Fluorination of carbanions

Until recently the electrophilic fluorination of enolates and carbanions was difficult because many of the procedures employed corrosive materials or reagents that were not readily accessible. Progress in the fluorination of carbanions and enolates with chiral sultam reagents... 

Fluorination of carbanions. These reagents selectively fluorinate a broad variety of carbanions in fair to good yield. Oxygen and nitrogen anions are not affected. The base can be NaH, KH, orn-BuLi, although lithium enolates are less reactive than potassium enolates. Nonpolar solvents are preferable to DMF, THF, or ether. Strongly basic anions can effect p-elimination of HF from 1 when R - CH,. Elimination is suppressed when R = neopentyl or norbomyl. 

Banks, R.E. Murtagh, V Tsiliopoulos, E. Al-Halo compounds. Part 12. Site-specific fluorination of carbanions with perfluoro-Al-fluoropiperidine. J. Fluorine Chem. 1991, 52(3), 389 1. 

Takeuchi, Y. et al., Enantioselective fluorination of organic molecules. 1. Synthetic studies of the agents for electrophilic, enantioselective fluorination of carbanions, Chem. Pharm. Bull., 45,1085,1997. 

Barnette WE (1984) iV-Fluoro-/V-alkylsulfonamides useful reagents for the fluorination of carbanions. J Am Chem Soc 106 452-454... 

Over the last few years the number of heterocyclic N—F reagents has developed tremendously (Fig. 1). The driving force for this interest has been the need for easily accessible and safe reagents capable of the selective fluorination of bioactive molecules. Generated by reaction of F2 with the parent compound, products are obtained that are capable of fluorinat-ing species as diverse as carbanions and aromatics depending on their fluorinating power. 

Fluorination of aromatic rings (other than via carbanions)... 

Fluorination of aromatic rings (other than those via carbanions described above) consists principally of fluorodehydrogenation and fluorodemetallation reactions, both ofwhich are thought to proceed via an arenium ion mechanism (Scheme 25) [85]. 

The stabilization of a carbanion brought by a- or )S-fluorine atoms is thermodynamic. Indeed, because of the great reactivity of carbanions toward elimination of a fluoride ion, they may have short lifetimes a-fluorinated carbanions easily undergo a-elimination processes to carbenes, while )S-fluorinated carbanions undergo jS-elimination reactions. 

Answer. Two factors contribute to the stabilization of carbanions by an adjacent trifluoromethyl group or other perfluorinated groups. Most obviously, the strong inductive effect of the highly electronegative fluorine atoms will tend to increase the... 

F-Teda BF4 (6) is very effective for the fluorination of a wide variety of organic substrates steroidal enol acetates (Table 7)92 and silyl enol ethers, certain carbanions, mildly activated aromatic compounds, and sulfides bearing oc-H atoms.73,75,76,77,84,88 90 The products are obtained with good yields and regioselectivity under very mild reaction conditions (Table 8). 

Table 8. Fluorination of Various Grignard Reagents, Aromatic Compounds and Carbanions with F-Teda BF4 (6)...

F-Teda BF4 is effective for the selective addition of fluorine to steroids in good yield, re-gioselectively and, in many cases, stereoselectively at the 6- and 16-positions, under very mild reaction conditions (Table 7).92 Further, 6 will also efficiently fluorinate silyl and alkyl enolates, enamides, carbanions, a-alkenes and actived aromatic compounds (Table 8). As an extension of this method F-Teda BF+ has been used for the electrophilic fluorination of (fluorovinyl)tin compounds affording terminal fluoroalkenes (see Table 9).88... 

Table 12. Fluorination of Enolates and Carbanions with 2-Fluoro-l,3,2-ben-zodithiazole 1,1,3,3-Tetraoxide (2) in Diethyl Ether134135...

Fluoromalonates can be obtained in moderate yields by fluorination of the corresponding carbanions with xenon difluoride, dimethyl sulfide and boron trifluoride-diethyl ether complex.29... 

Dixon and Smart71 examined a series of fluorine-substituted phosphonium ylides. Fluorine stabilizes carbanions via an inductive effect, favouring pyramidal carbanions. Dixon and Smart argued that the first substitution of F on the ylidic carbon (H3P=CHF) causes the carbon to become very pyramidal (the sum of the angles at C is 338.5°), which reduces the potential overlap of the anionic orbital with any P orbitals. The leads to the long P—C distance of 1.723 A. The second F substitution (H3P=CF2) actually breaks the P—C bond and the system is best described as a weak interaction of phosphine with CF2. Trifluoromethyl groups act to stabilize the anions via hyperconjugation. This leads to a planar ylidic carbon in H3P=C(CF3)2. 

The effect of fluorination on the reactivity of carbanions has been reviewed.65 66 Fluorination has the same influences on carbanion stability as does the effect of fluorination on acidity (see Section 1.2.). A lot of information has been derived from the effect of fluorination on CH acidity.43 The effect of fluorination on deuterium-hydrogen exchange processes in the case of highly fluorinated substances has been examined with estimates of pKa for highly fluorinaled substrates.67... 

Given that fluorine has a destabilizing influence upon planar carbanions, geometry considerations favor the formation of pyramidal anions.69 71 The influence of /(-fluorination on carbanion stability has been described in a variety of ways. In early work the role of negative hyperconjugation was proposed to account for these effects.72... 

Fluorination of a sulfoxide-stabilized carbanion provided a route to fluorinated estrones after elimination of the sulfoxide [111] (equation 62). 

The basicity of the anion CH2X , as a function of X, has been found to decrease in groups 16 (from OH to SH), 15 (from NH2 to PH2), and 14 (from CH3 to SiHs), because the a-stabilization of CH2X increases.5 In contrast, the basicity of CH2X along the series X = F, Cl, Br, I does not decrease, as commonly assumed. Fluorine has been found more effective than the heavier halogens for a-stabilization of carbanions. 

Trapping of carbanions by reactive fluorinated aromatic compounds gives a very simple method of introducing bulky perfluoro substituents (Scheme 28), and the more recent use of TDAE (43) to initiate these processes is discussed in the next section (see Scheme 32). 

The attack at the CFZ group of l,l-dichloro-2,2-difluoroethylene by EtMgBr (Tarrant and Warner, 1954), the attack at the CF2 group of phenoxytrifluoroethylene by phenoxide ion (England et al., 1960) and the replacement of the 1-fluorine of 1-diethylaminotrifluoroethylene with water (Yakubovich et al., 1966) are in line with predictions based on the carbanionic theory. On the other hand, the attack of triethyl phosphite at the terminal difluoro group of w-iodoperfluoro-1-olefins (Knunyants and Pervova, 1962) could be explained by steric control. 

Selective fluorination of a wide variety of carbanions has been carried out very effectively with iV-fluoro-Y-alkyl sulfonamides by Barnette63. Treatment of carbanions of malonates, enolates of ketones, acids and amides, and alkyl and aryl organometallics results in the transfer of fluorine from nitrogen to carbon (equation 43). Yields are fair to... 

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