The stable “F–SO2+” donor provides a mild and efficient approach to nitriles and amides

In this update, we developed a mild, efficient and practical method using fluorosulfuryl imidazolium salt A as an environment friendly promoter for conversion of oximes to nitriles or amides via β-elimination or Beckmann rearrangement in almost quantitative yield in 10 minutes. The target products were generated in gram-scale and could be collected through crystallization without silica gel column purification in excellent yield.

amide dehydration, 11 primary amine hydrogenation, 12 and cyanation with other nitrogen sources. 13 Amides are commonly formed by reacting carboxylic acid or its derivatives with amines via condensation or transition metal-catalyzed coupling (Scheme 2a (2)). 14 Aside from that, other protocols to amides have been reported, including carbonylative hydroamidation, 15 nitrile hydrolysis, 16 nitro-reduction amidation, 17 and N-arylation of activated amides. 18 The aforementioned strategies, however, were limited to toxic reagents, expensive transitionmetal catalysts, complex reaction systems, and harsh conditions, especially when two or more components are used as raw materials, which may result in low atom utilization and more by-products. As a result, developing a solution to the aforementioned difficulties is critical.
Oximes are simple and easily accessible class of chemical, 18 particularly aldoximes and ketoximes, which could be converted to nitriles and amides efficiently by b-elimination and Beckman rearrangement, 19 respectively (Scheme 2b). Various catalysts have been devised in recent years to facilitate the heterolysis of nitrogen-oxygen bond in order to achieve this transformation, but there are still certain drawbacks. Such as o-NosylOXY, 20 required microwave irradiation and high temperature. In 2020, Xu reported that HCl$DMPU assisted conversion of aldehydes into nitriles while HCl-DMPU is a solution emitting fumes. 21 Recently, Ding, Qin and Fokin groups reported rapid and mild SO 2 F 2 -promoted dehydration of oxime. 22 However, the use of a greenhouse gas SO 2 F 2 is not safe as it may leak out in operation. 23 Although the organoselenium-catalyzed dehydration of aldoximes can produce nitriles under environment friendly conditions, it required for hours up to days. 24 To some extends, those disadvantages restrict its wide applications.
In 2018, Dong and Sharpless reported a uorosulfuryl imidazolium salt A, which showned unprecedented reactivity, selectivity, and scope as an "F-SO 2 + " donor and is a far more reactive uorosulfurylating agent than SO 2 F 2 . 25 Subsequently, it was developed for the crucial precursor of diazotransfer reagent, which enables the preparation of azides from primary amines. 26 Moreover, uorosulfuryl imidazolium salt A provides a practical and efficient process to prepare unsymmetrical sulfamides via Sulfur(VI)-Fluoride Exchange (SuFEx) click chemistry. 27 Most recently, Liao and Wang groups reported that uorosulfuryl imidazolium salt could produce SO 2 F radical and enabled uorosulfonylation of olens. 28 Inspired by the wide application of uorosulfuryl imidazolium salt and its unprecedented reactivity, and upon viewing the limitations of the preparation of nitriles and amides from oximes, we tried to apply uorosulfuryl imidazolium salt A for the b-elimination of aldoximes and Beckmann rearrangement of ketoximes aer our continuous efforts on the utilization of SO 2 F 2 -promoted transformations. 29 As predicted, the alkylated imidazolium species served as good leaving groups and delivers the "F-SO 2 + " fragment, 27,30 and aldoximes or ketoximes would react with "F-SO 2 + ", with the assistance of the base, to generate the corresponding sulfonyl ester, and further produce the nitriles or amides via b-elimination or Beckmann rearrangement. As predicted, aldoximes or ketoximes would react with uorosulfuryl imidazolium salt A, with the assistance of the base, to generate the corresponding sulfonyl ester, and futher produce the nitriles or amides via b-elimination or Beckmann rearrangement (Scheme 2c). When 4-bromobenzaldehyde oxime (1d) or acetophenone oxime (3a) were used as model substrates, 4-bromobenzonitrile (2d) or N-phenylacetamide (4a) were obtained in 98% yields under the optimal reaction conditions (the more details please see ESI Tables S1 and S2 †).
Encouraged by the high yields of the aforementioned substrates, we tried further gram-scale reactions and aldehyde or ketone were used as starting material, to conrm that this method was more pragmatic than previous reports. As we can see in the Scheme 3, 4-phenylbenzaldehyde (B) or acetophenone (C) was treated with hydroxylamine, producing 4-phenylbenzaldoxime (1i) and acetophenone oxime (3a), that were concentrated to remove ethanol and reacted with uorosulfuryl imidazolium salt in the acetonitrile. It was worthy noted that 4phenylbenzonitrile (2i) and acetanilide (4a) could be obtained in excellent yields through extraction and crystallization without further column purications. There is no doubt that this is a more efficient and simple strategy for the synthesis of nitriles and amides.
To further demonstrate the applicability of this stable SO 2 F donor in the synthesis of complicated molecules, aldehyde D was used as the starting material under standard reaction condition and provided the key precursor for Tarceva in 95% yield (Scheme 4a). We also examined the synthesis of 2-cyano-4 ′methylbiphenyl G and obtained the desired precursor for the novel sartan antihypertensive drugs (e.g., Losartan, Valsartan, Eprosartan and Irbesartan) in 97% yield (Scheme 4b).
In conclusion, we have successfully applied uorosulfuryl imidazolium salt to facilitate the heterolysis of nitrogen-oxygen bond, which can provide an expeditious approach to the synthesis of nitriles and amides in almostly quantitative yield at room temperature. The reaction proceeded well with a broad range of aromatic and aliphatic oximes. Furthermore, the gramscale reaction was carried out without a hitch, and the target product were obtained in excellent yield through crystallization. Moreover, the cascade process was found to be applicable to the synthesis of key precursors for drug molecules in satisfactory yields. Despite the fact that uorosulfuryl imidazolium salt A is a stable and effective reagent for encouraging nitrogen-oxygen bond breakage, the production of uorosulfuryl imidazolium salt A necessitates the use of sulfuryl uoride, a greenhouse gas. Therefore, it is critical to nd more environmentally friendly Table 2 Scope of the synthesis of the amides a a Reaction conditions: ketoximes 3 (0.5 mmol), uorosulfuryl imidazolium salt A (0.75 mmol, 1.5 eq.), TEA (1.0 mmol, 2.0 eq.), CH 3 CN (2.0 mL, 0.25 M), room temperature, 10 min, isolated yields. b 30 min. c 1.5 equiv. of DBU was used.
Scheme 3 Gram-scale production of 2i and 4a by crystallization via cascade process. ways to develop a novel "F-SO 2 " donor that also have superior reactivity.

Conflicts of interest
There are no conicts to declare.