Efficient, one-step, cascade synthesis of densely functionalized furans from unprotected carbohydrates in basic aqueous media

• Main Authors: Lambu, Mallikharjuna Rao, Judeh, Zaher M. A.
• Other Authors: School of Chemical and Biomedical Engineering
• Format: Article
• Language: English
• Published: 2021
• Subjects: Engineering::Chemical engineering; Functionalized Furans; Unprotected Carbohydrates
• Online Access: https://hdl.handle.net/10356/150625
• Institution: Nanyang Technological University

Condensation of unprotected carbohydrates with malononitrile or malonamide nitrile in basic aqueous media gave in one-pot densely functionalized polyhydroxyalkyl 2-amino-3-furanonitriles and polyhydroxyalkyl 2-amino-3-furanocarboxamides in excellent 84–98% yields. Disaccharides afforded novel furano-glycosides. Based on the rate of formation of the furans, the ability of the tested bases to catalyze the reaction was concluded as Et₃N > DBU > K₂CO₃ > NaOMe. The reaction mechanism involved the formation of bicyclic furan-furan and furan-pyran intermediates observed for the first time. The reaction proceeded through a cascade mechanism involving Knoevenagel condensation, Oxo-Micheal addition, Thorpe-Ziegler type reaction and ring-opening-induced aromatization. This operationally simple and metal-free reaction proceeded with exclusive chemo-, regio-, and stereo-selectivities under environmentally benign conditions. As demonstrated on a 2 g scale, it holds promise for application in the large-scale synthesis of important intermediates such as densely functionalized furfural.