The mechanism of stereoselectivity has been elucidated for the formation of two stereogenic centers in the products of Michael addition to ethyl crotonate by lithiated α-anions of allylic sulfones bearing a remote chiral N-substituent. In order to single out reactive carbanion structures, their conformational analysis was performed by ab initio calculations, finally at the B3LYP/6-31+G(d) level. Low-energy reactant structures were aligned taking intermolecular steric contacts into account. It appeared that only two cyclic conformers of the sulfone nucleophile in which the Li cation is chelated by the anionic carbon, as well as the S=O and NH moieties, are sterically accessible to the crotonate approach. Chiral discrimination of one of these conformers is due to an additional Li-π interaction provided by the remote Ph group of the N-substituent. The enantioselectivity for the formation of the second stereocenter is due to a different asymmetry of the molecular electrostatic potential (calculated ab initio) in nucleophile-electrophile interactions. Thus, the observed diastereoselectivity is the result of a Ph-Li+ interaction, as well as a combination of steric and electrostatic factors.
- Conformational analysis
- Michael addition