Beyond Acylation: New Methodology and Mechanistic Studies of Anhydrides for Stereoselective Synthesis

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The Chemical Synthesis Program of the NSF Division of Chemistry supports this research project in the laboratory of Professor Jared Shaw in the Chemistry Department at the University of California, Davis. Professor Shaw discovers new reactions that enable simple, chemical starting materials to be converted into complex molecules with control of their overall shape. To accomplish this, Professor Shaw and his students are exploring three under explored modes of chemical reactivity. Each of these use a well-known molecular fragment, an anhydride, in a new way. The new reactions involve both the development of the new methods and an exploration of the factors that control the speed and specificity of the new reactions. Professor Shaw is the founding host of the Davis Science Cafe, which is a monthly event that brings scientists together to describe their work to the general public. This project support efforts to maximize the impact of the Science Cafe and other outreach events and bolster the spread of science communication in Northern California. This project also supports an array of outreach activities to achieve the goal of science education at all levels, including participation in a science fair at an elementary school, work with middle and high school students at Chemistry Camp for the Blind, and the revival of the Chapter of the Society for the Advancement of Chicanos/Latinos and Native Americans in Science (SACNAS) at UC Davis. This research may provide new, innovative approaches and advanced manufacturing opportunities for the chemical industry. Although the chemistry of anhydrides is dominated by their ability to serve as electrophilic acylating agents, new advances in the Shaw group exploit the ability of these compounds to serve as versatile nucleophiles. This project is pursuing three specific avenues of inquiry. First, the addition of anhydrides to alpha-chiral imines has shown stereocontrol that defy the rules established for carbonyl compounds. A broad investigation of the outcomes of these reactions paired with computational studies is being used to build a new stereochemical model to describe the behavior of imines in reactions with soft nucleophiles, i.e. electron-rich alkenes. Second, the base-mediated and, if possible, catalyzed reactions of anhydrides with new electrophiles are being studied. This effort involves the synthesis of a new class of chiral catalysts and the development of addition reactions between anhydrides and electron-deficient alkenes and aziridines. Third, the reactions of anhydride enol silanes is being nvestigated. Although a small number of these compounds have been made, the Shaw group has discovered new organocatalytic reactions that enable the reactivity to be steered toward at least two different products with the same imine electrophile. This investigation complements previous work examining the reactions of imines with anhydrides by providing novel reactivity leading to new and interesting products.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.