Greener synthesis using hydrogen peroxide in ethyl acetate of alicyclic ring-fused benzimidazoles and anti-tumour benzimidazolequinones

Environmentally-friendly and cost effective hydrogen peroxide in ethyl acetate was used to prepare in high yields pyrrolo[1,2-a]benzimidazoles from commercial o-(pyrrolidin-1-yl)anilines without the requirement for organic-aqueous extraction and chromatography. Six, seven and eight membered ring-fused analogues were similarly obtained in high yields with methanesulfonic acid required for the pyrido[1,2-a]benzimidazole. Anti-tumour benzimidazolequinone derivatives were obtained in high yield via the cyclization of 3,6-dimethoxy-2-(cycloamino)anilines.     

Synthesis of aryl ring-fused benzimidazolequinones using 6-exo-trig radical cyclizations

The preparation of alicyclic ring-fused tetracyclic and pentacyclic benzimidazoles containing one and two fused aryl rings, respectively, is achieved conveniently in three steps, including Bu₃SnH-mediated 6-exo-trig cyclization of σ-aryl radicals generated from 1-allyl-2-(ω-bromoaryl)benzimidazoles. Inclusion of 4,7-dimethoxy substituents on the radical precursors allows access to aryl ring-fused benzimidazolequinones, a unique family of potential bioreductive anti-cancer agents.     

Phosphine-mediated annulation of N-protected imines with DEAD

In the presence of triphenylphosphine, the reactions of N-protected imines or their precursors with DEAD proceeded smoothly to give the corresponding functionalized 1H-1,2,4-triazole-1,4(5H)-dicarboxylate derivatives in good to high yields under mild conditions. A plausible mechanism has been proposed on the basis of the control experiments.     

Pictet Spengler-type reactions in 3-arylmethylpiperazine-2,5-diones. Synthesis of pyrazinotetrahydroisoquinolines

The behavior of aldehydes and acetals as N-alkylating agents of 1-acetyl-3-arylmethylpiperazine-2,5-diones and the subsequent cyclization of the N-alkylated products was studied. Use of paraformaldehyde in different reaction conditions gave 6-unsubstituted 3,6,11,11a-tetrahydro-2H-pyrazino[1,2-b]isoquinoline-1,4-diones and, in some cases, benzo[f]pyrazino[1,2-c]1,3-oxazepine-1,4-diones. Succesful reactions with benzaldehyde required a first activation of the lactam function and a catalyzed N-alkylation with the aldehyde dimethyl acetal. The isolated O,N-amidoacetals thus obtained were submitted to a diastereoselective Pictet Spengler-type reaction that worked with arenes at several degrees of ring activation and with thiophene to give 6-phenylpyrazinoisoquinolinediones and the corresponding thieno analog.     

Facile synthesis of highly functionalized six-membered heterocycles via PPh3-catalyzed [4+2] annulations of activated terminal alkynes and hetero-dienes: scope, mechanism, and application

A novel [4+2] annulation between activated terminal alkynes and aza-dienes or oxo-dienes has been developed with the use of triphenylphosphine catalyst (20 mol %), which provides a facile method for synthesis of the corresponding highly functionalized dihydropyridines or dihydropyrans in good to excellent yields. The reaction mechanism has also been established, consisting formal hetero-Diels-Alder reaction catalyzed by PPh₃ and [1,3]-proton transfer, which exhibits a large isotopic effect.     

Annulations of isoquinoline and β-carboline ring systems: synthesis of 8-oxoprotoberberine derivatives

Annulation processes of isoquinoline and β-carboline compounds have been investigated leading to synthetic routes for the preparation of 8-oxoprotoberberine derivatives. The key steps combined a diene formation/Diels-Alder cycloaddition reaction to afford the targeted polycyclic skeletons. Further oxidative transformations of the cycloadducts produced the 8-oxoprotoberberine type products. The alkaloids of this class are important natural products with a wide range of biological activity and the synthethic methodology described in this paper could prove to be useful for the preparation of the D-ring functionalised derivatives.     

Synthesis of 3H-naphtho[2.1-b]pyran-2-carboxamides from cyclocoupling of β-naphthol,propargyl alcohols and isocyanide in the presence of Lewis acids

3H-Naphtho[2.1-b]pyran-2-carboxamides (3H-Benzo[f]chromene-2-carboxamides) can be synthesized from a three-component cyclocoupling reaction of β-naphthol, propargyl alcohols and isocyanide in the presence of ZnI₂ and FeCl₃ under air atmosphere. The reaction is proposed to involve the formation of aryl-zinc (II) σ-bond and its α-addition to isocyanide.     

Direct synthesis of benzoxazinones via Cp*Co(III)-catalyzed C–H activation and annulation of sulfoxonium ylides with dioxazolones

A highly novel and direct synthesis of benzoxazinones was developed via Cp*Co(III)-catalyzed C–H activation and [3 + 3] annulation between sulfoxonium ylides and dioxazolones. The reaction is conducted under base-free conditions and tolerates various functional groups. Starting from diverse readily available sulfoxonium ylides and dioxazolones, a variety of benzoxazinones could be synthesized in one step in 32%-75% yields.     

Directing Group Assisted Unsymmetrical Multiple Functionalization of Arene C−H Bonds

Multiple C?H bond functionalizations promptly install diverse groups on the molecular framework and consequently fabricate complex molecular entities. This review briefly surveys the conceptual development of directing group assisted unsymmetrical multiple functionalization of arene C(sp²)?H bonds, which is exceedingly appealing and highly important.     

Synthesis of seven- and eight-membered [1,2-a] alicyclic ring-fused benzimidazoles and 3-aziridinylazepino[1,2-a]benzimidazolequinone as a potential antitumour agent

Azepino and azocino[1,2-a]benzimidazoles were obtained either by treatment of 1-nitrophenyl-2-azacycloalkanes via a one-pot catalytic hydrogenation/acetylation or by treatment of the acetamides generated in the latter reaction with performic acid. This represents the first facile synthesis of eight-membered [1,2-a] alicyclic ring-fused benzimidazoles. 3-Methoxy-azepino[1,2-a]benzimidazole was elaborated to the novel potential cytotoxin, 3-(N-aziridinyl)-7,8,9,10-tetrahydro-6H-azepino[1,2-a]benzimidazole-1,4-dione. The synthesis included clarification of the reactivity of methoxy-substituted benzimidazoles towards nitration.