How Space-Filling Is a Pyridine Lone Pair?

The torsional barriers of 2′‐substituted 2‐arylpyridines have been probed experimentally (by using dynamic NMR spectroscopy) and computationally (by using density functional theory). Due to the compressibility of the lone pair, the torsional barriers of the arylpyridines are up to 4.2 kcal/mol smaller than those of the carba‐analogous biphenyls. Furthermore, the ground states of the 2‐arylpyridines are less twisted than those of the biphenyls. Finally, due to an out‐of‐collinearity distortion, the intramolecular repulsion is attenuated in both rotational transition states, in the syn coplanar conformer (in which the pyridine nitrogen and the substituent R face each other) and in the anti coplanar conformer (in which they are on opposite sides of the molecule). A series of 2‐arylpyridines bearing a diastereotopicity probe have been prepared and examined by DFT and dynamic NMR spectroscopy. The aryl–pyridyl torsional barriers were found by NMR analysis to be about 4 kcal/mol lower than those of the carba‐analogous biphenyls, which gives an indication of the steric compressibility of the lone pair.