Iron- and Ruthenium-Catalyzed Site-Selective C–C Forming Direct C–H Functionalizations

Abstract

Significant drawbacks of these reactions are the required prefunctionalization of starting materials and potential side reactions, such as ß-hydride elimination and the formation of stoichiometric metal salts as undesired byproducts (Scheme 2a). Therefore, more economically and environmental friendly alternatives are needed to circumvent these disadvantages. To avoid unnecessary and expensive prefunctionalization steps, unfunctionalized (hetero)arenes can be used in transition metal-catalyzed direct C-H bond functionalizations, as shown in Scheme 2b. Another pathway is the cross-dehydrogenative coupling, presented in Scheme 2c. In this context, the use of an external oxidant is required. Scheme 2: Comparison of classical cross-coupling and transition metal-catalyzed C-H transformations.Although a great number of published reactions are described as C-H bond activations, the term "C-H activation" should only be applied to a limited number of reactions. [7,8] True C-H activation involves an elementary C-H metalation step by the active metal species ML n . [9][10][11] First elaborations on the stoichiometric cyclometalations were performed by the groups of Shaw [12] and Reutov, [13] relating to base-promoted metalation reactions. Generally five different main mechanisms are widely accepted up to now (Scheme 3a-e). For example, an oxidative addition can occur if electron-rich, low-valent, late-transition metal complexes of iron, ruthenium, rhenium, osmium, iridium or platinum are employed as the catalysts (Scheme 3a). Electrophilic substitution is more likely occurring when late-or post-transition metals (Pd 2+ , Pt 2+ , Pt 4+ , Hg 2+ ) are used. The reaction starts with an electrophilic attack of the metal complex, acting in this case as a Lewis acid (LA) (Scheme 3b). Early transition metals with d 0 electronic configuration of the groups 3 and 4 as well as the lanthanoids can undergo σ-bond metathesis, highlighting a concerted formation and cleavage of bonds. Herein, usually an alkyl or hydride complex is involved (Scheme 3c). With unsaturated M=X bonds the C-H activation can occur through a 1,2-addition, where a heteroatom-based group bearing a lone electron pair acts as a H-acceptor (Scheme 3d). [9,11] This mechanism is related to the σ-bond metathesis with the constraint that the cleaved proton still remains in the structure of metalated product. This type of reactions can take place with imido and alkylidene complexes of early to middle transition metals. Experimental and theoretical analyses have offered a further type of C-H activation via "base-assisted" metalation (Scheme 3e). [9] The proton is abstracted by a carboxylate or carbonate ligand, which can act as an intramolecular base.Indeed, benzene has a bond dissociation energy of 113 kcal/mol [21] and a pK a value of 43.0-44.7, [21] the C-H bonds are of equal substitution and according to this of equal reactivity. The C-H bonds in heterocycles contain different electronic properties and marginal acidities within the molecule. The resulting pK a values of ...