Applications of Oxidatively Generated Carbocations in Organic Synthesis

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With the support of the Chemical Synthesis (SYN) Program in the Division of Chemistry, Professor Paul Floreancig of the University of Pittsburgh is studying new methods to prepare value-added materials from simple precursors via oxidative transformations. The approaches being developed are based on carbon-hydrogen bond cleavage reactions and include the use of electricity as an energy source in combination with an electrocatalyst to generate synthetically useful positively charged intermediates called carbocations. The pathways by which these intermediates emerge are being studied in detail and their inherent reactivity will be exploited to produce structurally complex molecules that are of potential utility as pharmaceutical agents, agrochemicals, and other materials of value to science, engineering, and commerce. The broader impacts of the funded project extend to the benefits accrued to society as Professor Floreancig and his coworkers engage in a variety of educational and outreach activities in the greater Pittsburgh area. In a signature effort designed to support future leaders in the chemical sciences, Professor Floreancig will lead workshops to prepare senior graduate students and post-doctoral associates at the University of Pittsburgh for possible transitions to independent careers as junior academics. Support for this project is also aiding Professor Floreancig's ongoing efforts to increase the diversity of the graduate student body at the University of Pittsburgh by the establishment of protocols designed to remove implicit biases during the graduate admissions process.The funded research is focused on fundamental mechanistic studies of oxidative carbon–hydrogen bond cleavage processes from allylic ethers and application of the insights gained to the design of new chemical reactions. A primary goal of the study is to understand the impact of remote functional groups on the kinetics of hydride-abstraction reactions with quinone (e.g., DDQ) and oxoammonium ion (e.g., Bobbitt's salt) oxidants. Understanding these effects will aid in the design of oxidative transformations that proceed at a sufficient rate to be applicable to an environmentally benign electrocatalytic protocol recently reported by the Floreancig group. Remote conformational effects impacting the oxidatively-generated oxocarbenium ions through electrostatic interactions will be investigated with the objective of enhancing stereocontrol in cationic cycloaddition reactions. Acyliminium ion formation will also be studied with the expectation of devising new oxidative processes for the synthesis of nitrogen-containing compounds. This objective is founded on understanding the conformational preferences of highly substituted acyliminium ions and exploiting the results for stereocontrolled heterocycle formation through rearrangement processes. Conformational preferences will also be used to instruct on the design of optimal substrates for stereoselective quaternary carbon formation with applications to complex alkaloid synthesis. The findings of the research are anticipated to provide the synthetic chemistry community with new transformations, valuable mechanistic insights, and blueprints for designing additional oxidative functionalization reactions going forward.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.