Density Functional Study of Organocatalytic Cross-AldolReactions between Two Aliphatic Aldehydes: Insight into Their FunctionalDifferentiation and Origins of Chemo- and Stereoselectivities.

Thechemo-, diastereo-, and enantioselectivities in proline and axiallychiral amino sulfonamide-catalyzed direct aldol reactions betweentwo enolizable aldehydes with different electronic nature have beenstudied with the aid of density functional theory (DFT) method. Thepotential energy profiles for the enamine formation between each aliphaticaldehyde and the catalyst confirm that two subject catalysts can successfullydifferentiate between 3-methylbutanal as an enamine component andα-chloroaldehydes as a carbonyl component. Transition statesassociated with the stereochemistry-determining C–C bond-formingstep with the enamine intermediate addition to the aldehyde acceptorfor proline and chiral amino sulfonamide-promoted aldol reactionsare reported. DFT calculations not only provide a good explanationfor the formation of the sole cross-aldol product between two aliphaticaldehydes both bearing α-methylene protons but also well reproducethe opposite syn vs anti diastereoselectivities in the chiral aminosulfonamide and proline-catalyzed aldol reactions. [ABSTRACT FROM AUTHOR]