The α-ketol rearrangement is the acid-, base-, or heat-induced 1,2-migration of an alkyl or aryl group in an α-hydroxy ketone or aldehyde to give an isomeric product.
(1)This rearrangement differs from similar isomerizations of carbohydrates, which involve the migration of hydrogen and proceed through discrete enediol intermediates.
α-hydroxy imines may also undergo the rearrangement, although the thermodynamic driving force to amino ketones is often weak (in the absence of protic acids; see below).
In the conversion of 1 to 2, for instance, coordination of both the hydroxyl and carbonyl groups to aluminum facilitates rapid, selective migration of the bond to the one-carbon bridge.
Hammett analysis and a very negative entropy of activation suggest that the reaction proceeds in a single step through a concerted transition state.
[11] (4)If the relative orientation of the carbonyl and hydroxy group can be controlled (through intramolecular hydrogen bonding, for instance), stereoselectivity can be achieved.
The scope of rearrangements of α-hydroxy ketones and aldehydes is limited only by the fact that the product must be more thermodynamically stable than the starting material.
[12] In many subtle cases, such as the one below, decreased nonbonding interactions in dominant conformations of the favored isomers are often invoked[13] (5)Alkoxyallenes with an α-hydroxy substituent may provide allylic alcohols after rearrangement.
[17] (9)Ketol isomerizations of secondary α-hydroxy carbonyl compounds, which proceed via tautomerization, are probably the closest relative of the α-ketol rearrangement discussed here.
Conditions for the rearrangement of α-hydroxy imines are similar, although the resulting amino ketone products are usually isolated as the corresponding acid salts.