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.     

Palladium‐Catalyzed Cascade Annulation To Construct Functionalized β‐ and γ‐Lactones in Ionic Liquids

A highly efficient and mild palladium‐catalyzed, one‐pot, four‐step cascade annulation has been developed to afford functionalized β‐ and γ‐lactones in moderate to good yields with high regio‐ and diastereoselectivities in ionic liquids. The employment of ionic liquids under mild reaction conditions makes this transformation green and practical. Especially, this reaction provided a novel and convenient methodology for the construction of naturally occurring biologically active β‐ and γ‐lactones.     

Ligand Bite Angle‐Dependent Palladium‐Catalyzed Cyclization of Propargylic Carbonates to 2‐Alkynyl Azacycles or Cyclic Dienamides

The regioselectivity of the palladium‐catalyzed cyclization of propargylic carbonates with sulfonamide nucleophiles is critically dependent on the bite angle of the bidentate phosphine ligand. Ligands with small bite angles favor attack on the central carbon atom of an allenylpalladium intermediate to afford cyclic dienamide products, whereas the use of those with large bite angles leads to alkynyl azacycles, with high stereoselectivity. A computational analysis of the reaction pathway is also presented.     

Rhodium(III)‐Catalyzed [3+2] Annulation of 5‐Aryl‐2,3‐dihydro‐1H‐pyrroles with Internal Alkynes through C(sp2)H/Alkene Functionalization

This study describes a new rhodium(III)‐catalyzed [3+2] annulation of 5‐aryl‐2,3‐dihydro‐1H‐pyrroles with internal alkynes using a Cu(OAc)₂ oxidant for building a spirocyclic ring system, which includes the functionalization of an aryl C(sp²)? H bond and addition/protonolysis of an alkene C?C bond. This method is applicable to a wide range of 5‐aryl‐2,3‐dihydro‐1H‐pyrroles and internal alkynes, and results in the assembly of the spiro[indene‐1,2′‐pyrrolidine] architectures in good yields with excellent regioselectivities.     

A Zinc-Mediated Deprotective Annulation Approach to New Polycyclic Heterocycles

A straightforward approach to new polycyclic heterocycles, 1H-benzo[4,5]imidazo[1,2-c][1,3]oxazin-1-ones, is presented. It is based on the ZnCl₂-promoted deprotective 6-endo-dig heterocyclization of N-Boc-2-alkynylbenzimidazoles under mild conditions (CH₂Cl₂, 40 °C for 3 h). The zinc center plays a dual role, as it promotes Boc deprotection (with formation of the tert-butyl carbocation, which can be trapped by substrates bearing a nucleophilic group) and activates the triple bond toward intramolecular nucleophilic attack by the carbamate group. The structure of representative products has been confirmed by X-ray diffraction analysis.     

Platinum‐Catalyzed Domino Reaction with Benziodoxole Reagents for Accessing Benzene‐Alkynylated Indoles

Indoles are omnipresent in natural products, bioactive molecules, and organic materials. Consequently, their synthesis or functionalization are important fields of research in organic chemistry. Most works focus on installation or modification of the pyrrole ring. To access benzene‐ring‐functionalized indoles with an unsubstituted pyrrole ring remains more challenging. Reported herein is a platinum‐catalyzed cyclization/alkynylation domino process to selectively obtain C5‐ or C6‐functionalized indoles starting from easily available pyrroles. The work combines, for the first time, a platinum catalyst with ethynylbenziodoxole hypervalent iodine reagents in a domino process for the synthesis of polyfunctionalized arene rings and gives access to important building blocks for the synthesis of bioactive compounds and organic materials.     

Zinc‐Catalyzed Asymmetric Formal [4+3] Annulation of Isoxazoles with Enynol Ethers by 6π Electrocyclization: Stereoselective Access to 2H‐Azepines

6π electrocyclization has attracted interest in organic synthesis because of its high stereospecificity and atom economy in the construction of versatile 5–7‐membered cycles. However, examples of asymmetric 6π electrocyclization are quite scarce, and have to rely on the use of chiral organocatalysts, and been limited to pentadienyl‐anion‐ and triene‐type 6π electrocyclizations. Described herein is a zinc‐catalyzed formal [4+3] annulation of isoxazoles with 3‐en‐1‐ynol ethers via 6π electrocyclization, leading to the site‐selective synthesis of functionalized 2H‐azepines and 4H‐azepines in good to excellent yields with broad substrate scope. Moreover, this strategy has also been used to produce chiral 2H‐azepines with high enantioselectivities (up to 97:3 e.r.). This protocol not only is the first asymmetric heptatrienyl‐cation‐type 6π electrocyclization, but also is the first asymmetric reaction of isoxazoles with alkynes and the first asymmetric catalysis based on ynol ethers.     

Organocatalytic Oxidative Annulation of Benzamide Derivatives with Alkynes

Organocatalytic annulation by functionalization of benzamide derivatives with alkynes has been developed. We report a new approach of cycloaddition under mild reaction conditions using simple catalysts, such as iodobenzene and peracetic acid, as oxidant. Those novel, mild reaction conditions provided a straightforward synthesis of isoquinolones with fast reaction rate. Notable selectivity in annulation of unsymmetrically disubstituted alkynes was demonstrated.     

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.     

Thermally Induced Denitrogenative Annulation for the Synthesis of Dihydroquinolinimines and Chroman‐4‐imines

A rapid growth in synthetic methods for the preparation of diverse organic molecules using N‐sulfonyl‐1,2,3‐triazoles is of great interest in organic synthesis. Transition metals are generally used to activate the α‐imino diazo intermediates. Metal‐free methods have not been studied in detail, but can be a good complement to transition metal catalysis in the mild reaction conditions. We herein report a novel method for the preparation of 2,3‐dihydroquinolin‐4‐imine and chroman‐4‐imine analogs from their corresponding N‐sulfonyl‐1,2,3‐triazoles in the absence of metal catalysts. To achieve intramolecular annulation, the introduction of an electron‐donating group is required at the meta position of N‐sulfonyl‐1,2,3‐triazole methyl anilines. The inclusion of tailored substituents on the aniline moieties and nitrogen atoms enhances the nucleophilicity of the phenyl π‐electrons, thus allowing them to undergo a Friedel–Crafts‐type reaction with the highly electrophilic ketenimines. This metal‐free method was carefully optimized to generate a variety of dihydroquinolin‐4‐imines and chroman‐4‐imines in moderate‐to‐good yields.     

A Versatile Iron‐Catalyzed Protocol for the One‐Pot Synthesis of Isoxazoles or Isoxazolines from the Same Propargylic Alcohols

The use N‐sulfonyl‐protected hydroxylamines as bi‐nucleophiles in iron‐catalyzed propargylic substitutions allows the selective one‐pot synthesis of four classes of substituted isoxazoles or isoxazolines from the same propargylic alcohols (21 examples) by simply tuning the nature of the base. By using an iron(III) catalyst and a base such as triethylamine (3 equiv), isoxazoles 3 are obtained in good isolated yields (56–95%), whereas N‐sulfonyl‐protected isoxazolines 6 are selectively obtained (77–93% yield) by using iron and gold catalysts in the presence of a catalytic amount of pyridine (10 mol%).     

Electrochemical Synthesis of Imidazo‐Fused N‐Heteroaromatic Compounds through a C−N Bond‐Forming Radical Cascade

We have developed a unified strategy for preparing a variety of imidazo‐fused N‐heteroaromatic compounds through regiospecific electrochemical (3+2) annulation reaction of heteroarylamines with tethered internal alkynes. The electrosynthesis employs a novel tetraarylhydrazine as the catalyst, has a broad substrate scope, and obviates the need for transition‐metal catalysts and oxidizing reagents.     

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 Three‐Component Cascade Reaction: Facial Access to Densely Functionalized Indolizines

A palladium‐catalyzed three‐component cascade reaction of 2‐(2‐enynyl)pyridines with nucleophiles and allyl halides has been developed, enabling the synthesis of densely functionalized indolizines in moderate to good yields. The newly developed methodology offers several practical advantages, including operational simplicity, ready availability of starting materials, and mild reaction conditions.     

Redox‐Neutral Manganese(I)‐Catalyzed C−H Activation: Traceless Directing Group Enabled Regioselective Annulation

A strategy is reported in which traceless directing groups (TDGs) are used to promote the redox‐neutral Mn^I‐catalyzed regioselective synthesis of N‐heterocycles. Alkyne coupling partners bearing a traceless directing group, which serves as both the chelator and internal oxidant, were used to control the regioselectivity of the annulation reactions. This operationally simple approach is highly effective with previously challenging unsymmetrical alkyne systems, including unbiased dialkyl alkynes, with perfect regioselectivity. The simple conditions and the ability to carry out synthesis on a gram scale underscore the usefulness of this method. The application of this strategy in the concise synthesis of the bioactive compound PK11209 and the pharmaceutical moxaverine is also described.