Cross-coupling of C(sp)-H Bonds with Organometallic Reagents via Pd(II)/Pd(0) Catalysis**

Palladium-catalyzed C-H activation/C-C bond-forming reactions have emerged as a promising class of synthetic tools in organic chemistry. Among the many different means of forging C-C bonds using Pd-mediated C-H activation, a new horizon in this field is Pd(II)-catalyzed cross-coupling of C-H bonds with organometallic reagents via a Pd(II)/Pd(0) catalytic cycle. While this type of reaction has proven to be effective for the selective functionalization of aryl C(sp(2))-H bonds, the focus of this review is on Pd(II)-catalyzed C(sp(3))-H activation/C-C cross-coupling, a topic of particular importance because reactions of this type enable fundamentally new methods for bond construction. Since our laboratory's initial report on cross-coupling of C-H bonds in 2006, this area has expanded rapidly, and the unique ability of Pd(II) catalysts to cleave and functionalize alkyl C(sp(3))-H bonds has been exploited to develop protocols for forming an array of C(sp(3))-C(sp(2)) and C(sp(3))-C(sp(3)) bonds. Furthermore, enantioselective C(sp(3))-H activation/C-C cross-coupling has been achieved through the use of chiral amino acid-derived ligands, offering a novel technique for producing enantioenriched molecules. Although this nascent field remains at an early stage of development, further investigations hold the potential to revolutionalize the way in which chiral molecules are synthesized in industrial and academic laboratories.     

Fe3O4-carbon spheres core–shell supported palladium nanoparticles:A robust and recyclable catalyst for suzuki coupling reaction

Suzuki-Miyaura(S-M) is regarded the most powerful way for synthesis biaryls, triaryls, or incorporating of substituted aryl moieties in organic preparation by the cross-coupling of aryl boronic acid with aryl halides using the Pd catalyst. This work reports the combining of the hydrothermal and microwaveassisted protocol to convert the glucose to magnetic carbon spheres(Fe₃O₄-CSPs) decorated with Pd nanoparticles(NPs) as the catalyst for Suzuki-Miyaura cross-coupling reacti...     

A Reusable Polymer-Anchored Palladium(II) Schiff Base Complex Catalyst for the Suzuki Cross-Coupling,Heck and Cyanation Reactions

A new polymer-anchored Pd(II) complex has been synthesized, characterized and its catalytic activity was investigated for the Suzuki cross-coupling reaction between aryl halides and arylboronic acid in the presence of K₂CO₃ as a base, for Heck olefination of aryl halides with alkenes, and for cyanation reaction of aryl iodides with K₄Fe(CN)₆ in presence of Et₃N as base. The key features of the catalyst include rapid reactions with excellent conversion without the use of phosphine ligands and total stability under the reactions conditions. The catalyst was recovered by simple filtration and reused five-times without significant loss of catalytic activity.     

钯催化草酸钾盐与碘苯脱羧偶联反应的研究

利用乙二酸单乙酯酸钾和碘苯在钯催化条件下脱羧偶联反应.通过改变催化剂、溶剂得到了最优化的反应条件:以三氟乙酸钯为催化剂,N-甲基吡咯烷酮为溶剂,乙二酸单乙酯酸钾和碘苯于140℃得到产率为82％的苯甲酸乙酯;同样乙二酸单丁酯酸钾也取得了理想的收率.     

Cross coupling of non-activated alkyl halides by a nickel pincer complex

Non-activated alkyl halides are challenging substrates for cross-coupling reactions because they are reluctant to undergo oxidative addition and because metal alkyl intermediates are prone to beta-H elimination. Despite recent progress, well-defined catalysts are rare. We recently prepared Ni complexes with a chelating pincer-type bis(amino)amide ligand. The chloride complex [((Me)NN2)NiCl] is an active (pre)catalyst for the coupling of non-activated alkyl halides with alkyl, aryl, and heteroaryl Grignard reagents. The catalysis tolerates a wide range of functional groups such as keto, ester, amide, acetal, indole, furan, nitrile, etc. The Ni complex also catalyzes direct alkylation of alkynes and aromatic heterocycles.     

Stille Reactions with Tetraalkylstannanes and Phenyltrialkylstannanes in Low Melting Sugar‐Urea‐Salt Mixtures

The transfer of simple alkyl groups in Stille reactions usually requires special solvents (HMPA) or certain organotin reagents (stannatranes, monoorganotin halides) to be efficient. Using low‐melting mixtures of sugar, urea and inorganic salt as solvent, a fast and efficient palladium‐catalyzed alkyl transfer with tetraalkyltin reagents was observed. The high polarity and nucleophilic character of the solvent melt promotes the reaction. Stille biaryl synthesis using electron‐poor and electron‐rich aryl bromides proceeds with quantitative yields in the sugar‐urea‐salt melt. Catalyst loading may be reduced to 0.001 mol % and the catalyst melt mixture remains active in several reaction cycles. Showing the same or improved performance for Stille reactions than organic solvents and allowing a very simple work up, sugar‐urea‐salt melts are a non‐toxic and cheap alternative reaction medium available in bulk quantities for the catalytic process.     

Enantioselective cross-coupling of anhydrides with organozinc reagents: the controlled formation of carbon-carbon bonds through the nucleophilic interception of metalacycles

The construction of carbon-carbon bonds, particularly with concomitant control of newly formed asymmetric centers, is of paramount importance for the development of synthetic routes to complex organic molecules. While cross-coupling reactions for the generation of sp(2) carbon centers are well established, similar methodology for the formation and control of sp(3)-hydridized carbon stereocenters is extremely limited. We suggest that the nucleophilic interception of metalacycles provides the means to achieve such a transformation, wherein the metal complex serves to activate electrophiles, facilitate nucleophile addition, and ultimately control stereochemistry. One means of accessing these intermediates is through the use of simple meso-carboxylic anhydrides, which upon reaction with transition metals readily generate the desired metalacycles. Interception of the metalacycle with an appropriate carbon-based nucleophile generates an enantioenriched ketoacid, the product of the asymmetric desymmetrization of achiral starting materials. Early successes with achiral nickel catalysts and organozinc reagents provided the foundations for our approach. Alkylation of both succinic and glutaric anhydrides proceeds with a wide range of organozinc nucleophiles, forming 1,4- and 1,5-ketoacids in excellent yields. This reaction manifold has been extensively examined with a detailed kinetic study and mechanistic investigations utilizing mixed zinc reagents and alkene directing groups. This work has highlighted a number of unusual phenomena, including rate-limiting reductive elimination to form an sp(3)-sp(2) carbon-carbon bond. Despite excellent results with the achiral system, to date, all efforts to render the nickel-catalyzed reaction asymmetric have been limited to modest success. Palladium and rhodium complexes, with the use of chiral P-P and P-N ligands, respectively, have been identified as competent catalysts for the enantioselective addition of organozinc reagents to anhydrides. The arylation of a series of succinic anhydrides with Ph2Zn can be achieved in greater than 95% enantioselectivity using a Pd/Josiphos catalyst. Rhodium catalysts have proven amenable for the incorporation of in situ formed organozinc reagents, nucleophiles traditionally troublesome in transition metal catalysis due to the deleterious effects of residual halide ions. Highly functionalized organozinc nucleophiles, including those containing indole and furan, participate in this chemistry to provide the corresponding 1,4- and 1,5-ketoacids in excellent yield with greater than 85% enantioselectivity. This metalacycle interception methodology is currently being expanded to the use of other systems, most notably the asymmetric [2 + 2 + 2] cycloaddition of alkenes, alkynes, and isocyanates. Ongoing studies promise the extension of existing methodology toward the development of modular, fully intermolecular three-component couplings in which both metalacycle formation and nucleophilic interception can be controlled. Ultimately, we envision the use of heterocumulenes in such methodology, providing a route to complex products utilizing CO2 as an inexpensive C1 feedstock.     

Recent advantages in the metal (bulk and nano)-catalyzed S-arylation reactions of thiols with aryl halides in water: a perfect synergy for eco-compatible preparation of aromatic thioethers

Transition-metal-catalyzed C–S cross-coupling reactions comprise one of the most efficient methods for the synthesis of biologically and synthetically important aryl sulfide derivatives. Among the various solvents used in this cross-coupling reaction (ionic liquids, water, organic, and aqueous biphasic solvents), neat water have attracted notable interest in recent years due to its properties such as non-toxicity, non-flammability, renewability, and widely availability compared with other solvents. Since several catalytic systems for this green synthesis of aryl sulfides have been reported from 2007 to present, a comprehensive review on this interesting field seems to be timely. In this study, we discuss the most representative and interesting reports on the synthesis of aryl sulfides via metal-catalyzed cross-coupling of thiols with aryl halides in water. Mechanistic aspects of the reactions are considered and discussed in detail.     

Direct functionalization of M-C (M = Pt(II), Pd(II)) bonds using environmentally benign oxidants, O2 and H2O2

Atom economy and the use of "green" reagents in organic oxidation, including oxidation of hydrocarbons, remain challenges for organic synthesis. Solutions to this problem would lead to a more sustainable economy because of improved access to energy resources such as natural gas. Although natural gas is still abundant, about a third of methane extracted in distant oil fields currently cannot be used as a chemical feedstock because of a dearth of economically and ecologically viable methodologies for partial methane oxidation. Two readily available "atom-economical" "green" oxidants are dioxygen and hydrogen peroxide, but few methodologies have utilized these oxidants effectively in selective organic transformations. Hydrocarbon oxidation and C-H functionalization reactions rely on Pd(II) and Pt(II) complexes. These reagents have practical advantages because they can tolerate moisture and atmospheric oxygen. But this tolerance for atmospheric oxygen also makes it challenging to develop novel organometallic palladium and platinum-catalyzed C-H oxidation reactions utilizing O(2) or H(2)O(2). This Account focuses on these challenges: the development of M-C bond (M = Pt(II), Pd(II)) functionalization and related selective hydrocarbon C-H oxidations with O(2) or H(2)O(2). Reactions discussed in this Account do not involve mediators, since the latter can impart low reaction selectivity and catalyst instability. As an efficient solution to the problem of direct M-C oxidation and functionalization with O(2) and H(2)O(2), this Account introduces the use of facially chelating semilabile ligands such as di(2-pyridyl)methanesulfonate and the hydrated form of di(2-pyridyl)ketone that enable selective and facile M(II)-C(sp(n)) bond functionalization with O(2) (M = Pt, n = 3; M = Pd, n = 3 (benzylic)) or H(2)O(2) (M = Pd, n = 2). The reactions proceed efficiently in protic solvents such as water, methanol, or acetic acid. With the exception of benzylic Pd(II) complexes, the organometallic substrates studied form isolable high-valent Pt(IV) or Pd(IV) intermediates as a result of an oxidant attack at the M(II) atom. The resulting high-valent M(IV) intermediates undergo C-O reductive elimination, leading to products in high yields. Guidelines for the synthesis of products containing other C-X bonds (X = OAc, Cl, Br) while using O(2) or H(2)O(2) as oxidants are also discussed. Although the M(II)-C bond functionalization reactions including high-valent intermediates are well understood, the mechanism for the aerobic functionalization of benzylic Pd(II) complexes will require a more detailed exploration. Importantly, further optimization of the systems suitable for stoichiometric M(II)-C bond functionalization led to the development of catalytic reactions, including selective acetoxylation of benzylic C-H bonds with O(2) as the oxidant and hydroxylation of aromatic C-H bonds with H(2)O(2) in acetic acid solutions. Both reactions proceed efficiently with substrates that contain a directing heteroatom. This Account also describes catalytic methods for ethylene dioxygenation with H(2)O(2) using M(II) complexes supported by facially chelating ligands. Mechanistic studies of these new oxidation reactions point to important ways to improve their substrate scope and to develop "green" CH functionalization chemistry.     

Copper/amino acid catalyzed cross-couplings of aryl and vinyl halides with nucleophiles

Copper-assisted Ullmann-type coupling reactions are valuable transformations for organic synthesis. Researchers have extensively applied these reactions in both academic and industrial settings. However, two important issues, the high reaction temperatures (normally above 150 degrees C) and the stoichiometric amounts of copper necessary, have greatly limited the reaction scope. To solve these problems, we and other groups have recently explored the use of special ligands to promote these coupling reactions. We first showed that the structure of alpha-amino acids can accelerate Cu-assisted Ullmann reactions, leading to the coupling reactions of aryl halides and alpha-amino acids at 80-90 degrees C. In response to these encouraging results, we also discovered that an l-proline ligand facilitated the following transformations: (1) coupling of aryl halides with primary amines, cyclic secondary amines, and N-containing heterocycles at 40-90 degrees C; (2) coupling of aryl halides with sulfinic acid salts at 80-95 degrees C; (3) azidation of aryl halides and vinyl halides with sodium azide at 40-95 degrees C; (4) coupling of aryl halides with activated methylene compounds at 25-50 degrees C. In addition, we found that N,N-dimethylglycine as a ligand facilitated Cu-catalyzed biaryl ether formation at 90 degrees C. Moreover, Sonogashira reactions worked in the absence of palladium and phosphine ligands, forming enamides from vinyl halides and amides at temperatures ranging from ambient temperature up to 80 degrees C. Furthermore, we discovered that an ortho-amide group can accelerate some Ullmann-type reactions. This functional group in combination with other ligand effects allowed for aryl amination or biaryl ether formation at ambient temperature. The coupling between aryl halides and activated methylene compounds even proceeded at -45 degrees C to enantioselectively form a quaternary carbon center. Taking advantage of these results, we developed several novel approaches for the synthesis of pharmaceutically important heterocycles: 1,2-disubstituted benzimidazoles, polysubstituted indoles, N-substituted 1,3-dihydrobenzimidazol-2-ones, and substituted 3-acyl oxindoles. Our results demonstrate that an l-proline or N,N-dimethylglycine ligand can facilitate most typical Ullmann-type reactions, with reactions occurring under relatively mild conditions and using only 2-20 mol % copper catalysts. These conveniently available and inexpensive catalytic systems not only accelerate the reactions but also tolerate many more functional groups. Thus, they should find considerable application in organic synthesis.     

Phosphoramidites: marvellous ligands in catalytic asymmetric conjugate addition

The development of an efficient catalytic system for enantioselective carbon-carbon bond formation by 1,4-addition of organometallic reagents (organolithium, Grignard, and organozinc reagents) to enones is a major challenge in organic synthesis. This Account presents the breakthrough realized in this field using chiral phosphoramidite ligands for copper-catalyzed dialkylzinc additions. Applications in catalytic routes to cycloalkanones as well as tandem and annulation procedures with excellent enantioselectivities are discussed.     

A highly efficient polymer‐anchored palladium(II) complex catalyst for hydrogenation,Heck cross‐coupling and cyanation reactions

BACKGROUND: Precise architectures of steric and electronic properties of palladium species play a crucial role in designing highly functionalized catalyst systems responsible for target organic transformations. Pd catalysts supported on polymer materials have been employed extensively as catalysts not only for hydrogenation but also for coupling reactions in the production of fine chemicals. RESULTS: A new polymer‐anchored Pd(II) complex has been synthesized and characterized. The catalyst shows high catalytic activity in the hydrogenation of styrene oxide, Heck cross‐coupling and cyanation reactions of aryl halides. The effect of various reaction parameters were investigated to optimize reaction conditions. The catalytic system shows good activity in the hydrogenation of styrene oxide (conversion 98%) with a selectivity to 2‐phenylethanol (93%) which is higher than its homogeneous analogues. The catalyst also exhibits excellent catalytic activity for the Heck cross‐coupling and cyanation reactions of various substituted and non‐substituted aryl halides. CONCLUSIONS: Results demonstrate that the catalyst is robust and stable and can be recovered quantitatively by simple filtration and reused several times without loss of activity. Copyright © 2010 Society of Chemical Industry     

Catalytic coupling of sp2- and sp-hybridized carbon-hydrogen bonds with vinylmetalloid compounds

In the Account given herein, it has been shown that silylative coupling of olefins, well-recognized as a new catalytic route for the activation of double bond C-H bond of olefins and double bond C-Si bond of vinylsilicon compounds with ethylene elimination, can be extended over both other vinylmetalloid derivatives (double bond C-E) (where E = Ge, B, and others) as well as the activation of triple bond C-H, double bond C aryl-H, and -O-H bond of alcohols and silanols. This general transformation is catalyzed by transition-metal complexes (mainly Ru and Rh) containing or initiating TM-H and/or TM-E bonds (inorganometallics). This new general catalytic route for the activation of double bond C-H and triple bond C-H as well as double bond C-E bonds called metallative coupling or trans-metalation (cross-coupling, ring-closing, and polycondensation) constitutes an efficient method (complementary to metathesis) for stereo- and regioselective synthesis of a variety of molecular and macromolecular compounds of vinyl-E (E = Si, B, and Ge) and ethynyl-E (E = Si and Ge) functionality, also potent organometallic reagents for efficient synthesis of highly pi-conjugated organic compounds. The mechanisms of the catalysis of this deethenative metalation have been supported by equimolar reactions of TM-H and/or TM-E with initial substances and reactions with deuterium-labeled reagents.     

Synthesis, catalytic activity, and leaching studies of a heterogeneous Pd-catalyst including an immobilized bis(oxazoline) ligand

The synthesis and characterization of a novel catalytic system including Pd(OAc)(2) attached to a bis(oxazoline) (=BOX) ligand that is covalently bonded to 3-mercaptopropyl-functionalized silica gel is presented. The catalyst was tested for Suzuki-Miyaura reactions of different aryl halides with phenylboronic acid. The heterogeneity of the catalytic system was investigated using different approaches, indicating that there is virtually no Pd leaching into the reaction solution under the applied reaction conditions. Furthermore, our results show that the catalytic system can be reused multiple times without significant loss of stability or structure.     

Activation of aryl chlorides in water for Suzuki coupling with a hydrophilic salen-Pd(II) catalyst

For exploiting aqueous condition, we have designed a simple water-soluble palladium Schiff-base catalyst for Suzuki-Miyaura reactions of aryl halides with arylboronic acids. The reactions could be performed in neat water with aryl bromides and iodides at room temperature and with aryl chlorides at 100 °C. Good-to-excellent yields of cross-coupling products were obtained with a diverse range of aryl halides including heteroaryl halides. Interestingly, the homogeneous catalyst could be conveniently recycled with aryl bromides or chlorides for at least four times, although a progressive decrease in the product yields were noticed.     

Catalytic Reactivities of Indenyl–nickel, Indenyl–palladium, and PCsp3P–nickel Complexes

This report describes the catalytic reactivities of a series of Ni and Pd complexes featuring substituted or functionalized indenyl ligands and Ni complexes featuring a PC_sp3P type ligand framework. The reactivities of the indenyl complexes encompass styrene homologation (dimerization, trimerization, oligomerization, and polymerization) and hydrosilylation, 1-hexene isomerization, ethylene dimerization and polymerization, phenylacetylene hydrosilylation, coupling reactions of aryl halides with styrene and amines. The reactivities of PC_sp3P–Ni complexes is focused on oligomerization of phenylsilane and its addition to styrene, and the addition of aniline to acrylonitrile. The various reactivities discussed herein demonstrate the importance of ligand properties on the catalysis promoted by a given metal.     

Copper(I)‐Mediated Highly Stereoselective syn‐Carbometalation of Secondary or Tertiary Propargylic Alcohols with Primary Grignard Reagents in Toluene with a High Linear Regioselectivity

A highly regio‐ and stereoselective syn‐carbometalation of terminal secondary or tertiary propargylic alcohols with primary alkyl Grignard reagents in toluene or phenylmagnesium bromide in Et₂O was developed, in which the alkyl or phenyl group from the Grignard reagents is introduced into the terminal position of the alcohols. The organometallic intermediate formed may be used directly for the coupling reaction with organic halides. Upon treatment with I₂ after the carbometalation, iodides may be obtained, which may undergo Sonogashira coupling reaction and highly stereoselective Novozym‐435‐catalyzed kinetic resolution to afford the optically active products.     

Cobalt-Catalyzed Cross-Coupling Reactions of Aryl Halides

Cobalt-catalyzed carbon–carbon bond-forming reactions are an indispensable class of reactions in organic synthesis. This economical and ecologically attractive catalyst could replace, in some cases, the well-etablished, expensive palladium and toxic nickel catalytic systems that have dominated the field for many years. Cobalt-catalyzed protocols tolerate various functional groups and present a wide range of reactivity. Moreover, these efficient reactions are very easy to carry out without complex ligands under varied conditions. This review intends to shed light on the fact that cobalt-catalyzed cross-coupling reactions offer an excellent alternative to the usual catalysts. Moreover, these methodologies are sometimes superior, especially for reactions involving alkyl halides.     

Metal–organic framework MOF-199-catalyzed direct and one-pot synthesis of thiols,sulfides and disulfides from aryl halides in wet polyethylene glycols (PEG 400)

A highly porous metal–organic frame work Cu₃ BTC₂ (copper(II)-benzene-1,3,5-tricarboxylate) that is known as MOF-199 was synthesized from the reaction of 1,3,5-benzenetricarboxylic acid and Cu(OAc)₂·H₂O by a solvothermal method and characterized by several techniques including FT-IR, XRD, EDX and scanning electron microscopy. The MOF-199 used as an efficient catalyst for one-pot synthesis of thiols by domino reactions of aryl halides and thiourea, and subsequently conversion to aryl alkyl sulfides and diaryl disulfides in polyethylene glycols (PEGs). A variety of aryl alkyl sulfides can be obtained in good to excellent yields in a relatively short reaction time and in the presence of the trace amount of catalyst. Also, the catalyst can be separated from the reaction mixture by decanting, and be reused without significant degradation in catalytic activity.