Chiral Substituted 3-Formylfurans from Carbohydrates: An Expedient Route via N-Bromosuccinimide (NBS)-Mediated Electrophilic Cyclization

Chiral, substituted 3-formylfurans have found widespread applications as synthetic intermediates and are key structural motifs in a variety of bioactive natural products. However, methods for their preparation are scant. We report herein an efficient and general route to synthesize them from suitably protected 2-iodoenones derived from glycals. The synthetic protocol involves Heck coupling between substituted 2-iodoenones and olefins followed by N-bromosuccinimide (NBS)-mediated electrophilic cyclization sequence, using H₂O as a nucleophile. Similarly, a fully substituted chiral 3-formylfuran can be prepared utilizing a two-step approach starting with β-methylstyrene as an olefinic partner in the Heck coupling. Further, to demonstrate the potential of our method, we have synthesized a furo[3,2-c]pyran derivative and a fully protected chiral furan.