Professor M. Cristina White has developed iron-based small molecule catalysts which, in conjunction with hydrogen peroxide, can selectively oxidize aliphatic C-H bonds in complex natural products.
Organic synthetic strategies are typically designed around the use of protecting or activating groups to yield desired products. While the use of these types of groups is well developed and widely used, this approach often generates waste and introduces unwanted complexity into the synthetic sequence. Methods which allow introduction of functionalities without activating or protecting groups can significantly impact synthetic methods. In particular, reactions which can predictively and selectively oxidize isolated, unactivated sp3 C-H bonds in complex substrates are of particular value as they enable introduction of functionalities in the later stages of synthetic sequences.
White has developed catalyst systems which achieve this oxidation of C-H bonds based solely on electronic and steric properties of the bond. With the additional use of carboxylate directing groups, diastereoselective lactonizations can be achieved.
A compelling example of the selective oxidation of a C-H bond is the conversion of the antimalarial compound artemisinin which contains five potential C-H sites for oxidation and a cleavage-sensitive peroxide functional group. Using White's iron-based catalyst and its designed selectivity, the targeted C-H bond is oxidized preferentially to give the desired product in higher yields, with shorter reaction times, and in higher volume throughputs compared to enzymatic reactions.
White's catalyst systems open powerful methods to greatly streamline synthetic methods by offering predictive and selective aliphatic C-H oxidation in complex substrates.
- Specialty Chemicals
- Predictive and selective oxidation of C-H bonds in complex systems
- Preparatively high yields and rapid reaction rates
- Elimination of need for activating and protecting groups
- Utilization of inexpensive and environmentally friendly oxidant, H202
- Enabling of late-stage introduction of oxidized functionalities