Merging gold catalysis and haloethynyl frames: emphasis on halide-shift processes

Digest paper Merging gold catalysis and haloethynyl frames: Emphasis on halide-shift processes Paula Fernández-Canelas, Pablo Barrio, José M. González ⇑ Departamento de Química Orgánica e Inorgánica and Instituto Universitario de Química Organometálica ‘‘Enrique Moles”, Universidad de Oviedo, C/Julián Clavería 8, Oviedo 33006, Spain article info Article history: Received 2 February 2022 Revised 22 April 2022 Accepted 6 May 2022 Available online 12 May 2022 Keywords: Gold(I) catalysis Haloalkyne Cycloisomerization Electrophilic activation Vinylidene abstract Haloalkynes can enter a wide variety of metal-catalyzed transformation giving rise to the formation of products with or without showing halide-shift. This article offers an overall view of the reactivity of these substrates under gold catalysis. Particular attention is devoted to intramolecular reactions that involve a concomitant halide-shift process for the case of alkynyl iodides as starting materials. Ó2022 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). Contents Introduction. . . . . ........................................................................................................ 1 Gold-catalyzed direct addition reactions to haloalkynes. . . . . . . . .................................................................. 3 Metal vinylidenes from terminal and internal alkynes: generalities and applications in organic synthesis. . ............................... 5 Gold vinylidenes from terminal alkynes: structural features and synthetic utility . . . . . ............................................... 5 Haloalkynes as precursors for metal vinylidene complexes. . . . . .................................................................. 7 Early observations using other metals than gold. ........................................................................... 8 1,2-Halogen shift events in catalytic gold-activation of heteroatom-substituted alkynes: gold vinylidenes as likely reaction intermediates . . 8 Other types of gold-catalyzed reactions of haloalkynes involving halogen-shifting: selective alkyne-alkyne and alkyne-alkene couplings . . 12 Perspective. . . . . . ....................................................................................................... 14 Declaration of Competing Interest . . . . .................................................................................... 14 Acknowledgments . . . . . . . . . . . . . . . . . .................................................................................... 14 References . . . . ....................................................................................................... 14 References . . . . ....................................................................................................... 15 Introduction Haloalkynes are unique acetylene derivatives [1]. They are of significance for the preparation of carbon-rich materials [2] and as intermediates for developing synthetic methodology, particularly through a variety of halide substitution processes (Scheme 1)[3]. They are valuable partners in cross-coupling reactions [4], and are useful reagents for an array of innovative catalytic processes involving selective CAH functionalization reactions (Scheme 2)[5]. Furthermore, catalytic CAC bond-forming transformations of halogen-masked terminal alkyne derivatives affording products showing halogen retention are known. The dimerization reaction of alkynyl halides offers interesting examples based on the consideration of complementary strategies Selective head-to-tail dimerization of aryl-substituted iodoalkynes can be catalytically accomplished using a proper source of iodonium ions through a cationic process. The substitution pattern onto the aryl ring dichttps://doi.org/10.1016/j.tetlet.2022.153857 0040-4039/Ó2022 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). ⇑ Corresponding author. E-mail address: [email protected] (J.M. González). Tetrahedron Letters 99 (2022) 153857 Contents lists available at ScienceDirect Tetrahedron Letters journal homepage: www.elsevier.com/locate/tetlet tates the efficiency of the overall transformation, with electron donor substituents affording better results (Scheme 3)[6]. A related photocatalytic coupling reaction of aryl-substituted bromoalkynes was recently disclosed, and yields the head-to-tail dimer in an efficient and selective manner (Scheme 4)[7]. Mechanistically, an energy transfer pathway promoted by visible-light photocatalysis resulting in the formation of bromine and arylacetylene radicals was proposed. Also recently, gold(I) complexes were identified as valuable catalysts to give the corresponding 1,1-diiodo-1-en-3-yne from the parent (iodoethynyl)arene precursor. So, when different iodoalkynes were treated in acetonitrile with a catalytic amount of a r , p - dinuclear propyne-gold acetylide (dual activation catalyst) the corresponding head-to-tail dimerization products were selectively assembled (Scheme 5)[8]. Interestingly, this reaction also allows the dimerization of alkylsubstituted iodoalkynes, expanding the scope previously described for this transformation. This observation is in line with the noticed reactivity of this type of catalyst for the dimerization of aliphatic terminal alkynes [9]. The bromoalkynylation of internal alkynes with bromoalkynes is another synthetically useful halogen-retentive transformation. Jiang showed that palladium acetate is an efficient catalyst to accomplish this demanding task. The CAC bond-making reaction nicely takes place at 30 °C, in acetonitrile as solvent (Scheme 6) [10]. The reaction can be also conducted using a iodoalkyne but in lower yield. So the iodine-containing analogue of the enyne depicted in Scheme 6 was prepared in a related manner from (iodoethynyl)benzene in 48% yield. In the context of the study of iodonium-promoted self-coupling reactions of (tert-butyldimethylsilyl)alkynes to furnish the corresponding head-to-tail dimerization product, it was also reported that iodoalkynes can add across the related TBDMS-substituted Scheme 1. Synthetic methodology from haloalkynes: formal halide displacement reactions. Scheme 2. Some recent cross-coupling processes involving alkynyl halides. Scheme 3. Iodonium-catalyzed iodoalkyne dimerization reaction. Scheme 4. Photocatalyzed self-coupling of bromoalkynes. Scheme 5. Gold-catalyzed head-to-tail coupling of iodoalkynes. Scheme 6. Palladium-catalyzed bromoalkynylation of alkynes. Scheme 7. Iodonium mediated cross-dimerization of a iodoalkyne and a silylsubstituted alkyne. P. Fernández-Canelas, P. Barrio and José M. González Tetrahedron Letters 99 (2022) 153857 2 acetylenes to afford the corresponding heterodimer, a process that was not further optimized (Scheme 7)[11]. All those reactions highlight some aspects of the rich chemistry of haloakynes. This contribution deals with the utility of this class of heteroatom-substituted alkynes to establish new transformations with incorporation of the halogen atom into the structure of the product, in particular through transformations that, reasonably, might be rationalize assuming the intermediacy of metal vinylidene species. Main attention will be devoted to the growing number of gold-catalyzed processes fulfilling this condition. Accordingly, this brief account will be arranged according to the discussion of the main following topics: – Gold-catalyzed direct addition reactions to haloakynes. – Metal-vinylidenes in organic synthesis. – Gold vinylidenes: structure and synthetic utility. – Haloakynes as a potential source for gold vinylidenes. – Gold-catalyzed reactions of haloalkynes involving halogen shifting: selective alkyne-alkyne and alkyne-alkene couplings. In this context we will briefly outline our work in this field, as well as recent contributions from other authors that, though evolving though differentiate reaction mechanisms, contribute to shape and develop another growing hot area for gold catalysis. Gold-catalyzed direct addition reactions to haloalkynes. The above presented transformations are a personal selection of representative reactions that contribute to highlight some significant aspects of the chemistry of haloalkynes. Interestingly, along the two past decades a plethora of gold-catalyzed new synthetic processes and a number of distinctive structural features were documented [12], with alkynes proving to be unique partners for gold [13]. In this scenario, gold-catalyzed hydrofunctionalization reactions of unsaturated CAC multiple bonds were rapidly developed [14]. These processes have an impact onto haloalkyne chemistry, which was put into context in another recent review [15]. The search for efficient alternatives to the use of mercury salts as catalysts in the addition reaction of water to alkynes offered a useful transformation for catalysts development. It has been an active research arena from the early days of the study of the synthetic utility of different gold species [16]. The merit of gold catalysis to access a -halomethylketones upon reaction of haloakynes with water was proved (Scheme 8,eqa)[17]. A related regioselective hydration reaction of halo-substituted proparagyl carboxylates under gold(I) catalysis was reported to produce valuable synthetic intermediates having the structure of a -acyloxy a ’-halo ketones [18]. Interestingly, the gold-catalyzed alkyne hydration can be also coupled with a ruthenium-catalyzed asymmetric transfer hydrogenation reaction to furnish chiral badrenergic receptor blockers, in a new one-pot cascade, as shown in Scheme 8, eq b for a selective synthesis of (R)-Nifelanol [19]. Furthermore, a -halomethyl ketones can be directly accessed from terminal alkynes conducting the gold-catalyzed hydration reaction in the presence of N-halosuccinimides [20]. In connection with the iodination reaction of terminal alkynes, Gagosz was the first to demonstrate the nice stereochemical complementarity of gold(I)-catalyzed cyclization reactions of terminal propargyl tert-butylcarbonates to prepare cyclic carbonates. To this end, both, the activation of a terminal alkyne under iodination conditions and, alternatively, the related hydro-functionalization process starting from the parent iodoalkyne were developed (Scheme 9)[21]. Scheme 8. Gold-catalyzed addition of water to bromoalkynes and its subsequent synthetic application. Scheme 9. Stereoselective synthesis of vinyl iodides from gold(I)-catalyzed cyclization reaction of propargyl carbonates. Scheme 10. (Z)-b-iodoenol esters by catalytic intermolecular addition reaction of carboxylic acids to iodoalkynes. Scheme 11. Catalytic hydrochlorinations of bromoalkynes. P. Fernández-Canelas, P. Barrio and José M. González Tetrahedron Letters 99 (2022) 153857 3 Interestingly, Cadierno, García-Garrido and their team reported a synthetically valuable intermolecular addition reaction of carboxylic acids to iodoalkynes, which resulted in the selective formation of (Z)-b-iodoenol esters, which were then elaborated into (Z)- enynyl esters by palladium-catalyzed Sonogashira cross-coupling reaction with terminal acetylenes (Scheme 10)[22]. Besides oxygen-based nucleophiles, other heteroatoms add across haloalkynes under gold catalysis. Stereoselective hydrochlorination reactions of haloalkynes are known. Catalysis based on both hydrogen-bonding-assisted Brønsted acid and on gold species were applied to this purpose. For instance, 4-(bromoethynyl)phenyl acetate can be selectively diversified into the (Z) and (E) isomers of 4-(2-bromo-1-chlorovinyl)phenyl acetate applying alternative catalytic conditions (Scheme 11)[23]. A gold(I) catalyzed Ritter-type process giving (Z)-b-halogenated enamides from the reaction of nitriles and water with bromoor chloroalkynes was recently disclosed (Scheme 12)[24]. Moreover, new carbon–carbon bond-forming events resulting from direct addition of C-based nucleophiles to haloalkynes are also known. Thus, the iodoalkyne carbocyclization reaction depicted in Scheme 13 represents an early example, which results in a synthetically valuable gold-catalyzed 5-endo-dig cyclization of internal alkynes, including both Cand halo-substituted precursors [25]. In some cases, In(III) demonstrated capability to complement Au(I) catalysis promoting addition reactions of C-based nucleophiles to CAC multiple bonds. Thus, Nakamura documented a valuable syn-addition of 1,3-dicarbonyl compounds to iodoalkynes. The resulting E-alkenyl iodides are partners for further derivatization to assemble trisubstituted alkenes with defined stereochemistry as depicted in Scheme 14 [26]. The catalytic reaction of phenols with 1-bromo-1,5-enynes gives 2-(halocyclopent-2-en-1-yl)phenols through a domino process (Scheme 15)[27]. The reaction also works for chloro enynes but fails for the related iodine-modified enynes. A chemoand regioselective CAH bond-functionalization of phenols by reaction with haloalkynes under gold catalysis was documented, and gave aryl-substituted alkenes bearing a phenol substituent (Scheme 16). [28]. Moreover, 1-iodoalkynes are particularly reactive substrates towards organic azides in the copper-catalyzed azide-alkyne cycloaddition chemistry (CuCAAC), affording 5-iodo-1,2,3-triazoles Scheme 12. Gold(I)-catalyzed Ritter reaction of haloalkynes. Scheme 13. Catalytic Conia-ene cyclization of a iodoalkyne. Scheme 14. Indium-catalyzed C-addition to iodoalkynes. Scheme 15. Catalytic reaction: 1-halo-1,5-enyne and phenols. Scheme 16. Selective addition of phenols to haloalkynes. Scheme 17. Iodoalkynes in the CuAAC reaction. Scheme 18. Catalysis by in-situ generated vinylidene species. P. Fernández-Canelas, P. Barrio and José M. González Tetrahedron Letters 99 (2022) 153857 4 in a selective manner, under mild catalytic reaction conditions (Scheme 17)[29]. In this synthetic scenario, the reactivity of this type of internal alkynes exceeds that of terminal alkynes. Metal vinylidenes from terminal and internal alkynes: generalities and applications in organic synthesis Different reaction pathways and precursors are available to access alkenylidene carbene (for short vinylidene) intermediate species [30]. The generation of vinylidene reactive species by isomerization of terminal alkynes attracted much interest over the years [31]. Transition metal vinylidene compounds allow for a fine tuning of the reactivity of these types of reaction intermediates, enabling unique catalytic applications in organic synthesis [32]. Seminal discoveries form Dixneuf resulted in the assembly of vinyl carbamates from ruthenium-catalyzed reactions of terminal alkynes, CO 2 and diethylamine (Scheme 18)[33]. First, polynuclear ruthenium complexes were used as the catalyst source [33s]. Conditions were then identified using mononuclear complexes [33b]. Ruthenium-vinylidene intermediates resulting from the initial interaction of terminal alkynes with the metal were proposed as the catalytic active species [33c]. Also very early, Trost disclosed a ruthenium-catalyzed addition of allylic alcohols to terminal alkynes affording b, c -unsaturated ketones. Mechanistic studies support the participation of a ruthenium vinylidine complex as the reaction intermediate (Scheme 19)[34]. Merlic presented a ruthenium-catalyzed cyclization reaction of dienylalkynes based on this principle. A variety of fused carboand heterocyclic structures were prepared in a catalytic manner [35]. Ruthenium catalysis greatly contributed to develop the synthetic potential associated with the terminal alkyne to metal vinylidene equilibria [36]. Nonetheless catalytic systems based on other metals were also documented [37–40]. The terminal alkyne to vinylidene isomerization at a metal center keeps on drawing much attention from the chemical community [41]. In addition to the potential associated with the use of terminal alkynes as substrates to access reactive metal vinylidene species, structural studies proving that internal alkynes can also generate metal vinylidine are known. Thus, the thermal reaction of a cyclotriphosphato ruthenium complex with an internal alkyne gave rise to the isolation and characterization, both in solution and in the solid state, of ruthenium-vinylidine complexes [42]. Besides disclosing the synthesis of additional cationic iron and ruthenium vinylidene complexes from isomerization reactions of diarylacetylene derivatives [43], as well as computational studies on this rearrangement process [44], Mutoh and Ishii reported catalytic applications for this elusive entry to vinylidene complexes [45–47]. Thus, based on the 1,2-carbon migration, a rutheniumcatalyzed N-[2-(arylethynyl)aryl]acetamide cycloisomerization leading to N-acyl-3-arylindoles was presented (Scheme 20)[48]. Metoxycarbonyl [49] and acyl [50] substituted alkynes are also proper sources of carbon-based groups that enter this alkyne to vinylidene isomerization step, at a transition metal center. Far from the above discussed C-substituted internal acetylene derivatives, heteroatom-substituted ones encode a wide set of differentiate classes of precursors. They found utility to assemble metal vinylidine complexes at transition metal centers, which keeps on expanding the borders of this field. Among them, structural studies on the complexes resulting from the 1,2-migration of elements belonging to group 14 other than carbon, as silicon [51] and tin [52], and group 16, as sulfur [53] and selenium [54], were early reported and conquered attention. More recently, the use of phosphorous-substituted alkynyl derivatives to access vinylidene species was also proved. [55]. Gold vinylidenes from terminal alkynes: structural features and synthetic utility Along the past two decades, research efforts aimed to promote the catalytic activation of alkynes by means of gold complexes underwent enormous advances [13,56]. Compared with significant discoveries of complex reaction settings based on gold-catalyzed activation of alkynes through an intermediate gold carbene, the number of studies and the progresses accomplished dealing with related vinylidene intermediates are scant and more recent [57]. From the structural point of view Widenhoefer revealed useful insights into the nature of this elusive intermediate species, characterizing the first gold vinylidene complex (Scheme 21)[58]. At present, the most advanced and practiced approach that exploits the potential of gold vinylidenes to move forward the field of organic synthesis relies on the notion of dual activation catalysis. Remarks on gold acetylides [59], and key findings in late 2011 independently accomplished by the groups of Zhang and Hashmi contributed to develop this notion (Scheme 22). Zhang documented a BrettPhosAuNTf 2 -catalyzed isomerization of (2-ethynylphenyl)alkynes to tricyclic indenes (Scheme 22,eqa) [60]. Mechanistic and computational studies support the involvement of gold vinylidenes as key intermediates. Almost simultaneScheme 19. Ruthenium-catalyzed reconstructive condensation of terminal acetylenes and allylic alcohols. Scheme 20. Indoles upon Ru-catalyzed 1,2-carbon shift. Scheme 21. Gold vinylidene synthesis and characterization. P. Fernández-Canelas, P. Barrio and José M. González Tetrahedron Letters 99 (2022) 153857 5 ously, studies by Hashmi proposed a key role for gold vinylidine intermediates to explain the unexpected formation of b-arylated naphthalene regioisomers in cyclization-hydroarylation reactions of 1,2-dialkynylarenes with benzene, using IPrAuNTf 2 as catalyst (Scheme 22,eqb)[61]. Hashmi also reported the synthesis of dibenzopentalenes from arene-1,2-diynes featuring an aryl-substituted and a terminal acetylene fragments (Scheme 22,eqc)[62– 64]. A dual activation mode of the two alkyne fragments was invoked. The involvement of gold vinylidene intermediate was crucial to rationalize this result. A detailed mechanistic picture of the events involved in the catalytic dual-activation mode was disclosed by Hashmi and his team (Scheme 23)[65], including the eventual catalyst transfer-step and the equilibrium between the active monogold species involved in such operation and the gem-diaurated species. The notion of dual gold catalysis rapidly matured and the resulting synthetic methodology was soon put into context and reviewed [66]. Besides, Hashmi and his group further reported relevant new transformations [67] and careful studies on the detection of intermediate species operating in the dual-gold-catalyzed activation of 1,5-diynes towards benzene, providing support to the conceptual basis behind the strategy [68]. Early, this group also recognized the merit of the dual goldcatalysis to get iodofulvenes from catalytic cycloisomerization reactions of 1-(3,3-dimethylbut-1-yn-1-yl)-2-(iodoethynyl)arenes (Scheme 24)[69]. The catalytic cycle comprises the generation of a gold acetylide. Subsequently a gold vinylide results out of the dual activation mode and evolves through different species to render a vinyl gold intermediate, which yields the iodo-containing fulvene via an unprecedented iodine/gold exchange. Nowadays, the dual gold-catalysis activation mode is a fairly active research arena and several groups are contributing to its further development. Additional intramolecular elaboration of diyne frames into synthetically useful products were reported [70–72]. Apart from dual gold-catalysis, Hashmi and his group reported a catalytic strategy for the cyclization of a , x -alkynyl tosylates to cycloalkylidenemethyl tosylates, which is proposed to involve as intermediate a gold-vinylidene (Scheme 25)[73]. The yield was optimized by fine tuning the NHC ligand. Replacing the 2,6-diisopropylphenyl unit attached to one of the nitrogens by a cyclopentadecyl group, increases the yield from 69% up 92%. Gold(I) acetylides offered additional alternative entries to gold vinylidenes. Zhang showed that the catalytic reaction of conjugated enynones with gold(I) in the presence of a bromonium donor renders cyclopentenone frames (Scheme 26)[74]. Fürstner also recognized a gold vinylidene as intermediate in the reaction of TBSOTf with the 2’-substituted IPr-gold acetylide derived from [1,1’-biphenyl]-2-carbaldehyde (Scheme 27)[75]. As shown in the previous section, several metals react with terminal alkynes to give vinylidene complexes via 1,2-hydrogen shift. Using gold catalysis, Gevorgyan and his group reported Scheme 22. Bases for the dual gold catalysis approach to catalytic gold vinylidene generation and synthetic applications. [IPr: 1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene]. Scheme 23. Dual gold-catalyzed approach to benzofulvenes. Scheme 24. Dual gold-catalysis involving a iodoalkyne. Scheme 25. Leaving group approach to gold vinylidenes. P. Fernández-Canelas, P. Barrio and José M. González Tetrahedron Letters 99 (2022) 153857 6 gold(III)-catalyzed cycloisomerization reactions of propargylic derivatives from N-containing heterocycles (Scheme 28)[76]. It features a 1,2-H shift from a terminal alkyne, as well as 1,2migrations of silyl, stannyl and germyl groups from the corresponding heteroatom-masked acetylene precursors. Based on the structure of the products and some control experiments, it was initially assumed that the reaction involves a gold vinylidene as intermediate. Subsequent, theoretical calculations fully supported an alternative mechanism (Scheme 29)[77]. Haloalkynes as precursors for metal vinylidene complexes Several transition metal complexes undergo oxidative addition processes in the presence of alkynyl halides, thus limiting the Scheme 26. Gold vinylidenes by intermolecular electrophilic activation of acetylides. Scheme 27. Gold vinylidenes by intramolecular electrophilic activation of acetylides. Scheme 28. Gold(III)-catalyzed cycloisomerization involving 1,2-hydrogen shift. Scheme 29. Catalytic isomerization of propargylpyridines. Scheme 30. 1,2-I shift to give b-iodo Mn-vinylidene complex. Scheme 31. Metal-vinylidene complex upon reaction of metal-acetylides with iodonium donors. Scheme 32. Catalytic elaboration and reactivity of an iodo-substituted tungsten vinylidene complex. Scheme 33. Pioneering work on 1,2-halogen migration from gold-catalyzed haloalkyne activation reactions. P. Fernández-Canelas, P. Barrio and José M. González Tetrahedron Letters 99 (2022) 153857 7 applicability of these heteroatom-substituted alkynes to furnish vinylidene complexes. Even though, some examples are known, virtually involving iodo-substituted acetylene derivatives. Early observations using other metals than gold. Berke prepared and characterized by X-ray diffraction a manganese vinylidene complex upon irradiation of a iodoalkyne and cyclopentadienyl manganese tricarbonyl (Scheme 30)[78]. An opposite entry to forge vinylidene complexes at transition metal centers is based on the reaction of transition metal acetylides with a proper halogen source of the electrophile, a process that selectively takes place at the b-carbon of the parent alkynyl complex (Scheme 31,eqa[79] and b [80]). The number of synthetic reports based on a catalytic 1,2-halogen rearrangement is limited. Iwasawa documented a catalytic isomerization of o-(iodoethynyl)styrenes into the corresponding iodo-substituted naphthalene derivatives featuring this iodinemigration process (Scheme 32)[81]. 1,2-Halogen shift events in catalytic gold-activation of heteroatomsubstituted alkynes: gold vinylidenes as likely reaction intermediates Fürstner discovered the 1,2-halogen shift reaction in gold-catalyzed cyclization reactions of o-alkynyl-substituted biphenyl derivatives (Scheme 33)[82]. Interestingly, within the general context of a search to obtain phenanthrenes, haloalkynes provide a complementary synthetic manifold, which is selectively driven by the catalyst. Thus, after testing different catalyst, InCl 3 successfully afforded the target 10-halophenanthrene derivatives. Moreover, adding AuCl as catalyst, the 9-halo-substituted regioisomer was exclusively formed [83]. This alternative process was explained assuming the formation of a gold vinylidene as the reactive species resulting from a 1,2halogen migration. Then, different groups reported DFT calculations on the mechanism of these transformations. The reached conclusions from these theoretical studies depend on the accuracy of the chosen functional. Thus, for the gold(I) catalyzed process, relying on B3LYP/6-31G* (LANL2DZ) calculations, an initial gold complexation to the haloalkyne, followed by the 1,2-halide shift to the vinylidene complex and subsequent 6-endo-dig electrocyclization and then a 1,2-H shift were identified as the steps outlining the energetically most favorable reaction pathway [84]. Then, years later, subsequent M06/6-31+G* (LANL2DZ) calculations originated a different sequence of events to explain the cycloisomerization leading to 9-halophenanthrenes under gold(I) catalysis [85]. Now, the outcome of the gold-catalyzed electrophilic hydroarylation results from an initial 6-endo-dig cyclization that renders the Wheland-type intermediate, which evolves through a 1,2 migration of H, followed by a kinetically favored 1,2-Br shift [86]. Anyway, the number of reports on CAC bond-formation based on gold-catalyzed reactions of haloalkynes via a 1,2-halogen shift is limited. In all the cases, the haloalkyne unit was bounded to the arene ring and the strategy was focused on its application to the synthesis of pyrene, picene and dibenzo[a,h]anthracene cores through catalytic events involving double migration-cyclization processes (Scheme 34)[87]. Considering the attention payed by our laboratory to establish different hydroarylation strategies, including iodonium-promoted and metal-catalyzed arylation reactions of different unsaturated motifs [88–90], we became interested in broaching the synthetic potential of that halogen-dancing cyclization mode under gold catalysis. Moreover, gold-catalyzed hydroarylation reactions of terminal N-propargyl aniline and phenol derivatives usually require the presence of additional activating substituent at the arene platform to be of synthetic utility [91]. On this ground, we first tested the merit of the process to assemble common heterocyclic frames with distinguishable regiocontrol. Also, we were attracted by the possibility of doing so on the basis of using as catalysts only goldbased complexes. Furthermore, exploring the outcome of the reaction when additional electron-withdrawing substituents are present at the arene platform is another attractive task to consider. On this ground, the reaction of N-(3-iodoprop-2-ynyl)-N-tosylanilines with different gold(I) complexes was tested, and some representative examples are depicted in below (Scheme 35)[92]. The intended points were validated proving that the nature of the ancillary ligand on gold is an essential element of control. Thus, the regular hydroarylation is the main cyclization pathway if the catalyst is based on a phosphite ligand. The performance of this electrophilic system based on a p -acceptor ligand attached to gold and a tetrafluoroborate anion can be additionally tuned by the substitution at the arene fragment of the propargyl aniline derivative. In fact, the introduction of a modest donor substituent enhances the efficiency and the regioselectivity of the cyclization. Just switching from H to Me-substitution at the para-position of the starting material renders a preparative useful transformation. Thus, affording a regioselective synthesis of the N-tosyl-4-iodo-6methyl-1,2-dihydroquinoline from a common hydroarylation pathway. The use as catalyst of IPrAuNTf 2 furnishes as main product the opposite regioisomer (Scheme 35, see X = H). In this case, the IPr is a strong r -donating NHC ligand and induces a 1,2-I shift prior Scheme 34. Polycyclic aromatics from migration-cyclization. Scheme 35. Catalytic assembly of regioisomeric heterocyclic frames. P. Fernández-Canelas, P. Barrio and José M. González Tetrahedron Letters 99 (2022) 153857 8 to the cyclization event. Again, the additional substituents at the aniline fragment modulate the intensity of this behavior. Interestingly, an electron-withdrawing substituent at the para-position disfavors the normal path and magnifies the formation of the cyclization product with concomitant 1,2-I-shift. For the case of a more electron-rich precursor the IPrAuNTf 2 -catalyzed reaction still gives the dihydroquinoline with the associated iodine shift as the main regioisomer from this cyclization event, as shown in Scheme 35 for the p-anisidine derivative (X = Me). Those examples evidence the strong control over the selectivity exerted by the ancillary ligand and the additional tuning over the selectivity dictated by the nature of the aryl moiety. Thus, the combination of a r -donor ligand with an arene moiety decorated with electron-withdrawing substituents is optimal to afford hydroarylated products showing additional 1,2-iodine dancing. On the contrary, a p -acceptor ligand acting in conjunction with electron-rich substituents at the arene ring tends to favor the formation of a normal hydroarylation product of the parent iodoalkyne. In a recent paper dealing with the design and preparation of strong p -acceptor ligands, Alcarazo showed the unique properties of a -cationic phosphole gold(I) complexes as ancillary ligands to access the normal cyclization, which provides strong support to the previously formulated hypothesis The new ligand allows a nice discrimination among the two competing cyclization paths, favoring the normal hydroarylation outcome with outstanding selectivity (Scheme 36)[93]. The resulting gold catalyst targets the preparation of 4-iodo2,3-dihydroquinolines from intramolecular hydroarylation of iodoalkynes with exquisite selectivity, without showing the previously noticed dependence on the presence of additional activating substituents at the arene. As we were interested in the less commonly reported pathway leading to cyclization with a concomitant halogen shift, it was challenging to target the synthesis of related 3-iodo-2H-chromene derivatives using this type of cyclization. At the same time, it is a demanding process as the tethering ether functional group is a more activating unit than the already studied sulfonamide precursor. Thus, on the basis of the previously gathered knowledge, the gold complex with the powerful r -donor IPr ligand was selected from the onset. Besides, phenolic moieties containing electronpoor substituents were chosen to conduct this study, searching for a rarely examined substitution pattern in alkyne hydroarylation processes. Aryl (3-iodoprop-2-yn-1-yl) ethers were cyclized using this approach. Among others, derivatives of phenol precursors substituted at the para-position by groups as: CN, CHO, CO 2 Et and NO 2 (Scheme 37)[94]. In all cases, the iodo-shifting process was the major reaction pathway, defining a highly regioselective entry to the catalytic synthesis of 6-substituted 3-iodo-2H-chromenes. The reaction of a substrate containing chiral information at the propargylic position renders the corresponding 1,2-iodo-shifted cyclized product without eroding the stereochemical information, highlighting an additional attractive feature associated with this elaboration of 3-iodo-2H-chromene scaffolds. The formation of this type of product was rationalized according to the mechanistic scenario depicted in the equation a, in Scheme 38. Scheme 36. Normal hydroarylation pathway for iodoalkynes catalyzed by gold(I) complexes with a -cationic phospholes. Scheme 37. 1,2-Iodo-shift in the hydroarylation reaction of iodoalkynes catalyzed by a gold(I)-complex with a NHC-ligand. Scheme 38. Mechanistic rationale for the 1,2-iodine shifting iodoalkyne hydroarylation reaction. Scheme 39. Intramolecular CAH activation by gold-catalyzed activation of iodoalkynes. P. Fernández-Canelas, P. Barrio and José M. González Tetrahedron Letters 99 (2022) 153857 9 [49] P. King, S.A.R. Knox, M.S. Legge, A.G. Orpen, J.N. Wilkinson, E.A. Hill, J. Chem. Soc., Dalton Trans. (2000) 1547–1548. [50] (a) M.J. Shaw, S.W. Bryant, N. Rath, Eur. J. Inorg. Chem. (2007) 3943–3946; (b) V.K. Singh, E. Bustelo, I. de los Ríos, I. Macías-Arce, C. Puerta, P. Valerga, M. A. Ortuño, G. Ujaque, A. Lledós, Organometallics 30 (2011) 4014–4031; (c) F.E. Fernández, M.C. Puerta, P. Valerga, Inorg. Chem. 52 (2013) 6502– 6509; (d) T. Kuwara, S. Takamori, S. Kishi, T. Watanabe, Y. Ikeda, S. Kodama, Y. Minami, T. Hiyama, Y. Ishii, Synlett 29 (2018) 727–730. [51] (a) H. Werner, M. Baum, D. Schneider, B. Windmüller, Organometallics 13 (1994) 1089–1097; (b) H. Katayama, K. Onitsuka, F. Ozawza, Organometallics 15 (1996) 4642– 4645; (c) M.V. Jiménez, E. Sola, F.J. Lahoz, L.A. Oro, Organometallics 24 (2005) 2722–2729; (d) K. Ilg, M.L. Paneque, M. Poveda, N. Rendón, L.L. Santos, E. Carmona, K. Mereiter, Organometallics 25 (2006) 2230–2236; (e) C.-F. Yeung, L.-H. Chung, H.-S. Lo, C.-H. Chiu, J. Cai, C.-Y. Wong, Organometallics 34 (2015) 1963–1968; (f) H. Kanno, K. Nakamura, K. Noguchi, Y. Shibata, K. Tanaka, Org. Lett. 18 (2016) 1654–1657. [52] (a) K. Venkatesan, O. Blacque, T. Fox, M. Alfonso, H.W. Schmalle, S. Kheradmandan, H. Berke, Organometallics 24 (2005) 920–932; (b) K. Venkatesan, Blacque, H. Berke, Organometallics 25 (2006) 5190–5200. [53] (a) D.C. Miller, R.J. Angelici, Organometallics 10 (1991) 79–89; (b) recent work:T. Kuwabara, K. Sakajiri, Y. Oyama, S. Kodama, Y. Ishii, Organometallics 38 (2019) 1560–1566. [54] (a) A.F. Hill, A.G. Hulkes, A.J.P. White, D.J. Williams, Organometallics 19 (2000) 371–373; (b) H. Kim, C. Lee, J. Am. Chem. Soc. 127 (2005) 10180–10181. [55] T. Kuwabara, Y. Aoki, K. Sakajiri, K. Deguchi, S. Takamori, A. Hamano, K. Takano, H. Houjou, Y. Ishii, Organometallics 39 (2020) 711–718. [56] (a) For recent reviews on specific aspects or applications of gold(I)-catalyzed activation of alkynes: Z. Lu, T. Li, R. Mudshinge, B. Xu, G.B. Hammond Chem. Rev. 121 (2021) 8452–8477; (b) A. Collado, D.J. Nelson, S.P. Nolan, Chem. Rev. 121 (2021) 8559–8612; (c) M. Mato, A. Franchino, C. Gracía-Morales, A.M. Echavarren, Chem. Rev. 121 (2021) 8613–8684; (d) R.L. Reyes, T. Iwai, M. Sawamura, Chem. Rev. 121 (2021) 8926–8947; (e) Z. Zheng, X. Ma, X. Cheng, K. Zhao, K. Gutman, T. Li, L. Zhang, Chem. Rev. 121 (2021) 8979–9038; (f) L.-W. Ye, X.-Q. Zhu, R.L. Sahani, Y. Xu, P.-C. Qian, R.-S. Liu, Chem. Rev. 121 (2021) 9039–9112. [57] (a) Review: F. Gagosz Synthesis 51 (2019) 1087–1099; (b) , For a review on gold-catalyzed reactions of specially activated alkynes, allenes and alkenes, touching the reactivity of haloalkynes, see:D. Campeau, D.F. León Rayo, A. Mansour, K. Muratov, F. Gagosz Chem. Rev. 121 (2021) 8756–8867. [58] (a) R.J. Harris, R.A. Widenhoefer, Angew. Chem. Int. Ed. 54 (2015) 6867– 6869; (b) R.J. Harris, R.A. Widenhoefer, Angew. Chem. Int. Ed. 54 (2015) 6867–6869. [59] (a) For inspiring early mechanistic proposals relating to this point, see for instance: P.H.-Y. Cheong, P. Morganelli, M.R. Luzung, K.N. Houk, F.D. Toste J. Am. Chem. Soc. 130 (2008) 4517–4526; (b) Y. Odabachian, X.F. Le Goff, F. Gagosz, Chem. Eur. J. 15 (2009) 8966–8970; (c) A. Simonneau, F. Jaroschik, D. Lesage, M. Karanik, R. Guillot, M. Malacria, J.-C. Tabet, J.-P. Goddard, L. Fensterbank, V. Gandon, Y. Gimbert, Chem. Sci. 2 (2011) 2417–2422; (d) , for a review on the significance of gold alkynyls in catalysis, see:C.J.V. Halliday, J.M. Lynam Dalton Trans. 45 (2016) 12611–12626. [60] L. Ye, Y. Wang, D.H. Aue, L. Zhang, J. Am. Chem. Soc. 134 (2012) 31–34. [61] A.S.K. Hashmi, I. Braun, M. Rudolph, F. Rominger, Organometallics 31 (2012) 644–661. [62] A.S.K. Hashmi, M. Wieteck, I. Braun, P. Nösel, L. Jongbloed, M. Rudolph, F. Rominger, Adv. Synth. Catal. 354 (2012) 555–562. [63] For a DFT study: M.H. Vilhelmsen, A.S.K. Hashmi Chem. Eur. J. 20 (2014) 1901–1908. [64] (a) For subsequent advances: M.M. Hansmann, S. Tsupova, M. Rudolph, F. Rominger, A.S.K. Hashmi Chem. Eur. J. 20 (2014) 2215–2223; (b) J. Bucher, T. Wurm, S. Taschinski, E. Sachs, D. Ascough, M. Rudolph, F. Rominger, A.S.K. Hashmi, Adv. Synth. Catal. 359 (2017) 225–233; (c) S. Tsupova, M. Rudolph, F. Rominger, A.S.K. Hashmi, Chem. Eur. J. 23 (2017) 12259–12263; (d) S. Tsupova, M.M. Hansmann, M. Rudolph, F. Rominger, A.S.K. Hashmi, Chem. Eur. J. 22 (2016) 16286–16291; (e) A.J. Plajer, L. Ahrens, M. Wieteck, D.M. Lustosa, R. Babaahmadi, B. Yates, A. Ariafard, M. Rudolph, F. Rominger, A.S.K. Hashmi, Chem. Eur. J. 24 (2018) 10766–10772. [65] A.S.K. Hashmi, I. Braun, P. Nösel, J. Schädlich, M. Wieteck, M. Rudolph, F. Rominger, Angew. Chem. Int. Ed. 51 (2012) 4456–4460. [66] (a) I. Braun, A.M. Asiri, A.S.K. Hashmi, ACS Catal. 3 (2013) 1902–1907; (b) A.S.K. Hashmi, Acc. Chem. Res. 47 (2014) 864–876; (c) X. Zhao, M. Rudolph, A.S.K. Hashmi, Chem. Commun. 55 (2019) 1227– 1235. [67] J. Bucher, T. Stöber, M. Rudolph, F. Rominger, A.S.K. Hashmi, Angew. Chem. Int. Ed. 54 (2015) 1666–1670. [68] J.-F. Greisch, P. Weis, K. Brendle, M.M. Kappes, J.R.N. Haler, J. Far, E. De Pauw, C. Albers, S. Bay, T. Wurm, M. Rudolph, J. Schulmeister, A.S.K. Hashmi, Organometallics 37 (2018) 1493–1500. [69] (a) P. Nösel, T. Lauterbach, M. Rudolph, F. Rominger, A.S.K. Hashmi, Chem. Eur. J. 19 (2013) 8634–8641; (b) , for general aspects and synthesis of the catalyst:A.S.K. Hashmi, T. Lauterbach, P. Nösel, M.H. Vilhelmsen, M. Rudolph, F. Rominger Chem. Eur. J. 19 (2013) 1058–1065. [70] C. Yu, B. Chen, T. Zhou, Q. Tian, G. Zhang, Angew. Chem. Int. Ed. 54 (2015) 10903–10907. [71] (a) Q. Zhao, D.F. León Rayo, D. Campeau, M. Daenen, F. Gagosz, Angew. Chem. Int. Ed. 57 (2018) 13603–13607; (b) H.-F. Wang, S.-Y. Wang, T.-Z. Qin, W. Zi, Chem. Eur. J. 24 (2018) 17911– 17914; (c) D.F. León Rayo, Y.J. Hong, D. Campeau, D. Tantillo, F. Gagosz, Chem. Eur. J 27 (2021) 10637–10648; (d) , For a formally related gold-catalyzed transformation using internal diynes and implying a different mechanism:W. Xu, G. Wang, X. Xie, Y. Liu Org. Lett. 20 (2018) 3273–3277. [72] F. Zamani, R. Babaahmadi, B.F. Yates, M.G. Gardiner, A. Ariafard, S.G. Pyne, C.J. T. Hyland, Angew. Chem. Int. Ed. 58 (2019) 2114–2119. [73] (a) J. Bucher, T. Wurm, K.S. Nalivela, M. Rudolph, F. Rominger, A.S.K. Hashmi, Angew. Chem. Int. Ed. 53 (2014) 3854–3858; (b) L. Nunes dos Santos Comprido, J.E.M.N. Klein, G. Knizia, J. Kästner, A.S.K. Hashmi, Chem. Eur. J. 22 (2016) 2892–2895. [74] Y. Wang, M. Zarca, L.-Z. Gong, L. Zhang, J. Am. Chem. Soc. 138 (2016) 7516– 7519. [75] W. Debrouwer, A. Fürstner, Chem. Eur. J. 23 (2017) 4271–4275. [76] (a) I.V. Seregin, V. Gevorgyan, J. Am. Chem. Soc. 128 (2006) 12050–12051; (b) I.V. Seregin, A.W. Schammel, V. Gevorgyan, Tetrahedron 64 (2008) 6876– 6883; (c) For a review on further related metal-catalyzed cycloisomerization reactions giving heterocyclic five-membered rings:A.S. Dudnik, N. Chernyak, V. Gevorgyan, Aldichim. Acta 43 (2010) 37–46; (d) for computational studies on gold-catalyzed synthesis of silylfurans from the cycloisomerization of allenyl and homopropargyl ketones involving 1,2-Si and 1,2-H migrations:A.S. Dudnik, Y. Xia, Y. Li, V. Gevorgyan, J. Am. Chem. Soc. 132 (2010) 7645–7655. [77] Y. Xia, A.S. Dudnik, Y. Li, V. Gevorgyan, Org. Lett. 12 (2010) 5538–5541. [78] C. Löwe, H.-U. Hund, H. Berke, J. Organomet. Chem. 371 (1989) 311–319. [79] M.P. Gamasa, J. Gimeno, E. Lastra, B.M. Martín, A. Anillo, A. Tiripicchio, Organometallics 11 (1992) 1378–1381. [80] M.I. Bruce, M. Jevric, C.R. Parker, W. Patalinghug, B.W. Skelton, A.H. White, N. N. Zaitseva, J. Organomet. Chem. 693 (2008) 2915–2920. [81] T. Miura, N. Iwasawa, J. Am. Chem. Soc. 124 (2002) 518–519. [82] V. Mamane, P. Hannen, A. Fürstner, Chem. Eur. J. 10 (2004) 4556–4575. [83] The same trend was reported for the cycloisomerization reactions of (biaryl2-yl)ethynyl(phenyl)selanes catalyzed by either InCl 3 or AuCl to give 10and 9-substituted phenanthrenyl(phenyl)selane derivatives, respectively: W. Lim, Y.H. Rhee Eur. J. Org. Chem. (2013) 460–464. [84] E. Soriano, J. Marco-Contelles, Organometallics 25 (2006) 4542–4553. [85] G. Huang, B. Cheng, L. Xu, Y. Li, Y. Xia, Chem. Eur. J. 18 (2012) 5401–5415. [86] (a) Y. Xia, A.S. Dudnik, V. Gevorgyan, Y. Li, J. Am. Chem. Soc. 130 (2008) 6940–6941; (b) A.W. Sromek, M. Rubina, V. Gevorgyan, J. Am. Chem. Soc. 127 (2005) 10500–10501. [87] (a) D.B. Walker, J. Howgego, A.P. Davis, Synthesis (2010) 3686–3692; (b) T. Nakae, R. Ohnishi, Y. Kitahata, T. Soukawa, H. Sato, S. Mori, T. Okujima, H. Uno, H. Sakaguchi, Tetrahedron Lett. 53 (2012) 1617–1619. [88] For an overall view of different aspects of our research activity: S. SuárezPantiga, J.M. González Pure Appl. Chem. 85 (2013) 721–739. [89] (a) Selected example on iodonium-triggered arylation reactions: J. Barluenga, M. Trincado, E. Rubio, J.M. González J. Am. Chem. Soc. 126 (2004) 3416–3417; (b) J. Barluenga, M. Trincado, M. Marco-Arias, E. Rubio, A. Ballesteros, J.M. González, Chem. Commun. (2005) 2008–2010; (c) J. Barluenga, E. Campos-Gómez, A. Minatti, D. Rodríguez, J.M. González, Chem. Eur. J. 15 (2009) 8946–8950; (d) J. Barluenga, M. Trincado, E. Rubio, J.M. González, Angew. Chem. Int. Ed. 45 (2006) 3140–3143; (e) J. Barluenga, M. Trincado, E. Rubio, J.M. González, Angew. Chem. Int. Ed. 42 (2003) 2406–2409; (f) J. Barluenga, H. Vázquez-Villa, A. Ballesteros, J.M. González, J. Am. Chem. Soc. 125 (2003) 9028–9029; (g) J. Barluenga, H. Vázquez-Villa, I. Merino, A. Ballesteros, J.M. González, Chem. Eur. J. 12 (2006) 5790–5805. [90] (a) Representative work: S. Suárez-Pantiga, D. Palomas, E. Rubio, J.M. González Angew. Chem. Int. Ed. 48 (2009) 7857–7861; (b) J. Barluenga, M. Piedrafita, A. Ballesteros, J.M. González, Chem. Eur. J. 16 (2009) 11827–11831; (c) S. Suárez-Pantiga, E. Rubio, C. Álvarez-Rúa, J.M. González, Org. Lett. 11 (2009) 13–16; (d) A. Ballesteros, P. Morán-Poladura, J.M. González, Chem. Commun. 52 (2016) 2905–2908. [91] (a) C. Nevado, A.M. Echavarren, Chem. Eur. J. 11 (2005) 3155–3164; (b) X.-Y. Liu, P. Ding, J.-S. Huang, C.-M. Che, Org. Lett. 9 (2007) 2645–2648. P. Fernández-Canelas, P. Barrio and José M. González Tetrahedron Letters 99 (2022) 153857 16 [92] P. Morán-Poladura, S. Suárez-Pantiga, M. Piedrafita, E. Rubio, J.M. González, J. Organomet. Chem. 696 (2011) 12–15. [93] T. Johannsen, C. Golz, M. Alcarazo, Angew. Chem. Int. Ed. 59 (2020) 22779– 22784. [94] P. Morán-Poladura, E. Rubio, J.M. González, Beilstein J. Org. Chem. 9 (2013) 2120–2128. [95] (a) For reviews on gold-catalyzed C-H activation reactions: J. Xie, C. Pan, A. Abdukader, C. Zhu Chem. Soc. Rev. 43 (2014) 5245–5256; (b) G. Meera, K.R. Rohit, G.S.S. Treesa, G. Anilkumar, J. Asian, Org. Chem. 9 (2020) 144–161; (c) For selected representative examples on gold-catalyzed C(sp 3 )-H bond activation:Y. Harrak, A. Simonneau, M. Malacria, V. Gandon, L. Fensterbank, Chem. Commun. 46 (2010) 865–867; (d) G. Cera, M. Chiarucci, F. Dosi, M. Bandini, Adv. Synth. Catal. 355 (2013) 2227–2231; (e) M.M. Hansmann, M. Rudolph, F. Rominger, A.S.K. Hashmi, Angew. Chem. Int. Ed. 52 (2013) 2593–2598. [96] P. Morán-Poladura, E. Rubio, J.M. González, Angew. Chem. Int. Ed. 54 (2015) 3052–3055. [97] For intramolecular C-H insertions of alkylidenecarbenes, see: a) J.C. Gilbert, D. H. Giamalva, M.E. Baze J. Org. Chem. 50 (1985) 2557–2563. [98] (a) For work on formally related gold-catalyzed cyclization reactions using aryl-substituted internal alkynes that involve an alternative hydride-transfer mechanism: T. Yamada, K. Park, T. Tachikawa, A. Fujii, M. Rudolph, A.S.K. Hashmi, H. Sajiki Org. Lett. 22 (2020) 1883–1888; (b) A.A. Hussein, H.S. Ali, J. Org. Chem. 85 (2000) 12682–12691; (c) see also:P.D. Nahide, J.O.C. Jimenez-Halla, K. Wrobel, C.R. SolorioAlvarado, R. Ortiz Alvarado, B. Yahuaca-Juárez, Org. Biomol. Chem. 16 (2018) 7330–7335. [99] M. Murai, K. Takai, Org. Lett. 21 (2019) 6756–6760. [100] P. Fernández-Canelas, E. Rubio, J.M. González, Org. Lett. 21 (2019) 6566–6569. [101] Our group has discovered new synthetic scenarios where the consideration of generating gold-vinylidene-like species upon catalytic activation of an haloalkyne plays a main role for the functionalization of otherwise elusive bonds, manuscripts in preparation. [102] P. Nösel, V. Müller, S. Mader, S. Moghimi, M. Rudolph, I. Braun, F. Rominger, A. S.K. Hashmi, Adv. Synth. Catal. 357 (2015) 500–506. [103] M. Kreuzahler, A. Daniels, C. Wölper, G. Haberhauer, J. Am. Chem. Soc. 141 (2019) 1337–1348. [104] M. Kreuzahler, G. Haberhauer, Angew. Chem. Int. Ed. 59 (2020) 9433–9437. [105] M. Kreuzahler, G. Haberhauer, Angew. Chem. Int. Ed. 59 (2020) 17739– 17749. [106] P.D. García-Fernández, J. Iglesias-Sigüenza, P.S. Rivero-Jerez, E. Díez, E. Gómez-Bengoa, R. Fernández, J.M. Lassaletta, J. Am. Chem. Soc. 142 (2020) 16082–16089. [107] For ruthenium-catalyzed trans-hydroalkynylation and transchloroalkynylation of internal alkynes: N. Barsu, M. Leutzsch, A. Fürstner J. Am. Chem. Soc. 142 (2020) 18746–18752. [108] (a) Y.-B. Bai, Z. Luo, Y. Wang, J.-M. Gao, L. Zhang, J. Am. Chem. Soc. 140 (2018) 5860–5865; (b) For relevant work on gold-catalyzed [2+2] alkyne-alkene cycloaddition reactions:M.E.de Orbe, L. Amenós, M. Kirillova, Y. Wang, V. López-Carillo, F. Maseras, A.M. Echavarren, J. Am. Chem. Soc. 139 (2017) 10302–10311; (c) M.E. Orbe, de; Echavarren, A. M, Eur. J. Org. Chem. (2018) 2740–2752. [109] X.-Y. Qin, F.-T. Meng, M. Wang, S.-J. Tu, W.-J. Hao, J. Wang, B. Jiang, ACS Catal. 11 (2021) 6951–6959. [110] M.E. Orbe, de; Zanini, M., Quinonero, O., Echavarren, A, ACS Cat. 9 (2019) 7817–7822. [111] (a) For a recent review on 1,2-carbohalogenation of C-C multiple bonds: D. Bag, S. Mahajan, S.D. Sawant Adv. Synth. Catal. 362 (2020) 3948–3970; (b) For approaches to prepare 1,4-enynes from haloalkynes and alkenes using an alternative transition metal as the catalyst: (iridium)S. Mondal, T. Pinkert, C.G. Daniliuc, F. Glorius, Angew. Chem. Int. Ed. 60 (2021) 5688–5692; (c) Della-Felice, M. Zanini, X. Jie, E. Tan, A.M. Echavarren, Angew. Chem. Int. Ed. 60 (2021) 5692–5698. [112] M. Kreuzahler, G. Haberhauer, J. Org. Chem. 84 (2019) 8210–8224. [113] P.D. García-Fernández, C. Izquierdo, J. Iglesias-Sigüenza, E. Díez, R. Fernández, J.M. Lassaletta, Chem. Eur. J. 26 (2020) 629–633. P. Fernández-Canelas, P. Barrio and José M. González Tetrahedron Letters 99 (2022) 153857 17