Fluorination of cyclic ketones

The authors suggest that this conformational difference itself is the reason making TS7 (6.8 kcal/mol) more stable than TS8. From our point of view, a more reasonable explanation is the more effective stabilization of the transferred fluorine atom by noncovalent C-H...F interactions in the case of the TS7. In this transition state the fluorine atom has seven close contacts with the hydrogens, the shortest one (2.28 A) being with the axial proton on C9 adjacent to the quinoline substituent. 

On the other hand, in the TS8 the fluorine atom must move away from this proton, and the whole number of the stabilizing noncovalent C-H... F interactions is reduced to five. One of these interactions is with the ortho-proton of the quinolone substituent that explains its axial orientation. 

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

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. 

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). ... 

Kwiatkowski P, Beeson TD, Conrad JC, MacMillan DWG. Enantioselective organocatalytic a-fluorination of cyclic ketones. J. Am. Chem. Soc. 2011 133 1738-1741. 

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)... 

Iodine fluoride is a more versatile reagent than molecular fluorine in geminal fluorination of other hydrazones and related compounds under milder reaction conditions [55] Substrates fluorinated include hydrazones of simple cyclic or steroidal ketones (e g, 4 tert butylcyclohexanone, 70%, 3 cholestanone, 70%), W methyl and A/N dimethylhydrazones [R2C=NNH(CH3) 70%, R2C=NNC(CH3)2, 50%], semicarbazones (R2C=NNHCONH2, 25-50%), and 2,4-dinitrophenylhy-drazones [R2C==NNH-C6H3-2,4(N02)2, 25-50%]... 

Direct regioselective conversion of a variety of cyclic and acyclic ketones to a-fluoro ketones was achieved in high to excellent yield using NFTh (21) in acetonitrile solution.96 The collected results (Table 10) of this highly effective direct transformation show that a comprehensive range of ketones can be fluorinated a to the carbonyl group, without prior activation. 

The CCl4-HF-SbF5 system developed by Jouannetaud and co-workers and used in the selective fluorination of imines (see Section 5.10.1) can be applied in the oxygenation of ketones and carboxamides as well. The hydroxylation of ketones is selective [Eq. (5.229)], provided that a five- or six-membered cyclic carboxonium ion preventing fluorination is involved.534,659 Fluorination, however, may be a side reaction with product distributions depending on quenching conditions (aqueous Na2CC>3 or HF-pyridine). Similar features are characteristic of the transformation of carboxamides.659... 

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... 

Partially fluorinated vinyl ethers of fluoroolefins are quite susceptible to the action of Lewis acids. Reaction usually proceeds with ionization of the allylic C-F bond and results in formation of C=0 group and elimination of alkyl halide. Indeed, 3-chloro-2-methoxyhexafluoro-2-butene 82 reacts with A1C13 with formation of trichlorovinyl ketone 83, and cyclic alkoxyfluoroalkenes demonstrate similar behavior in reaction with aluminum or tin(IV) halides [170] ... 

Various cycloalkanones were converted to rearranged cyclic ethers in the presence of a catalytic amount of hydrogen fluoride in 16-18% yield, while increasing the amount of hydrogen fluoride resulted in a higher conversion of starting ketone, but the ethers were further fluorinated on the aromatic ring23,24,107. 

Oxidation with ozone is a common method for the preparation of fluorinated compounds. Cyclic or linear alkenes can be treated with ozone and, depending on the workup of the reaction mixture, aldehydes, ketones or carboxylic acids are produced. This is illustrated by the ozonoly-sis of. l,.3,4.4-tetrafluorocyclohexene. Oxidative workup gives, depending on the oxidizing agent, formylpentanoic acid 3 or the diaeid 4 with reductive workup the dialdehyde 2 is obtained. If the alkene is substituted by an alkyl group, the product is a ketone. 

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. 

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