Barluenga José, Fernández M Alejandro, Aznar Fernando, Valdés Carlos
Instituto Universitario de Química Organometálica Enrique Moles, Universidad de Oviedo, 33071 Oviedo, Spain.
Chemistry. 2004 Jan 23;10(2):494-507. doi: 10.1002/chem.200305406.
The palladium-catalyzed cross-coupling reaction of alkenyl bromides with secondary and primary amines gives rise to enamines and imines, respectively. This new transformation expands the applicability of palladium-catalyzed C-N bond forming reactions (the Buchwald-Hartwig amination), which have mostly been applied to aryl halides. After screening of different ligands, bases, and solvents, the catalytic combination [Pd(2)(dba)(3)]/BINAP in the presence of NaOtBu in toluene gave the best results in the cross-coupling of secondary amines with 1-bromostyrene (dba=dibenzylideneacetone, BINAP=2,2'-bis(diphenylphosphino)-1,1'-binaphthyl). The corresponding enamines are obtained cleanly and in nearly quantitative yields. However, steric hindrance seems to be a limitation of the reaction, as amines carrying large substituents are not well converted. The same methodology can be applied to the coupling of secondary amines with 2-bromostyrene. Moreover, the reaction with substituted 2-bromopropenes allows regioselective synthesis of isomerizable terminal enamines without isomerization of the double bond. The best catalytic conditions for the cross-coupling of 1-bromostyrene with primary amines include again the use of the Pd(0)/BINAP/NaOtBu system. The reaction gives rise to the expected imines in very short times and with low catalyst loadings. A set of structurally diverse imines can be prepared by this methodology through variations in the structure of both coupling partners. However, 2-bromostyrene failed to give good results in this coupling reaction, probably due to product inhibition of the catalytic cycle. Competition experiments of vinyl versus aryl amination reveal that the reaction occurs preferentially on vinyl bromides.
烯基溴化物与仲胺和伯胺的钯催化交叉偶联反应分别生成烯胺和亚胺。这种新的转化扩展了钯催化形成C-N键反应（布赫瓦尔德-哈特维希胺化反应）的适用性，该反应大多应用于芳基卤化物。在筛选了不同的配体、碱和溶剂后，在甲苯中，[Pd₂(dba)₃]/联萘二苯基膦（BINAP）催化组合在叔丁醇钠存在下，在仲胺与1-溴苯乙烯的交叉偶联反应中给出了最佳结果（dba = 二亚苄基丙酮，BINAP = 2,2'-双（二苯基膦基）-1,1'-联萘）。相应的烯胺能够被干净地得到，且产率接近定量。然而，空间位阻似乎是该反应的一个限制，因为带有大取代基的胺转化效果不佳。相同的方法可应用于仲胺与2-溴苯乙烯的偶联反应。此外，与取代的2-溴丙烯的反应能够区域选择性地合成可异构化的末端烯胺，而双键不会异构化。1-溴苯乙烯与伯胺交叉偶联的最佳催化条件同样包括使用Pd(0)/BINAP/叔丁醇钠体系。该反应在极短时间内以低催化剂用量生成预期的亚胺。通过改变两种偶联反应物的结构，利用这种方法可以制备一系列结构多样的亚胺。然而，2-溴苯乙烯在该偶联反应中未能给出良好结果，可能是由于产物对催化循环的抑制。乙烯基与芳基胺化的竞争实验表明，反应优先发生在乙烯基溴上。
