Porphyrin Synthesis

A significant amount of work has been performed in the Senge laboratory towards more efficient and robust methods of porphyrin synthesis. Symmetrical porphyrins are widely available through classic condensation routes but demand in recent years for more useful nonsymmetrical porphyrins has risen significantly. To this end we have developed a new and highly versatile method to install virtually any aryl or alkyl residue to a free meso position on a pre formed porphyrin scaffold.

Our method relies on the intrinsic reactivity of the meso positions of porphyrins towards nucleophilic attack by strong nucleophiles. In a very straightforward addition oxidation mechanism virtually any starting porphyrin can be selectively functionalized to yield less symmetrical systems. The mechanism first goes through a porphyrin “anion” following attack by the nucleophile. This can then be hydrolyzed to a porphodimethene by water and oxidized to the target porphyrin. A modification of the procedure also developed by us involves the trapping of this “anion” in situ with an organic electrophile. This is a very useful way to convert a meso-disubstituted and a tetra-substituted one in a one-pot synthesis.

The synthetic methods used in our lab also rely heavily on the use of transition metal catalyzed reactions, particularly the palladium catalyzed reactions like Suzuki, Sonogashira and Heck. These allow rapid conversion of haloporphyrins into desired target systems.

The group is constantly involved in looking for new and better methods of porphyrin synthesis. Current research projects are focused on new fusing techniques and ß-modification reactions.

Cubane Synthesis

Considering the geometry of cubane, it is noteworthy that the distance across the cube (the body diagonal) is 2.72 Ĺ, which is almost equivalent to the distance across a benzene ring, i.e., 2.79 Ĺ,11,12 which has led to renewed interest in it as an isostere in drug development. Our interest in the cubane scaffold emerged from a search for rigid linking units which would inhibit electronic communication between bound electron transfer systems.

The cubane framework thus stood out, but the chemistry of cubane has remained somewhat stagnant for much of the last three decades and, as such, many modern avenues in synthetic chemistry, e.g., transition-metal-catalyzed cross-coupling reactions, have not been rigorously applied to the cubane system. The aim of this project is to develop appropriate cubane building blocks and test their applicability in cross-coupling reactions.

The group is constantly involved in looking for new and better methods of porphyrin synthesis. Current research projects are focused on new fusing techniques and ß-modification reactions.