Recent developments in organic synthesis for constructing carbon frameworks using transposition strategies

Abstract

Transposition reaction has remained as the versatile and eco-friendly approach in organic synthesis, providing a sustainable route for generating complex molecules with lower negative impact on the environment. In particular, transposition reaction facilitates selective rearrangement of molecular fragments, which aid the strategic bond disconnections that cover the synthetic pathways and improve the atom economy of the reaction. Moreover, it minimizes the need for high-energy intermediates or reagents, where as in transposition methods support green chemistry principles, including waste reduction, energy efficiency, and sustainability. Besides, transposition strategies render the reaction to occur under mild conditions, making them appealing alternatives to conventional synthetic methods. Due to the limited availability of well-structured reviews in this domain, we first present distinct classes of transposition reactions, with an emphasis on the influence of catalytic systems, reaction conditions, and substrate characteristics on both efficiency and selectivity predominantly relevant to the individual significance of carbonyl, alkene, chirality, allylic alcohol, and functional group transpositions. The versatility of these reactions for creating diverse molecular scaffolds from readily available substrates opens up new avenues for the synthesis of bioactive compounds, pharmaceuticals, natural products and merely represent a compelling tool for advancing greener, more efficient approaches for organic synthesis.

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Savita Narayanaro Gat

Savita Narayanrao Gat completed her M.Sc in chemistry at Dr Babasaheb Ambedkar Marathwada University, Sambhajinagar, India in 2021. She worked as a research trainee at Symbol Discovery Pvt. Ltd, Hyderabad, India. Currently, she is pursuing her Ph.D. in the group of Prof. Rambabu Dandela at the Institute of Chemical Technology, Mumbai, IOCB campus. Her research area is focused on organic synthesis for preparing various functionalized heterocyclic organic compounds with modern synthesis methodologies.

Piyusa Priyadarsan Pattanaik

Dr Piyusa Priyadarsan Pattanaik received his Ph.D. in Heterogeneous Catalysis from the CSIR-Indian Institute of Chemical Technology, Hyderabad, India, in 2024. He served as an Assistant Professor in Chemistry at the Gandhi Institute for Technology, Bhubaneswar, India. Currently, he is a Postdoctoral Research Associate in the group of Prof. Rambabu Dandela at the Institute of Chemical Technology, Mumbai, IOCB Campus. His research area is focused on organic synthesis, crystallography, and heterogeneous catalysis for organic transformations and biomass and CO2 utilization in both batch and continuous flow processes.

Rambabu Dandela

Dr Rambabu Dandela, born in Khammam, Telangana, India, in 1981, completed his M.Sc. in Organic Chemistry at Kakatiya University (2004) and worked as a research chemist at Matrix Labs, Hyderabad (2004–2008). He earned his Ph.D. from Dr Reddy's Institute of Life Sciences in 2013 and later joined Ben-Gurion University as a PBC Outstanding Postdoctoral Fellow (2013–2017). In 2017, he became a Ramanujan Faculty Fellow at CSIR-NCL, Pune, and since 2018, he has served as Assistant Professor at ICT, Bhubaneswar. His research spans drug design, bacterial signaling, and pharmaceutical polymorphism, with over 215 publications, 10 patents, and book chapters.

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1. Introduction

In organic synthesis, transposition denotes the rearrangement of atoms, functional groups (FGs), or double bonds within a molecule, often involving carbonyls, alkenes, or allylic alcohols, to yield more stable or reactive structures. Methods such as directing groups, template strategies, asymmetric catalysis, and selective protection/deprotection enable the precise manipulation of FG placement, ensuring high regio- and stereoselectivity in the design of complex molecules.¹ The spatial arrangement of FGs significantly impacts the physical properties of molecules, including solubility and reactivity, as well as their biological activity, thereby influencing interactions with enzymes and receptors.²

The transposition of FG is crucial in modern chemical processes, such as alkene metathesis, where it enables the rearrangement of molecules to form desired products.³ It is critical to address the fact that a minor positional shift can lead to substantial variations in functionality, as exemplified by drug isomers, where one isomer may exhibit biological activity while another remains inactive.⁴ This determines the critical importance of precise functional group positioning in drug design and materials (Fig. 1).

Fig. 1 Plethora of multi-purpose transposition reactions.

Repositioning a carbonyl group in organic structures is complex, impacting physical properties, biological activity, and reactivity; this is crucial in synthesis and drug design. This process often requires intricate routes and careful control to avoid side reactions. The 1,2-transposition of a carbonyl group is particularly challenging.⁵ Wu et al. developed a triflate-mediated α-amination method, converting ketones into alkenyl triflates, which underwent regioselective α-amination and ipso-hydrogenation to form transposed enamines.⁶

Alkenes are vital in drug design and as intermediates for valuable chemicals, gasoline, and polymers. Metal-catalyzed transposition with noble and transition metals enables C=C bond migration. These complexes can isomerize double bonds, with radical and oxidative catalysis controlling alkene transposition; this is influenced by the reaction conditions and ligands. Molloy et al. highlighted the role of atom economy and stimuli in alkene transposition, espcially geometric isomerization in retinal, where they mainly focused on α-functionalization of ketones, followed by subsequent transformations.⁷

Alkenes serve as crucial building blocks in the design of drug-like compounds and also play a significant role as intermediates in synthetic chemistry.⁸ They are key reactive intermediates in functionalization reactions, underpinning the preparation of valuable chemicals such as chemicals, gasoline, and polymers, etc. Metal-catalyzed transposition utilizing noble metals like Ir, Rh, Pd, and Ru and transition metals like Co, Ni, Fe, and Mo has emerged as a critical approach for C=C bond migration.⁹ Transition metal complexes possess the unique ability to isomerize double bonds within a carbon framework; radical and oxidative catalysis have enabled the controlled transposition of alkenes in the terminal position to their regioisomers, emphasizing the pivotal role of specific reaction conditions and most importantly ligand selection.¹⁰ Notably, a review by Xinlan et al. highlighted the significance of atom economy and external stimuli in the positional and geometrical transposition of alkenes, drawing parallels to the geometric transposition in retinal.⁷ The polyene retinal demonstrates how the combined effects of alkene position and geometry drive its function.¹¹ This selective alkene transposition, based on the geometric isomer of alkene, can form the chemical basis of future scope. The current standard approach employs α-functionalization of ketones to add a carbonyl substituent, followed by multiple subsequent transformations.¹²

Allylic transposition is a crucial strategy in organic synthesis, enabling molecular rearrangement to construct complex structures and drive selective reactions.¹³ The catalytic [1,3]-transposition of FGs offers an atom-economical and step-efficient approach.¹⁴ Notably, in allylic alcohols, this transposition enhances regio- and stereoselectivity.¹⁵ Especially, the optimization of catalytic conditions has broadened its scope, particularly in natural product and pharmaceutical synthesis.¹⁶ A prominent example involves Re-catalyzed allylic alcohol transposition, converting 1,3-diols into acetal-bearing 2-methyl-1,3-syn-diols with remarkable diastereoselectivity. This transformation also facilitates stereoselective heterocycle formation, benefiting from tunable stereocontrol influenced by diastereomer stability and reaction reversibility. The resulting acetal intermediates are vital in synthetic chemistry, especially for hydroxyl-rich natural products.¹⁷

Considering chiral transposition, it plays a vital role in terms of molecular behavior within biological systems, thereby significantly impacting drug design, synthesis, and safety.¹⁸ A notable aspect of assymertric allylic transposition is the enantiospecific chirality transfer to the newly originated allylic stereocenter demonstrate the diversity of chiral molecules utilizing this chiral transposition strategies.¹⁹

Moreover, FGs are the fundamental components that drive the key functionalities of molecular structure. Thus, transpositions that modify FGs, whether by addition, removal, or alteration, are pivotal steps in organic chemistry and further synthetic applications.²⁰ Beyond conventional reactions, they are more suitable for C–H functionalization, where by Chen et al. demonstrated the FG transposition of CN groups via a reversible C–H mechanism, emphasizing CN transposition in cyclic systems via a transannular mechanism.²¹ There is limited precedent for direct FG transposition reactions, aside from in-chain transposition in alkenes and alkynes. Examples of biocatalysis using substrate-specific mutases include the selective modification of substrates for the synthesis of pharmaceuticals and chemicals, where mutases catalyze specific functional group transfers, enabling regio- and stereoselective transformations.²² Therefore, exploiting the reaction diversity of cyano groups is a prominent cyano relocation event, where the molecules formed have prominent bioactivity.²³

To the best of our knowledge, there are very few reviews significantly reporting recent advances made in transposition reactions. Uma et al. reviewed only allylic alcohol transposition, emphasizing the catalytic roles of transition metals like palladium, rhodium, and ruthenium, but they did not discuss the limitations of certain complexes that restricted their applicability to specific substrates, ultimately reducing the reaction diversity.²³ Molloy et al. focused on the challenges of achieving selectivity related to the transposition of alkenes, crucial for enhancing atom economy, but their analysis fell short of addressing undesirable side reactions that complicated purification and led to reduced yield and lacked in-depth insights into these issues.⁷ Volchkov et al. summarized advancements in Re catalyzed [1,3]-transpositions, noting their efficiency associated with chirality transfer.²⁴ These oversights lead to the need for more comprehensive studies addressing substrate specificity, side reactions, and catalytic reactivity for the applicability of these methodologies in complex organic synthesis, which has yet to be explored.

In this review, we elucidate the comprehensive strategies for functional group interconversion, highlighting the essential role of functional group relocation, specifically focusing on carbonyl, alkene, allylic, chiral, and functional group transpositions (Scheme 1). They comprehensively analyzed the advancements in catalytic methods over the past decade, detailing proposed reaction mechanisms and optimization processes. Furthermore, we lightly discuss the influence of metal catalysts, emphasizing the critical importance of precise control over molecular structures. The insights from this review can advance research on tailored molecular designs, significantly impacting organic synthesis, medicinal chemistry, and biological applications.

Scheme 1 Schematic presentation of the scope of this review.

2. Carbonyl transposition

The presence of a carbonyl group within a molecular structure critically influences its bio-physical properties, along with its potential opportunities as an intermediate. For instance, hydroxyl group transposition in ursolic acid, where the C₃ position changed to the C₂ position, resulted in a 13-fold increase in glycogen phosphorylase inhibiting activity,^25,26 and for the isomer, where the C₂-carbonyl position translocated to the C₃ position, there was a nine-fold enhancement for combating hearing loss with aminoglycoside. From the synthetic perspective, effective carbonyl 1,2-transposition methodologies can streamline the creation of complicated target compounds, such as cascarillone and lycoraminone, by permitting strategic bond disconnections with more accessible substrates, hence optimizing the overall synthesis.²⁷ However, current methods for achieving carbonyl 1,2-transposition often entail lengthy synthesis sequences and may encounter challenges related to substrate specificity and regioselectivity.²⁰ Consequently, establishing a widely applicable, regioselective, and straightforward method for the 1,2-transposition of carbonyls, with broad tolerance for various FGs, remains a significant objective in synthetic organic chemistry.

A method with even-numbered carbonyl transpositions for synthesizing polyenes was reported by Satyanarayana et al., where they used cyclopropyl polyenones and demonstrated a regio- and stereoselective approach via 1,2-reduction followed by solvolysis addition using BF₃·Et₂O/HgCl₂/MeOH to yield polyene esters.²⁸ Takagi et al. discovered 4,5-epoxy-2-cyclohexen-1-one in another investigation, establishing a route attributed to scyphostatin. This reaction proceeded via a rearrangement mechanism, where the molecular structure underwent an internal reorganization to form a new epoxide ring, a Diels–Alder adduct, which underwent 4,5-epoxide ring reductive cleavage in addition to migration of 1,3-carbonyl via the Wharton reaction (Scheme 2) and additionally, stereoselective bromination of an intermediate yielded a trans bromohydrin derivative, which was then desilylated to obtain the target compound. In the final step, the epoxide ring was regenerated, achieving high stereoselectivity in both epoxidation and bromination, highlighting an accurate approach for synthesizing scyphostatin analogues (Scheme 3).²⁹

Scheme 2 Transposition of 1,3-carbonyl and regeneration of epoxide rings.

Scheme 3 Pathway for the reduction of the (4,5)-epoxide ring to alcohol with transposed 1,3-carbonyl and rearrangement of the (4,5)-epoxide.

A heteroatom-facilitated ortho-lithiation followed by shifting of the carbonyl group was addressed by Bracca et al. (Scheme 4), who synthesized 2-(2,3-dimethoxy-phenyl) cycloheptanone by avoiding the use of expensive reagents and complex starting materials, resulting in a simple and efficient synthesis of the target ketone 9. The method overcome unwanted rearrangement to aldehyde 10, demonstrating its effectiveness in the carbonyl transposition pathway. However, few limitations accounted for the scope of substrate, complex starting material, and reagent accessibility in this particular carbonyl transposition.³⁰

Scheme 4 Synthesis of the 2-arylcycloheptanone derivative via carbonyl transposition.

In the Stork–Danheiser transposition reaction, Samuel et al. introduced the use of soluble lanthanides as mediators for the synthesis of 3-substituted cyclic enones from organometallic reagents and vinylogous esters. They noted that traditional lanthanide salts, like cerium(III) chloride, have been employed to reduce basicity and enhance the nucleophilicity of sterically hindered aryl or alkyl nucleophiles. However, they observed reproducibility issues with CeCl₃. The study demonstrated the effectiveness of organic-soluble lanthanides, such as LnCl₃/R₄NX and LnCl₃·2LiCl, at promoting the Stork–Danheiser transposition across various classes of organomagnesium reagents (Fig. 2), offering a more reliable alternative for this transformation.³¹

Fig. 2 Stork–Danheiser via transpositions of 1,2 carbonyl.

Echinocandin derivatives formed by carbonyl transpositionwas documented by Aszodi et al. where he observed that an alpha-hydroxy hemiaminal moiety can undergo a pinacol-type rearrangement when treated with trimethylsilyl iodide, leading to the formation of ketone derivatives, which is indicative of a transposition mechanism. They also employed deoxymulundocandin as antifungal antibiotic, showcasing the potential of this methodology for preparing modified echinocandin structures.³²

The 1,2-carbonyl-migrated product can then be obtained by hydrolyzing the enamine intermediate (Scheme 5).³³ A novel method for the 1,2-carbonyl shift of alkyl carbonyl substances based on the Willgerodt–Kindler reaction was recently presented by Bhawal and Morandi.³⁴ For this reversible transition, elemental sulfur and pyrrolidine were used as catalysts. Dixon's group later studied that carbon atoms in cyclic and acyclic tertiary amides underwent 1,2-transposition at the oxidation level, leading to the one-pot synthesis of 1,2- and 1,3-oxytertiary amines.³⁵

Scheme 5 Carbonyl chain walking and carbonyl 1,2-transposition using various methods.

Wu et al. studied a triflate-mediated 1,2-carbonyl transposition method using palladium- and norbornene (NBE) based catalyst for regioselective amination,⁶ where a ketone was first transformed into an alkenyl triflate that go through regioselective alpha-amination and ipso-hydrogenation in the presence of a Pd catalyst and norbornene, leading to single regioisomers with high yield of 51–53% which is mainly relied on the transposition of the carbonyl group. The method outperformed previous multi-step approaches by offering fewer steps with improved yields of 55–75% and complete regioselectivity, making it applicable to the preparation of complex molecules of bioactive analogs and key intermediates. A bifunctional donor of hydrogen and nitrogen enabled these reactions through the formation of an intermediate. The “transposed enamine” was later hydrolyzed to yield the product resulting from a 1,2-carbonyl shift.

In an attempt to achieve the desired α-amination as well as ipso-hydrogenation in alkenyl triflates using Pd/NBE catalysis, there were two main challenges, as shown in Fig. 3. Challenges were encountered during the cyclization process, particularly in controlling the unintended 3-exo-trig cyclization, which resulted in by-products. They found that Pd(0) was oxidatively added to NBE, and alkenyl–Pd(II) migration into it was essential. Furthermore, refining the NBE co-catalyst and carefully designing the amine reagent were vital steps in minimizing the formation of side products.

Fig. 3 α-Amination of alkenyl triflates catalyzed by Pd/NBE.

The moderate steric hindrance present in the NBE catalyst effectively restricted the cyclopropanation pathway while favoring β-carbon elimination. This approach facilitated the electrophile reacting with the alkenyl–norbornyl palladacycle, thereby minimizing the generation of by-products A and B. Moreover, the use of a bulky hydride source considerably minimized instances of premature hydride terminations, consequently decreasing the production of side products C and D. Using α-tetralone as a model substrate, β-tetralone 23 was synthesized in 88% yield via a one-pot reaction under optimized conditions. Lithium tetramethylpiperidide (LiTMP) emerged as an effective base for forming the intermediate, leading to a Pd/NBE-catalyzed step that produced 91% of product 22 and 71% of product 23 (Scheme 6).

Scheme 6 Scope of substrates and reaction conditions for carbonyl transposition with alkenyl triflates.

Triflic anhydride was employed as a triflation reagent, with cesium carbonate (Cs₂CO₃) proving optimal in a toluene/1,4-dioxane mixture, resulting in alkenyl triflate product 22 in 77% yield. The piperidine-based compound (R8) facilitated complete conversion with minimal side products. They anticipated that palladium and NBE were critical, while the absence of pyridone significantly reduced the yield. Structural analyses indicated that azetidine–amide NBE N₁₀ exhibited the highest efficacy, achieving a yield of 88%, while N₁₀ reduction to 50 mol% led to decrease in yield to 76%.^36,37

2.1. 1,3-Allylic carbonyl transposition

Jitender et al. showcased the 1,3-allylic carbonyl rearrangement of chalcones by first reducing them to 1,3-diarylpropan-1-ol, which were then dehydrated to yield 1,3-diarylpropenes and subsequently subjected to benzylic/allylic oxidation. This reaction proceeds via a rearrangement mechanism (Scheme 7).³⁸

Scheme 7 1,3-Allylic carbonyl transposition in chalcones.

3. Alkene transposition

Despite the numerous existing protocols for introducing alkene FGs such as olefination, elimination, condensation, and dehydrogenation, these methodologies often face challenges related to low stereoselectivity and limitations on functional group compatibility. All alkene transposition reactions are generally categorized as rearrangement reactions.

Conversely, the transposition of pre-existing alkenes represents a compelling and atom-efficient strategy for the incorporation and modification of C=C bonds. This approach not only enhances the versatility of synthetic pathways but also holds significant potential for industrial applications.³⁹ Massad et al. demonstrated the development of a stereoselective method for the preparation of iridium-catalyzed alkene transposition resulting in fully substituted aldehyde silyl enol ethers. This method effectively transformed one-pot transposition–aldol and transposition–allylation processes to convert simple allylic silyl ethers into useful enolate derivatives with substantial stereoselectivity.

The catalytic process operated via a 1,3-hydride transfer mechanism, with the stereoselectivity being affected by the configuration of the intermediate π-allyliridium species. It was noted that Ir-based systems effectively stereoselectively isomerized highly substituted alkenes, revealing two distinct mechanistic pathways: 1,2-hydride transfer and 1,3-hydride transfer (Fig. 4). In the mechanism involving 1,3-hydride transfer, the conformational stability of intermediate II, favoring the zig-zag arrangement (IIa), played a crucial role in reducing steric hindrance between the inward-facing substituents and the metal coordination sphere. Consequently, the steric variations between R¹ and R² exerted little influence on the stereoselectivity of the reaction, contrasting with other transposition mechanisms that associated stereoselectivity with the influence of substituent sterics on the resulting alkene.

Fig. 4 Stereoselective synthesis of substituted aldehyde-based silyl enol ethers via iridium-catalyzed alkene transposition.

As shown in Scheme 8, they achieved the stereoselective synthesis of fully substituted aldehyde silyl enol ethers from accessible allylic silyl ethers; employing alkene transposition to selectively generate the enolate double bond was particularly crucial. In this context, the geometry of the π-allyliridium intermediate dictates both the stereoselectivity and the orientation of the alkene.⁴⁰

Scheme 8 Alkene transposition using an Ir catalyst and generation of stereoisomeric silyl enol ethers from regioisomeric substrates.

3.1. Nickel catalyzed transposition

Felicia et al. studied a nickel-catalyzed method for rearranging homoallyl pinacol boronic esters utilizing a reactive NiCl₂(dppp) system in conjunction with ZnI₂, Zn powder, and Ph₂Ph and it was likely to proceed via a rearrangement mechanism. This approach yielded Z-crotyl pinacol boronic esters, which later interacted with aldehydes to generate syn-homoallylic alcohols with high diastereoselectivity. This approach employed Ni based catalyst in place of Murakami's iridium-catalyzed method generating anti-homoallylic alcohols.

Furthermore, the nickel-mediated pentenyl pinacol boronic esters undergo transposition to achieve moderate diastereoselectivity while facilitating the addition of an ethyl group for favorable selectivity. As per Scheme 9, after allowing benzaldehyde to react with homoallyl pinacol boronic ester 33 using the straightforward procedure, target product 39 was produced in 81% yield after activating the nickel catalyst precursor NiCl₂(dppp) (where dppp is 1,3-bis(diphenylphosphino)propane) with zinc powder, zinc iodide, and diphenylphosphine.^41,42 The activity depended on nickel iodide, however, the reaction could still proceed in the absence of it.⁴³

Scheme 9 Nickel catalyzed alkene transposition of benzaldehyde.

Transposition was exhibited at a low temperature of −50 °C, facilitating the allylboration process and yielding the desired product syn 39, in 81% yield and with an exceptional diastereoselectivity of 98 : 2. Notably, the incorporation of the phenyl group at the α-carbon was achieved by using an E-configuration in the final product 41.⁴² This study demonstrated the effectiveness of nickel catalysts in rearranging double bonds in alkenyl boronates under mild conditions, achieving a notable 97% yield of the desired product 41 (Scheme 10). The method is versatile, applicable to various substrates, and showcases high syn-selectivity during allylboration, which involves the addition of an allyl group to carbonyl compounds like aldehydes and ketones. This selectivity was crucial for synthesizing complex molecules with predictable structures (Scheme 11); the nickel catalyst not only facilitated double bond migration but also enhanced the allylboration process through its unique electronic properties and substrate coordination.

Scheme 10 Transposition of substituted homoallyl boronic esters.

Scheme 11 Ru and Ni catalyzed long-chain positional transposition.

A structure-dependent nickel-catalyzed reaction facilitating N-allyl amide transposition into E- or Z-enamides was reported by Felicia et al., where the specific isomer formed was determined by the structural features of the substrates. This allowed for the selective synthesis of valuable enamide intermediates in organic chemistry. For acyclic N-allyl amides, the reaction favored Z-enamides, while their cyclic counterparts yielded exclusively E-enamides. As seen in Scheme 12, utilizing a nickel-based catalyst with an HPPh₂ ligand, the transposition of N-allyl amides produced Z-configured enamides in good yield, whereas lactam systems yielded E-enamides with an excellent efficiency of 83%. The study emphasized the critical role of temperature in directing the reaction outcomes; lower temperatures promoted Z-selective transposition, resulting in product 52 with approximately 88% conversion and good Z-selectivity up to 84%. In contrast, elevating the temperature to 25 °C shifted the reaction toward the thermodynamically favored E-isomer 53, achieving 100% yield and complete E-selectivity. They observed a Z/E ratio of 0 : 100 suggesting a nickel-induced kinetic mechanism rather than thermodynamic equilibrium, highlighting the precision of the nickel catalyst in controlling stereochemistry, as shown in Scheme 13, and compared the reactivities and selectivity in N-homoallylic transposition.

Scheme 12 Temperature-dependent sequential transposition of N-homoallylic oxazolidinone alkenes.

Scheme 13 Nickel-catalyzed transposition of urethanes.

They highlighted that a better outcome for the Z-configured product came from the nickel-catalyzed transposition of 54 into 55. On the other hand, the reaction did not work with the comparable N-methyl derivative 56, and cyclic amide 59, but produced the E-configured product with exceptional yield and E-selectivity.⁴⁴

Rubel et al. developed a nickel-catalyzed stereodivergent transposition that was kinetically controlled, allowing the transformation of terminal alkenes into internal alkenes, which favored selective conversion into either the E- or Z-configuration or internal alkenes at room temperature, using the commercially available reagent Ni(COD)₂ (Scheme 14). The one-carbon transposition method offered significant advantages over existing strategies, addressing issues of generality and scalability. This study highlighted the promise of nickel catalysis for more efficient and accessible synthesis of internal alkenes.⁴⁵

Scheme 14 Stereodivergent and kinetically controlled transposition of terminal alkenes using a Ni catalyst.

Chen et al. presented a stereoselective synthesis of alkenes through olefin functionalization and transposition, employing a catalytic N-heterocyclic carbene–Ni(I) combination with a sterically hindered base. This approach facilitated the trans-selective coupling of monosubstituted olefins with various electrophilic reagents (Scheme 15), resulting in the efficient formation of tri- and tetrasubstituted alkenes, reaching yield up to 92%, as well as regional and stereoselectivity exceeding 98%, thus the approach led to the exchange of carbon and C=C bonds with heteroatoms, presenting significant benefits versus traditional techniques.⁴⁶

Scheme 15 Transposition of alkenes to access boron-containing olefins.

3.2. Mn catalyzed alkene transposition

An efficient, site-specific olefin transposition reported by Yang et al. achieved the highly effective conversion of various allyl arenes into higher-value 1-propenylbenzenes with near-quantitative yield and excellent stereoselectivity using a Mn(I) pincer complex for the Mn-catalyzed dehydrogenation of carbonyl compounds. This study demonstrated that the Mn-catalyzed reaction displayed significant regioselectivity, favoring the generation of 2-alkenes (Fig. 5), which had lower thermodynamically stability, even in the case of substrates with long-chain alkenes, achieving yields of 72–99% with E/Z ratios of >90 : 10 for industrially relevant compounds (Schemes 16 and 17). Notably, the catalytic activity is enhanced by disrupting cooperative interactions.

Fig. 5 Mn metal complex mediated olefin transposition and reactivity of Mn–H toward C=C and C=O bonds.

Scheme 16 Manganese catalyzed transposition of 4-allylanisol.

Scheme 17 Olefin transposition using a Mn-7 catalyst.

Initial tests on various Mn(I) complexes showed limited transposition reactivity, except for Mn-3, which led to 18% product. Upon optimizing the conditions, the use of Mn-7 demonstrated excellent conversion of a diverse range of substrates, achieving yields of 72–99% with E/Z ratios of >90 : 10 for industrially relevant compounds (Schemes 16 and 17). Notably, the catalytic activity is enhanced by disrupting the cooperative interactions in manganese catalysts typically used for carbonyl hydrogenation (Fig. 6). The findings suggested a metal–alkyl mechanism (Fig. 7) where the active Mn(I) hydride precursor underwent hydride transfer and β-hydride elimination to yield the desired olefin.⁴⁷

Fig. 6 Reactivity of Mn(I) CNP complexes with C=O and C=C functionalities.

Fig. 7 Mechanism for Mn(I) pincer complexes catalyzing olefin transpositions.

Blaha et al. described a catalyst that operated without additives, namely, the borohydride complex cis-[Mn(dippe)(CO)₂(κ²-BH₄)], which effectively converted terminal alkenes into internal alkenes. Under room temperature conditions and with a catalyst loading of only 2.5 mol%, they demonstrated significant reactivity, achieving conversion rates between 50 and 70%, along with excellent E-selectivity (Scheme 18) especially for derivatives of allylbenzene. Although the method shows good reactivity with aliphatic compounds, the selectivity tends to decrease. However, enhancing the steric bulk of these substrates can lead to a restoration of high E-selectivity. Preliminary findings suggested that chain-walking transposition was possible at elevated temperatures of 25–30 °C. On the other hand, additives such as TEMPO (12.5 mol%) or pyridine (12.5 mol%) with THF solvent achieved 97% yield and 99 : 1 E/Z or 77% yield and 96 : 4 E/Z, respectively.⁴⁸

Scheme 18 1,2-Transposition reactions of alkenes with a Mn₄ catalyst.

3.3. Rh catalyzed alkene transposition

Yudin et al. developed a Rh catalyst to synthesize Z-enamines through the alkene transposition of specific substrates, such as allylaziridines that efficiently controlled the E/Z ratio, shifting from 99 : 1 to 1 : 3 in a mixture of acetone and CH₂Cl₂. They demonstrated that the Z-selectivity observed in these reactions stemmed from the preferential heteroatom ligation in the substrates with a catalytic metal centre. In their experiments involving the olefin transposition of substrate 71 under reaction condition of 5 mol% of [Rh(CO)₂Cl]₂ in DCE at 75 °C, a mixture of reactant and enone 72 was produced, as shown in Schemes 19 and 20. However, the reaction resulted in only 78% conversion, leading to a moderate Z-product yield of 51%. Additional investigations revealed that terminally substituted substrates 74 and 75, as well as substrate 76 with an R substituent, did not undergo Z-selective olefin transposition in the presence of the Rh(I) catalyst. The carbonyl group was found to be critical for the reaction; substrate 77, which contained a cyano group instead of a carbonyl, failed to isomerize, while substrate 78, lacking a carbonyl group, predominantly formed the E-alkene rather than the Z-alkene (Scheme 21).

Scheme 19 Rh catalyzed synthesis of Z-enamines through alkene transposition.

Scheme 20 Z-Selective olefin transposition reactions involving β,γ-unsaturated ketones using a Rh catalyst.

Scheme 21 Effect of Rh(I) catalysis on Z-selective olefin transposition in both substituted and α substituted substrates.

The coordination of the carbonyl oxygen to the rhodium catalyst was identified as a key factor contributing to the observed Z-selectivity. Furthermore, the development of Z-selective olefin transposition over the Rh(I) complex to convert β,γ-unsaturated ketones into α,β-unsaturated ketones is an effective and adaptable method for synthesizing challenging Z-alkenes.⁴⁹

3.4. Iron catalyzed alkene transposition

A catalytic approach for effectively controlling C=C bond migration in both cyclic and acyclic systems, facilitating the synthesis of disubstituted and trisubstituted alkenes, is a key step for complex molecule synthesis. By employing an iron-based complex, which is abundant and cost-effective, there is the potential for a general catalytic strategy that enables precise manipulation of C=C bond migration.⁵⁰ The use of catalytic quantities of this iron complex, in conjunction with a base and a boryl compound, promoted the selective transposition of alkenes. Mechanistic investigations indicate that the process likely involves the in situ generation of an iron–hydride intermediate, which facilitates olefin transposition through a series of olefin insertions followed by β-hydride elimination. This approach allowed for the regiodivergent synthesis of products from a single substrate and transformed isomeric olefin mixtures commonly found in petroleum feedstocks into a singular alkene product, while also generating unsaturated moieties within linear and heterocyclic biologically active compounds. This work introduced a versatile catalytic system that led to the regiodivergent conversion of low-cost terminal and internal alkenes, whether cyclic or acyclic, into products with either single-position or multi-position shifts. Furthermore, this system effectively achieves the regioconvergent transformation of isomeric olefin mixtures, typically present in unrefined petroleum-derived raw materials, into valuable, isometrically pure products (Fig. 8).

Fig. 8 Design principles for achieving tunable and regioselective olefin transposition.

Controlling C=C bond migration in both cyclic and acyclic systems to facilitate the synthesis of disubstituted and trisubstituted alkenes presents significant challenges for catalytic methods (Scheme 22). Skrydstrup et al. demonstrated that by employing an Earth-abundant iron-based complex in conjunction with a base and a boryl compound, it was possible to achieve controllable alkene transposition. Mechanistic studies revealed that an iron hydride species was generated in situ, which facilitated olefin transposition via a sequence of olefin insertion followed by β-hydride elimination by converting low-cost terminal and internal alkenes into both single-position and multi-position products. Furthermore, it achieved regioconvergent transformations, producing isometrically pure compounds from complex mixtures.¹⁰

Scheme 22 Transposition with internal olefins and regioselective convergent and divergent reactions.

3.5. Ru catalyzed alkene transposition

A Ru catalyzed method for the positional transposition of allyl benzenes, relying on the metal-radical-induced intramolecular 1,3-hydrogen atom shift, to achieve E-configured styrene was studied by Schoenebeck et al.

They utilized this process for long-chain alkene transposition, fully generating styrenyl products from allyl benzenes with up to nine carbons in the chain, with most substrates demonstrating complete geometric selectivity (Scheme 23).⁵¹

Scheme 23 Long chain alkene transposition using a Ru catalyst.

3.6. Co catalyzed alkene transposition

A recent study conducted by Kim et al. introduced a methodology for attaining high Z-selectivity in double bond transposition involving simple alkenes and allylarenes. This approach leverages a spin-accelerated allyl mechanism to facilitate efficient positional shifts (Fig. 9). This approach addresses the challenge of producing Z-alkenes, which are often thermodynamically less favorable than E isomers. The study presented a high-spin cobalt(I) complex stabilized by a β-dialdiminate, which efficiently converted terminal alkenes, including the more challenging allylbenzenes, into Z-2-alkenes with remarkable regio- and stereoselectivity. Deuterium labeling studies indicated that the catalyst functioned through a π-allyl mechanism in contrast to the conventional alkyl mechanisms utilized by other Z-selective catalysts. In line with computational studies, it indicated a spin state transition from triplet to singlet during C–H activation, allowing the differentiation of stereo-defining barriers.

Fig. 9 Proposed Co catalyzed allyl mechanism with spin accelerated transposition.

Further optimization revealed that adding an optimum amount of catalyst to the alkenes in pentane achieved a high selectivity of 92 : 8, resulting in Z-2-alkenes with less than 1% of other isomers. Significantly, the cobalt complex achieved the highest reported Z selectivity of 90% for aliphatic alkenes, with Z/E ratios reaching as high as 94 : 6. Additionally, it effectively isomerized a range of phenylpropenoids while maintaining high Z selectivity, demonstrating its notable capability for Z-selective transposition.⁵²

Athawale et al. investigated methods to modify the reactivity of α-silyl carbocations to promote enone transposition. This method was effectively applied in the synthesis of various compounds, such as peribysin D, E-volkendousin, and E-guggulsterone. This reliable method utilized a silyl group as a masking tool, allowing for enantio-switching, substituent rearrangement, and Z-selectivity.

They achieved the total synthesis and structural reconfiguration of peribysin D, in addition to completing the formal syntheses of E-guggulsterone and E-volkendousin through a streamlined reaction sequence. This strategy showcased substantial synthetic potential by facilitating the in situ generation and rearrangement of α-silyl carbocations across various substrates, yielding significant results, including substituent rearrangement and enhanced Z-selectivity (Scheme 24). The commercially available enone provided an overall yield of 56% for the predominant Z-enone, while a large isopropyl substituent skewed the reaction toward E-selectivity. Additionally, three other enones obtained from R-citronellal, cyclohexane carboxaldehyde, and hexanal were efficiently transformed into their respective Z-enones with yields of 46%, 44%, and 43%, respectively.⁵³

Scheme 24 Substrate scope for enone transposition and Z-selectivity.

4. Radical catalyzed alkene transposition

Wang et al. developed a strategy for initiating transposition through a radical mechanism of carbon–carbon double bonds and FGs. While multi-site functionalization is effective at creating complex molecules, enabling the concurrent modification of both reactive sites and distant, unreactive C(sp³)–H bonds is challenging due to traditional reactions favoring more reactive sites. In this study, the authors introduced a modular approach to alkene difunctionalization integrating radical-induced functional group migration with desaturation of distant C(sp³)–H bonds using a dual catalytic system featuring photochemical and cobalt catalysts. This strategy enabled precise site selectivity and notable E/Z selectivity while allowing for the migration of various FGs, including benzoyloxy, acetoxy, and cyano groups. The approach is distinguished by its gentle reaction conditions, wide compatibility with various FGs, and high regioselectivity. Investigations into the mechanism revealed the successful combination of radical addition with functional group migration, and metal-catalyzed processes enabled simultaneous alkene difunctionalization and selective activation of remote C(sp³)–H bonds for desaturation (Scheme 25).⁵⁴

Scheme 25 Transposition of the C–C double bond via radicals.

5. Oxygenative catalyzed alkene transposition

Shota et al. introduced catalytic oxygenative alkene transposition utilizing an oxoammonium salt catalyst (Scheme 26) effectively transforming tri- and trans-disubstituted alkenes into the corresponding enones; this rearrangement takes place under standard conditions, without requiring elevated temperatures. The probable mechanism is likely to proceed via a rearrangement mechanism.

Scheme 26 Oxygenative allylic transposition facilitated by an oxoammonium salt catalyst for the transformation of unreactive alkenes into enones.

The process proceeds effectively at room temperature, yielding the desired products. The study highlights a method for synthesizing enones by employing a less sterically hindered azaadamantane-type oxoammonium salt in conjunction with two stoichiometric oxidants: iodobenzene diacetate and magnesium mono-peroxyphthalate hexahydrate (MMPP·6H₂O), as shown in Scheme 27. This method provided a gentle yet effective route to the functionalization of unreactive alkenes, marking a significant step forward in enone synthesis. Catalytic oxygenative allylic transposition demonstrates high efficiency and is compatible with various FGs, including trans-disubstituted alkenes. The reactivity observed in this reaction can be ascribed to the distinctive characteristics of the azaadamantane-type oxoammonium salt in conjunction with the chosen oxidants, providing a noteworthy instance of an oxidative reaction facilitated by oxoammonium salts. This method is anticipated to facilitate the synthesis of enones.⁵⁵

Scheme 27 Catalytic oxygenation-based allylic transposition of alkenes to enones, substrate scope and FG compatibility.

6. Allylic alcohol transposition

The [1,3]-oxidative rearrangement of tertiary allylic alcohols is a significant reaction in organic synthesis that is likely to proceed via a rearrangement mechanism. It is particularly useful for generating α-substituted and β,β-disubstituted cyclic enones, which are frequently encountered in various chemical applications in fragrance chemistry and serve as both critical intermediates and end products.⁵⁶

Wang et al. developed a ketyl–ynamide coupling using a visible light method for the synthesis of eneindolin-3-ols by utilizing ynamides with alkyl sulfonyl groups. It is further enhanced by a one-pot, 1,3-allylic alcohol transposition, leading to the formation of 2-hydroxymethylindoles (Scheme 28) and carried out under mild conditions; this method provides an efficient and alternative route to the desired transformation for synthesizing 2-hydroxymethylindoles. The overall process aligns more closely with addition–elimination, where the initial nucleophilic addition is followed by the elimination of a leaving group to complete the reaction. Aryl-substituted ynamides with electron-withdrawing groups also efficiently produced the desired product, as shown in Scheme 29.

Scheme 28 Photoredox mediated regioselective coupling of ketyls and ynamides via allylic alcohol-1,3-transposition.

Scheme 29 Synthesis of 2-hydroxymethylindoles via allylic alcohol transposition.

A series of control experiments were conducted, showing that at 80 °C in DMSO, eneindolin-3-ol 98 remained largely unreacted, with more than 95% of starting material 98 being unchanged with no conversion to 99 (Scheme 30). Through experimental investigations, the authors elucidated a feasible mechanism for the formation of the target compound, as illustrated in Scheme 31. Under blue LED irradiation, Ir(III) is excited to its excited state, Ir(III)*, where it undergoes reductive quenching with Hantzsch ester (HE), resulting in the generation of HE˙⁺ and Ir(II). The activated ynamide 96a then participates in a process beginning with single-electron transfer (SET) to Ir(II), generating a ketyl radical (A), which then reacts with the ynamide to form a vinyl radical intermediate (B). This intermediate undergoes hydrogen atom transfer (HAT), leading to the formation of enamide 97, which exists as a mixture of E/Z isomers. Subsequently, enamide 96 undergoes acid-catalyzed 1,3-allylic alcohol transposition to produce the 2-hydroxymethylindole 97 (Scheme 31). This work demonstrates a photoredox-catalyzed coupling between ketyls and ynamides, particularly those containing alkyl sulfonyl groups, effectively generating eneindolin-3-ols.⁵⁷

Scheme 30 Control experiment for allylic alcohol transposition using eneindolin-3-ol.

Scheme 31 Reaction mechanism for the synthesis of 2-hydroxymethylindoles via allylic alcohol transposition.

Brenna et al. investigated a chemoenzymatic approach employing a catalytic system that combined Bobbitt's salt with laccase from Trametes versicolor to facilitate the [1,3]-oxidative rearrangement of cyclic allylic tertiary alcohols to enones in an oxygen-rich aqueous environment. The [1,3]-oxidative rearrangement of tertiary allylic alcohols is an important reaction in organic chemistry. It is especially valuable for producing α-substituted and β,β-disubstituted cyclic enones, compounds commonly found in fragrance chemistry (Fig. 10). This method led to excellent yields (50–70%) for substrates such as cyclopent-2-en-1-ol and cyclohex-2-en-1-ol, which did not contain electron-withdrawing groups. For macrocyclic alcohols or those with electron-withdrawing groups, the reactions were effectively performed in acetonitrile using immobilized laccase. Significantly, this study demonstrated dynamic kinetic resolution in the transformation of exocyclic allylic alcohols, resulting in α,β-unsaturated ketones with high diastereomeric excess and (E)-configuration. A one-pot, three-step process was developed to synthesize cis or trans-3-methylcyclohexan-1-ol through a cascade reaction, in which TEMPO + BF₄/laccase-catalyzed oxidative rearrangement was followed by reactions with ene-reductase and alcohol dehydrogenase, giving optically pure products. This work also introduced the use of the tetrafluoroborate salt of TEMPO as a safer, non-toxic alternative to hazardous Cr(VI) oxidants, with efficient regeneration of Bobbitt's salt by laccase at room temperature.⁵⁸

Fig. 10 [1,3]-Oxidative rearrangement of tertiary allylic alcohols of cyclic enones used in fragrance formulations.

Di Wu et al. investigated processes involved in oxorhenium-catalyzed deoxy dehydration and the transposition of allylic alcohols, and the probable mechanism was most likely to proceed via a rearrangement reaction. Their study provided valuable insights into how the oxorhenium catalyst facilitates the reaction of 1,2-n-deoxydehydration (DODH), involving the use of 1-butanol as a reducing agent, along with methyltrioxorhenium(VII) as the catalyst, as analyzed through DFT calculations. The active catalytic species for both allylic alcohol transposition and the DODH process was identified as methyl oxo dihydroxy rhenium(V), a reduced form of rhenium. The research highlighted that a two-step pathway (Pathway B) exhibited a lower activation energy compared to the three-step [1,3]-transposition pathway (Pathway A), making it a more efficient option. Pathway A is a three-step process that goes through 1,2-DODH and allylic alcohol transposition. Pathway B is a two-step process that goes through direct 1,4-DODH.

Furthermore, the initial hydrogen transfer during the reduction of methyltrioxorhenium(VII) was determined to be the DODH process, which was limited by the rate of a key step. Furthermore, the study observed that increasing the separation between the hydroxyl groups in 1,2-n-DODH reactions involving C₄ and C₆ diols led to a higher energy barrier for the reaction, as shown in Scheme 32.

Scheme 32 Mechanistic routes for the 1,4-DODH reaction catalyzed by CH₃ReO₃.

Homberg et al. observed that in a kinetic study with respect to both the catalyst and the alcohol substrate for Ph₃SiOReO₃-catalyzed [1,3]-transposition, the reaction was found to follow first-order kinetics. The observed negative activation entropy suggests that the reaction occurs through a highly organized [3,3]-sigmatropic mechanism, characterized by polarized transition state 103. In this chair-type transition state, an allyl group with a partial positive charge undergoes intramolecular migration of the negatively charged perrhenate group, supporting the proposed mechanism (Fig. 11).

Fig. 11 Mechanistic pathway for [1,3]-allylic transposition catalyzed by oxovanadium complexes.

Based on these findings, Grubbs and colleagues established a more refined mechanistic framework in line with Osborn's rationale. Their model suggested that transposition proceeded through an asynchronous [3,3]-sigmatropic rearrangement, where the breaking of the C–O bond occurred before the formation of a new C–O bond. This mechanism led to the generation of a partial positive charge on the allyl fragment and a partial negative charge on the perrhenate group. The pronounced polarization of the C–O bond in transition state 108 (Fig. 12) enables the possible formation of ion pair intermediate 110, which can lead to side reactions such as elimination (111) and condensation (112), while also promoting the racemization of enantiomerically pure substrates.⁵⁹

Fig. 12 Mechanistic pathway for Ph₃SiOReO₃ catalyzed allylic transposition.

The initial use of the Ph₃SiOReO₃-catalyzed allylic transposition strategy was demonstrated in the enantioselective total synthesis of (±)-galanthamine, a well-known alkaloid for the treatment of vascular dementia and Alzheimer's disease. Due to challenges encountered with traditional allylic oxidation at the C₃ position of advanced intermediate 114, a new synthesis route was developed (Scheme 33). The process began with the reaction of a tosyl ammonium salt derived from tertiary amine 114 with dimethyldioxirane, which led to the formation of epoxide 115 upon treatment with DBU. Regioselective opening of the epoxide with sodium phenylselenide, followed by chemoselective oxidation with NaIO₄ and elimination of selenoxide, yielded precursor 115 for [1,3]-transposition. Treatment of compound 115 with p-toluenesulfonic acid protonated the nitrogen, thus preventing catalyst deactivation.

Scheme 33 Synthesis of (−)-galanthamine through Ph₃SiReO₃ catalyzed allylic transposition.

Upon reacting the ammonium salt with a stoichiometric amount of Ph₃SiReO₃, a 3 : 1 mixture of alcohols was obtained and 116 was generated, along with (±)-galanthamine, which was isolated in 50% yield after separating the regioisomers. Importantly, the cyclic allylic alcohol was unaffected throughout the [1,3]-transposition process, providing compelling evidence for a mechanism consistent with a [3,3]-sigmatropic rearrangement. The [1,3]-transposition of allylic alcohol 117 plays a crucial role as an intermediate in the synthesis of amphidinolide B₁, demonstrating remarkable product selectivity (Scheme 34). When allylic alcohol substrate 117 was reacted with 1 mol% of Ph₃SiReO₃ in ether at −60 °C. Transposition to the regioisomeric allylic alcohol 118 occurred within 5 min, leading to full conversion.

Scheme 34 Synthesis of (−)-amphidinolidine through Ph₃SiReO₃ catalyzed allylic alcohol transposition.

Hutchison et al. detailed the preparation of the diterpenoid cladiell-11-ene-3,6,7-triol, which required a notable rearrangement process of a β-hydroxyketone catalyzed by MeReO₃ to generate a conjugated enone at a later stage of the synthesis process (Scheme 35). Allylic transposition was achieved by reacting substrate 120 with 10 mol% of MeReO₃ in benzene at room temperature for 48 h, leading to the desired enone 121 in an impressive yield of 99%, while preserving the stereochemistry of the alcohol.

Scheme 35 Synthesis of cladiell-11-ene-3,6,7-triol via allylic alcohol transposition using a MeReO₃ catalyst.

This effective transfer of chirality can be attributed to the adjacent carbonyl group exerting a strong electron-withdrawing effect, making substrate 120 electron-deficient. Additionally, the electron-donating effect of the methyl group reduces the carbonyl's ability to withdraw electrons, thereby enhancing the reactivity of 120 and facilitating the effective application of the relatively less reactive MeReO₃ catalyst.⁶⁰

A selective method for rearranging tertiary allylic alcohols was developed that favored the silylation of the isomer with less steric hindrance. N,O-Bis(trimethylsilyl)acetamide (BSA) was used in this process and it was observed that the resulting silyl ethers exhibited a slower rate of transposition. This method was applied to substrate 123 (Scheme 36) and resulted in primary alcohol 124 in 84% yield and an E/Z selectivity ratio of 4.6 : 1 following silyl group removal.⁶⁰

Scheme 36 BSA mediated allylic alcohol transposition using a Ph₃SiOReO₃ catalyst.

The regulation of regioselectivity in the [1,3]-transposition enabled the swift synthesis of the carboxylic acid subunit, a crucial component for the cytotoxic marine natural product (±)-apratoxin A, which began with the rhenium-catalyzed rearrangement of tertiary alcohol 127. This reaction was performed using N,O-bis(trimethylsilyl)acetamide (BSA) as the reagent, with a 3 mol% catalyst loading at 0 °C. Afterward, a one-pot deprotection of the trimethylsilyl group led to the formation of a separable mixture of the allylic alcohols (E)-A and (Z)-B in a 1 : 1 ratio (Scheme 37). The E-isomer was then isolated and converted into a carboxylic acid, which served as an essential intermediate in the total synthesis of (±)-apratoxin A.⁶¹

Scheme 37 BSA catalyzed allylic transposition for the synthesis of (−)-apratoxin.

Alexandre et al. described a stereoselective strategy for synthesizing chiral macrocycles in a process that began with amidation, catalyzed by TBD, a guanidine derivative, followed by olefin transposition using a small excess of t-BuOK. The products were isolated in yields of up to 59% and exhibited high syn diastereoselectivity (dr > 49 : 1). When enantiopure α-branched groups were incorporated, mixtures of diastereomers were obtained. The reaction yielded diastereomeric mixtures, and the compounds were assessed as phase-transfer catalysts in the synthesis of phenylalanine analogs, achieving up to 43% enantiomeric excess (ee). Interestingly, a marked matched–mismatched effect was observed across the two diastereomeric series. Using the readily accessible unsaturated macrocyclic precursor 134, researchers successfully synthesized chiral crown ethers with two aliphatic amide FGs. The synthesis distinctly separated the amidation step, catalyzed by TBD, from olefin transposition, which was facilitated by a slight excess of t-BuOK. The resulting compounds were obtained in up to 59% yield and demonstrated excellent syn diastereoselectivity (de > 49 : 1).

Incorporating enantiopure α-branched substituents produced diastereomeric mixtures, which were then tested as phase-transfer catalysts in the preparation of enantioenriched phenylalanine derivatives, resulting in a maximum enantiomeric excess (ee) of 43%. The observed matched–mismatched effect in the two diastereomeric series was particularly noteworthy. The probable mechanism proceeds via a rearrangement mechanism.

After optimization, a range of linear and α-branched amines were employed under optimized conditions for both amidation and olefin transposition, leading to a substantial yield in the two-step synthesis, as depicted in Scheme 38. Generally, a moderate yield (35–55%) was achieved when employing linear primary amines, with side-chain-specific characteristics having minimal influence on the final outcomes. In the standard procedure, macrocycle 135 was synthesized in a total yield of 54%. Derivatives with methyl, propyl, octyl, and allyl substituents were also produced, in yields between 42% and 55%. Furthermore, the inclusion of silyl or methyl-protected amino alcohols was explored, resulting in the formation of macrocycles with yields ranging from 35% to 54%.⁶²

Scheme 38 Amidation and olefin transposition in chiral crown ethers.

Homberg et al. investigated the use of rhenium-based catalysts, including O₃ReOSiPh₃ and Re₂O₇, to help drive the reaction forward for [1,3]-allylic alcohol transposition. The probable mechanism most likely proceeds via a rearrangement mechanism. Nonetheless, these reactions typically show limited regiochemical selectivity, resulting in a thermodynamic mixture of allylic alcohols, such as A and B (Scheme 39). To overcome this challenge, recent advancements have introduced various strategies aimed at improving regiochemical outcomes in these transformations.⁶³

Scheme 39 Transposition of [1,3]-allylic alcohol using O₃ReOSiPh₃ and Re₂O₇ catalysts.

Xie et al. outlined a stereoselective gateway for synthesizing heterocycles, including a reversible allylic alcohol rearrangement, followed by a nucleophilic addition step facilitated by the Re₂O₇ catalyst. This strategy enabled the efficient formation of heterocycles with significant stereocontrol, primarily governed by oxocarbenium ion intermediate; the thermodynamic stability of the optimal stereoselectivity occurred when the energy difference between diastereomers was substantial, enhancing reaction reversibility and promoting stereochemical scrambling via increased substitution on the intermediate allylic cation.

The method effectively generated bridged and spirocyclic ketals, allowing the establishment of remote stereocenters without requiring labor-intensive asymmetric techniques. However, the scope of substrates is limited, as not all allylic alcohols or nucleophiles are suitable. The study highlighted the importance of intermediate cation stability for product equilibration (Scheme 40), demonstrating that alcohol 136 produced lactol 137 in 20% yield due to side products, while using acetal 138 increased the yield to 83% for compound 140, albeit without stereocontrol. Moreover, by combining allylic alcohol transposition with an oxa-Michael reaction, tetrahydropyran is obtained exclusively as a single stereoisomer, achieving near-quantitative yield within a mere 10 min.⁶⁴

Scheme 40 Allylic alcohol transposition in oxa-Michael reactions.

Jiaming et al. presented a stereoselective method, where 2-methyl-1,3-diol acetals were produced via rhenium-catalyzed [1,3]-allylic alcohol transposition, which most likely proceeded via a rearrangement mechanism. By using just 1 mol% of Re₂O₇, they successfully converted both (E)- and (Z)-D-hydroxymethyl-anti-homoallylic alcohols into their respective 2-methyl-1,3-syn-diol acetals, achieving impressive diastereoselectivity. Moreover, they demonstrated that the preparation of 1,3-syn-diol acetals from (E)-D-hydroxymethyl-syn-homoallylic alcohols was accomplished under similar reaction conditions. The reactions yielded products 144a with excellent yields ranging from 87% to 93%, showcasing notable 1,3-syn selectivity (Scheme 41). In addition to 2,2-dimethoxy propane, a variety of other acetals were effectively utilized in these reactions.¹⁷

Scheme 41 Allylic alcohol transposition over a Re catalyst using different acetals with 1,3-syn selectivity.

Volchkov et al. demonstrated that reducing ring strain in medium-sized rings could significantly enhance the regioselective migration of C–O bonds in allylic systems, which could be effectively facilitated using rhenium oxide as a catalytic agent. This transformation allows for selective shifts in the position of FGs, enabling controlled manipulation of the molecular structure in a regio-specific manner. The key aspect of the reaction involves the migration of C–O bonds, which typically indicates a rearrangement mechanism. They proposed that eight-membered cyclic silyl ethers could be transformed into six-membered siloxenes through an allylic transposition reaction by taking advantage of decreased ring strain to induce ring contraction. In this approach, eight-membered siloxadiene rings are transformed into six-membered siloxene derivatives, containing an endocyclic double bond and an alkenyl substituent, which are synthesized using a sequence of three metal-catalyzed reactions (Scheme 42). The process begins with the intramolecular transfer of an allyl group from silyl alkynes, which leads to the formation of the (Z)-configured vinylsilyl group in 145. This is followed by ring-closing metathesis (RCM) to create the eight-membered ring, and finally, silyl-directed allylic transposition to yield 146 (Scheme 42), which facilitates the contraction of the ring (Fig. 13). This comprehensive approach yields functionalized (Z)-trisubstituted vinylsilanes. In the case of 148 and 151, allylic transposition, with two distinct mechanisms for the rhenium oxide-catalyzed transposition, was suggested. Breaking the Si–O bond triggers σ-bond metathesis, subsequently leading to allylic transposition that can proceed either through a [3,3]-sigmatropic shift or by the generation of an ion pair. When performed at ambient temperature, 152 was isolated. Enantiomeric excesses of 79% and 76% were observed (Scheme 43), suggesting that the extent of racemization during the Re₂O₇ catalyzed reaction was influenced by the reaction duration, with prolonged times leading to diminished enantiomeric excess. The mechanisms underlying the allylic transposition are also impacted by substituents R¹ and R² owing to steric and electronic characteristics; the presence of an electron-withdrawing group at R¹ facilitates a concerted mechanism, while electron-donating substituents have the opposite effect, achieving an allyl cation intermediate influenced by an ion pair.²⁴

Scheme 42 Ring-formation via allylic transposition in cyclic silyl ethers.

Fig. 13 Mechanistic study of allylic transposition and ring contraction facilitated by silyl functionalities.

Scheme 43 1,3-Transposition using a Re₂O₇ catalyst for the relocation of chirality.

Xie et al. explored a novel method for synthesizing heterocycles through the transposition of allylic alcohols, utilizing traceless trapping groups. In this study, transposition reactions of allylic alcohols using the Re₂O₇ catalyst shifted the equilibrium by trapping one isomer with a pendant electrophile. In the case of using an aldehyde or ketone as the trapping agent, the process involved subsequent ionization, leading to the generation of cyclic oxocarbenium ions. This method, which concluded with bimolecular nucleophilic addition, proved to be a flexible strategy for producing heterocycles bearing an oxygen atom. Upon investigating the relative rates of each reaction step, the researchers designed processes capable of generating multiple stereocenters with commendable stereocontrol. The study illustrated that the generation of heterocycles followed a sequential transposition of allylic alcohols leading to intramolecular trapping (Scheme 44) and intermolecular termination, with the initial trapping group remaining traceless. This is a classic feature of a rearrangement mechanism, where FGs move within the molecule to form a new structure.⁶⁵

Scheme 44 π-Electrophile allylic alcohol transposition-based heterocycle.

In addition to primary derivatives, secondary allylic alcohols were also studied as substrates, while for trapping groups aldehydes and ketones were effective. Silanes, p-nucleophiles, and alcohols were used as terminating agents, facilitating the formation of tetrahydrofurans and tetrahydropyrans. The reactivity was influenced by both the concentration of the oxocarbenium ion and the nucleophilicity of the trapping agent. Important factors included the substitution pattern of the allylic alcohol, the choice of trapping agent, and the properties of the nucleophile, all of which were crucial in determining the reaction rate by strategically adjusting the rates of transposition and termination. Researchers achieved relative stereocontrol, enabling access to different stereoisomers, which were produced via reductive and alkylative quenching. Significantly, enhanced stereocontrol was achieved with an increased transposition rate, while maintaining a low termination rate.⁶⁵

7. Chiral transposition

An asymmetric or chiral allylic substitution transposition process was demonstrated by Sun et al. that eased the formation of chiral enamides assisted by central-to-axial chirality via H-bonding. The most likely mechanism for the formation of chiral enamides assisted by H-bonding and central-to-axial chirality is an addition–elimination mechanism. Axially chiral enamides featuring the N–C axis are an important class of chiral building blocks, thereby a stereoselective process was established in this study. The authors presented enantioselective synthesis via a catalytic strategy involving Ir catalyzed asymmetric allylation to form a C(sp²)–N bond, followed by in situ transposition, which occurred mainly via 1,3-hydrogen transfer in the presence of an organic base, resulting in excellent chirality transfer. This chiral ion-pair intermediate facilitates stepwise deprotonation and re-protonation events via 1,3-H transfer (Fig. 14), where hydrogen bonding to the enamide carbonyl enhances reactivity and stereospecificity. Interestingly, different types of axially chiral enamides with configurational stability led to excellent yield (80–90%) as well as enantioselectivity for the N-vinylation reaction (Scheme 45), marking a significant advance in atroposelective synthesis. Mechanistic studies suggested that transposition followed asymmetric allylic amination, facilitated by hydrogen bonding, which stabilized the chiral ion-pair intermediate and transition state while minimizing undesired enantiomer formation due to steric hindrance. Under optimized conditions, the substrate scope was explored, revealing that various substituted cinnamyl carbonates were well tolerated for C–H amination. Notably, electron-neutral, electron-donating and electron withdrawing groups containing para-substituted cinnamyl carbonates offered products 161 with 90–97% enantiomeric excess (ee) and 80–95% yield.⁶⁶

Fig. 14 Mechanistic pathway for stereospecific (1)-H-transfer via H-bonding.

Scheme 45 Axially chiral enamide formation via asymmetric allylic substitution–transposition.

In 2022, Sun and coworkers reported asymmetric allylic substitution coupled with intramolecular transposition that effectively transferred chirality from a central to an axial configuration, providing a strategy for synthesizing chiral compounds with high stereocontrol. In this method, 2-indole imine methide generated from in situ racemic tertiary indolyl methanol. Asymmetric allylic substitution coupled with intramolecular transposition that transfers chirality from a central to an axial configuration is most likely to proceed through an addition–elimination mechanism. As per Scheme 46, employing an ortho-directing group and a chiral phosphoric acid-based catalyst, the process formed regioselective C–C bonds at the 3-position and the stereogenic 2-benzylic position with high enantioselectivity. Interestingly, racemic indol-2-ylmethanols react with indole nucleophiles through a catalytic asymmetric allylic substitution (AAS) process to produce enantioenriched triarylmethanes with high regioselectivity and enantioselectivity. While enantiocontrol was prominently affected by electron-donating and electron-withdrawing groups, the o-OMe group alone was pivotal for achieving good enantioselectivity.⁶⁷

Scheme 46 Reaction scope for 2-indolylmethanols in axial chiral transposition.

Zhang et al. reported the enantioselective design and preparation of axially chiral naphthyl–indole frameworks, achieving high enantioselectivity. The probable mechanism for this method most likely proceeded through an addition–elimination mechanism. This was accomplished through an organocatalytic approach, where 2-naphthols and 2-indolylmethanols underwent asymmetric coupling reactions to achieve product 165 in yields up to 99% and an enantiomeric ratio of 97 : 3. The method certainly produces a sort of heterobiaryl backbone containing axial chirality, which holds promise for developing not only ligands and chiral catalysts, but also for establishing an emergent enantioselective approach that exploits the 2-indolylmethanols exhibiting C₃-electrophilicity for constructing biaryl frameworks of axial chirality. Notably, this work represented the catalytic enantioselective C₃-arylation of 2-indolylmethanes, paving the way for future advancements in C₃-functionalization. Following optimization of the reaction conditions, the authors explored the substrate scope concerning 2-indolylmethanols, demonstrating the reaction's applicability across various R¹/Ar groups (Scheme 47). Indole imine methides (IIMs) serve as valuable intermediates for the efficient synthesis of enantioenriched indole-containing compounds.^68–72

Scheme 47 Constructing an axial chiral aryl–indole skeleton.

8. Functional group transposition

FG transformations emphasize the repositioning, introduction, or removal of FGs, which are essential for synthetic applications. Unlike standard FG interconversion, where a specific group is replaced by another, research focuses on reactions that merely shift FGs. Chen et al. developed a method that employed photocatalytic, reversible carbon–hydrogen sampling to facilitate the transfer of cyano (CN) groups inside nitriles. With this technique, CN groups can be directly exchanged with inactivated C–H bonds, particularly favouring 1,4-CN transposition, which often contrasts with typical conventional C–H functionalization, demonstrating site selectivity. The authors also showcased the movement of cyano groups in the cyclic structure, featuring complex architectures that were difficult to achieve through traditional synthesis methods; the most likely mechanism for the photocatalytic transfer of cyano groups in this reaction is a rearrangement mechanism.

By harnessing the versatility of CN groups, they successfully synthesized bioactive building blocks (Figs. 15 and 16). Moreover, this method enabled the formation of unconventional C–H derivatives by integrating C–H cyanation with CN transposition (Scheme 48), thus presenting a novel strategy for site-selective C–H transformations without requiring specific cleavage of the C–H bond at target sites.²¹

Fig. 15 Transposition mechanism of transannular CN.

Fig. 16 Direct FG transposition of the CN group.

Scheme 48 Reversible CN transposition for continuous C–C bond construction and FG transposition of the CN group.

Maximiliano et al. highlighted the significance of FG transposition or exchange for enhancing palladium-catalyzed reactions. By utilizing reversible oxidative addition and reductive elimination at the palladium center, this method enabled the selective swapping of aryl iodides and acid chlorides, bypassing the need for traditional transmetallation or dissociation steps. Notably, the Xantphos ligand played an essential role in stabilizing Pd(0) and facilitating efficient reductive elimination, allowing for the exchange of FGs. This approach was compatible with a wide range of functional groups, avoiding the formation of free intermediates, and eliminating the need for harsh reagents.

Notably, this method allowed for the synthesis of acid chlorides without high-energy halogenating agents or hazardous reagents using aryl iodide metathesis with acid chlorides. The authors reported metathesis involving σ-bonded functionalities in the Ar–X group (Scheme 49). The reaction occurs via reversible oxidative addition and reductive elimination over Pd, accompanied by the large angle exhibited by the Xantphos ligand. As seen in Fig. 17, the reaction is most accurately characterized as a transposition or exchange reaction rather than a conventional organometallic process involving transmetallation and dissociation as critical steps. This transformation hinges on a reversible oxidative addition and reductive elimination mechanism, which directly facilitates the exchange of functional groups (Ar–X) between aryl iodides and acid chlorides at the palladium center. Evidence from NMR studies and kinetic analyses revealed that the exchange of halide and acyl ligands occurred through a bimolecular mechanism between palladium complexes, bypassing the traditional transmetallation or dissociation pathways. The large bite-angle Xantphos ligand played a pivotal role by stabilizing Pd(0) and reducing the energy barrier for reductive elimination, ensuring efficient and selective FG transposition. Importantly, the mechanism avoids the formation of free intermediates or reliance on additional reagents, distinguishing it from typical organometallic reactions. This reaction exemplifies Ar–X σ-bond metathesis, offering a unique, mild, and selective method for synthesizing acid chlorides from aryl iodides, demonstrating its novelty compared to standard palladium-catalyzed coupling reactions.

Scheme 49 Pd catalyzed aryl–halogen transposition.

Fig. 17 Reversible C–X bond formation via oxidative addition and reductive elimination in FG transposition.

This technique emerged as a practical and environmentally friendly alternative for aryl iodide conversion into acid chlorides in the absence of carbon monoxide or harsh chemicals. The broader implications of σ-bond exchange over a Pd catalyst include the development of mild methods for producing various functionalized aromatic compounds from stable Ar–X reagents. One strategy to enhance exchange reactions involves use of ortho-substituted acid chlorides, owing to preferential p-methoxybenzoyl chloride generation. Electronic effects, particularly from strong electron-withdrawing groups like p-COCl and NO₂ over acid chloride, significantly drive the transposition, resulting in high efficiency (Scheme 50). By employing a slight excess of either acid chloride or aryl iodide, this transposition proceeds with near-quantitative efficiency.⁷³

Scheme 50 Substrate scope of Pd catalyzed functional group transposition.

Chen et al. reported a remote enantioselective desymmetrization catalyzed by bisguanidinium, involving a 1,2-acyl shift, as shown in Scheme 51, which was more likely to be classified as a rearrangement. In their study, cesium carboxylate was added to (cis)-α,α′-dibromocyclohexanone, resulting in the formation of a 6-oxocyclohex-1-enyl ester with high enantioselectivity (Scheme 52). The reaction mechanism involved nucleophilic attack by the carboxylate, followed by keto–enol tautomerism, which facilitated the acyl shift to a neighboring alcohol. Pentanidinium and bisguanidinium (BG) compounds have been employed as phase-transfer catalysts and ion-pair catalysts in various chemical reactions. These species are known for their ability to facilitate the transfer of ions between immiscible phases, enhancing reaction rates and selectivity.^74,75

Scheme 51 Remote enantioselective desymmetrization with a 1,2-acyl shift using a bisguanidinium catalyst.

Scheme 52 Cesium carboxylates and (cis)-2,6-dibromo-4-substituted cyclohexanone via a 1,2-acyl shift using a bisguanidinium catalyst.

The proposed mechanism of S_N2 and intramolecular acyl transfer was also supported by computational study. They applied this method for the synthesis of a tropinone derivative, demonstrating efficient carbonyl chain walking (Scheme 5). High enantioselectivities were achieved using the chiral ion pair catalyst BG7 in light of asymmetric synthesis (Scheme 52).³³

9. Cyclic transpositions

Cao and co-workers explained intramolecular heteroaryl migration, which was used to achieve radical-mediated heteroarylation of unactivated distant C(sp³)–H bonds, producing a range of heteroaryl-substituted aliphatic ketones. Azido radical-mediated hydrogen atom removal from inactive aliphatic C(sp³)–H bonds initiated heteroaryl migration. Transposition has broad compatibility with FGs, strong selectivity for tertiary C(sp³)–H bonds, and mild C–C bond cleavage. Multiple tertiary alcohols with an electron-rich or electron-deficient substituent underwent conversion to yield their respective ketone derivatives. The application of para-substrates provided comparable results for meta or ortho-substitution, likely indicating that the reaction yield was unaffected by the tertiary alcohols’ steric hindrance. The migration technique can be applied to a variety of O–/S–N containing heteroaryls, including benzofuryl, benzothiazolyl, benzothienyl, benzoxazolyl, oxazolyl, and thiazolyl as shown in Scheme 53.⁷⁶

Scheme 53 Radical-directed heteroarylation of remote and unactivated C(sp³)–H bonds through intramolecular migration of a heteroaryl group.

Indoles are more capable of migrating than phenyl groups, according to Zhang et al. Overall, the simultaneous selective cleavage and reconstruction of C(sp³)–C(sp²) bonds made possible by this catalytic system allowed for the quick synthesis of β-indolyl ketones with a wide range of substrates and improved yield of the 1,3-indolyl migration model with a variety of alcoholic substances (Scheme 54). They studied several substituents on the α-phenyl ring of allylic alcohols. The corresponding β-indolyl was achieved together with electron-donating or electron-withdrawing substituents, where ketones formed in the range of 65–94% yield.⁷⁷

Scheme 54 Migration of 1,3-indolyl within α,α-disubstituted allylic alcohols mediated by a Ru catalyst.

Liu et al. explained the 1,3-acyloxy migration, demonstrating that reaction was occured via a cascade 1,2- or 1,3-acyloxy migration followed by 1,5-acyl migration pathway. This resulted in the formation of azaspiro[4.5] decadienone with 97–83% yield when substrates contained an internal alkyne group. The proposed spirocyclization technique is the first instance of using an acyclic precursor to access two members of the family of compounds with an all-carbon quaternary core (Scheme 55).⁷⁸

Scheme 55 Spirocyclization of 3-ene-1,7-diyne esters and migrating acyl groups using a Au(I) catalyst.

10. 1,3-O-Transposition

According to Aikonen et al. the reaction proceeds intermolecularly through a cyclic organo–Au acetal intermediate, which forms when a second ynone undergoes nucleophilic attack. This reaction proceeded via a rearrangement mechanism, and their kinetic studies showed that the reaction's intermolecular nature and rate were significantly enhanced by the presence of electron-rich aldehydes. This study supported both experimental and computational modeling to favor the intermolecular oxo attack of carbonyl compounds over intramolecular attacks, wherein nucleophilic molecular orbitals (MOs) of aldehydes was analyzed and correlated their energy levels with experimental reaction rates (Scheme 56).⁷⁹

Scheme 56 1,3-O-Transposition using a Au(I) catalyst.

Shiroodi et al. described an effective 1,3-O-transposition reaction of ynones catalyzed by Au(I), showcasing its strong potential for synthesizing heterocyclic structures that included an alkyne group. This method enabled the formation of complex structures with alkyne functionality, which could be further employed in various synthetic applications. The work showcased the utility of Au(I) catalysis in constructing diverse heterocycles. The 1,3-O-transposition reaction catalyzed by Au(I) provides a more flexible strategy for organic synthesis than conventional techniques.⁸⁰

Sun et al. explored and used computational methods to investigate how Cu(I) catalyzed the stereoselective generation of trisubstituted Z-enol esters via 1,3-O-transposition. This reaction proceeds via a rearrangement mechanism (Scheme 57). Results indicated that the existence of a hydrogen bond between the substrate and carboxylic acid was vital for disrupting this transposition. Furthermore, final product formation in the presence of a second carboxylic acid was also inevitable.

Scheme 57 Z-Enol ester synthesis of ynone with a CuI catalyst and 1,3-O-transposition of ynone using a Au(I) catalyst.

The method for selectively making trisubstituted Z-enol esters from ynones and carboxylic acids was reported by Zhang et al. where the traditional 1,3-O-transposition mechanism allowed for the selective production of Z-enol esters and they showed an effective approach for controlling the reaction pathways in ynone conversion; where the reaction proceeds via a rearrangement mechanism (Scheme 58).⁸¹

Scheme 58 Stereoselective synthesis of trisubstituted Z-enol esters by a Cu(I)-catalyzed 1,3-O-transposition process.

In the case of the Z-enol ester, stereoselectivity resulted from hydrogen bonding interactions. Additionally, the influence of the Au cation helped to explain the key role of the Au(I) catalyst for promoting 1,3-O-transposition.⁸²

For producing ynamides under mild conditions, Li et al. introduced an Au-catalyzed 1,3-O-transposition reaction. As shown in Scheme 59, ynesulfonamides that contained a nitrogen atom at the terminal position of the alkyne allowed for the straightforward generation of two useful compounds through a simple transposition reaction. Control experiments and DFT calculations provided both experimental and theoretical insights into the proposed mechanism of atom transfer intramolecular 1,3-O transposition (Scheme 59).⁸³

Scheme 59 1,3-O-Transposition in the transformation of ynesulfonamides to ynamides using a Au(I) catalyst.

11. Conclusion and outlook

In summary, we have discussed the efficient method for development of complex natural product, total synthesis, and regio- and stereoselective products using transposition strategies especially for transposition of carbonyl groups, alkenes, allylic alcohols, chirality, functional groups, and 1,3-O-transposition. We have highlighted the challenges in achieving selective carbonyl migration, particularly in regioselective 1,2-transposition within molecular frameworks. The major observation included the triflate-mediated approach for carbonyl 1,2-transposition, utilizing palladium and norbornene-catalyzed alpha-amination, although issues like low yield, and formation of by-products remain persisted. Iron-based catalysts for C=C double bond transposition offered a cost-effective alternative, showing excellent activity when combined with boryl reagents. Re-based catalysts enabled selective diol-to-acetal conversion, although regioselectivity issues are noticed. Chiral transposition demonstrated the promising for creating enantioenriched triarylmethanes, but environmental concerns required for the exploration of greener reagents. Direct CN transposition remained a potential method for synthesizing valuable structures, but challenges of selectivity and efficiency still remain to adressed. Besides, functional group transposition, particularly in carbonyl and ketone chemistry, holds great promise for advancing synthetic chemistry. These methods showcased the creation of complex molecules and biologically active compounds, which are vital for medicinal and organic chemistry. Future research should focus on improving catalytic systems, expanding substrate compatibility, and increasing yield. Further research on efficient transposition methods could lead to novel therapeutic compounds which will open the new platform in organic synthesis.

Author contributions

Savita Narayanrao Gat: Writing – original draft, methodology, data curation. Piyusa Priyadarsan Pattanaik: Writing – review & editing, validation, methodology, investigation, formal analysis conceptualization, visualization. Rambabu Dandela: Writing – review & editing, validation, supervision, resources, project administration, investigation, funding acquisition, conceptualization. All authors read and endorsed this article.

Data availability

The authors confirm that the data supporting the findings of this study are available within the article.

Conflicts of interest

There are no conflicts of interest to declare.

Acknowledgements

Rambabu Dandela thanks DST-SERB for core research grants (CRG/2023/001402 and CRG/2022/001855). The authors acknowledge ICT-IOC Bhubaneswar for providing necessary support.

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