Oxidative dicarbonylation, alkynes

The two major characteristic oxidation processes of alkynes are their transformation to 1,2-dicarbonyl compounds and their cleavage reaction to carboxylic acids.710 The structure of the starting compounds has a decisive effect on the selectivity of oxidation. Since 1,2-dicarbonyl compounds proved to be intermediates in further oxidations, carefully controlled reaction conditions are often necessary to achieve selective synthesis. Certain oxidizing agents such as peroxyacids and ozone are nonselective oxidants. 

Isoxazoles and their partially or fully saturated analogs have mainly been prepared, both in solution and on insoluble supports, by 1,3-dipolar cycloadditions of nitrile oxides or nitrones to alkenes or alkynes (Figure 15.10). Nitrile oxides can be generated in situ on insoluble supports by dehydration of nitroalkanes with isocyanates, or by conversion of aldehyde-derived oximes into a-chlorooximes and dehydrohalogenation of the latter. Nitrile oxides react smoothly with a wide variety of alkenes and alkynes to yield the corresponding isoxazoles. A less convergent approach to isoxazoles is the cyclocondensation of hydroxylamine with 1,3-dicarbonyl compounds or a,[3-unsatu-rated ketones. 

Hatakeyama et al. [115] have also carried out detailed product studies in the HO-initiated oxidation of the alkynes both in the presence and in the absence of NOx. The major products consisted of a-dicarbonyl compounds, i.e., HC(0)CHO from acetylene, CH3C(0)CH0 from propyne and CH3Q0)C(0)CH3 from 2-butyne, as well as HC(0)OH from acetylene and propyne and CH3C(0)OH from 2-butyne. The formation of these products was attributed to 02-reactions of the hydroxyvinyl radicals resulting from the addition reaction of HO with the alkynes, e.g.,... 

A great variety of substituted radicals for dimerization can be generated by anodic oxidation of anionic species r5"Me5+, e.g., sodium salts of 1,3-dicarbonyl compounds, aliphatic nitro compounds, phenols, oximes, alkynes, thio-lates or organometallics (Eq. (157) ). 

The problem of regioselectivity remains. Monosubstituted alkynes usually react cleanly using the HOMO of the alkyne and the LUMO of the nitrile oxide. The product is exactly that type of isoxazole (72 or 73) that was so difficult to make from dicarbonyl compounds and hydroxylamine. Here regioselectivity is controlled because the two substituents (R1 and R2) are on different reagents. Conditions are very mild. 

To produce a 1,2-azole, a 1,3-dicarbonyl-compound needs to be condensed with a unit providing the two heteroatoms - a hydrazine or hydroxylamine. The 1,3-dipolar cycloaddition of nitrile oxides or nitrile imines to alkynes provides an important route to isoxazoles and pyrazoles. 

Manganese(III) can oxidize carbonyl compounds and nitroalkanes to carboxy-methyl and nitromethyl radicals [186]. With Mn(III) as mediator, a tandem reaction consisting of an intermolecular radical addition followed by an intramolecular electrophilic aromatic substitution can be accomplished [186, 187). Further Mn(III)-mediated anodic additions of 1,3-dicarbonyl and l-keto-3-nitroalkyl compounds to alkenes and alkynes are reported in [110, 111, 188). Sorbic acid precursors have been obtained in larger scale and high current efficiency by a Mn(III)-mediated oxidation of acetic acid acetic anhydride in the presence of butadiene [189]. Also the nitromethylation of benzene can be performed in 78% yield with Mn(III) as electrocatalyst [190]. A N03 radical, generated by oxidation of a nitrate anion, can induce the 1,4-addition of aldehydes to activated olefins. NOj abstracts a hydrogen from the aldehyde to form an acyl radical, which undergoes addition to the olefin to afford a 1,4-diketone in 34-58% yield [191]. 

The phase-transfer-assisted permanganate oxidation of alkynes and alkenes has been reviewed. Terminal and internal alkynes are oxidized to 1,2-dicarbonyl compounds by the combined action of diphenyl disulphide, ammonium peroxidisulphate and water or by sodium periodate in the presence of ruthenium dioxide (equation 34). Other reagents for the conversion of acetylenes into 1,2-dicarbonyl compounds are hydrogen peroxide in the presence of (2,6-dicarboxylatopyridine)iron(II), the complex oxo(A, A -ethylenebissalicylideneiminato)chromium(V) trifluoromethanesulphonate (216)and ruthenium tetroxide as a mediator in electrooxidation. l-Acetoxyalkan-2-ones 217 are obtained by the oxidation of terminal acetylenes with sodium perborate and mercury(II) acetate in acetic acid ". Terminal alkynes give a-ketoaldehydes 218 on treatment with dilute hydrogen peroxide, combined with mercury(II) acetate and sodium molybdate or sodium tungstate under phase-transfer conditions. ... 

Hydroxy radical initiated oxidation of alkynes is important from the point of view of both atmospheric and combustion chemistry. Hatakeyama and coworkers have measured rate constants for the reaction of HO with acetylene, propyne and 2-butyne under atmospheric conditions. It has been suggested, based on product studies, that the jS-hydroxyvinyl radicals further react with molecular oxygen to form the corresponding peroxyl radicals and their subsequent reactions give carboxylic acid, a-dicarbonyl compounds and acyl radicals. 

Acylphosphoranes are oxidized to Q ,/3-dicarbonyl compounds in fair yields using aqueous NaI04 (eq 20). This method complements other methods such as the Potassium Permanganate or Ruthenium(VIII) Oxide oxidation of alkynes. NalOa is also used for the oxidation of hydroxamic acids and N-hydroxycarbamic esters at pH 6 to generate highly reactive ni-troso conqiounds. The oxidations are usually conducted in the presence of conjugated dienes so that the nitroso intermediates are trapped as their Diels-Alder cycloadducts (eq 21). 

An efficient and selective dicarbonylation of terminal alkynes mainly to E form can be carried out under mild conditions using Pdl2 and KI under pressure of CO and air. From 1 -hexyne, dimethyl butylmaleate (336) was obtained as a main product and the acetal of butylmaleic anhydride 337 as a minor product [133], Iodine is an oxidant. The usefulness of this reaction was demonstrated by the smooth preparation of a synthetic intermediate of CP-263,114 339 from the terminal alkyne 338 in high yield [134],... 

Sol 2. (b) It is an example of a widely used masked-aldol reaction. 1,3-Dipolar cycloaddition of nitrile oxides with an alkene (or alkyne) gives a cyclic product, isoxazoline (or isoxazole). These cyclic compounds are readily cleaved by reduction of the N—O bond and subsequent hydrolysis of the resulting imine to give aldol-type p-hydroxycarbonyl (or Claisen-type P-dicarbonyl) products. 

The asymmetric reduction of y-phenylseleno ketones and the intramolecular substitution of the phenylselenone residue by the oxygen atom of a hydroxy group led to 2-substituted tetrahydrofurans (13OL3906). Polysubstituted furans were formed in the photoredox neutral coupling of alkynes with 2-bromo-1,3-dicarbonyl compounds. The reaction was carried out without any external stoichiometric oxidants (130L4884). 

Pd-catalyzed cyclocarbonylation of alkynes can also afford furan-2(5 f)-ones. The stoichiometry of the process clearly requires a reducing agent. In the earlier examples reported in the literature,the aUcyne itself simultaneously underwent reductive dicarbonylation to furanone and oxidative dialkoxycarbonylation to maleic diester, so the overall process corresponded to that represented in Scheme 8. 

Cyclopropylalkynes (27) readily react with hexacarbonylchromium to produce (3-cyclopropylpropynylidine)pentacarbonylchromium complexes (28) whose dimethyl-amine Michael adducts (29) undergo 3 -I- 2-cycloaddition with alkynes to yield cyclopropyl-substituted 3-ethoxy-5-dimethylaminocyclopentadienes (30) in very good yields (Scheme 11). A one-step synthesis of 2-arylfurans involves the cerium ammonium nitrate-mediated oxidative cycloaddition of cyclic and acyclic 1,3-dicarbonyl compounds to alkynes.The new chiral Ai-(ethynyl)allylglycines (31)... 

Compared with aUylic C-H bond, benzylic C-H bond has similar BDE. Under the oxidative conditions, it is still susceptible to undergo SET to form a benzyl radical or carbocation, which would like to be trapped by a series of C(sp )-H nucleophiles or electron-rich aromatic rings (Scheme 2.30). For example, active methylenic 1,3-dicarbonyl compounds [148-153], nitrogen nucleophiles (amines or amides or almidine), [154—158] IV-hydroxyamides [159], ketones [160, 161], aldehydes [162], electron-rich alkenes [163], aromatic rings [164, 165], and terminal alkynes [166] are good coupling partners in the oxidative benzylic C-H bond... 

The radicals formed by oxidation of 1,3-dicarbonyl compounds will add to electron-rich naphthalenes (eq 11). Tetralins and dihydronaphthalenes can be formed by oxidation of diethyl a-benzylmalonate in the presence of an alkene or alkyne (eq 12). 20-22... 

---