On-DNA Synthesis of β-Sulfonyl-α,β-Unsaturated Carbonyl Scaffolds via Hydrosulfonation of Alkynylcarbonyl Compounds

The development of new on-DNA synthetic methods is crucial for efficient drug discovery using DNA-encoded libraries (DELs). Herein, we present a novel on-DNA approach based on hydrosulfonation of alkynylcarbonyl compounds to access β-sulfonyl-α,β-unsaturated carbonyl scaffolds bearing vinyl and γ-carbonyl sulfone skeletons. The reaction proceeds via a simple mix of alkynylcarbonyl compound and sodium sulfinate at 80 °C, showing moderate to good conversions, <i>Z</i>-geometry preference, and good DNA compatibility, supporting its utility in DEL construction.