Annulation Reaction Research Articles

Asymmetric Synthesis of Hydroindoles via Desymmetrizing [3+2] Annulation of p-Quinamines and Arylalkylketenes.

The asymmetric desymmetrizing [3+2] annulation reaction of p-quinamines and arylalkylketenes to synthesize hydroindoles was realized. Catalyzed by chiral bisguanidinium hemisalt via multiple hydrogen bond interactions, enantiomerically enriched products with reversal of diastereoselectivity in comparison with the racemic version were afforded in good yields under mild reaction conditions. Diaryl-substituted hydroindoles could also perform the Friedel-Crafts type of addition to give more complicated multicycles. Density functional theory calculations revealed that the enantio- and diastereoselectivity stem from varied hydrogen-bonding manners.

Ru/O2-Catalyzed Oxidative C-H Activation/Alkyne Annulation Using Quinoline-Functionalized NHC as a Directing and Functionalizable Group.

The ruthenium/O2-catalyzed oxidative annulation reaction of imidazo[1,5-a]quinolin-2-ium salts with alkynes via N-heterocyclic carbene-directed C-H activation to obtain π-conjugated fused imidazo[1,5-a]quinolin-2-ium derivatives is reported. Molecular oxygen has been explored as an economic and clean oxidant and an alternative to metal oxidants. The current protocol exhibits a wide range of substrate scope including bioactive (±)-α-tocopherol derivatives. Moreover, most of the annulated products show strong fluorescence properties, indicating their potential for making new light-emitting materials.

NHC-Catalyzed Enantioselective Transformations Involving α-Bromoenals.

α-Haloenals, especially, α-bromoenals considered as one of the important building blocks in organic synthesis. They can participate in various (3+2)-, (3+3)-, (3+4)-, and (2+4)-annulation reactions with other organic molecules in the presence of an NHC catalyst to produce enantioenriched carbo-, and heterocyclic compounds. Herein, we have described NHC-catalyzed enantioselective transformations of α-bromoenals in the synthesis of various heterocycles, and carbocycles, as well as acyclic organic compounds.

Phosphine‐Catalyzed Domino Annulation Reactions of <i>o</i>‐Aminotrifluoroacetophenone Derivatives with Morita−Baylis−Hillman Carbonates: Construction of Tetrahydrofuro[3,2‐b]indolines

The domino annulation reactions of <i>o</i>‐aminotrifluoroacetophenone derivatives and MBH carbonates enabled by PPh<sub>3</sub> have been reported, which provide a series of tetrahydrofuro[3,2‐b]indolines containing a CF<sub>3</sub>‐substituted tetrasubstituted carbon stereocenters in yields of 74 to 95% and >20:1 dr. In this process, MBH carbonates were used as C1/C3 synthons. The MTT assay shows that the products exhibit the activity of inhibitory effect on proliferation on Hela cancer cell line.

Synthesis of Pyridazino[4,5-b]indoles by [3+3] Annulation of 2-Alkenylindoles and Hydrazonyl Chlorides.

A novel [3+3] annulation reaction of 2-alkenylindoles with hydrazonyl chlorides in the presence of base for the formation of pyridazino[4,5-b]indoles was developed. This approach provided a convenient and efficient way to synthesize a series of functionalized pyridazino[4,5-b]indoles derivatives. The method exhibited a broad substrate scope and provided the corresponding pyridazino[4,5-b]indoles products with excellent yields.

Zirconium-Catalyzed Synthesis of 6-(Trifluoromethyl)-2H-pyran-2-ones via C-C Bond Cleavage.

A strategy for the annulation reaction of alkynones with ethyl 4,4,4-trifluoro-3-oxobutanoate through C-C bond cleavage is described. The zirconium-catalyzed transformation provides access to a wide range of structurally diverse 6-(trifluoromethyl)-2H-pyran-2-ones in moderate to good yields, utilizing Na2CO3 as a base. Further transformations into trifluoromethylated arene derivatives have been demonstrated as well. Furthermore, plausible reaction pathways are proposed by conducting various control experiments and isolating a β-diketone intermediate (X-ray) containing an intramolecular hydrogen bond.

Phosphine-Catalyzed Asymmetric Dearomative [3+2] Annulation Reaction of Benzimidazoles with Cyclopropenones

Phosphine-Catalyzed Asymmetric Dearomative [3+2] Annulation Reaction of Benzimidazoles with Cyclopropenones

Nickel‐Catalyzed Intramolecular Dual Annulation Reaction of Alkyl Nitrile‐Containing 1,2,3‐Benzotriazin‐4(3H)‐ones: A Pathway to Access Diversely Polycyclic Quinazolinone Alkaloids

AbstractHerein, we report a nickel‐catalyzed intramolecular dual annulation reaction of alkyl nitrile‐containing 1,2,3‐benzotriazin‐4(3H)‐ones to synthesize polycyclic quinazolinones. This catalytic reaction can construct the core structure of polycyclic quinazolinone alkaloids; therefore, we also apply this reaction as the critical step to access fifteen relevant alkaloids to demonstrate efficacy.

PIFA-mediated room temperature dehydrogenative annulation for the synthesis of 2-alkenyl oxazoles

The annulation reactions of N-substituted enamides via intramolecular dehydrogenative CC bond formation has been developed for the synthesis of 2-alkenyl oxazoles with phenyliodine(III) bis(trifluoroacetate) (PIFA) as the only oxidant. The method exhibits excellent synthetic scope at room temperature without using any metal reagent. In addition, the method has been proven to be applicable for the synthesis of 2-aryl oxazoles via the reactions of aroyl-based enamides. The reaction process initiated by the free radical resulting from the homo-cleavage of I-O bond in PIFA has been demonstrated by control experiments.

Organocatalytic Enantioselective Synthesis of Chiral Spiro‐indoline‐pyrazolones through a formal [4+1] Annulation Reaction of 4‐Bromopyrazolones and aza‐ortho‐Quinone Methides

AbstractIn this communication, a straighforward asymmetric synthesis of spiro‐indoline‐pyrazolone compounds is described. This methodology consists in a formal [4+1] cycloaddition reaction of 4‐bromopyrazolones and aza‐ortho‐quinone methides generated in situ catalyzed by a bisquinine‐derived squaramide in CHCl3 under basic conditions. A variety of chiral spirocyclic compounds bearing a pyrazolone and an indoline moieties were obtained in moderate to good yields (up to 68 %) and moderate to excellent enantioselectivities (up to 93 % ee).

Cu+-based composite metal oxides enable the efficient [4+2] annulation reactions between tertiary anilines and tetrahydrofuran

An efficient heterogeneous catalytic system for the [4 + 2] annulation reactions between tertiary anilines and tetrahydrofuran has been developed based on CuCoFe layered double oxide in the study. Cu+ species was believed to play the crucial role in the catalytic transformation, and synergistic effect between Cu and CoFe species was observed in the reaction. Various tertiary anilines could be tolerated by the present catalytic system. A series of control experiments were conducted to determine the reaction intermediates. A distinctive reaction mechanism has been described for the annulation reaction based on these results and kinetic isotopic effects experiments.

A Palladium‐Catalyzed Regioselective [3+2] Annulation Strategy to 1,2,3‐Oxathiazolidine‐2‐oxides

AbstractA palladium‐catalyzed [3+2] annulation reaction of N‐sulfinylanilines with vinylethylene carbonates and vinyl epoxides is developed. It affords 1,2,3‐oxathiazolidine‐2‐oxides under mild reaction conditions through allylic palladium intermediates. The versatile synthetic utility of 1,2,3‐oxathiazolidine‐2‐oxides in preparing sulfoxides, β‐amino alcohols, and substituted amines has also been demonstrated.

Palladium-Catalyzed Annulative π-Extension of Bay-Iodinated Triphenylenes to Access Polycyclic Aromatic Compounds.

A palladium-catalyzed annulative π-extension reaction of bay-iodinated triphenylenes with aryl iodides/o-chloroaromatic carboxylic acids was developed. This approach enabled the synthesis of diverse polycyclic aromatic compounds, including dibenzo[fg,op]tetracenes, azadibenzo[fg,op]tetracenes, and tribenzo[a,g,m]coronenes. Initial studies indicate that the resulting product, 2,3,8,9,14,15-hexakis(decyloxy)tribenzo[a,g,m]coronene, exhibits good liquid-crystalline properties.

Visible-Light-Initiated Catalyst-Free Radical Annulation Reactions of 1,6-Enynes and Aryl Sulfonyl Bromide to Assemble Sulfonation/Bromination Succinimide Derivatives.

In the present study, the environment-friendly visible-light-promoted strategy is used to perform an efficient, simple, and straightforward photocatalytic succinimide derivative synthesis from the reaction of 1,6-enynes and aryl sulfonyl bromide at room temperature under air ambient conditions. This method features mild conditions, broad substrate scope, high yields, and excellent configurational selectivity. In addition, all the atoms of the substrates involved in the reaction converge in the product structures, showing a high atomic economy. Moreover, the most important characteristic of this study is that no photocatalyst and additives are used, while the key factor that triggers the reaction is visible light, indicating that this study has an important practical value.

Three-Component Reaction for the Synthesis of Spiro-Heterocycles from Isatins, Substituted Ureas, and Cyclic Ketones.

We reported an efficient three-component reaction to access new spiro heterocycles through the annulation reactions of isatins, substituted ureas, and cyclic ketones under normal laboratory conditions, which is another example of isatins being used to build spiro compounds by the ring-opening and recyclization processes. The wide range of substrates, simple operation, normal experimental conditions, and high yields make the approach of high practical value.

Amine Catalyzed Remote [4+2]‐annulation Of Indole Tethered Enal And Oxindole Olefin To Access Optically Pure Hydrocarbazole Spirooxindole Scaffolds

This research showcases a methodology for crafting highly intricate hydrocarbazole spirooxindole frameworks endowed with three consecutive stereocenters. Achieved through a trienamine‐catalyzed remote [4+2]‐annulation reaction, the method's significance is underscored by synthesizing an extensive array of library molecules (up to 27 examples). These compounds mimic natural products and exhibit good yields (up to 85%) and exceptional diastereo‐ and enantiomeric ratios (up to 17:1 dr and 99.9:0.1 er). The practicality of our strategy is further exemplified by successfully synthesizing a hexahydroepoxy‐ethanocarbazole spirooxindole scaffold via a sequential [4+2]‐annulation/‐reduction/epoxidation‐cyclization reaction, achieving a 75% overall yield and maintaining an excellent stereoselectivity (99.5:0.5 er).

Unveiling Novel Synthetic Pathways through Brook Rearrangement

AbstractThe Brook rearrangement is a valuable synthetic tool that facilitates the controlled construction of complex molecules. Conventionally, it generates carbanion intermediates utilized in subsequent functionalization reactions. In this review, we will explore recent advancements in the Brook rearrangement that extend beyond the traditional functionalization reactions. Specifically, we will highlight its involvement in unusual bond cleavage, annulation reactions, and dearomatization efforts. The novelty of this rearrangement is underscored by showcasing its most recent applications.1 Introduction2 Novel Synthetic Pathways Involving the Brook Rearrangement2.1 C–C and C–X Bond Formation2.2 C–C and C–X Bond Cleavage2.3 Stereodefined Substituted Silyl Enol and Allenol Ethers2.4 Annulation Reactions2.5 Dearomatization3 Synthetic Applications4 Conclusion

N-Heterocyclic Carbene Catalysis for Facile Access to Pentasubstituted 4H-Pyran Derivatives

AbstractThe synthesis of polysubstituted 4H-pyran derivatives has attracted considerable attention due to its wide application in agrochemicals, pharmaceuticals, and other functional molecules. We report an N-heterocyclic carbene-catalyzed [3+3] annulation reaction of β-ketone esters with enynals for rapid access to pentasubstituted 4H-pyran derivatives through a regioselective activation of the ynal. A series of 4H-pyran derivatives bearing various substituents were obtained in moderate to excellent yields. This method could find further applications in the synthesis of structurally diverse 4H-pyran-derived functional molecules from readily available starting materials.

Copper‐Catalyzed Sequential C(sp2)−H/C(sp3)−H Annulation of Indoles with Propargylic Alcohols to Access Hydrobenzo[b]carbazoles

AbstractHerein, we describe a copper‐catalyzed sequential C(sp2)−H/C(sp3)−H annulation of indoles with propargylic alcohols for the synthesis of diversely functionalized hydrobenzo[b]carbazole scaffolds. The reaction involves a Friedel‐Crafts addition, 1,5‐H shift, 6π electrocyclization, and dearomatization‐aromatization cascade. Importantly, this is a report of the use of 2‐(diarylmethyl)indoles as three‐carbon synthons in a (3+3) annulation reaction involving C(sp3)−H indole functionalization under oxidant‐free conditions.

Synthesis of gem-Difluoro-3,4-dihydro-2H-pyrans via a TfOH-Catalyzed [4 + 2] Annulation of Difluoroenoxysilanes with α-Cyano Chalcones.

Difluoroenoxysilane, a commonly used difluoroallylating reagent, has attracted considerable attention in recent years. However, its application in the annulation reaction for the construction of fluorinated heterocyclic compounds remains relatively limited. Presented here is the Brønsted acid-catalyzed efficient formal [4 + 2] annulation of difluoroenoxysilanes with α-cyano chalcones. The developed protocol demonstrates tolerance to various substituents under mild reaction conditions, providing a reliable approach to construct gem-difluoro-3,4-dihydro-2H-pyrans in good to excellent yields with high diastereoselectivities.