The site-selective formation of carbon-carbon bonds through direct functionalizations of otherwise unreactive carbon-hydrogen bonds constitutes an economically attractive strategy for an overall streamlining of sustainable syntheses. In recent decades, intensive research efforts have led to the development of various reaction conditions for challenging C-H bond functionalizations, among which transition-metal-catalyzed transformations arguably constitute thus far the most valuable tool. For instance, the use of inter alia palladium, ruthenium, rhodium, copper, or iron complexes set the stage for chemo-, site-, diastereo-, and/or enantioselective C-H bond functionalizations. Key to success was generally a detailed mechanistic understanding of the elementary C-H bond metalation step, which depending on the nature of the metal fragment can proceed via several distinct reaction pathways. Traditionally, three different modes of action were primarily considered for CH bond metalations, namely, (i) oxidative addition with electronrich late transition metals, (ii) σ-bond metathesis with early transition metals, and (iii) electrophilic activation with electrondeficient late transition metals (Scheme 1). However, more recent mechanistic studies indicated the existence of a continuum of electrophilic, ambiphilic, and nucleophilic interactions. Within this continuum, detailed experimental and computational analysis provided strong evidence for novel C-H bond metalationmechanisms relying on the assistance of a bifunctional ligand bearing an additional Lewis-basic heteroatom, such as that found in (heteroatom-substituted) secondary phosphine oxides or most prominently carboxylates (Scheme 1, iv). This novel insight into the nature of stoichiometric metalations has served as stimulus for the development of novel transformations based on cocatalytic amounts of carboxylates, which significantly broadened the scope of C-H bond functionalizations in recent years, with most remarkable progress being made in palladiumor ruthenium-catalyzed direct arylations and direct alkylations. These carboxylate-assisted C-H bond transformations were mostly proposed to proceed via a mechanism in which metalation takes place via a concerted base-assisted deprotonation. To mechanistically differentiate these intramolecular metalations new acronyms have recently been introduced into the literature, such as CMD (concerted metalationdeprotonation), IES (internal electrophilic substitution), or AMLA (ambiphilic metal ligand activation), which describe related mechanisms and will be used below where appropriate. This review summarizes the development and scope of carboxylates as cocatalysts in transition-metal-catalyzed C-H functionalizations until autumn 2010. Moreover, experimental and computational studies on stoichiometric metalation reactions being of relevance to the mechanism of these catalytic processes are discussed as well. Mechanistically related C-H bond cleavage reactions with ruthenium or iridium complexes bearing monodentate ligands are, however, only covered with respect to their working mode, and transformations with stoichiometric amounts of simple acetate bases are solely included when their mechanism was suggested to proceed by acetate-assisted metalation.

Carboxylate-assisted transition-metal-catalyzed C-H bond functionalizations: mechanism and scope.

The direct functionalization of C-H bonds in organic compounds has recently emerged as a powerful and ideal method for the formation of carbon-carbon and carbon-heteroatom bonds. This Review provides an overview of C-H bond functionalization strategies for the rapid synthesis of biologically active compounds such as natural products and pharmaceutical targets.

C-H bond functionalization: emerging synthetic tools for natural products and pharmaceuticals

The direct functionalization of heterocyclic compounds has emerged as one of the most important topics in the field of metal-catalyzed C–H bond activation due to the fact that products are an important synthetic motif in organic synthesis, the pharmaceutical industry, and materials science. This critical review covers the recent progresses on the regioselective dehydrogenative direct coupling reaction of heteroarenes, including arylation, olefination, alkynylation, and amination/amidation mainly utilizing transition metal catalysts (113 references).

Recent advances in the transition metal-catalyzed twofold oxidative C–H bond activation strategy for C–C and C–N bond formation

Rhodium(III)-catalyzed direct functionalization of C-H bonds under oxidative conditions leading to C-C, C-N, and C-O bond formation is reviewed. Various arene substrates bearing nitrogen and oxygen directing groups are covered in their coupling with unsaturated partners such as alkenes and alkynes. The facile construction of C-E (E = C, N, S, or O) bonds makes Rh(III) catalysis an attractive step-economic approach to value-added molecules from readily available starting materials. Comparisons and contrasts between rhodium(III) and palladium(II)-catalyzed oxidative coupling are made. The remarkable diversity of structures accessible is demonstrated with various recent examples, with a proposed mechanism for each transformation being briefly summarized (critical review, 138 references).

C–C, C–O and C–N bond formation via rhodium(III)-catalyzed oxidative C–H activation

The applications of copper (Cu) and Cu-based nanoparticles, which are based on the earth-abundant and inexpensive copper metal, have generated a great deal of interest in recent years, especially in the field of catalysis. The possible modification of the chemical and physical properties of these nanoparticles using different synthetic strategies and conditions and/or via postsynthetic chemical treatments has been largely responsible for the rapid growth of interest in these nanomaterials and their applications in catalysis. In addition, the design and development of novel support and/or multimetallic systems (e.g., alloys, etc.) has also made significant contributions to the field. In this comprehensive review, we report different synthetic approaches to Cu and Cu-based nanoparticles (metallic copper, copper oxides, and hybrid copper nanostructures) and copper nanoparticles immobilized into or supported on various support materials (SiO2, magnetic support materials, etc.), along with their applications i...

http://pubs.acs.org/doi/pdfplus/10.1021/acs.chemrev.5b00482

Cu and Cu-Based Nanoparticles: Synthesis and Applications in Catalysis.

The induction period of Negishi coupling catalyzed by pincer thioamide-palladium complex 1 was investigated. A heterogeneous mechanism was excluded by kinetic studies and comparison with Negishi coupling reactions promoted by Pd(OAc)(2)/Bu(4)NBr (a palladium-nanoparticle system). Tetramer 2 was isolated from the reaction of 1 and organozinc reagents. Dissociation of complex 2 by PPh(3) was achieved, and the structure of resultant complex 8 was confirmed by X-ray diffraction analysis. A novel alkylated pincer thioimido-Pd(II) complex, 7, generated from catalyst precursor 1 and basic organometallic reagents (RM), was observed by in situ IR, (1)H NMR, and (13)C NMR spectroscopy for the first time. The reaction of 7 with methyl 2-iodobenzoate afforded 74% of the cross-coupled product, methyl 2-methylbenzoate, together with 60% of Pd(II) complex 2. Furthermore, the catalyst, as an electron-rich Pd(II) species, efficiently promoted the Negishi coupling of aryl iodides and alkylzinc reagents without an induction period, even at low temperatures (0 degrees C or -20 degrees C). To evaluate the influence of the catalyst structure upon the induction period, complex 9 was prepared, in which the nBu groups of 1 were displaced by more bulky 1,3,5-trimethylphenyl groups. Trimer 10 was isolated from the reaction of complex 9 and basic organometallic reagents such as CyZnCl or CyMgCl (Cy: cyclohexyl); this is consistent with the result obtained with complex 1. The rate in the induction period of the model reaction catalyzed by 9 was faster than that with 1. Plausible catalytic cycles for the reaction, based upon the experimental results, are discussed.

Identification of a highly efficient alkylated pincer thioimido-palladium(II) complex as the active catalyst in Negishi coupling.

Effective Pd-nanoparticle (PdNP)-catalyzed Negishi coupling involving alkylzinc reagents at room temperature.

The first nickel-catalyzed aromatic C–H borylation is described. In the presence of catalytic amounts of [Ni(cod)2], tricyclopentylphosphine, and CsF, benzene and indole derivatives can be borylate...

Aromatic C–H Borylation by Nickel Catalysis

The transition-metal-catalyzed cyclization of 1,6-enynes is one of the most convenient and efficient methods for the synthesis of a variety of carbocyclic and heterocyclic compounds. By this approach, enynes can be transformed into cyclic skeletons in a one-pot fashion with impressive regioand stereoselectivity. 6] The readily available and inexpensive metal nickel stands out for its remarkable power in catalyzing cycloisomerization and cycloaddition reactions of enynes. Important examples include a Ni-catalyzed [4+2] cycloaddition developed by Wender and co-workers and a series of cyclization reactions of activated 1,6-enynes described by Montgomery and co-workers [Scheme 1,

Nickel-catalyzed reductive cyclization of unactivated 1,6-enynes in the presence of organozinc reagents.

For a direct quantitative investigation of the Csp(2)-Csp(2) reductive elimination rate within a catalytic cycle, a novel oxidative coupling system in the presence of a Ni catalyst and desyl chloride as the oxidant is devised. The reaction progress profiles of arylzinc reagents exhibit zero-order kinetic behavior, and a reductive elimination step is confirmed as the rate-determining step. This allows direct measurement of the Csp(2)-Csp(2) reductive elimination rate constant within a catalytic cycle. The rate constants of p-MePhZnCl are obtained in the range 0.23 to 3.5 s(-1) from 0 to -35 degrees C, which are unusually fast reaction rates. According to the Arrhenius equation, the values of DeltaH(double dagger) and DeltaS(double dagger) (DeltaH(double dagger) = 9.7 kcal mol(-1), DeltaS(double dagger) = 35 J mol(-1) K(-1)) are obtained. The small value of DeltaH(double dagger) reveals that the reductive elimination step of Csp(2)-Ni-Csp(2) is an extremely facile process.

Hua Zhang

Papers

Identification of a highly efficient alkylated pincer thioimido-palladium(II) complex as the active catalyst in Negishi coupling.

Effective Pd-nanoparticle (PdNP)-catalyzed Negishi coupling involving alkylzinc reagents at room temperature.

Aromatic C–H Borylation by Nickel Catalysis

Nickel-catalyzed reductive cyclization of unactivated 1,6-enynes in the presence of organozinc reagents.

What is the rate of the Csp2-Csp2 reductive elimination step? Revealing an unusually fast Ni-catalyzed Negishi-type oxidative coupling reaction.