One‐Pot Synthesis of Fluorovinyl Acetates and β,β‐Difluoro Carboxylates from a Hypervalent Iodine and Hydrogen Fluoride‐Based Fluorination Reagent

Abstract

A new strategy for the synthesis of fluorovinyl acetates and β,β‐difluoro carboxylates using a hypervalent iodine and hydrogen fluoride‐based fluorination reagent is established through a silver‐catalyzed one‐pot reaction involving formation of carbon‐oxygen and carbon‐nitrogen bonds. The generated fluoroalkenes substituted with the carbon‐oxygen and carbon‐nitrogen bond on the β‐position have the potential to be transformed into various products which would be difficult to obtain via direct fluorination.magnified image

Fluorination and Fluoroalkylation Reactions Mediated by Hypervalent Iodine Reagents

“…A synthetic route to fluorovinyl acetates ( 158 ) and β , β ‐difluoro carboxylates ( 159 ) using PhI(OCOR) 2 and TEA ⋅ 3HF was established through a silver‐catalyzed one‐pot difunctionalization of terminal alkynes ( 157 ) (Scheme ) . The reaction involved hydrofluorination and oxygenation and generated fluoroalkenes bearing the C−O bonds on the β ‐positions, in which TEA ⋅ 3HF was employed as a readily available fluorination source and hypervalent iodine(III) reagents PhI(OCOR) 2 as the cheap oxidants and the sources of esters.…”

“…Alternatively, further hydrofluorination of 162 generats 163 , which undergoes reductive elimination to form β , β ‐difluoro carboxylate ( 159 a ). Furthermore, use of hypervalent iodine(III) reagent and TEA ⋅ 3HF in the presence of phthalimide as a nitrogen source allowed the fluorination and amination of alkynes in a similar manner, affording the corresponding fluoroalkene phthalimide derivatives in good yields …”

Synthesis of Monofluoroalkenes: A Leap Forward

“…In 2016, Yi and Song examined the acyloxyfluorination of terminal alkynes to give 2-fluorovinyl acetates. 109 The reaction proceeded smoothly in the presence of aromatic and aliphatic terminal alkynes, iodonium salts, triethylamine trihydrofluoride, and a silver catalyst to give the monofluoroalkenes with Z selectivity (Scheme 93).…”

Hypervalent iodine(iii)-mediated ring-expansive difluorination of alkynylcyclopropanes en route to the synthesis of difluorinated alkylidenecyclobutanes

“…The terminal alkyne was compatible with the current reaction conditions as well (2w), which was in accordance with Yi's observations in the absence of a silver catalyst. 15 Moreover, the successful scale-up experiments demonstrated the synthetic practicality of this methodology (eqn (1)). a General reaction conditions: 1a (0.1 mmol, 1.0 equiv.…”

“…Interestingly, Yi et al found that the reaction of ethynylcyclopropane with iodobenzene diacetate (PIDA) and HF•Et 3 N under silver catalysis mainly led to 1,2-oxyfluorination product, retaining the cyclopropyl ring in the product. 15 At the outset of our investigation, the easily accessed methyl 4-(cyclopropylethynyl)benzoate 1a was selected as the model substrate to optimize the reaction conditions (Table 1). With PIDA as the oxidant in dichloromethane (DCM) at −15 °C, nucleophilic fluorine source screening revealed that only HF•Py was effective for the ring-expansive difluorination, resulting in the formation of difluorinated alkylidenecyclobutane 2a in 53% yield as a mixture of E/Z (86 : 14) isomers (entries 1-3).…”