Pinacol-pinacolone rearrangement

What is pinacol-pinacolone rearrangement?

The acid-promoted 1,2-rearrangement of vicinal diols to aldehydes or ketones is known as the pinacol-pinacolone rearrangement, or pinacol rearrangement, named after the commonly used pinacols. Although commonly carried out in sulfuric acid H2SO4, many other acidic conditions have been successful, including Brønsted and Lewis acids.

The reaction is a stepwise rearrangement involving the formation of a carbocation intermediate by the dehydration of the protonated diol, which is the rate-limiting step, followed by the skeletal rearrangement by the migration of a neighboring substituent to the carbocation site.

pinacol-pinacolone rearrangement - general reaction scheme - pinacol rearrangement
Pinacol-pinacolone rearrangement

Computational studies and experimental results in gas-phase or aprotic solvents indicate that a concerted mechanism dominates over the stepwise mechanism due to the stabilization of the resulting carbocation facilitating the dehydration of protonated diols. The activation energy for the 1,2-rearrangement of the stabilized carbocation is higher than a concerted pinacol rearrangement.

For the practical application of the pinacol-pinacolone rearrangement in organic synthesis, it is crucial to determine which hydroxyl group will be dehydrated and which group will migrate, especially in symmetric and asymmetric pinacols. Several factors affect the regioselectivity of this rearrangement, including the acid used, migratory aptitudes of the substituents, and the formation of primarily formed carbocations. The regioselectivity may also be influenced by the electron density and steric hindrance of the substituent groups. For instance, groups such as cyclopropyl, vinyl, 2-thienyl, 2,5-dimethyl-3-thienyl, and 2-furyl are good migratory groups due to their high electron density, while 2- and 3-pyridyl groups have lower migratory aptitudes. The migration of a group is stereospecific, retaining the configuration of the migrating group. Moreover, the migratory aptitude of groups may differ between symmetric and asymmetric pinacols. Solvent and temperature are additional factors that may influence the outcome of the pinacol rearrangement. For example, primary or secondary alcohols regularly undergo the pinacol rearrangement, while tertiary alcohols do not due to their protonation and hydration.

In addition to pinacols, several other molecules can undergo a similar reaction where a carbocation is formed and a group migrates to it. This includes α-halohydrins, α-hydroxy epoxides, and aziridines. The rearrangement of aziridines under similar conditions is known as the aza-pinacol rearrangement, while α-hydroxy epoxides undergo semi-pinacol rearrangements to give aldols. The vinylogous pinacol rearrangement involves a double bond. Furthermore, this rearrangement can occur without the presence of an acid, through photo-irradiation, thermolysis, or in supercritical CO2, and is generally referred to as a photochemical pinacol rearrangement.