These are preliminary reports that have not been peer-reviewed. They should not be regarded as conclusive, guide clinical practice/health-related behavior, or be reported in news media as established information. For more information, please see our FAQs.
3 files

Accelerated SuFEx Click Chemistry for Modular Synthesis

submitted on 21.01.2021, 22:20 and posted on 25.01.2021, 05:49 by Christopher J. Smedley, Timothy Gialelis, John Moses
Click chemistry is a method for the rapid synthesis of functional molecules with desirable properties. We report the development of accelerated SuFEx, a powerful click reaction for the efficient coupling of aryl and alkyl alcohols directly with SuFExable hubs catalyzed by 2-tert-butyl-1,1,3,3-tetramethylguanidine (BTMG, Barton's base). The new method circumvents the need to synthesize silyl ether substrates while allowing the use of sub-stoichiometric catalyst loadings. This is made possible through a synergistic effect between BTMG and hexamethyldisilazane (HMDS) additive. The powerful combination drives the in situ formation of reactive TMS-ether intermediates while exploiting the silicon-fluoride bond formation's thermodynamic driving force. Comparatively, the required BTMG base's catalyst loading is generally low (1.0–20 mol%) compared to the dominant SuFEx catalyst, DBU (10–30 mol%). In line with click chemistry principles, the scalable reaction only requires simple evaporation of the volatile side products (NH3, Me3Si-F, TMS-OH, BTMG) under reduced pressure instead of extensive purification. The new SuFEx protocol is tolerant of a wide selection of functional groups and meets all the demands of a click reaction, thereby dramatically shortening reaction times and delivering products in excellent yield.


NCI Cancer Center Support Grant 5P30CA045508


Email Address of Submitting Author


Cold Spring Harbor Laboratory


United States

ORCID For Submitting Author


Declaration of Conflict of Interest

No conflict of interest