Sequential Annulation Research Articles

Facile access to 2,2-diaryl 2H-chromenes through a palladium-catalyzed cascade reaction of ortho-vinyl bromobenzenes with N-tosylhydrazones.

A palladium-catalyzed cascade reaction of ortho-vinyl bromobenzenes with N-tosylhydrazones has been developed, which provides a facile approach to 2,2-disubstituted 2H-chromenes. The migration of palladium from the aryl to vinyl position is crucial, as the in situ produced vinyl palladium intermediate could further react with diazo compounds to generate the reactive species for the sequential annulation.

1-(2H-Azirine-2-carbonyl)benzotriazoles: building blocks for the synthesis of pyrrole-containing heterocycles.

A one-pot method was developed for the preparation of 2H-azirine-2-carbonylbenzotriazoles, formed by the reaction of benzotriazole with 2H-azirine-2-carbonyl chlorides, which were generated by the Fe(ii)-catalyzed isomerization of 5-chloroisoxazoles. The Co(ii)-catalyzed reaction of 2H-azirine-2-carbonylbenzotriazoles with 1,3-diketones provides 2-((benzotriazol-1-yl)carbonyl)pyrroles in moderate to good yields. Base-promoted annulations of 2-((benzotriazol-1-yl)carbonyl)pyrroles with aldehydes, ketones, isocyanates and isothiocyanates afford various substituted pyrrolo[1,2-c]oxazole and 1H-pyrrolo[1,2-c]imidazole derivatives in moderate to high yields. The 6-acyl group of these adducts can be removed by triflic acid, giving further new pyrrolo-fused O- and N-heterocycles, such as 6-unsubstituted pyrrolo[1,2-c]oxazol-1(3H)-one and 1H-pyrrolo[1,2-c]imidazole-1,3(2H)-dione, while the 6-acetyl substituent of 1H-pyrrolo[1,2-c]imidazole-1,3(2H)-dione, when treated with POCl3/pyridine, is transformed into the 6-ethynyl substituent.

Phosphine-Catalyzed (3 + 2)/(3 + 2) Sequential Annulation of γ-Vinyl Allenoates: Access to Fused Carbocycles.

The first (3 + 2)/(3 + 2) sequential annulation of γ-vinyl allenoates with alkylidenemalononitriles enabled by phosphine catalysis has been reported. A broad range of structurally dense tetra- and penta-substituted bicyclic[3,3,0]octene derivatives, containing a quaternary center and three sequential stereogenic center, were synthesized in good to excellent yields. In this approach, three new C-C bonds are formed in one pot, and εC and αC of γ-vinyl allenoate are two electrophilic centers, whereas its γC exhibits nucleophilic reactivity.

Cascade Reaction for the Synthesis of Carbolines from O‐Methylketoximes and Styrenes via Palladium‐Catalyzed C–H Activation and Sequential Annulation

A novel cascade reaction has been described for the synthesis of Carbolines via palladium‐catalyzed successive C–C/C–N formation from O‐methylketoximes and styrenes. The oxime ether auxiliary not only serves as a traceless directing group, but is also partly transformed into the value‐added pharmacophore in a two‐step, one‐pot fashion.

Tandem C-C/C-N Formation via Palladium-Catalyzed C-H Activation/Styrenation and Sequential Annulation of O-Methylketoxime with Styrenes.

A novel route for tandem C-C/C-N formation via palladium-catalyzed C-H activation/styrenation and annulation of O-methylketoxime with styrenes to synthesize benzothienopyridines and benzofuropyridines has been developed. Furthermore, the intermolecular alkenylation of the ketoxime with acrylates produces 3-alkenyl O-methylketoximes in good to excellent yields. The method features mild reaction conditions and good functional group tolerance, providing a direct approach for the preparation of fused heterocycles.

Phosphine-mediated sequential annulations of allenyl ketone and isocyanide: a bicyclization strategy to access a furan-fused eight-membered ring and a spirocycle.

Phosphine-mediated cascade annulations of allenyl ketone and isocyanide have been disclosed. Two molecular allenyl ketones work as different four-carbon synthons to form two rings, respectively, and thus enables the efficient synthesis of a furan-fused eight-membered ring and a spirocycle.

Phosphine-catalyzed (3+2)/(2+3) sequential annulation involving a triple nucleophilic addition reaction of γ-vinyl allenoates.

A phosphine-catalyzed (3+2)/(2+3) sequential annulation involving a triple nucleophilic addition reaction of γ-vinyl allenoates was successfully developed. The reaction provided efficient and more practical access to functionalized hydropyrroloimidazolones with good to excellent yields under mild reaction conditions. Notably, γ-vinyl allenoate served as a triple-electrophilic intermediate in this protocol.

Manganese‐Catalyzed Sequential Annulation between Indoles and 1, 6‐Diynes

AbstractManganese‐catalyzed selective annulation reaction between indoles and 1,6‐diynes is described. Various carbazole derivatives were isolated in moderate to good yields. The formation of the fused ring compounds involves the construction of three C−C bonds in one‐pot through manganese‐catalyzed C−H bond activation, alkyne insertion, and oxidative dehydrogenation.magnified image

Ca(II)‐Mediated Regioselective One‐pot Sequential Annulation of Acyclic compounds to Polycyclic Fluorenopyrans

AbstractHerein we report a facile synthesis of tetracyclic fluorenopyrans from simple acyclic reactants, propargyl alcohols and 3‐methylpentane‐2,4‐dione under calcium catalysis. This one‐pot, 3‐component reaction proceeds through a sequential allene formation, Friedel‐Crafts cyclization/cycloisomerization, intramolecular aldol reaction, Claisen rearrangement, and 6‐endo dig cyclization to result in the formation of fluorenopyrans (indeno[2,1‐g]chromenes). This strategy was further used in the synthesis of 3‐iodo‐fluorenopyrans, by adding iodocyclization to the above sequence of reactions (4‐CR). Noticeably, this highly practical, atom and the step‐economic procedure is catalyzed by a sustainable (alkaline earth) metal salt and tolerates the broad substrate scope, allowing the further transformations and synthetic utilities of these complex polycyclic moieties.magnified image

One-pot sequential double annulations cascade reaction for imidazo[1,2-b]pyrazoles synthesis

We have developed efficient and green methods for the synthesis of imidazo[1,2-b]pyrazole derivatives by Groebke–Blackburn–Bienayme (GBB) reaction of 5-aminopyrazole, aldehyde and trimethylsilyl cyanid under thermal condition in 1-n-butyl-3-methylimidazolium tetrafluoroborate [Bmim]BF4 ionic liquid. A one-pot sequential double annulation cascade reaction has also been demonstrated for imidazo[1,2-b]pyrazoles synthesis.

Phosphine-Mediated Sequential Annulation Reaction: Access to Functionalized Benzofurans and 4,5-Dihydrobenzofurans.

A new strategy for the facile access to multi-functionalized benzofurans and 4,5-dihydrobenzofurans has been explored. The advantages of the present protocol include readily obtainable starting materials, mild and metal-free conditions, expedient and practical processes, excellent yields, and easy scale-up. The reaction demonstrated high efficiency to construct two rings in a single step. The zwitterionic intermediate generated from the conjugated attack of PPh3 to the ene-yne-ketone was proposed to be the key intermediate toward these valuable scaffolds.

A phosphine mediated sequential annulation process of 2-tosylaminochalcones with MBH carbonates to construct functionalized aza-benzobicyclo[4.3.0] derivatives

A novel phosphine mediated sequential annulation process to construct functionalized aza-benzobicyclo[4.3.0] derivatives has been developed involving a one-pot sequential catalytic and stoichiometric process, which generates a series of benzobicyclo[4.3.0] compounds containing one quaternary center with up to 94% yield and 20 : 1 dr value. In this reaction, MBH carbonates act as 1,2,3-C3 synthons.

Gold-catalyzed sequential annulations towards 3,4-fused bi/tri-cyclic furans involving a [3+2+2]-cycloaddition.

A gold-catalyzed sequential annulation reaction to prepare 3,4-fused bicyclic furan compounds has been realized by employing 2-(1-alkynyl)-2-alken-1-ones and 1,3,5-triazines as the starting materials under mild reaction conditions. This protocol features multiple bond formation in a single operation with the incorporation of two nitrogen and two carbon atoms into the final products. A mechanistic investigation reveals that the sequential annulations involved an unprecedented stepwise [3+2+2]-cycloaddition.

ChemInform Abstract: Bifunctional‐Phosphine‐Catalyzed Sequential Annulations of Allenoates and Ketimines: Construction of Functionalized Poly‐Heterocycle Rings.

AbstractA highly stereoselective sequential annulation reaction between γ‐substituted allenoates and ketimines is reported.

ChemInform Abstract: Sequential Annulation Domino Reaction of Sulfur Ylides and α,β‐Unsaturated Cyclic Ketimines: Synthesis of Cyclic 2‐Alkenyl Aziridines.

A sequential annulation domino reaction of sulfur ylides and α,β-unsaturated cyclic ketimines for the construction of cyclic 2-alkenyl aziridines has been developed. Readily accessible starting materials, a one-pot procedure, excellent functional group compatibility, and mild conditions make this transformation a powerful tool for the synthesis of cyclic 2-alkenyl aziridines.

Bifunctional‐Phosphine‐Catalyzed Sequential Annulations of Allenoates and Ketimines: Construction of Functionalized Poly‐heterocycle Rings

AbstractA highly stereoselective sequential annulation reaction between γ‐substituted allenoates and ketimines was reported. By using bifunctional N‐acyl aminophosphine catalysts, poly‐heterocycle rings were obtained with high stereocontrol in good to excellent yields. The desired products have four contiguous stereogenic centers (one quaternary and three tertiary carbon centers), and only one isomer was obtained in all reactions.

Bifunctional-Phosphine-Catalyzed Sequential Annulations of Allenoates and Ketimines: Construction of Functionalized Poly-heterocycle Rings.

A highly stereoselective sequential annulation reaction between γ-substituted allenoates and ketimines was reported. By using bifunctional N-acyl aminophosphine catalysts, poly-heterocycle rings were obtained with high stereocontrol in good to excellent yields. The desired products have four contiguous stereogenic centers (one quaternary and three tertiary carbon centers), and only one isomer was obtained in all reactions.

ChemInform Abstract: BF3·OEt2 Mediated Metal‐Free One‐Pot Sequential Multiple Annulation Cascade (SMAC) Synthesis of Complex and Diverse Tetrahydroisoquinoline Fused Hybrid Molecules.

Abstract5‐Bromo‐N3‐Boc‐pyridine‐2,3‐diamine as well as 2‐(N‐Boc‐aminomethyl)aniline as diamino substrates do not give the desired products.

Sequential Annulation Domino Reaction of Sulfur Ylides and α,β-Unsaturated Cyclic Ketimines: Synthesis of Cyclic 2-Alkenyl Aziridines.

A sequential annulation domino reaction of sulfur ylides and α,β-unsaturated cyclic ketimines for the construction of cyclic 2-alkenyl aziridines has been developed. Readily accessible starting materials, a one-pot procedure, excellent functional group compatibility, and mild conditions make this transformation a powerful tool for the synthesis of cyclic 2-alkenyl aziridines.

Cover Picture: Copper(II)/Silver(I)-Catalyzed Sequential Alkynylation and Annulation of Aliphatic Amides with Alkynyl Carboxylic Acids: Efficient Synthesis of Pyrrolidones (Adv. Synth. Catal. 5/2016)

Cover Picture: Copper(II)/Silver(I)-Catalyzed Sequential Alkynylation and Annulation of Aliphatic Amides with Alkynyl Carboxylic Acids: Efficient Synthesis of Pyrrolidones (Adv. Synth. Catal. 5/2016)