Regiodivergent Synthesis of Methylene and Methyl Ring-Fused Isoquinolinones: Base-Promoted Isomerization of N-Allyl Amides.

Methylene and methyl tricyclic isoquinolinones were selectively prepared using a palladium(II)-catalyzed aerobic aza-Wacker reaction, followed by a base- and temperature-controlled Heck reaction catalyzed by palladium(0). Exo- to endo-double-bond migration in isoquinolinones was achieved with 93-99% yields by treatment of the Heck products with Cs2CO3 in dimethyl sulfoxide (DMSO) at 150 °C. A probable mechanism for Cs2CO3-promoted olefin isomerization was proposed and examined using D-isotope labeling experiments. Finally, yuanamide, a 13-methyl-8-oxoprotoberberine alkaloid, was synthesized using the palladium-catalyzed aza-Wacker/Heck/migration sequence.

One-Pot Oxidative Coupling/Decyanation of 6,7-Diphenylindolizine-5-carbonitriles and 2,3-Diphenylquinolizine-4-carbonitriles.

The one-pot oxidative coupling/decyanation reactions of 6,7-diphenylindolizine-5-carbonitriles and 2,3-diphenylquinolizine-4-carbonitriles were investigated using aryl-aryl oxidative coupling reagents. The phenanthroindolizidinones and phenanthroquinolizidinones were produced in 52-89% yields under VOF3/trifluoroacetic acid or [bis(trifluoroacetoxy)iodo]benzene/BF3-mediated conditions. This represents a mild and efficient approach to construct these types of pentacyclic skeletons from the corresponding cyano group-activated aza-Diels-Alder cycloadducts. A plausible mechanism of the one-pot oxidative coupling/decyanation reaction was proposed.

Palladium-Catalyzed Stereoselective Aza-Wacker-Heck Cyclization: One-Pot Stepwise Strategy toward Tetracyclic Fused Heterocycles.

Palladium-catalyzed intramolecular tandem cyclization reactions were conducted for the synthesis of densely cis/cis-fused aza-tetracyclic structures. The process involved a palladium(II)-catalyzed aerobic aza-Wacker reaction, followed by a palladium(0)-catalyzed Heck reaction. The effects of the solvent and benzene substitution pattern on the one-pot, two-step cascade reaction were studied systematically, and a probable mechanism was proposed. Strained pentahydrobenzo[f]cyclopenta[hi]indolizin-6-one and racemic γ-lycorane can also be synthesized rapidly using this palladium-catalyzed aza-Wacker-Heck cyclization reaction.