C─H Bond Cleavage by Bioinspired Non-Heme Metal Complexes

The functionalization of C─H bonds is one of the most challenging transformations in synthetic chemistry. In biology, these processes are well known and are achieved with a variety of metalloenzymes, many of which contain a single metal center within their active sites. The most well studied are those with Fe centers and the emerging experimental data show that high valent Fe–oxido species are the intermediates responsible for cleaving the C─H bond. This Forum describes the state of this field with an emphasis on non-heme Fe enzymes and current experimental results that provide insights into the properties that make these species capable of C─H bond cleavage. These parameters are also briefly considered in regard to Mn-oxido complexes and Cu-containing metalloenzymes. Synthetic Fe–oxido complexes are discussed to highlight their utility as spectroscopic and mechanistic probes, and reagents for C─H bond functionalization. Avenues for future research are also examined. The cleavage of unactivated C─H bonds is a challenging transformation in synthetic chemistry yet is readily accomplished in biology by metalloenzymes. A sub-class of these enzymes contain active sites with single Fe centers that generate high valent Fe–oxido intermediates whose function is to cleave C─H bonds. This Forum describes the current state of this field from spectroscopic, mechanistic, and synthetic perspectives. Discussions on relevant Mn and Cu systems are also included.