定义Definition
布赫瓦尔德-哈特维希偶联是钯催化下芳基卤化物（或三氟甲磺酸酯）与伯胺、仲胺（或酰胺、氨等氮亲核试剂）在强碱存在下形成芳基 C–N 键的反应。
The Buchwald–Hartwig amination forms aryl C–N bonds by palladium-catalysed coupling of aryl halides (or triflates) with primary or secondary amines (or amides, ammonia equivalents) in the presence of a strong base.
催化循环Catalytic cycle
Pd(0)L 氧化加成 Ar–X；胺配位并被碱去质子化形成钯–氨基配合物；C–N 还原消除得芳胺。竞争副反应是 β-氢消除（使芳基卤还原为芳烃）。
Pd(0)L adds Ar–X; the amine binds and is deprotonated by base to a palladium amido complex; C–N reductive elimination gives the arylamine. The competing side reaction is β-hydride elimination, reducing the aryl halide to arene.
由来与配体发展Origin and ligand development
1994 年斯蒂芬·布赫瓦尔德与约翰·哈特维希分别独立报道。此后发展了 BINAP、DPPF 等双膦配体，以及 XPhos、BrettPhos 等大位阻联芳基单膦配体，使芳基氯、弱亲核胺在温和条件下也能偶联。
Independently reported in 1994 by Stephen Buchwald and John Hartwig. Bidentate ligands (BINAP, DPPF) and bulky biaryl monophosphines (XPhos, BrettPhos) later enabled aryl chlorides and weak amine nucleophiles to couple under mild conditions.
意义Significance
芳胺是药物、农药和有机电子材料（空穴传输材料）的常见结构，该反应取代了需要苛刻条件的乌尔曼偶联与 SNAr，是药物化学中使用最频繁的反应之一。
Arylamines are ubiquitous in drugs, agrochemicals and organic electronics (hole-transport materials); this reaction replaced harsh Ullmann and SNAr methods and is among the most used reactions in medicinal chemistry.
反应Reactions
Pd₂(dba)₃ 或 Pd 预催化剂 + XPhos/BINAP，NaOtBu 或 Cs₂CO₃，甲苯或二氧六环，80–110 °C
Pd₂(dba)₃ or a Pd precatalyst with XPhos/BINAP, NaOtBu or Cs₂CO₃, toluene or dioxane, 80–110 °C
Pd(0) 氧化加成。
Oxidative addition to Pd(0).
胺配位、去质子化成氨基钯。
Amine binding and deprotonation to the amido complex.
C–N 还原消除。
C–N reductive elimination.
芳基氯的胺化。
Amination of an aryl chloride.
年表Timeline
- 1983
右田、小杉报道芳基溴与氨基锡的钯催化偶联
Migita and Kosugi report Pd-catalysed coupling of aryl bromides with aminostannanes
- 1994
布赫瓦尔德与哈特维希独立报道无锡胺化
Buchwald and Hartwig independently report tin-free amination
- 2008
BrettPhos 等新一代配体问世
New-generation ligands such as BrettPhos appear