Application of N,N-Dimethylethanolamine as a One-Carbon Synthon for the Synthesis of Pyrrolo[1,2-a]quinoxalines, Quinazolin-4-ones, and Benzo[4,5]imidazoquinazolines via [5 + 1] Annulation

Abstract

The synthesis of N-heterocycles composes a significant part of synthetic chemistry. In this report, a Cu(II)-catalyzed green and efficient synthesis of pyrrolo[1,2-a]quinoxaline, quinazolin-4-one, and benzo[4,5]imidazoquinazoline derivatives was developed, employing N,N-dimethylethanolamine (DMEA) as a C1 synthon. Green oxidant O 2 is critical in these transformations, facilitating the formation of a key intermediate�a reactive iminium ion. The method conducted under mild conditions is compatible with a diversity of functional groups, providing an appealing alternative to the previously developed protocols.

Cu(ii)-catalyzed domino construction of spironaphthalenones by dearomatization of β-naphthols and using N,N-dimethylaminoethanol as a C1 synthon

“…Based on the control experiments aforementioned and previous literature reports, 11–13 a plausible mechanism of the Cu-catalyzed spirocyclization is proposed, as depicted in Scheme 3. The reaction initiates from the formation of cationic copper complex A , which proceeds through Fenton-like reactions 14 to form a reactive iminium C .…”

“…Recently, N , N -dimethylethanolamine (DMEA) has been developed as a novel C1 synthon by our group. 12 It has been successfully applied to several types of transformations and has shown some unique activities, compared to conventional C1 synthons such as DMF, DMSO, formaldehyde and methanol. Herein, we present the development of a Cu( ii )-catalyzed facile construction of spironaphthalenones from β-naphthols and DMEA in air.…”

Cu-Catalyzed Carbocyclization for General Synthesis of N-Containing Heterocyclics Enabled by BrCF2COOEt as a C1 Source

“…To our delight, a number of o-phenylenediamines containing electron-donating or electron-withdrawing substituent groups easily reacted with 1.5 equiv of BrCF 2 COOEt, yielding the corresponding benzimidazoles 4a – 4f in synthetically useful yields. More interestingly, N -difluoromethyl benzimidazoles 4g – 4k could be obtained in good yields when 3 equiv of BrCF 2 COOEt was used, in which BrCF 2 COOEt played dual roles as a C1 synthon and difluoromethyl source. Moreover, 2-aminophenols and 2-aminothiophenols were also successfully employed as substrates, and the corresponding benzoxazoles 4l – 4p and benzothiazoles 4q – 4r were obtained in moderate to good yields.…”

Recent Progress in the Catalytic Synthesis of Pyrrolo[1,2‐α]quinoxaline

“…In 2022, Kuang's group [22] used N,N ‐dimethylethanolamine 82 as a C 1 synthon to synthesize the pyrrolo[1,2‐ α ]quinoxalines through 5+1 cyclization. Using BuOH as a solvent, CuBr 2 was used as a catalyst, and in the presence of oxygen at 120 °C for reaction 24 hours.…”

“…Throughout the reaction, with the activation of trimethylamine oxide, the Knölker complex Fe I acts as a carrier for the active hydrogen, and the alcohol 101 a transfers the hydrogen through the catalyst to the nitro group 100 a , which in turn generates the amine and aldehyde in situ, undergoes Pictet‐Spengler type cyclization, oxidation, etc., to obtain the corresponding products, which are highly tolerant and universal for the reaction substrate, but less suitable for some large site resistances and alcohols containing strong electron‐donating groups, such as 4‐dimethylaminophenethyl alcohol, the corresponding products cannot be obtained. The synthetic method avoids the use of large amounts of concentrated hydrochloric acid compared with the method reported by Pereira's group, [22] uses inexpensive iron as the catalyst, and the catalyst maintains extremely strong catalytic activity at 160 °C, which provides a worthy idea for the efficient construction of pyrrolo[1,2‐ α ]quinoxalines skeleton and the design of catalyst. Possible mechanisms show in Scheme 14.…”