Professor Denmark has held the Reynold C. Fuson Professorship in Chemistry since 1991. His research is primarily focused on the invention of new synthetic reactions and elucidating the mechanisms and origins of stereocontrol in novel, asymmetric reactions. He has pioneered the concept of chiral Lewis base activation of Lewis acids for catalysis in main group synthetic organic chemistry. The first demonstration of the concept involved the invention of a new class of silicon-promoted carbonyl addition reactions that are notable for their rate, selectivity and generality. Further application of this concept to organoselenium and organosulfur chemistry led him to establish the configurational stability of the -iranium ions and thereafter the first, catalytic enantioselective thiofunctionalization of isolated alkenes with oxygen, nitrogen, and carbon nucleophiles. His group has also developed palladium-catalyzed cross-couplings with organofunctional silicon and boron compounds. In detailed mechanistic studies his group demonstrated the intermediacy of discrete species containing a B-O-Pd linkage which has opened a new avenue for accelerating the rate of the coupling reaction through modulation of the boronate ester. In recent years, his group has investigated the use of chemoinformatics and machine learning to identify and optimize enantioselective catalysts and reaction conditions for a variety of organic and organometallic reactions. The implementation of this approach begins with a fully informatics-driven workflow that incorporates newly invented descriptors for both steric and electronic contributions that capture the conformational flexibility of molecules in statistical modeling. Central to the implementation of this workflow is his introduction of the concept of the “Universal Training Set”. This set of catalysts accurately represents the features of large in-silico libraries. In a related program, Denmark has reported the first example of using machine learning to identify and experimentally validate optimal conditions for a C–N bond forming reaction that is ubiquitous in the pharmaceutical industry. An open-source version has been launched for the entire chemical community to employ.

Denmark has won a number of honors including: selection as a University Scholar (UIUC), the Alexander von Humboldt Senior Scientist Award, the Pedler and Robert Robinson Medals (RSC), the A. C. Cope Scholar Award (ACS), the ACS Award for Creative Work in Synthetic Organic Chemistry, the Yamada-Koga Prize, the Prelog Medal (ETH-Zürich), the Brown Award for Creative Research in Synthetic Methods (ACS), the Senior Award in Heterocyclic Chemistry (ISHC), the Kipping Award for Research in Silicon Chemistry (ACS), the Ryoji Noyori Prize (Society of Synthetic Organic Chemistry of Japan), the Paracelsus Prize (Swiss Chemical Society) and the Arthur C. Cope Award (ACS). In 2017 he was elected as a fellow of the American Academy of Arts and Sciences and in 2018 he became a member of the National Academy of Sciences. He edited Volume 85 of Organic Syntheses and currently serves on the Board of Directors, was Editor of Volumes 22-25 of Topics in Stereochemistry and was a founding Associate Editor of Organic Letters (1999-2004). After serving on the editorial board from 1994-2003, he was Editor in Chief and President of Organic Reactions, Inc. (2008-2018) and remains on the Board of Directors. He currently serves on the advisory boards of Org. Lett., J. Org. Chem., and J. Am. Chem. Soc.