Synthesis of Clickable Pyrazolo-fused N -heterocycles using a Diversity Oriented Clicking Strategy

Diversity-Oriented Clicking (DOC) provides a powerful platform for the rapid assembly of structurally complex, SuFEx-enabled molecules. Here, we report a regioselective, catalyst-free [3+2] cycloaddition between 2-substituted-alkynyl-1-sulfonyl fluorides (SASFs) connectors and N -iminium ylides to access a library of sulfonyl fluoride functionalized fused N-heterocycles. Under mild conditions, N -iminopyridinium ylides react smoothly with a range of aromatic and aliphatic SASFs to furnish pyrazolo[1,5- a ]pyridinyl sulfonyl fluorides as single regioisomers. The methodology is applicable to N -iminoisoquinolinium and N- iminoquinazolium ylides, enabling access to pyrazolo[2,1- a ]isoquinoline and pyrazolo[1,5- c ]quinazoline sulfonyl fluorides, respectively, expanding the structural diversity accessible from SASF hubs. The transformation proceeds without additives or transition metals and tolerates diverse functional groups. Importantly, the sulfonyl fluoride moiety enables rapid late-stage diversification with phenols and amines, demonstrating the utility of these fused heterocyclic scaffolds as clickable connective hubs. Finally, we propose a detailed stepwise reaction mechanism.