Rotation Barriers of 1-Adamantyl-Csp(3) Bonds Measured with Dynamic NMR

摘要

abstract_textpAdamantane is a lipophilic symmetrical hydrocarbon cage, which has been successfully used as a valuable fragment in drug design. The bond rotations of the 1-adamantyl group in Ad-CEt2OH (11) and Ad-CEt2Cl (12) were investigated, and the bond rotation barriers were compared with energy values from similar compounds measured previously. Exchange rate constants were estimated from lineshape fitting of low temperature C-13 NMR data for compound 11, and used to estimate the free energy of the 1-adamantyl group's single bond rotation at 8.8 kcal mol(-1). Spectra analyses for compound 12 were hampered by impurities, and only an estimate of the respective rate constant was possible from a single coalescence point. The free energy for bond rotation of 1-adamantyl group in 12 was found to be similar to 10 kcal mol(-1), based on decoalescence of signals at -100 C-omicron. The barrier for 12 is comparable with the single bond rotation barrier of Ad-CMe2Cl (2) (9.3 kcal mol(-1)), or the analogous barrier of tBu-CMe2Cl (1) (10.4 kcal mol(-1)). As previously suggested, single bond rotational barriers Csp(3)-Csp(3) were found lower than expected when one Csp(3) is included in a bulky but rigid tertiary residue (e. g. 1-adamantyl), compared to a smaller but more flexible residue (e. g. tert-butyl)./p/abstract_text