Copper-catalyzed synthesis of pyrido-fused quinazolinones from 2-aminoarylmethanols and isoquinolines or tetrahydroisoquinolines?

Organic & Biomolecular Chemistry Pub Date: 2021-04-28 DOI: 10.1039/D1OB00229E

Abstract

Pyrido-fused quinazolinones were synthesized via copper-catalyzed cascade C(sp2)–H amination and annulation of 2-aminoarylmethanols with isoquinolines or pyridines. The transformation proceeded readily in the presence of a commercially available CuCl2 catalyst with molecular oxygen as a green oxidant. Moreover, the dehydrogenative cross-coupling of 2-aminoarylmethanols with tetrahydroisoquinolines was explored, in which CuBr exhibited higher catalytic activity than CuCl2. Broad substrate scope with good tolerance of functionalities was observed under the optimized reaction conditions. The bioactive naturally occurring alkaloid rutaecarpine could be obtained by this strategy. The remarkable feature of this protocol is that complicated heterocyclic structures are readily achieved in a single synthetic step from easily accessible reactants and catalysts. This pathway to pyrido-fused quinazolinones would be complementary to existing protocols.

Graphical abstract: Copper-catalyzed synthesis of pyrido-fused quinazolinones from 2-aminoarylmethanols and isoquinolines or tetrahydroisoquinolines
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