on style="text-indent: 2em;">2000年Libeskind和Srogl提出了一种在中性条件下，过渡金属催化硫代酸酯和硼酸进行偶联得到酮的新方法。在化学计量的噻吩-2-羧酸亚铜（CuTC）和催化量的钯催化下，硫代酸酯和芳基硼酸或烷基硼进行偶联得到酮的反应被称为Liebeskind–Srogl偶联反应。此反应是非常重要的把羧酸及其衍生物转化为酮的方法，此反应中硼酸或烷基硼为非碱性亲核试剂，因此反应条件比Fuyama偶联更温和。与Suzuki反应不同，芳基硼酸的偶联无需使用碱。该法用于制备N-保护的α-氨基酸或二肽、三肽酮时不发生外消旋化。

由N保护的氨基酸制备二肽酮时不发生外消旋化。

Libeskind后来又开发出了利用有机锡试剂和有机铟试剂和硫代酸酯进行偶联的方法。

此反应经过十几年的发展，底物已经由硫酯逐步扩展到杂芳基硫醚、炔基硫醚、环状硫代酰胺，异硫脲和硫氰酸酯等，应用范围进一步扩大：

合成炔：

合成脒：

合成腈：

反应机理

首先硫代酸酯和CuTC进行配位，氧化加成插入钯，金属转移，还原消除得到产物。

图片来源：https://cheminfographic.files.wordpress.com/2018/03/80_liebeskind-srogl_coupling1.jpg

反应实例

【J. Am. Chem. Soc. 2000, 122, 11260】

A mixture of 415 mg 4-methoxyphenylboronic acid (2.73 mmol), 446 mg CuTC(2.34 mmol), 523 mg tert-butyl [5-bromo-2-(methylthio)-6-oxopyrimidin-1(6H)-yl]acetate(1.56 mmol), and 5 mol % Pd(PPh3)4 was placed in a flflask. After three vacuum/argon cycles,15 mL dry and degassed THF was added. The reaction was stirred for 12–18 h at 50–60◦Cand monitored by LC/MS. When the reaction was complete, the mixture was cooled toambient temperature, EtOAc was added, and the mixture was fifiltered through a mediumfrit sintered glass funnel. The fifiltrate was washed with 1 N NaHSO4, saturated NaHCO3,and brine. The organic layer was dried over MgSO4, fifiltered, and concentrated to a viscous solid. The residue was purifified by flflash chromatography (CH2Cl2/MeOH, 200:1) toafford 439 mg tert-butyl [5-bromo-2-(4-methoxyphenyl)-6-oxopyrimidin-1(6H)-yl]acetateas a pale yellow solid, in a yield of 71%.

【Org. Lett., 2003, 5, 4349】

A microwave process vial was charged with a stir bar. To this vessel were added DHPM(69.1 mg, 0.25 mmol), 45.7 mg PhB(OH)2 (0.375 mmol), 142.9 mg Cu(I) thiophene-2-carboxylate (CuTC) (0.75 mmol), and 8.7 mg Pd(PPh3)4 (3.0 mol %). The reaction vesselwas flflushed with argon and sealed. Through the septum was added 5 mL anhydrous THF,and the reaction vessel was irradiated at 100◦C for 25 min. After cooling, the mixturewas transferred to a round-bottomed flflask and was adsorbed on silica gel. The residuewas purifified by flflash chromatography on silica gel (hexanes/EtOAc, 3:1) to yield 81%dihydropyrimidine as a semisolid.

【Org. Lett., 2004, 6, 771】

【J. Org. Chem.  2004, 69, 3554】

【J. Am. Chem. Soc. 2007, 129, 1132】

【J. Org. Chem.  2005, 70, 4851】

(2-Bromophenyl)(p-tolyl)methanone (3).3 Copper catalyst (83 mg, 0.013 mmol) was added to thioester 1 (83 mg, 0.25 mmol) followed by 2 (124 mg, 0.625 mmol) and 2 mL dry DMF. The mixturewas stirred at 50℃ in open air and monitored by TLC. Sat NH4Cl was added and the aq layer wasextracted with ether. The organic layers were washed with water. Workup and chromatography (silica,EA:hexane 1:5) afforded 60 mg, 86% of 3 (yellow oil).

【Liebeskind LS, J .Am. Chem. Soc.  2007, 129, 15734】

【 J. Org. Chem. 2009, 74, 5118–5121】

参考资料：

一、《有机人名反应、试剂与规则》，黄培强等。

二、Comprehensive Organic Name Reactions and Reagents, by Zerong Wang，P1754-1757