Yb(OTf)3-promoted synthesis of 3-fluoroquinoline via a decarboxylative Mannich-type reaction

Abstract

We report a concise and practical method for the synthesis of 3-fluoroquinolines via a decarboxylative Mannich-type addition of α,α-difluoro-β-ketoesters with N-aryl imines in the presence of Yb(OTf)₃. The method is broadly applicable to a variety of N-aryl imines and α,α-difluoro-β-ketoesters, affording the corresponding 3-fluoroquinolines in moderate to high yields. Control experiments strongly suggest that Yb(OTf)₃, likely converted in situ into YbCl₃ in the presence of NaCl, promotes both the cyclisation to the quinoline ring and the decarboxylation step. Unlike conventional quinoline synthesis, which often requires harsh conditions, this approach provides a milder, versatile, and efficient entry into 3-fluoroquinoline scaffolds, which are valuable motifs in medicinal chemistry.