Excited state intramolecular proton transfer-based photoassisted methodologies to access complex molecular architectures

University Of Denver, Denver CO

Investigators

Abstract

In this project funded by the Chemical Synthesis Program, Professor Andrei Kutateladze of the Department of Chemistry and Biochemistry at University of Denver develops new methods for the synthesis of complex organic heterocycles. These are substances which contain nitrogen in a ring, a common feature of natural products and pharmaceuticals. New synthetic routes are primarily based on novel cycloaddition reactions initiated by ultraviolet light. Complex multi-ring heterocyclic molecular architectures are accessed and alkaloid mimics are synthesized. Fundamental new science includes the development of cascade photoreactions to form multiple chemical bonds in one experimentally simple step. In addition, this award supports research experiences for undergraduate and graduate students, especially those from historically underrepresented groups in science. This research expands the excited state intramolecular proton transfer (ESIPT) based synthetic photochemistry tool box with new photoassisted cascade methodology. New reactions provide access to complex polyheterocyclic compounds in a controlled atom- and step-economical fashion. The mechanism of these cascade processes, including quantum mechanical tunneling at the hydrogen transfer step, is elucidated to better modulate stereochemical and regiochemical outcomes. Such control is needed to develop the capability of systematically screening the chemical space in search of novel polyheterocyclic molecular architectures with the requisite scaffold diversity. To further grow scaffold complexity and diversity and to decorate the core scaffolds with additional functional groups and heterocyclic pendants, experimentally simple postphotochemical steps are deployed after the light-induced transformation. This experimental work is accompanied by the development of computational methods for fast and accurate predictions of NMR spectra, which is critical for success of this project, but also has broader implications for structure elucidation of complex synthetic and natural organic molecules. Additionally, this research provides hands-on laboratory training for graduate and undergraduate students, especially those from historically underrepresented groups in science.