Palladium-Catalyzed Multistep Tandem Carbonylation/N-Dealkylation/Carbonylation Reaction: Access to Isatoic Anhydrides

Abstract

A novel and efficient synthesis of isatoic anhydride derivatives was developed via palladium-catalyzed multistep tandem carbonylation/N-dealkylation/carbonylation reaction with alkyl as the leaving group and tertiary anilines as nitrogen nucleophiles. This approach features good functional group compatibility and readily available starting materials. Furthermore, it provided a convenient approach for the synthesis of biologically and medicinally useful evodiamine.

No Making Without Breaking: Nitrogen-Centered Carbonylation Reactions

“…136 Very recently, Ji and co-workers documented an efficient palladium-catalyzed multistep tandem carbonylation/N-dealkylation/carbonylation to synthesize isatoic anhydride derivatives (Scheme 49). 138 2-(Dimethylamino)benzoic acid was the intermediate generated from the ortho−C−H carboxylation with the N,N-dimethyl group as the directing group first. The C−N bond activation occurs in the presence of Cu(II) salts and O 2 , to form the N−Cu species, then transmetalation of Pd(OAc) 2 , insertion of CO, nucleophilic reaction, and reductive elimination to give the desired isatoic anhydride in moderate to good yields.…”

Discovery of Novel Polycyclic Heterocyclic Derivatives from Evodiamine for the Potential Treatment of Triple-Negative Breast Cancer

“…Polycyclic heterocycles are crucial motifs that widely exist in drugs and alkaloids, and the construction of polycyclic heterocycle skeletons is always a hotspot in synthetic chemistry. , The preparation of Evo and its analogues is arduous and usually suffers from multi-step preparation, employing toxic reagents as well as low yields. − In this study, the incorporation of a quinoline core into Evo using a scaffold-hopping strategy makes the de novo synthesis of novel polycyclic compound 6 challenging. Encouragingly, the synthesis of this Evo analogue bearing a quinoline moiety was accomplished in 18% total yield over 12 steps (Scheme ).…”

“…The crude product was purified by silica gel column chromatography (PE/EA 5:1, v/v) to afford a white solid (400 mg, 78.5%). 1 Methyl 4,9-Dihydro-3H-pyrido [3,4-b]indole-6-carboxylate (41). To a cooled solution (0 °C) of compound 40 (344 mg, 1.4 mmol) in 20 mL of dry THF under N 2 , freshly distilled POCl 3 (385 μL, 5.2 mmol) was added slowly using a syringe.…”

Convenient Novel Method to Access N-Benzylated Isatoic Anhydride: Reaction Behavior of Isatoic Anhydride with 4-Chlorobenzyl Chloride in the Presence of Bases

“…Owing to the significant importance of N -alkylated/benzylated isatoic anhydride, various methodologies for its synthesis have been developed earlier. − However, these methods have significant shortcomings and disadvantages of product conversion, time, excess energy and cost-intensive processes, nonrenewable, and usage of toxic chemicals. Hence, there is a pressing need to develop a simple, generic, time, energy, and cost-efficient eco-sustainable method for the synthesis of N -benzylated isatoic anhydride and its derivatives.…”