Synthesis of Quinazolin-4-ones by Copper-Catalyzed Isocyanide Insertion

Abstract

Herein, we report a novel copper-catalyzed imidoylative cross-coupling/cyclocondensation reaction between 2-isocyanobenzoates and amines efficiently producing quinazolin-4-ones. The reaction utilizes Cu­(II) acetate as an environmentally benign catalyst in combination with a mild base and proceeds well in anisole, a recommended, sustainable solvent. Additionally, the reaction does not require dry conditions or inert atmospheres for optimal performance. The scope of this isocyanide insertion reaction is rather broad, tolerating various functionalized isocyanobenzoates and a range of substituted amines, although the use of aromatic amines as nucleophiles requires microwave heating.

A Facile C‐H Insertion Strategy using Combination of HFIP and Isocyanides: Metal‐Free Access to Azole Derivatives

“…In recent years, the isocyanide insertion strategy under non‐metal, Lewis‐acid, base and photocatalyzed reaction conditions become familiar in the field of organic synthesis [8,12] . It is noteworthy that the isocyanide insertion chemistry under transition metal‐free and non‐transition metal‐free conditions are very rare and remained asserting task for the synthetic chemists [8–12] . In particular, utilizing isocyanides as C1‐source has always been explored under transition metal‐catalysis [13–15] .…”

“…[1a] A large number of useful reports have been noticed on isocyanide insertion owing to their reactivities and efficiencies. In literature, it has been shown that the isocyanides have been utilized as CÀ NÀ C, [4][5][6][7][8][9] CÀ N [10][11][12] and C1-source [13][14][15] to construct various complex molecules (Scheme 1).Further, the reported methodologies are mainly concerned on using the transition metals such as Pd, [4,13,15] Cu, [5,11] Co [6] and Ni. [7,14] In recent years, the isocyanide insertion strategy under non-metal, Lewis-acid, base and photocatalyzed reaction conditions become familiar in the field of organic synthesis.…”

“…[1a] A large number of useful reports have been noticed on isocyanide insertion owing to their reactivities and efficiencies. In literature, it has been shown that the isocyanides have been utilized as CÀ NÀ C, [4][5][6][7][8][9] CÀ N [10][11][12] and C1-source [13][14][15] to construct various complex molecules (Scheme 1).…”

“…Further, the reported methodologies are mainly concerned on using the transition metals such as Pd, [4,13,15] Cu, [5,11] Co [6] and Ni. [7,14] In recent years, the isocyanide insertion strategy under non-metal, Lewis-acid, base and photocatalyzed reaction conditions become familiar in the field of organic synthesis.…”

Palladium‐Catalyzed Carbonylative Synthesis of 2‐(Trifluoromethyl)quinazolin‐4(3H)‐ones from Trifluoroacetimidoyl Chlorides and Nitro Compounds

“…[2] Therefore, numerous elegant synthetic routes have been established for the assembly of structurally diverse quinazolin-4(3H)-ones in the past decades. [3] The most frequently used strategies lie in the condensation reactions of benzoic acid derivatives and also palladium-catalyzed carbonylative cyclization reactions of 2-haloanilines. [4] Palladium-catalyzed carbonylative transformations have emerged as a powerful and straightforward pathway for the synthesis of various carbonyl-containing heterocycles.…”