Diversity-Oriented Synthesis of Benzo[f][1,4]oxazepine-, 2H-Chromene-, and 1,2-Dihydroquinoline-Fused Polycyclic Nitrogen Heterocycles under Microwave-Assisted Conditions

An efficient, diversity-oriented synthesis of oxazepino[5,4-b]quinazolin-9-ones, 6H-chromeno[4,3-b]quinolines, and dibenzo[b,h][1,6]naphthyridines was established involving a substrate-basedapproach under microwave-assisted and conventional heating conditionsin high yields (up to 88%). The CuBr2-catalyzed, chemoselectivecascade annulation of O-propargylated 2-hydroxybenzaldehydesand 2-aminobenzamides delivered oxazepino[5,4-b]quinazolin-9-onesinvolving a 6-exo-trig cyclization-airoxidation-1,3-proton shift-7-exo-dig cyclizationsequence. This one-pot process showed excellent atom economy (-H2O) and constructed two new heterocyclic rings (six- and seven-membered)and three new C-N bonds in a single synthetic operation. Onthe other side of diversification, the reaction between O/N-propargylated 2-hydroxy/aminobenzaldehydes and2-aminobenzyl alcohols delivered 6H-chromeno[4,3-b]quinolines and dibenzo[b,h][1,6]naphthyridines involving sequential imine formation-[4 + 2]hetero-Diels-Alder reaction-aromatization steps. The influenceof microwave assistance was superior to conventional heating, wherethe reactions were clean, rapid, and completed in 15 min, and theconventional heating required a longer reaction time at a relativelyelevated temperature.

Automated summary

An efficient synthetic method for oxazepino[5,4-b]quinazolin-9-ones, 6H-chromeno[4,3-b]quinolines, and dibenzo[b,h][1,6]naphthyridines was established using a substrate-based approach under microwave-assisted and conventional heating conditions, achieving high yields (up to 88%). The one-pot process involved CuBr2-catalyzed cascade annulation and delivered oxazepino[5,4-b]quinazolin-9-ones with two new heterocyclic rings and three new C-N bonds. Microwave assistance was found to be superior, providing clean and rapid reactions completed in 15 minutes, compared to longer reaction times and elevated temperatures required for conventional heating.