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

硫代醛是非常不稳定的化合物，因为它们倾向于经历快速的寡聚反应，并且必须在相应的反应伙伴存在的情况下原位制备。因此，它们在有机合成中一直没有得到充分的研究和利用。一种特别直接和非常温和的制备方法是诺里什ii裂解法。然而，它有许多缺点，如辐照时间长、反应混合物加热、产物分解和产量损失。为了克服这些缺点，我们打算开发一种强大的、广泛适用的连续流工艺来生产硫醛，并充分利用硫醛的合成潜力。初步研究表明，在流动反应器的细管中辐照后，在短停留时间内产生高产量的硫代醛，这些硫代醛可以在[4+2]-环加成反应中被富电子二烯成功截获。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代醛，以提供硫代嘌呤。进一步研究连续流条件下硫醛的烯反应和[2+2]-环加成反应。此外，硫醛的形成将通过光谱方法和dft计算进行在线跟踪，以阐明thia Diels-Alder反应的机理。最后，两种不对称策略将被用于对映选择性硫吡喃的合成。

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.