Enantioselective Pd-Catalyzed Reactions Enabled by Imidazole-based Chiral Biaryl Ligands

With support of the Chemical Synthesis program in the Division of Chemistry, Professor Aaron Aponick of the University of Florida will study new palladium-catalyzed reactions designed to improve the manufacture of chemical compounds used in agriculture, clean energy technologies, and human health. A prominent feature of the research is that it will enable the generation of products in a so-called 'optically active form' in which one 'enantiomeric configuration' (approximately equivalent to the concept of handedness) of the molecule predominates.

The broader impacts of the project will extend to providing hands-on training for students, preparing them for the modern workforce. In addition, public outreach in science, technology, engineering, and mathematics (STEM) will be achieved through an educational event called "Chemistry Day at the Mall, Molecular Mania." This event is popular with children and fosters interactions with the public, in general. Many visitors with diverse socioeconomic backgrounds participate.

Palladium-catalyzed reactions of olefins have long been recognized as excellent starting points for the preparation of feedstock and fine chemicals. Many such transformations involve a nucleopalladation reaction; however, subtle changes in reaction parameters impact reaction mechanism making it difficult to design reliable enantioselective processes.

The funded project specifically addresses challenges in carbofunctionalization by the utilization of Pd(II)•StackPhos complexes in enantioselective endo-1,2-alkene difunctionalization reactions. Herein, the catalyst controls the stereochemical configuration of products by recognizing a specific olefin pi-face, leading to net enantioselective olefin functionalization reactions.

A key goal of the research is to identify catalysts that exhibit high levels of stereoselectivity for both syn- and anti-addition reactions. Mechanistic probes will be used to glean information in regard to the mode of addition. Further studies are aimed at carbocycle-forming reactions, primarily through the endo-mode cyclization and complementing the more highly developed exo-mode cyclizations currently available.

Additional work will expand on the kinds of transformations hitherto investigated to encompass alternative substrates that may also lead to useful enantioenriched products. Successful realization of the goals of the funded project will have a significant impact on the field of transition metal-mediated catalysis by providing a fundamental understanding of the factors necessary for enantioselective endo-1,2-difunctionalization reactions.

It is anticipated that the findings will enable widespread deployment of this strategy across a range of synthetic applications in both academic and industrial laboratories.

This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.