Protons, from carboxylic acids, reduction

From a study of the decompositions of several rhodium(II) carboxylates, Kitchen and Bear [1111] conclude that in alkanoates (e.g. acetates) the a-carbon—H bond is weakest and that, on reaction, this proton is transferred to an oxygen atom of another carboxylate group. Reduction of the metal ion is followed by decomposition of the a-lactone to CO and an aldehyde which, in turn, can further reduce metal ions and also protonate two carboxyl groups. Thus reaction yields the metal and an acid as products. In aromatic carboxylates (e.g. benzoates), the bond between the carboxyl group and the aromatic ring is the weakest. The phenyl radical formed on rupture of this linkage is capable of proton abstraction from water so that no acid product is given and the solid product is an oxide. 

The nature of the cathode material is not critical in the Kolbe reaction. The reduction of protons from the carboxylic acid is the main process, so that the electrolysis can normally be conducted in an undivided cell. For substrates with double or triple bonds, however, a platinum cathode should be avoided, as cathodic hydrogenation can occur there. A steel cathode should be used, instead. 

The Grignard reagents prepared from the activated magnesium appear to react normally with electrophiles. Thus reactions with proton donors, ketones, and carbon dioxide afford hydrocarbons, alcohols, and carboxylic acids, respectively. The reductive coupling of ketones to pinacols had also been accomplished with the activated magnesium. ... 

The bis-DIOP complex HRh[(+)-DIOP]2 has been used under mild conditions for catalytic asymmetric hydrogenation of several prochiral olefinic carboxylic acids (273-275). Optical yields for reduction of N-acetamidoacrylic acid (56% ee) and atropic acid (37% ee) are much lower than those obtained using the mono-DIOP catalysts (10, II, 225). The rates in the bis-DIOP systems, however, are much slower, and the hydrogenations are complicated by slow formation of the cationic complex Rh(DIOP)2+ (271, 273, 274) through reaction of the starting hydride with protons from the substrate under H2 the cationic dihydride is maintained [cf. Eq. (25)] ... 

Therefore, using either direct Birch reduction alkylation or Birch reduction-protonation-enolate formation alkylation, both followed by auxiliary removal, it is possible to prepare either enantiomer of a desired 2,5-cyclohexadiene-l -carboxylic acid derivative in excellent enantiomeric purity from the same starting materials. 

In the first step of the conversion catalyzed by pyruvate decarboxylase, a carbon atom from thiamine pyrophosphate adds to the carbonyl carbon of pyruvate. Decarboxylation produces the key reactive intermediate, hydroxyethyl thiamine pyrophosphate (HETPP). As shown in figure 13.5, the ionized ylid form of HETPP is resonance-stabilized by the existence of a form without charge separation. The next enzyme, dihydrolipoyltransacetylase, catalyzes the transfer of the two-carbon moiety to lipoic acid. A nucleophilic attack by HETPP on the sulfur atom attached to carbon 8 of oxidized lipoic acid displaces the electrons of the disulfide bond to the sulfur atom attached to carbon 6. The sulfur then picks up a proton from the environment as shown in figure 13.5. This simple displacement reaction is also an oxidation-reduction reaction, in which the attacking carbon atom is oxidized from the aldehyde level in HETPP to the carboxyl level in the lipoic acid derivative. The oxidized (disulfide) form of lipoic acid is converted to the reduced (mer-capto) form. The fact that the two-carbon moiety has become an acyl group is shown more clearly after dissocia-... 

In ergosterol biosynthesis, side chain alkylation of lanosterol normally takes place to build 24-methylenedihydrolanosterol, which itself is then the substrate for demethylation reactions at and C. The C -demethylation has been studied in detail. It is an oxidative demethylation catalyzed by a cytochrome P -system. The first step involved in this reaction is the hydroxylation of the Cj -methy1-group to form the C -hydroxymethyl derivative. A second hydroxylation and loss of water lead to the C -formyl intermediate, which is hydroxylized a third time to form the corresponding carboxylic acid. Decarboxylation does not directly take place, but proceeds instead by abstraction of a proton from C, followed by elimination and formation of a A 4-double bond. The NADPH-dependent reduction of the A14 -double bond finishes the demethylation reaction. Subsequently, demethylation at has to take place twice, followed by a dehydrogenation reaction in A" -position and isomerization from A8 to A7 and A24(28) to A22. respectively. 

Preparation of Derivatives. Enoate derivatives are prepared from the corresponding chiral alcohol by treatment with acry-loyl chloride in the presence of Triethylamine and catalytic 4-Dimethylaminopyridine or the appropriate carboxylic acid chloride and Silveril) Cyanide. Alkynyl ethers are readily available from the potassium alkoxide by treating with Trichloroethylene, in situ dechlorination with n-Butyllithium, and electrophilic trapping. Trapping the intermediate anion with a proton source or lodomethane followed by Lindlar reduction of the alkynyl ether affords the corresponding vinyl and l-(Z)-propenyl ether, respectively, while reduction of the alkynyl ether with Lithium Aluminum Hydride affords the l-( )-propenyl ether. 

In a later development by Bedenbaugh et methylamine was used as solvent and lithium as electron donor. No proton donor was required, suggesting that the lithium salt (28) of hemiaminal (27) is stable under the reaction conditions (both aldehydes and aldimines are reduced by the reagent cf. the analogous reduction of carboxylic acids, Section 1.12.2 and Scheme 2). Yields of aldehydes produced by this method are shown in Table 8. It is notable that only tertiary amides are reduced satisfactorily. A major limitation of the reaction is the substantial formation of side products resulting from transamid-ation by the methylamine solvent (/. e. RCONHMe from RCONR 2). 

Aromatic acids are reduced by metal-ammonia solutions very much more readily than simple hydrocarbons and ethers. In contrast to the normal requirements for the latter derivatives, it is often possible to achieve reduction with close to stoichiometric quantities of metal. The addition of aromatic carboxylic acids to liquid ammonia (or vice versa) results in the immediate precipitation of the ammonium salt. As the metal is added, however, the precipitate usually dissolves as reduction proceeds, especially if lithium is used. If reduction is carried out in carefully dried, redistilled ammonia, as little as 2.2 mol of lithium are consumed in some cAses, thereby demonstrating that the substrate is reduced much more readily than the ammonium ions, which instead react with the intermediates from reduction of the substrate. However, protonation by NH4 is not essential since reduction proceeds equally well on preformed metal car-boxylates (although low solubility is then often a problem). The addition of an alcohol is not necessary, but it may serve as a useful buffer and can often improve solubility. The presence of alcohol can nevertheless be deleterious, since it facilitates isomerization of the initially formed 1,4-dihydro isomer to the 3,4-isomer and in this way affords the possibility of further reduction. ... 

Controlled addition of a suitable proton donor or electrophile (reductions) or nucleophile (oxidations) is often useful in determining a reaction mechanism. The strength of a proton donor may vary from perchloric acid through acetic acid and a phenol to an alcohol C acids, such as malonic ester, or N acids, such as urea, may also be used. Used as bases may be pyridine, carboxylate ions, alkoxides, or salts of malonic ester. Sometimes it is of interest to determine whether it is the basic or the nucleophilic properties of the compound that are important. The use of two bases with approximately the same pK values but widely differing in nucleophilicity, such as pyridine and a 2,6-dialkylpyridine, might answer the question. 

Similar to the concept described for the Oj-Hj cell system, the reductive activation of oxygen can be expected at the cathode in the presence of a suitable catalyst. On the basis of this zinc-air battery model, we have designed a number of catalytic systems from mixtures of zinc powder, carboxylic acid and various metal chlorides for oxygenations of alkanes and alkenes. In these catalytic systems, zinc powder works as the reductant as well as the electron conducting medium. The carboxylic acid works as a proton-conducting medium. Oxygen is reductively activated on the metal cations by protons from the carboxylic acid and electrons from zinc powder. 

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