N-Arylation of 3-Formylquinolin-2(1 H)-ones Using Copper(II)-Catalyzed Chan-Lam Coupling

Abstract

3-formyl-2-quinolones have attracted the scientific community's attention because they are used as versatile building blocks in the synthesis of more complex compounds showing different and attractive biological activities. Using copper-catalyzed Chan-Lam coupling, we synthesized 32 new N-aryl-3-formyl-2-quinolone derivatives at 80 °C, in air and using inexpensive phenylboronic acids as arylating agents. 3-formyl-2-quinolones and substituted 3-formyl-2-quinolones can act as substrates, and among the products, the p-methyl derivative 9a was used as a substrate to obtain different derivatives such as alcohol, amine, nitrile, and chalcone.

Keywords: 3-formylquinolones; Chan–Lam coupling; N-arylation; copper(II).

Scheme 1

Reported methodologies for N-arylation of 2-quinolones through copper-catalyzed Chan–Lam cross-coupling.

Scheme 2

Methodology for 3-formylquinolone formation.

Figure 1

Crystal structure of 9a determined by single-crystal X-ray diffraction.

Scheme 3

Derivatization of N-p-methylphenyl-3-formylquinolone. Conditions (a) 9a (0.3 mmol), MeOH (4.5 mL), NaBH₄ (0.9 mmol). (b) 9a (0.3 mmol), hydroxylammonium chloride (0.36 mmol) and DMSO (2.5 mL), 110 °C, 90 min. in mono-wave reactor. (c) 9a (0.3 mmol), p-methoxybenzylamine (0.32 mmol) in MeOH (1.2 mL), 4 h, rt. 2. NaBH₄ (0.48 mmol), 20 min. (d) 9a (0.3 mmol), 4-methoxyacetophenone (0.3 mmol), NaOH (sol. 10% w/v, 0.3 mL) in MeOH (1.5 mL), 24 h r.t.