Final Report Summary - C-H ACTIVATION (New Concepts for Utilizing a Ubiquitous (Non-)Functional Group - C-H Bond Activation for Increased Efficiency in Organic Synthesis)
We have recognized 4 most important present and future trends within this research field:
a) The formation and functionalization of heterocycles by C-H activation chemistry, especially by means of formation of strategic (complexity creating) bonds. Directed ortho-C-H activation is perfectly suited to build up heterocycles in an efficient manner, as can be seen be the formation of indoles (Angew. Chem. Int. Ed. 2013, 52, 12426), isoquinoline and pyridine N-oxides (J. Am. Chem. Soc. 2013, 135, 12204) or azepinones, also in a more complex natural product-like set up (Angew. Chem. Int. Ed. 2013, 52, 5393).
b) The development of mild C-H activation reactions. The last 5 years have seen a dramatic change of the field of C-H activation towards milder reaction conditions. It is probably fair to say that our work has also contributed to this and inspired others (Leading review: Chem. Soc. Rev. 2011, 40, 4740; specific example reporting on the build-up of 4 different classes of heterocycles under rather mild conditions using an directing group that acts as oxidant at the same time: J. Am. Chem. Soc. 2012, 134, 19592). This development is very important for the applicability of the developed transformations.
c) The development of non-chelate assisted C-H activations. This is one of the most challenging fields of C-H activation and it stands in stark contrast to the vast majority of reports on directed C-H activation. We were able to introduce the first undirected Rh(III)-catalyzed C-H activation, which allows the formation of unsymmetrical biaryls by a cross-dehydrogenative coupling (Angew. Chem. Int. Ed. 2012, 51, 2247). In this process, one of the substrates is activated in the ortho-position and the coupling partner in the meta- or para-position, which is nicely complementary. Even more impressive is the selective cross-coupling between two different heteroarenes, which is chemo- and site-selective (Angew. Chem. Int. Ed. 2012, 51, 8230).
d) The application of C-H activation methods to important compounds and materials, especially by late stage and strategic C-H activations. In my opinion, this is one of the most valuable aspects of C-H activation methodology. We were the first to C-H functionalize a MOF (metal organic framework) in a challenging crystal-to-crystal transformation. As another example, we have also contributed to the formation of strategic bonds (synthesis of the homoprotoberberine motif: Angew. Chem. Int. Ed. 2013, 52, 5393).