Carboxylate complexes acylation

Coenzyme A (see also p. 106) is a nucleotide with a complex structure (see p. 80). It serves to activate residues of carboxylic acids (acyl residues). Bonding of the carboxy group of the carboxylic acid with the thiol group of the coenzyme creates a thioester bond (-S-CO-R see p. 10) in which the acyl residue has a high chemical potential. It can therefore be transferred to other molecules in exergonic reactions. This fact plays an important role in lipid metabolism in particular (see pp. 162ff), as well as in two reactions of the tricarboxylic acid cycle (see p. 136). 

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 alkyl peroxide then can decompose to give PFe OH and 0=CR2, or, if a tertiary alkyl group, Acyl complexes such as PFe C(0)C4H9 react with dioxygen to yield only PFe carboxylate complexes and the fi-oxo dimer, PFe -0-Fe -P, with no evidence of ferryl complexes being formed. 

Pericyclic electrochemical reactions are increasingly developed. They involve chain reactions with a radical cation as chain transferring step or the generation of reactive dienophiles (see Chapter 22, Sec. V). Transition metal complexes are increasingly applied in electrochemistry as electrocatalysts for reductive carboxylation [47], acylation or alkylation [41], or activation [51]. 

In synthetic target molecules esters, lactones, amides, and lactams are the most common carboxylic acid derivatives. In order to synthesize them from carboxylic acids one has generally to produce an activated acid derivative, and an enormous variety of activating reagents is known, mostly developed for peptide syntheses (M. Bodanszky, 1976). In actual syntheses of complex esters and amides, however, only a small selection of these remedies is used, and we shall mention only generally applicable methods. The classic means of activating carboxyl groups arc the acyl azide method of Curtius and the acyl chloride method of Emil Fischer. 

When a Br nsted base functions catalytically by sharing an electron pair with a proton, it is acting as a general base catalyst, but when it shares the electron with an atom other than the proton it is (by definition) acting as a nucleophile. This other atom (electrophilic site) is usually carbon, but in organic chemistry it might also be, for example, phosphorus or silicon, whereas in inorganic chemistry it could be the central metal ion in a coordination complex. Here we consider nucleophilic reactions at unsaturated carbon, primarily at carbonyl carbon. Nucleophilic reactions of carboxylic acid derivatives have been well studied. These acyl transfer reactions can be represented by... 

As acylating agent, a carboxylic anhydride may be used instead of the acyl halide. The reaction then yields the arylketone together with a carboxylic acid, each of which forms a complex with the Lewis acid used. The catalyst therefore has to be employed in at least twofold excess ... 

Because hydride ion is a base as well as a nucleophile, the actual nucleophilic acyl substitution step takes place on the carboxylate ion rather than on the free carboxylic acid and gives a high-energy dianion intermediate. In this intermediate, the two oxygens are undoubtedly complexed to a Lewis acidic aluminum species. Thus, the reaction is relatively difficult, and acid reductions require higher temperatures and extended reaction times. 

The Hell-Volhard-Zelinskii reaction is a bit more complex than it looks and actually involves substitution of an acid bromide enol rather than a carboxylic acid enol. The process begins with reaction of the carboxylic acid with PBr3 to form an acid bromide plus HBr (Section 21.4). The HBr then catalyzes enolization of the acid bromide, and the resultant enol reacts with Br2 in an cr-substitution reaction to give an cv-bromo acid bromide. Addition of water hydrolyzes the acid bromide in a nucleophilic acyl substitution reaction and yields the a-bromo carboxylic acid product. 

In acid solution 1-acyl-1//-azepines and alkyl l//-azepine-l-carboxylates undergo rapid aromatization to A-arylcarbamates,115,139,142 whereas 1/Z-azepine-l-carbonitrile suffers quantitative rearrangement and hydrolysis to phenylurea.163 Rearrangement of ethyl l//-azepine-l-carboxylate to ethyl A-phenylcarbamate is also rapid (5 min) and quantitative with boron trifluoride-diethyl ether complex in benzene.245... 

Table 5. Carboxylic Acids 5 by Removal of the Chiral Auxiliary from Iron-Acyl Complexes 4...

Oxidative decomplexation of iron acyl complexes in the presence of alcohols provides the corresponding carboxylates 7. Usual conditions employ ca. 7% alcohol in dichloromethane or dichloromethane/carbon disulfide as the solvent with bromine as the oxidant. 

The rates of reaction vary with the isomer in the order 3 > 4 > 2. The imido complex may then be hydrolyzed under more vigorous acid conditions to give ammonium ion and the carboxylic acid, probably via the intermediate formation of the acyl complex. In this case the 2-isomer reacts more rapidly than the others. Treatment of the imido complexes with alkali, however, liberates the nitrile (see also Seetion B,l,e) ... 

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