定义Definition
迈克尔加成是稳定化的碳负离子（迈克尔供体，如丙二酸酯、β-酮酸酯的烯醇负离子）对 α,β-不饱和羰基化合物等迈克尔受体的 β-碳进行 1,4-共轭加成，形成新 C–C 键的反应。
The Michael reaction is the 1,4-conjugate addition of a stabilised carbanion (Michael donor, e.g. a malonate or β-keto ester enolate) to the β-carbon of an α,β-unsaturated carbonyl compound or other Michael acceptor, forming a C–C bond.
机理与选择性Mechanism and selectivity
受体的羰基通过共轭使 β-碳带部分正电。软的、稳定化的亲核试剂（烯醇负离子、铜锂试剂、胺、硫醇）倾向 1,4-加成；硬的、强碱性亲核试剂（格氏、有机锂）倾向直接进攻羰基（1,2-加成）。加成后得到的烯醇负离子质子化成 1,5-二羰基化合物。
Conjugation with the carbonyl makes the β-carbon electrophilic. Soft, stabilised nucleophiles (enolates, cuprates, amines, thiols) prefer 1,4-addition; hard, strongly basic ones (Grignard, organolithium) attack the carbonyl (1,2). The resulting enolate is protonated to a 1,5-dicarbonyl compound.
由来Origin
美国化学家亚瑟·迈克尔于 1887 年报道。
Reported by the American chemist Arthur Michael in 1887.
应用Applications
罗宾森环化的第一步；杂原子迈克尔加成（氮、硫）用于药物和高分子交联；有机催化（手性胺、硫脲）的不对称迈克尔加成应用广泛。生物体内许多共价药物（如依鲁替尼）以迈克尔受体与蛋白半胱氨酸成键。
The first step of the Robinson annulation; hetero-Michael additions (N, S) are used in drugs and polymer cross-linking; organocatalytic asymmetric versions are widespread. Covalent drugs such as ibrutinib bond to protein cysteines as Michael acceptors.
反应Reactions
催化量 NaOEt、DBU 或 Et₃N，室温；或铜锂试剂 R₂CuLi，低温
Catalytic NaOEt, DBU or Et₃N at room temperature; or R₂CuLi at low temperature
生成供体碳负离子。
Generate the donor carbanion.
进攻受体 β-碳，生成烯醇负离子。
Attack at the β-carbon gives an enolate.
质子化得 1,5-二羰基化合物。
Protonation gives the 1,5-dicarbonyl.
丙二酸酯对甲基乙烯基酮加成。
Malonate addition to methyl vinyl ketone.
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
- 1887
迈克尔报道共轭加成
Michael reports the conjugate addition
- 1935
罗宾森环化利用迈克尔加成
The Robinson annulation employs it