Cobalt-Catalyzed Isocyanide-Based Three-Component Cascade for the Synthesis of Quinazolines

Abstract

A Co-catalyzed cyclization reaction of isocyanides, azides, and amines to access quinazoline derivatives was described. This protocol features a high atom economy, mild reaction conditions, excellent yields, and a broad substrate scope. This cascade reaction involved three or four C–N bonds and the formation of one or two rings. The quinazolin-4­(H)-imines obtained are proven to be versatile intermediates for further valuable transformations. It was also found that the cobalt catalyst could be isolated from the reaction mixture and reused.

Transition metal-catalysed carbene- and nitrene transfer to carbon monoxide and isocyanides

“…Substituted aromatic isocyanides bearing electron-donating or electron-withdrawing groups are generally accepted. Noteworthy is that the reaction with aliphatic isocyanides did not afford the corresponding imidates (89). In addition, the reaction tolerates a wide variety of primary and secondary alcohols furnishing the corresponding imidates 89 in moderate to good yields (31-83%).…”

“…In recent work of this group, the Co II -catalysed nitrene transfer of sulfonyl azides ( 151 ) to cyanoarylisocyanides was applied for the formation of quinazolin-4(3 H )-imines ( 192 ) (Scheme 53a). 89 The cascade process commences with Co II -catalysed formation of the corresponding carbodiimide following the mechanism illustrated in Scheme 47. Subsequent nucleophilic addition of aromatic as well as aliphatic amines ( 140 ) furnished the corresponding N -sulfonyl guanidines ( 193 ).…”

“…For example, Zhao et al reported multiple Rh I -catalysed carbene transfers based on trifluorodiazoethane (87) (Scheme 19a-c). 49 First the authors present a three-component reaction towards imidates (89) Scheme 17 Proposed catalytic cycle of the CoBr 2 -catalysed carbene transfer to isocyanides (5) via a Co III -carbene radical intermediate 79 followed by trapping of ketenimine 81 with amine.…”

[4 + 1 + 1] Tandem Cyclization Reaction Involving Isocyanides: Access to 2-(Trifluoromethyl)quinazolin-4(3H)-imines

“…Compound 3h was prepared according to the literature methods with minor modifications. 18 General Procedure for the Synthesis of Compounds 4/5/6. Take 4aaa as an example; in a 25 mL Schlenk tube, to a mixture of Pd(OAc) 2 (2.2 mg, 0.01 mmol, 5 mol %), PPh 3 (5.2 mg, 0.02 mmol, 10 mol %), Cs 2 CO 3 (130.3 mg, 0.4 mmol, 2.0 equiv), and 1a (0.0666g, 0.2 mmol, 1.0 equiv) were added 2a (0.0175g, 0.24 mmol, 1.2 equiv) and 3a (0.0332g, 0.4 mmol, 2.0 equiv) in 2 mL of 1,4-dioxane.…”

Transition‐Metal‐Catalyzed Cross‐Coupling and Sequential Reactions of Azides with Isocyanides

“…A proposed plausible mechanism is as follows: carbodiimide intermediate 119 was initially obtained via a Co- In the same year, this group described another highly efficient and atom economic syntheses of quinazoline derivatives through a Co-catalyzed cascade three-component cyclization of 2-isocyanobenzonitriles, sulfonyl azides, and amines (Scheme 39). [47] By this approach, two kinds of heterocycles, quinazolin-4(H)-imines 125 and pyrido[2,3,4-de]-quinazolines 127, were prepared with a broad substrate scope and excellent yields. The control experiments suggested that this reaction first proceeded through the carbodiimide intermediate 123 using Co-catalysts.…”