About the “physiological size” of fluorine substituents: Comparison of sensorially active compounds with fluorine and methyl substituted analogues

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

“…[105] When another group is located in the meta position, the site flanked by the two substituents, even if doubly activated, may be sterically too congested to be reached by a bulky reagent. This opens the door to optional site selectivity.…”

Preparation of α,β-Unsaturated Ketones Bearing a Trifluoromethyl Group and Their Application in Organic Synthesis

“…It is known that a trifluoromethyl moiety is almost double the bulk of a methyl group and does not fall much behind that of a tert-butyl group. The energy required for the conformational promotion from the equatorial to the axial position for a trifluoromethyl group is more, than for an isopropyl group [107].…”

A Fluorine Scan of Thrombin Inhibitors to Map the Fluorophilicity/Fluorophobicity of an Enzyme Active Site: Evidence for CF⋅⋅⋅CO Interactions

“…150) of fluorinated drugs in clinical use. The substitution of hydrogen by fluorine often causes minimal steric effects despite their different van der Waals radii (1.20 and 1.47 , respectively), [1,2] while a number of properties, such as lipophilicity, pK a values, and metabolic stability, can be affected in a favorable way. Multiple fluorination of aromatic rings changes the quadrupole moment, [3] which profoundly affects aromatic-aromatic interactions.…”