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

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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.