Sequential Annulation Research Articles

(5+1)−1] Cyclization of Nitroepoxides to Pyridinium 1,4‐Zwitterionic Thiolates for the Synthesis of Indolizine Derivatives

AbstractThe synthesis of indolizine derivatives was achieved through the reaction of pyridinium 1,4‐zwitterionic thiolates with a diverse array of 2‐methyl‐2‐nitro‐3‐aryloxiranes. Subsequent investigations unveiled a synthetic route to indolizines via a stepwise [(5+1)−1] pathway, with unstable pyridothiazines serving as transient intermediates. DFT calculations elucidated that this transformation entails sequential annulation, deacylation, desulfurization, and oxidation steps.

Recent advances in phosphine-mediated sequential annulations

Recent advances in phosphine-mediated sequential annulations

Sequential Annulation of Arene Diamines

Sequential Annulation of Arene Diamines

A simple and efficient sequential (3+2) annulation toward the construction of a novel contiguous dispiroheterocyclic scaffold

A diastereoselective (3+2) annulation of 4-isothiocyanato pyrazolones and 2-arylidene-indan-1,3-dione in the presence of 4-dimethylaminopyridine is explored. A wide range of novel dispiroheterocyclic products were achieved in high yield (up to 95 %) and excellent diastereoselectivity (up to >20:1 dr) via a simple sequential Michael addition/cyclization.

Sequential annulation of bidentate diamines for modular access to N-fused/helical/spiro-carbazole scaffolds

A facile access to N-fused/helical/spiro-carbazole scaffolds through sequential annulation of bidentate diamines with cyclic diaryliodonium salts has been disclosed.

Multicomponent All-Carbon Cascade and Sequential Annulation: Construction of Functionalized Decalins.

The decalin skeleton is found in numerous bioactive molecules. The present study describes a multicomponent all-carbon cascade and sequential annulation involving benzoylacetonitrile derivatives and 2-arylidene-1,3-indanediones that yields highly functionalized decalin derivatives. The reaction strategy consisted of a consecutive Michael/Michael/tautomerization/Michael/Aldol annulation sequence and involved organic amine catalysts, mild conditions, and high stereoselectivity. This strategy, using a one-pot approach, resulted in the construction of four C-C bonds and the formation of fused carbocyclic decalin derivatives.

Sequential annulation and isomerisation reaction of 3-acylmethylidene oxindoles with Huisgen zwitterions and synthesis of 5-(3-oxindolyl)oxazoles.

Herein, we report a facile synthesis of 5-(3-oxindolyl)oxazole derivatives via a sequential annulation and isomerisation reaction of 3-acylmethylidene oxindoles with in situ generated Huisgen zwitterions (HZs) from PPh3 and azodicarboxylates. This reaction exhibits good functional group tolerance with 30 examples of structurally diverse products prepared with moderate to good efficiencies (up to 88% yield), thus providing a generally applicable route to the biologically important 5-(3-indolyl)oxazole structural motifs. Key to the success of this sequential one-pot strategy is the utilization of DBU as a base to promote the isomerisation process of the corresponding intermediate annulation products.

CO2-facilitated radical sequential (3 + 2) annulation of 1,6-enynes via cooperation of sulfinate catalysis and photocatalysis

Reported here is the radical sequential (3 + 2) annulation of 1,6-enynes under the concerted catalysis of sulfinate and PC. Importantly, CO2 as a green additive facilitates the unusual 1,4-elimination via proton transfer to provide desulfonylated products.

Regioselective synthesis of indazolo[2,3-a]quinazolines enabled by I2/S-facilitated annulation relay dehydrogenative aromatization of cyclohexanones.

A method for concise and efficient synthesis of indazolo[2,3-a]quinazolines has been developed via a sequential annulation of 3-aminoindazoles and dehydrogenative aromatization of cyclohexanones. This high regioselectivity is attributed to the fact that the Mannich reaction is superior to the aldol reaction in this system. It is worth mentioning that this convenient process is successfully extended to 3-aminopyrazoles for assembling another class of medicinally prevalent pyrazolo[1,5-a]quinazolines.

A Novel Palladium-Based Heterogeneous Catalyst for Tandem Annulation: A Strategy for Direct Synthesis of Acridones

AbstractIn order to develop an efficient, rapid, and modular cascade strategy for the direct synthesis of acridones, palladium supported on sulfated alumina and microwave activation are employed. Multifunctional heterogeneous palladium catalysts were prepared in order to carry out the sequential annulation via a Buchwald–Hartwig amination followed by an intramolecular annulation in a one-pot process. This new protocol represents the first report on a catalytic tandem synthesis of acridone derivatives from commercially available starting materials, under ligand-free conditions. The scope of the present methodology is extended to the generation of a library of functionalized acridones, showing high functional group compatibility, in moderate to excellent yields. The applicability of this novel transformation was demonstrated by the concise total synthesis of the natural product arborinine.

Construction of novel penta cyclic indolo-furo[3,2-c]quinoline and dihydrochromeno-furo[2,3-b]indol via sequential annulation strategy

An efficient, rapid and green synthesis of indolo-furo-quinoline and chromeno-furo-indoles has been developed by one-pot reaction of 2,4-quinolinediol or 4-hydroxycoumarin, phenylglyoxal and aromatic amine in the presence of acetic acid as an reaction medium cum promoter at room temperature. This scalable tandem reaction affords a series of novel dihydro-indolo-furo-quinoline and dihydro-chromeno-furo-indole derivatives with two adjacent stereogenic centers in good to excellent yields and with high regioselectivity and stereoselectivity. Moreover, this cascade reaction provides a distinct Knoevenagel, Michael and through intramolecular cyclization in sequential manner under mild reaction conditions to access the diversely decorated indolo-furo-quinoline and chromeno-furo-indoles of considerable importance to natural product synthesis and medicinal chemistry.

One-Pot Synthesis of 1,2,3-Triazole-Fused Polycyclic Systems via Sequential Annulation of 1,n-Enynes with Tosyl Azide

AbstractAn efficient one-pot sequential annulation of 1,n-enynes with tosyl azide is reported, providing a series of novel N-alkyl 1,2,3-triazole-fused polycyclic scaffolds in moderate to excellent yields under mild reaction conditions.

Rh(III)-Catalyzed C-H Activation and [4+1+1] Sequential Cyclization Cascade to Give Highly Fused Indano[1,2-b]azirines.

A Rh(III)-catalyzed C-H activation of α-keto oximes and a cyclization cascade with diazo compounds were developed to construct the highly fused indano[1,2-b]azirine frameworks in good yields with a broad range of substrates under mild reaction conditions. More intriguingly, a [4+1+1] sequential annulation cascade is demonstrated for the first time in this reaction and opened a new reaction mode for α-keto oximes. These fused indano[1,2-b]azirine derivatives could also be further transformed into intriguing privileged drug scaffolds.

Phosphine-Mediated Sequential [2+4]/[2+3] Annulation to Construct Pyrroloquinolines.

A domino [2+4]/[2+3] sequential annulation reaction of MBH carbonates with N-unprotected indoles has been developed to provide various pyrroloquinoline derivatives in ≤94% yield and 20:1 dr. The reaction could be either mediated by stoichiometric PCy3 or catalyzed by R3PO via PIII/PV═O redox cycling in the presence of phenylsilane. This method assembles polycyclic 1,7-fused indoles in one step diastereoselectively.

One-pot catalyst-free synthesis of benzopyrroxazine derivatives by a mutually activated sequential annulation process.

A one-pot catalyst-free reaction of o-hydroxyaryl azomethine ylides, vinyl pyridines and paraformaldehyde for the synthesis of benzopyrroxazines is reported, which offers a straightforward and atom-economical procedure for the preparation of benzopyrroxazine derivatives in moderate to excellent yields under mild conditions. A self-catalyzed [3 + 2] annulation through a mutual activation method and a sequential non-catalyzed [5 + 1] annulation process contribute to this strategy. The corresponding control experiments have been conducted to reveal the mechanism of this reaction.

Electrophilically Activated Nitroalkanes in Double Annulation of [1,2,4]Triazolo[4,3-a]quinolines and 1,3,4-Oxadiazole Rings.

Nitroalkanes activated with polyphosphoric acid could serve as efficient electrophiles in reactions with amines and hydrazines, enabling various cascade transformations toward heterocyclic systems. This strategy was developed for an innovative synthetic protocol employing simultaneous or sequential annulation of two different heterocyclic cores, affording [1,2,4]triazolo[4,3-a]quinolines with 1,3,4-oxadiazole substituents.

Ru(II)-catalyzed allenylation and sequential annulation of N-tosylbenzamides with propargyl alcohols.

We hereby report Ru(ii)-catalyzed C(sp2)-H allenylation of N-tosylbenzamides to access multi-substituted allenylamides. Furthermore, the allenylamides were converted to the corresponding isoquinolone derivatives via base mediated annulation. The current protocol features low catalyst loading, mild reaction conditions, high functional group compatibility and desired scalability. The unique functionality of the afforded allenes allowed further transformations to expand the practicality of the protocol.

Auto-tandem palladium/phosphine cooperative catalysis: synthesis of bicyclo[3.1.0]hexenes by selective activation of Morita–Baylis–Hillman carbonates

A new palladium/phosphine cooperatively catalytic sequential annulation strategy has been developed for the synthesis of bicyclo[3.1.0]hexene derivatives.

Synthesis of 2-Arylindoles by Iridium(III)-Catalyzed Sequential Annulations

Key words iridium catalysis - indoles - C–H activation - chloro ketones

Construction of CF3-Containing Tetrahydropyrano[3,2-b]indoles through DMAP-Catalyzed [4+1]/[3+3] Domino Sequential Annulation.

A [4+1]/[3+3] domino sequential annulation reaction of o-aminotrifluoroacetophenone derivatives and β'-acetoxy allenoates enabled by DMAP has been reported. A variety of CF3-containing tetrahydropyrano[3,2-b]indoles were obtained as a single diastereomer in high yields (≤98%) under mild conditions. The reaction can build one C-N bond, one C-C bond, and one C-O bond sequentially in a single step. The synthetic utility was demonstrated with gram-scale reactions and various transformations of the products.