Facile synthesis and functionalization of fluoranthenes via intramolecular [4 + 2] annulations between thiophenes and alkynes

Fluoranthenes have attracted tremendous attention due to their unique optoelectronic properties and extensive applications. Although several synthetic methodologies have been developed for the preparation of fluoranthene derivatives, it is still unfavorable to functionalize the fluoranthene framework at different positions due to the relatively low selectivity and reactivity. Herein, a catalyst-free intramolecular [4 + 2] annulation between thiophenes and alkynes is developed towards the synthesis of fluoranthenes. Altogether 20 examples have been demonstrated using this method. Various functional groups can be precisely introduced into the fluoranthene skeleton at different positions by simply tuning the substituents on the thiophenes and alkynes. The conjugation of the fluoranthene can be facilely extended through different directions. Furthermore, the feasibility of this [4 + 2] annulation reaction is also investigated by density functional theory calculations. Therefore, this protocol provides not only a synthetic methodology towards fluoranthenes with substituents functionalized at different positions, but also an effective pathway to construct large polycyclic aromatic hydrocarbons containing fluoranthene moieties.     

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.     

Synthesis of tetrasubstituted thiophenes from pyridinium 1,4-zwitterionic thiolates and modified activated alkynes

Pyridinium 1,4-zwitterionic thiolates were applied to a formal [3 + 2] annulation reaction with modified activated alkynes, affording various tetrasubstituted thiophenes with aryl, alkenyl, alkyl or silyl group at the special position. The structural modification of alkyne substrates enabled the synthesis of diverse thiophenes to be achieved using the pyridinium 1,4-zwitterionic thiolates as the sulfur-containing building blocks. This approach is metal-free and catalyst-free.     

Dimerization of Dimethyl 2‐(Naphthalen‐1‐yl)cyclopropane‐1,1‐dicarboxylate in the Presence of GaCl3 to [3+2], [3+3], [3+4], and Spiroannulation Products

In the presence of a catalytic amount of GaCl₃, dimethyl 2‐(naphthalen‐1‐yl)cyclopropane‐1,1‐dicarboxylate 5 undergoes selective [3+2]‐annulation‐type dimerization to give a polysubstituted cyclopentane containing two naphthalenyl substituents in the vicinal position (Scheme 2). Treatment of the same cyclopropane with an equimolar amount of GaCl₃?THF results in dimerization with electrophilic attack on each of the benzene rings to give [3+3] and [3+4] annulation products. The latter represent a new type of dimerization of donor? acceptor cyclopropanes. Finally, under conditions of double catalysis with GaCl₃, 3,3,5,5‐tetrasubstituted 4,5‐dihydropyrazole, this cyclopropane‐dicarboxylate undergoes stereospecific dimerization as a result of electrophilic ipso‐attack to give a tetracyclic pentaleno[6a,1‐a]naphthalene derivative (Scheme 5). Possible reaction mechanisms are proposed.     

Rhodium(III)‐Catalyzed [3+2]/[5+2] Annulation of 4‐Aryl 1,2,3‐Triazoles with Internal Alkynes through Dual C(sp2)H Functionalization

A rhodium(III)‐catalyzed [3+2]/[5+2] annulation of 4‐aryl 1‐tosyl‐1,2,3‐triazoles with internal alkynes is presented. This transformation provides straightforward access to indeno[1,7‐cd]azepine architectures through a sequence involving the formation of a rhodium(III) azavinyl carbene, dual C(sp²)? H functionalization, and [3+2]/[5+2] annulation.     

Strain‐Promoted 1,3‐Dithiolium‐4‐olates–Alkyne Cycloaddition

Reported here is the reactivity of mesoionic 1,3‐dithiolium‐4‐olates towards strained alkynes, leading to thiophene cycloaddition products. In the process, the potential of these dipoles towards orthogonal reaction with azides, allowing efficient double ligation reactions, was discovered. A versatile process to access benzo[c]thiophenes, in an unprecedented divergent fashion, was developed and provides a new entry to unconventional polyaromatic thiophenes.     

Facile Synthesis of Polysubstituted Indolizines via One‐Pot Reaction of 1‐Acetylaryl 2‐Formylpyrroles and Enals

An efficient method for the synthesis of polysubstituted indolizines has been developed based on formal [4+2] annulation of 1‐acetylaryl 2‐formylpyrroles with enals, followed by oxidative aromatization. Pyridine‐type six‐membered rings were constructed in this transformation. This transition metal‐free reaction features mild reaction conditions, a broad substrate scope, and excellent functional group tolerance. Notably, the formyl group is well tolerated under reaction conditions.     

Iron‐Carbonyl‐Catalyzed Redox‐Neutral [4+2] Annulation of N−H Imines and Internal Alkynes by C−H Bond Activation

Stoichiometric C?H bond activation of arenes mediated by iron carbonyls was reported by Pauson as early as in 1965, yet the catalytic C?H transformations have not been developed. Herein, an iron‐catalyzed annulation of N?H imines and internal alkynes to furnish cis‐3,4‐dihydroisoquinolines is described, and represents the first iron‐carbonyl‐catalyzed C?H activation reaction of arenes. Remarkablely, this is also the first redox‐neutral [4+2] annulation of imines and alkynes proceeding by C?H activation. The reaction also features only cis stereoselectivity and excellent atom economy as neither base, nor external ligand, nor additive is required. Experimental and theoretical studies reveal an oxidative addition mechanism for C?H bond activation to afford a dinuclear ferracycle and a synergetic diiron‐promoted H‐transfer to the alkyne as the turnover‐determining step.     

(SCp)Rhodium-Catalyzed Asymmetric Satoh–Miura Reaction for Building-up Axial Chirality: Counteranion-Directed Switching of Reaction Pathways

Satoh–Miura reaction is an important method for extending π-systems by forging multi-substituted benzene rings via double aryl C−H activation and annulation with alkynes. However, the development of highly enantioselective Satoh–Miura reaction remains rather challenging. Herein, we report an asymmetric Satoh–Miura reaction between 1-aryl benzo[h]isoquinolines and internal alkynes enabled by a SCpRh-catalyst. Judiciously choosing the counteranion of the Rh-catalyst is crucial for the desired reactivity over the competitive formation of azoniahelicenes. Detailed mechanistic studies support the proposal of counteranion-directed switching of reaction pathways in Rh-catalyzed asymmetric C−H activation.     

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.     

Oxidative Annulation of Arenecarboxylic and Acrylic Acids with Alkynes under Ambient Conditions Catalyzed by an Electron‐Deficient Rhodium(III) Complex

It has been established that an electron‐deficient Cp^E rhodium(III) complex catalyzes the oxidative [4+2] annulation of substituted arenecarboxylic and acrylic acids with alkynes under ambient conditions (at RT–40 °C, under air) without using excess amounts of substrates to produce the corresponding substituted isocoumarins and α‐pyrones in high yields. Minor modification of reaction conditions depending on the coordination ability of alkynes realized the high efficiency.     

FeCl3-Mediated Reaction of 1,4-Dilithio-1,3-dienes with Alkynes Affording Benzene Derivatives

Unactivated alkynes reacted with 1,4-dilithio-1,3-diene derivatives in the presence of FeCl3 affording substituted benzene derivatives via a formal[4 2] cycloaddition.     

Synthesis of Silaphenalenes by Ruthenium‐Catalyzed Annulation between 1‐Naphthylsilanes and Internal Alkynes through CH Bond Cleavage

Ruthenium‐catalyzed annulation of 1‐naphthylsilanes with internal alkynes afforded silaphenalenes through cleavage of the C?H bond at the 8‐position of the naphthalene. [RuH₂(CO){P(p‐FC₆H₄)₃}₃] efficiently catalyzed the reaction. The use of 1‐naphthyldiphenylsilane as a substrate resulted in a better yield of the annulation product compared to the use of silanes with alkyl groups on the silicon atom. Internal alkynes with both aryl and alkyl groups were tolerated in this reaction.     

Copper‐Promoted Annulation of Terminal Alkynes with 2‐Aminopyridines to Assemble 2‐Halogenated Imidazo[1,2‐a]pyridines

Copper‐promoted annulation reactions of terminal alkynes with 2‐aminopyridines have been developed for the synthesis of 2‐halogenated imidazo[1,2‐a]pyridines using copper halide as the halogen source. A variety of substrates survived under the reaction conditions and gave the desired products in good yields. This reaction features advantages such as easily available starting materials, broad substrate scope, and mild reaction conditions.     

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.     

Manganese‐Catalyzed Dehydrogenative [4+2] Annulation of NH Imines and Alkynes by CH/NH Activation

Described herein is a manganese‐catalyzed dehydrogenative [4+2] annulation of N? H imines and alkynes, a reaction providing highly atom‐economical access to diverse isoquinolines. This transformation represents the first example of manganese‐catalyzed C? H activation of imines; the stoichiometric variant of the cyclomanganation was reported in 1971. The redox neutral reaction produces H₂ as the major byproduct and eliminates the need for any oxidants, external ligands, or additives, thus standing out from known isoquinoline synthesis by transition‐metal‐catalyzed C? H activation. Mechanistic studies revealed the five‐membered manganacycle and manganese hydride species as key reaction intermediates in the catalytic cycle.     

Skeletal Rearrangement in the ZnII‐Catalyzed [4+2]‐Annulation of Disubstituted N‐Hydroxy Allenylamines with Nitrosoarenes to Yield Substituted 1,2‐Oxazinan‐3‐one Derivatives

This work reports zinc‐catalyzed [4+2]‐annulation reactions of disubstituted N‐hydroxy allenylamines with nitrosoarenes to afford substituted 1,2‐oxazinan‐3‐ones with a skeletal rearrangement. This annulation is applicable to a reasonable scope of allenylamines and nitrosoarenes. Our control experiments indicate that nitrosobenzene can also implement this annulation through a radical annulation path, but with poor efficiency. Zn(OTf)₂ or AgOTf greatly improves the efficiency of this [4+2]‐annulation; the effect of these metal species is discussed in detail.     

Highly Stereoselective Synthesis of Imine‐Containing Dibenzo[b,d]azepines by a Palladium(II)‐Catalyzed [5+2] Oxidative Annulation of o‐Arylanilines with Alkynes

A novel palladium(II)‐catalyzed [5+2] oxidative annulation of readily available o‐arylanilines with alkynes has been developed for building a seven‐membered N‐heterocyclic architecture containing a biaryl linkage. This method is applicable to a wide range of unprotected o‐arylanilines and internal alkynes, and results in the chemoselective preparation of imine‐containing dibenzo[b,d]azepines in high yields with excellent diastereoselectivity with respect to the two types of stereogenic elements.     

Azaruthena(II)‐bicyclo[3.2.0]heptadiene: Key Intermediate for Ruthenaelectro(II/III/I)‐catalyzed Alkyne Annulations

A ruthenium‐catalyzed electrochemical dehydrogenative annulation reaction of imidazoles with alkynes has been established, enabling the preparation of various bridgehead N‐fused [5,6]‐bicyclic heteroarenes through regioselective electrochemical C?H/N?H annulation without chemical metal oxidants. Novel azaruthenabicyclo[3.2.0]heptadienes were fully characterized and identified as key intermediates. Mechanistic studies are suggestive of an oxidatively induced reductive elimination pathway within a ruthenium(II/III) regime.     

Asymmetric synthesis of dihydroindanes by convergent alkoxide-directed metallacycle-mediated bond formation

A convergent synthesis of highly substituted and stereodefined dihydroindanes is described from alkoxide-directed Ti-mediated cross-coupling of internal alkynes with substituted 4-hydroxy-1,6-enynes (substrates that derive from 2-directional functionalization of readily available epoxy alcohol derivatives). In addition to describing a new and highly stereoselective approach to bimolecular [2 + 2 + 2] annulation that delivers products not available with other methods in this area of chemical reactivity, evidence is provided to support annulation by way of regioselective alkyne-alkyne coupling, followed by metal-centered [4 + 2] rather than stepwise alkene insertion and reductive elimination. Overall, the reaction proceeds with exquisite stereochemical control and defines a convenient, convergent, and enantiospecific entry to fused carbocycles of great potential value in target-oriented synthesis and medicinal chemistry.