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

Abstract

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 À 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 À 1 , based on decoalescence of signals at À 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 À 1 ), or the analogous barrier of tBu-CMe 2 Cl (1) (10.4 kcal mol À 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).