Hydrocarboxylation, alkenes

As a unique reaction of Pd(II), the oxidative carbonylation of alkenes is possible with Pd(ll) salts. Oxidative carbonylation is mechanistically different from the hydrocarboxylation of alkenes catalyzed by Pd(0), which is treated in Chapter 4, Section 7.1. The oxidative carbonylation in alcohol can be understood in the following way. The reaction starts by the formation of the alkoxy-carbonylpalladium 218. Carbopalladation of alkene (alkene insertion) with 218 gives 219. Then elimination of /3-hydrogen of this intermediate 219 proceeds to... 

The hydrocarboxylation of suitably substituted hydroxyalkylacetylenes and alkenes has been widely used to prepare a variety of butenolides and butyrolactones (see Scheme 63101,102 and Refs. 8 and 10a for reviews of earlier literature) a closely related reaction is shown in Scheme 64.103,104... 

The related field involving the hydrocarboxylation of alkenes is also under investigation11481, not least because of its potential importance in the synthesis of NSAI drugs. An indirect way to the latter compounds involves the hydro-vinylation of alkenes. For example catalysis of the reaction of ethylene with 2-methoxy-6-vinylnaphthalene at 70°C using (allylNiBr)2 and binaphthyl (63)... 

The acid-catalyzed hydrocarboxylation of an alkene is known as the Koch Reaction. When the source of both the CO and the H20 is formic acid, the process is called the Koch-Haaf Carbonylation. 

The reaction is also called hydrocarboxylation. According to a later modification, the alkene first reacts with carbon monoxide in the presence of the acid to form an acyl cation, which then is hydrolyzed with water to give the carboxylic acid.97 The advantage of this two-step synthesis is that it requires only medium pressure (100 atm). Aqueous HF (85-95%) gave good results in the carboxylation of alkenes and cycloalkenes.98 Phosphoric acid is also effective in the carboxylation of terminal alkenes and isobutylene, but it causes substantial oligomerization as well.99 100 Neocarboxylic acids are manufactured industrially with this process (see Section 7.2.4). The addition may also be performed with formic acid as the source of CO (Koch-Haaf reaction).101 102 The mechanism involves carbocation formation via protonation of the alkene97 103 [Eq. (7.10)]. It then reacts with carbon monoxide... 

The aqueous-organic two-phase system was successfully applied to perform hydrocarboxylation.300 Palladium complexes of trisulfonated triphenylphosphine ligands were shown to exhibit high activity.301-303 The application of cosolvents and modified cyclodextrins allow to eliminate solubility problems associated with the transformation of higher alkenes.304... 

Non-oxidative hydrocarboxylation of alkenes to carboxylic acids with CO and H20 is catalyzed by palladium complexes such as PdCl2(PhCN)2 or PdCl2(PPh3)2, and a-methyl acids predominate in the presence of HC1.374,443 A recent improvement of this reaction consisted of the use of a PdCl2/CuCl2/HCl catalyst under oxidative conditions.377 Almost quantitative yields of a-methyl carboxylic acids and dicarboxylic acids were obtained from terminal alkenes and terminal dialkenes respectively, at room temperature and atmospheric pressure (equation 174).377... 

The hydrocarboxylation reaction of alkenes and alkynes is one which utilizes carbon monoxide to produce carboxylic acid derivatives. The source of hydrogen is a protic solvent (equation 35) dihydrogen is not usually added to the reaction. There are a number of variations to this reaction, since the solvent can be water, alcohols, amines, acids, etc. The catalysts can be Group VIII-X transition metals, but cobalt, rhodium, nickel, palladium and platinum have found the most use. 

The hydrocarboxylation can take place by insertion of the alkene into a metal-hydride bond followed by CO insertion and finally reaction of the acyl complex with solvent as illustrated in equation (36). Alternatively, a transition metal-carboxylate complex can be generated initially. Insertion of the alkene into the metal-carbon bond of this carboxylate complex followed by cleavage of the metal-carbon bond by solvent completes the addition, as shown in equation (37). Both sequences provide the same product. 

The final step in the catalytic cycle is the cleavage of the metal-alkyl bond with acid, which must take place faster in the hydrocarboxylation of alkenes than -elimination. 

Branched acids and esters are obtained from the palladium-catalyzed reaction in the absence of phosphines, and in the presence of copper chloride and HC1.79 The mild reaction conditions and the regio-specificity make this a very attractive carboxylation procedure (entry 5, Table 5). Internal straight chain alkenes can be hydrocarboxylated, but the rates are slower and the reaction is not regiospecific. 

Although the hydrocarboxylation of 1 -alkenes is not of interest for the synthesis of more complex organic molecules, the information obtained from the hydrocarboxylation reactions with various catalysts can be applied to the synthesis and reactions of other alkene substrates. 

The hydrocarboxylation reaction of simple alkenes and alkynes in the presence of primary or secondary amines or ammonia yields amides (equations 48 and 49). The fact that formamides can be used in place of amines suggests that a key intermediate in the reaction is the hydride metal carboxamide (20). 

Direct hydrocarboxylation of conjugated dienes with carbon monoxide and formic acid, using Pd—C catalysis and in the presence of triphenylphosphine and 1,4-bis(diphenylphosphino)butane (dppb), gives good yields of what is essentially addition of formic acid to the terminal alkene (equation 98)393. This is an extremely useful synthetic route to y,<5-unsaUirated acids. 

The 1,2-addition of H and CO2H, or CO2R to alkenes and alkynes is called hydrocarboxylation, or hydroesterification, and proceeds with catalytic amounts of... 

Hydrocarboxylation Alkene, water, and CO Carboxylic acid All in Chapter 4... 

In the previous chapters we discussed alkene-based homogeneous catalytic reactions such as hydrocarboxylation, hydroformylation, and polymerization. In this chapter we discuss a number of other homogeneous catalytic reactions where an alkene is one of the basic raw materials. The reactions that fall under this category are many. Some of the industrially important ones are isomerization, hydrogenation, di-, tri-, and oligomerization, metathesis, hydrocyana-tion, hydrosilylation, C-C coupling, and cyclopropanation. We have encountered most of the basic mechanistic steps involved in these reactions before. Insertions, carbenes, metallocycles, and p -allyl complexes are especially important for some of the reactions that we are about to discuss. 

The HCo(CO)4-catalyzed hydrocarboxylation of alkenes has also been known for a long time. The mechanism is analogous to that presented for hydroformyla-tion (Scheme 1), except that H2O is used instead of H2. Hydrocarboxylation is generally slower than hydro-formylation, and it is believed that the concentrations of the intermediate species are quite low relative to those seen for hydroformylation. Pyridine has a rateenhancing effect that is believed to be due to the facile cleavage of the (acyl)Co(CO)4 intermediate. This reaction forms [pyridine-acyl] + [Co(CO)4] , which is more rapidly hydrolyzed by water to form the product carboxylic acid and HCo(CO)4. 

One of the first mechanistic proposals for the hydrocarboxylation of alkenes catalyzed by nickel-carbonyl complexes came from Heck in 1963 and is shown in Scheme 24. An alternate possibility suggested by Heck was that HX could add to the alkene, producing an alkyl halide that would then undergo an oxidative addition to the metal center, analogous to the acetic acid mechanism (Scheme 19). Studies of Rh- and Ir-catalyzed hydrocarboxylation reactions have demonstrated that for these metals, the HX addition mechanism, shown in Scheme 24, dominates with ethylene or other short-chain alkene substrates. Once again, HI is the best promoter for this catalytic reaction as long as there are not any other ligands present that are susceptible to acid attack (e g. phosphines). 

Hydrocarboxylation reactions generally do not have very high regioselectivities when carried out with C4 or higher alkenes, due to alkene isomerization side reactions catalyzed by both acid and metal. Thus, many of the reactions done industrially involve substrates such as acetylene and ethylene where isomerization side reactions will not present any problems. 

Chiral Ligand for Asymmetric Catalysts. (5)-(+)- and (R)-(—)-BNPPA are efficient chiral ligands for the Pd-catalyzed hydrocarboxylation of alkenes. Naproxen can be obtained re-gioselectively in 91% ee (eq 2). 

Asymmetric Hydrocarboxylation. The title reagent was used in the first example of an asymmetric hydrocarboxylation (eq 1). With the a-methylstyrene, the straight chain isomer was formed. The regiospecificity was much less pronounced, however, for other alkenic substrates. The influence of some reaction variables on the reaction shown in eq 1 was studied. For example, the presence of a solvent such as THF or benzene, the alcohol source, the effect of CO pressure, the effect of substitution on the phenyl ring, the PdC /DIOP molar ratio, or the presence of PPha along with DIOP, were varied to improve the optical yield. ... 

The acid-catalyzed hydrocarboxylation of alkenes (the Koch reaction) can be performed in a number of ways. In one method, the alkene is treated with carbon monoxide and water at 100-350°C and 500-1000-atm pressure with a mineral acid catalyst. However, the reaction can also be performed under milder conditions. If the alkene is first treated with CO and catalyst and then water added, the reaction can be accomplished at 0-50°C and 1-100 atm. If formic acid is used as the source of both the CO and the water, the reaction can be carried out at room temperature and atmospheric pressure.The formic acid procedure is called the Koch-Haaf reaction (the Koch-Haaf reaction can also be applied to alcohols, see 10-77). Nearly all alkenes can be hydrocarboxylated by one or more of these procedures. However, conjugated dienes are polymerized instead. Hydrocarboxylation can also be accomplished under mild conditions (160°C and 50 atm) by the use of nickel carbonyl as catalyst. Acid catalysts are used along with the nickel carbonyl, but basic catalysts can also be employed. Other metallic salts and complexes can be used, sometimes with variations in the reaction procedure, including palladium, platinum, and rhodium catalysts. The Ni(CO)4-catalyzed oxidative carbonylation with CO and water as a nucleophile is often called Reppe carbonylationP The toxic nature of nickel... 

An indirect method for hydrocarboxylation involves the reaction of an alkene with a borate, (RO)2BH and a rhodium catalysts. Subsequent reaction with LiCHCl2 and then NaC102 gives the Markovnikov carboxylic acid (RC=C RC(C00H)CH3. " When a chiral ligand is used, the reaction proceeds with good enantioselectivity. 

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