Palladium-catalyzed cross-coupling reactions of 2-diazonaphthoquinones with arylboronic acids

Palladium-catalyzed cross-coupling reactions of 2-diazonaphthoquinones and arylboronic acids proceeded by the treatment with Pd(OAc)₂ in acetic acid to afford 2-aryl-1-naphthols.     

Palladium-catalyzed cross-coupling reactions of silanolates: a paradigm shift in silicon-based cross-coupling reactions

This paper chronicles the conceptual development, proof of principle experiments, and recent advances in the palladium-catalyzed cross-coupling reactions of the conjugate bases of organosilanols. The discovery that led to the design and refinement of this process represents a classical illustration of how mechanistic studies can provide a fertile ground for the invention of new reactions. On the basis of a working hypothesis (which ultimately proved to be incorrect) and the desire to effect silicon-based cross-coupling without the agency of fluoride activation, a mild and practical palladium-catalyzed cross-coupling of alkenyl-, aryl-, and heteroaryl silanolates has been developed. The mechanistic underpinnings, methodological extensions, and the successful applications of this technology to the synthesis of complex molecules are described.     

Palladium-catalyzed cross-coupling reactions in total synthesis

In studying the evolution of organic chemistry and grasping its essence, one comes quickly to the conclusion that no other type of reaction plays as large a role in shaping this domain of science than carbon-carbon bond-forming reactions. The Grignard, Diels-Alder, and Wittig reactions are but three prominent examples of such processes, and are among those which have undeniably exercised decisive roles in the last century in the emergence of chemical synthesis as we know it today. In the last quarter of the 20th century, a new family of carbon-carbon bond-forming reactions based on transition-metal catalysts evolved as powerful tools in synthesis. Among them, the palladium-catalyzed cross-coupling reactions are the most prominent. In this Review, highlights of a number of selected syntheses are discussed. The examples chosen demonstrate the enormous power of these processes in the art of total synthesis and underscore their future potential in chemical synthesis.     

The effect of vicinyl olefinic halogens on cross-coupling reactions using Pd(0) catalysis

(trans) 1-Chloro-2-iodoethylene (3), (trans) 1-bromo-2-iodoethylene (4), (trans) 1,2-diiodoethylene (5) and (cis and trans) 1,2-dibromoethylene (11) were reacted under Suzuki, Sonogashira and Negishi cross-coupling conditions using Pd catalysis to obtain mono coupled products. Only olefin template 3 provided the desired coupling products reliably under all reaction conditions. Compound 5 did not provide cross coupled products under any of the reaction conditions used. The Negishi reaction was the only one that worked for templates 4 and 11. Studies indicate that oxidative addition of the most reactive carbon-halogen bond to Pd(0) is followed by elimination of the second halide, when the second halide is a bromide or an iodide. This happens to a much lesser degree when the second halogen is a chloride.     

Bifunctional solid catalysts for chemoselective hydrogenation-cyclisation-amination cascade reactions of relevance for the synthesis of pharmaceuticals

The benzodiazepines olanzapine and clozapine are nowadays manufactured by a three-step process with a final yield below 50%. An approach to environmentally-friendly intensive processes consists in the development of multifunctional solid catalyst able to catalyze multistep reactions. Here, a bifunctional metal-acid solid catalyst has been prepared and is able to carry out hydrogenation-cyclisation-amination reactions in a cascade process. The catalytic system is illustrated for the synthesis of these important antipsychotics, being an alternative for the current industrial process that requires three steps batch reactions, using mineral acids and bases, and stoichiometric amounts of SnCl₂.     

Pd-CNT-catalyzed ligandless and additive-free heterogeneous Suzuki-Miyaura cross-coupling of arylbromides

Pd-CNT efficiently catalyzed Suzuki-Miyaura coupling of arylbromides under ligandless and additive-free conditions in aqueous media. For hydrophilic substrates, the reaction could be carried out in neat water.     

A new palladium catalyzed protocol for atom-efficient cross-coupling reactions of triarylbismuths with aryl halides and triflates

A new palladium catalyzed protocol for an atom-efficient cross-coupling reaction of triarylbismuths with aryl halides and triflates has been described. The palladium catalytic system with Cs₂CO₃ base was found to be very efficient in DMA solvent to furnish excellent yields of cross-coupled functionalized biaryls in short reaction times.     

钯纳米颗粒负载在聚苯胺材料上制得催化Suzuki-Miyaura偶联反应的高效催化剂

在最近的几十年里,金属钯催化的Suzuki-Miyaura偶联反应已经得到了越来越多的关注,被广泛应用于药物、天然产物以及新材料的合成.与此同时均相催化剂发展迅速,高效的配体和大量的设计被用于Suzuki-Miyaura偶联反应中,但是钯催化剂的配体通常很昂贵和难以合成,因此钯催化剂系统的回收是非常有价值的,不仅是经济上的原因,同时也避免了产品的污染,所以发展非均相催化剂是必要的.近年来,研究学者们致力于设计非均相的钯催化剂,如将钯纳米颗粒负载到金属有机骨架、介孔分子筛以及活性炭等多种材料上得到的非均相钯催化剂并应用于Suzuki-Miyaura偶联反应中.我们主要介绍了钯纳米颗粒被负载在含磷配体的交联的聚苯胺材料上制得负载的钯催化剂,首先通过钯催化的三(4-碘苯基)胺与金刚烷基膦的C–P偶联,再由钯催化三(4-碘苯基)胺与对苯二胺的C–N偶联,进而得到钯纳米颗粒负载在含金刚烷基膦的聚苯胺材料上的催化剂Pd@PAN-Ad-0.5(钯含量为0.58 wt%),同时我们对催化剂进行了一些表征,如TEM,SEM,XRD,EDX,XPS,FT-IR,ICP等.通过TEM分析,我们发现钯纳米颗粒在聚合物表面分布均匀,并且金属钯的平均粒径为2–3 nm;EDX检测显示催化剂含有C,N,P,Pd,I元素,说明钯负载到含金刚烷基膦的聚苯胺材料上的催化剂Pd@PAN-Ad-0.5已经形成,并被用于Suzuki-Miyaura偶联反应.我们对反应体系中的各种影响因素进行了优化,包括溶剂、碱、反应时间、催化剂加入量以及不同的催化剂的优化,最终确定了最佳反应条件;对于带有不同取代基(如腈基、甲氧基、醛基、酮基以及硝基)的氯代芳烃和溴代芳烃与苯硼酸的Suzuki-Miyaura反应,以较少的催化剂使用量(0.075 mol%Pd)就能获得较高的相应的联苯产物收率.此外,催化剂Pd@PAN-Ad-0.5在偶联反应中具有较高的反应活性的同时,还具有较好的回收使用能力(至少能够回收使用5次),循环使用4次以后还具有较高的催化活性.为了探索催化剂Pd@PAN-Ad-0.5在工业上的应用,由于4'-氯-2-硝基-1,1'-联苯是合成啶酰菌胺药物的重要中间体,因此我们使用催化剂Pd@PAN-Ad-0.5催化2-硝基氯苯与4-氯苯硼酸的偶联反应,目标产物4'-氯-2-硝基-1,1'-联苯的收率高达96%.我们相信这类催化剂应用于实验室或工业上合成联苯化学品具有较大的潜力.     

A general and efficient method for the palladium-catalyzed cross-coupling of thiols and secondary phosphines

The general and efficient cross-coupling of thiols with aryl halides was developed utilizing Pd(OAc)₂/1,1′-bis(diisopropylphosphino)ferrocene as the catalyst. The substrate scope is broad and includes a variety of aryl bromides and chlorides, which can be coupled to aliphatic and aromatic thiols. This catalyst system has the widest substrate scope of any reported to date. The present catalyst system also enables the palladium-catalyzed coupling of secondary phosphines with aryl bromides and chlorides.     

Palladium-catalyzed cross-coupling reaction of allyl acetates with pinacol aryl- and vinylboronates

Pinacol boronates 2 couple efficiently with allyl acetates 1 in the presence of a palladium catalyst prepared in situ from PdCl₂ and TFP to give the coupled products 3 in moderate to good yields under mild conditions.     

Palladium-catalyzed cross-coupling of trimethoxysilylbenzene with aryl bromides and chlorides using phosphite ligands

Phosphites were employed as ligands in palladium-catalyzed Hiyama coupling reactions. The optimized reaction conditions were equimolar amounts (5 mol % each) of Pd(acac)₂ and phosphite 1 in p-xylene at 80 °C with TBAF as an additive. This catalyst system exhibited high activities in the reactions with trimethoxysilylbenzene and aryl bromides that have electron-donating or electron-withdrawing groups. In the case of aryl chlorides, substrates possessing electron-withdrawing groups gave the coupled products in high yields.     

Palladium-catalyzed cross-coupling reactions of amines with alkenyl bromides: a new method for the synthesis of enamines and imines

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.     

Functionalised butanediacetal-protected 1,2-diols as suitable partners for Pd-catalysed cross-coupling reactions

A new method for the synthesis of dienes and enynes containing chiral 1,2-diols is described. The strategy is based on the Pd-catalysed cross-coupling reactions of a series of vinyl and alkynyl asymmetric butanediacetal-protected building blocks. After the coupling, removal of the protecting group leads to the desired functionalised dienes and enynes.     

Double Heck Cross‐Coupling Reactions of Dibrominated Pyridines

Double Heck cross‐coupling reactions of 2,3‐ and 3,5‐dibromopyridine with various alkenes afforded the corresponding novel di(alkenyl)pyridines. The Heck reaction of 2,5‐dibromopyridine unexpectedly afforded 5,5′‐di(alkenyl)‐2,2′‐bipyridines by palladium‐catalyzed dimerization to give 5,5′‐dibromo‐2,2′‐bipyridine and subsequent twofold Heck reaction.     

Preparation of 2,3-disubstituted indoles by sequential Larock heteroannulation and silicon-based cross-coupling reactions

A simple and convergent synthesis of 2,3-disubstituted indoles has been developed using a sequential Larock indole synthesis and silicon-based, cross-coupling reaction. Substituted 2-iodoanilines reacted with an alkynyldimethylsilyl tert-butyl ether to afford indole-2-silanols under the Larock heteroannulation conditions after hydrolysis. The corresponding sodium 2-indolylsilanolate salts successfully engaged in cross-coupling with aryl bromides and chlorides to afford multi-substituted indoles. The development of an alkynyldimethylsilyl tert-butyl ether as a masked silanol equivalent enabled a smooth heteroannulation process and the identification of a suitable catalyst/ligand combination provided for a facile cross-coupling reaction.     

Regioselectivity in alkenyl(aryl)-heteroaryl Suzuki cross-coupling reactions of 2,4-dibromopyridine. A synthetic and mechanistic study

2,4-Dibromopyridine undergoes a regioselective Suzuki cross-coupling reaction at position 2 with several alkenyl(aryl) boronic acids to render 4-bromo-2-carbon substituted pyridines, difficult to be prepared otherwise, in good yields under palladium catalysis, either Pd(PPh₃)₄/TlOH or Pd₂dba₃/PCy₃/K₃PO₄ at 25 °C. This behavior is explained on the basis of the electrophilic character of both C-Br bonds, being their relative reactivity in 2,4-dibromopyridine similar to that in the corresponding monobromopyridines. In addition, the dicoupled compound 6 is not formed through a double oxidative addition of 2,4-dibromopyridine to Pd(PPh₃).