Catalytic Cycloaddition Reactions and Their Applications

With the support of the Chemical Catalysis (CAT) and Chemical Synthesis (SYN) Programs in the Division of Chemistry, Professor Michael Doyle of the University of Texas, San Antonio is working to develop new ways to construct molecules using vinyl diazo compounds, organic building blocks that have a carbon-carbon double bond next to an electron-poor carbon, formally known as a carbenoid center. Catalysts are being studied to tune and control the reactivity of vinyl diazo compounds with compatible reagents to access value-added products.

These investigations are working toward establishing new ways to construct challenging bonds and heteroaromatic structures that are common components of valued added target molecules, particularly heterocyclic structures of value to biological and medicinal chemistry. Synergistically, these activities will provide opportunities for students of different levels to broaden their knowledge and experience in catalytic and synthetic chemistry.

Undergraduate students are being integrated into the research program with strong mentoring that prepares them for careers in STEM (science, technology, engineering and mathematics) disciplines, and opportunities are being provided to postdoctoral research associates to prepare them for positions in the chemical sciences in both the private sector and in academia.

New modular methods for the synthesis of heterocycles and functionalized carbocycles are in high demand due to the prevalence of these structures in pharmaceutical, agrochemical, and new material targets. Professor Michael Doyle and his research team are identifying catalysts that extrude molecular nitrogen from vinyl diazo-compounds to form highly energetic metallocarbene intermediates that condense with a variety of dipolar cycloaddition partners to form novel adduce with a high degree of regio- and stereo control.

The stereodefined products of [3+1]-cycloaddition reactions of silyl-protected enoldiazo compounds will be studied for subsequent strain-induced ring-opening reactivity and used to explore cycloaddition reactions of donor-acceptor cycloalkenes. Acid-catalyzed conditions with triflimide are being developed to engage vinyl diazo [3+1] cycloaddition products in subsequent cycloaddition reactions that lead to intermediate structures capable of ring expansion to medium-sized products.

Highly enantioselective catalytic cyclopropanation reactions of enoldiazo compounds are being tested to prepare donor-acceptor cyclopropanes that are capable of engaging in cycloaddition reactions with retention of enantioenrichement. These activities will take place at the University of Texas, San Antonio, and augment the inclusive training and research opportunities at this minority-serving institution.

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.