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

Article abstract of DOI:10.1016/0040-4020(95)00886-D

The taste of four fluoro substituted derivatives (2a, 2b, 2c and 2d) is almost indistinguishable from that of the parent compound 4-(4-hydroxyphenyl)butan-2-one (1), the main flavor component of raspberries. The same holds for the comparison between the corresponding acetate, another raspberry ingredient, and its 1-fluoro analogue (2e). In contrast, methyl substituents (as present in compounds 3a, 3b, 3c, 3d and 3e) profoundly alter the organoleptic properties. - The preparation of the fluorinated derivatives (2) involved the three principal options existing for the incorporation of fluorine into organic molecular skeletons : the use of "prefabricates" (i.e., of fluoroaromatic building blocks), the formation of chlorofluorocarbene cycloadducts followed by their solvolytic ring opening and the addition of fluoride to olefinic double bonds. Copyright