Victor Duran Arroyo

My work deals with the replacement of fluorine atoms with hydrogen atoms in medically relevant chemicals using a catalyst. The catalyst uses nickel metal supported by a chemical scaffold to enact the chemical change desired with the goal of
making the manufacture of pharmaceuticals with fluorines more cost-effective because fluorine atoms impart beneficial medicinal effects in pharmaceutical drugs such as: metabolic stability, potency, and bioavailability.

A new molecule, [Ni( iPr PN)(COD)] (Ni1), was found to be an efficient catalyst for the replacement of fluorine atoms with hydrogen atoms (hydrodefluorination or HDF) in pyridines, which are pharmaceutically relevant molecules, at specifically targeted positions. Production of the defluorinated pyridines was achieved at mild temperatures in 3 hours and 30 min and without the use of harsh reagents. Investigations into the the reaction mechanism revealed that Ni1 performed a stepwise hydrodefluorination (HDF) of pyridines and led to the detection and isolation of another novel nickel complex, [Ni( iPr PN)(F)(Py F )] (Ni2), that showed comparable catalytic efficiency to that of Ni1. Comparing and contrasting the reactivity of Ni1 and Ni2 provided evidence for: 1) the COD component’s stabilizing effect on Ni1 in the reaction, 2) the slowest step of the reaction is the decoordination of the COD component from Ni1, and 3) Ni2 is a highly reactive intermediate after its formation within the catalytic reaction. Understanding these fundamental steps allow later rational modification and improvement of the catalytic system.