Carbonylation of alcohols to acids, table

Carbonylation of alcohols to acids, table of examples, 46, 74 Carboxylation, by formic acid, 46, 74 of 2-methylcyclohexanol by formic acid-sulfuric acid to 1-methyl-cyclohexanecarboxylic acid, 46, 72... 

The functions of flavoprotein enzymes are numerous and diversified.151-1533 A few of them are shown in Table 15-2 and are classified there as follows (A) oxidation of hemiacetals to lactones, (B) oxidation of alcohols to aldehydes or ketones, (C) oxidation of amines to imines, (D) oxidation of carbonyl compounds or carboxylic acids to a,(3-unsaturated compounds,... 

The oxidation of alcohols to carbonyl compounds with the stable nitroxyl radical TEMPO (86) as catalyst is a well-known preparative method [134, 135]. Hypochlorite or peracetic acid is usually used as the final oxidizing agent and ca. 1 mol% of catalyst 86 is used. In 1996 Rychnovsky et al. reported the synthesis of the chiral, binaphthyl-derived TEMPO analog 87 [136], Results obtained by use of 0.5-1 mol% of catalyst 87 [136] are listed in Table 10.12. In these oxidation reactions 0.6-0.7 equiv. sodium hypochlorite were used as the final oxidizing agent (plus... 

The two most commonly used types of allyl alcohol linker are 4-hydroxycrotonic acid derivatives (Entry 1, Table 3.7) and (Z)- or ( )-2-butene-l, 4-diol derivatives (Entries 2 and 3, Table 3.7). The former are well suited for solid-phase peptide synthesis using Boc methodology, but give poor results when using the Fmoc technique, probably because of Michael addition of piperidine to the a, 3-unsaturated carbonyl compound [167]. Butene-l,4-diol derivatives, however, are tolerant to acids, bases, and weak nucleophiles, and are therefore suitable linkers for a broad range of solid-phase chemistry. 

Support-bound carbonyl compounds can be converted into alcohols by treatment with suitable carbon nucleophiles. Aldehydes react readily with ketones or other C,H-acidic compounds under acid- or base-catalysis to yield the products of aldol addition (Table 7.2). Some types of C,H-acidic compound, such as 1,3-dicarbonyl compounds, can give the products of aldol condensation directly (Section 5.2.2.2). 

Alcohols can also be prepared from support-bound carbon nucleophiles and carbonyl compounds (Table 7.4). Few examples have been reported of the a-alkylation of resin-bound esters with aldehydes or ketones. This reaction is complicated by the thermal instability of some ester enolates, which can undergo elimination of alkoxide to yield ketenes. Traces of water or alcohols can, furthermore, lead to saponification or transesterification and release of the substrate into solution. Less prone to base-induced cleavage are support-bound imides (Entry 2, Table 7.4 see also Entry 3, Table 13.8 [42]). Alternatively, support-bound thiol esters can be converted into stable silyl ketene acetals, which react with aldehydes under Lewis-acid catalysis (Entries 3 and 4, Table 7.4). 

Isothioureas can be prepared on insoluble supports by S-alkylation or S-arylation of thioureas (Entry 7, Table 14.6). Further methods for the preparation of isothioureas on insoluble supports include the N-alkylation of polystyrene-bound, A/,/V -di(alkoxy-carbonyl)isothioureas with aliphatic alcohols by Mitsunobu reaction (Entry 7, Table 14.6) and the addition of thiols to resin-bound carbodiimides [7]. Resin-bound dithio-carbamates, which can easily be prepared from Merrifield resin, carbon disulfide, and amines [76], react with phosgene to yield chlorothioformamidines, which can be converted into isothioureas by treatment with amines (Entry 8, Table 14.6). The conversion of support-bound a-amino acids into thioureas can be accompanied by the release of thiohydantoins into solution (see Section 15.9). The rate of this cyclization depends, however, on the type of linker used and on the nucleophilicity of the intermediate thiourea. 

The synthesis of succinic acid derivatives, /3-alkoxy esters, and a,j3-unsaturated esters from olefins by palladium catalyzed carbonylation reactions in alcohol have been reported (24, 25, 26, 27), but full experimental details of the syntheses are incomplete and in most cases the yields of yS-alkoxy ester and diester products are low. A similar reaction employing stoichiometric amounts of palladium (II) has also been reported (28). In order to explore the scope of this reaction for the syntheses of yS-alkoxy esters and succinic acid derivatives, representative cyclic and acyclic olefins were carbonylated under these same conditions (Table I). The reactions were carried out in methanol at room temperature using catalytic amounts of palladium (II) chloride and stoichiometric amounts of copper (II) chloride under 2 atm of carbon monoxide. The methoxypalladation reaction of 1-pentene affords a good conversion (55% ) of olefin to methyl 3-methoxyhexanoate, the product of Markov-nikov addition. In the carbonylation of other 1-olefins, f3-methoxy methyl esters were obtained in high yields however, substitution of a methyl group on the double bond reduced the yield of ester markedly. For example, the carbonylation of 2-methyl-l-butene afforded < 10% yield of methyl 3-methyl-3-methoxypentanoate. This suggests that unsubstituted 1-olefins may be preferentially carbonylated in the presence of substituted 1-olefins or internal olefins. The reactivities of the olefins fall in the order RCH =CHo ]> ci -RCH=CHR > trans-RCH =CHR >... 

Many of the common laboratory methods for the preparation of alcohols have been discussed in previous chapters or will be considered later thus to avoid undue repetition we shall not consider them in detail at this time. Included among these methods are hydration (Section 10-3E) and hydroboration (Section 11-6D), addition of hypohalous acids to alkenes (Section 10-4B), SN1 and Sn2 hydrolysis of alkyl halides (Sections 8-4 to 8-7) and of allylic and benzylic halides (Sections 14-3B and 14-3C), addition of Grignard reagents to carbonyl compounds (Section 14-12), and the reduction of carbonyl compounds (Sections 16-4E and 16-5). These methods are summarized in Table 15-2. 

Nafion-H has also been found to be a suitable catalyst to carry out Koch-type carbonylation of a variety primary, secondary, and tertiary alcohols.402 Under optimal conditions, tertiary carboxylic acids are formed in moderate-to-good yields (Table 5.29). Increased CO pressure was shown to increase acid yields by enhancing the carbonylation of the intermediate tertiary carbocation prior to dimerization and oligomerization. Solvents had a small effect on catalyst performance, which is in contrast to the findings of Lange.403 Over Nafion NR50, acid yields of 39% and 42%... 

Oxidations of alcohols with water-free Cr(VI) reagents, such as the ones in rows 3-5 in Table 17.5, always result in the formation of carbonyl compounds. In particular, a carbonyl compound is obtained even if it is an aldehyde and therefore in principle could be oxidized to give the carboxylic acid. On the other hand, aldehydes are oxidized further (rows 1 and 3 in Table 17.5) if one uses water-containing Cr(VI) reagents (e. g., oxidations with K2Cr207 in sulfuric acid) or the Jones reagent (unless the latter is used under really mild conditions). Fig-... 

A detailed study has been made of the reaction of nuclear substituted benzyl alcohols with synthesis gas in the presence of dicobalt octa-carbonyl (Wender, Greenfield, Metlin, and Orchin, 19). Under the conditions of the reaction it was postulated that some of the dicobalt octacarbonyl is converted to cobalt hydrocarbonyl, HCo(CO)4, which is a strong acid. It was of interest to determine the effect of different substituent groups on (a) the variations in the speed of the reaction and (b) the relative proportions of the hydrogenated and homologated product. All reactions were conducted in as nearly an identical fashion as possible. The results are shown in Tables II and III. 

Acidities of / -Dicarbonyl Compounds Table 22-1 compares the acidities of some carbonyl compounds with the acidities of alcohols and water. Notice the large increase in acidity for compounds with two carbonyl groups beta to each other. The a protons of the jS-dicarbonyl compounds are more acidic than the hydroxyl protons of water and alcohols. This enhanced acidity results from increased stability of the enolate ion. The negative charge is delocalized over two carbonyl groups rather than just one, as shown by the resonance forms for the enolate ion of diethyl malonate (also called malonic ester). 

Maruoka and co-workers reported a conceptually new MPV reduction system based on bidentate Lewis-acid chemistry [29]. The initial formation of bidentate aluminum catalyst 9 derived from (2,7-dimethyl-l,8-biphenylenedioxy)bis(dimethylalu-minum) (8 prepared from 2,7-dimethyl-l,8-biphenylenediol and 2 equiv. MesAl) and i-PrOH (4 equiv.), followed by treatment of benzaldehyde with the in situ generated (2,7-dimethyl-l,8-biphenylenedioxy)bis(diisopropoxyaluminum) (9) at room temperature instantaneously produced the reduced benzyl alcohol almost quantitatively (Table 2, entry 2). Even with 5 mol% catalyst 9 the reduction proceeds quite smoothly at room temperature to furnish benzyl alcohol in 81 % yield after 1 h (Table 2, entry 3). This remarkable efficiency can be ascribed to the double electrophilic activation of carbonyls by the bidentate aluminum catalyst (Sch. 7). 

The majority of aliphatic ketones give the secondary alcohol on reduction at electrodes of carbon, mercury, lead, or platinum. The usual choice of electrolyte has been dilute sulfuric acid, acetate buffer, or a neutral salt solution, which will become alkaline during the course of reaction that consumes protons. Relatively few studies have been recorded of the isomer ratio obtained by reduction of open chain ketones with a prochiral center adjacent to the carbonyl function [32,33]. Results are collected in Table 2, and one aromatic carbonyl compound is included here for convenience. In general, the erythro-alcohol is favored and in an excess over that present in the equilibrium mixture [32,33]. These results are explained in terms of adsorption of intermediates at the electrode surface. For many of the examples in Table 2, the total yield of alcohol is low and this result is not generally typical of aliphatic carbonyl compounds, as can be seen from Table 3. 

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