An introduction to diastereoselective aldol reactions using soft enolisation techniques to selectively synthesise one enolate geometry and a ZimmermanTraxler transition state model to form the new CC bond and two new stereogenic centres (stereocentres) at the same time.

#organicchemistry #chemistry #orgo #ochem #education #curlyarrows

Cyclohexylboron chloride (Cy2BCl) is used as a Lewis acid to promote the soft enolisation of a ketone. Precoordination of the Lewis acid makes the alpha protons much more acidic, such that they can be deprotonated by even a weak base like triethylamine (TEA, Et3N). In this enolisation there is a requirement that the molecular orbitals (MOs) that are involved in the mechanism are properly overlapped and able to interact. This means that the reactive conformation for forming the boron enolate is one where the CH bond is perpendicular to the carbonyl bond; in this way it can overlap with the CO pi star antibonding orbital. There are two reactive conformers, but one is more populated than the other as there is less steric clash with the big Lewis acid. Hence enolisation proceeds diastereoselectively to the Eenolate (trans enolate).

The boron enolate is both itself a Lewis acid and a nucleophile. Indeed, when it coordinates and activates an aldehyde electrophile, it becomes a better nucleophile itself. As the enolate can precoordinate to the electrophile, an aldol reaction is now favourable that is intramolucular. This intramolecular aldol reaction proceeds through a 6membered ring transition state. This transition state can be modelled using the ZimmermanTraxler model.