Preparation of Fused Tetracyclic Quinazolinones by Combinations of Aza-Wittig Methodologies and Cu-I-Catalysed Heteroarylation Processes

A number of linear quinazolinones fused to five-membered rings - benzimidazo[2,1-b]quinazolinones 8 and benzothiazolo[2,3-b]quinazolinones 10 - have been prepared from iminophosphoranes 4, derived from N-substituted o-azidobenzamides by a combination of the aza-Wittig methodology and Cu-I-catalysed heteroarylation. The presence of a nitrogen functionality in the N-aryl substituent of 4 promotes heterocyclization after an aza-Wittig reaction/reductive process, either across the 2-position, to afford quinazolino[2,1-b]quinazolinones 11-14, or across the 4-position, to afford the benzimidazo[1,2-c]quinazoline 16 from the initially formed 3H-quinazolin-4-one. When an acetyl group is present in the N-aryl substituent of 4, aza-Wittig reactions with isocyanates lead directly to 4-methylene-4H-3,1-benzoxazines 18; this transformation involves the initial formation of a carbodiimide, which undergoes ring-closure through the enol form of the carboxamide group and eventually an unprecedented iminobenzoxazine/methylenebenzoxazine rearrangement. ((C) Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)