Efficient Synthesis via Organosulfur Intermediates

我们的研究计划致力于开发有用的合成方法，以提高化学家从简单的积木构建复杂分子的能力。为了实现这一目标，我们打算以创新的方式利用含有C-S官能团的中间体的多功能性来实现高效的合成转化。这份NSERC发现拨款提案描述了我们开发一系列使用亚硫化物和硫化乙烯基底物的新反应的计划。这项工作得到了我们实验室最近令人兴奋的结果的支持和启发。我们已经证明了第一个基于膦的Pummerer反应，它在一个单一的操作简单的过程中将亚硫醚直接转化为有价值的烷基硫代烷基膦盐。这些盐反过来又是Wittig反应的底物，可以产生不同取代的乙烯基硫化物产品，这些产品是适用于一系列进一步转化的有用的合成中间体。我们的短期目标是：1)对这种新的Pummerer-Wittig方法进行全面的探索和优化，以制备乙烯基硫化物；2)将这种化学方法扩展到广泛适用的醛和酮的单碳同系化，这将是成本高效的，并且是与当前方法的正交法。从长远来看，我们建议追求其他四个广泛的反应开发目标，利用我们更容易获得乙烯基硫化物中间体的机会，实现高效的新的成键反应和策略。该项目开发的方法对在各种行业工作的合成化学家具有实用价值，包括特种化学品、农用化学品和制药。此外，我们将产生有机硫化学领域的基础知识，并在许多领域的科学文献中做出智力贡献，包括：亚砜和硫化物化学、Wittig化学、还原自由基化学、过渡金属催化和杂环合成。

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.