Microwave-Assisted Metal Catalysis
Status
Established Project
Background
Transition metal-catalyzed coupling reactions of aryl halides or pseudohalides have emerged as one of the most versatile types of carbon-carbon and carbon-heteroatom bond forming processes. Numerous elegant transformations in natural and non-natural product synthesis have been reported. Cross-couplings and Heck reactions constitute important tools in medicinal chemistry since they allow preparation of compounds substituted with a variety of functional groups, with diverse physicochemical properties, from a common precursor. Despite the extensive use of the Heck coupling, the reaction still suffers from severe limitations. These include unsatisfactory control of chemoselectivity, regioselectivity, stereoselectivity, double bond migration and selectivity in multifunctionalizations. Provided these factors could be controlled, the Heck reaction would have a considerably greater potential in selective organic synthesis and in combinatorial organic chemistry, in particular. In addition, the possibility to perform metal-catalyzed chemistry in neat water employing energy-efficient microwave heating appears attractive from a green perspective.
Aim
To develop new highly selective metal-catalysed coupling reactions. To investigate high-temperature water as an environmentally friendly solvent.
Method
In the Heck chemistry arena, we are focusing our research efforts on the oxidative addition, insertion and double bond migration processes with the ultimate goal of developing robust and general synthetic methods. We investigate and expand the scope of chelation-controlled and ligand controlled Heck reactions. Furthermore, we are examining the unique properties of neat water at high temperature as the reation medium. A profound mechanistic insight on metal-ligand interactions is a prerequisite for a successful program. The use of microwave "flash-heating" for accelerating palladium-catalyzed coupling reactions is further examined.