Synthesis of Spirocyclic β‐ and γ‐Sultams by One‐Pot Reductive Cyclization of Cyanoalkylsulfonyl Fluorides

Authors:
Publisher website
Google Scholar
Abstract
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, NiCl2·6H2O in MeOH). Cyclization proceeds smoothly with considerable efficiency (48–84 %, 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.
Funding Information
  • Foundation for the National Institutes of Health (GM133836)

This publication has 74 references indexed in Scilit: