Chan rearrangement


The Chan rearrangement is a chemical reaction that involves rearranging an acyloxy acetate in the presence of a strong base to a 2-hydroxy-3-keto-ester.
This procedure was rediscovered and employed in the Holton Taxol total synthesis.

Reaction mechanism

The methylene bridge in the reactant with adjacent carbonyl and acetyl substituents is acidic and can be deprotonated by strong non-nucleophilic bases such as lithium tetramethylpiperidide or lithium diisopropylamide as in an aldol reaction. The thus formed enolate then gives a nucleophilic acyl substitution with the adjacent carbonyl of the acetyl group through a short lived intermediate oxirane. Acidic workup liberates the free hydroxyl group.