Role of metal-oxo complexes in the cleavage of C-H bonds

Abstract

The functionalization of C-H bonds has yet to achieve widespread use in synthetic chemistry in part because of the lack of synthetic reagents that function in the presence of other functional groups. These problems have been overcome in enzymes, which have metal-oxo active sites that efficiently and selectively cleave C-H bonds. How high-energy metal-oxo transient species can perform such difficult transformations with high fidelity is discussed in this tutorial review. Highlighted are the relationships between redox potentials and metal-oxo basicity on C-H bond activation, as seen in a series of bioinspired manganese-oxo complexes.

Fig. 1

(a) Proposed structure of Compound I in cytochrome P450, (b) possible reaction sequence for C–H bond functional by cytochrome P450, (c) proposed reaction sequence for C–H bond activation in non-heme monooxygenases, (d) proposed active site of compound Q in pMMO. Atom legend for the structure in 1A: carbon atoms (grey), sulfur atoms (yellow), nitrogen atoms (blue), oxygen atoms (red), iron atoms (orange).

Fig. 2

(a) comparison of redox potentials for some common chemicals to low-potential manganese-oxo complexes (highlighted in orange), (b) square scheme illustrating the thermodynamic components that contribute to MO–H bond energies, (c) plot of redox potential versus pK_a values need to cleave the C–H bond in methane (see equation 1).

Fig. 3

(a) Structures of bioinspired iron and manganese complexes with terminal oxo and hydroxo ligands, (b) reaction wheel highlighting the C–H bond reactivity of [Mn^IIIH₃buea(O)]²⁻.

Fig. 4

Thermodynamic square schemes used to determine the BDE_OH in [Mn^IIIH₃buea(O)]²⁻ and [Mn^IVH₃buea(O)]⁻.

Fig. 5

Plots of rate data for reaction of 9,10-dihydroanthracene with [Mn^IIIH₃buea(O)]²⁻ (●) and [Mn^IVH₃buea(O)]−(■).

Fig. 6

Proposed mechanism for C–H bond activation of (a) [Mn^IVH₃buea(O)]⁻ and (b) [Mn^IIIH₃buea(O)]²⁻ with 9,10-dihydroanthracene.