Rapid Deoxyfluorination of Alcohols with N‐Tosyl‐4‐chlorobenzenesulfonimidoyl Fluoride (SulfoxFluor) at Room Temperature

Abstract

The deoxyfluorination of alcohols is a fundamentally important approach to access alkyl fluorides, and thus the development of shelf‐stable, easy‐to‐handle, fluorine‐economical, and highly selective deoxyfluorination reagents is highly desired. This work describes the development of a crystalline compound, N‐tosyl‐4‐chlorobenzenesulfonimidoyl fluoride (SulfoxFluor), as a novel deoxyfluorination reagent that possesses all of the aforementioned merits, which is rare in the arena of deoxyfluorination. Endowed by the multi‐dimensional modulating ability of the sulfonimidoyl group, SulfoxFluor is superior to 2‐pyridinesulfonyl fluoride (PyFluor) in fluorination rate, and is also superior to perfluorobutanesulfonyl fluoride (PBSF) in fluorine‐economy. Its reaction with alcohols not only tolerates a wide range of functionalities including the more sterically hindered alcoholic hydroxyl groups, but also exhibits high fluorination/elimination selectivity. Because SulfoxFluor can be easily prepared from inexpensive materials and can be safely handled without special techniques, it promises to serve as a practical deoxyfluorination reagent for the synthesis of various alkyl fluorides.

Efficient synthesis of dipeptide analogues of α-fluorinated β-aminophosphonates

“…4-Chloro-N-tosylbenzene-1-sulfonimidoyl fluoride (SulfoxFluor, 3, Figure 1) may be an interesting alternative to 1 or 2. It is not commercially available yet, however, it can be obtained from inexpensive materials [24]. Very often small organic molecules containing a fluorine atom are transformed into biologically active compounds.…”

Sulfonyl Fluorides and Their Analogs Deoxofluorination

“…Sulfonimidoyl fluorides [RS(O)(NR')F] are the monoaza analogues of sulfonyl fluorides (R F SO 2 F). In 2019, Hu and coworkers first demonstrated that sulfonimidoyl fluorides can serve as much more robust reagents than sulfonyl fluorides in the deoxofluorination of alcohols [9,24]. Among various sulfonimidoyl fluorides, N-tosyl-4-chlorobenzenesulfonimidoyl fluoride (SulfoxFluor) was selected as the optimal reagent due to its ready availability and high reactivity.…”

“…SulfoxFluor is a thermally stable crystalline compound (m.p. 110-112 C) that can be operated easily under air atmosphere and stored on the bench-top for more than 2 years without decrease in reactivity [9]. For industrial application, SulfoxFluor can be easily prepared in large scale The deoxofluorination of primary and secondary alcohols with SulfoxFluor in the presence of DBU proceeds smoothly at room temperature, affording the corresponding alkyl fluorides in good yields in 10-30 min (Scheme 11) [9].…”

“…110-112 C) that can be operated easily under air atmosphere and stored on the bench-top for more than 2 years without decrease in reactivity [9]. For industrial application, SulfoxFluor can be easily prepared in large scale The deoxofluorination of primary and secondary alcohols with SulfoxFluor in the presence of DBU proceeds smoothly at room temperature, affording the corresponding alkyl fluorides in good yields in 10-30 min (Scheme 11) [9]. When multiple alcohols were subjected to the reaction conditions, the deoxofluorination occurs preferentially at the less sterically hindered position to afford the monofluorination products in synthetically useful yields [9].…”

“…Deoxofluorination with S-F reagents is one of the most effective approaches to construct aliphatic or aromatic C-F bonds [1][2][3][4][5][6][7][8][9]. Among various S-F reagents, sulfonyl fluorides and their derivatives have emerged as promising reagents for deoxofluorination of alcohols, phenols, aldehydes, and ketones in recent years due to their ready availability, high stability, and tunable reactivity [6][7][8][9].…”