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

硫代醛是极不稳定的化合物，因为它们倾向于进行快速齐聚反应，并且必须在各自的反应伙伴存在的情况下原位制备。因此，它们在有机合成中的研究和利用不足得多。一种特别直接和非常温和的制备方法是苯环硫化物的Norrish II-裂解。然而，由于硫代醛存在辐照时间长、反应混合物加热、产物分解和产率损失等缺点，为了克服这些缺点，我们打算开发一种健壮的、广泛适用的硫代醛连续流生产工艺，充分挖掘硫代醛的合成潜力。初步研究表明，在流动反应器的薄管中进行辐射，在很短的停留时间后，硫代醛的产率很高，在[4+2]-环加成反应中可以被电子富二烯成功截留。我们的目标是进一步优化这一连续流动过程，并将其扩展到更广泛的芳基、杂芳基和烷基取代硫代醛，以提供噻喃类化合物。并进一步研究了硫代醛在连续流动中的烯反应和[2+2]-环加成反应。此外，硫代醛的生成将通过光谱手段进行在线跟踪，并将进行密度泛函计算以阐明Thia Diels-Alder反应的机理。最后，我们将采用两种不对称策略来合成对映体选择性的硫代吡喃。

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.