CAREER: Establishing Ligand Platforms to Enable Selective, Catalytic Olefin Difunctionalization Reactions for Constructing Diverse Heterocyclic Scaffolds

University Of Rochester, Rochester NY

Investigators

Abstract

With the support of the Chemical Synthesis Program in the Division of Chemistry, Shauna Paradine of the University of Rochester is studying new metal-catalyzed chemical processes that may enable more efficient preparation of important classes of so-called 'heterocyclic' molecules. The kinds of heterocycles being targeted have potential applications as therapeutic agents, agrochemicals, and advanced materials, and as such the outcome of the research could have a variety of societal benefits. The potential advances being offered are made possible with the design of new ligands for palladium that possess unconventional properties. Through both hypothesis-driven and data-driven ligand design strategies, the Paradine laboratory expects to discover selective and broadly useful reactions that will allow for refined tuning of the properties of the molecules of interest. In parallel with research activities, Dr. Paradine will expand mentoring experiences for chemistry graduate students at the University of Rochester and develop a formal course in scientific communication for undergraduate and graduate students. These activities are designed to support the personal and professional development of chemistry students, with a special focus on addressing the needs of students from marginalized groups, and to equip students of all backgrounds with the capacity to be effective scientific communicators in a broad range of contexts and media. The ability of palladium to form broadly reactive organometallic species has led to the introduction of a diverse array of practical methodologies for synthetic organic chemistry. Indeed, Pd-catalyzed methods have become ubiquitous for the construction of molecular scaffolds rich in sp2-hybridized carbon atoms. Ligand development has been a key driver of this innovation, with electron-rich and bulky ligands such as phosphines and N-heterocyclic carbenes being predominantly used in efforts to uncover new Pd-catalyzed reactivity. However, the success of these ligand families has led to other areas of ligand space for palladium being left largely unexplored, leaving considerable opportunities for reaction discovery, particularly in regard to methods for the construction of sp3-hybridized carbon-rich domains. To address this imbalance, the funded project involves study of unconventional ligand platforms derived from ureas and phosphines to facilitate Pd-catalyzed selective olefin difunctionalization reactions, with an emphasis on heteroannulation processes leading to non-planar heterocyclic scaffolds. The investigation is divided across four aims: (1) development of urea ligand-enabled heteroannulation reactions involving ambiphiles (e.g., 2-bromoanilines) and 1,3-dienes; (2) exploration of the reactivity of new pi-coupling partners with urea-enabled Pd catalysis; (3) elucidation of the fundamental properties of urea ligands and their role in catalysis; and, (4) realization of ligand-controlled site-selectivity in olefin functionalization reactions. Pursuit of these aims will include the foundation of data-driven, predictive models for ligand design that are anticipated to facilitate general strategies for ligand development in the field of transition metal catalysis with associated benefits for future reaction discovery. 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.