Chiral Superbases with Extended Hydrogen Bond Networks

Extended hydrogen bond networks can substantially increase basicity through stabilization of the resultant conjugate acid. In this study, the chiral superbases (9-11) having anilinyl substituents attached to the prototype superbase 1,8-bis(dimethylamino)naphthalene 1 are examined using DFT methods (PBE1PBE/6-311+G(d,p). While in the gas phase, these are more basic than 1, in THF solution they are slightly weaker bases than 1. While 9-11 are chiral, their rotational barrier about the C_aryl-C_aryl bond is about 20 kcal mol^-1. Aminonaphthyl substituents (18-20) increase the rotational barrier by about 10 kcal mol^-1. As a proof-of-concept, deprotonation of propanal by the chiral bases 9-11 is predicted to have ee's ranging from 58% (with 9) to 95% (with 11). The deprotonation of 4- tert-butylcyclohexanone and cyclohexanoxide by 9 are predicted to have modest (23%) and excellent (97%) ee's, respectively.