Copper-catalysed cross-coupling affected by the Smiles rearrangement: a new chapter on diversifying the synthesis of chiral fluorinated 1,4-benzoxazine derivatives

Abstract

Synthesis of different chiral fluorinated Boc-[1,4]benzoxazins from their open chain precursors were investigated. The NMR spectra and crystallographic data showed the presence of the Smiles Rearrangement (SR) followed by copper catalysed coupling. The influence of the Boc protecting group, solvent, base, catalyst and the conformational changes of adducts was explored in detail by careful reaction optimization. No product was obtained in the absence of Boc, indicating its crucial role. Finally, a new mechanism for the SR copper catalysed ring closure was proposed.