在过去的几年里，钯催化的胺的芳基化已得到很大的进展。但酰胺的芳基化进展缓慢。在九十年代后期，Buchwald研究小组曾成功的实现了钯催化下（Pd2(dba)3 / 2(2-furyl)3P, Cs2CO3）的酰胺分子内芳基化。其它催化剂体系如Pd(PPh3)4, Pd2(dba)3 / 2P (o-tolyl)3, Pd2(dba)3 / 2PPh3 需要较长的反应时间或收率较低。当用Ph3As 或 (C6F5)3P做配体时，得不到产物。当用其它碱金属的碳酸盐做碱时，效果较差，如果NaOtBu, NaOAc和 KOAc 做碱时则效果更差。 

       用类似的条件也实现了磺酰胺的分子内酰化，而且反应速度更快，催化剂的用量也少。这可能因为磺酰胺上N-H的酸性更强的缘故。但酰胺或磺酰胺的分子间芳基化却得不到很好的结果。 

      1999年， Shakespeare成功地实现了内酰胺与芳基溴的分子间芳基化。但也只有五元环（n = 2）时，反应能得到好的收率。其它内酰胺（n = 1，3，4）的收率较低，如果溴代芳烃上有拉电子等活化基团时也能得到较好的收率。 

      同年，Skerjl 报道了取代的芳基溴在DPPF/Pd(OAc)2 催化体系下可以与Boc保护 的肼进行选择性的芳基化，从而得到酰胺芳基化或胺的芳基化产物。 

      另外，Hartwig报道了芳基溴或氯在Pd2(dba)3 / 2P(t-Bu)3催化体系中，以苯酚钠做碱可以与胺基甲酸叔丁酯进行芳基化从而得到Boc保护的苯胺衍生物。

      Beletskaya 和他的同事报道了钯催化下的脲的芳基化， 该反应进行的条件是芳卤的对位有缺电子基团，催化剂为 Pd2dba3·CHCl3/Xantphos，以Cs2CO3 为碱，二氧六环中 100℃反应可以得到较好的收率。 

      随后， Buchwald发现用Pd(OAc)2或Pd2(dba)3  做催化剂，Xantphos为配体，Cs2CO3为碱，在四氢呋喃,1，4-二氯六环或甲苯里回流可以使大部分酰胺与芳基溴或氯顺利进 行芳基化。在这里， Cs2CO3做碱有其独特的优势，如它可以耐受腈基、硝基、酯和醛等一些常见的基团。但这种反应不太适用于含有酮的酰胺的芳基化，因为酮的a位存 在竞争性的芳基化反应。如下表，作者对不同类型的酰胺芳基化进行了研究： 

      对位有拉电子基的芳基溴可以与不同的酰胺在45-80℃下，以Pd(OAc)2为催化剂顺利进行 (Table 1, entries 1, 3, 4, and 8)。当芳卤的邻或间位有活化基团时，其活性稍低，酰胺芳基化需要更高一点的温度和更多量的催化剂。此时，Pd2(dba)3 比Pd(OAc)2更有效 (Table 1, entries10-14)。同时，活化的芳基碘、芳基氯和 aryl triflate也可以参与酰胺芳基化的反应。除酰胺外，伯、仲碳酰胺和磺酰胺也可以与活化的芳基溴进行 N -芳基化反应。从上表可以看出，碳酰胺的活性和酰胺差不多，但磺酰胺的活性就要差一些了，需要更高的温度如100℃。 

       另外，作者还对未活化的芳卤进行了研究，发现用用Xantphos做配体，Cs2CO3 做碱，二氧六环为溶剂, 电中性或弱富电性的芳卤也可以进行酰胺的芳基化反应（Table 2）。这种情况，用Pd2(dba)3做催化剂才可以使N-芳基化得以进行。芳溴可以和芳酰胺、脂肪酰胺、 (Table 2, entries 3-5), N-甲基酰胺(Table 2, entries 6, 8) 和内酰胺 (Table 2,entries 7, 9-13)在100℃下进行反应。 

合成实例一 

General  Procedure  for  Pd-Catalyzed  Couplings  of  Aryl Halides，Triflates andAmides/Carbamates/Sulfonamides 

     A flame-dried resealable Schlenk tube was charged with Pd(OAc)2 (2.2 mg, 0.01 mmol, 1mol %), Xantphos (8.7 mg, 0.015 mmol, 1.5 mol %), the solid reactant(s) (1.0 mmol of the aryl halide/triflate and 1.2 mmol of the amide/carbamate/sulfonamide), and Cs2CO3 (456mg, 1.4 

mmol).  The Schlenk tube was capped with a rubber septum, evacuated and backfilled with argon; this evacuation/backfill sequence was repeated one additional time.  The liquid reactant(s) and 1,4-dioxane (1 mL) were added through the septum.  The septum was replaced with a teflon screwcap.  The Schlenk tube was sealed, and the mixture was stirred at the indicated temperature (45-110 ) for 6 ℃ -44 h until the starting aryl halide or triflate had been completely consumed as judged by GC analysis or TLC.  The reaction mixture was 

then cooled to room temperature, diluted with dichloromethane (10 mL), filtered, and concentrated in vacuo.  The crude material was purified by flash chromatography on silica gel to give the desired compound with moderate to good yield. 

合成实例二

      A flame-dried resealable Schlenk tube was charged with Pd2(dba)3 (4.6 mg, 0.005 mmol, 1 mol %of Pd), Xantphos (8.7 mg, 0.015 mmol, 1.5 mol %), 2-azetidinone (85 mg,1.2 mmol), and Cs2CO3 (456 mg, 1.4 mmol).  The Schlenk tube was capped with a rubber septum, evacuated, and backfilled with argon; this evacuation/backfill sequence was repeated one additional time.  Methyl 2-bromobenzoate (0.140 mL, 215 mg, 1.0 mmol) and 1,4-dioxane (1 mL) were added through the septum.  The septum was replaced with a Teflon screwcap. The Schlenk tube was sealed, and the mixture was stirred at 100℃ for 35 h until the starting aryl bromide had been completely consumed as judged by GC analysis.  The reaction mixture was then cooled to room temperature, diluted with dichloromethane (10 mL), filtered, and concentrated in vacuo.  The crude material was purified by flash chromatography on silica gel to afford 163 mg (80%) of N-(2-carbomethoxyphenyl)-2-azetidinone as a pale yellow oil. 

来源：化学视角