Efficient Synthesis via Organosulfur Intermediates

我们的研究项目致力于开发有用的合成方法，以提高化学家从简单的构建块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功能的中间体的多功能性来实现有效的合成转换。这项NSERC发现资助提案描述了我们开发一系列使用亚砜和乙烯基硫化物的新反应的计划。这项工作是由我们实验室最近令人兴奋的结果所推动和启发的。我们已经演示了第一个基于磷化氢的Pummerer反应，该反应在一个操作简单的过程中将亚砜直接转化为有价值的烷基硫代烷基膦盐。反过来，这些盐是Wittig反应的底物，可以产生多种取代的乙烯基硫化物产物，这些产物是适用于一系列进一步转化的有用合成中间体。我们的短期目标是：1)对这种新的制备乙烯基硫化物的pummer - wittig方法进行全面的探索和优化，2)将这种化学扩展到广泛适用的醛和酮的单碳同质化，这将具有成本效益，并且是一种与现有方法正交的方法。从长远来看，我们建议追求其他四个广泛的反应发展目标，利用我们对硫化乙烯中间体的增强获取来实现高效的新成键反应和策略。在这个程序中开发的方法可以在包括特种化学品，农用化学品和药品在内的一系列行业的合成化学家工作的实用价值。此外，我们将在有机硫化学领域产生基础知识，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，维蒂格化学，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.