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Biomimetic C-H Oxidation Catalysis in Aqueous Solution

  • Author(s): Djernes, Katherine Elizabeth
  • Advisor(s): Hooley, Richard J.
  • et al.
Abstract

The ability to convert feedstock chemicals into synthetically useful derivatives is a major goal in the search for more sustainable and efficient chemical processes. One limitation in the field is the inability of known catalysts to oxidize C-H bonds regioselectively. Traditional synthetic approaches require extreme temperatures and pressures to break the C-H bond; in addition to the high energy cost of these processes, each reaction yields multiple products and over-oxidation is a common problem. In contrast to these harsh reaction conditions, enzymes catalyze C-H oxidations at ambient temperature and pressure with excellent selectivity. More recently, transition metal catalysts have been developed that can oxidize C-H bonds under more mild conditions, but a key difference between enzymes and most synthetic catalysts is that while synthetic catalysts can achieve chemoselectivity based on steric and electronic factors, enzymes exhibit regioselectivity and can selectively oxidize a position on a substrate in the presence of other chemically identical positions.

One problem with using enzymes as catalysts in synthetic organic chemistry is their limited substrate scope. As an alternative, water-soluble synthetic receptors with catalytic functions are an attractive target because they offer the potential to allow regioselective oxidations on a broader range of substrates.

Cavitands provide an alluring scaffold for metalloenzyme mimics because they are capable of displaying four rigid coordinating motifs at defined distances around a hydrophobic cavity that acts as a size-selective recognition motif. A cavitand scaffold is presented that can be smoothly derivatized by CuAAC chemistry to incorporate ligand species at the cavitand rim. The coordination of one or more metals to the scaffold allows self-folding to form a water soluble molecular receptor, without the need for covalent introduction of solubilizing groups such as sulfates or phosphates. Furthermore the hydrophobic binding site allows the cavitands to bind appropriately sized neutral guests. In the presence of a stoichiometric oxidant, the metallocavitands can selectively oxidize unactivated C-H bonds in high yield with good turnover numbers. The catalysts are wide in scope and oxidations are performed cleanly under mild conditions without side oxidation of solvent or catalyst. The cavitands retain the catalytic metal throughout the reaction, and can be recovered from the reaction system by simple filtration. Alternatively, the metallocavitands can be mounted on an SBA-15 solid support, forming highly effective heterogeneous catalysts that can be recovered after reaction in quantitative yield and re-used more than ten times without any decrease in reactivity.

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