Synthesis of 1,3-Oxazin-6-ones from Enamides Catalyzed by Palladium

Significance

Reported is the palladium-catalyzed synthesis of 1,3-oxazin-6-ones 2 from enamides 1 via an oxidative carbonylation of the alkenyl C–H bonds. Under the optimum conditions, electron-donating and electron-withdrawing groups containing aryl enamides gave the corresponding oxazinones, generally in good yields (>70%). However, the reaction of β-substituted enamides resulted only in low yield of 3. Complex A was isolated in the reaction of 1 (R¹ = Ph, R² = Me) with Pd(OAc)₂ in DMSO-d ₆. The reaction of intermediate A with CO under the optimized reaction conditions (without palladium catalysis) gave the corresponding oxazinones in 70% yield. On the basis of this result and literature reports, a tentative mechanism for this carbonylation was proposed.

Comment

Transition-metal-catalyzed carbonylation is an efficient method to synthesize various carbonyl compounds (see Reviews below). The current method is the first palladium-catalyzed carbonylation of alkenyl C–H bonds of enamides using CO for the synthesis of 1,3-oxazin-6-ones. The reaction is significant because palladium-­catalyzed C–H carbonylation preferentially proceeds under acidic conditions, while enamides are ­usually susceptible under these conditions. This method tolerates a wide range of functional groups and utilizes readily available enamides and common reagents under an atmospheric pressure of CO.

Reviews

X.-F. Wu, H. Neumann, M. Beller ChemSusChem 2013, 6, 229–241; B. Gabriele, R. Mancuso, G. Salerno Eur. J. Org. Chem. 2012, 6825–6839.