Steric effects of fluorine substituents

Discussion of the physicochemical sizes of substituents on the basis of conformational analysis of the torsional process of substituted cyclohexanes, cyclophanes, and diaryl derivatives have been summarized by Schlosser [5]. The energies required for the conformational exchange of an equatorial position to the axial position for each substituent in cyclohexane are listed in Table 1.47 [6]. For fluorine, the energy difference between the axial and equatorial environment is negligibly small as compared with methyl, while that of CF3 seems larger than that of z-Pr so far observed in the cyclohexane torsional system. From the 

These steric dissimilarities between hydrogen and fluorine, and methyl and trifluo-romethyl groups, often result in a noticeable difference of reactivity and product selectivity in a number of reactions. 

X-ray crystallographic analysis for 18 [15]. The fluorinated imines 16, 17, and 18 provided (S, S) amines (20) exclusively on reduction with NaBH4, where hydride attacked from the less hindered face via the preferred conformation 19. Regioselective Pd-catalyzed hydrogenolysis of 20 afforded enantiomerically pure 2-fluoro-, 2,2-difluoro-, and 2,2,2-trifluoro -1 -phenylethylamines [16]. 

A keen human nose as an excellent sensor for an odor 

Schlosser, M. (1999) In V.A. Soloshonok, (ed), Enantiocontrolled Synthesis of Fluoro-organic Compounds Stereochemical Challenges and Biomedical Targets Wiley, New York, pp. 613-659. 

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