For the C-H activation, several methods have become available. However, reliable methods for selective C-H functionalization are still only available for a very limited number of C-H bond positions in a small range of substrates. Expanding the range of substrates and developing new types of selective C-H functionalization reactions remains one of the most challenging and rewarding goals in synthetic chemistry. Nature's approach of orienting a substrate in a three dimensional binding pocket creates selectivity without relying on directing groups or electronic and steric factors. While biocatalysts can be optimized by protein and metabolic engineering as well as directed evolution, chemical catalysts offer a more versatile palette of C-H functionalization reactions than found in nature. This fundamental limitation of biocatalytic C-H activation results from the small number of available cofactors, and, correspondingly, a narrow range of activation mechanisms nature evolved. It is intriguing that the limitations in selective C-H functionalization reactions are orthogonal for homogeneous and biological catalysts. Therefore, the combination of homogeneous and bio-catalytic concepts will help to bring advances not only to the individual fields, but more importantly for the field of C-H functionalization and catalysis in general.
- Michael Groll, Full Professor, TU Muenchen, Germany