Cyclization of arylacetoacetates to indene and dihydronaphthalene derivatives in strong acids. Evidence for involvement of further protonation of O,O-diprotonated beta-ketoester, leading to enhancement of cyclization.
The chemical features, such as substrate stability, product distribution, and substrate generality, and the reaction mechanism of Brønsted superacid-catalyzed cyclization reactions of aromatic ring-containing acetoacetates (beta-ketoesters) were examined in detail. While two types of carbonyl cyclization are possible, i.e., keto cyclization and ester cyclization, the former was found to take place exclusively. The reaction constitutes an efficient method to synthesize indene and 3,4-dihydronapthalene derivatives. Acid-base titration monitored with (13)C NMR spectroscopy showed that the acetoacetates are fully O(1),O(3)-diprotonated at H(0) = -11. While the five-membered ring cyclization of the arylacetoacetates proceeded slowly at H(0) = -11, a linear increase in the rate of the cyclization was found with increasing acidity in the high acidity region of H(0) = -11.8 to -13.3. Therefore, the O(1),O(3)-diprotonated acetoacetates exhibited some cyclizing reactivity, but they are not the reactive intermediates responsible for the acceleration of the cyclization in the high acidity region. The reactive cationic species might be formed by further protonation (or protosolvation) of the O(1),O(3)-diprotonated acetoacetates; i.e., they may be tricationic species. Thermochemical data on the acid-catalyzed cyclization of the arylacetoacetates showed that the activation energy is decreased significantly as compared with that of the related acid-catalyzed cyclization reaction of a compound bearing a single functional group, such as a ketone. These findings indicate that intervention of the trication contributes to the activation of the cyclization of arylacetoacetates in strong acid, and the electron-withdrawing nature of the O-protonated ester functionality significantly increases the electrophilicity of the ketone moiety.
Kurouchi
Hiroaki
H
Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
Sugimoto
Hiromichi
H
Otani
Yuko
Y
Ohwada
Tomohiko
T
D000090:Acetoacetates / Q000138:chemical synthesis* / Q000737:chemistry; D003500:Cyclization; D004952:Esters / Q000737:chemistry*; D007192:Indenes / Q000737:chemistry*; D015394:Molecular Structure; D009281:Naphthalenes / Q000737:chemistry*; D011522:Protons; D013237:Stereoisomerism; D013464:Sulfuric Acids / Q000737:chemistry*
D000090:Acetoacetates; D004952:Esters; D007192:Indenes; D009281:Naphthalenes; D011522:Protons; D013464:Sulfuric Acids; C093581:indene; C033158:sulfuric acid