Sustainable Strategies for Site-Selective C−VC Bond Formations through Direct C−H Bond Functionalizations

Abstract

Transition-metal-catalyzed direct arylations have emerged as a viable alternative to traditional cross coupling chemistry in recent decades, as they constitute an economically attractive strategy for an overall streamlining of sustainable syntheses. Thus, the main focus of the present work was set on the development of generally applicable methodologies for site-selective formations of C−C bonds through direct C−H bond functionalizations. In the first part an efficient and generally applicable protocol for palladium-catalyzed direct C−H bond arylations of electron-deficient heteroarenes with aryl and alkenyl sulfonates was elaborated. The optimized catalytic system provided the direct arylation products with excellent chemo- and site-selectivites in high isolated yields. Various tosylates, as well as more atom-economical aryl mesylates could be successfully used as inexpensive, moisture-stable electrophiles for C−H bond functionalizations. Remarkably, the highly-active catalytic system also allowed the direct arylations of electron-deficient fluoroarenes with deactivated tosylates. In a second project of this thesis, research efforts were directed towards sustainable ruthenium-catalyzed annulations of alkynes by benzhydroxamic acid esters, through C−H/N−O bond functionalizations, under environmentally benign conditions. Intriguingly, ruthenium-catalyzed redox-neutral isoquinolone syntheses with ample scope and excellent regioselectivities were accomplished via carboxylate-assistance in water as a green solvent. The outstanding robustness and chemoselectivity of the ruthenium(II)-carboxylate complex also set the stage for the direct use of free hydroxamic acids for the synthesis of annulated lactames. It was further focused on the development of an efficient strategy for site-selective C−H bond funtionalizations on indoles in the absence of a transition-metal-catalyst. Regioselective C3-arylations on various N-alkyl-substituted, as well as free (NH)-indoles were achieved using diaryliodonium salts as mild arylating reagents. The protocol was not restricted to the functionalization of indoles, but also allowed for direct arylations of pyrroles, hence featuring access to a large number of variously decorated, ubiquitous bioactive heterocycles. In order to benefit from the abundance of carbon dioxide in the earth¡¦s atmosphere, its use as an inexpensive, renewable C1 source for various chemical transformations constitutes a contemporary issue. Thus, in the last project of the presented work, a direct approach towards (hetero)aromatic carboxylic acid derivatives by C−C bond formation through carbon dioxide fixation under mild conditions was investigated. Carboxylic acid esters derived from diverse heteroarenes with moderately acidic C−H bonds were obtained in good isolated yields in the absence of a transition-metal-catalyst, using inexpensive potassium tert-butoxide as the base.