【作者】 李新建；

【导师】 吴养洁； 吴豫生；

【作者基本信息】 郑州大学 ， 有机化学， 2014， 博士

【摘要】 以2-吡啶甲酸为原料通过脱羧交叉偶联反应，实现了2-吡啶芳（杂）基化；完成了芳（杂）基硼酸酯及其衍生物的叔丁氧羰基化反应，合成了一系列芳（杂）基叔丁醇酯；在硝酸银存在的条件下，以TMS-CF3为原料，实现了吡啶氮氧化物的三氟甲基化。1.通过钯催化的2-吡啶甲酸与溴代芳烃的脱羧交叉偶联实现2-吡啶的芳（杂，苄）基化反应以廉价稳定的2-吡啶甲酸和溴代芳烃为反应底物、5mol%PdCl2为催化剂，6mol%的BINAP作为配体，以K2CO3作为碱，DMA为溶剂，在少量亚铜存在的条件下实现了2-吡啶芳（杂）基化，并用该催化体系合成了一系列的2-芳基吡啶的衍生物。研究发现该催化体系几乎不受取代基团的电子效应的影响。该反应同样适用于2-杂芳类吡啶，可以得到较好收率的目标产物(Scheme1)。Scheme1Decarboylative cross-coupling reactions of2-picolinic acid2.通过钯催化的芳（杂）基硼酸酯及其衍生物与BOC酸酐偶联反应实现的芳（杂）环的叔丁氧羰基化以芳（杂）基硼酸酯及其衍生物和BOC酸酐为原料，醋酸钯为催化剂，三苯基膦为配体，二氧六环为反应溶剂，通过偶联反应实现了芳（杂）环的叔丁氧羰基化，避免了一氧化碳的使用，为羧酸的合成提供了一个新思路。该催化体系有很好的稳定性和广泛的适用性。底物无毒适用性好，而且廉价易得。反应操作简单，环境友好，专一性强，可以得到中等到高的收率。一系列含有苯基，吡啶，以及喹啉的硼酸或硼酸酯都适用于该催化体系(Scheme2)。Scheme2Preparation of tert-butyl esters via Pd-catalyzed tert-butoxycarbonylation3.通过Ag促进的吡啶氮氧化物α-H的活化实现2-吡啶氮氧化物的三氟甲基化反应以TMSCF3（Rupper-Prakash试剂）为原料，在Ag存在的条件下，与吡啶氮氧化物的α位反应，生成2-三氟甲基吡啶氮氧化物及其衍生物。需要指出的是，该反应不同于Prakash试剂的常见的亲核取代反应。该方法通过自由基反应机理引入三氟甲基，定位效应好、反应条件温和、操作方便(Scheme3)。Scheme3Ag promoted trifluoromethylation of pyridine nitrogen oxides更多还原

【Abstract】 In this thesis, the novel palladium-catalyzed decarboxylative cross-coupling reactions of2-picolinic acid with aryl-and heteroaryl-bromides including benzenes, naphthalenes, pyridinesand quinolines for C-C bond formation has been successfully achieved. A series of tert-butylesters (Ester tert-butoxide) was synthesised via the palladium-catalyzed alkoxycarbonylreactions of boronic acid or boronic acid pinacol esters with di-tert-butyl dicarbonate. A novelmethod has been developed for the preparation of2-trifluoromethyl pyridine and derivative fromthe reaction of pyridine nitrogen oxides with TMS-CF3under mild reaction conditions.1. Arylation of2-Substituted pyridines via Pd-Catalyzed Decarboxylative Cross-CouplingReactions of2-Picolinic acidA novel synthetic route to2-aryl-and heteroaryl-pyridines was discovered and developedvia the palladium-catalyzed decarboxylative cross-coupling reactions of2-picolinic acid witharyl-and heteroaryl-bromides using5mol%PdCl2as catalyst,6mol%BINAP as ligand,K2CO3as base, DMA as solvent. In addition, a series of substituted2-aryl-and heteroaryl-pyridines compounds including benzenes, naphthalenes, pyridines and quinolines were suitablefor this reaction (Scheme1).Scheme1Decarboylative cross-coupling reactions of2-Picolinic acid2. Preparation of tert-Butyl Esters via Pd-catalyzed tert-Butoxycarbonylation ofAryl(hetero) Boronic Acid DerivativesA novel one-step route to aryl (heteroaryl) tert-butyl esters was developed via thepalladium-catalyzed cross-coupling reactions of boronic acid or boronic acid pinacol esters with di-tert-butyl dicarbonate. The cross-coupling reactions can produce up to94%yields desiredproducts by using palladium acetate and triphenylphosphine as catalyst system, dioxane as asolvent. In the reaction, cheaper, greener and non-toxic di-tert-butyl dicarbonate has been usedcompared to traditional tert-butyloxycarbonylation method. Moreover, a wide range of substratesincluding benzenes, pyridines and quinolines boronic acids or boronic acid pinacol esters can fitthis system as well.(Scheme2).Scheme2Preparation of tert-butyl esters via Pd-catalyzed tert-butoxycarbonylation3. Ag Promoted Trifluoromethylation of Pyridine Nitrogen Oxides via α-H of PyridineNitrogen Oxides ActivationA novel method has been developed for the preparation of2-trifluoromethyl pyridinederivatives from the reaction of pyridine nitrogen oxides with TMS-CF3under mild conditions. Itis worthy to note that the reaction could be carried on in the presence of F-resouce and Ag+. Thecorresponding products were obtained in good selectivity (Scheme3).Scheme3Ag promoted trifluoromethylation of pyridine nitrogen oxides更多还原