Aryl derivatives double carbonylation

Carbonyl compounds will be taken in this chapter to mean any organic compound that contains at least one carbon-oxygen double bond where we limit the substitution to only saturated aliphatic, saturated alicyclic and aryl hydrocarbyl groups. Carbonyl compounds with a variety of unsaturated substituents have earlier been discussed within the context of enones4. Non-hydrocarbyl substituents, X , may be directly attached to the carbonyl and elsewhere in the molecule. The first type of species, RCOX, is alternatively identified as acyl derivatives such as carboxylic acids and their esters, halides and amides and have already been discussed in a recent Patai thermochemistry... 

A number of double carbonylations have been reported. In these reactions, two molecules of CO are incorporated in the product, leading to a-keto acids or their derivatives. When the catalyst is a palladium complex, best results are obtained in the formation of a-keto amides. R is usually aryl or vinyhc. The formation... 

Double carbonylation of aryl halides to a-keto acid derivatives... 

Scheme 1.44. Mechanism of double carbonylation to convert aryl halides, CO, and nucleophiles into a-keto acid derivatives.

B. DOUBLE CARBONYLATION OF ARYL HALIDES TO GIVE a-KETO ACID DERIVATIVES CATALYZED BY PALLADIUM COMPLEXES... 

Before discussing the double carbonylation processes it may be helpful to understand the mechanism of the single carbonylation of aryl halides into carboxylic acid derivatives (Heck processes). The first step in the catalytic process is oxidative addition of an aryl halide to Pd(0) species formed from a catalyst precursor to yield an arylpal-ladium halide intermediate (A) in Scheme 1. Insertion of carbon monoxide into the aryl-palladium bond in A gives an acylpalladium halide complex (B). Attack of a nucleophile such as alcohol, amine, and water assisted by a base on the acylpalladium complex yields carboxylic ester, amide, and carboxylic acid, although details of the mechanism have not been unequivocally established. The palladium(O) species regenerated in the process further undergoes oxidative addition to carry out the catalytic cycle (Scheme 1). 

The a-keto amides are less susceptible to hydrolysis and preparation of a-keto esters and acids are preferable for synthesizing various derivatives thereof. Various aryl iodides and bromides can be converted into a-keto esters on reactions with alcohols and carbon monoxide in the presence of a base such as tertiary amines or potassium acetate with catalytic amounts of tertiary phosphine-coordinated palladium complexes (Eq. 11).[42]-[46] jjjgjj yields of a-keto esters can be achieved only when iodide substrates are used. Double carbonylation of aryl bromides to a-keto esters can be accomplished with difficulty at much slower rates. Alkyl and benzyl iodides give no double carbonylation products. 

Khorana [43,45] has studied a very limited number of examples and noted absorption at 2150 cm" A more detailed study of both frequency and intensity has been made by Meakins and Moss [44]. Nine carbodiimides were examined by these authors, and all showed a very intense absorption in the range 2152—2128 cm" accompanied in three instances by a much weaker combination band at lower frequencies. Little frequency or intensity differences was found between alkyl and aryl derivatives. The intensity of the band was assessed by a variety of methods, and the extinction coefficient e was of the order of 1400. This is some IV2 times as strong as a normal ketonic carbonyl absorption. Mogul [60] has reviewed the infra-red and Raman spectra of carbodiimides. The findings confirm those of Meakins, and others in the infra-red, but add the additional observation that the band doubles when an aromatic ring is directly attached to the diimide group. In the Raman spectra the symmetric vibration is of course the more intense and this occurs near 1460 cm" ... 

In the palladium-catalysed carbonylation of aryl bromides to yield benzaldehyde derivatives, IV-formylsaccharin is used as the source of the acyl function. A double carbonylation has been observed in the reaction of aryl halides with carbon monoxide and terminal alkenes which yields 4-arylfuranones such as (152). The proposed mechanism involves oxidative addition of the aryl halide to palladium and insertion of the carbon monoxide to give an acyl palladium species. This is followed by coordination and insertion of the alkene. A second carbon monoxide insertion is faster than -hydride elimination and, after intramolecular attack, leads to the product. The palladium-catalysed reaction of aryl iodides with simple ketones such as acetone in the presence of carbon monoxide has been shown to yield 1,3-diketones such as... 

Several papers deal with the products of (formally) "double carbonylation" reactions. The carbonylation product of styrene oxide in the presence of a Co2(C0)g/MeI catalyst under phase-transfer conditions contains two CO derived carbons (eqn.17). Two groups report the synthesis of a-keto esters from aryl iodides, CO, alcohols and tertiary amines the selectivity depends on Replacement of alcohol by water leads to a-keto acids. a-Keto-amides are prepared similarly from secondary amines. In this case the mechanism has been studied in detail oxidative addition of the aryl halide is the rate-determining step (Scheme 5). °... 

Dediazoniations which give aryl-addition or aryl-substitution derivatives of compounds with double bonds are discussed in this and the following section. Reactions at the C or S atom of carbonyl or sulfonyl groups are treated in this section and those at C = C double bonds in Section 10.9. 

Polar C=Y double bonds (Y = NR, O, S) with electrophilic carbon have been added to suifinic acids under formation of sulfones. As in the preceding section one must distinguish between carbonyl groups and their derivatives on the one hand, and carboxylic acids (possessing leaving groups at the electrophilic carbon) on the other. Aldehydes " of sufficient reactivity—especially mono-substituted glyoxals - —and their aryl or arylsulfonyl imines have been added to suifinic acids (in a reversible equilibrium) to yield a-hydroxy or a-amino sulfones the latter could also be obtained from the former in the presence of primary amines (equation 26). 

The arylation of alkenes was discovered by Meerwein146 in 1939 using ,/)-unsaturated carbonyl compounds, namely coumarin and cinnamic derivatives. Diazotizations for Meerwein reactions are made in aqueous HC1. The substitution proper may be combined with addition of HC1 to the double bond. As catalyst, CuCl2 is used. Various observations (see elsewhere7k) demonstrate that in typical Meerwein systems, part of Cu11 is reduced to Cu1. 

This microwave-accelerated double alkylation reaction was applicable to a variety of aniline derivatives and dihalides, furnishing N-aryl azacycloalkanes in good to excellent yields [89]. The reaction was applicable to alkyl chlorides, bromides and iodides and was extended to include hydrazines [90]. This improved synthetic methodology provided a simple and straightforward one-pot approach to the synthesis of a variety of heterocycles such as substituted azetidines, pyrrolidines, piperidines, azepanes, N-substituted-2,3-dihydro-Iff-isoindoles, 4,5-dihydro-pyrazoles, pyrazolidines, and 1,2-dihydro-phthalazines [91]. The mild reaction conditions tolerated a variety of functional groups such as hydroxyls, carbonyls, and esters. 

Alkenyl and aryl substituents stabilize the C=0 double bond of carbonyl compounds even more than alkyl substituents. This is due to their pi electron-donating (+M) effect, which allows one to formulate additional zwitterionic resonance forms for carbonyl compounds of this type. Thus, no hydrates, hemiacetals, oligomers, or polymers can be derived from unsaturated or aromatic aldehydes. 

A great variety of tertiary enamines derived from aliphatic ketones, aryl alkyl ketones and functionalized ketones were reduced by formic acid, most of them in good yields, even in the presence of other functional groups, such as carbonyl, cyano and other carbon-carbon double bonds205 (Scheme 137). 

Electrolysis of carbonyl compounds provides pinacols, alcohols or hydrocarbons, depending on the conditions, such as pH, the nature of the electrode, and its potential. Fundamental studies have been carried out on the mechanisms of hydrocarbon formation using acetone as a substrate. Although several electrodes, such as Cd, Pt, Pb or Zn, are recommended, carbonyl compounds, including aryl and alkyl derivatives, require strong aqueous acidic media for reduction to the hydrocarbons. The mechanism of the electrolytic reduction is probably similar to that of Clemmensen reduction, which starts from anion radical formation by one-electron transfer, as indicated in Scheme 3. The difference is that electrolytic reduction takes place in an electric double layer, rather than on the surface of the zinc metal. 

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