Total synthesis of natural products is one of the most important driving force for finding new chemical reactions, assessing physical organic theories, testing the power and scope of synthetic methods, and, most importantly, making new medicines. The Nazarov cyclization reaction, which is catalyzed by strong Lewis acids, is a powerful reaction for the assembly of five membered rings and has been successfully used in the total synthesis of natural products. This study focuses on computational modeling using DFT calculations to study the details of the mechanism of the palladium catalyzed Nazarov cyclization in collaboration with Dr. Marcus Tius. Dr. Tius has found that for a specific class of substrates, palladium (II) complexes do not catalyze their cyclization, while palladium (0) complexes do. This is not only surprising as palladium (II) is more Lewis acidic and hence is expected to be a better catalyst than palladium (0), but it also indicates that the cyclization of these substrates might be going through a different mechanism. Our calculations are focusing on computing the relative energies of different interactions between the transition metal catalyst and the substrates in order to determine which ones could play a role in the cyclization reaction. One important question that we are focusing on is the possibility of an oxidative addition reaction that would convert palladium (0) to palladium (II) during the reaction cycle.  The finer details of the mechanism could help to design a better catalyst that would make Nazarov cyclization reaction a more powerful synthetic method.

Mechanistic investigation of Nazarov cyclization reaction catalyzed by palladium(0) complexes

247th National Meeting (2014)

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