Continuous flow synthesis of sulfur heterocycles via cycloaddition reactions of photochemically generated transient thioaldehydes

通过光化学产生的瞬时硫醛的环加成反应连续流动合成硫杂环

• 批准号: 275642803
• 负责人: Professor Dr. Christoph Schneider
• 金额: --
• 依托单位: Institut für Organische Chemie
• 依托单位国家: 德国
• 项目类别: Research Units
• 财政年份: 2015
• 资助国家: 德国
• 起止时间: 2014-12-31 至 2022-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/275642803?language=en
• 关键词: Continuous; flow; synthesis; sulfur; heterocycles

Thioaldehydes are extremly labile compounds since they tend to undergo rapid oligomerization reactions and have to be prepared in situ in the presence of the respective reaction partner. As a consequence they have been much underinvestigated and underutilized in organic synthesis. A particularly straightforward and very mild method of preparation is the Norrish II-cleavage of phenacycl sulfides. However, it suffers from a number of drawbacks such as long irradiation times, heating of the reaction mixture, decomposition of products and losses in yield.To overcome these shortcomings we intend to develop a robust and broadly applicable continuous flow process for thioaldehyde production and fully exploit the synthetic potential of thioaldehydes. Preliminary studies have revealed that irradiation in the thin tubes of a flow reactor produce high yields of thioaldehydes after short residence times that can be successfully intercepted by an electronich diene in [4+2]-cycloaddition reactions. It is our objective to further optimize this continuous flow process and extend it to a broad range of aryl-, heteroaryl-, and alkyl-substituted thioaldehydes to furnish thiopyranes. It is further intended to also study ene reactions and [2+2]-cycloaddition reactions of thioaldehydes in continuous flow. Furthermore, thioaldehyde formation will be followed online by spectroscopic means and DFT-calculations are to be conducted to elucidate the mechanism of the thia Diels-Alder reaction. Finally, two asymmetric strategies will be pursued toward an enantioselective thiopyran synthesis.

硫醛是极其不稳定的化合物，因为它们往往会发生快速的低聚反应，并且必须在各自的反应伙伴存在下原位制备。因此，它们在有机合成中的研究和利用远远不够。一种特别简单且非常温和的制备方法是非那环硫化物的 Norrish II 裂解。然而，它存在许多缺点，例如辐照时间长、反应混合物加热、产物分解和收率损失。为了克服这些缺点，我们打算开发一种稳健且广泛适用的连续流程来生产硫醛，并充分利用开发硫醛的合成潜力。初步研究表明，连续反应器细管中的辐照在短停留时间后会产生高产率的硫醛，这些硫醛可以在[4+2]-环加成反应中被电子二烯成功拦截。我们的目标是进一步优化这种连续流动工艺，并将其扩展到广泛的芳基、杂芳基和烷基取代的硫醛，以提供噻喃。它还旨在研究连续流中硫醛的烯反应和[2+2]-环加成反应。此外，将通过光谱手段在线跟踪硫醛的形成，并进行 DFT 计算以阐明硫代狄尔斯-阿尔德反应的机理。最后，将采用两种不对称策略来合成对映选择性噻喃。