Applications of Chalcogen-based Oxidation State Alternating Organocatalysts

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With the support of the Chemical Catalysis Program in the Division of Chemistry, Professor Patrick J. Walsh of the University of Pennsylvania is studying a new principle for catalysis based on the use of sulfur- and selenium-containing compounds that change their oxidation state reversibly during a reaction cycle that results in the formation of value-added products from inexpensive and widely available starting materials. Significantly, the products of the processes under investigation are typically useful in their own right, sometime displaying biological activity, and they may also serve as building blocks from which other more elaborate molecules can be prepared. As such, the research will facilitate the manufacture of materials of importance to society including fine chemicals. Development of the catalysts and processes of interest will be aided by extensive mechanistic studies and the use of modern high throughput experimental (HTE) methods. The broader impacts of the funded project extend to the education and training of the graduate students conducting the research and societal benefits accrued as Professor Walsh and his coworkers engage in outreach activities at high schools and other venues. Of note, this award will enable Professor Walsh to continue to participate in an international outreach program with Mexican scientists that fosters cross-border collaborations and that promotes science and technical education broadly.The funded research leverages the reversible redox chemistry of chalcogen-based organocatalysts in the +2 and +4 oxidation states, to enable new reaction manifolds that may offer solutions to contemporary problems in synthetic organic chemistry. Two objectives, one focused on the synthesis of aziridines and the other on cyclopropanes, will be pursued and in each case, enantioselective variants will be explored once the basic premise of the reaction chemistry has been established. Objective 1 is to develop a base mediated sulfenate anion-catalyzed aziridination reaction between imines and benzylic chlorides that proceeds via in situ sulfoxide formation (alkylation of sulfenate anion on S-atom) followed by a Darzens-like process that regenerates the sulfenate catalyst. This method gives high diastereoselectivity for the formation of trans-aziridines and potential applications of it for the synthesis of trans-2,3-diaryl, 2-aryl-3-alkyl and even 2,3-dialkyl aziridines will be examined. In Objective 2, a related sulfenate/selenoate anion catalysis principle will be applied to the cyclopropanation of styrene derivatives. Significantly, the approaches being explored achieve atom transfer chemistry without the use of the hazardous 'enoid' reagents traditionally used for this purpose (e.g., azides and diazoalkanes) and without recourse to expensive and scarce transition metal catalysts. Throughout, the scope and limitations of the methods developed will be explored and extensive parameter screening and mechanistic investigations conducted. In addition to the aforementioned societal benefits, it is anticipated that the fundamental advances made by the Walsh research group during their pursuit of the above endeavors will stimulate further research into the hitherto little investigated area of oxidation state alternating organocatalysis and which promises opportunities beyond the processes of interest herein.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.