The synthesis of sulfonyl fluoride functionalised tetrasubstituted thiophenes using a diversity oriented clicking approach

We present a diversity-oriented clicking (DOC) approach for the synthesis of a library of novel clickable, highly functionalised thiophenes that serve as versatile hubs for sulfur fluoride exchange (SuFEx) click chemistry diversification. Using 2-substituted-alkynyl-1-sulfonyl fluorides (SASFs) as DOC connectors, we investigated their reactivity with zwitterionic pyridinium thiolates to selectively access two classes of sulfur-containing heterocycles, namely pyridothiazepines and thiophenes, as SuFExable heterocyclic hubs. However, due to the instability of the pyridothiazepine products, our efforts were redirected toward the selective synthesis and isolation of the thiophene products. Accordingly, 12 highly functionalised SuFExable thiophenes were isolated in yields of up to 87%. The transformation is straightforward to perform, tolerates a broad range of functional groups and proceeds under mild reaction conditions. The potential for diversification of the thiophene scaffold was further demonstrated through SuFEx click chemistry.