Regioselective Synthesis of 1,4,6-Trisubstituted-2-Pyridinones and 2,3-Disubstituted (2H)-Isoquinolin-1-ones via Tandem Stille Reaction/Heterocyclisation

ABSTRACT A general route to 1,4,6-trisubstituted 2-pyridinones and 2,3-disubstituted (2H)-isoquinolin-1-ones from (Z)-3-iodovinylic amides 1A-H and 2-iodo N-substituted benzamides 2A-F is described, including compounds bearing a substituent on the aromatic ring. Treatment of (Z)-β-iodovinylic amides 1A-H and 2-iodobenzamides 2A-F with various allenyltributyltin reagents in the presence of palladium acetate, triphenylphosphine and tetrabutylammonium bromide in acetonitrile provided good yields of the corresponding 1,4,6-trisubstituted 2-pyridinones 3A-K and 2,3-disubstituted (2H)-isoquinolin-1-ones 4A-I via tandem Stille reaction and 6-ENDO-DIG azacyclisation.