Sulfur-Azide Exchange (SuAEx): A Click Reaction for Chemoselective Sulfonate Ester Formation

Area of Science:

• Organic Chemistry
• Synthetic Chemistry
• Chemical Biology

Background:

• Sulfonate esters are important functional groups in organic synthesis.
• Existing methods for sulfonate ester synthesis often require harsh conditions or lack selectivity.
• There is a need for mild and orthogonal methods for functionalizing complex molecules.

Purpose of the Study:

• To report a novel reaction, sulfur-azide exchange (SuAEx), for the synthesis of sulfonate esters.
• To demonstrate the mild conditions, functional group tolerance, and selectivity of the SuAEx reaction.
• To showcase the utility of SuAEx in complex molecular editing and iterative ligation strategies.

Main Methods:

• Reaction of sulfonyl azides with phenolic substrates.
• Optimization of reaction conditions for mildness and efficiency.
• Demonstration of selectivity for phenolic hydroxyls over aliphatic alcohols.
• Integration of SuAEx with azide-alkyne cycloaddition for iterative synthesis.

Main Results:

• SuAEx efficiently synthesizes sulfonate esters under mild conditions.
• The reaction exhibits broad functional group tolerance.
• SuAEx shows high selectivity for phenolic hydroxyls versus aliphatic alcohols.
• Iterative ligation strategies combining SuAEx and click chemistry were successfully demonstrated.

Conclusions:

• Sulfur-azide exchange (SuAEx) provides an efficient and mild route to sulfonate esters.
• The orthogonality of SuAEx is valuable for selective functionalization in complex synthesis.
• SuAEx is a versatile tool for applications in organic synthesis and chemical biology.