Substituent effect of fluorine

Parametrization of Substituents Effects of Fluorine and Other Heteroatoms on OH, NH, and CH Acidities ... 

Effect of Fluorine Substituents on the Acidity and Basicity of Compounds... 

T. Nakano, M. Makino, Y. Morizawa, Y. Matsumura, Synthesis of novel difluoropros-tacyclin derivatives Unprecedented stabilizing effect of fluorine substituents, Angew. Chem. Int. Ed. Engl. 35 (1996) 1019. 

Fluorination has a particularly profound effect on the additions of nucleophiles to per-fluorinated alkenes where the intermediate is anionic. Such processes are dramatically assisted by the strongly stabilizing influence of perfluoroalkyl groups substituted at the incipient anionic site.66 Similar to carbocations (see Section 1.4.), the effect of fluorination in such systems is often ambiguous when monofluorination is involved. a-Halogens generally stabilize anions in the order bromine > chlorine > fluorine, which is the exact opposite to the inductive electron-withdrawing order of the substituents. This effect reflects the importance of l7t-repulsion.67... 

According to the rule formulated in [15], the combined a- and /1-effects (of fluorine substituents) imply that fluoroolefins will react with electrophiles so as to minimize the number of fluorines f to electron-deficient carbon in the transition state. In accordance with this rule, reaction of CH2=CF2 with HF starts as an attack of electrophile (H+) on the CH2 group of ethylene (Eq. 32, pathway A), since this process leads to carbocation 12 stabilized by two a-fluorines in contrast to the much less stable intermediate 13 containing two /1-fluorines and derived from the initial attack of H+ on the CF2 group of the olefin ... 

On the other hand, for RCXJ and R2CF+ the cation stability increases along with the increase of resonance (crR) effect of a halogen F > Cl > Br > I [59]. The significant stabilizing effect of fluorine substituent was explained as a result of back-donation of an unshared electron pair of F on the vacant orbital of carbon. Stability of substituted fluoromethyl cations in gas phase increases going from CF3 to 12 [15] ... 

Substituent Effects of Aryl Fluorides versus Benzylic Fluorides. A remarkable difference is observed for the effect of para substituents on the chemical shifts of aryl fluorides versus benzyl fluorides. In the case of aryl fluorides, electron-donor substituents cause shielding of the fluorine nucleus, whereas such substituents give rise to deshielding of the fluorine nuclei of benzylic fluorides (Scheme 2.2).2... 

THE EFFECT OF FLUORINE SUBSTITUENTS ON PROTON CHEMICAL SHIFTS 17... 

In general, fluorine substitution has exactly the impact upon proton chemical shifts that one would expect from a substituent of its high electronegativity. That is, its effect is largely inductive in nature. Schemes 2.7 and 2.8 provide a comparison of the relative effect of fluorine substituents as compared with those of other halogens and oxygen, which is closest in electronegativity to fluorine. 

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