C-H Bond Functionalization in Complex Organic Synthesis

Abstract

Direct and selective replacement of carbon-hydrogen bonds with new bonds (such as C-C, C-O, and C-N) represents an important and long-standing goal in chemistry. These transformations have broad potential in synthesis because C-H bonds are ubiquitous in organic substances. At the same time, achieving selectivity among many different C-H bonds remains a challenge. Here, we focus on the functionalization of C-H bonds in complex organic substrates catalyzed by transition metal catalysts. We outline the key concepts and approaches aimed at achieving selectivity in complex settings and discuss the impact these reactions have on synthetic planning and strategy in organic synthesis.

Catalytic C–H functionalization by metal carbenoid and nitrenoid insertion

“…A partial solution to this problem has been to use neighbouring functionality to direct less reactive metal complexes to the site for functionalization. Numerous reviews have been written about this method for C-H functionalization [11][12][13][14][15][16][17] . Here, however, we highlight another approach, in which a divalent carbon (carbene) 18 or a monovalent nitrogen (nitrene) 19 , coordinated to a metal complex, inserts into a C-H bond 20 .…”

Platinum(II) and palladium(II) complexes with (N,N′) and (C,N,N′)− ligands derived from pyrazole as anticancer and antimalarial agents: Synthesis, characterization and in vitro activities

“…Cyclometallated complexes derived from N-donor ligands have attracted great interest during the last decade due to their properties and applications in a wide variety of fields [10,[20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36] and compounds of this kind containing Pd(II), Pt(II), Ru(II), Ir(III) Rh(III) and Au have shown promising cytotoxic activities [10,20,[27][28][29][30][31][32][33][34][35][36]. Few cyclopalladated complexes derived from pyrazole are known [37][38][39][40][41] and, to the best of our knowledge, their cytotoxicity has only been reported once [41].…”

O desafio da ativação das ligações C-H em síntese orgânica

“…No entanto, o mais complicado não é o desenvolvimento metodológico, mas a sua aplicação na síntese de moléculas orgânicas complexas, área na qual a ativação C-H tem adentrado paulatinamente. 6 A idealidade nesta química é a modificação pontual, seletiva e sem danos para o restante da estrutura, que tenha reatividade e produtos previsíveis, assim como compatibilidade com estruturas complexas, dotadas de grupos funcionais, de preferência não protegidos. Se possível, regiosseletividade, diastereo-e enantiosseletividades devem ser obtidas com o uso mínimo de ligantes/catalisadores quirais.…”

“…5 Neste sentido, o presente texto visa proporcionar uma reflexão acerca das metodologias aplicadas recentemente para a funcionalização direta das ligações C-H no contexto de desenvolvimento metodológico e aplicação na síntese de substâncias orgânicas complexas. 6 Sendo assim, serão discutidas algumas alternativas promissoras e inovadoras à "química orgânica sintética tradicional", além dos aspectos pertinentes sobre o mecanismo e a seletividade desses processos. …”