Sequential Processes in Palladium-Catalyzed Silicon-Based Cross-Coupling

Although developed somewhat later, silicon-based cross-coupling has become a viable alternative to the more conventional Suzuki–Miyaura, Stille–Kosugi–Migita, and Negishi cross-coupling reactions because of its broad substrate scope, high stability of silicon-containing reagents, and low toxicity of waste streams. An empowering and yet underappreciated feature unique to silicon-based cross-coupling is the wide range of sequential processes available. In these processes, simple precursors are first converted to complex silicon-containing cross-coupling substrates, and the subsequent silicon-based cross-coupling reaction affords an even more highly functionalized product in a stereoselective fashion. In so doing, structurally simple and inexpensive starting materials are quickly transformed into value-added and densely substituted products. Therefore, sequential processes are often useful in constructing the carbon backbones of natural products. In this review, studies of sequential processes involving silicon-based cross-coupling are discussed. Additionally, the total syntheses that utilize these sequential processes are also presented.     

钯催化卤代芳烃的胺化反应研究

钯催化卤代芳烃胺化是形成CAr-N的重要方法。配体的发展扩展了底物的适用范围，提高了反应的选择性，实现了廉价易得的氯代芳烃的胺化，弱碱的使用提高了官能团的兼容性，因此Pd催化芳胺化广泛应用于合成芳胺类化合物。本文以卤代芳烃为线索，对钯催化偶联胺化反应的研究进展进行了综述和展望。     

Tandem C(sp3)−H Arylation/Oxidation and Arylation/Allylic Substitution of Isoindolinones

Isoindolinones comprise an important class of medicinally active compounds. Herein we report a straightforward functionalization of isoindolinones with aryl bromides (22 examples) using a palladium(II) acetate/NIXANTPHOS‐based catalyst system. Additionally 3‐aryl‐3‐hydroxyisoindolinone derivatives, which exhibit anti‐tumor activity, can be accessed via a tandem reaction. Thus, when the arylation product is exposed to air under basic conditions, in situ oxidation takes place to install the 3‐hydroxy group. Furthermore, a tandem arylation/allylic substitution reaction is advanced in which both the arylation and allylic substitution are catalyzed by the same palladium catalyst. Finally, a tandem arylation/alkylation procedure is presented. These tandem reactions enable the synthesis of a variety of structurally diverse isoindolinone derivatives from common starting materials.

     

三丁基芳基(苄基)锡在芳烃化合物合成中的应用

本文研究了以二（三苯基膦）苄基氯化钯为催化剂，以三丁基芳基（苄基）锡为试剂与芳基、苄基卤化物的交叉偶联反应，并对反应的溶剂，催化剂等反应条件进行了比较和选择     

钯催化脱羧偶联环化反应合成2-取代吡唑并[1,5-a]吡啶类化合物

在Pd Cl2/PPh3催化条件下,N-氨基吡啶盐和取代丙炔酸反应,合成了6个2-取代吡唑并[1,5-a]吡啶类化合物。考察了不同催化剂、配体、溶剂和碱等因素对反应的影响,获得优化反应条件:Pd Cl2/PPh3作催化体系,碳酸钾作碱,二氯甲烷为溶剂,80℃下反应24 h,收率为59%~77%。     

A Coherent Mechanistic Rationale for Additive Effects and Autoinductive Behaviour in Proline‐Mediated Reactions

Differences in the kinetic behaviour of aldol reactions compared to aminoxylation and amination reactions are rationalized by consideration of the rate‐determining step in each case. Both autoinductive behaviour and the rate‐enhancing effect of additives are attributed to an effect on the enamine formation step.     

Layered-Double-Hydroxide-Supported Pd(TPPTS)2Cl2: A New Heterogeneous Catalyst for Heck Arylation of Olefins

The Pd(TPPTS)₂Cl₂ (TPPTS: triphenylphosphine trisulfonate, sodium salt) complex is immobilized on layered double hydroxides by the ion-exchange method. This heterogeneous catalyst is successfully used in Heck arylation of olefins. The catalyst can be recycled several times with almost consistent activity.     

钯催化Suzuki偶联反应的研究进展

金属Pd催化的Suzuki偶联反应是碳-碳偶联反应中重要的反应之一。综述了近年来Pd催化Suzuki偶联反应的研究进展,其中包括Suzuki反应机理、配体种类及其在有机合成中的应用。介绍了含N、P配体的钯催化剂和碳纳米管、磁性材料、多孔材料、水滑石、金属氧化物、高分子材料等负载的无配体钯催化剂的研究进展。     

Simple Methodology for Heck Arylation at C‐8 of Adenine Nucleosides

A simple method for the arylation of 8‐vinyladenine nucleoside derivatives is reported. With a broad set of aryl iodides and bromides, the reaction is catalyzed by the simple combination palladium acetate/tris(o‐tolyl)phosphine/triethylamine [Pd(OAc)₂/(o‐tol)₃P/Et₃N]. As expected, aryl chlorides are more difficult coupling partners but some undergo reactions with more exotic catalysts. Although trans‐olefins are the major products, minor amounts of cis‐isomers are detected in some cases, and a post‐arylation mechanism for their formation is proposed. Finally, by subtle catalyst modulation chemoselective N‐arylation of the nucleoside can be achieved in the presence of the vinyl moiety.     

Palladium‐Catalyzed Regioselective and Stereoselective Oxidative Heck Arylation of Allylamines with Arylboronic Acids

A general and convenient palladium‐catalyzed oxidative Heck arylation of both N‐protected and N,N‐diprotected allylic amines with arylboronic acids under mild conditions has been developed. The catalyst system, consisting of Pd(OAc)₂ (palladium acetate), AgOAc (silver acetate) and KHF₂ (potassium hydrogen fluoride), could efficiently catalyze the coupling reaction in acetone without the aid of any ligand, leading exclusively to the γ‐arylated allylic amine products in good to excellent yields. This method is highlighted with excellent regio‐ and stereocontrol and remarkable functional group tolerance. The carbamate moiety in allylic amine substrates is of crucial importance to the catalytic performance, and the chelation between the carbonyl O (oxygen) and Pd (palladium) atoms is believed to be responsible for the high regioselectivity and stereoselectivity observed.     

Mechanistic Insights from Substrate Preference in Unsaturated Glucuronyl Hydrolase

Natural and synthetic unsaturated glucuronides were tested as substrates for Clostridium perfringens unsaturated glucuronyl hydrolase to probe its mechanism and to guide inhibitor design. Of the natural substrates, a chondroitin disaccharide substrate with sulfation of the primary alcohol on carbon 6 of its N‐acetylgalactosamine moiety was found to have the highest turnover number of any substrate reported for an unsaturated glucuronyl hydrolase, with k_cat=112 s^?1. Synthetic aryl glycoside substrates with electron‐withdrawing aglycone substituents were cleaved more slowly than those with electron‐donating substituents. Similarly, an unsaturated glucuronyl fluoride was found to be a particularly poor substrate, with k_cat/K_m=44 nM ^?1 s^?1—a very unusual result for a glycoside‐cleaving enzyme. These results are consistent with a transition state with positive charge at carbon 5 and the endocyclic oxygen, as anticipated in the hydration mechanism proposed. However, several analogues designed to take advantage of strong enzyme binding to such a transition state showed little to no inhibition. This result suggests that further work is required to understand the true nature of the transition state stabilised by this enzyme.     

Palladium(II)/Copper Halide/Solvent Combination for Selective Intramolecular Domino Reactions of Indolecarboxylic Acid Allylamides: An Unprecedented Arylation/Esterification Sequence

Intramolecular oxidative palladium‐catalyzed reactions of indolylallylamides in the presence of the couple bis(acetonitrile) palladium dichloride and copper(II) halide are described. Starting from 2‐ and 3‐indolylallylamides and involving in both cases the C‐3 position of the indole nucleus, variously substituted β‐carbolinones were obtained by arylation/halogenation, arylation/esterification or arylation/carboalkoxylation processes. On the other hand, an unusual aminohalogenation/halogenation sequence performed on 2‐indolylallylamides gave rise to pyrazino[1,2‐a]indole products. The carboesterification process is the result of an unknown path that involves the DMF or DMA used as solvent. The outcome of the reactions of the 3‐indolylallylamides arises from a totally selective 1,2‐migration of the acyl group on the supposed spiro intermediates formed from the nucleophilic attack of the C‐3 indole position.     

Palladium‐Catalyzed,Highly Efficient,Regiocontrolled Arylation of Electron‐Rich Allylamines with Aryl Halides

The highly efficient and regioselective palladium‐catalyzed Heck coupling of aryl bromides with electron‐rich allylamine derivatives is described. It was found that the choice of solvent, olefin, ligand and additive had a fundamental influence on the regioselectivity and reactivity of the reaction. The combination of palladium acetate [Pd(OAc)₂] and 1,3‐bis(diphenylphosphino)propane (dppp) in ethylene glycol (EG) constitutes a highly effective catalyst system for internal arylation of N‐Boc‐allylamine (tert‐butyl methyl allyliminodicarbonate) with aryl bromides to give good to excellent regioselectivities, while the catalyst system consisting of Pd(OAc)₂, tetrabutylammonium bromide (TBAB) and 2,2,6,6‐tetramethyl‐1‐piperidinyloxy (TEMPO) additive allows for a variety of aryl bromides to react efficiently with N,N‐(Boc)₂‐allylamine (di‐tert‐butyl allyliminodicarbonate) in water to exclusively afford the linear (E)‐allylamine products in high yields.     

Intramolecular Direct Arylation and Heck Reactions in the Formation of Medium‐Sized Rings: Selective Synthesis of Fused Indolizine,Pyrroloazepine and Pyrroloazocine Systems

The intramolecular palladium‐catalyzed reaction of N‐(iodoarylalkyl)pyrroles can be applied for the selective synthesis of medium‐sized rings by choosing the appropriate catalytic systems to direct the reaction to the alkene or to the pyrrole nucleus. These reactions can also be extended to the corresponding heteroaryl halides. Thus, reaction conditions have been established to access selectively to (hetero)fused indolizine, pyrroloazepine and pyrroloazocine systems.

     

Heck–Matsuda Arylation of Olefins Through a Bicatalytic Approach: Improved Procedures and Rationalization

The scope of the palladium‐catalyzed Heck–Matsuda reaction, proceeding through the catalytic activation of anilines into the corresponding diazonium salts, has been considerably extended and is now working with deactivated electrophiles. Two different procedures, using catalytic amounts of both palladium and acid, have been optimized allowing the concept of bicatalysis to cover the complete electronic range of anilines. These environmentally friendly procedures proceed under very mild conditions, at room temperature in methanol, and only generate tert‐butyl alcohol, water and nitrogen as by‐products. Rationalization of reaction outcomes encountered in this work has been discussed with the support of computational studies.

     

2-Aminopyridine functionalized cellulose based Pd nanoparticles: An efficient and ecofriendly catalyst for the Suzuki cross-coupling reaction

A palladium catalyst supported on 2-aminopyridine functionalized cellulose was synthesized and fully characterized by inductively coupled plasma atomic emission spectroscopy, transmission electron microscope, Fourier transform infrared spectroscopy, thermogravimetric analysis and X-ray photoelectron spectrometry. This catalyst can be applied in the Suzuki cross-coupling reaction of aryl halides with arylboronic acids in 50% ethanol to afford biaryls in good yields, and easily recycled by simple filtration after reaction without the loss of metal Pd.

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Palladium‐Catalyzed Suzuki Carbonylative Reaction of α‐Halomethyl Oxime Ethers: A Regioselective Route to Unsymmetrical 1,3‐Oxyiminoketones

The three‐component reaction of α‐halomethyl oxime ethers, boronic acids and carbon monoxide at atmospheric pressure catalyzed by tetrakis(triphenylphosphine)palladium(0) gives efficiently unsymmetrical β‐alkoxyimino carbonyl compounds with total control of the regioselectivity, in high yield and atomic economy. Simple commercially available starting materials are used in this synthetic procedure. The three components assembly takes place preferentially versus the competing direct coupling or other possible side reactions. The mechanism of the transformation was investigated by NMR and intermediate palladium(II) complexes were detected.

     

Control of the β-Hydride Elimination Making Palladium-Catalyzed Coupling Reactions more Diversified

Pd(II)-catalyzed coupling reactions were developed using β-heteroatom elimination and protonolysis reaction to quench the carbon–palladium bond in the presence of halide ions or nitrogen ligands (pyridine, bipyridine, phenanthroline, etc.) for regenerating the divalent palladium species. Halide ions or nitrogen ligands are necessary for the catalytic cycle and high yield of the reactions. For Pd(0)-catalyzed reactions, control of β-hydride elimination is also a challenge for making coupling reactions more diversified. Different kinds of ligands were used to make the coupling reaction suitable for aliphatic compounds. Recently, examples using chloride ion or bathophenanthroline for this purpose were also developed.     

Competing Regiochemical Pathways in the Heck Arylation of 1,2‐Dihydronaphthalene

The Heck reaction of aryl iodides with 1,2‐dihydronaphthalene has been examined. Two separate reaction pathways are observed under all the conditions tried. Arylation adjacent to the aromatic ring leads to a subsequent double bond shift such that the product is a 1‐aryl‐1,2‐dihydronaphthalene. The alternative regiochemistry leads to production of the corresponding 3‐aryl‐1,2‐dihydronaphthalene, and labelling studies with specifically deuterated alkenes demonstrate that this is most likely to be the result of a trans Pd‐H elimination pathway. The ratio always varies between 75 : 25 in favour of the 3‐aryl product (Jeffery conditions) to 70 : 30 in favour of the 1‐aryl product.