Transfer of Electrophilic NH Using Convenient Sources of Ammonia: Direct Synthesis of NH Sulfoximines from Sulfoxides

Abstract

A new system for NH transfer is developed for the preparation of sulfoximines, which are emerging as valuable motifs for drug discovery. The protocol employs readily available sources of nitrogen without the requirement for either preactivation or for metal catalysts. Mixing ammonium salts with diacetoxyiodobenzene directly converts sulfoxides into sulfoximines. This report describes the first example of using of ammonia sources with diacetoxyiodobenzene to generate an electrophilic nitrogen center. Control and mechanistic studies suggest a short‐lived electrophilic intermediate, which is likely to be PhINH or PhIN+.

Synthesis of NH-sulfoximines from sulfides by chemoselective one-pot N- and O-transfers

“…22 We report herein a direct preparation of NH--sulfoximines from sulfides by using readily available sources of ammonia in the presence of PhI(OAc) 2 . We reasoned that our protocol for NH transfer to sulfoxides 19 could be extended to sulfides to generate the corresponding sulfilimines, by reaction with the electrophilic nitrene intermediate. However, we were both surprised and delighted to find that when sulfide 1a was reacted with 4 equiv of ammonium carbamate (NH 2 COONH 4 ) in the presence of 2.5 equiv of PhI(OAc) 2 in MeOH at 25 °C, exclusive formation of the corresponding sulfoximine 2a was observed (Scheme 2, conditions i).…”

“…The data reported in Table 1 suggest that two equivalents of oxidant are mandatory to reach full conversion. Based on our previous mechanistic investigation on the direct NH--transfer to sulfoxides, 19 we reasoned that one equivalent of PhI(OAc) 2 would be required to generate the nitrene intermediates (PhI=NH or PhIN + ), whereas the second equivalent would promote the oxygen transfer. To investigate whether N or O is transferred first, we set a series of experiments using diphenyl sulfide derivatives (Scheme 3).…”

One‐Pot Synthesis of Aryl‐ and Alkyl S‐Perfluoroalkylated NH‐Sulfoximines from Sulfides

“…Bolm confirmed the ineffective nitrene transfer to phenyl trifluoromethyl sulfide and its corresponding sulfoxide and thus developed a three‐step synthesis of N ‐protected trifluoromethyl sulfoximines . The same tendency was observed by Luisi and Bull during the metal‐free nitrene transfer to 4‐bromophenyl trifluoromethyl sulfoxide . The first synthesis of fluorinated NH ‐sulfoximines was described by Shreeve's group by using sulfur oxydifluorides and ammonia .…”

Design, synthesis, and antiplasmodial evaluation of a series of novel sulfoximine analogues of carbohydrate‐based thiochromans

“…In order to investigate whether replacing the sulfone moiety with a sulfoximine improves the antiplasmodial activity of the thiochroman scaffolds, sulfoximines 6a and 6b were prepared as shown in Scheme 1 using the protocol reported by Zenzola et al [30,31] our previously reported protocol, [32] was oxidized using 1.2 equiv. of oxone ® to afford sulfoxides 8a and 8b as a separable mixture in 1:3 diastereoisomeric ratio, while oxidation with excess oxone ® led to the formation of sulfone 5 in reasonable yields (Scheme 1).…”