Computational analysis of cyclophane-based bisthiourea-catalyzed Henry reactions.

The Henry reaction between benzaldehyde and nitromethane catalyzed by a cyclophane-based bisthiourea has been studied with density functional theory [M06-2X-D3/def2-TZVPP/IEFPCM//TPSS-D2/6-31G(d)/IEFPCM]. The results of our study reveal that the transformation involves the reaction of a thiourea-nitronate complex with the uncoordinated aldehyde. On the basis of our calculations, the formation of the major stereoisomer is kinetically preferred. Employing smaller model systems, we show that the observed stereoselectivity arises primarily from differences in hydrogen bonding in diastereomeric transition states.