Merging Ullmann-type cyclization and ring-expansion: a facile assembly of pyrimidine-fused quinazolinones by copper catalysis?

Organic Chemistry Frontiers Pub Date: 2023-03-07 DOI: 10.1039/D3QO00172E

Abstract

A copper-catalyzed tandem cyclization reaction of readily available 4-bromoisatins and amidine hydrochlorides has been developed for the first time, enabling the efficient synthesis of pyrimidoquinazolinones in useful yields. This protocol was realized by subtly combining Ullmann-type cyclization and ring expansion with the use of bimolecular amidine salts as [NCN]- and [1N]-synthons. This reaction features a simple operation, mild conditions and a wide substrate range, and it is also scalable to multigram synthesis. The reaction mechanism was supported by control experiments and detection of key intermediates in the catalytic cycle.

Graphical abstract: Merging Ullmann-type cyclization and ring-expansion: a facile assembly of pyrimidine-fused quinazolinones by copper catalysis
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