Azidoperfluoroalkanes: Synthesis and Application in Copper(I)‐Catalyzed Azide–Alkyne Cycloaddition

Abstract

We report an efficient and scalable synthesis of azidotrifluoromethane (CF 3 N 3 )a nd longer perfluorocarbonchain analogues (), which enables the direct insertion of CF 3 and perfluoroalkyl groups into triazole ring systems.T he azidoperfluoroalkaness how good reactivity with terminal alkynes in copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC), giving access to rare and stable N-perfluoroalkyl triazoles.A zidoperfluoroalkanes are thermally stable and the efficiency of their preparation should be attractive for discovery programs. Dr.V .M atoušek CF Plus Chemicals s.r.o. Kamenice 771/34, 625 00 Brno (Czech Republic) Supportinginformation and the ORCID identification number(s) for the author(s) of this article can be found under http://dx.Scheme 2. Activationa nd decomposition of 2a. 19 FNMR (376 MHz, CDCl 3 )o f5 (QA = CsF): d = À60.3 ppm (s).Scheme 3. Synthesis of azidoperfluoroalkanes 1.Y ields were determined by 19 FNMR, using PhCF 3 as an internal standard. [a] R = Ts. Yield range of 8p reparationsona10-20 mmol scale. [b] R = Nf. Yield range of 2p reparationsona1-2 mmol scale. [c] R = Nf. Yield range of 3p reparations on a1 -2 mmol scale.Scheme 4. Synthesis of azidopentafluoroethane (1b).

1-Iodobuta-1,3-diynes in Copper-Catalyzed Azide–Alkyne Cycloaddition: A One-Step Route to 4-Ethynyl-5-iodo-1,2,3-triazoles

“…The literature search revealed that low conversion and reductive deiodination are common problems for the Sonogashira coupling of 5-iodo-1,2,3triazolecarboxylates, 118 carboxamides, 119,120 nitriles, 121 and even 5-iodo-4-phenyl-triazoles. 122 It is particularly remarkable that for 5-iodotriazoles with an EWG at N 1 the Sonogashira reaction proceeded smoothly, 123 while for triazole with bulky EDG (ferrocenyl) the yields also were low. 124 The best and the simplest solution was found by David These conditions also worked perfectly for the crosscoupling of 4-ethynyl-5-iodotriazoles with acetylenes, providing unsymmetrically substituted enediynes 13a−g fused to 1,2,3-triazole ring in high yields (Scheme 5).…”

Preparation of 1-Azido-2-Bromo-1,1,2,2-Tetrafluoroethane and Its Use in the Synthesis of N-Fluoroalkylated Nitrogen Heterocycles

“…Probing reactivity of azide 1 in [3 + 2] cycloaddition with aromatic or aliphatic terminal alkynes revealed that with 5 mol % of a Cu­(I) source (CuMeSal, copper­(I) 3-methylsalicylate), which was previously used in the click reaction with azidotrifluoromethane and other azidoperfluoroalkanes, the reaction was highly efficient and regiospecific at room temperature and afforded a range of N -bromotetrafluoroethyl-substituted 1,2,3-triazoles ( 2 ) in good to high yields (Table ). To demonstrate scalability of the reaction, triazole 2a was prepared on ca.…”

“…One such unique class of fluorinated building blocks, which has attracted attention recently, is α-fluorinated azides. , Fluorinated azidomethanes have witnessed a renaissance with the introduction of unknown azidofluoromethane, rebirth of known but forgotten and unused azidodifluoromethane, and new synthesis of azidotrifluoromethane and other azidoperfluoroalkanes, including highly synthetically useful azidopentafluoroethane . α-Fluorinated azidoethanes are synthetically accessible by azide addition to fluorinated ethylenes (such as tetrafluoroethylene or chlorotrifluoroethylene) and by quenching of the resulting fluorinated carbanion with a suitable electrophilic reagent (H + , CO 2 , ICl, Br 2 , electrophilic ester, or ArSCN) (Scheme A). − Tetrafluoroethylene-containing azides were prepared from the corresponding bromides via organomagnesium compounds generated using turbo Grignard reagents (Scheme B). , Finally, 1-azido-2-iodo-1,1,2,2-tetrafluoroethane was prepared from sodium azide and 1,2-diiodotetrafluoroethane (Scheme C) .…”

Stable and Storable N(CF3)2 Transfer Reagents

“…In contrast to perfluoroalkyl and perfluoroalkoxy groups, the chemistry of related perfluoroalkyl nitrogen substituents has been studied to a much lesser extent. Some synthetic strategies towards N ‐trifluoromethylamines and related N ‐perfluoroalkylnitrogen derivates have been developed in recent years [28–38] . Efficient strategies towards N , N ‐bis(perfluoroalkyl)nitrogen compounds remain scarce, presumably, because of the lack of suitable starting materials [18,39–40] .…”

“…Some synthetic strategies towards N ‐trifluoromethylamines and related N ‐perfluoroalkylnitrogen derivates have been developed in recent years. [ 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 ] Efficient strategies towards N , N ‐bis(perfluoroalkyl)nitrogen compounds remain scarce, presumably, because of the lack of suitable starting materials. [ 18 , 39 , 40 ] Especially the N , N ‐bis(trifluoromethyl)amino group is of interest as its organic derivatives are known to exhibit high stability, for example against acids and bases,[ 1 , 41 ] and because its potential as substituent in pharmaceuticals was demonstrated, earlier.…”