Malononitrile is a readily available feedstock chemical distinguished by its high acidity and unusual electronic structure. Guided by a “Freedom of Choice” philosophy in reaction discovery, we are exploring this underutilized reagent as a platform for inventing new, often enantioselective, transformations with the potential to simplify access to sp3-rich drug-like molecules. This lecture will highlight historical milestones in malononitrile chemistry and describe reactions developed in our laboratory. Unifying transformations include the Knoevenagel condensation, asymmetric allylic alkylation, Cope and Claisen rearrangements, nucleophilic aromatic substitution, and strategic malononitrile functional-group interconversions. Collectively, these studies illustrate how the exceptional acidity and electronic structure of malononitrile can be leveraged to access new reactivity modes and topological landscapes in the synthesis of complex, pharmaceutically relevant molecules.
 

Alex Grenning grew up in the northern suburbs of Chicago. He received his B.A. from Lake Forest College and his Ph.D. from the University of Kansas, followed by postdoctoral training at Boston University. He began his independent career in 2014.

From 2014–2023, Alex served as an assistant and later associate professor in the Department of Chemistry at the University of Florida. In 2024, he joined the Department of Chemistry at the University of Minnesota as an associate professor.

Research in the Grenning laboratory focuses on (i) reaction discovery guided by physical organic chemistry principles and enantioselective catalysis to enable new strategies for complex molecule synthesis, and (ii) identifying opportunities where advances in organic chemistry can address diseases with unmet therapeutic needs, including CNS disorders and infectious diseases. Alex believes science is serious, but scientists don’t have to be! So go ahead and be true to yourself while you tackle those hard and hopefully creative tasks!

Alex is deeply committed to strengthening the organic chemistry community. His leadership emphasizes inclusivity, representation, diversity of scientific perspectives, and affordability, with the goal of advancing both the science and the scientists who practice it. His service spans several organizations and conferences, including The FloHet Conference, the ACS Division of Organic Chemistry, the Telluride Conference, and the Organic Reactions and Process Gordon Research Conference.

Outside the laboratory, Alex balances his enthusiasm for organic chemistry with other creative pursuits. He takes pride in raising his daughters and encouraging them to enjoy the adventures of Minneapolis tween life. Around the city, he gravitates toward places that “smell a little funny.” The record shops, music stores, and tiny music venues, where he collects records, guitars, and memorable shows. His musical tastes lean heavily toward punk and punk-adjacent rock and roll. When time allows, he enjoys cooking Italian food, playing pickleball and tennis (in that order), and embracing the sauna/cold plunge ritual that seems nearly mandatory for surviving and enjoying a cold, long, Minneapolis winter.