Accelerated SuFEx Click Chemistry for Modular Synthesis

Smedley, Christopher, Gialelis, Timothy, Moses, John (2021) Accelerated SuFEx Click Chemistry for Modular Synthesis. chemRxiv. (Submitted)

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Abstract

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.

Item Type:	Paper
Subjects:	chemistry > techniques > click chemistry > Accelerated SuFEx Click Chemistry chemistry > techniques > click chemistry
CSHL Authors:	Moses, John E.
Communities:	CSHL labs > Moses lab
SWORD Depositor:	CSHL Elements
Depositing User:	CSHL Elements
Date:	2021
Date Deposited:	03 Oct 2023 21:07
Last Modified:	27 Dec 2023 21:04
Related URLs:	Publisher
URI:	https://repository.cshl.edu/id/eprint/41125

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