The toolkit of organic synthesis has vastly expanded and allowed to access molecular frameworks of high complexity. Therefore, we seek new types of reactivity with controllable selectivity to empower the arsenal further. Notably, beyond the rational design of the chemical environment, dispersion and electrostatic interactions have contributed to the advancement of the field. One of the ways to enable these interactions is the employment of water as a solvent for water-immiscible systems. In addition, the aqueous-organic interface carries significant potential for taming, which offers possibilities to control reactivity. Earlier, we have shown that 1,4-substituted triazoles can be formed in a mixed aqueous-organic aerosol, switching the selectivity of a recently developed process for the reaction between bromoethenesulfonyl fluoride and organic azides. When the reaction is conducted in a polar solvent, -SO2F triazoles are formed,1 while bromo-triazoles form on-water microdroplets.2 A detailed mechanistic study, including solvent effects, isotope studies and computational details, helped us understand the role of the water interface and promoted synthetic methodology development. We have designed the system and optimized the conditions to achieve the best performance of the reaction to translate the aerosol reactivity into an emulsion. We obtained bromo-triazoles by this new reaction with yields up to 96% and Br:SO2F selectivity up to 64:1, which has not been reported to date. Notably, the chemoselectivity can be reversed in the presence of water. The addition of surfactants re-establishes the formation of sulphonyl fluoride triazoles with selectivity up to 1:40. This represents an unprecedented control of chemoselectivity via alternation of the water-organic interface structure. Scope and limitations of the developed methodology, the origin of selectivity, kinetic studies and computational details will be presented and discussed.

Water controls selectivity in triazole synthesis

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