The Origin of endo Stereoselectivity in the Hetero-Diels-Alder Reactions of Aldehydes with ortho-Xylylenes: CH-π, π-π, and Steric Effects on Stereoselectivity

Theoretical studies of stereoselectivity have been carried out with B3LYP and MP2 calculations. The high endo selectivity of hetero‐Diels–Alder reactions of ortho‐xylylenes with acetaldehydes is shown to result from attractive CH–π interactions between alkyl groups of the aldehyde and the aromatic ring in the transition states of the reaction. For the hetero‐Diels–Alder reactions of ortho‐xylylenes with benzaldehyde, the stereoselectivity is shown to be mainly governed by the attractive π–π interactions between the phenyl rings of the benzaldehyde and the ortho‐xylylene. MP2 calculations are necessary to reproduce the stabilizing dispersion interactions. B3LYP and MP2 calculations show that the high endo selectivities of hetero‐Diels–Alder reactions of ortho‐xylylenes with substituted aldehydes are a result of CH–π or attractive π–π interactions between the aldehyde substituent and the ortho‐xylylene π system (see picture).