【作者】 崔歆；

【导师】 郭庆祥；

【作者基本信息】 中国科学技术大学 ， 有机化学， 2008， 博士

【摘要】 钯催化的碳碳键偶联反应在现代有机合成中正发挥越来越重要的作用,如Heck反应和Suzuki反应等。这些偶联反应通常需要1-5 mol%的钯作为催化剂,有机膦化合物作为配体方可顺利进行。由于膦化合物价格昂贵,毒性强以及对空气敏感,使得它们的应用成为问题。因此,在钯催化体系中引入无毒无害价格低廉的非膦配体具有重要意义。在本论文中作者系统研究了一类新型高效的非膦钯催化体系,发现3-(N,N-二甲胺基)丙酸可以替代最近报道的N,N-二甲基甘氨酸,作为一个更加高效的配体参与钯催化的溴苯,碘苯,活化氯苯的Heck反应和Suzuki反应,其TON分别高达10~3和10~4。动力学研究和理论计算表明3-(N,N-二甲胺基)丙酸能比N,N-二甲基甘氨酸更快地促进氧化加成反应,从而具有更好的催化效果。此外,作者制备了新型的化合物3-(N,N-二甲胺基)丙酸钯,能作为溴苯和碘苯Suzuki偶联反应的高效非膦催化剂,这种化合物对空气和水都稳定,廉价易置备,可以使反应获得很高的TON,并且反应条件简单而温和。作者观察到烯烃对Suzuki反应的毒化作用,通过研究这一现象,对Heck反应的活性低于Suzuki反应这一问题提出了机理方面的解释。苯脲是本文中研究的另一种高效的非膦配体,它可以在短时间内使溴苯类化合物的Heck反应,TON高达到10~3,并可以实现室温下TON=10~4的溴苯Suzuki反应。此外,苯脲还可作为Larock吲哚化反应的配体,促使2-溴苯胺与内部炔烃的环化反应,产率高,区域选择性好。1,3-二羰基类化合物(如乙酰丙酮)可以作为氧配体参与溴苯和碘苯类化合物的Heck反应和Suzuki反应,TON为10~3-10~4。作为对羧基配体的改造,对N,N-二齿配体作了深入研究,发现烷基胺或吡啶做为羧基的邻位基团时,可以构成好的N,O-二齿配体。其中性能最好的配体是喹啉-8-羧酸。进而制备出的喹啉-8-羧酸钯是一个结构简单,性质稳定的新型催化剂,促使溴苯,碘苯等的Heck反应和Suzuki反应,TON达到=10~4。更多还原

【Abstract】 Pd-catalyzed C-C bond formation reactions such as the Heck and Suzuki cross couplings are playing increasingly more important roles in modern organic synthesis. These cross coupling reactions are usually performed with 1-5 mol%of Pd catalyst along with phosphine ligands,which sometimes creates practical problems because organophosphines tend to be cxpensive,poisonous,and air sensitive.Accordingly,an important current challenge is to develop Pd catalysts that can utilize inexpensive phosphine-free ligands.In this paper we report several novel and effective phosphine-free Pd catalytic systems.N,N-dimethyl-β-alanine was found to be a more powerful phosphine-free ligand than the previously reported ligand,N,N-dimethylglycine,in the Pd-catalyzed Heck reaction and Suzuki reaction for a variety of aryl bromides,aryl iodides,and activated aryl chlorides with a practical turnover number of 10³.Both kinetic and theoretical studies suggested that N,N-dimethyl-β-alanine led to faster oxidative addition of an aryl halide to Pd than N,N-dimethylglycine.Furthermore,we have synthesized a novel crystalline,air-stable,and moisture-stable Pd salt,Pd（N,N-dimethyl-β-alaninate）₂.This salt was demonstrated to constitute a low-priced,phosphine-free,yet high-turnover-number catalyst for the Suzuki reactions of various aryl bromides and iodides under mild and simple reaction conditions,we observed that the presence of an olefin could dramatically hamper the Suzuki reaction.To the best of our knowledge,this new finding provided interesting mechanistic insights into the lower reactivity of the Heck reaction as compared to the Suzuki reaction.N-phenylurea was found to constitute a highly efficient,yet low-priced, phosphine-free ligand for the Pd-catalyzed Heck and room-temperature Suzuki reactions of aryl bromides and iodides with very high turnover numbers（ca.10³-10⁴）. It is also found that N-phenylurea can be an excellent ligand in Larock indolization of 2-bromoaniline and internal alkynes with high regioselectivity.Some 1,3-dicarbonyl compounds（such as pentane-2,4-dione）as oxygen ligands were found to constitute highiy efficient,yet low-priced and phosphine-free ligands for the Pd-catalyzed Heck and Suzuki reactions of aryl bromides and iodides with very high turnover numbers（ca.10³-10⁴）.Systematic study on N,O-bidentate ligand were held.It was found that alkylamine and pyridine were good neighboring groups to enhance the effect of a carboxylate group in Pd catalysis.The best N,O-bidentate ligand turned out to be quinoline-8-carboxylatc,and Pd（quinoline-8-carboxylalc）₂ constituted an ideal Pd catalyst that was structurally simple,synthetically inexpen ive,and chemically stable. Synthetic examinations demonstrated that Pd（quinoline-8-carboxylate）₂ could smoothly catalyze the Heck and Suzuki reactions of unactivatcd aryl bromides and iodides with fairly high turnover numbers up to ca.10⁴.更多还原