Synthesis of Carbamoyl Fluorides via a Selective Fluorinative Beckmann Fragmentation

Abstract

A fluorinative Beckmann fragmentation of α-oximinoamides was devised to provide synthetically useful carbamoyl fluorides. High selectivity for fragmentation over a potentially competing Beckmann rearrangement was observed. This protocol has a distinct mechanism and thus a different substrate scope compared with other synthetic methods. α-Oximinoamides derived from the readily available secondary amines, lactams, or isatins were converted into structurally diverse carbamoyl fluorides.

Study of Carbamoyl Fluoride: Synthesis, Properties and Applications

“…With these properties in hand, we considered the application of carbamoyl fluorides. Some chemical reactivities of carbamoyl fluorides have been described in the literature with heteronucleophiles to access ureas, carbamates or thiocarbamates [9c,10,11,13] . In the case of N−CF 3 carbamoyl fluorides, reaction with Grignard reagents and Ni‐catalyzed coupling have also been described to obtain the corresponding amides.…”

“…This approach is limited to N−CF 3 ‐substituted compounds and also required an excess of silver salt. A DAST‐mediated Beckmann fluorinative fragmentation of α‐oximinoamides, mediated by DAST, has also been described [11] . Not only did this method require the prior synthesis of the starting α‐oximinoamides but it also used the toxic and explosive DAST [12] .…”

“…A DAST-mediated Beckmann fluorinative fragmentation of α-oximinoamides, mediated by DAST, has also been described. [11] Not only did this method require the prior synthesis of the starting α-oximinoamides but it also used the toxic and explosive DAST. [12] Finally, the reaction of difluorocarbene, thermally generated from BrCF 2 CO 2 Na, with hydroxylamines provided the corresponding carbamoyl fluorides.…”

Synthesis of Carbamoyl Fluorides Using a Difluorophosgene Surrogate Derived from Difluorocarbene and Pyridine N-Oxides

“…In instances where the signals for the two rotamers overlap in the 13 C NMR spectrum, a "2C" notation is provided in the chemical shift listing. 21 N-Benzyl-N-phenyl-carbamoyl Fluoride (3a). The title compound was synthesized using 1a (0.073 g, 0.40 mmol) and isolated as a colorless oil, or a white solid upon standing (0.089 g, 0.39 mmol 97%, mp 36−37 °C), after purification by flash column chromatography: 1% EtOAc in hexanes.…”

Ring-opening fluorination of bicyclic azaarenes

“… 7,8 Very recently, the Lim group disclosed acyl fluoride synthesis through C–C bond cleavage of carbocycles and cyclic amides. 9 In 2018, the Sarpong group reported an elegant ring-opening fluorination of cyclic amines ( Fig. 1B ).…”