Synthesis of Benzoxazinones via Palladium-Catalyzed Intramolecular C-O Coupling

Significance

Reported is the synthesis of benz­oxazinones 2 via palladium-mediated intramolecular C-O coupling-annulation of secondary and tertiary alcohols 1. Optimization studies examined the importance of palladium source, base, and ligand choice. Interestingly, when t-Bu₃P was used as the ligand, several reproducibility issues were encountered. Fortuitously, recourse to the stable tetrafluoroborate salt (BF₄[HPt-Bu₃]) eliminated these problems (M. R. Netherton, G. C. Fu Org. Lett. 2001, 3, 4295). Examination of the substrate scope demonstrated the tolerance of the reaction to alkyl and aryl substitution, with electron-rich and electron-poor aryl groups performing equally well. Substituted anilines were not widely examined. In the single 2-aminopyridyl case examined, moderate conversion into product was observed due to a competing retro-Smiles rearrangement. Extension to the coupling chiral alcohols was additionally demonstrated, proceeding with high stereofidelity (3 → 4).