Gold(III) Chloride Catalyzed Synthesis of Chiral Substituted 3-Formyl Furans from Carbohydrates: Application in the Synthesis of 1,5-Dicarbonyl Derivatives and Furo[3,2-c]pyridine

摘要

This report describes a gold(III)-catalyzed efficient general route to densely substituted chiral 3-formyl furans under extremely mild conditions from suitably protected 5-(1-alkynyl)-2,3-dihydropyran-4-one using H_2O as a nucleophile. The reaction proceeds through the initial formation of an activated alkyne–gold(III) complex intermediate, followed by either a domino nucleophilic attack/anti-endo-dig cyclization, or the formation of a cyclic oxonium ion with subsequent attack by H_2O. To confirm the proposed mechanistic pathway, we employed MeOH as a nucleophile instead of H_2O to result in a substituted furo[3,2-c]pyran derivative, as anticipated. The similar furo[3,2-c]pyran skeleton with a hybrid carbohydrate–furan derivative has also been achieved through pyridinium dichromate (PDC) oxidation of a substituted chiral 3-formyl furan. The corresponding protected 5-(1-alkynyl)-2,3-dihydropyran-4-one can be synthesized from the monosaccharides (both hexoses and pentose) following oxidation, iodination, and Sonogashira coupling sequences. Furthermore, to demonstrate the potentiality of chiral 3-formyl furan derivatives, a TiBr_4-catalyzed reaction of these derivatives has been shown to offer efficient access to 1,5-dicarbonyl compounds, which on treatment with NH_4OAc in slightly acidic conditions afforded substituted furo[3,2-c]pyridine.