Iodocyclization-Cross-Coupling Route to Trisubstituted 3-Fluorofurans

Significance

The synthesis of fully substituted 3-fluorofurans via combined iodocyclization of gem-difluoropropargyl alcohols and Suzuki cross-coupling is reported. For the first step, various conditions were screened and microwaves were required as an efficient heating source to afford the 4-iodofurans (A) in satisfactory yields after silica gel column chromatography. Interestingly, when the silica gel was deactivated with Et₃N, the 3,3-difluoro-4-iododihydrofurans (B) were isolated as the products. Either one could be used further in a Suzuki cross-coupling to afford the trisubstituted 3-fluorofurans. The homopropargyl alcohols were synthesized from difluorohomopropargyl bromide and the corresponding aldehydes (R²CHO). Substrate scope was sufficiently studied, but the overall yields from the two-step process were only poor to moderate. A one-pot process would be desirable for this transformation.