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

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 (I), 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.