Palladium-catalyzed heteroannulation leading to heterocyclic structures with two heteroatoms:: A highly regio- and stereoselective synthesis of (Z)-4-Alkyl-2-alkyl(aryl)idene-3,4-dihydro-2H-1,4-benzoxazines and (Z)-3-alkyl(aryl)idene-4-tosyl-3,4-dihydro-2H-1,4-benzoxazines

A highly convenient method has been developed for the synthesis of (Z)-4-alkyl-2-alkyl(aryl)idene-3,4-dihydro-2H-1, 4-benzoxazines 9 and (Z)-3-alkyl(aryl)idene-4-tosyl-3,4-dihydro-2H-1,4-benzoxazines 34-38 through palladium-copper-catalyzed reactions. Aryl. halides 7 reacted with 2-[N-alkyl(benzyl)-N-prop-2'-ynyl]aminophenyl tosylate 6 in the presence of(PPh3)(2)PdCl2 (3 mol %), CuI(5 mol %) in triethylamine at room temperature to yield 2- [N-alkyl(benzyl)-N-(3-aryl-prop-2'-ynyl)]-aminophenyl tosylates 8 in extremely good yields (72-96%). The latter: could then be cyclized with KOH in ethanol-water to Z-9 in a highly regio- and stereoselective manner. Similarly, palladium-copper-catalyzed reaction of 2-(prop-2'-ynyloxy)aniline (21) with aryl iodides 7 led to 22-26 which after tosylation and cyclization with cuprous iodide in CH3CN in the presence of K2CO3 and BU4-NBr led to the (Z)-3-alkyl(aryl)idene-4-tosyl 3,4-dihydro-2H-1,4-benzoxazines 34-38 in good overall yields. The Z-stereochemistry of the products was established from H-1 NMR spectra, (3)J(CH) values (between vinylic proton and methylenic carbon of the heterocyclic ring), NOE experiments, and X-ray analysis. The method was also found to be suitable for the synthesis of bis(benzoxazinylated) derivatives 17, 39, and 2-alkyl-3,4-dihydro-2H-1,4-benzoxazines 18. Our method for the synthesis of 3,4-dihydro-2H-1,4-benzoxazines is highly efficacious, using easily available starting materials under very mild conditions. Also the synthesis of some novel 5-substituted uracil derivatives 40 and 41 containing the benzoxazinyl moiety and of potential biological interest is being reported.