Alkyne-Based Cascade Strategies for the Construction of Diverse Carbo/Heterocycles

Abstract

Carbocycles/heterocycles are fundamental structural motifs in natural products, pharmaceuticals, and functional materials. Alkyne-based cascade strategies have emerged as powerful tools for the efficient construction of these frameworks, enabling rapid access to diverse ring systems through domino cyclization pathways. This account highlights the representative recent advances of alkyne-mediated cascade reactions, covering transition-metal catalysis and acid-mediated reactions. These methods facilitate multiple bond-forming events in a single operation, offering high atom and step economy. Special focus is given to illustrative transformations, mechanistic insights, and the broad utility of alkynes as precursors for the concise synthesis of diverse carbocyclic and heterocyclic molecular frameworks.

Keywords

Carbocyclic - Heterocyclic - Domino - Cascade - Cyclization - Alkyne

1

Introduction

Domino/Cascade/Tandem reactions represent a powerful synthetic approach for constructing complex molecular architectures through sequential bond-forming events in a single operation.[1] These transformations maximize efficiency by combining multiple steps into a unified process, offering superior atom economy and reduced purification demands. Among diverse precursors employed in domino reactions, alkynes stand out as particularly versatile building blocks due to their unique structural and electronic properties.[2] [3] [4] [5] [6] [7] [8] [9] [10] [11] [12] [13] [14] [15] [16] [17] [18] [19] [20] The linear geometry of the carbon–carbon triple bond provides a rigid template for controlled cyclizations, while its π-electron density enables diverse activation pathways, including transition metal coordination, electrophilic activation, and radical additions. Alkyne-based domino processes have been widely exploited in the synthesis of carbocyclic and heterocyclic compounds, where carefully designed substrates undergo programmed reaction cascades to rapidly assemble polycyclic frameworks. Transition metals such as gold, rhodium, silver, and palladium effectively initiate such a kind transformations by activating alkyne moieties toward nucleophilic attack or cycloaddition, triggering subsequent ring-forming steps.[21] [22] [23] [24] [25] [26] [27] [28] [29] [30] [31] [32] [33] [34] [35] [36] [37] [38] [39] [40] [41] [42] [43] For instance, the [2+2+2] cyclotrimerization of alkynes exemplifies a domino cyclization pathway, enabling direct construction of aromatic systems through a single catalytic cycle. Similarly, palladium-catalyzed cyclization of alkynes facilitates selective C–C and C-heteroatom bond formations, while acid-mediated transformations provide efficient routes to functionalized carbocycles and heterocycles via electrophilic activation.[44] [45] [46] Likewise, radical-mediated domino reactions leverage alkyne substrates as key intermediates in cascade cyclizations, often proceeding under mild conditions with excellent functional group tolerance.[47] [48] [49] [50] [51] [52] The synthetic utility of alkyne precursors in domino reactions stems from their ability to participate in diverse bond-forming processes while maintaining structural simplicity and modularity; this adaptability allows for the systematic development of new cascade transformations, making alkynes indispensable tools for the efficient synthesis of complex molecular targets. Recent advances continue to expand the scope of these methodologies, demonstrating their broad applicability across organic chemistry and materials science.

This account aims to provide a comprehensive overview of recent advancements in the use of alkyne-based synthetic precursors for the construction of tri-, tetra-, and pentacyclic carbocycles, along with the synthesis of heterocycles. We highlight key reaction types, mechanistic insights, and representative examples that showcase the synthetic significance and elegance of alkyne chemistry in complex molecule construction, especially under domino one-pot operation. Special emphasis is placed on transition metal–catalyzed annulations, tandem and cascade cyclizations, and emerging methodologies that continue to push the boundaries of complexity and efficiency in the synthesis of cyclic products.

2

Results and Discussion

2.1

Acid-mediated Cyclizations

Palladium-catalyzed cascade reactions have emerged as powerful tools for the rapid and efficient construction of complex polycyclic frameworks.[53] [54] [55] [56] [57] Among the various cascade strategies, those involving alkynes are particularly valuable due to the high reactivity and versatile transformation potential of the alkyne functional group.[58] [59] [60] Palladium-catalysts enable a wide array of bond-forming events, including oxidative addition, insertion, and cyclization, that can be orchestrated in a single reaction sequence. In these cascades, alkynes often act as key π-components, participating in intramolecular or intermolecular couplings with nucleophilic or electrophilic partners to generate diverse polycyclic architectures with excellent atom and step economy. In line with this, our research focuses on developing versatile methodologies that harness the unique reactivity of alkynes under transition metal catalysis, particularly with palladium-catalysis.[61] [62] [63] [64] [65] This section highlights some of our recent advancements in this area, showcasing the potential of alkyne-based cascade strategies in modern synthetic chemistry.

In 2017, we reported a Pd-catalyzed domino reaction that efficiently converted symmetrical diarylethynes 1 and iodoarene-tethered alkenes 2 into complex tetracyclic structures 3 through a sequential alkyne insertion/alkene insertion/C-H activation cascade strategy ([Scheme 1]). The reaction proceeded smoothly with symmetrical diaryl alkynes 1 bearing a variety of functional groups, including bis(thienyl)acetylene, and tolerated both electron-donating and electron-withdrawing substituents on the aromatic rings. While unsymmetrical alkynes led to regioisomeric mixtures. However, when ester-substituted to one of the arenes of the alkyne system, in a controlled fashion (i.e., at slightly low temperature), it enabled the selective formation of a single tetracyclic regioisomer, furnishing it in a 52% yield. This methodology elegantly demonstrated how strategic alkyne design can govern both reaction efficiency and selectivity in constructing intricate tetracyclic architectures.[48]

Scheme 1. Selected examples of tetracyclic products 3.

Scheme 2. Plausible reaction mechanism for the formation of 3.

A pivotal palladium-catalyzed aerobic oxidative coupling of ortho-(alkynyl)styrenes 8 with allylic alcohols 9 that efficiently constructed polysubstituted naphthalenes 10 under open-air conditions was explored in 2019 ([Scheme 3]). The reaction proceeds through a regioselective 6-endo-dig cyclization initiated by alkyne 8 coordination to palladium-catalyst, followed by oxidative coupling with allylic alcohols 9, using ambient oxygen as the sole oxidant. Remarkably, diverse internal alkynes 8 participated efficiently, including those with heteroaryl groups, strong electron-withdrawing substituents (esters and nitro), and even less reactive aliphatic alkynes bearing hydroxyl or acetoxy groups. Mechanistically, the Pd(II) coordination to the alkyne 11 triggers a 6-endo-dig cyclization, forming a naphthyl–palladium intermediate 12, which then engages in oxidative addition of the allylic alcohol and β-hydride elimination ([Scheme 4]). This alkyne-driven process forges two new C–C bonds while exhibiting exceptional functional group tolerance, highlighting the versatility of alkynes in controlling reactivity and selectivity in polycyclic construction.[66]

Scheme 3. Selected examples of polysubstituted naphthalenes 10.

Scheme 4. Plausible Mechanism for the formation of naphthalenes 10.

In another study, we developed a time- and temperature-dependent Pd-catalyzed stereo- and regio-selective alkoxy-arylation of ortho-alkynyl benzylic alcohols 16, providing efficient access to (E)- and (Z)-1,1-disubstituted-3-(1-arylalkylidene)-1,3-dihydroisobenzofurans 18/19, valuable motifs in natural products and drug synthesis. A domino Heck/oxo-cyclization sequence enabled stereodivergence through modulation of reaction conditions; kinetic Z-isomers (≤80% yield) predominated when the reaction was conducted at 80 °C for 6 hours, while prolonged heating at 100 °C (12 h) favored thermodynamic E-isomers (up to 88% yield). The protocol tolerated a diverse alkynols 16 (primary, secondary, tertiary, chloro, methoxy, naphthyl), as well as a wide array of haloarenes 17, including electron-rich (Me, and OMe) and strong electron-withdrawing (NO₂, CN, and COMe) containing aryl bromides, enabling the construction of a tetra-substituted exocyclic C=C bond together with two C–C/C–O σ-bonds in a single operation ([Scheme 5]). Control experiments confirm that a stepwise pathway via initial Heck coupling forms the alkenyl–Pd intermediate 21/22, followed by base-promoted cyclization, while in situ and NMR-tube studies reveal spontaneous Z to E isomerization that rationalizes the temperature and time dependence ([Scheme 6]). These control studies were governed predominantly by temperature; incremental increase of temperature shifted the ratio decisively toward the thermodynamically favored E-isomer, whereas lower temperatures preserved the kinetically Z-isomer; thus, reaction time exerted a minor influence on the E/Z isomerization. A scale-up experiment and X-ray crystallography validated scalability and stereochemical control, respectively, offering a practical, modular route to densely functionalized dihydroisobenzofurans. While the reaction tolerated various bromoarenes, however, less reactive aryl chlorides or heteroaryl halides remained challenging substrates.[67]

Scheme 5. Representative examples of (E)/(Z)-1,1-disubstituted-3-(1-arylalkylidene)-1,3-dihydroisobenzofurans 18/19.

Scheme 6. Proposed mechanism for dihydroisobenzofurans 18/19.

Another robust methodology was developed for the construction of benzo[b]furans 28 through a Pd-catalyzed domino sequence featuring terminal alkynes 27 as key building blocks ([Scheme 7]). The process begins with a Sonogashira coupling between haloaryl ethers 26 and diverse terminal alkynes 27, forming the intermediate 31, which subsequently undergoes a spontaneous 5-exo-dig cyclization to forge the benzofuran core. While the Pd-catalyst exclusively mediates the alkyne coupling step to generate 31, the intrinsic reactivity of the alkyne 31 drives the cyclization, demonstrating that alkynes can orchestrate multistep transformations when strategically paired with Pd-catalysis. The optimized reaction conditions employ a catalytic system consisting of Pd(OAc)₂ and xantphos as the ligand, with K₃PO₄ as the base in toluene at 120 °C. A wide range of electron-rich, electron-poor, and heteroaryl-substituted terminal alkynes 27 participated successfully in this transformation, highlighting the method’s broad applicability. Significantly, the reaction could be scaled up to gram quantities without compromising efficiency, and the products were unequivocally characterized by X-ray crystallographic analysis. Mechanistic studies suggest a stepwise process involving the initial Sonogashira coupling to form the alkyne intermediate 31, followed by base-promoted cyclization and isomerization to deliver the aromatic products 28. Control experiments confirmed that the 5-exo-dig cyclization proceeds independently of palladium, driven solely by the base. Although the reaction is less effective with strongly electron-deficient alkynes, it offers a modular, scalable, and operationally simple approach for constructing structurally diverse benzofuran frameworks through a tandem catalytic sequence.[68]

Scheme 7. Key examples of benzo[b]furans 28 (top) and plausible mechanism (bottom).

In 2022, a streamlined two-step approach was developed for converting readily available propargylic alcohols 35 into pharmacologically relevant 2H-pyran-2-ones 38. The sequence begins with a metal-free Meyer–Schuster rearrangement mediated by N-iodosuccinimide (NIS), which efficiently transformed alkynols 35 into densely functionalized α-iodoenones 36 under mild conditions (DCE, 60–80 °C). This operationally simple protocol demonstrated remarkable substrate scope, accommodating dialkyl, diaryl, fluoro, spiro-acetal, and cycloalkyl variants while maintaining excellent scalability (76% yield at 1 g scale) ([Scheme 8]). The synthetic utility of these α-iodoenones 36 was further showcased in their subsequent domino transformation through a Pd-catalyzed Heck coupling with acrylates 37, followed by base-mediated Michael addition, isomerization, and cyclocondensation reactions. This cascade forges two C–C bonds and one C–O bond in a single operation, delivering 3,5,6-trisubstituted 2H-pyran-2-ones 38 in good to excellent yields (70–93%). The optimized conditions (Pd(OAc)₂/PPh₃ 5/10 mol%, K₂CO₃, DMF, 140 °C) highlight the efficiency of this process. Mechanistic studies reveal that palladium is necessary only for the initial Heck step, while the subsequent steps proceed exclusively driven by base, as validated by control experiments. However, propargyl alcohols bearing strong electron-deficient aryl substituents exhibited lower efficiency in forming the corresponding α-iodoenones, likely due to their reduced reactivity in the electrophilic rearrangement step. As a result, the substrate scope of the 2H-pyran-2-ones was somewhat limited. Overall, this methodology represents significant advances on multiple fronts: (i) it establishes a metal-free route to α-iodoenones from alkynols, (ii) demonstrates their versatile application in constructing complex pyrones, and (iii) minimizes precious metal usage by limiting Pd involvement to a single step in the domino sequence.[69]

Scheme 8. Selected examples of 3,5,6-trisubstituted 2H-pyrones 38.

Scheme 9. Plausible reaction mechanism for the formation of 2H-pyrones 38.

In another study, we have demonstrated diphenylacetylenes 1 as pivotal building blocks for assembling complex benzo[a]fluorenones 46 and spirochromenone indenes 48 through a Pd-catalyzed double Heck cascade. The transformation begins with alkyl 2-bromocinnamate esters 44 and symmetrical diarylacetylenes 1, where the alkyne first undergoes an intermolecular Heck coupling, followed by intramolecular cyclization to form precursors, the indene-esters 45 ([Scheme 10]). The catalytic system employing Pd(OAc)₂, DPE-Phos, and a quaternary ammonium salt proved to be the most effective for generating the enoate ester intermediate 45, which was further converted into benzo[a]fluorenones 46 using triflic acid (TfOH) as the cyclization promoter. However, when unsymmetrical alkynes 1 were used, the reaction resulted in an inseparable 1:1 mixture of regioisomers, a trend that persisted through to the formation of the corresponding benzo[a]fluorenones 46. Moreover, the reactions in the presence of external phenols 47 under acidic conditions enabled the synthesis of spirochromenone indenes 48 ([Scheme 11]). A plausible mechanism was proposed outlining the formation of the enoate ester intermediate 45, the subsequent benzo[a]fluorenone 46, and the spirocyclic product 48, highlighting the key steps and intermediates involved in this cascade transformation ([Scheme 12]). This study highlights both the versatility of diarylalkynes 1 in directing Heck cascades and their regiochemical constraints in unsymmetrical cases, advancing domino strategies for fused and spirocyclic synthesis.[70]

Scheme 10. Selected examples of indene enoate esters 45.

Scheme 11. Selected examples of benzo[a]fluorenones 46 and spirochromenone indenes 48.

Scheme 12. Proposed mechanisms of indene enoate esters 45, benzo[a]fluorenones 46, and spirochromenone indenes 48.

An exceptionally efficient palladium-catalyzed domino process that converts simple alkyne precursors 60 and 1 into structurally complex polycyclic frameworks 61 featuring two adjacent quaternary carbon centers was reported recently ([Scheme 13]). The transformation employs 1,2-bis(2-bromoaryl)ethynes 60 and 1,2-diarylethynes 1 as starting materials, which undergo a remarkable six-fold domino annulation mediated by a Pd/DPE-Phos catalytic system. This process is unusual in its ability to construct six new carbon-carbon bonds in a single operation through two consecutive domino sequences, each creating three C–C bonds via distinct but interconnected catalytic cycles. The alkyne substrates 60 and 1 play pivotal and differentiated roles in this transformation. The 1,2-bis(2-bromoaryl)ethynes 60 serve as rigid, pre-organized templates that direct the formation of the polycyclic core structure, while the 1,2-diarylethynes 1 act as versatile coupling partners that can be varied to produce either C₂-symmetric or unsymmetric products 61. This dual alkyne approach provides exceptional control over the reaction pathway, allowing for the precise formation of two adjacent quaternary centers, a challenging feat in synthetic organic chemistry. The methodology offers several significant advantages: (i) broad substrate tolerance that accommodates various functional groups and substitution patterns, (ii) the ability to isolate tetracyclic intermediates (65) through careful reaction time control, enabling stepwise construction of even more complex architectures, and (iii) practical scalability facilitated by the efficient recovery and reuse of excess 1,2-diarylethyne reactants 1. Mechanistic studies suggest the process proceeds through a series of carefully orchestrated oxidative addition, alkyne insertion, and reductive elimination steps that are templated by the palladium-catalyst and guided by the DPE-Phos ligand ([Scheme 14]). This work represents a significant advancement in domino reactions, demonstrating how strategically designed alkyne substrates can enable the rapid assembly of highly complex molecular architectures from simple synthetic precursors. The ability to form six bonds and two quaternary centers in one-pot with such control highlights the power of palladium-catalyzed alkyne transformations for constructing challenging polycyclic frameworks relevant to materials science and medicinal chemistry.[71]

Scheme 13. Selected examples of six-fold domino cyclization to produce polycyclic frameworks 61.

Scheme 14. Plausible mechanism of formation of polycyclic frameworks 61.

Similarly, in another report under a similar kind of catalytic pathway, we demonstrate a rapid and efficient synthesis of complex heteroatom-containing polycycles through a Pd/DPE-Phos-catalyzed domino annulation of ortho-alkynylaryl halides 69 with dihydrobenzofuran derivatives 70 under microwave irradiation, where the alkyne moiety serves as both a directing group and reactive handle to control regioselective cyclization and deliver fused polycyclic products 71 in excellent yields (>85%) within minutes ([Scheme 15]). While the method shows broad substrate scope across various heterocycles (benzofurans, benzothiophenes, indoles) and allows for efficient recovery/reuse of excess dihydrobenzofurans 70, it faces limitations with strongly electron-deficient alkynes, restricting its general applicability. However, the method does present some limitations that merit consideration. First, the reaction shows diminished efficiency with strongly electron-deficient alkynes (such as those bearing nitro or cyano groups), likely due to impaired coordination with the palladium-catalyst. Despite this work representing a significant advancement in the field of domino reactions, it showcases how the strategic combination of alkyne chemistry, palladium-catalysis, and microwave irradiation can enable the rapid assembly of structurally complex, medicinally relevant heterocyclic systems.[72]

Scheme 15. Selected examples of heteroatom-containing polycyclic frameworks 71.

Scheme 16. Plausible reaction pathway of heteroatom-containing polycyclic frameworks 71.

2.2

Acid-mediated Cyclizations

On the other hand, acid catalysis has emerged as a powerful and versatile tool in the synthesis of polycyclic frameworks, particularly when employing alkynes as key building blocks.[73] [74] [75] [76] [77] [78] [79] [80] [81] Alkynes are highly reactive and structurally flexible substrates that can undergo a variety of transformations under Lewis/Brønsted acid activation, enabling the construction of complex molecular architectures with high efficiency and selectivity. Specifically, the ability of Lewis acids to coordinate with the alkyne’s π-electrons activates the triple bond toward nucleophilic attack, cyclization, or rearrangement reactions, often facilitating cascade or domino processes that form multiple carbon–carbon bonds in a single-pot operation. Our research group is actively exploring the potential of alkynes under acid-mediated conditions,[82] [83] [84] [85] [86] and some of our recent advancements in this area are discussed in this section.

An atom-economical, one-pot synthesis of 2,3-disubstituted benzofurans 77 has been developed through a ZnCl₂-mediated oxidative annulation of phenols 76 with internal alkynes 1 under solvent-free conditions (140 °C, 24–48 h), where the alkyne 1 acts as both the coupling partner and regioselectivity director ([Scheme 17]). The transformation proceeds via a proposed six-membered ZnCl₂/phenol/alkyne transition state that facilitates initial C–C bond formation to generate an ortho-alkenyl phenol intermediate 81, followed by intramolecular C–O cyclization, as supported by X-ray crystallography and low-temperature trapping experiments. While symmetrical diarylalkynes 1 afford products in good yields (66–86%), unsymmetrical alkynes (diaryl or aryl–alkyl) exhibit excellent electronic bias-controlled regioselectivity (>20:1). The method demonstrates broad substrate scope, tolerating various phenol substituents 76 (chloro, methoxy, methyl) and alkyne 1 types, though aliphatic alkynes give moderate yields. Particularly, this ZnCl₂-mediated method avoided precious metals and the use of organic solvents. In addition, its excellent regioselectivity with unsymmetrical arylalkynes (>20:1) and green profile make it a valuable alternative to metal-catalyzed benzofuran synthesis.[87]

Scheme 17. Selected examples of 2,3-disubstituted benzofurans 77.

A Lewis acid-mediated domino intramolecular cyclization method for synthesizing dihydrobenzo[a]fluorenes 83 from readily accessible alkynols 82 was demonstrated in 2021 ([Scheme 18]). This strategy employed BF₃·OEt₂ as a mild Lewis acid catalyst to facilitate dual C–C bond formation under mild conditions, achieving high yields (up to 82%) and broad substrate compatibility. Secondary and tertiary alkynols were successfully transformed into the corresponding tetracyclic dihydrobenzo[a]fluorenes 83. The reaction proceeds via an electrophilic cascade cyclization, offering advantages such as operational simplicity, scalability, and tolerance for diverse functional groups. The method was optimized through extensive screening of catalysts and conditions, with BF₃·OEt₂ proving most effective. The synthetic utility was demonstrated on a molar scale, and the products’ structures were confirmed by spectroscopic techniques, including X-ray crystallography. This approach provides a practical route to dihydrobenzo[a]fluorenes 83, addressing limitations of previous methods that relied on precious metals or harsh conditions.[88]

Scheme 18. Selected examples of dihydrobenzo[a]furans 83.

Similarly, another BF₃·OEt₂-triggered intramolecular cascade cycloaromatization of 1,7-ynones 84 has been developed to access structurally diverse benzo[a]fluorenes 85, benzo[b]fluorenes 86, and indenes 87 ([Scheme 19]). This methodology enabled the formation of two consecutive C–C bonds in a single operation, affording complex fused aromatic scaffolds with high efficiency. The protocol tolerates a wide range of functional groups on all three aryl units, including electron-rich, electron-deficient, heteroaromatic, and aliphatic substituents, and is applicable on a gram scale. Mechanistic investigations reveal divergent cyclization pathways influenced by electronic effects: the ynones 84 with electron-rich bromo-iodoarenes in conjugation with the alkyne favor indene 87 or benzo[b]fluorene formation 86, while other substrates preferentially yield benzo[a]fluorenes 85. Indenes 87 are shown to be key intermediates for the formation of benzo[b]fluorenes 86 under thermodynamic conditions. Despite its broad scope, the method shows certain limitations: reactions with strongly electron-donating groups at nonconjugated positions can lead to regioisomeric mixtures, reducing selectivity; high acid loading (up to 2.5 equiv of BF₃·OEt₂) and elevated temperatures (up to 100 °C) are required for some transformations; and the approach is non-enantioselective, limiting its immediate application in asymmetric synthesis. Nevertheless, this metal-free cascade strategy represents a robust and modular approach to constructing functionalized polycyclic aromatic hydrocarbons from simple precursors.[89]

Scheme 19. Selected examples of benzo[a]fluorenes 85, benzo[b]fluorenes 86, and indenes 87.

Scheme 20. Mechanisms of benzo[a]furans 85, benzo[b]furans 86, and indenes 87.

We recently developed a novel acid-triggered cyclization strategy for enyne biaryl systems 92/97, leading to the formation of distinct phenanthrene-fused polycyclic products 93/94/98, including tri-, tetra-, and pentacyclic frameworks. The specific cyclization outcome was found to be strongly influenced by the stereoelectronic nature of substituents ([Scheme 21]). Remarkably, the pentacyclic products obtained through this method represent the complete core scaffolds of natural products such as clostrubin and borolithochromes, offering a concise and efficient synthetic route. A particularly notable case involved a substrate bearing a para-methoxy group (OMe) on R¹, where the OMe group is conjugated with the enoate ester. Under optimized conditions, this substrate 92 yielded a unique phenanthrene-fused pentacyclic product 94. This outcome is attributed to the strong electron-donating effect of the OMe group, which likely facilitates the cyclization pathway. A similar result was observed with an ethoxy (OEt) substituent. However, substrates bearing benzyloxy or benzodioxole substituents failed to produce the desired products, possibly due to increased electron density leading to competing or uncontrolled reaction pathways. Furthermore, this methodology was successfully applied to synthesize benzo[gh]tetraphen-8-one 96 from a benzoate-derived precursor 95([Scheme 22]). Additionally, phenanthrene-based diketone products 98 were efficiently generated from 4′-methoxy-2′-(phenylethynyl)-[1,1′-biphenyl]-2-yl)-1-phenylethan-1-one derivatives 97, under notably shorter reaction times.[90]

Scheme 21. Selected examples of phenanthrene-fused polycyclic products 93/94.

Scheme 22. Selected examples of phenanthrene-fused polycyclic products 96/98.

Scheme 23. Mechanism for phenanthrene-fused polycyclic products 93/94/96/98.

3

Conclusion

In summary, this account highlights the versatility of alkyne-based cascade strategies for the efficient construction of diverse carbo- and hetero-cycles, ranging from bicyclic to complex polycyclic frameworks. Spanning around transition-metal catalysis and acid-mediated transformations, these methods facilitate multiple bond-forming events in a single operation, offering exceptional atom and step economy. Mechanistic understanding of these processes has enabled enhanced control over reactivity and selectivity, driving further innovation in the field. Looking ahead, the continued development of novel catalytic systems along with emerging technologies such as electrochemistry and photocatalysis promises to expand the synthetic potential of alkynes even further.

Dr. Dasari Srinivas

Dr. Dasari Srinivas is from Telangana, India. He earned his integrated MSc. in Chemistry from the Department of Chemistry, Kakatiya University, Warangal, Telangana. During his academic journey, he completed an internship fellowship at the Indian Association for the Cultivation of Science (IACS), Kolkata, under the Indian Academy of Sciences (IAS) program. He later pursued his PhD in Chemistry at the Indian Institute of Technology Hyderabad (IITH), which he successfully completed in February 2024 under the guidance of Prof. G. Satyanarayana. His doctoral research specialized in transition metal–catalyzed template-assisted meta-C-H activation of aromatic compounds. Currently, he is working as a Research Associate in the Department of Chemistry, IIT Hyderabad.

Dr. Dakoju Ravi Kishore

Dr. Dakoju Ravi Kishore was born and brought up in Andhra Pradesh, India. He obtained his BSc degree from V. S. M. College (Ramachandrapuram, Andhra Pradesh, India), affiliated with Andhra University. Subsequently, he pursued his MSc in Chemistry from the same college. He received his doctoral degree under the supervision of Prof. G. Satyanarayana in the Department of Chemistry at the Indian Institute of Technology Hyderabad, India, where he studied acid- and transition metal–catalyzed organic transformations. He later began his postdoctoral research in the Department of Chemistry at the University of Illinois, Chicago, USA. Currently, he is working as a postdoctoral research associate in the Department of Chemistry at Northwestern University, USA

Dr. Chinnabattigalla Sreenivasulu

Dr. Chinnabattigalla Sreenivasulu was born in Andhra Pradesh, India. He completed his master’s degree (MSc in Chemistry) from the Department of Chemistry, Sri Venkateswara University, Andhra Pradesh. He briefly served as an internship fellow at the Indian Institute of Science (IISc), Bangalore, under the Indian Academy of Sciences (IAS) program. Later, he earned his PhD in Chemistry from the Indian Institute of Technology, Hyderabad in May 2022, under the supervision of Prof. G. Satyanarayana. His doctoral research focused on transition metal–mediated reactions, including the synthesis of dihydrobenzofurans, 2H-pyrones, para-C-H allylation of phenols, and remote meta-C-H functionalization. Following his PhD, he pursued postdoctoral research at the University of Illinois, Chicago, and Argonne National Laboratory. Currently, he is working as a postdoctoral fellow in the Department of Chemistry at Virginia Tech, USA.

Prof. G. Satyanarayana

Prof. G. Satyanarayana received his PhD from the Department of Organic Chemistry, Indian Institute of Science (Bangalore, Karnataka, India) in 2005, under the supervision of Prof. A. Srikrishna (late). Subsequently, he worked as a Research Associate in the same Department under the supervision of Prof. K. R. Prasad. He then moved to the Universität Tübingen, Germany, where he pursued his postdoctoral research as an Alexander von Humboldt (AvH) Post-Doctoral Fellow (2007–2008) under the guidance of Prof. Martin E. Maier. Afterward, he joined the research group of Prof. Günter Helmchen, Institute for Organic Chemistry, University of Heidelberg (2008–2009). Subsequently, he joined the Department of Chemistry, IIT Hyderabad, India, as an Assistant Professor in 2009; currently, he is working as a Professor in the same Institute. His research interests include developing new methodologies based on transition metal catalysis, remote C–H functionalization, electro-organic synthesis, photocatalysis, and domino transformations.

Conflict of Interest

The authors declare that they have no conflict of interest.

Acknowledgement

The authors gratefully acknowledge the financial support from the Indian Institute of Technology Hyderabad. D.S. thanks the IITH, while D. R. K. and C. B. S. thank the University Grants Commission (UGC), New Delhi, for providing fellowships.

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Publication History

Received: 30 June 2025

Accepted after revision: 28 July 2025

Accepted Manuscript online:
29 July 2025

Article published online:
17 September 2025