Cyclization Of Alkynes Research Articles

Phosphazene superbase mediated cyclization and annulation reactions of functionalized alkynes for the synthesis of heterocyclic compounds

Base-mediated cyclization and annulation reactions are very useful methods in the heterocyclic synthesis. Different types of conventional bases, i.e., inorganic bases or organometallic bases have been traditionally used for carrying out these reactions in the past. Over the years, the phosphazene organic superbases have emerged as effective alternatives to inorganic and organometallic bases. The phosphazene superbase was first used for alkyne cyclization in 2008, and its use has become quite popular over the last decade. This review is aimed to provide an analysis of the use of phosphazene superbase, especially P4–t-Bu as a robust and highly efficient catalyst/reagent in various intra- or intermolecular reactions of substituted alkynes for the synthesis of O,N-heterocycles such as isoindolin-1-ones, benzofurans, isobenzofurans, proline derivatives, pyrroles, etc.

One-Pot Oxidative C-H Activation/Aza-Prins-Type Reaction of Tertiary Alkynylamines: A Counter Ion-Induced Iminium Ion-Alkyne Cyclization.

Herein, the design and development of a new one-pot and metal-free oxidative C-H activation/aza-Prins type cyclization of alkynylamines is reported. The scope of this method was demonstrated by the preparation of ten new pyrido[2,1-a]isoquinolines in moderate to high yields (38-92%). Furthermore, a mechanistic proposal for the alkyne aza-Prins cyclization is described based on DFT calculations.

Synthesis of Indanones and Spiroindanones by Diastereoselective Annulation Based on a Hydrogen Autotransfer Strategy.

An unprecedented nickel-catalyzed domino reductive cyclization of alkynes and o-bromoaryl aldehydes is described. The reaction features broad substrate scope and is tolerant of a variety of functional groups, providing straightforward access to biologically significant indanones and spiroindanone pyrrolidine derivatives in good yields with excellent regio- and diastereoselectivity. Preliminary mechanistic studies have shown that indanones are formed by the cyclization of o-bromoaryl aldehydes and alkynes to form indenol intermediates, followed by hydrogen autotransfer.

Synthesis of Indanones and Spiroindanones by Diastereoselective Annulation Based on a Hydrogen Autotransfer Strategy

AbstractAn unprecedented nickel‐catalyzed domino reductive cyclization of alkynes and o‐bromoaryl aldehydes is described. The reaction features broad substrate scope and is tolerant of a variety of functional groups, providing straightforward access to biologically significant indanones and spiroindanone pyrrolidine derivatives in good yields with excellent regio‐ and diastereoselectivity. Preliminary mechanistic studies have shown that indanones are formed by the cyclization of o‐bromoaryl aldehydes and alkynes to form indenol intermediates, followed by hydrogen autotransfer.

Visible-Light-Catalyzed Tandem Cyanoalkylsulfonylation/ Cyclization of Alkynes

Visible-Light-Catalyzed Tandem Cyanoalkylsulfonylation/ Cyclization of Alkynes

Molecular engineering enabling reversible transformation between helical and planar conformations by cyclization of alkynes.

Molecular engineering enabling reversible transformation between helical and planar conformations is described herein. Starting from easily available 2-(pyridin-2-yl)anilines and alkynes, a one-pot strategy is set up for the synthesis of aza[4]helicenes via two successive rhodium-catalyzed C–H activation/cyclizations. Helical pyrrolophenanthridiziniums can be transformed into planar conformations through the cleavage of acidic pyrrole N–H, leading to turn-off fluorescence. NMR spectra, single crystal X-ray diffraction and DFT calculations demonstrate that the formation of an intramolecular C–H⋯N hydrogen bond is beneficial to stabilize the pyrrole nitrogen anion of the planar molecule and provide increased planarity. The reversible conformation transformations can be finely adjusted by the electron-donating and -withdrawing groups on the π+-fused pyrrole skeleton in the physiological pH range, thus affording an opportunity for pH-controlled intracellular selective fluorescence imaging. Pyrrolophenanthridiziniums show turn-on fluorescence in lysosomes owing to the acidic environment of lysosomes and turn-off fluorescence out of lysosomes, indicating the occurrence of the deprotonation reaction outside lysosomes and the corresponding transformation from helical to planar conformations.

Selective Synthesis of Non-Aromatic Five-Membered Sulfur Heterocycles via Multicomponent Cyclization of Alkynes

Selective Synthesis of Non-Aromatic Five-Membered Sulfur Heterocycles via Multicomponent Cyclization of Alkynes

Recent progress towards the transition-metal-catalyzed Nazarov cyclization of alkynes via metal carbenes.

In recent years, transition-metal-catalyzed tandem cyclization reactions of alkynes, especially those involving a metal carbene intermediate, have received worthwhile interest, as this type of reaction does not require the use of risky and potentially explosive diazo compounds as starting materials for carbene generation. A significant and general strategy for the stereospecific synthesis of 5-membered cycles is Nazarov cyclization based on the 4π-conrotatory electrocyclization of a conjugated pentadienyl cation to afford a cyclopentenyl cation. In this review, we introduce an overview of recent advances in the transition-metal-catalyzed Nazarov cyclization of alkynes via a metal carbene intermediate, and categorize these reactions according to the structure of the metal carbene. Our aim is to accelerate advancements in this enchanting area of research.

Ultra-fast covalent molecular printing on cellulose paper by photo-strain-triggered click ligation: UV LED versus laser irradiations

The use of cyclopropenone derivatives as latent photo-released strained cyclic alkynes is reported for the covalent printing of complex patterns on cellulose paper. Two different approaches using either a UV LED or a laser as light irradiation source are discussed. While the high intensity of the laser damages the grafted molecular layer, the use of a simple UV LED allows the printing in only 8 min at room temperature with a good resolution at the micrometer scale with negligible diffusion. The validity of this strategy is demonstrated through the sequential printing of a QR code and a logo on the same paper sheet.

Chrysene-Based Blue Emitters.

Chrysene and its bisbenzannulated homologue, naphtho[2,3‐c]tetraphene, were synthesized through a PtCl2‐catalyzed cyclization of alkynes, which also furnished corresponding biaryls subsequent to a Glaser coupling reaction of the starting alkynes. The optoelectronic properties of 5,5′‐bichrysenyl and 6,6′‐binaphtho[2,3‐c]tetraphene were compared to their chrysene‐based “monomers”. Oxidative cyclodehydrogenations of bichrysenyl and its higher homologue towards large nanographenes were also investigated.

Synthesis of Coumarins via [4+2] Cyclization of Siloxy Alkynes and Salicylaldehydes

AbstractA new approach for the synthesis of coumarins from siloxy alkynes and salicylaldehydes is disclosed. Unlike the previous benzannulation reactions of siloxy alkynes that all proceed by electron-inversed Diels–Alder mechanism, this process represents a new [4+2] cyclization. In the presence of the superior HNTf2 catalyst, a wide range of coumarins were efficiently synthesized. This process was also extended to the synthesis of 2-quinolones. The polarized electron-rich triple bond might react sequentially with the aldehyde and hydroxy group by polarity switching in the stepwise formation of the C–C and C–O bonds. Control experiments provided insights into the mechanistic understanding.

Electrochemically Enabled Intramolecular and Intermolecular Annulations of Alkynes

AbstractElectrosynthesis is recognized as one of the most powerful and sustainable methods in organic chemistry. Recently, electrochemically enabled annulations of carbon‐carbon triple bonds have been successfully achieved, and have broadened prospects for the application of the emerging method with cyclization of alkynes. Thus, herein we outline the recent progress made on electrochemically enabled annulations of alkynes. In addition, an emphasis on the scope, limitations and the mechanisms of these reactions is made in this review.magnified image

Intercepting fleeting cyclic allenes with asymmetric nickel catalysis.

Strained cyclic organic molecules, such as arynes, cyclic alkynes and cyclic allenes, have intrigued chemists for more than a century with their unusual structures and high chemical reactivity1. The considerable ring strain (30-50 kilocalories per mole)2,3 that characterizes these transient intermediates imparts high reactivity in many reactions, including cycloadditions and nucleophilic trappings, often generating structurally complex products4. Although strategies to control absolute stereochemistry in these reactions have been reported using stoichiometric chiral reagents5,6, catalytic asymmetricvariants to generate enantioenriched products have remained difficult to achieve. Here we report the interception of racemic cyclic allene intermediates in a catalytic asymmetric reaction and provide evidence for two distinct mechanisms that control absolute stereochemistry in such transformations: kinetic differentiation of allene enantiomers and desymmetrization of intermediate π-allylnickel complexes. Computational studies implicate a catalytic mechanism involving initial kinetic differentiation of the cyclic allene enantiomers through stereoselective olefin insertion, loss of the resultant stereochemical information, and subsequent introduction of absolute stereochemistry through desymmetrization of an intermediate π-allylnickel complex. These results reveal reactivity that is available to cyclic allenes beyond the traditional cycloadditions and nucleophilic trappings previously reported, thus expanding thetypes of product accessible from this class of intermediates. Additionally, our computational studies suggest two potential strategies for stereocontrol in reactions of cyclic allenes. Combined, these results lay the foundation for the development of catalytic asymmetric reactions involving these classically avoided strained intermediates.

Copper‐Catalyzed Azide–Ynamide Cyclization to Generate α‐Imino Copper Carbenes: Divergent and Enantioselective Access to Polycyclic N‐Heterocycles

AbstractHere an efficient copper‐catalyzed cascade cyclization of azide‐ynamides via α‐imino copper carbene intermediates is reported, representing the first generation of α‐imino copper carbenes from alkynes. This protocol enables the practical and divergent synthesis of an array of polycyclic N‐heterocycles in generally good to excellent yields with broad substrate scope and excellent diastereoselectivities. Moreover, an asymmetric azide–ynamide cyclization has been achieved with high enantioselectivities (up to 98:2 e.r.) by employing BOX‐Cu complexes as chiral catalysts. Thus, this protocol constitutes the first example of an asymmetric azide–alkyne cyclization. The proposed mechanistic rationale for this cascade cyclization is further supported by theoretical calculations.

Palladium-Catalyzed Imidoylation-Triggered [2 + 2 + 1] Cyclization of Internal Alkyne with Isocyanides.

In this work, a palladium-catalyzed [2 + 2 + 1] cyclization of internal alkynes with double isocyanides is described. This facile procedure is efficient for synthesizing various pyrrolo[3,2-c]quinolin-2-amines. The reaction worked well with a broad reaction scope. In the process, it is believed that sequential double isocyanide insertion, 6-exo-dig cyclization of alkyne, and addition of an imino group are involved.

Synthesis of Seleno‐Heterocycles via Electrophilic/Radical Cyclization of Alkyne Containing Heteroatoms

Abstractcontaining heterocyclic scaffolds by virtue of their interesting reactivities and a broad range of applications in the medicinal and materials chemistry. This review involves the electrophilic/radical cyclization of alkynes containing heteroatoms which resulted into the novel Se‐heterocycles. The synthesis of seleno‐heterocycles via different nucleophiles including O, N, S, Se, Te, and C‐nucleophiles is exhaustively discussed. Also, one‐pot electrophilic cyclization of 1,3‐diynes and 1,3,5‐triynes was described in details. Furthermore, the various mechanisms underlying the synthesis of selenium‐β‐lactam, carbapenem heterocycle, bis‐ and tris‐selenide alkene, β‐selenosulfonation and selenated alkynes were discussed. The Se‐heterocycles reported in this review allow preparing these selenated compounds bearing the selenium moiety both on the rings (outside) and inside the ring (e. g. selenophenes). The review demonstrates the growing opportunities to construct selenium containing heterocycles from alkynes containing heteroatoms.magnified image

Enantioselective Type II Cycloaddition of Alkynes via C-C Activation of Cyclobutanones: Rapid and Asymmetric Construction of [3.3.1] Bridged Bicycles.

Synthesis of bridged scaffolds via Type II cyclization constitutes substantial challenges due to the intrinsic ring strain accumulated in reaction transition states. Catalytic enantioselective Type II-cyclization methods are even rarer. Here, we describe a detailed study of developing a Rh(I)-catalyzed enantioselective intramolecular Type II cyclization of alkynes via C-C activation of cyclobutanones. This method offers a rapid approach to access a wide range of functionalized [3.3.1]-bridged bicycles along with an exocyclic olefin and an all-carbon quaternary stereocenter. Excellent enantioselectivity has been achieved using a combination of cationic rhodium(I) and DTBM-segphos. Attributed to the redox neutral and strong acid/base-free reaction conditions, high chemoselectivity has also been observed. For the oxygen-tethered substrates, the reaction can proceed at room temperature. In addition, partial kinetic resolution has been achieved for substrates with existing stereocenters, forging interesting chiral tricyclic scaffolds. The methylalkyne-derived substrates gave unexpected dimeric structures in good yield with excellent enantioselectivity and complete diastereoselectivity. Furthermore, the bridged bicyclic products can be diversely functionalized through simple transformations. Finally, mechanistic studies reveal a surprising reaction pathway that involves forming a metal-stabilized anti-Bredt olefin intermediate.

Ruthenium-Induced Cyclization of Heteroatom-Functionalized Alkynes: Progress, Challenges and Perspectives.

Metal-induced cyclization of functionalized alkynes represents one of the most general approaches to prepare organic heterocycles. Although RuII centers are well-established to promote alkyne to vinylidene rearrangements and many RuII -mediated alkyne cyclizations have been rationalized to be the results of post-vinylidene transformations, recent discoveries indicate that RuII centers can serve as electrophiles and induce alkyne cyclizations without vinylidene intermediacy. In this Minireview, an overview of the RuII -induced cyclization of heteroatom-functionalized alkynes in the last decade is provided, with an emphasis on the discoveries and validations of the unconventional "non-vinylidene-involving" pathways.

Continuous Microwave-Assisted Synthesis of Silver Nanoclusters Confined in Mesoporous SBA-15: Application in Alkyne Cyclizations

Metal nanoclusters are becoming exciting candidates as highly efficient catalysts for heterogeneous processes in view of their extraordinary surface to volume ratio and the high concentration of uncoordinated atoms that contribute to enhanced catalytic activity. For this reason, the development of accurate and reliable procedures for the synthesis of stable and supported metal nanoclusters is highly desirable. Although Ag nanoclusters (Ag NCs) stabilized by anion templates with a structure like Agm+nm+ and a long lifetime have been widely investigated, supported clusters present significant advantages regarding their recovery and recyclability. In spite of their potential, the stabilization of clusters of precious metals on porous substrates is scarcely investigated. Herein, we present an innovative approach for the synthesis of stable Ag nanoclusters designed with the aim of achieving a strict control of key phases such as mixing, microwave heating, and quenching. The catalyst was used for the activation of alkynes showing excellent activity for the formation of C–O, C–N, and C–C bonds. When compared with commonly used homogeneous Ag salts, Ag NCs enhanced the catalytic activity toward the cyclization of a wide range of substrates, thereby minimizing the metal loading and allowing the separation as well as the reuse of the catalyst for multiple cycles.

Gold/Lewis acid catalyzed oxidative cyclization involving activation of nitriles.

A gold-catalyzed oxidative cyclization of alkyne-nitriles using water or alcohol as the external nucleophiles has been developed. The catalytic system, featured with gold and Lewis acid dual catalysis, allows a facile synthesis of functionalized isoquinolin-1(2H)-ones and 1-alkoxy-isoquinolines with a wide structural diversity.