Fluorinated compounds Gauche effect

A related stereoelectronic effect with particular relevance to fluoroaliphatic compounds is the gauche effect [38]. Contrary to expectations based solely on the steric repulsion of fluorine, 1,2-difluorocthanc prefers the gauche rather than antiparallel alignment of the fluorine substituents, by 0.5-0.9 kcal mol [39]. The same is observed for related compounds in which one fluorine atom is replaced... 

As mentioned before, compounds with a C-3 -F down (i.e., compound 1) are anti-HIV effective. This is particularly true for the case in which the base equals thymine or uracil (Table 1). The C-2 -F up substituent found in 2 is equally consistent with anti-HIV activity. However, inversion at either one of these two centers results in the complete disappearance of antiviral activity. One can invoke the aforementioned gauche effect between fluorine and the furanose oxygen to explain why in both active templates of 1 and 2 the S conformation is favored in solution. The inactivity of the inverted conformers, on the other hand, could be explained... 

Derivatives in which the vicinal difluoromethylene motif is extended to include 3,4, 5 and 6 fluorine atoms have been examined to determine conformational preferences [24], The most sophisticated study focused on the hexafluo-romethylene motif, carefully assembled in the diastereomers 3 and 4, that extended earlier studies on tetra- and pentafluoro alkanes [24, 27]. The conformation of these compounds, both in the solid state and in solution, indicates that in order to avoid unfavorable 1,3-dipolar interactions between F atoms, 3 adopts a helical topography that simultaneously allows the vicinal fluorine atoms to adopt the preferred gauche arrangement. The same effect favors an extended anti conformation for 4 that presents no unfavorable 1,3-dipolar interactions and facilitates 3 out 5 possible gauche arrangements of the vicinal fluorine atoms [24, 27],... 

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