由N保護(hù)的氨基酸制備二肽酮時(shí)不發(fā)生外消旋化。
Libeskind后來(lái)又開(kāi)發(fā)出了利用有機(jī)錫試劑和有機(jī)銦試劑和硫代酸酯進(jìn)行偶聯(lián)的方法。
此反應(yīng)經(jīng)過(guò)十幾年的發(fā)展，底物已經(jīng)由硫酯逐步擴(kuò)展到雜芳基硫醚、炔基硫醚、環(huán)狀硫代酰胺，異硫脲和硫氰酸酯等，應(yīng)用范圍進(jìn)一步擴(kuò)大：
合成炔：
合成脒：
合成腈：
反應(yīng)機(jī)理
首先硫代酸酯和CuTC進(jìn)行配位，氧化加成插入鈀，金屬轉(zhuǎn)移，還原消除得到產(chǎn)物。
圖片來(lái)源：https://cheminfographic.files.wordpress.com/2018/03/80_liebeskind-srogl_coupling1.jpg
反應(yīng)實(shí)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】
參考資料：
一、《有機(jī)人名反應(yīng)、試劑與規(guī)則》，黃培強(qiáng)等。
二、Comprehensive Organic Name Reactions and Reagents, by Zerong Wang，P1754-1757
