Selectivity in the Synthesis of Cyclic Sulfonamides

Kimberly Geoghegan graduated from University College Dublin (UCD) with a B.Sc. in Chemistry in 2009. She continued on in UCD and joined the research group of Dr. Paul Evans. She was awarded a National University of Ireland (NUI) Travelling Studentship to undertake her doctoral studies on the regioselective Heck reaction and its applications in the synthesis of natural products, and graduated with her Ph.D. in 2013. Since 2014, Kimberly has been a postdoctoral researcher in the group of Prof. Jeffrey W. Bode at ETH Zürich, where she is developing novel reagents for the synthesis of saturated nitrogen containing heterocycles.

In the area of organic chemistry one major challenge we are currently faced with is how to assemble potentially useful molecules in new ways that generate molecular complexity and in sequences that are as efficient as possible. Our efforts in this regard, specifically for the preparation of amino containing compounds incorporating an aromatic ring, are described in this doctoral thesis. We discovered an interesting regioselectivity in an intramolecular Heck reaction, which we studied for a series of substrates that are unbiased in terms of the size of the newly formed ring, where very high levels of selectivity in relation to the new carbon-carbon bond are typically observed. DFT calculations were performed to attempt to shed light on the reaction sequence. This regioselective Heck reaction, combined with the reductive removal of the temporary amino-protecting group, allowed us to synthesize the Sceletium alkaloids: mesembrane, mesembranol and mesembrine.

Nominated as an Outstanding Ph.D. thesis by the University College Dublin, Ireland

Introduction.- Regioselectivity in the Heck (Mizoroki-Heck) Reaction.- Wagner-Meerwein Rearrangement of Cyclic Sulfonamides.- An Investigation into the One-Pot Heck Olefination-Hydrogenation Reaction.- Double Reduction of Cyclic Aromatic Sulfonamides.- Experimental.