Reinvestigation of the Mechanism of gem‐Diacylation: Chemoselective Conversion of Aldehydes to Various gem‐Diacylates and Their Cleavage under Acidic and Basic Conditions

Abstract The mechanism of gem ‐diacylate formation has been studied extensively using tetrabutylammonium tribromide (TBATB) as the catalyst. The reaction proceeds by a nucleophilic attack of an anhydride on an aldehydic carbonyl group, nucleophilic attack of the hemiacylate intermediate on a second molecule of the anhydride, followed by an intermolecular attack of a second acetate group to regenerate the anhydride. gem ‐Diacylates of various aliphatic and aromatic aldehydes were obtained directly from the reaction of a variety of aliphatic and aromatic acid anhydrides in the presence of a catalytic quantity of tetrabutylammonium tribromide (TBATB) under solvent‐free conditions. A significant electronic effect was observed during its formation as well as deprotection to the corresponding aldehyde. Chemoselective gem ‐diacylation of the aromatic aldehyde containing an electron‐donating group has been achieved in the presence of an aldehyde containing an electron‐withdrawing group. Deprotection of the gem ‐diacylate to the parent carbonyl compound can be accomplished in methanol in presence of the same catalyst. Here again, chemoselective deprotection of the gem ‐diacylate of a substrate containing an electrondonating group has been achieved in the presence of a substrate containing an electron‐withdrawing group. Both the acid and base stability order of the various gem ‐diacylates examined follow a similar order. The stability order determined from the present study is: gem ‐dibenzoate > gem dipivalate > gem ‐diisobutyrate > gem ‐diacetate > gem ‐dipropionate. All the gem ‐diacylals are more stable under basic conditions than acidic condition. No correlation was found between the stability order and the p K a ’s of the corresponding acids; rather, the stability order is directly related to the steric crowding around the carbonyl carbon. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)