Assembly of Functionalized 4‐Alkynylisoxazoles by Palladium‐Catalyzed Three‐Component Cascade Cyclization/Alkynylation

A novel N‐heterocyclic carbene (NHC)‐palladium‐catalyzed three‐component cascade cyclization/alkynylation for the synthesis of structurally diverse 4‐alkynylisoxazoles was efficiently developed in ionic liquids. The operational simplicity, without additives, no additional ligands, and 0.5 mol % catalyst loading under air are some of the attractive features of this present protocol.     

Palladium‐Catalyzed Annulation of 9‐Halophenanthrenes with Alkynes: Synthesis,Structural Analysis,and Properties of Acephenanthrylene‐Based Derivatives

The palladium‐catalyzed annulation of 9‐bromo‐ and 9‐chlorophenanthrenes with alkynes gave 4,5‐disubstituted acephenanthrylenes in yields of 58–95 % (9 examples). Asymmetric alkynes, such as 1‐phenyl‐1‐propyne, 1‐phenyl‐1‐hexyne, and 1‐cyclopropyl‐2‐phenylethyne, regioselectively form (cyclo)alkyl‐substituted products, following the regular rule that governs the carbopalladation of alkynes. This synthetic protocol can also be utilized in annulations with several π‐extended bromoarenes, such as 7‐bromo[5]helicene, 5‐bromo[4]helicene, 9‐bromoanthracene, 3‐bromoperylene, and 3‐bromofluoranthene, to give the corresponding annulated products in moderate to good yields (51–86 %; 6 examples). Similarly, bromocorannulene produced highly curved 1,2‐disubstituted cyclopentacorannulenes. Reactions of 6,12‐dibromochrysene and 4,7‐dibromo[4]helicene with di(4‐tolyl)ethyne provided the twofold annulated products in moderate yields. 4,5‐Diphenylacephenanthrylene and 6,7‐diphenylbenzo[a]acephenanthrylene thus generated were converted into phenanthro[9,10‐e]acephenanthrylene and benzo[a]phenanthro[9,10‐e]acephenanthrylene, respectively, by oxidative cyclodehydrogenation. The structures of 4,5‐diphenylacephenanthrylene, 4,5‐diphenyldibenzo[a,l]acephenanthrylene, 1,2‐diarylcyclopentacorannulenes, and benzo[a]phenanthro[9,10‐e]acephenanthrylene were verified by X‐ray crystallography. The photophysical and electrochemical properties of the selected annulated products were investigated.     

NHC-Palladium-Catalyzed Cascade Annulation of Alkynoic Acids with Unactivated Alkenes in Ionic Liquids

An N-heterocyclic carbene palladium (NHC-palladium)-catalyzed cascade annulation of alkynoic acids with unactivated alkenes under an oxygen atmosphere in ionic liquids is described. This protocol enables facile access for the preparation of diverse alkyl substituted α-methylene-γ-lactones in moderate to good yields with excellent Z/E selectivity. Moreover, the ionic liquid not only acts as the green solvent, but also as the eco-friendly chlorine source, thus avoiding the use of excess metal halides such as cupric chloride. Some preliminary mechanistic studies were performed, which further revealed possible pathways for this cascade annulation.     

Silver‐Catalyzed Nitration/Annulation of α‐Alkynyl Arylols toward 3‐Nitrated Benzofurans

A silver‐catalyzed nitration/annulation of α‐alkynyl arylols is reported by using tert‐butyl nitrite (TBN) as a NO₂ radical precursor, from which a set of 3‐nitrated benzofurans were synthesized with moderate to good yields. This transformation initiated by an in situ generated NO₂ radical proceeds efficiently under mild and neutral redox conditions, which provides a new pathway toward the 3‐nitrobenzofuran framework via catalytic difunctionalization of internal alkynes.     

Palladium‐Catalyzed Oxidative Synthesis of α‐Acetoxylated Enones from Alkynes

We report a palladium‐catalyzed oxidative functionalization of alkynes to generate α‐acetoxylated enones in one step. A range of functional groups are well‐tolerated in this reaction. Mechanistic studies, including the use of ¹⁸O‐labeled DMSO, revealed that the ketone oxygen atom in the product originates from DMSO.     

Palladium‐Catalyzed Cascade Cyclization/Alkynylation Reactions

Palladium‐catalyzed cascade cyclization reactions have witnessed significant improvements in recent years. Among them, palladium‐catalyzed cascade cyclization/alkynylation are especially attractive, which can assemble structurally diverse monocyclic, bicyclic, fused polycyclic, and spirocyclic skeletons with excellent chemoselectivities. In this Minireview, palladium‐catalyzed cascade cyclization/alkynylation have been summarized and discussed in detail with focus on oxypalladation and aminopalladation‐initiated cascade cyclization, intramolecular Heck‐type cascade cyclization, carbocyclizations, cascade cyclizations, and other types of cascade cyclization reactions. Some significant and representative synthetic methodologies and their synthetic applications and reaction mechanisms have also been described.     

Nickel‐Catalyzed Cascade Annulation for the Rapid Synthesis of Carbocyclic Nitriles

We report a Ni‐catalyzed cascade annulation reaction that proceeds through two sequential carbometallation steps followed by C?CN reductive elimination. This reaction transforms two simple starting materials into complex, carbocyclic nitriles.     

Palladium‐Catalyzed [3+3] Annulation between Diarylamines and α,β‐Unsaturated Acids through CH Activation: Direct Access to 4‐Substituted 2‐Quinolinones

A C?H activation strategy has been successfully employed for the high‐yielding synthesis of a diverse array of 4‐substituted 2‐quinolinone species by a palladium‐catalyzed dehydrogenative coupling involving diarylamines. This intermolecular annulation approach incorporates readily available α,β‐unsaturated carboxylic acids as the coupling partner by suppressing the facile decarboxylation. Based on preliminary mechanistic studies, a reaction sequence is proposed, involving ortho palladation, π‐coordination, β‐migratory insertion, and β‐hydride elimination.     

Synthesis of Highly Substituted γ‐Butyrolactones by a Gold‐Catalyzed Cascade Reaction of Benzyl Esters

Easily accessible benzylic esters of 3‐butynoic acids in a gold‐catalyzed cyclization/rearrangement cascade reaction provided 3‐propargyl γ‐butyrolactones with the alkene and the carbonyl group not being conjugated. Crossover experiments showed that the formation of the new C?C bond is an intermolecular process. Initially propargylic–benzylic esters were used, but alkyl‐substituted benzylic esters worked equally well. In the case of the propargylic–benzylic products, a simple treatment of the products with aluminum oxide initiated a twofold tautomerization to the allenyl‐substituted γ‐butyrolactones with conjugation of the carbonyl group, the olefin, and the allene. The synthetic sequence can be conducted stepwise or as a one‐pot cascade reaction with similar yields. Even in the presence of the gold catalyst the new allene remains intact.     

Palladium‐Catalyzed Cross‐Coupling of Styrenes with Aryl Methyl Ketones in Ionic Liquids: Direct Access to Cyclopropanes

The combined use of Pd(OAc)₂, Cu(OAc)₂, and dioxygen in molten tetrabutylammonium acetate (TBAA) promotes an unusual cyclopropanation reaction between aryl methyl ketones and styrenes. The process is a dehydrogenative cyclizing coupling that involves a twofold C? H activation at the α‐position of the ketone. The substrate scope highlights the flexibility of the catalyst; a reaction mechanism is also proposed.     

Microwave‐Assisted,Rhodium(III)‐Catalyzed N‐Annulation Reactions of Aryl and α,β‐Unsaturated Ketones with Alkynes

New Rh^III‐catalyzed, one‐pot N‐annulation reactions of aryl and α,β‐unsaturated ketones with alkynes in the presence of ammonium acetate have been developed. Under microwave irradiation conditions, the processes lead to rapid formation of the respective isoquinoline and pyridine derivatives with efficiencies that are strongly dependent on the steric nature of the aryl ring and enone substituents. By employing this protocol, a variety of isoquinoline and pyridine derivatives were prepared in high yields. In addition, a new one‐pot approach to the synthesis of pyridines, involving four‐component reactions of ketones, formaldehyde, NH₄OAc, and alkynes, has been uncovered. This process takes place through a route involving initial aldol condensation of the ketone with formaldehyde to generate a branched α,β‐unsaturated ketone that then undergoes Rh^III‐catalyzed N‐annulation with NH₄OAc and the alkyne.     

Palladium‐Catalyzed Annulation of 1,2‐Diborylalkenes and ‐Arenes with 1‐Bromo‐2‐[(Z)‐2‐bromoethenyl]arenes: A Modular Approach to Multisubstituted Naphthalenes and Fused Phenanthrenes

(Z)‐1,2‐Diaryl‐1,2‐bis(pinacolatoboryl)ethenes underwent double‐cross‐coupling reactions with 1‐bromo‐2‐[(Z)‐2‐bromoethenyl]arenes in the presence of [Pd(PPh₃)₄] as a catalyst and 3 M aqueous Cs₂CO₃ as a base in THF at 80 °C. The double‐coupling reaction gave multisubstituted naphthalenes in good to high yields. Annulation of 1,2‐bis(pinacolatoboryl)arenes with bromo(bromoethenyl)arenes in the presence of a catalyst system that consisted of [Pd₂(dba)₃] (dba=dibenzylideneacetone) and 2‐dicyclohexylphosphino‐2′,6′‐dimethoxybiphenyl (SPhos) under the same conditions produced fused phenanthrenes in good to high yields. The first annulation coupling occurred regiospecifically at the bromoethenyl moiety. This procedure is applicable to the facile synthesis of polysubstituted anthracenes, benzothiophenes, and dibenzoanthracenes through a double annulation pathway by using the corresponding dibromobis[(Z)‐2‐bromoethenyl]benzenes as diboryl coupling partners.     

Palladium‐Catalyzed CH Activation and Intermolecular Annulation with Allenes

A new and efficient Pd^II‐catalyzed intermolecular annulation of N‐benzoylsulfonamide with allenes for the synthesis of 3,4‐dihydroisoquinolin‐1(2H)‐ones is reported. This C?H functionalization is compatible with ambient air and moisture, and it can be applied to terminal or internal allenes with di?erent synthetically attractive functional groups. Control experiments and a kinetic isotope effect study are conducted and a plausible mechanism is proposed.     

Ionic Liquids as Precatalysts in the Highly Stereoselective Conjugate Addition of α,β‐Unsaturated Aldehydes to Chalcones

Imidazolium‐based ionic liquids (ILs) serve both as recyclable reaction media and as precatalysts for the N‐heterocyclic carbene‐catalyzed conjugate addition of α,β‐unsaturated aldehydes to chalcones. The reaction produces a broad scope of 1,6‐ketoesters incorporating an anti‐diphenyl moiety in high yields and with high stereoselectivity. In recycling experiments, the IL can be reused up to five times with retained reactivity and selectivity. Moreover, the 1,6‐ketoesters form self‐assembled organogels in aliphatic hydrocarbons. The reaction protocol is robust, easily operated, scalable and highly functionalized compounds can be obtained from inexpensive and readily accessible starting materials.