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)2PdCl2 (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 Bu4NBr 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 e...