Carbonylation of alkynes

The polymer of MMA is known as Perspex. It is a clear transparent glasslike material with high hardness, resistance to fracture, and chemical stabihty. As shown by reaction 4.5.1, the conventional route for the manufacture of MMA involves several steps. This process generates large quantities of ammonium salts, thereby increasing the E factor significantly (see Section 1.6 and reaction 1.6.1). 

An alternative route based on a homogeneous palladium catalyst was developed by Shell. In this process, a palladium complex catalyzes the reaction between propyne (methyl acetylene), methanol, and carbon monoxide. This is shown by reaction 4.5.2, and the product is formed with a regioselectivity that could be as high as 99.95%. 

Note that a hydrogen atom and an ester group are added onto the two carbon atoms of the alkyne substrate. For this reason, carbonylation 

The Shell process for MMA is operated at about 60°C and 10-60 bar pressure. The reaction is usually carried out in methanol, which acts both as a solvent and as a reactant. The precatalyst is palladium acetate, which is mixed with an excess of a special phosphine ligand, L, to generate the active catalytic intermediates in situ. An important requirement for efficient catalysis is the presence of an acid HX as a cocatalyst. 

Note that in the presence of an acid, the nitrogen atom of the pyridine ring is protonated and the equilibrium between L and LHX, as shown by reaction 4.5.3, is set up. This in turn means that in the presence of an acid, both chelation and monodentate coordination, as shown by reaction 4.5.4, may occur. 

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The presence of formates, oxalates, formic acid, and oxalic acid in the carbonylation of alkynes affects the regioselectivity. Also, the regioselectivity can be controlled to some extent by the proper selection of the ligands. A linear a,... 

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]. 

The direct combination of selenium and acetylene provides the most convenient source of selenophene (76JHC1319). Lesser amounts of many other compounds are formed concurrently and include 2- and 3-alkylselenophenes, benzo[6]selenophene and isomeric selenoloselenophenes (76CS(10)159). The commercial availability of thiophene makes comparable reactions of little interest for the obtention of the parent heterocycle in the laboratory. However, the reaction of substituted acetylenes with morpholinyl disulfide is of some synthetic value. The process, which appears to entail the initial formation of thionitroxyl radicals, converts phenylacetylene into a 3 1 mixture of 2,4- and 2,5-diphenylthiophene, methyl propiolate into dimethyl thiophene-2,5-dicarboxylate, and ethyl phenylpropiolate into diethyl 3,4-diphenylthiophene-2,5-dicarboxylate (Scheme 83a) (77TL3413). Dimethyl thiophene-2,4-dicarboxylate is obtained from methyl propiolate by treatment with dimethyl sulfoxide and thionyl chloride (Scheme 83b) (66CB1558). The rhodium carbonyl catalyzed carbonylation of alkynes in alcohols provides 5-alkoxy-2(5//)-furanones (Scheme 83c) (81CL993). The inclusion of ethylene provides 5-ethyl-2(5//)-furanones instead (82NKK242). The nickel acetate catalyzed addition of r-butyl isocyanide to alkynes provides access to 2-aminopyrroles (Scheme 83d) (70S593). 

Carbonylation of alkynes is a convenient method to synthesize various carbonyl compounds. Alper et al. found that carbonylation of terminal alkynes could be carried out in aqueous media in the presence of 1 atm CO by a cobalt catalyst, affording 2-butenolide products. This reaction can also be catalyzed by a cobalt complex and a ruthenium complex to give y-keto acids (Scheme 4.8).92... 

Recent investigations confirmed earlier findings on diphenyl cyclopropenone277 278 ruling out the intermediacy of cyclopropenones in the catalytic carbonylation of alkynes ... 

It is worth mentioning that some precursors easily catalyze the reductive carbonylation of alkynes from the C0/H20 couple. Here, the main role of water is to furnish hydrogen through the water-gas-shift reaction, as evidenced by the co-production of CO2. In the presence of Pd /KI terminal alkynes have been selectively converted into furan-2-(5H)-ones or anhydrides when a high concentration in CO2 is maintained. Two CO building blocks are incorporated and the cascade reactions that occur on palladium result in a cyclization together with the formation of an oxygen-carbon bond [37,38]. Two examples are shown in Scheme 4. 

In an alternative strategy functionalized phenols, such as iodophenol, were involved in palladium-catalyzed carbonylation of alkynes or allenes, producing coumarin or chromone derivatives (Scheme 23) [130-133]. After oxidative addition of the iodoarene to the Pd(0) catalyst the order of insertion of either CO or the unsaturated substrate mainly depends on the nature of the substrate. In fact, Alper et al. reported that CO insertion occurs prior to allene insertion leading to methylene- or vinyl-benzopyranone derivatives [130]. On the contrary, insertion of alkynes precedes insertion of CO, affording couma-rine derivatives, as reported by Larock et al. According to the authors, this unusual selectivity can be explained by the inability of the acyl palladium species to further react with the alkyne, hence the decarbonylation step occurs preferentially [131-133]. 

Intramolecular alkoxycarbonylation of alkynols is parallel to what has been described for alkenols except that functionalization of the triplebond produces a double bond. No lactone formation is observed in the Pd(II)-catalyzed oxidative cyclization-carbonylation of alkynes. Instead [(methoxycarbonyl)methylene]tetrahydrofurans are selectively formed [134, 135]. Moreover, starting from an enynol, furan-2-acetic ester is obtained resulting from a final aromatization step [136]. 

Carbonylation of alkynes to give 2-substituted 4-methyl-y-butyro-lactones (Table 8.9)... 

Rhodium carbonyl cluster catalysts [Rh4(CO)i2] and [Rh6(CO)i6] were effective to produce lactones in carbonylation of alkynes (Scheme 5.10) [32,33]. In these systems, however, water is rather a reagent than a solvent and its amount can be as low as 216 pL in 45 mL CHCI3 [33]. 

A regiospecific synthesis of hydroxybutenolides (59) has been carried out by Alper et al.,l0S using cobalt carbonyl-catalyzed carbonylation of alkynes. More such examples of PTC in organometallic chemistry106-108 undoubtedly will be developed. 

A number of reports have appeared on the carbonylation of alkynes in presence of alcohols. Using the synthesis of methyl trans-2-octenoate from 1-heptyne (equation 129) as type reaction, various catalysts were compared.533 The best results were obtained with the complexes [PdCl2 P(p-tol)3 2] and [PdCl2(PPhMe2)2], both in the presence of SnCl2. Some of the branched chain product is also formed. Other alkynes were studied, and the mechanism of Scheme 48 was suggested. 

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). 

In the 1930s, the Reppe group developed commercial processes for the production of carboxylic acids and esters by the carbonylation of alkynes and alkenes using metal carbonyls [4], In particular, an industrial process for producing acrylic acid or ester by the carbonylation of highly explosive acetylene, catalysed by extremely toxic Ni(CO)4, was established (eq. 1.3). 

When hydrosilane is used instead of hydrogen in the Rh-catalysed carbonylation of alkynes, the silylformylation of alkynes occurs to give the / -silyl-a,/ -unsaturated aldehydes 71 [38,39]. Oxidative addition of silane to Rh generates the silylrhodium hydride 69. It should be noticed that insertion of alkyne to the Rh-SiR.3 bond, but not... 

Alkynes undergo stoichiometric oxidative reactions with Pd(II). A useful reaction is oxidative carbonylation. Two types of oxidative carbonylation of alkynes are known. The first one is the synthesis of alkynic carboxylates 211 by the oxidative carbonylation of terminal alkynes using PdCty and CuCty in the presence of a base [127]. Dropwise addition of the alkyne is recommended as a preparative-scale procedure of this reaction, in order to minimize the oxidative dimerization of alkynes as a competitive reaction [128]. The reaction has been applied to the synthesis of the intermediate 213 of the carbapenem 214 from the terminal alkyne 212 [129],... 

SAFETY PROFILE Mutation data reported. Human systemic effects by intradermal route dermatitis. When heated to decomposition it emits toxic fumes of K2O and Cl". Used as a catalyst for carbonylation of alkynes. See also PLATINUM COMPOUNDS. 

In contrast to the carbonylation of alkynes, the advantages of nickel as the catalyst metal are much less pronounced with alkenes. As a result, various catalytic systems have been developed. They can be roughly subdivided into two classes, i. e., halogen-containing and halogen-free. So far, none of these catalyst systems has achieved industrial significance. 

Under comparable reaction conditions, the carbonylation of alkynes can be steered in another direction by varying the catalyst metals. For instance, using iron pentacarbonyl [25] or ruthenium carbonyl [26] as catalysts, the principal product is hydroquinone (eq. (11)). 

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