Cyclic ketones fluorination

Irradiation of cyclic ketones having perfluoroalkyl groups causes cleavage of a ring to yield acyclic products [I74 (equation 44) Similarly, perfluonnated ketones undergo decarbonylation when irradiated [775]. Gas-phase photolysis of perfluorodiazoketones, in the presence of a trapping agent, yields fluorinated furan as a major product [176] (equation 45)... 

There are several examples of similar reactions of enaminonitriles [9,10,11, 12, 13, 14]. Katsuyama et al. [9] determined that refluxing 3-aminobut-2-enenitrile 16 with fluorinated unsaturated ketone 17 in ethanol leads to high yields of dihydropyridines 18 (Scheme 3.6). The reaction of 16 with fluorinated cyclic ketone 19 leading to heterocycle 20 can be carried out in glacial acetic acid and does not need any additional catalyst or reagent [14] (Scheme 3.6). On the other hand, treatment of aminobutenenitrile 16 with ketones without strong... 

Several cyclic a-fluoro ketones 8 have been obtained from the corresponding cyclic ketones via the enamines 7, using difluorodiazene as the fluorinating agent. 

Selective anodic fluorination of aldehyde and cyclic ketones can be successfully carried out in Et3N-5HF to give the corresponding acyl fluorides and fluoroacyl fluorides, respectively, in good yields, as shown in Eqs. (10) and (11) [41]. In these reactions, fluoride salts such as Et3N-3HF lead to lower yields, reflecting the fact that this salt is discharged prior to oxidation of the carbonyl compounds. 

An enamine-catalyzed asymmetric a-fluorination of ketones, which are notoriously challenging substrates for this reaction, was reported by MacMillan and coworkers in 2011 [27]. After exhaustive automated screening of over 250 organo-catalysts, a Cinchona alkaloid-derived primary amine organocatalyst was identified as the optimal catalyst for this transformation (Scheme 13.11). Only cyclic ketones provided fluorinated products in high yields and enantiomeric excesses. 

Selective Electrochemical Fluorination, Scheme 15 Solvent-free electrochemical fluorination of cyclic ketones in poly HF salt... 

Chen S-Q, Hatakeyama T, Fukuhara T, Hara S, Yoneda N (1997) Electrochemical fluorination of aliphatic aldehydes and cyclic ketones using EtsN-flHF electrolyte. Electrochim Acta 42 1951-1960... 

Lam, Y.-H. Houk, K. N. How Cinchona Alkaloid-Derived Primary Amines Control Asymmetric Electrophilic Fluorination of Cyclic Ketones. /. Am. Chem. Soc. 2014,136,9556-9559. 

Cyclic a-fluorinated ketones undergo solvent-assisted addition of TMSCN in DMF, giving TMS-promoted cyanohydrins in good yields and up to 91% de, with the c/i -product predominating. Interaction of the carbonyl of DMF with TMSCN is proposed to activate the reagent, by weakening the Si-CN bond. Simple reduction of the product with lithium aluminium hydride affords the corresponding fluorinated 1,2-amino alcohols. 

Enantioselective a-fluorination of cyclic ketones can be achieved with excellent enantioselectivity by the use of NFSi in the presence of a primary amine functionalized cinchona alkaloid catalyst (eq 29). ... 

Gas-phase photolysis of the cyclic ketones CFa-(CFj) CF,-C 0 x = 2—5) at 3130 A does not involve migration of fluorine atoms, and the products can be explained on the basis of the general Scheme 11. Reactions 1 and la are the only ones of importance for perfluorocyclopentanone and perfluorocyclohexanone (c/. photolysis of perfiuorocyclobutanone to per-fluorocyclopropane and carbon monoxide ), and reactions 3a and 3b are important only for perfluorocyclo-octanone. 

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