A Practical Guide to SuFEx Chemistry: An Overview of S(VI)-SuFEx Linkers and their Reactivity

Abstract Sulfur(VI)–fluoride exchange (SuFEx) is a second generation, metal-free click chemistry concept introduced by Sharpless in 2014. Since the introduction of the concept, a large variety of synthetic methodologies to S(VI)-SuFEx hubs, and their derivatization with oxygen-, nitrogen-, and carbon-based nucleophiles have been developed. Herein, we provide a concise and practical overview for their preparation, SuFExability, inclusive of which substituents are tolerated. The stereoselective synthesis of aza-derivatives is also discussed. 1 Introduction 2 Synthesis of SuFEx Hubs 2.1 Sulfonyl Fluorides 2.2 Fluorosulfates 2.3 Sulfamoyl Fluorides 2.4 Sulfonimidoyl Fluorides 2.5 Sulfuramidimidoyl Fluorides and Sulfurofluoridoimidates 2.6 Sulfondiimidoyl Fluorides 3 Reactivity of SuFEx Hubs 3.1 Reactivity of Sulfonyl Fluorides 3.2 Reactivity of Fluorosulfates 3.3 Reactivity of Sulfamoyl Fluorides 3.4 Reactivity of Sulfonimidoyl Fluorides 3.5 Reactivity of Sulfurofluoridoimidates 3.6 Reactivity of Sulfondiimidoyl Fluorides 4 Stereochemical Considerations in SuFEx Chemistry 5 Conclusion and Outlook