Rotation Barriers of 1-Adamantyl-Csp3 Bonds Measured with Dynamic NMR

Adamantane 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 13C 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 ∼ 10 kcal mol−1, based on decoalescence of signals at −100 οC. 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 Csp3-Csp3 were found lower than expected when one Csp3 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).