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Environmental concerns have and will continue to have a significant role in determining how chemistry is carried out. Chemists will be challenged to develop new, efficient synthetic processes that have the fewest possible steps leading to a target molecule, the goal being to decrease the amount of waste generated and reduce energy use. Along this path, chemists will need to develop highly selective reactions with atom-economical pathways producing nontoxic byproduct. In this context, C-H bond activation and functionalization is an extremely attractive method. Indeed, for most organic transformations, the presence of a reactive functionality is required. In Total Synthesis, the "protection and deprotection" approach with such reactive groups limits the overall yield of the synthesis, involves the generation of significant chemical waste, costs energy, and in the end is not as green as one would hope. In turn, if a C-H bond functionalization were possible, instead of the use of a prefunctionalized version of the said C-H bond, the number of steps in a synthesis would obviously be reduced. In this case, the C-H bond can be viewed as a dormant functional group that can be activated when necessary during the synthetic strategy. One issue increasing the challenge of such a desired reaction is selectivity. The cleavage of a C-H bond (bond dissociation requires between 85 and 105 kcal/mol) necessitates a high-energy species, which could quickly become a drawback for the control of chemo-, regio-, and stereoselectivity. Transition metal catalysts are useful reagents for surmounting this problem; they can decrease the kinetic barrier of the reaction yet retain control over selectivity. Transition metal complexes also offer important versatility in having distinct pathways that can lead to activation of the C-H bond. An oxidative addition of the metal in the C-H bond, and a base-assisted metal-carbon bond formation in which the base can be coordinated (or not) to the metal complexes are possible. These different C-H bond activation modes provide chemists with several synthetic options. In this Account, we discuss recent discoveries involving the versatile NHC-gold(I) and NHC-copper(I) hydroxide complexes (where NHC is N-heterocyclic carbene) showing interesting Brønsted basic properties for C-H bond activation or C-H bond functionalization purposes. The simple and easy synthesis of these two complexes involves their halide-bearing relatives reacting with simple alkali metal hydroxides. These complexes can react cleanly with organic compounds bearing protons with compatible pK(a) values, producing only water as byproduct. It is a very simple protocol indeed and may be sold as a C-H bond activation, although the less flashy "metalation reaction" also accurately describes the process. The synthesis of these complexes has led us to develop new organometallic chemistry and catalysis involving C-H bond activation (metalation) and subsequent C-H bond functionalization. We further highlight applications with these reactions, in ...

A range of ortho-metalated catalysts with alkylphosphine ligands of the general formula [Pd(X)(κ2 N,C-C6H4CH2NMe2)(PR3)] have been synthesized, and the crystal structures of five examples (R = Cy, X = TFA, OTf, Cl, I; PR3 = PCy2(o-biphenyl), X = TFA) have been determined. The crystal structures of two dimeric precursor complexes, [{Pd(μ-TFA)(κ2 N,C-C6H4CH2NMe2)}2] and [{Pd(TFA)(κ2 N,C-C6H4CHNiPr)}2], have also been determined. The application of the phosphine adducts to both Suzuki coupling and Buchwald−Hartwig amination reactions with aryl chloride substrates was examined, and the performance of these catalysts versus conventional palladium sources was evaluated. In general the palladacyclic complexes show considerably enhanced activity. Typically, the best activity is seen with tricyclohexylphosphine adducts in Suzuki coupling and tri-tert-butylphosphine analogues in amination reactions. In nearly all the amination reactions performed, small amounts of a second product species were observed, namely 4,6-bis(aryl)-3,4-dihydro-2H-[1,4]oxazines. The crystal structure of one example, 4,6-bis(4-methoxyphenyl)-3,4-dihydro-2H-[1,4]oxazine, was determined. Studies on the activation of palladacyclic precatalysts in the coupling of morpholine led to the isolation of a morpholine adduct, [Pd(TFA)(κ2 N,C-C6H5CH2NMe2){NH(CH2CH2)O}], which was structurally characterized by X-ray analysis.

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A novel synthetic route leading to N-heterocyclic carbene copper complexes has been developed by using air-stable and commercially available copper(I) oxide and imidazolium salts starting materials.

The bigger the better: The new well-defined [Pd(IPr*)(cin)Cl] pre-catalyst is described. This complex proves to be highly active in the Suzuki-Miyaura cross-coupling for the synthesis of tetra-ortho-substituted biaryls under mild conditions. IPr* is reported as the largest N-heterocyclic carbene (NHC) to date for [Pd(NHC)(cin)Cl] complexes, explaining the high reactivity observed for this complex in this challenging transformation.

A method is described that makes use of easily prepared, inexpensive copper synthons as N-heterocyclic carbene (NHC) transfer agents to generate catalytically relevant gold and palladium complexes.

A series of complexes of the type [Cu(X)(NHC)] (X = I, Br, Cl, NHC = N-heterocyclic carbene) was synthesised using a one-pot, mild and user-friendly (aerobic, tech. grade solvents) procedure.