Oxidative cleavage of alkynes: a review of the methods invented so far and their application possibilities in green organic synthesis

Oxidative cleavage products of alkynes are used just as frequently in preparative organic synthesis as in industry. Compared to the number of methods for the oxidative cleavage of olefins, fewer methods for the oxidative cleavage of alkynes have been described, and most of these have only been tested on selected substrates. It is assumed that chemists avoid direct oxidative cleavage reactions of alkynes in their planning and instead prefer to use the corresponding oxidized olefin product for oxidative cleavage. In the review, the oxidative cleavage methods invented so far are presented in the literature. Among them are ozonolysis, transition metal-catalyzed oxidative cleavage methods, oxidative cleavages using main-group elements and lanthanide catalyzed oxidative cleavage methode.


Introduction to Oxidative Cleavage of Alkenes and Alkynes
Oxidative cleavage of olefins is considered one of the most commonly used reactions both in preparative organic synthesis and in the industry. 1 The reaction consists of one or more C=C double bonds that normally are cleaved to aldehydes, ketones and/or carboylic acids. The reagents and/or catalysts are used here as strong oxidizing agents to react with olefins ( Figure 1).  Figure 1. Oxidative cleavage of olefins to the corresponding aldehydes, ketones and/or carboxylic acids.
for a comparably broad range of substrates as the ozonolysis method. The second disadvantage is that the used transition metals are either expensive and/or toxic, cause pollution and/or are not easily manageable in the lab. Because of latent risks of explosion using ozone, chemists apply the transition metal regents for preparative applications. Last but not least, one of the methods developed so far can include oxidative cleavage with the use of enzymes 1,66-72 through the use of hypervalent iodine compounds [73][74][75][76][77][78][79][80][81][82] as reagents and/or oxidizing agents. In addition, reagents and/or oxidizing agents have been used for the oxidative cleavage of olefins, which do not fit into the above-mentioned categories. These include e.g. the radical oxidative cleavage of olefins using AIBN 83 or TEMPO; 84 electrochemical oxidative cleavage 85 or with the use of: -LiClO4 86 light and oxygen excited by porphyrin as a photosensitizer 87 -KHSO5 88 triethylsilyl hydrotrioxide 89 disulfides 90 -basic, neutral or acidic alumina and oxygen 91 -InCl3 and TBHP 92 -Ceric ammonium nitrate 93 -N-hydroxyphthalimide (NHPI) and oxygen 94,95 metal-organic framework (MOF): MIL-101 and H2O2 96 -Organoselenium compounds and H2O2 97 -Methane tetrabromide with the use of oxygen 98 -KSF montmorillonite 99 -CeO2 using H2O2 100,101 Although the oxidative cleavage of olefins has been studied very well, so far, there is only one review about the oxidative cleavage of alkynes. 102 In this review, not all methods discovered so far were discussed. Therefore, we want to take a closer look at the oxidative cleavage of alkynes in some detail. In order to create a better overview, the methods have been grouped according to the type of oxidative cleavage.

Importance of the Oxidative Cleavage of Alkynes in Synthesis
Compared to the oxidative cleavage of alkynes, the methods of oxidative cleavage of olefins are mostly used in the preparative synthesis and total synthesis of natural products. Most chemists avoid the direct oxidative cleavage of the alkynes, instead reducing the alkynes to the corresponding olefins. After that they mostly use the ozonolysis method or the catalyst OsO4 with an oxidizing agent (e.g. m-CPBA or H2O2, etc.) ( Figure 2  In the third part, the oxidative cleavage of alkynes using ozone known as "ozonolysis" will be studied. In the fourth part, we want to study the oxidative cleavage of alkynes using transition metal and an oxidizing agent such as O2, TBHP, m-CPBA, NaIO4, NaIO3, H2O2…etc. In the fifth part, the oxidative cleavage of alkynes using main group elements will be studied. Although the ozonolysis method can be subordinated to the part of the oxidative cleavage with the use of main group elements, we want to treat it in detail as a separate method.

Ozonolysis of Alkynes
Ozonolysis is a method that is used not only for the oxidative cleavage of alkenes but also for the oxidative cleavage of alkynes. The first known and widely accepted mechanism for the ozonolysis of alkynes was proposed by Criegee et al. and Bailey et al. Reaction intermediates 2-7 were detected and/or characterized based on the different acetylene derivatives that were produced in different reaction conditions. [103][104][105] When compound 1c was used as a substrate in carbon tetrachloride, an amorphous, polymer product 12 was obtained. In contrast, in the ozonolysis of the same substrate in acetic acid, intermediate 4 was detected instead (G = OCOCH3). The addition of pyridine to the reaction medium effected an oxidative cleavage of the C-C σ-bond to form the corresponding products 16a-b over probable intermediates 4 and 5. The investigation into the reaction mechanism of Bailey et al. confirmed the formation of these intermediates ( Figure 3).  Silbert et al. have studied the ozonolysis of 2-undecyne (1d) and 1-dodecyne (1e). They were able to show in both MS and GC analysis that intermediates 3a-f are detected at -70 °C. However, with rising temperature, they have described that the intermediates 3a-f convert to product 11. 106 Bailey et al. have further studied the mechanism of peroxide ozonolysis and non-peroxide ozonolysis with the use of the substrate 1f and 1g in methanol and ethanol. They have also confirmed that the first intermediate should be 3a-f, resulting from a 1,3-dipolar cycloaddition. Intermediate 18 (4: G = OEt or OMe) was isolated with a 25% yield in the solvent. The decomposed main product was proven by the detailed studies as intermediate 19, which could not be isolated. As a reason for the formation as the main product, they gave the resonance stabilization of the carbonyl oxide moiety in intermediate 17b by the benzene ring. They suspect that the intermediate 17b was formed in a ratio of 2.5:1 to the intermediate 17a in the reaction environment. However, the intermediate 17b is decomposed at room temperature 105,107 (Figure 4). Their results reinforce the assumption that ozone performs a 1,3-dipolar cycloaddition to the alkyne to form the first intermediate 2. 108 DeMore et al. determined the rate constant, the Arrhenius parameters and the activation energy for the ozonolysis of acetylenes and simple alkynes. [109][110][111] Later in situ IR studies by DeMore et al. 111 and Dallwingk et al. 112 have shown that at -45 °C, the carbonyl oxide peak slowly disappears and an anhydride carbonyl peak is formed instead. Another study of the reaction mechanism was carried out by using 2-butyne as a substrate in methylene chloride at -70 °C. After completion of the ozonolysis of 2butyne, the resulting intermediate was immediately epoxidized in order to capture the intermediate. The intermediates that they analyzed, which decomposed at -50°C, confirmed the formation of trioxolene (2, R 1 , R 2 = CH3). 113,114 Further investigations have shown that the intermediate 3 can immediately cleave using a reducing agent with dissociation of oxygen to form product 4 or rearrange to the product 6 ( Figure 3 and Figure 5). 108,115 Arkivoc 2023 (i) 202211942 Havare, N. Page   Later, Desvergne et al. studied the ozonolysis of crystals of diphenyl acetylene and methoxylated tolan and characterized adsorbed products on silica gel. The products resulting from crystalline diphenylacetylene and the products obtained from solutions were identical. For tolan, 80% benzoic anhydride and 15% benzil were obtained 116,117 (Figure 6). Kinetic studies were conducted in the gas phase for the ozonolysis of acetylene and its derivatives. Studies have shown that ozonolysis in the gas phase differs from the liquid phase, which also have different intermediates and products compared to the gas phase reaction. 109,[118][119][120][121] The following reaction mechanism for the gas phase ozonolysis was proposed by DeMore ( figure 7). 110 C C R R In 2001, the reaction mechanism of the ozonolysis of acetylene "1a" was theoretically calculated and described in detail by Cremer et al., which is shown in figure 3 122 . The ozonolysis of acetylene was investigated using CCSD(T), CASPT2, and B3LYP-DFT in connection with a 6-311+G (2d,2p) basis set. The reaction is initiated by the formation of a van der Waals complex followed by a [4+2] cycloaddition between ozone and acetylene (activation enthalpy ΔHa = 298 kcal/mol; experiment, 10.2 kcal/mol), yielding 1,2,3trioxolene 2, which rapidly opens to α-ketocarbonyl oxide 3. Alternatively, an oxygen atom can be transferred from ozone to acetylene, thus leading to formyl carbene, which can rearrange to oxirene or ketene. They found that the key compound is 3 in the ozonolysis of acetylene, because it is the starting point for the isomerization to the corresponding dioxirane 7, for the cyclization to trioxabicyclo[2.1.0]pentane 6, for the formation of hydroperoxy ketene 8, and for the rearrangement to dioxetanone 9. Intermediates 6-9 rearrange or decompose with barriers between 13 and 16 kcal/mol to yield as major products formanhydride, glyoxal, formaldehyde, formic acid, and (to a minor extent) glyoxylic acid. Ozonolysis of alkynes has already been tested for a wide variety of substrates: an example of the oxidation of alkynes to 1,2-dicarbonyl compounds was investigated by Wisaksono et al. They have taken acetylenic ethers as the starting materials. They have obtained α-keto ester in moderate yields. In order to obtain α-keto ester, reducing agents were used in the reaction ( Figure 8). 123  Cannon et al. have tested three different propargylic alcohols 24a-c for ozonolysis. They obtained glycolic acid products 25a-c in moderate to good yields as oxidative cleavage products, if ozone was not used in excess. When compounds 24b was used as starting material by the application of ozone in excess, the product 26 was obtained quantitatively. Another experiment showed that when sodium hydrogen carbonate was added, product 27 was immediately formed in 15% yield upon ozonolysis of starting material 24b ( Figure  9). 125 Another unusual reaction was performed by Lehmann et al.: the ozonolysis of 2,5-dimethyl-3-hexyne-2,5-diol (28a) in carbon tetrachloride, wherein only the oxidative aging product hydroxyisobutyric acid 36 was obtained. In aqueous solutions, 28a-b react to form product 35 in ozonolysis. Lehmann et al. have also proven that the compound 32 reacts in hydrogen peroxide to compound 35. 126 Bailey et al. suspected that the associated anhydride 31 should also be produced in aqueous hydrogen peroxide solution via Baeyer-Villiger rearrangement 30. Their presumption was that compound 35 would arise in aqueous hydrogen peroxide solution via the cyclization of the intermediate 30 ( Figure 10). 104  Figure 10. Ozonolysis of 2,5-dimethyl-3-hexyne-2,5-diol.  Figure 11. Ozonolysis of acetylenedicarboxylic acid 36.
Eichelberger et al. developed a synthesis of phosphorus compounds which have an alkyne functional group in α-position. Ozonolysis of phenyl ethynyl diphenyl phosphine oxide (41) gave benzoic acid (42), formic acid (45), and diphenyl phosphinic acid (44), which was formed from diphenyl phosphinic carboxylic acid 43. They obtained the products in very good yields ( Figure 12). 128 As can be seen, it depends on the reaction condition whether 1,2-dicarbonyl compounds or a peroxo compound are obtained as the main product(s) in the ozonolysis of alkynes.

Ru-catalyzed oxidative cleavage of alkynes
Ruthenium-catalyzed oxidative cleavage of the olefins was discussed above. It is mostly used for the oxidative cleavage of olefins; RuCl3 is used as a catalyst with a strong oxidizing agent (see introduction).  Figure 13. Ozonolysis of alkynes using RuO2 as catalyst and KHSO5 as oxidizing agent.
According to Yang et al., the reaction mechanism of oxidative cleavage consists mainly of two steps. The first step in the reaction mechanism is the formation of the active catalyst by peroxomonosulfate anion (HSO5 -). This is responsible as an oxidizing agent to oxidize ruthenium dioxide in situ to produce the active catalyst ruthenium tetroxide "RuO4". The ruthenium tetroxide adds to alkyne to form intermediate 62. Step: Figure 14. Proposed general mechanism of oxidative cleavage of alkynes using RuO2 as catalyst and KHSO5/NaHCO3 as oxidazing agent.
Griffith et al. found out that the yields of the oxidative cleavage products using RuCl3 as a catalyst and IO(OH)5 as an oxidizing agent are strongly dependent on the used solvent(s). The best yields were obtained in carbon tetrachloride. 21 Griffith et al. have described the following in general terms in their detailed review of the ruthenium-based oxidation of organic substances: The reagent consists of a strong oxidizing agent (such as O2, H2O2, TBHP, NaIO4, NaIO3,…etc.) and a catalyst, which is a salt of a transition metal (ruthenium dioxide) in oxidation state IV. Generally, the catalyst is first oxidized with a strong oxidizing agent to form the active catalyst in situ, which reacts with the starting material. In this case, ruthenium is oxidized by sodium periodate to achieve oxidation state VIII, whereby the oxidizing agent is reduced. In this case, sodium periodate is reduced to sodium iodate, which is used in stoichiometric amounts. In other words, Ru(VIII) oxidizes the substrate to the product, reducing itself to Ru(IV). During the oxidation, a total of two oxygen atoms is transferred to the substrate via the catalyst per using one molecule substrate. This, in turn, is oxidized by NaIO4, whereby the catalytic cycle starts anew ( Figure 15). 133   Potential diagram of RuO4 runs over [RuO4]to dianion [RuO4] 2-, then to RuO2 with +1.0 V, +0.59 V and +0.2 V respectively ( Figure 16). 134 Figure 16. Reaction of RuO4 to RuO2.

Substrate
The infrared spectra of gaseous and pure liquid ruthenium tetroxide show that, on the assumption of Td molecular symmetry, v3(F2) is at 913 cm -l and v4(F2) at 330 cm -l . The formation of RuO4 was also confirmed by Raman spectroscopy (Figure 17). 136 Kumar et al. found a method using charcoal-supported and recyclable elemental ruthenium (Ru/C (5%)). The catalyst is prepared in benzene using charcoal (KB, 100 mesh, surface area 1500 m 2 /g, 1.25 g) and [RuCl2(p-cymene)]2 (250 mg) at room temperature, which is filtered off and washed with DMF. 137 Herein, they report for the first time a recyclable catalytic system for performing the oxidative cleavage of alkynes to carboxylic acids and alkenes to aldehydes, respectively, by using Ru/C (5% grafted), which can be reused without loss of activity. In this methodology, Ru/C (5%) was used. Initially, oxidation of phenylacetylene (1 mmol, 120 mL) was checked using Ru/C (2.5 mol%, 50 mg) in a biphasic solvent of wateracetonitrile (1:1, 5 mL), NaHCO3 (2.5 equiv.) at room temperature using oxone (614 mg, 1 mmol) as the stoichiometric oxidizing agent ( Figure 19) Figure 19. Oxidative cleavage using Ru/C (5 % grafted) as recyclable catalyst and oxone as oxidazing agent.
The advantage of this method is that the catalyst Ru/C is a heterogeneous catalyst and can be easily separated from the reaction environment by simple filtration and can be restored (Table 1). This catalyst also has the advantage that it can be used in environmental friendly solvents such as water.  Figure 20).
Another catalyst ruthenium complex is [(Me3tacn(CF3CO2)2Ru III (OH2)](CF3CO2) 76 which is used as a silica gel-immobilized or supported form "76-SiO2" where Me3tacn = 1,4,7-trimethyl-1,4,7 -triazacylcononane 74, was prepared by Che et al. and used for the oxidative cleavage of alkynes ( Figure 21). The catalyst is heterogeneous and recyclable that is easily separable from the reaction environment and for the oxidation of alcohols and also can be used for the oxidative cleavage of olefins. 25    Che et. al. have tested not only alkyne substrates, but a range of olefin substrates and 1,2-diols. Unfortunately, they did not propose a mechanism for the oxidative cleavage of alkyne in their manuscript. Instead, they studied the reaction mechanism with a few substrates using ESI-MS.Based on their studies using the ESI-MS and starting materials, the reaction mechanism could proceed based on their studies as follow: 25,136 (Figure 22): first, the trifluoroacetate ligands and the water cleave from the catalyst 76, which was fully characterized by X-Ray analysis 25 , and at the same time the ruthenium is oxidized using the oxidizing agent (here is the oxidizing agent: hydrogen peroxide). The intermediate 77 is formed in situ, complexes the olefin under formation of 78. The simultaneous addition of two oxygen atoms to olefin forms en-1,2-diol complex 79. They believe that the rate-determining step is the [3+2] addition of the ruthenium  Figure 22. Proposed reaction mechanism for the oxidative cleavage of alkyne using catalyst 80 and aqua H2O2 as oxidizing agent.
Che et al. have tested the oxidative cleavage of alkynes and olefins with ruthenium nanoparticles immobilized on hydroxyapatite "nano-RuHAP", which is a heterogeneous catalyst and recyclable 140 . They mostly used this heterogeneous catalyst for the oxidative cleavage of olefins. In their manuscript, only one alkyne substrate is tested for the oxidative cleavage using "nano-RuHAP". The catalyst "nano-RuHAP" was prepared as followed: First, according to Fievet's protocol, 141 ruthenium colloids were synthesized by the reduction of RuCl3•X H2O (0.32 mmol) in 1,2-propanediol (100 mL) in the presence of sodium acetate (1 mmol) at 150 °C. The ruthenium reduction was scanned using UV/VIS spectroscopy. The disappearance of the peak in 400 nm indicated that the reaction has already ended. The ruthenium colloid (3.2 mm) that is produced in this way, showed excellent stability. Successful immobilization of the ruthenium nanoparticles was achieved by treating the colloidal solution with calcium hydroxyapatite (0.4 g) and H2O (50 mL) for 24 h 140,142 . The following reaction was tested with the catalyst "nano-RuHAP". The nano-RuHAP with 1-(prop-1ynyl)benzene (82a) as substrate and oxidant (oxone) in acetonitrile-water mixture was used. The oxidative cleavage took place in 82% yield for benzoic acid (82b) (Figure 23). Che et al. have not suggested a mechanism in their manuscript. However, they propose that the oxidative cleavage of phenylacetylenes with nano-RuHAP would proceed in a similar way to the reaction mechanism described and discussed in figure 20. The only difference is that no charcoal is used here, instead the ruthenium nanoparticles are surrounded by calcium hydroxyapatite.
Another interesting example is presented by Datta  The following mechanism has been proposed for the oxidative cleavage of 1,1-dialkyl ethynyl alcohols: According to Datta et al. through the dissociation of the catalyst 83, the active catalyst 84 is formed in situ. An acetonitrile ligand is removed and the triple bond coordinates to the Ru-metal forming a weak π-alkyne complex 85. 145,146 The π-alkyne complex changes to a σ-complex through the rearrangement of the alkyne proton to ruthenium and the intermediate 86 is formed, whereby the triphenylphosphine ligand is cleaved. In the presence of lithium triflate, the hydroxide anion is cleaved by lithium, whereby ruthenium allenylidenium species 87 is formed. [147][148][149][150][151] The attack of the hydroxide anion produces ruthenium acyl species 88, which is further formed into intermediate 89 through decarbonylation. The product is formed by the elimination of carbon monoxide, and the catalyst is regenerated in situ ( Figure 25). 152     Another interesting reaction was published by Shimada et al. in 2003. This type of reaction is the oxidative cleavage of alkyne followed by the addition of 2-aminophenol. They studied the oxidative cleavage of diynes. They found that the diynes react in the presence of Ru3(CO)12 as a catalyst and NH4PF6 as an additive to the corresponding ketones and benzoxazoles ( Figure 29). 158 The reaction proceeds through oxidative cleavage of the C-C triple bond (path a) as well as of the C-C σ-bond (path b). They obtained a mixture of product(s) with relation 3:1 product mixtures (path a (benzoxazoles): path b (benzoxazoles)). 12 (1 mol %), NH 4 PF 6 (3 mol %) 80°C, 1 day

Mn-catalyzed oxidative cleavage of alkynes
There are only a few references on the oxidative cleavage of alkynes with the use of potassium permanganate. Lee et al. have tested a series of alkyne using potassium permanganate. They have found that, depending on the alkyne used, either 1,2-dicarbonyl compounds or the corresponding acids were obtained. The Mn(VII) species is meanwhile reduced to Mn (IV) ( Figure 30). Figure 30. Oxidative cleavage of alkynes using potassium permanganate.  Figure 31. Reaction mechanism of oxidative cleavage of alkynes using permanganate. 159 According to Lee et al., the reaction mechanism is similar to the mechanism of the oxidative cleavage of olefins using permanganate. With the use of permanganate, the oxidative cleavage of alkyne proceeds as    Although Shaikh et al. investigated the reaction mechanism for the oxidative cleavage of olefins with GC-MS, however, there was no specific reaction-mechanistic investigation for the alkynes (see supporting information) 160 . The reaction mechanism of Fe-catalyzed oxidative cleavage of olefins has also been studied by Islam et al. 161 Enthaler et al. have studied the Fe-catalyzed oxidative cleavage in more detail. They have tested a range of iron salts with different ligands and additives in hydrogen peroxide as an oxidant. They found out that ligands, additives and the different iron salts that they used in the reaction, have a very big effect on the yield of the products. Several salts such as FePO4, FeBr3 and FeCl3 have been used. With the use of iron phosphate, they obtained less than 1% benzil as a product. With the use of iron bromide, they isolated 14% of benzil. The rest was unreacted tolane The best yield (99%) was isolated by the use of iron chloride. The reason for the difference in yields with the use of different iron salts was not explained in their paper. Without the use of ligands, they had a very good yield after a reaction time of 4 hours. Furthermore, the use of iron chloride leads to a reduction in the reaction time by one hour compared to the lack of use of a catalyst. For this purpose, they had carried out a GC-MS investigation for the formation of incorporated oxygen in diphenyl acetylene. The study of GC-MS confirmed their proposal and, (194 g*mol -1 (116 + oxygen = 117) was a peak detected. The best yield of benzil was achieved using N,N,N',N'tretramethylethylenediamine (TMEDA). The unligated iron produced the intermediate 117 with 49% after one hour. Comparing the oxygen incorporation of the modified (49%) and unmodified (26%) iron-catalyzed oxidation reactions, significant advantages were observed with the addition of a ligand. A serious of aromatic amines were tested, the best performances were demonstrated by 4-dimethylamino pyridine (DMAP) with 55% incorporated oxygen. DMAP was tested as a ligand for 8 different alkynes as starting materials. In the case of R 1 ,R 2 = -COOEt or -COOMe, less than 1% cleavage product was obtained. The best yields (37-99%) were obtained using arylalkynes as substrates ( Figure 33). They tested in total 9 different substrates. They obtained 82-99% of 1,2-carbonyl compounds as products. 162 [  Figure 33. Oxidative cleavage of alkynes using FeCl3 as catalyst, H2O2 as oxidizing agent and/or DMAP as ligand. 162 Based on the reference, the reaction mechanism proceeds in the opinion of Enthaler et al. as follows. [163][164][165][166][167][168][169][170] As a key step, the oxidation reaction of the triple bond of starting material 116 proceeds to form an oxirene intermediate 117, which was probably detected by using GC-MS. 162 The active catalyst is here iron(V)-oxo species. 160 Based on this, two follow-up reactions for the intermediate 117 are feasible. First, a rearrangement to a ketene 118 could occur, which would subsequently be either oxidized to a ketone 119 or hydrolyzed to a carboxylic acid 120. Second, the oxirene could be oxidized to the corresponding 2,4-dioxabicyclo [1.1.0]-butane 121, which could easily rearrange to the desired 1,2-dione 122 ( Figure 34).   The method was not only tested for oxidative cleavage of alkynes but also for the oxidative cleavage of olefins. They tested in total ten olefins and obtained up to 84% yield. However, no oxidative cleavage was observed for the alkyl substituted olefins. 171 According to Yap et al. the reaction mechanism with 1ethynylbenzene proceeds as followed: first the active catalyst 124 is formed in situ with hydrogen peroxide. According to Yap

Mo-and W-catalyzed oxidative cleavage of alkynes
Another method for oxidative cleavage of the alkynes was developed with the use of molybdenum or tungsten. However, there is a known method in the literature with the use of molybdenum, which was developed by Ballistreri et al. As additive a Na2MO4 (M = Mo (IV), W (VI)) and Hg(OAc)2 salt were used and a dilute hydrogen peroxide solution as an oxidizing agent. This catalysis system is based on phase transfer catalysis. The catalysts were first tested in dioxane in homogeneous solution. However, low yields were obtained. A two-phase system brought much better results. The substrate, shown in figure 37, and Hg(OAc)2 were placed in DCM and aqueous hydrogen peroxide and Na2MoO4•2H2O or Na2WO4•2H2O in a buffered solution. With these reaction conditions, the best yields for the oxidative cleavage of alkynes have been obtained. However, for two substrates the reaction conditions were optimized and applied. For the oxidative cleavage of 1-phenylacetylene with the catalyst Na2WO4•2H2O 129 and Aliquat 336 as phase transfer agent, they obtained 93% benzoic acid. In contrast, the yield decreased if they used Na2MoO4•2H2O 130 as the catalyst instead and HEPT (hexaethylphosphoric triamide) as the phase transfer agent. In the oxidative cleavage of 1-hexyne, a better yield (90%) was also obtained when tungsten salt was used as the catalyst. With molybdenum as a catalyst, they were able to isolate a 59% yield of the cleavage product. In both cases, HEPT as the phase transfer agent was used. The tungsten (VI) apparently plays a crucial role in improving the yield regardless of which phase transfer agent is used 172 . In fact it is known that cationic PT agents such as Aliquat or Adogen extract anionic oxidant species such as [MO5(OH)(H2O)]while neutral ligands such as HMPT or HEPT extract neutral species such as MO5 (H2O). 173,174 It has been reported that these two peroxo species display different reactivities toward substrates such as olefins or alcohols ( Figure 37).  However, Ballistreri et al. did not suggest any reaction mechanism in their manuscript. It is assumed that the reaction mechanism proceeds with the use of W(IV) and Mo (IV) similarly to the standard Ru-catalyzed reaction mechanism ( Figure 38) Figure 38. Suggested oxidative cleavage of alkynes using Na2Mo4•2H2O or Na2WO4•2H2O as catalysts.
That is, the attack of the tetraoxo metal anion occurs first to bind the alkyne triple, whereby the

W-catalyzed oxidation and/or oxidative cleavage of alkynes
Ishii et al. have developed a method for the oxidation of alkynes. A catalyst has been synthesized that can be used to a large extent in the oxidation of various organic compounds. 54,[175][176][177][178][179][180][181][182][183] The method was mainly tested on different substrates. For instance, it has been applied to 4-octyne and diphenylacetylenes. In the oxidation of diphenylacetylenes, benzil in a high yield of 93% was obtained. When 4-octyne was oxidized, three different products were isolated in 5%, 15% and 62%. These are as followed: butyric acid (5%), (E,Z)oct-5-en-4-one (15%) and 1-(3-ethyloxiran-2-yl) butan-1-one (62%) (Figure 39)  According to Ishii et al. the reaction mechanism proceeds exactly as described in Figure 74. The same intermediates result as in Figure 74. However, which active catalyst intermediates the reaction proceeds was not reported in the article.

Pd-catalyzed oxidative cleavage of alkynes
The oxidative cleavage of alkynes by Pd(OAc)2, which was obtained commercially, to the ester was published in 2008 by Wang et al. (Figure 40) Figure 40. Oxidative cleavage of alkynes using Pd(OAc)2 as catalyst Totally 11 substrates were tested. During the oxidative cleavage of 4-octyne, they were able to isolate 18% butyric acid. With the remaining substrates, esters, as cleavage products between 73-89% yields were received. A number of additives were tested. It has been found out that the additives play a crucial role in improving the yields. For example, when they used CuCl2•2H2O as an additive, they isolated 43% yield of methyl benzoate for the oxidative cleavage of diphenylacetylene at 100 °C. When ZnCl2•2H2O was used as an additive at 100 °C, 90% yield Methyl benzoate was obtained. It has been also found that zinc chloride gives just a poor yield (43%) at 60 °C. Unfortunately, why the use of zinc chloride produces higher yields at high temperatures than the other additives in the same reaction conditions, this could not be explained. In addition to the normal alkynes, two 1,2-dialkyneses as substrates in the same reaction conditions were tested. In the oxidative cleavage of diphenyl-buta-1,3-diyne (143a) in methanol, 83% yield for methyl benzoate (144a) were able to be isolated. Use of hexadeca-7,9-diyne (143b), gave 77% yield on n-propyl heptanoate (144b) (Figure 41). 185

Me
Me + n-PrOH  Figure 41. Oxidative cleavage of 1,2-dialkynes using Pd(OAc)2 Here, according to the list of carbons for the substrates, formic acid, carbon monoxide and/or carbon dioxide should actually be produced as residual decomposition products. This is however not being mentioned in the article. The disadvantage of the method is that they did not test the reaction in solvents other than alcohols and used other alkyl substituted alcohols or aryl substituted alcohols which are solids as reactants. The reaction mechanism was investigated using the oxidative cleavage of diphenylacetylene. According to Wang et al. The reaction mechanism proceeds as follows ( Figure 42): They propose that the alcohol used is first added to the triple bond of the alkyne, which is also used as a solvent, with the help of the catalyst, with methoxy-    Figure 43. Oxidation of alkynes using Pd-metal to 1,2-dicarbonyl compounds.
Heterodimer nanocrystaline catalyst "Pd-Fe3O4" can also be used for the oxidation of alkynes to 1,2diketones, which can be easily separated from the reaction environment by magnetic separation and can be reused. The Pd-Fe3O4 synthesis was performed by two-step thermal decomposition of a mixture solution composed of iron acetate, palladium acetate, oleic acid and oleylamine. In a general synthesis, Pd(acac)2 and Fe(acac)3 was added into a solution of containing oleic acid and oleylamine and the mixture was heated.
Fifteen derivatives of diphenylacetylene were tested in the presence of Pd-Fe3O4 and CuBr2 as additive in a solvent mixture of 1,4-dioxane-H2O (5: 1). They obtained 1,2-diketones as products between 77 and 98% yields. However, the authors did not propose a reaction mechanism for the oxidation of alkynes in their manuscript ( Figure 44).

Rh-catalyzed oxidative cleavage of alkynes
Rhodium is a highly flammable, expensive and rare transition metal. In recent years, rhodium has been used frequently as a transition metal in catalysis. One would expect that it was also used in the oxidative cleavage of alkynes. However, few scientific articles on the Rh-catalyzed oxidative cleavage of alkynes have been published until now. For example; Park et al. have developed a method in which both an oxidative cleavage of the triple bond and an addition of the aryl groups were occurred. After phenylacetylene reacted with Ntosyl azide in the presence of copper (I) thiophene-2-carboxylate (CuTC, 10 mol%) in toluene, Rh2(Oct)4 (1 mol %) and azulene 156 were added to the reaction mixture, which was subsequently treated with Cs2CO3, resulting in the formation of 1-benzoyl azulene 157 in 66% yield in one pot ( Figure 45). They tested the same reaction for the olefins and the reaction mechanism of the olefins was only studied. The reaction mechanism was proposed using the labeling method ( 18 O2) in the manuscript. 188

Ni-catalyzed oxidative cleavage of alkynes
Another oxidative cleavage method was presented by Urgoitia et al. in 2015. They found that mild oxidation conditions would be enough to split off the alkyne oxidative. In this method, atmospheric oxygen is used as the oxidizing agent under normal atmospheric pressure. They have tested a number of aryl substituted alkynes. The method is valuable because compared to other transition metals such as rhodium, ruthenium, osmium, palladium, tungsten and molybdenum, nickel is relatively cheap, nontoxic and often easy to handle. However, what may have been lacking for the industry to present a better method than ozonolysis is that the method has not been extended to include alkylalkynes (figure 47). They have dissolved fourteen substrates with the use of nickel bromide in 10 -5 mol% as a catalyst in low-molecular-weight grade of polyethylene glycol (PEG-400) and 159 or 160 as ligands in 10-5 mol% in the presence of sodium acetate tested in acetonitrile. Except for (1-(4-(2-phenylethynyl)phenyl)ethanone), they got good to very good yields. 188 The ligands are either commercially available, such as Ligand 169, or can simply be prepared in one step, such as ligand 170 (Figure 47).

Re-catalyzed oxidative cleavage of alkynes
Rhenium is a transition metal which is not toxic but is very rare and expensive and some of its reagents flammable. Hence, using this metal in large quantities as a catalyst in industry would not be beneficial. Methylrhenium trioxide (CH3ReO3, MTO) is one of the catalysts, which is used for both the oxidative cleavage of olefins and alkynes. 168,192 The catalyst has two active forms 176 and 177, which have been characterized crystallographically ( Figure 49). Zhu et al. have found that the oxidation of both terminal and internal alkynes by hydrogen peroxide is also catalyzed by MTO.   Figure 50. Oxidative cleavage of alkynes using MeReO3 as catalyst and H2O2 as oxidizing agent in methanol or acetone.
Zhu et al. tested a total of 5 substrates in different solvents. They received either 1,2-diketones or carboxylic acids or esters, depending on the solvent and / or substrate. For example, when using acetone, the oxidative cleavage products were obtained to very good yields. When using methanol as a solvent, they have mainly obtained esters. Here, the solvent methanol not only acts as a solvent but reacts with one of the intermediates to form ester as the end product.

Os-catalyzed oxidative cleavage of alkynes
Strangely enough, although osmium tetroxide is a toxic substance, it is often used in the oxidative cleavage of olefins. Because in many organic chemistry textbook is given as an example for the oxidative cleavage, the second famous method under the chemist after ozonolysis..The method leads to very good yields both in the oxidative cleavage of olefins and in the oxidative cleavage of alkynes. There are many examples of the oxidative cleavage of alkynes. [11][12][13][14][15]17 The first example is the selective oxidative cleavage of alkyne building blocks with the use of OsO4 (5 mol%) as the catalyst and NaIO4 (10 eq.) as the oxidizing agent. A general method for the solid-phase synthesis of carboxy-functionalized peptides by oxidative cleavage of the corresponding alkynes is presented. Clean and quantitative conversion is enabled by the addition of bases, such as DABCO (1,4-Diazabicyclo (2.2.2) octane) and hexamethylenetetramine (HMTA), to the classical OsO4/NaIO4 mixture. It is surprising with the method that the reaction proceeds quite selectively. This means that the strong oxidation reaction conditions (OsO4/NaIO4) do not decompose the starting material or a reaction only takes place between OsO4 and alkyne. Nielsen et al. have shown that, regardless of the length of the peptides, the alkyne-functionalized peptide molecules bound to one side with a long amino acid polymer residue (eg Gly-HMBA-PEGA800), which is also known as solid-phase synthesis, can be selectively oxidized be split off. Depending on the method, either DABCO (1,4-diazabicyclo (2.2.2)octane) or HMPA were used as additive bases in the method. A number of peptides were used in the method using the solid phase synthesis method. For example, peptide 184 with an alkyne group can be cleaved to the corresponding carboxylic acid peptide 185 in the presence of a strong base (hexamethylenetetramine = HMPA) and over 95% yield. It is important to note that the free amine groups were protected with a Boc group. This is done, for example, in the oxidative cleavage of 186 to 187. Since OsO4 reacts with NaIO4 also with a double bond, the double bond and the triple bond of the compound 188 cleaves oxidatively to 189. The resulting carbonyl group reacts with the nitrogen atom of the amide group and creates a cyclized peptide molecule 189. Twenty amino acid residues were used in compound190. Besides tryptophan (yield: 32%), the oxidative cleavage product 191 was obtained in very good yields. Even simple α-alkynyl amino acids react like compound 190 under this reaction condition to give 191, whereby the polymer residue (HMBA-PEGA800) is also split off ( Figure 52). 193 The development of the method with solid-phase oxidative cleavage with other substrates is Le Quement et al. succeeded. However, they used a different peptide-polymer residue (R = Ala-Phe-Gly-HMBA-PEGA800). Just like the peptides, they had obtained good to very good yields. Three different reaction conditions were optimized and seven different substrates each based on (ortho, meta or para) trimethylsilylphenyl peptide polymer residue 194 were tested. In the first reaction condition, the corresponding carboxylic acids 195 were isolated in high yields by oxidative cleavage. Here, OsO4 was used as the catalyst, NaIO4 as the oxidizing agent, HMTA as the base and tert-butylammonium fluoride as the phase transfer catalyst in a THF and water mixture. The second reaction condition is optimized for the synthesis of α-ketocarboxylic acids 196. A total of seven substrates were also tested here. The third optimization is the synthesis of (ortho, meta or para)acylphenyl peptide polymer residue 197 only through the use of trifluoracetic acid (Figure 53). 194   Figure 53. Solid-phase oxidative cleavage using OsO4 and NaIO4 Oxidative cleavage of alkynes with the use of OsO4 and NaIO4 are often used in the total synthesis of natural products. For example, one of the many examples is the synthesis of β-lactam antibiotics thienamycin and PS-5. Compound 188 was first treated with the KMnO4/NaIO4 oxidant. The compound decomposed and left many products that could not be characterized. However, with the use of OsO4 and NaIO4, the oxidative cleavage product 189 was obtained in high yield ( Figure 54). 195,196   Another example for the use of OsO4 and NaIO4 is the total synthesis of miharamycin A and B. During the synthesis of building blocks, compound 203 is oxidized to compound 204 by oxidative cleavage ( Figure  55). 197 Arkivoc 2023 (i) 202211942  Figure 55. Total synthesis of Miharamycin A and B using OsO4 as catalyst and NaIO4 as oxidizing agent.

4.12.Au-catalyzed oxidative cleavage of alkynes
Gold is very expensive, but easy to handle a transition metal in the lab. A detailed review of the goldcatalyzed alkyne oxidation was given by Ye et al. 198 Figure 56. Oxidative cleavage of (Z)-enynols to cyclic butenolides using AuCl(PPh3) as catalyst and O2 as oxidizing agent.
Although no precise reaction mechanism was described in their manuscript, according to Liu et al. in the reaction mechanism first Au(I) acts as a single-pot catalyst to catalyze cyclization to dihydrofurans followed by an efficient oxidative cleavage reaction, which resulted in the cleavage of C≡C triple bonds in (Z)-enynols 205 and converting it to butenolides 206 directly. It is also indicated that the cyclization was not hampered by the atmosphere of dioxygen. 199 Another example of the oxidative cleavage of alkynes using gold as a catalyst was described by Das et al. They have found that the 1-(1-alkyloxybut-2-ynyl)benzenes are cleaved oxidatively to form the corresponding alkyl benzoate 208 and alkyl acetic acid 210. Part of the starting material is oxidized to the olefins (E) -4-phenylbut-3-en-2-ones 209. 200 The solvent plays a decisive role both for improving the yield and for the alkyl part of the ester formed, because the solvent attacks after the oxidative cleavage or after the formation of the carboxylic acid. When no solvent was used, poor yields were obtained. When methanol is used as the solvent, there is almost only an oxidative cleavage of the triple bond. In this reaction condition, the compounds 208 and 210 were isolated in very good yields. When the reaction was carried out in water, only the substrates were oxidized to (E)-4-phenylbut-3-en-2-one 210 in very good yield. Oxidative cleavage products 208 and 210 were mainly observed with the use of ethanol. With the use of long-chain alcohols such as n-propanol, the product contains more of compounds 208, 209 and 210 ( Figure 57).  Twelve further derivatives of the compound 207 were tested with the use of PPh3AuCl as a catalyst and oxygen as the oxidizing agent in methanol and the oxidative cleavage products 212 were isolated in good yields. Surprisingly, the substrate 211 reacts by cleaving the C−C σ-bond to form the compound 213 if the tert-butyl group was used in the alkyl radical. They justified the formation of compound 213 through the mechanism of oxidative cleavage. Derivatives of thiophene (2-(1-methoxybut-2-ynyl)-3-methylthiophenes) and derivatives of naphthalene (2-(1-methoxybut-2-ynyl)naphthalenes) also cleave oxidatively to their corresponding esters in this reaction condition ( Figure 58). 198    To confirm the proposed reaction mechanism, the starting material was labeled with heavy oxygen. They have carried out two experiments to clarify the mechanism. They first labeled the oxygen of the methoxy group and as a result, they discovered the labeled oxygen only formed on one of the esters. The second experiment was marking the water. They did not observe any labeled oxygen in the products (Figure 61).

Oxidative Cleavage of Alkynes Using Main Groups Elements (C, Br, I, In)
Another method for the oxidative cleavage of alkynes is the use of the main group elements in high oxidation states. The hypervalent compounds with high oxidation levels are mostly used here. A great advantage of the method is that the reagents are relatively cheaper compared to transition metal reagents and that they have less environmental impact compared to transition metal reagents. However, they are mostly explosive reagents when exposed to heat.

Oxidative cleavage of alkynes using hypervalent λ 3 -iodane reagents
Moriarty et al. developed a metal-free method in 1988 that can be used practically. This method is important because it is less polluting compared to using transition metals. They tested one of the many hypervalent iodine reagents in oxidative cleavage. [201][202][203][204] The hypervalent iodine reagents that are most commonly used in the oxidative cleavage of organic molecules are iodosylbenzene, 205 Figure 63. Mechanism of oxidative cleavage of alkynes using FPIFA.
A recently published work is on the use of phenyliodinebis(trifluoroacetate) 235 (PIFA) in the oxidative cleavage of alkynes in mild reaction conditions, which can be easily prepared in one step from iodobenzene in 87% yield. 207 Jiang et al. found out that the alkynes can be cleaved oxidatively directly to the ester. They tested a total of 28 substrates and isolated the esters in yields between 52 and 90%. No reaction took place with an 4-aminophenyl group (R = 4-H2N-Ph-) and a 3-hydroxyphenyl group (R = 3-HO-Ph-). They suspect that the amine group and the hydroxyl group react with the iodine of the PIFA 235 and therefore there is no cleavage and therefore no esterification ( Figure 64). 210 Arkivoc 2023 (i) 202211942 To confirm this, they detected the masses of α-hydroxyacetophenone and 1-phenyl-1,2-propanedione. Separately, they conducted two experiments. α-hydroxyacetophenone and 1-phenyl-1,2-propanedione were tested again with PIFA in methanol and they have almost the same yields as the oxidative cleavage reaction starting from phenylacetylene and 1-phenylpropyne with PIFA to give the methyl benzoate ( Figure 65). 210 Arkivoc 2023 (i) 202211942   Figure 66. Oxidative cleavage of alkynes using iodine as oxidizing agent. Miyamoto et al. have used iodomesitylene as a catalyst. They have tested this method not only for the alkynes but also for the oxidative cleavage of olefins. In this method the active reagent, which is the hypervalent iodine compound and is responsible for oxidative cleavage, was formed in situ. Compared to the above methods, the iodine compound is not used in the equivalent amount, but in the amount of catalyst ( Figure 67). 77 Arkivoc 2023 (i) 202211942  Miyamoto's CSI-MS studies have also confirmed the presence of 245 and 247. 77 For the oxidative cleavage of alkynes, one can suggest the following reaction mechanism with the prior knowledge of the intermediates of the oxidative cleavage of olefins in situ 77,203 and the reaction mechanism of the other similar reagents (e.g. FPIFA) 218 for alkynes ( Figure 68). First, just like in the oxidative cleavage of olefins, 77 the active catalyst hydroxy-λ 3 -iodane 245 is formed in situ. This catalyst probably oxidizes the alkyne in several intermediate stages to α-hydroxy ketone 246, while this intermediate product was previously detected with the use of FPIFA in GC-MS with different substrates (see figure 65) 218. This intermediate product reacts with the active catalyst hydroxy-λ 3 -iodane 235 to form the cyclic dialkoxy-λ 3 -iodane 247, which further cleaves oxidatively to the corresponding aldehydes. These aldehydes oxidize further under these strong oxidation conditions to the corresponding end products "carboxylic acids". Unfortunately, in the article no further studies were carried out on the reaction mechanism towards the formation of the aldehydes. This important intermediate for the explanation of the reaction mechanism could have been easily demonstrated with the variable temperature (VT)-NMR study. After the formation of the products, iodomesitylene is formed again in the reaction, which react again with m-CPBA to form the active catalyst hydroxy-λ 3 -iodane 245 and the catalysis cycle starts again (Figure 68).

Oxidative cleavage of alkynes using carbon tetrabromide and molecular oxygen
Another environmentally friendly and metal-free method was developed by Yamaguchi et al. They used tetrabromomethane as the catalyst and molecular oxygen as the oxidant in a water/EtOAc mixture, where molecular oxygen was electronically excited with the use of a 400 W mercury lamp and water was used in catalytic amounts. A total of 12 substrates, including phenylacetylenes and its derivatives, 1-nonyne, 2acetylenyl pyridine and 3-acetylenyl thiophene, were tested with this method. In the same reaction condition in the dark or with the use of a fluorescent lamp, no reaction took place. To optimize the reaction conditions, the oxidative cleavage of phenylacetylene was selected as the standard reaction and a number of catalysts such as CBr4, NBS, Br2, HBr (48% aq.), LiBr, NaBr, KBr, AlBr3 and SmBr3 were tested. The lowest yield (1%) was achieved with the use of sodium bromide and the highest yield (86%) was achieved with the use of tetrabromomethane. They also found that the addition of water in catalytic amounts plays a crucial role in improving the yield. Without ethyl acetate only in water as solvent, 8% benzoic acid was isolated ( Figure  69). 214   Figure 70. Proposed mechanism for the oxidative cleavage of alkynes using CBr4 as catalyst and O2 as oxidizing agent.

Oxidation of aryl substituted alkyne to 1,2-diketone using 9,10-dicyanoanthracene and biphenyl
A method for the synthesis of 1,2-diketones through the mild and metal-free catalytic photooxygenation of alkynes is described by Qin et al. This reaction, using 9,10-dicyanoanthracene (DCA) 266 as a catalytic sensitizer with / without biphenyl (BP) as a co-sensitizer, readily delivers a variety of desired products upon visible-light irradiation. They tested a total of 23 diaryl-substituted alkynes and arylalkyl-substituted alkynes ( Figure 71). Without the use of biphenyl 271, they received poorer yields for these substrates. The radical cation of biphenyl is more reactive and thus the radical cation can be more easily transferred to the substrate. The photocatalyst / redox mediator pair 9,10-dicyanoanthracene (DCA) and biphenyl (BP) has often been employed as a photooxidation system. [215][216][217] The singlet excited state of DCA ( 1 DCA*), which is traditionally generated in acetonitrile by irradiation with a Hg lamp, is an excellent one-electron oxidant [(E1/2) = 1.99 V vs. saturated calomel electrode (SCE)]. 215 Figure 72. Oxidation of alkyne using DCA and BP as catalysts, O2 as oxidizing agent

In-catalyzed oxidative cleavage of alkynes
An efficient and general method for the oxidative cleavage of alkenes and alkynes using tert-butyl hydroperoxide and indium (III) chloride as catalyst in water to give the corresponding carboxylic acids or ketones has been achieved by Ranu et al. They tested alkenes with peptide bonds, tert-butyl carboxylic esters and N-Boc-protected tryptophan and obtained very high chemoselectivity. The catalyst has been recycled successfully. They have tested transition metals such as CuCl2, CeCl3, FeCl3, ZnCl2 and TiCl4 for oxidative cleavage. However, they were not as effective as InCl3 and brought between 38 and 55% yield for the oxidative cleavage of α-phenylstyrene to benzophenones in the same reaction condition. Under the same reaction conditions, 84% benzophenone was isolated with the use of InCl3 as a catalyst with no side product being obtained. Unfortunately, although they tested this method for 17 different olefins, they used this  Figure 73. Oxidative cleavage of alkynes using InCl3 as catalyst and t-BuOOH as oxidizing agent.
In their manuscript, a reaction mechanism was suggested only for the oxidative cleavage of olefins. According to Ranu et al., the oxidative cleavage of the olefins takes place via first the formation of epoxide, then the formation of 1,2-diol, which leads to the corresponding carboxylic acids. These intermediates were isolated from the reaction mixture. Unfortunately, no reaction mechanism for the oxidative cleavage of alkynes has been proposed. 92

Oxidation of alkynes using dioxirane
Potassium peroxymonosulfate, well-known as oxone, can normally be synthesized from potassium carbonate and peroxomonosulfuric acid. 221 Potassium peroxomonosulfate is a crystalline white odorless solid that is readily soluble in water. 222 It decomposes when heated above 90 °C. Its aqueous solution is very acidic. This reagent is often used as a strong oxidant in chemical synthesis. 223 There is also a monohydrate with a monoclinic crystal structure. Curci et al. have the dioxiranes 278 and 279 from potassium peroxymonosulfate and acetone or trifluoroacetone in in aqueous buffer at pH 7.0-7.5. Curci et al. have developed a method for using these dioxiranes as oxidants for the oxidation of alkyne. They tested four alkynes in different reaction conditions. They have not isolated any oxidative cleavage products, instead a mixture of ketone, aldehyde, carboxylic acid and 1,2-dicarbonyl compounds. The yield of the products varies depending on the use of the dioxiranes (278 or 279). When phenylacetylene was reacted in the presence of dimethyldioxirane 278, mainly 2-oxo-2-phenylacetic acid 279 was obtained in 20% yield and benzaldehyde in 64% yield. With the use of methyl (trifluoromethyl) dioxirane 279 as the oxidizing agent, mainly benzaldehyde was isolated in the oxidation of phenylacetylene. In the oxidation of diphenylacetylene, mainly benzilin 30% and benzophenone in approximately 60% yield were obtained using both dioxirane reagents (278 and 279). Using both oxidizing agents 278 and 279, aliphatic alkynes such as hexadec-8-yne (e,f) oxidizes to form α,β-unsaturated ketone 288 in 77-78% and hexadecane-8,9-diones 289 in 18-19%. In the oxidation of cyclodecyne (a conformationally rigid cycloalkyne), cis-bicyclo (5.3.0] decan-2-one 290 was isolated in 86% yield and cisbicyclo [4.4.0] decan-2-one 291 in 13% yield ( Figure 74). 170 Arkivoc 2023 (i) 202211942  Figure 75. Oxidation of alkynes using dioxirane, which is synthesized by KHSO5.

Summary and Outlook to Oxidative Cleavage of Alkynes in Green Synthesis
In general, the oxidative cleavage or oxidation of the alkynes mainly results in the following products, depending on the reaction conditions or on the substrates used: carboxylic acid anhydrides, 1,2-diketones, carboxylic acids, carboxylic acid esters, α,β-epoxy-ketones and α,β-unsaturated ketones (in case, bearing the substrate a CH2 group in α-position) are mainly formed. Ketones, α,α-dialkyl-substituted carboxylic acid and α-hydroxyketones are mostly formed as by-products in the methods developed up to present. Unfortunately, no method has hitherto been developed that oxidatively cleaves the alkynes directly to the corresponding aldehydes ( Figure 78).  The principle of the ozonolysis of alkynes is the same as in the ozonolysis of olefins. The triple bond attacks react with ozone under [3+2] cycloadddition, with many more intermediates being formed compared to the oxidation of the olefins. These intermediates oxidize or cleave oxidatively to form 1,2-diketones, anhydrides or ultimately to carboxylic acids. When metals (Ru, Mn, Fe, Mo, W, Pd, Rh, Ni, Ta, Re, Os, Au and Ce) are used, the following principle was applied: the salts of the metals were used in combination with an oxidizing agent in a solvent. The salts are oxidized to a higher oxidation state under these conditions. The triple bond of the alkynes attacks the active catalyst formed in situ (mostly oxometallic complexes); after the bonds have been reformed, the intermediates are mostly cleaved to form the carboxylic acids or carboxylic acid esters. When using main group elements, the principle of oxidation or oxidative cleavage of the alkynes varies. For example, if hypervalent λ 3 -iodanes are used, the hypervalent iodane is reduced to iodine, while alkynes are oxidized to the carboxylic acids or carboxylic acid esters. When using tetrabromomethane, the C-Br bond is first cleaved homolytically when the energy is transferred by light. Then a series of radical reactions begin that activate the oxygen in the air. The radically negatively charged oxygen in the air reacts with the substrate and causes this substrate to cleave oxidatively. When using the DCA-BP system ( Figures  71-72). The reagent is activated with visible light, whereby a radical anion intermediate is formed. This intermediate activates the substrate used via BP. When using the dioxiranes, the reactive dioxiranes are in situ with the addition of oxones, which oxidizes the acetone or 1,1,1-trifluoropropane-2-oneto dioxiranes.
In the oxidation of olefins, no oxidative cleavage method for the alkyne that is enzyme-catalyzed has yet been published.
Unfortunately, apart from the oxidative cleavage method using the OsO4/NaIO4/HMPT system ( Figure  50-52), only one method has been published that is chemoselective or that only reacts with alkyne triple bonds. For example, using gold as catalyst, triple bond of enyne as substrate is cleaved (Figure 56).
The best method in terms of environmental friendliness using metal-catalyzed oxidative cleavage seems to be the methods Fe-catalyzed oxidative cleavage with TBHP (chapter 4.3) and Ni-catalyzed oxidative cleavage with molecular oxygen (chapter 4.8). Because the catalyst is recyclable, the used reagent is not so expensive, it is not toxic and easy to handle in the laboratory. Ruthenium (chapter 4.1), rhenium (4.10) and osmium (chapter 4.11) are commonly used in the scientific world and are well-known transition metals for the oxidative cleavage of alkynes. However, these metals are under the category heavy metals and are more expensive and more toxic for human and environment compared to nickel and iron-catalyzed oxidative cleavage. The best methods without any use of transition metal in terms of efficiency, environmental friendliness, cost, easy handling in lab., non-toxicity and satisfying yield seem to be the methods: the ozonolysis (chapter 3), hypervalent λ 3 -iodine catalyzed oxidative cleavage (chapter 5.1), DCA-catalyzed oxidative cleavage with molecular oxygen (chapter 5.1) and carbon tetrabromide catalyzed oxidative cleavage with molecular oxygen (chapter 5.2), because on one hand, it is a metal-free catalyzed oxidative cleavage, on the other hand a broad range of substrates were tested using these methods and the oxidizing agents are mostly molecular oxygen or the reagent itself. Using these methods, the oxidative cleavage products were isolated in up to very good yields. However, these methods are not chemoselective for the oxidative cleavage of triple bond of enyne substrate. Other methods have to be improved for a broad range of alkynes or be optimized with regard to stereo and/or chemoselectivity. With another words, the future of the oxidative cleavage of the alkyne should be more chemoselective, cheap, environmentally friendly and atom-efficient.