Oxidative carbonylation alkynes

Alkynes undergo stoichiometric oxidative reactions with Pd(II). A useful reaction is oxidative carboiiyiation. Two types of the oxidative carbonyla-tion of alkynes are known. The first is a synthesis of the alkynic carbox-ylates 524 by oxidative carbonylation of terminal alkynes using PdCN and CuCh in the presence of a base[469], Dropwise addition of alkynes is recommended as a preparative-scale procedure of this reation in order to minimize the oxidative dimerization of alkynes as a competitive reaction[470]. Also efficient carbonylation of terminal alkynes using PdCU, CuCI and LiCi under CO-O2 (1 I) was reported[471]. The reaction has been applied to the synthesis of the carbapenem intermediate 525[472], The steroidal acetylenic ester 526 formed by this reaction undergoes the hydroarylalion of the triple bond (see Chapter 4, Section 1) with aryl iodide and formic acid to give the lactone 527(473],... 

As an application of maleate formation, the carbonylation of silylated 3-butyn-l-ol affords the 7-butyrolactone 539[482], Oxidative carbonylation is possible via mercuration of alkynes and subsequent Lransmetallation with Pd(II) under a CO atmosphere. For example, chloromercuration of propargyl alcohol and treatment with PdCF (1 equiv.) under 1 atm of CO in THF produced the /3-chlorobutenolide 540 in 96% yield[483]. Dimethyl phenylinale-ate is obtained by the reaction of phenylacetylene, CO, PdCU, and HgCl2 in MeOH[484,485]. 

Using a catalyst system of PdCl2, CuCH, HCl, and O2, the internal alkyne 20 is carbonylated at room temperature and 1 atm to give unsaturated esters[19]. This apparently oxidizing system leads to non-oxidative cu-hydroesterilica-tion. With terminal alkynes, however, oxidative carbonylation is observed. 

Carbonylation of the tetrasubstituted bispropargyiic amine 23 using PdCP and thiourea under mild conditions affords the carboxylated pyrrolidine derivatives 24a and b in good yields. Thiourea is regarded as effective for the oxidative carbonylation of alkynes, but no oxidative carbonylation was observed in this case[21]. 

Later, a nickel-catalyzed cascade conversion of propargyl halides and propargyl alcohol into a pyrone in water was reported. The reaction involved a carbonylation by CO and a cyanation by KCN (Eq. 4.55).96 Recently, Gabriele et al. explored a facile synthesis of maleic acids by palladium catalyzed-oxidative carbonylation of terminal alkynes in aqueous DME (1,2-dimethoxyethane) (Eq. 4.56).97... 

Abstract The basic principles of the oxidative carbonylation reaction together with its synthetic applications are reviewed. In the first section, an overview of oxidative carbonylation is presented, and the general mechanisms followed by different substrates (alkenes, dienes, allenes, alkynes, ketones, ketenes, aromatic hydrocarbons, aliphatic hydrocarbons, alcohols, phenols, amines) leading to a variety of carbonyl compounds are discussed. The second section is focused on processes catalyzed by Pdl2-based systems, and on their ability to promote different kind of oxidative carbonylations under mild conditions to afford important carbonyl derivatives with high selectivity and efficiency. In particular, the recent developments towards the one-step synthesis of new heterocyclic derivatives are described. 

Depending on the metal promoter and reaction conditions, alkynes may undergo several different oxidative carbonylation reactions, most of which are promoted by Pd(II) species and are usually carried out in the presence of an oxidizing agent (such as Q1CI2 or 02). 

PdCl2-promoted stoichiometric dichlorocarbonylation of acetylene (Eq. 20) is the first example of oxidative carbonylation of an alkyne that appeared in the literature [69,70], and presumably occurs through the mechanism shown in Scheme 13, involving addition of PdC to the triple bond followed by CO insertion, reductive elimination, oxidative addition to the C - Cl bond, further CO insertion and reductive elimination (Scheme 13, path a). 

Particularly significant results have been obtained in the oxidative carbonylation of simple and functionalized alkynes. Thus, the PdI2/KI-catalyzed oxidative carbonylation of simple alkyl- or arylacetylenes, as well as of propy-nyl alcohol and propynyl acetate, carried out in alcoholic solvents under mild conditions (15-25 atm of CO, 4-9 atm of air, 25-80 °C), led to the formation of maleic derivatives (together with small amounts of fumaric derivatives) and 5,5-dialkoxyfuran-2(5H)-ones, in high yields and with unprecedented catalytic efficiencies for this kind of reaction (up to ca. 4000 mol of product... 

Silylformylation, defined as the addition of RsSi- and -CHO across various types of bonds using a silane R3SiH, CO, and a transition metal catalyst, was discovered by Murai and co-workers, who developed the Co2(CO)8-catalyzed silylformylation of aldehydes, epoxides, and cyclic ethers [26]. More recently, as described in detail in Section 5.3.1, below, alkynes and alkenes have been successfully developed as silylformylation substrates. These reactions represent a powerful variation on hydroformylation, in that a C-Si bond is produced instead of a C-H bond. Given that C-Si groups are subject to, among other reactions, oxidation to C-OH groups, silylformylation could represent an oxidative carbonylation of the type described in Scheme 5.1. 

The alkyne-cobalt carbonyl complex 3 formed from the alkyne 1 and dicobalt octacarbonyl 2 should lose at least one of the GOs on the metal to provide the vacancy for the incoming olefins. Subsequently, an olefin-bound complex 5 rearranged oxidatively to yield a metallacyclic intermediate 6. Migratory insertion of GO of 6 would provide the homologated ring intermediate 7, and the following two successive reductive eliminations afford the cyclopentenone... 

Although the oxidative promoters have been quite effective, the reaction with less reactive olefins is still troublesome. Under the conditions with the oxidative promoter, the PKR is inevitably competing with the demetallation of the alkyne-cobalt carbonyl complex to give the metal-free alkynes. This competition is insignificant when the reactive olefins are employed, but it is prone to give more demetallated alkynes when the less reactive olefins are used (Scheme 3). This is reasoned by the fact that it is hard to expect from those promoters to oxidize only one of the COs on metal, and, in other words, the decarbonylation is not discriminative. As a result, the finding of the optimum condition is critical to favor the desired PKR product. 

By use of stoichiometric quantities of CuCl2, again in presence of a catalytic amount of PdCl2, an oxidative carbonylation of alkynes to the corresponding esters has been achieved.540 Sodium acetate was used as base. In its absence the reactions were no longer clean. The function of CuCl2 and NaOAc is indicated in equations (132)-(134). 

Addition of H and CO to alkenes and alkynes catalysed by transition metal complexes is called hydrocarbonylation, and is useful for the syntheses of carboxylic acids, their esters, aldehydes and ketones [1]. Oxidative carbonylation of alkenes and alkynes with Pd(II), treated in Section 11.1.5, differs mechanistically from hydrocarbonylation. Some carbonylation reactions occur at under 1 atm or low pressures, without using a high-pressure laboratory apparatus. Several commercial processes based on hydrocarbonylation have been developed. 

Chapter 4 centers on two key transformations in organic synthesis (1) oxidation of alcohols and of unsaturated hydrocarbons (i.e., alkenes and alkynes) to carbonyl compounds (2) reduction of various carbonyl compounds to alcohols. 

Oxidation of alkenylboranes by alkaline hydrogen peroxide gives aldehydes or ketones depending on the substituent pattern of the alkenyl group thus, when alkaline hydrogen peroxide oxidation is combined with alkyne hydroboration, the resulting two-step process is a procedure for converting alkynes to carbonyl compounds (Equations B2.7 and B2.8). 

Stable, isolable metallacycles are also obtained from reaction of complexes that serve as sources of the CpCo fragment (e.g. CpCo(PPh3)2) and alkynes. Upon carbonylation diese typically give high yields of cobalt-complexed cyclopentadienones. Direct reaction of CpCo(CO)2 with alkynes is similarly useful. The cycloaddition of di(t-butoxy)acetylene upon photolysis with CpCo(CO)2 is an example (Scheme 5). In all these systems the final complexes lack coordinated CO, and therefore amine oxides are not suitable reagents for liberating the stable cyclopentadienones. Tetra(t-butoxy)cyclopentadienone is accessible on a preparative scale via controlled electrochemical oxidation. Other oxidants such as Cr have been used as well in other systems. 

Alkynes undergo simple hydroesterification under mild conditions to give a,B-unsatuiated esters. Addition of the ester function to terminal alkynes frequently occurs at the substituted carbon atom to give branched products, but linear esters may be obtained witfi high selectivity using palladium-tin catalysts (equation 36). Under oxidative carbonylation conditions cir-diesters are formed. ... 

Finally, it should be pointed out that the oxidation of certain hydrocarbons can produce aerosols even in the absence of S02. Grosjean (1977) has reviewed organic particulate formation. Smog-chamber experiments have shown that straight-chain alkanes, alkynes, and carbonyl compounds... 

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]. 

Palladium(II) chloride-copper(Il) chloride-carbon monoxide. 13, 235-236 Oxidative carbonylation. This combination of reagents is commonly used for homologation of alkynes. The products are usually obtained as the methyl esters. Heterocyclization attends C-C bond formation when a proper functional group is present at a short distance. 

---