Quinazoline copper catalyzed synthesis

Scheme 3.59 Copper-catalyzed synthesis of fused quinazolines.

Since Watanabe s synthesis of 4(3H)-quinazolinones in 1993 via transition-metal catalyzed reductive N-heterocychzation [ 181 ], several catalytic methods for quinazoline synthesis have been developed [182-186]. For example, palladium-catalyzed cyclocarbonylations of halides with appropriate reactants provided regioselective synthesis of 4(3H)-quinazolinone derivatives [182] and indoloquinazolines [184]. Also selenium-catalyzed reductive N-heterocyclization to quinazolinones has been developed by Sonoda et al. [183]. Copper-catalyzed heteroannulation with alkynes has been developed as highly region- and stereoselective route to 2-(2-arylvinyl)-l,2,3,4-tetrahydroquinazolin-4-ones 64 by Kimdu et al. [ 185] (Scheme 12). Recently, condensation of anthranylamide with various aldehydes to 4-quinazotinones has been found to give excellent yields in the presence of cupric chloride [186]. 

A number of procedures for the preparation of 2-substituted quinazo-lines were reported in 2013. Wu and coworkers prepared 2-substituted quinazolines via a copper-catalyzed cascade synthesis by treating (2-ami-nophenyl) methanols 68 with aromatic aldehydes in the presence of copper(I) chloride, cerium nitrate hexahydrate, ammonium chloride, and potassium hydroxide in acetonitrile in moderate-to-high yields (Scheme 31) (13JOC11342). Electron-withdrawing substituents on either the (2-aminophenyl)methanol or the aromatic aldehyde resulted in a decrease in yield. 

Jiang M, Li J, Wang F, Zhao YC, Zhao F, Dong XC, Zhao WL (2012) A facile copper-catalyzed one-pot domino synthesis of 5,12-dihydroindolo[2,l-b] quinazolines. Org Lett 14 1420-1423... 

Wu and co-workers presented an efficient domino reaction for the rapid synthesis of 5-phenyl-[l,2,3]triazolo[l,5-c]quinazolines derivatives (80) from simple and readily available (E)-l-bromo-2-(2-nitrovinyl)benzenes 79, aldehydes, and sodium azide (Scheme 7.56) [124]. This reaction cascade comprised [3 + 2] cycloaddition, copper-catalyzed SnAt, reduction, cyclization, and oxidation. It is noteworthy that sodium azide is used as a dual nitrogen source in the construction of these fascinating fused A-heterocycles. 

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