Fluorine, stabilizing effect

A subsequent project focused on DFT study aimed at understanding structure/ reactivity relationships and fluorine substitution effects on carbocation stability in... 

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. 

Substituting a leucine residue within the hydrophobic core as discussed above has been shown to generally retard the replication. EGly side chain fluorination, although it has a stabilizing effect on coiled coil folding, does not accelerate product formation (Fig. 9b). The first step of the cycle is highly dependent on the... 

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. 

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] ... 

M. C. The fluorine gauche effect. Langmuir isotherms report the relative conformational stability of ( )-erythro- and ( )-threo-9,10-difluorostearic acids. Chem. Commun. 2002, 1226-1227. 

The stabilizing effect of two fluorine atoms means that difluorocarbene is the least reactive (the most selective) in the series of dihalocarbenes. Therefore, satisfactory yields of 1,1-dif-luorocyclopropanes are usually only reached in the case of decidedly nucleophilic alkenes. 

A more recent development of the same general type of reagent is 2,2-difluoro-1,3-dimethylimidazolidine (DPI), which is even more reactive, because of the stabilizing effects of two nitrogen atoms at the active center [124] (Scheme 2.55). By reaction with the inexpensive phosgene and subsequent nucleophilic fluorination the reagent can be recycled on an industrial scale. 

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