Mono- and bis-quinidine organocatalysts in the asymmetric methanolysis of cis-1,2,3,6-tetrahydrophthalic anhydride: A conformational and mechanistic NMR study

• Published in: Chirality (New York, N.Y.) Vol. 23; no. 9; pp. 784 - 795
• Main Authors: Balzano, Federica, Jumde, Ravindra P., Mandoli, Alessandro, MASI, SOFIA, PINI, DARIO, UCCELLO-BARRETTA, GLORIA
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01.10.2011
• Subjects: Alkaloids; Anhydrides; Asymmetry; Catalysis; Catalysts; chiral recognition; chiral solvating agent; Chirality; Cinchona alkaloids; conformation; Derivatives; desymmetrization; enantioselective organocatalysis; Nuclear magnetic resonance; ring opening
• ISSN: 0899-0042; 1520-636X; 1520-636X
• DOI: 10.1002/chir.20993

The enantioselective organocatalytic methanolysis of cis‐1,2,3,6‐tetrahydrophthalic anhydride mediated by quinidine derivatives with pyridazine or anthraquinone core was investigated, carrying out a detailed nuclear magnetic resonance study of the conformational preferences of the alkaloid catalysts in the pure solvent and in the presence of the reaction substrates and products. No significant interaction between the meso‐anhydride and the alkaloid derivatives was detected. In contrast, evidence for a considerable influence of the alcohol reactant on the conformational state of some of the chiral organocatalysts could be obtained, which lends support to the hypothesis of general‐base catalysis mechanism, as opposed to the nuclephilic one. The catalytic properties of the studied derivatives showed no obvious correlation with their conformational prevalence in the resting state, suggesting that the alkaloid 9‐O substituent should have a more active role than merely enforcing the chiral fragments to adopt a preferential reactive conformation. A strong enantioselective interaction between the enantiomers of the hemiester product and the alkaloid derivatives was also observed, leading to the conclusion that in the actual reaction conditions a relatively large fraction of the latter is in the protonated form. Chirality, 2011. © 2011 Wiley‐Liss, Inc.