Conformational studies of N-carbomethoxy-2-alkoxyindolenines by dynamic NMR, crystallography, and molecular mechanics

The synthesis of N-carbomethoxy-2-alkoxyindolenines and the transformation to their tautomeric indoles is reported. Variable-temperature 1H NMR studies of these 2-alkoxyindolenines evidenced dynamic processes involving two low-energy E and Z equilibrating conformers around the N–C(double bond; length as m-dashO) carbamate bond, for which the barriers (ΔG≠) between the two conformations are in the order of 12.5–13.9 kcal/mol, as deduced from computational NMR line shape simulations. The rotational barrier decreases as the bulkiness of the alkoxyl group increases, with the E conformer being always more stable. Molecular mechanics calculations evidenced a preferred quasi-axial position of the alkoxyl group in the five-membered ring as the steric effect increases, in agreement with X-ray diffraction studies.