Work

Ethene‐1,1‐disulfonyl Difluoride (EDSF) for SuFEx Click Chemistry: Synthesis of SuFExable 1,1‐Bissulfonylfluoride Substituted Cyclobutene Hubs

Year: 2023

Type: article

Abstract: We present the synthesis of 1,1‐bis(fluorosulfonyl)‐2‐(pyridin‐1‐ium‐1‐yl)ethan‐1‐ide, a bench‐stable precursor to ethene‐1,1‐disulfonyl difluoride (EDSF). The novel SuFEx reagent, EDSF, is demonstrated in the preparation of 26 unique 1,1‐bissulfonylfluoride substituted cyclobutenes via a cycloaddition reaction. The regioselective click cycloaddition reaction is rapid, straightforward, and highly efficient, enabling the generation of highly functionalized 4‐membered ring (4MR) carbocycles. These carbocycles are valuable structural motifs found in numerous bioactive natural products and pharmaceutically relevant small molecules. Additionally, we showcase diversification of the novel cyclobutene cores through selective Cs2CO3‐activated SuFEx click chemistry between a single S−F group and an aryl alcohol, yielding the corresponding sulfonate ester products with high efficiency. Finally, density functional theory calculations offer mechanistic insights about the reaction pathway.

Source: Angewandte Chemie International Edition

DOI: 10.1002/anie.202303916

Authors: Christopher J. Smedley, Marie‐Claire Giel, Thomas Fallon, John E. Moses

Institutions: La Trobe University, Monash University, University of Newcastle Australia, Cold Spring Harbor Laboratory, Cancer Center at Cold Spring Harbor Laboratory

Language: English

Topic: Click Chemistry and Applications

Subfield: Organic Chemistry

Field: Chemistry

Domain: Physical Sciences

Open Access status: bronze