Year: 2025
Type: article
Abstract: Sulfur Fluoride Exchange (SuFEx) chemistry represents an emerging class of click reactions that has found broad applications in drug discovery and materials science. Traditionally, SuFEx reactivity has been regarded as the exclusive privilege of sulfur and fluorine. Accordingly, the scaffolds exhibiting SuFEx-like reactivity without sulfur or fluorine have remained underdeveloped. Indeed, SuFEx reactions may represent a more generalizable mode of chemical reactivity. By enhancing the electrophilicity of the carbonyl group and increasing the steric hindrance around the carbon center, we identified disubstituted Meldrum's acid as a novel carbon-based scaffold with SuFEx-like reactivity. Various O-, S-, and N-nucleophiles are viable exchange partners in the presence of Barton's base or DBU. In addition to the original method, a catalytic protocol was developed and successfully applied to drug derivatization, including the gram-scale modification of acetaminophen.
Source: Molecules
Authors: Baoqi Chen, Zhenguo Wang, Xiaole Peng, Jijun Xie, Zhixiu Sun, Le Li
Institution: Sun Yat-sen University
Language: English
Subfield: Organic Chemistry
Field: Chemistry
Domain: Physical Sciences
Open Access status: gold
Estimated APC paid: $3,258
Awards: G1557227940, G8887624980
OpenAlex ID: W4413826801