A computational study of the enantioselective addition of n-BuLi to benzaldehyde in the presence of a chiral lithium N,P amideElectronic supplementary information (ESI) available: Figure of constrained bonds in initial geometry optimization. Cartesian coordinates, potential energies, free energies, solvation energies, and dispersion correction energies for the different TSs. See DOI: 10.1039/c2ob06910e

In the presence of a chiral lithium N,P amide, alkylation of benzaldehyde results in an enantioselective formation of 1-phenyl-pentanol. This stereoselective addition reaction has herein been studied using dispersion-corrected density functional theory. For five different chiral ligands originating from amino acids the resulting enantioselectivity has been computationally determined and compared with experimentally available enantiomeric ratios (e.r.). In all cases the experimentally preferred enantiomer could be reproduced by the computational model. The selectivity trend among the ligands was found strongly sensitive to the amount of dispersion correction included. The origin of selectivity in the alkylation reaction is found to be composed of many combined interactions. For the most selective ligand 2A the most important factors found, which are favouring the ( R )-TS, are a CH interaction between benzaldehydedimethyl ether (DME), stronger Li-solvation, and Li interactions with the phenyl ring in the backbone of the chiral lithium N,P amide. In addition, solvation by the bulk solvent and the size of the substituent on the nitrogen are also found important factors for the enantioselectivity. The origin of enantioselectivity in alkylations of benzaldehyde using chiral lithium N,P amides has been investigated.