Synthesis of acridinesviacopper-catalyzed amination/annulation cascades between arylboronic acids and anthranils

Abstract

Copper-catalyzed tandem cyclization reactions between arylboronic acids and anthranils have been established, providing new approaches for one-pot assembly of azacycle acridines. This one-pot protocol features simple operation, precious-metal-free conditions and...

Thermo-promoted annulation of arylboronic acids with anthranils under catalyst-free conditions: Access to acridines

“…According to the above results and the previous literature, 23,24,31 a possible mechanism is proposed as shown in Scheme 2. Anthranils can be converted into nitrenes through a thermolytic N–O cleavage at high temperature.…”

“…When 3-substituted boronic acids were used, the annulation could occur at two positions after site-specific C–N cross-coupling according to the literature. 23 However, 1-chloroacridine was not found possibly due to the steric hindrance of the Cl atom. When the polycyclic arylboronic acids, 1- and 2-naphthylboronic acids, were used, benzo[c]acridine and benzo[b]acridine were obtained in 62% and 71% yields, respectively (Table 2).…”

“…23 The crude compound was purified by flash column chromatography over silica gel (EtOAc/n-hexane = 1/20) to provide the product as a yellow powder (104 mg, yield 51%); m.p. 198 °C-201 °C (literature 23 200 °C-202 °C); R f 0.30 (5:1 hexane/EtOAc). 1 H NMR (500 MHz, CDCl 3 ) δ 8.82 (s, 1H), 8.42 (s, 1H), 8.28 (d, J = 9.0 Hz, 1H), 8.24 (d, J = 8.5 Hz, 1H), 8.03 (d, J = 8.5 Hz, 1H), 7.89-7.86 (m, 1H), 7.82 (dd, J = 9.0, 1.5 Hz, 1H), 7.62 (t, J = 8.0, 1H).…”

“…23 The crude compound was purified by flash column chromatography over silica gel (EtOAc/n-hexane = 1/40) to provide the product as a yellow powder (118 mg, yield 53%); m.p. 158 °C-161 °C (literature 23 6-Fluoro-2-methylacridine (4a). The title compound was prepared according to the general procedure.…”

“…More recently, Gao et al 22 developed an efficient copper-catalyzed electrophilic amination of arylboronic acids and anthranils to produce N-aryl-2-aminophenones, which provided acridine derivatives via condensation in TFA (trifluoroacetic acid). Li et al 23 established a Cu-catalyzed one-pot synthesis of acridines using aryl boronic acids and anthranils (Scheme 1).…”