Linkage Chemistry of S(VI) Fluorides

Abstract

Sulfur(VI)-fluoride exchange linkage as a next generation of click chemistry was introduced by Sharpless and coworkers in 2014. Distinguished from CuAAC, the SuFEx reaction proceeds under metal-free conditions, and the reactive linkers are variable, enabling access to a diverse class of linkage compounds. Therein, a series of SuFEx linkers emerged has been widely prevalent in diverse fields. The S VI À F bond in comparison to S VI À Cl bond features excellent stability and chemoselectivity. The linkage chemistry primarily involves the formation of SÀ O and SÀ N bonds via commercially available phenols and amines, yet less study on C-SuFEx linkage. This review will focus on three types of linkage for SuFEx linkers comprising SÀ O, SÀ N, and SÀ C bonds, and we hope to provide a practical guidance for SuFEx linkage chemistry.

Functional Polythioamides Derived from Thiocarbonyl Fluoride**

“…[2][3] Among these, the click chemistry, grounded in the principles of modularity and orthogonality, has revolutionized design strategies and the overall approach to synthetic problems. [4] Notably, SuFEx [5][6] -the new-generation click chemistry, has unlocked the potential to engineer novel polymers encompassing sulfone and sulfoxide building blocks with captivating properties, facilitated by the utilization of discrete hubs such as sulfuryl fluoride (SO 2 F 2 ), [7][8][9] thionyl tetrafluoride (SOF 4 ), [10][11][12] ethene-sulfonyl fluoride (ESF) [13] and sulfonimidoyl fluoride (R-SO(N)-F) [14][15] (Figure 1a).…”

Click Chemistry and Targeted Degradation: A Winning Combination for Medicinal Chemists?

“…[13] Specifically, SuFEx exploited the elevated reactivity of sulfur(VI) fluorides with appropriate nucleophiles, including amines (Figure 1C). [13,14] Similar to CuAAC, SuFEx reactions have been reported to be highly efficient (high conversion), water friendly and easy to set up, while significantly differing from the previous one for harnessing metal catalyst-free protocols. Moreover, the easy preparation and good properties of sulfonyl fluorides, such as the insensitivity to ambient oxygen and the hydrolytical stability, are other important advantages.…”

SVI–C Linkage for Allylsulfonximines via BF3-Mediated Allylation

“…The functional group on the nitrogen with variable electronic and steric properties ensures the precise adjustment of stability and reactivity with vast prospects for further exploration. 8 Within the realm of the SuFEx linkage, 9 sulfonimidoyl fluorides serve as stable sulfonimidoyl skeleton precursors, typically forming S VI −O 5c,d,10 and S VI −N 11 bonds via nucleophilic coupling with heteroatom partners. However, S VI −C bond linkage, which dramatically depends on the intensively nucleophilic metal reagent, has been rarely explored (Scheme 1A).…”

“…Within the realm of the SuFEx linkage, sulfonimidoyl fluorides serve as stable sulfonimidoyl skeleton precursors, typically forming S VI –O ,, and S VI –N bonds via nucleophilic coupling with heteroatom partners. However, S VI –C bond linkage, which dramatically depends on the intensively nucleophilic metal reagent, has been rarely explored (Scheme A). , We discovered boron trifluoride enabled the C–SuFEx linkage of TMS-capped alkynes and unactivated alkenes via a hydride transfer-driven process, with the divergent S–C linkage switched by the N-substituent (Scheme B).…”