Efficient Synthesis via Organosulfur Intermediates

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Our research program is committed to developing useful synthetic methods that enhance the capacity of chemists to construct complex molecules from simple building blocks. To accomplish this, we intend to leverage the versatility of intermediates containing C-S functionalities in innovative ways to achieve efficient synthetic transformations. This NSERC Discovery Grant proposal describes our plans to develop a range of new reactions that employ sulfoxide and vinyl sulfide substrates. This work is enabled and inspired by recent exciting results from our laboratory. We have demonstrated the first phosphine-based Pummerer reaction which converts sulfoxides directly to valuable alkylthioalkylphosphonium salts in a single operationally-simple process. These salts are, in turn, substrates for Wittig reactions that can yield diversely-substituted vinyl sulfide products which are useful synthetic intermediates suitable for a range of further transformations. Our short term goals are: 1) to conduct a comprehensive exploration and optimization of this new Pummerer-Wittig approach to the preparation of vinyl sulfides, and 2) to extend this chemistry into a broadly applicable one-carbon homologation of aldehydes and ketones that will be cost-efficient and an orthogonal approach to current methods. In the longer term, we propose to pursue four other broad reaction development objectives that leverage our enhanced access to vinyl sulfide intermediates to achieve efficient new bond-forming reactions and strategies. The methods developed in this program can be of practical value to synthetic chemists working in a range of industries including specialty chemicals, agrochemicals, and pharmaceuticals. Furthermore, we will generate fundamental knowledge in the field of organosulfur chemistry and make intellectual contributions to scientific literature in many areas including: sulfoxide and sulfide chemistry, Wittig chemistry, reductive radical chemistry, transition metal catalysis, and heterocyclic synthesis.