Accelerated SuFEx Click Chemistry For Modular Synthesis. (7th December 2021)

• Record Type: Journal Article
• Authors: Smedley, Christopher J.; Homer, Joshua A.; Gialelis, Timothy L.; Barrow, Andrew S.; Koelln, Rebecca A.; Moses, John E.
• Is Part Of: Angewandte Chemie. Volume 134:Number 4(2022)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2021-12-07
• Subjects: click chemistry -- guanidines -- organocatalysis -- SuFEx -- synthetic methods; Chemistry -- Periodicals; 540
• DOI: 10.1002/ange.202112375
• Languages: English
• ISSNs: 0044-8249

Abstract

Abstract: SuFEx click chemistry is a powerful method designed for the selective, rapid, and modular synthesis of functional molecules. Classical SuFEx reactions form stable S−O linkages upon exchange of S−F bonds with aryl silyl‐ether substrates, and while near‐perfect in their outcome, are sometimes disadvantaged by relatively high catalyst loadings and prolonged reaction times. We herein report the development of accelerated SuFEx click chemistry (ASCC), an improved SuFEx method for the efficient and catalytic coupling of aryl and alkyl alcohols with a range of SuFExable hubs. We demonstrate Barton's hindered guanidine base (2‐tert‐butyl‐1, 1, 3, 3‐tetramethylguanidine; BTMG) as a superb SuFEx catalyst that, when used in synergy with silicon additive hexamethyldisilazane (HMDS), yields stable S−O bond linkages in a single step; often within minutes. The powerful combination of BTMG and HMDS reagents allows for catalyst loadings as low as 1.0 mol % and, in congruence with click‐principles, provides a scalable method that is safe, efficient, and practical for modular synthesis. ASSC expands the number of accessible SuFEx products and will find significant application in organic synthesis, medicinal chemistry, chemical biology, and materials science. Abstract : We report accelerated SuFEx click chemistry utilizing a synergistic BTMG‐HMDS catalytic system. The power and versatility of the reaction are showcased by the SuFEx synthesis of >100 unique molecules from diverse SuFExable hubs. Accelerated SuFEx is a next generation click reaction that improves upon existing protocols and expands the scope of accessible products.