Palladium-Catalyzed [3+2] and [2+2+2] Annulations of 4-Iodo-2-quinolones with Activated Alkynes through Selective C−H Activation

The palladium-catalyzed reaction of 4-iodo-2-quinolones with activated alkynes was investigated. Cyclopenta[de]quinoline-2(1 H)-ones and/or phenanthridine-6(5 H)-ones were obtained through [3+2] annulation involving aromatic C−H activation or [2+2+2] annulation involving vinylic C−H activation, respectively. Reasonable mechanisms for the formation of these annulation products have been proposed based on density functional theory calculations.     

Development of Gold‐catalyzed [4+1] and [2+2+1]/[4+2] Annulations between Propiolate Derivatives and Isoxazoles

Two new gold‐catalyzed annulations of isoxazoles with propiolates have been developed. Most isoxazoles follow an initial O attack on the alkyne to afford a [4+1] annulation product. This process results in a remarkable alkyne cleavage of initial propiolates. Unsubstituted isoxazoles proceed through an N attack step to yield formal [2+2+1]/[4+2] annulation products. These two annulation products arise initially from two seven‐membered heterocyclic intermediates, which then lead to products.     

Recent advances in radical-mediated [2+2+m] annulation of 1,n-enynes

1,n-Enynes are a versatile class of unsaturated hydrocarbons that found broad applications in the synthetic community of natural products, biologically active structures and functional materials. Typical methods for the transformations of 1,n-enynes include the radical-mediated [2+2+m] annulation reaction as they are particularly efficient accesses to functionalized polycyclic compounds. We herein highlighted recent process in the radical-mediated [2+2+m] annulation of 1,n-enynes, including [2+2+1] and[2+2+2] modes, for the construction of five-to six-membered-ring-fused polycyclic scaffolds. Meanwhile, the mechanisms for these transformations were described.     

Divergent amine-catalyzed [4 + 2] annulation of Morita-Baylis-Hillman allylic acetates with electron-deficient alkenes

An amine-catalyzed [4 + 2] annulation of Morita-Baylis-Hillman allylic acetates 2 with electron-deficient alkenes or diazenes has been developed for efficient syntheses of highly functionalized cyclohexenes, tetrahydropyridazines, and important spirocycles. This reaction unveils a new reactivity pattern of the intensely studied allylic compounds 2 acting as a C(4) synthon in Lewis base catalyzed annulation reactions and also showcases divergent catalysis between tertiary amines and phosphines.     

Rhodium-catalyzed [2 + 2 + 2] cyclotrimerization in an aqueous-organic biphasic system

Macrocyclization via rhodium-catalyzed intramolecular [2 + 2 + 2] annulation of triynes has been explored in an aqueous-organic biphasic system. The biphasic system controls the concentration of hydrophobic substrates in the aqueous reaction phase and offers diluted reaction conditions without the use of a slow addition technique. The system also achieves selective cross-annulation between hydrophobic diynes and hydrophilic alkynes.     

Cobalt(II)-Catalyzed [4+2] Annulation of Picolinamides with Alkynes via C−H Bond Activation

A cobalt(II)-catalyzed [4+2] annulation of picolinamides with alkynes via C−H bond activation has been developed. The operationally simple annulation reaction allows for the synthesis of acyl-substituted 1H-benzoquinoline bearing multiple aromatic rings (up to 96 % yield) without co-oxidant or other oxidation factors under mild conditions. Several control experiments were carried out. This practical [4+2] annulation provides an efficient route to access highly functionalized compounds.     

Visible‐Light‐Induced [4+2] Annulation of Thiophenes and Alkynes to Construct Benzene Rings

The [4+2] annulation represents an elegant and versatile synthetic protocol for the construction of benzene rings. Herein, a strategy for visible‐light induced [4+2] annulation of thiophenes and alkynes, to afford benzene rings, is presented. Under simple and mild reaction conditions, the ready availability and structural diversity of thiophenes and alkynes permit the facile synthesis of several substituted aromatic rings. Valuable drugs and amino acids are also well tolerated. Moreover, DFT calculations explain the high regioselectivity of the reaction.     

Synthesis of 2-indanones via [4 + 1] annulation reactions of (trialkylsilyl)arylketenes

[reaction: see text] (Trialkylsilyl)arylketenes combine with (trimethylsilyl)diazomethane in a new [4 + 1] annulation process leading to 2-indanone derivatives. The (trialkylsilyl)arylketene annulation substrates are available via the photochemical Wolff rearrangement of alpha-silyl-alpha-diazo ketones, which are themselves prepared by silylation of the corresponding diazo ketones. The mechanism of the annulation reaction is proposed to involve the formation of a 2,3-bis(silyl)cyclopropanone, which is in equilibrium with an oxyallylic cation. Electrocyclic closure of this intermediate forms the new cyclopentenone ring.     

An expedient phosphine-catalyzed [4 + 2] annulation: synthesis of highly functionalized tetrahydropyridines

Ethyl 2-methyl-2,3-butadienoate acts as a 1,4-dipole synthon and undergoes [4 + 2] annulation with N-tosylimines in the presence of an organic phosphine catalyst. The resulting adducts, ethyl 6-substituted-1-(4-tosyl)-1,2,5,6-tetrahydro-pyridine-3-carboxylates, are formed in excellent yields with complete regioselectivity. Mechanistic reasoning for this new annulation has led to an expansion of the reaction scope by employing ethyl 2-(substituted-methyl)-2,3-butadienoates to give ethyl 2,6-cis-disubstituted-1-(4-tosyl)-1,2,5,6-tetrahydro-pyridine-3-carboxylates with high diastereoselectivities.     

Synthesis of functionalized allylic sulfoxides and their use in the construction of 2,3,4-trisubstituted furans via a [3 + 2] annulation

A route to 2,3,4-trisubstituted furan derivatives based on a [3 + 2] annulation of functionalized allylic sulfoxides and aldehydes is described. In this strategy, the precursors of allylic sulfoxides 4, allylic sulfides 3, were synthesized via a thiomethylation reaction of an alpha-EWG ketene-S,S-acetal 1 (EWG: electron-withdrawing group), formaldehyde, and a thiol 2 in high to excellent yields. Allylic sulfoxides 4 were prepared by a highly regioselective oxidation of 3, using m-chloroperoxybenzoic acid as oxidant. Thus, starting from these readily available sulfoxides 4, 2-alkylthio-3,4-disubstituted furans 6 were efficiently constructed via the [3 + 2] annulation reaction of 4 with aldehydes 5 under mild conditions. Further replacement of the 2-alkylthio group of 6 with amines led to the formation of 2-amino-3,4-disubstituted furan derivatives 7.     

Cationic palladium-catalyzed [5 + 2] annulation of 2-acylmethoxyarylboronic acids and allenoates: synthesis of 1-benzoxepine derivatives

The 1-benzoxepine derivatives were synthesized conveniently by cationic palladium-catalyzed [5 + 2] annulation reaction of 2-acylmethoxyarylboronic acids with allenoates in high yields. This annulation involves the intramolecular nucleophilic addition to ketones without the formation of π-allylpalladium species.     

Gold-catalyzed intermolecular reactions of propiolic acids with alkenes: [4 + 2] annulation and enyne cross metathesis

A gold-catalyzed intermolecular reaction of propiolic acids with alkenes led to a [4 + 2] annulation or enyne cross metathesis. The [4 + 2] annulation proceeds with net cis-addition with respect to alkenes and provides an expedient route to α,β-unsaturated δ-lactones, for which preliminary asymmetric reactions were also demonstrated. For 1,2-disubstituted alkenes, unprecedented enyne cross metathesis occurred to give 1,3-dienes in a completely stereospecific fashion. DFT calculations and experiments indicated that the cyclobutene derivatives are not viable intermediates and that the steric interactions during concerted σ-bond rearrangements are responsible for the observed unique stereospecificity.     

Phosphine-catalyzed dearomative [3+2] annulation of 3-nitroindoles and allenoates

The efficient phosphine-catalyzed dearomative [3+2] annulation of 3-nitroindoles with allenoates has been successfully developed, providing a facile access to cyclopenta[b]indolines with good to excellent yields and high diastereoselectivities. This strategy features mild reaction conditions, high functional group tolerance, and scalability. Additionally, the 2-nitrobenzofuran and 2-nitrobenzothiophene were good dearomative [3+2] annulation partners.     

Selective Oxidative [4+2] Imine/Alkene Annulation with H2 Liberation Induced by Photo‐Oxidation

The oxidative [4+2] annulation reaction represents an elegant and versatile synthetic protocol for the construction of six‐membered heterocyclic compounds. Herein, a photoinduced oxidative [4+2] annulation of NH imines and alkenes was developed by utilizing a dual photoredox/cobaloxime catalytic system. Various multisubstituted 3,4‐dihydroisoquinolines can be obtained in good yields. This method is not only obviated the need of stiochiometric amounts of oxidants but also exhibited excellent atom economy by generating H₂ as the only byproduct. Remarkably, high regioselectivity and trans diastereoselectivity can be achieved in this transformation even if the Z/E mixture of alkenes were employed.     

Enantioselective three-component synthesis of 4-arylated dehydroprolines: [3+2] annulation of allenylstannane and α-imino ester

An enantioselective [3+2] annulation reaction of allenylstannane and α-imino ester was developed. Stille coupling of the resulting 4-stannyl dehydroproline gave optically active 4-arylated dehydroprolines in good yields.     

Synthesis of Sulfamate‐Fused 2‐Aminopyrroles via an Isocyanide‐Based Three Component [1+2+2] Annulation

An efficient preparation of sulfamate‐fused 2‐aminopyrroles was achieved through an isocyanide‐based three‐component [1+2+2] annulation of isocyanides, dialkyl acetylenedicarboxylates, and sulfamate‐derived cyclic imines in good to excellent yields (up to 99 %). This reaction proceeds smoothly without any activation or modification of substances under neutral and metal‐free conditions. The reaction could also be conveniently performed on a gram scale.     

N‐Heterocyclic Carbene‐Catalyzed [2+2+2] Annulation of Allenoates with Trifluoromethylketones

In contrast with the reported phosphine‐ and DABCO‐catalyzed [3+2] and [2+2] annulation of allenoates with trifluoromethylketone, the [2+2+2] annulation of allenoates and two molecules of trifluoromethylketone was found under the condition of N‐heterocyclic carbene catalysis.     

Cobalt(III)‐Catalyzed Dehydrative [4+2] Annulation of Oxime with Alkyne by CH and NOH Activation

Efficient, scalable cobalt‐catalyzed redox‐neutral [4+2] annulation of readily available oximes and alkyne is reported. The developed synthetic methodology is widely applicable and tolerates various functional groups including heterocycles. A stable Cp*Co^III neutral complex is employed as the catalyst for this redox‐neutral [4+2] annulation reaction, which progresses smoothly by way of a reversible cyclometallation without any external oxidizing agent, and produces only water as the side product.     

N-heterocyclic carbene-catalyzed [4 + 1] annulation of phthalaldehyde and imines

The diastereoselective synthesis of cis-2-amino-3-hydroxyindanones was realized by the N-heterocyclic carbene-catalyzed [4 + 1] annulation of phthalaldehyde and imines, which may involve a tandem aza-benzoin reaction and aldol reaction.     

Unusual Formal [1+4] Annulation through Tandem P(NMe2)3‐Mediated Cyclopropanation/Base‐Catalyzed Cyclopropane Rearrangement: Facile Syntheses of Cyclopentenimines and Cyclopentenones

An unusual formal [1+4] annulation of α‐dicarbonyl compounds with 1,1‐dicyano‐1,3‐dienes has been realized, leading to facile syntheses of cyclopentenimines and cyclopentenones in a unique manner. Mechanistic investigation implies that this reaction takes place through a P(NMe₂)₃‐mediated cyclopropanation followed by a base‐catalyzed cyclopropane rearrangement. It therefore represents an unprecedented [1+4] annulation mode involving Kukhtin–Ramirez adducts.