The palladium-catalysed modular annulative synthesis of cyclic sulfonimidamides

Abstract

Acyclic sulfonimidamides have gained increasing attention in medicinal chemistry programs; however, examples of their cyclic counterparts are much rarer, reflecting the dearth of convenient synthetic methods to access these unusual heterocycles. Herein, we report a modular one-pot Pd-catalysed method for the synthesis of cyclic sulfonimidamides from the combination of ortho-halo benzaldehydes and acyclic sulfonimidamides. The protocol includes a broad scope for both reaction partners and tolerates a diverse range of functional groups, placing substituents at every position of the ring system. The chemistry can be extended to achieve access to alternative cyclic S(IV) and S(IV) functional groups, including sulfinamides, sulfonimidoyl fluorides, and sulfonimidate esters. Preliminary findings on the functionalisation of the cyclic sulfonimidamide products are included. We also demonstrate that enantiomerically enriched cylic sulfonimidamdes can be prepared when starting from an enantiopure building block. Additionally, we report the first synthesis of cyclic sulfondiimidamides via a related Chan–Lam coupling.