Recent Advances in the Synthesis and Transformation of Carbamoyl Fluorides, Fluoroformates, and Their Analogues

Abstract

Carbamoyl fluorides, fluoroformates, and their analogues are a class of important compounds and have been evidenced as versatile building blocks for the preparation of useful molecules in organic chemistry. While major achievements were made in the synthesis of carbamoyl fluorides, fluoroformates, and their analogues in the last half of 20th century, an increasing number of reports have focused on using O/S/Se=CF2 species or their equivalents as the fluorocarbonylation reagents for the direct construction of these compounds from the parent heteroatom‐nucleophiles in recent years. This review mainly summarizes the advances in the synthesis and typical application of carbamoyl fluorides, fluoroformates, and their analogues by the halide exchanges and fluorocarbonylation reactions since 1980.

Synthesis of Fluorinated Amines: A Personal Account

“…19 In parallel to carbamoyl fluorides, thiocarbamoyl fluorides are also attractive class of compounds. 17,36 The synthesis of these compounds has gained much attention these last years by using amine derivatives as starting materials and several complementary approaches have been developed. 37 It has been demonstrated that nucleophilic trifluoromethylthiolation reagents could be used in conjunction with amines to access the desired thiocarbamoyl fluorides (Scheme 5).…”

“…The synthesis of carbamoyl fluorides has attracted much attention these last five years due to the increased stability of such a motif in comparison to other halogenated analogues. − However, historical synthetic strategies were mainly based on the use of toxic difluorophosgene derivatives. − More friendly alternatives were since developed relying on the in situ generation of difluorophosgene from a trifluoromethoxy anion − or the use of PDFA as a difluorocarbene source in the presence of an oxidant (Scheme ). It should also be mentioned that other starting materials were used for the synthesis of carbamoyl fluorides including hydroxylamine derivatives. − …”

eFluorination for the Rapid Synthesis of Carbamoyl Fluorides from Oxamic Acids

“…Fluorine has long held a special place in many areas of chemistry as a result of its ability to impart or enhance remarkable physical and chemical properties to a molecule when present in its framework. − Carbamoyl fluorides have attracted much attention for their use as insecticides and esterase inhibitors. − In addition, because carbamoyl fluorides exhibit greater stability and selectivity than carbamoyl chlorides, they represent exceptional building blocks in the synthesis of hydrazines, isocyanates, carbamates, thiocarbamates, ureas, and amides. − ,, Unfortunately, their synthesis can remain a challenge (Figure ). , The primary preparation method is to treat a carbamoyl chloride with nucleophilic sources of fluoride. , While this method seems straightforward, it still requires the preparation of the highly reactive and often unstable chloride analogue, which is usually produced using expensive and highly toxic phosgene derivatives. , The past decade has seen a rapid increase in the development of novel methods for preparing carbamoyl fluorides, confirming the growing interest of the synthetic community in this fluorinated motif. − However, most use impractical conditions, often combined with highly air- and water-sensitive, toxic, hazardous, and expensive reagents, such as carbonyl difluoride, ,− carbon disulfide, highly reactive and unstable carbamoyl chlorides, or explosive diethylaminosulfur trifluoride (DAST)-type reagents. , Some other methods need expensive Ag salts, significant excess of reagents leading to time-consuming chromatographic purifications, , or high temperatures . Although some early work has yielded the desired products in single-step reactions, using DAST and silver salts presents a significant challenge to scale up the reaction, especially under process-friendly conditions. ,− There is an urgent need to develop a novel, practical, sustainable, inexpensive, and milder way to access carbamoyl fluorides rapidly.…”

“… 19 , 20 The past decade has seen a rapid increase in the development of novel methods for preparing carbamoyl fluorides, confirming the growing interest of the synthetic community in this fluorinated motif. 21 − 24 However, most use impractical conditions, often combined with highly air- and water-sensitive, toxic, hazardous, and expensive reagents, such as carbonyl difluoride, 13 , 25 − 28 carbon disulfide, 29 highly reactive and unstable carbamoyl chlorides, 28 or explosive diethylaminosulfur trifluoride (DAST)-type reagents. 30 , 31 Some other methods need expensive Ag salts, 32 significant excess of reagents leading to time-consuming chromatographic purifications, 33 , 34 or high temperatures.…”

Visible-Light-Induced DDQ-Catalyzed Fluorocarbamoylation Using CF3SO2Na and Oxygen

“…Carbamoyl fluoride (R 2 NCOF) is one of the unexplored functional groups in organofluoride chemistry, which has great potential for biological applications . Initially, it has been utilized in medicinal chemistry as a precursor of carbamate with exceptional stability and chemical reactivity .…”