Towards mild metal-catalyzed C–H bond activation

Abstract

Functionalizing traditionally inert carbon-hydrogen bonds represents a powerful transformation in organic synthesis, providing new entries to valuable structural motifs and improving the overall synthetic efficiency. C-H bond activation, however, often necessitates harsh reaction conditions that result in functional group incompatibilities and limited substrate scope. An understanding of the reaction mechanism and rational design of experimental conditions have led to significant improvement in both selectivity and applicability. This critical review summarizes and discusses endeavours towards the development of mild C-H activation methods and wishes to trigger more research towards this goal. In addition, we examine select examples in complex natural product synthesis to demonstrate the synthetic utility of mild C-H functionalization (84 references).

Anaerobic Activation of p -Cymene in Denitrifying Betaproteobacteria: Methyl Group Hydroxylation versus Addition to Fumarate

“…This difference should not be due to energetic constraints, as both strains can yield the same high energy from p-cymene degradation (⌬G 0= ϭ Ϫ5,354 kJ mol Ϫ1 p-cymene). The distinctiveness of the herein reported enzymes from other known anaerobic hydrocarbon-activating enzymes with respect to substrate type (p-cymene) and phylogenetic branching could add to (i) the compound-specific resolution power of biogeographic studies on genes encoding these enzymes (78) and (ii) the prospects of biomimetic approaches for the industrially relevant COH bond activation (79). Further degradation of 4-isopropylbenzoylCoA is currently being investigated by pursuing possibilities of degradation via a route similar to the recently described 4-methylbenzoyl-CoA pathway (80) or the classical anaerobic benzoylCoA pathway (8).…”

Development of Cobalt-Catalyzed C–H Bond Functionalization Reactions

“…Thus, besides exploration of novel reactions and methods, development of cost-effective and mild alternative catalytic systems also represents an important subject. 3,4 Our group at Nanyang Technological University started in July 2009, and since then the major part of our research program has revolved around catalysis of the group 9 first-row transition metal, cobalt, for CH functionalization. This personal account illustrates how cobalt catalysts have emerged as viable alternatives to noble metal catalysts, rhodium(I) catalysts in particular, for existing CH functionalization reactions.…”

“…9 The Brookhart catalyst is also capable of H/D exchange between benzene and tetradeuterioethylene via aromatic CH activation. 10 Besides these catalytic examples, a cobalt(I) complex [Co(Me)(PMe 3 ) 4 ] has been known since 1993 to participate in stoichiometric cyclometalation of aromatic and olefinic substrates bearing various heteroatom directing groups, 11 when Klein and co-workers reported on its reaction with azobenzene (Scheme 2). 12 The reaction is proposed to go through chelation-assisted oxidative addition of the ortho CH bond to cobalt(I) followed by reductive elimination of methane.…”

Synthesis of Tetrahydrobiphenylene <i>via</i> Pd(0)-Catalyzed C(<i>sp</i>²)–H Functionalization

“…[13][14][15][16][17][18][19][20] Methods for the formation of benzocyclobutenes based on intramolecular C-H functionalization have been developed by the Catellani, Baudoin, Wolfe, and Martin groups. [21][22][23][24][25][26][27] Recently, we have investigated Pd(0)-catalyzed benzylic C(sp 3 )-H functionalization for the synthesis of various heterocycles and tetrahydro-2H-fluorenes.…”