Difluorocarbene Enables Access to 2,2-Difluorohydrobenzofurans and 2-Fluorobenzofurans from -Vinylphenols.

2-Fluorobenzofurans are the backbone structures of many drug molecules and have many potential therapeutic bioactivities. Despite the potential applications in medicinal chemistry, practical and efficient synthetic methods for the construction of 2-fluorobenzofuran are very limited. Herein, we report an efficient and general method for the construction of 2-fluorobenzofurans. Contrary to the previous functionalizations of the existing backbone of benzofuran, our strategy directly constructs benzofuran scaffolds alongside the incorporation of fluorine atom on C2 position in a formal [4 + 1] cyclization from readily accessible -vinylphenols and difluorocarbene. In our strategy, ClCFH decomposes into difluorocarbene in the presence of base, which is further captured by the oxygen anion from the hydroxy group in -hydroxychalcones; subsequent intramolecular Michael addition to the α, β-unsaturated system leads to 2,2-difluorohydrobenzofurans, and further fluorine elimination renders 2-fluorobenzofurans by forming one C-O bond and one C-C double bond. Of note, various complex 2,2-difluorohydrobenzofurans and 2-fluorobenzofurans could be readily accessed through our protocol via the late-stage elaborations.