Solvent dependence of the stereoselectivity in bipyridine N,N′-dioxide catalyzed allylation of aromatic aldehydes: A computational perspective

Abstract The impact of solvent on the enantioselectivity of the allylation of aromatic aldehydes catalyzed by a bipyridine-N,N'-dioxide [(S)-bis-1,1′-(5,6,7,8-tetrahydro-3-phenylisoquinoline)-N,N'-dioxide] has been studied using modern density functional theory methods. The computational results confirm that the pronounced changes in the enantioselectivity originate from changes in the operative mechanism depending on the solvent used. In CH3CN, CH2Cl2 and CHCl3, the allylation of aldehydes proceeds along the ionic dissociative route, which favors the formation of the (R)-alcohol. However, in PhCl and PhCH3, a neutral non-bonded mechanism is favored and the (S)-alcohol is formed predominantly. In each case, electrostatic interactions, π-stacking interactions, and steric repulsion between the catalyst and the substrates all contribute to the enantioselectivity. The present data rationalize the experimental findings and unveil the crucial role of non-covalent interactions in the enantioselectivity of these Lewis-base promoted asymmetric allylations of aldehydes.