Functionalization of Organic Molecules by Transition‐Metal‐Catalyzed C(sp³)H Activation

Abstract

Transition-metal-catalyzed C-H activation has recently emerged as a powerful tool for the functionalization of organic molecules. While many efforts have focused on the functionalization of arenes and heteroarenes by this strategy in the past two decades, much less research has been devoted to the activation of non-acidic C-H bonds of alkyl groups. This Minireview highlights recent work in this area, with a particular emphasis on synthetically useful methods.

Cross-Dehydrogenative Couplings between Indoles and β-Keto Esters: Ligand-Assisted Ligand Tautomerization and Dehydrogenation via a Proton-Assisted Electron Transfer to Pd(II)

“…displacement of the ester group from the coordination sphere, see TS rear and int 2 in Figure 4) is predicted to be at 16.9 kcal/mol, giving rise to a barrier of 20.3 kcal/mol (relative to int 1 ). 18 Additional ligand rearrangement can lead to an intermediate involved directly in the -hydride elimination step (see int 3 in Figure 5). In this species, the enolate is bound covalently to Pd via the -carbon atom ( 1 (C) complex) and it displays characteristic -agostic interactions with the metal center.…”

“…TS rear ). 24 The choice between '-H vs. '-D abstraction has already been made in the turnover-determining ligand rearrangement step which leads to the formation of Cbound enolate int 3 , The effect of deuterium substitution in the ' position of the ligand on the ligand rearrangement step is expected to be small, resulting in a negligible primary KIE.…”

“…The finding that the turnover is determined by the ligand tautomerization step (from a O,O'-chelate int 1 to C-bound int 3 ) is interesting. -Substituted -dicarbonyl compounds are known to be unproductive in -arylation reactions, 25 and our results suggest that such low reactivity might have a kinetic origin.…”

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

“…Outro complicador é o perfil energético dos orbitais da ligação C(sp 3 )-H, pouco suscetível à interação com o centro metálico. Assim sendo, algum artifício deve ser usado para direcionar a ativação da ligação C(sp 3 )-H. Os dois exemplos seguintes são relativamente simples, mas já dão uma boa ideia do seu potencial, pois utilizam estratégias diferentes para tornar eficiente e regiosseletiva a ativação C-H. 44 Em 2008, Shibata e colaboradores 45 relataram a preparação de alil amidas através da alquenilação de metil amidas, catalisada por um complexo catiônico de irídio, na presença de (±)-BINAP como ligante. Os tempos reacionais ficaram entre 6 e 72 h, à temperatura de 135 °C, com os rendimentos variando entre 29 e 82% (Esquema 9).…”

“…44 No primeiro exemplo citado (Esquema 9), o grupo diretor foi a carbonila da amida, mas em outros casos, uma ligação π C-C pode também realizar esta função. A ativação de ligações C-H alílicas é um dos exemplos mais recorrentes na literatura.…”