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.

硫醇醛是非常不稳定的化合物，因为它们倾向于经历快速低聚反应，并且必须在相应反应伴侣的存在下原位制备。因此，它们在有机合成中的研究和利用不足。一种特别直接和非常温和的制备方法是Norrish II-裂解苯甲酰硫化物。然而，它遭受了一些缺点，如长的照射时间，加热的反应混合物，产品的分解和损失的收率。为了克服这些缺点，我们打算开发一个强大的和广泛适用的连续流工艺生产硫代醛，充分利用硫代醛的合成潜力。初步研究表明，在流动反应器的细管中的照射在短停留时间后产生高收率的硫代醛，其可以在[4+2]-环加成反应中被富电子二烯成功地拦截。我们的目标是进一步优化这种连续流方法，并将其扩展到广泛的芳基，杂芳基和烷基取代的硫代醛，以提供噻喃。它进一步打算也研究烯反应和[2+2]-环加成反应的硫代醛在连续流。此外，硫代醛的形成将通过光谱手段在线跟踪，并进行DFT计算以阐明thia Diels-Alder反应的机理。最后，两个不对称策略将追求对映选择性噻喃合成。