Synthesis of spirocyclic β‐ and γ‐sultams by one‐pot reductive cyclization of cyanoalkylsulfonyl fluorides

One‐pot intramolecular cyclization of novel sp³‐enriched cyanoalkylsulfonyl fluorides into spirocyclic β‐ or γ‐sultams is disclosed. The method relies on nitrile group reduction followed by sulfonylation of amino group thus formed upon mild conditions (NaBH₄, NiCl₂⋅6H₂ O in MeOH). Cyclization proceeds smoothly with considerable efficiency (58–85%, 10 examples) on up to 30 g scale. The cyanoalkylsulfonyl fluoride intermediates can be obtained via S‐nucleophilic substitution in β‐functionalized alkanenitriles or double alkylation of α‐alkylthioacetonitrile, followed by oxidative chlorination with Cl₂ and further reaction with KHF₂. The title mono‐ and bifunctional sultams are advanced sp³‐enriched building blocks for drug discovery and organic synthesis providing novel substitution patterns and frameworks mimicking saturated nitrogen heterocycles such as pyrrolidine/pyrrolidone.