Rotation Barriers of 1‐Adamantyl‐Csp 3 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‐CEt 2 OH ( 11 ) and Ad‐CEt 2 Cl ( 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 13 C 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 ο C. The barrier for 12 is comparable with the single bond rotation barrier of Ad‐CMe 2 Cl ( 2 ) (9.3 kcal mol −1 ), or the analogous barrier of tBu‐CMe 2 Cl ( 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).