Copper-catalysed heteroannulation with alkynes: a general and highly regio- and stereoselective method for the synthesis of (E)-2-(2-arylvinyl) quinazolinones

Abstract A highly regio- and stereoselective procedure for the synthesis of 2-substituted-1,2,3,4-tetrahydroquinazolinones through a two-step procedure, e.g. (i) palladium–copper catalysed C -arylation of terminal alkynes and (ii) copper-catalysed cyclisation of disubstituted alkynes, is described. 2-( N -Alkyl- N -prop-2′-ynyl)amino- N ′- p -tolyl benzamides 5a and 5b reacted with aryl iodides 2 in the presence of (Ph 3 P) 2 PdCl 2 (2.5 mol%), CuI (5 mol%), Et 3 N (5 equiv.) in CH 3 CN at rt for 16 h to yield the disubstituted alkynes 6 – 18 which could then be cyclised with CuI (20 mol%), K 2 CO 3 (2.5 equiv.), Bu 4 NBr (1 equiv.) in CH 3 CN at 80°C for 16–24 h to yield 1-methyl (benzyl)-( E )-2-(2-arylvinyl)-3- p -tolyl-1,2,3,4-tetrahydroquinazolin-4-ones 19 – 31 in good yields. Only in a few cases, the benzodiazepinones 32 – 34 could be obtained in poor yield. The synthesis of novel uracil derivatives 35 and 36 is also described.