Energy barriers to rotation in axially chiral analogues of 4-(dimethylamino)pyridine

The barriers to enantiomerization of a series of axially chiral biaryl anal ogues of 4-(dimethylamino)pyridine (DMAP) 1-10 were determined experimental ly by means of dynamic HPLC measurements and racemization studies. The barr iers to rotation in derivatives 1-6 (based on the bicyclic 5-azaindoline co re) were lower than those in the corresponding derivatives 7-10 (based on t he monocyclic DMAP core). Semiempirical (PM3), ab initio Hartree-Fock (HF/S TO-3G), and density functional theory (DFT/B3LYP/6-31G*) calculations revea l that these differences in barriers to rotation are the result of differin g degrees of hybridization of the non-pyridyl nitrogen in the enantiomeriza tion transition states (TSs). The importance of heteroatom hybridization as a factor in determining nonsteric contributions to barriers to rotation in azabiaryls of this type is discussed.