LARGE RATE ACCELERATIONS IN ALDOL REACTION OF ORTHO-SUBSTITUTED BENZALDEHYDES

The relative reactivities of ortho- and para-substituted benzaldehydes with the dibutylboron enolate of pinacolone have very different substituent dependences: ortho substituents give large rate enhancements with electron-releasing substituents, while para substituents give extremely small rate effects. Since chelation is inaccessible to the boron enolate (which must also complex to the aldehyde), the origin of the large ortho effects was investigated by multiple regression analysis, which shows that the rates are insensitive to steric effects, but are dominated by resonance interactions. The polarizability and, to a small extent, the field effect of the substituents also affect the reactivity. The most consistent mechanistic explanation involves a variable transition structure with the relative degrees of aldehyde C...O bond-breaking and enolate-aldehyde C...C bond-making changing with substituents.