Sulfonimidamides and Imidosulfuric Diamides: Compounds from an Underexplored Part of Biologically Relevant Chemical Space

Abstract

Two novel solid reagents—1‐sulfonimidoyl‐ and 1‐sulfamimidoyl‐3‐methylimidazolium derivatives—for the synthesis of sulfonimidamides and imidosulfuric diamides, respectively, were developed. It is shown that these reagents are very effective in substitution reactions with various N‐ and O‐nucleophiles; therefore, they significantly extend the accessibility to the chemical space covered by organosulfur(VI) compounds with S=N bonds. In addition, previously unknown imidosulfuric diamides with free imino nitrogen groups were prepared, and their physical and chemical properties were characterized (including molecular geometry, pKa, Log P, microsomal stability, and reactivity towards typical electrophiles). Similar to other organosulfur(VI) derivatives with S=N bonds, these compounds can be considered as promising bioisosteres of amides, ureas, or sulfonamides.

Synthesis of Sulfonimidamides from Sulfenamides via an Alkoxy‐amino‐λ6‐sulfanenitrile Intermediate

“…[28] In 2017, Reboul described alkoxy-l 6 -sulfanenitrile 18 in the mechanistic investigation on the NH and O transfer to sulfides to form sulfoximines. [17a] Compounds 5a and 5b isolated here represent an ew class of l 6 -sulfanenitriles,a nd have been fully characterized (IR, 1 Ha nd 13 CNMR, and HRMS) along with small quantities of the corresponding sulfonimidamide.T he calculated S NI R stretch (DFT) was consistent with that observed for 5b,a nd for 17. [22] In situ IR experiments in the absence of acid also indicated formation of an intermediate ascribed as 5b (1387 cm À1 ).…”

“…[12] Sulfonamides have also been converted into sulfonimidamides,w ith this approach being recently extended by Grygorenko and co-workers to form imidazolium salts as precursors to sulfonimidamides and imidosulfuric diamides. [13] In 2016, we reported af acile metal-free protocol for the direct synthesis of NH-sulfoximines from sulfoxides in high yields and with good functional group compatibility. [14] The NH transfer occurred with sources of ammonia, with ammonium carbamate preferred, in the presence of bis-(acetoxy)iodobenzene as the oxidant.…”

Synthesis of Sulfonimidamides from Sulfenamides via an Alkoxy‐amino‐λ6‐sulfanenitrile Intermediate

“…There are very few reports of related SN-containing compounds.I n1 989, Yoshimura [27] and coworkers reported an example of an alkoxy-l 6 -sulfanenitrile 17 ( Figure 1). [17a] Compounds 5a and 5b isolated here represent an ew class of l 6 -sulfanenitriles,a nd have been fully characterized (IR, 1 Ha nd 13 CNMR, and HRMS) along with small quantities of the corresponding sulfonimidamide.T he calculated S NI R stretch (DFT) was consistent with that observed for 5b,a nd for 17. [28] In 2017, Reboul described alkoxy-l 6 -sulfanenitrile 18 in the mechanistic investigation on the NH and O transfer to sulfides to form sulfoximines.…”

“…[10] TheB olm group has reported copper-catalyzed methods to form sulfonimidamides involving across-coupling of sulfinamides [11] and the oxidation of methyl sulfoximines. [13] In 2016, we reported af acile metal-free protocol for the direct synthesis of NH-sulfoximines from sulfoxides in high yields and with good functional group compatibility. [13] In 2016, we reported af acile metal-free protocol for the direct synthesis of NH-sulfoximines from sulfoxides in high yields and with good functional group compatibility.…”

Additions to N‐Sulfinylamines as an Approach for the Metal‐free Synthesis of Sulfonimidamides: O‐Benzotriazolyl Sulfonimidates as Activated Intermediates

“…Functional‐group sensitivity is also an issue when highly basic and nucleophilic organometallic reagents are applied, as demonstrated by Willis and co‐workers, because they not only require strictly anhydrous and/or otherwise inert conditions, but also do not tolerate important functional groups such as the carbonyl groups of esters, ketones and aldehydes. Grygorenko and co‐workers fine‐tuned the stability of the reactive intermediates by converting the sulfoximinoyl chlorides to the corresponding N ‐methylimidazolium triflates . The same can be achieved by using their relatively stable fluorine‐containing counterparts.…”