Abstract
Efficient synthesis of N,O-heterocyclic tetra-substituted trifluoromethyl-3,1-benzoxazines via a transition-metal-catalyzed decarboxylative intramolecular cyclization was achieved. The decarboxylation of N-benzoyl trifluoromethyl-benzoxazinones generated the amide oxygen nucleophile, allowing a selective internal C(1) -attack on Pd- or Cu-coordinated zwitterions, affording medicinally attractive tetra-substituted vinyl- or ethynyl-trifluoromethyl-3,1-benzoxazines. This protocol can be applied to the synthesis of perfluoroalkyl- and non-fluorinated 3,1-benzoxazines.