dehydrate
烯醇负离子对 MVK 迈克尔加成。
Michael addition of the enolate to MVK.
分子内羟醛加成形成六元环。
Intramolecular aldol closes the six-membered ring.
脱水得到环己烯酮。
Dehydration gives the cyclohexenone.
甾体合成的关键砌块。
A key building block for steroids.
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.
稳定碳负离子进攻 α,β-不饱和酮的 β-碳（1,4-加成）
The stabilised carbanion attacks the β-carbon of the enone (1,4-addition)
烯醇负离子在 α-碳上质子化
The enolate is protonated on its α-carbon
1,5-二羰基化合物（罗宾逊成环的第一步）
A 1,5-dicarbonyl compound (the first stage of a Robinson annulation)
年表Timeline
- 1935
罗宾森报道该环化
Robinson reports the annulation
- 1947
罗宾森获诺贝尔化学奖
Robinson receives the Nobel Prize
- 1971
脯氨酸催化不对称版本
Proline-catalysed asymmetric version