Decarboxylation procedure

In the same research line is the decarboxylation procedure developed for the transformation of indolizidinones bearing a carboxylic group in the 8a-position <1996TL5581>. Of practical interest is the possibility to selectively reduce the double bond of unsaturated indolizindiones <2001JOC2181>. 

More recently, radical additions to fluoroethenes have attracted attention. Eguchi et al. [125] applied the Barton decarboxylation procedure to add a range of alkyl radicals to l,l-dichloro-2,2-difluoroethene. Addition was regioselective and the terminal carbon could be hydrolysed to a carboxyl group with silver(I) mediation (Eq. 39). The fluoroalkene is effectively an equivalent for either difluoroacetyl anion or cation synthons, because the adding radical can be approached from either polarity manifold. 

Nonell and coworkers (01JPP846) have also reported a non-decarboxylative procedure based on 2,2 -bipyrrole derivative 39 (Scheme 18), bearing two sets of orthogonal esters. The tetraester 39 could readily be transformed to dialdehyde 36 (R=C6H5) through the intermediacy of 40 by use of the MacFadyen-Stevens sequence (1962JA635) even as the direct conversion of 40 to 36 (R =C6H5) was not facile. 

Use of analytical methods for determination of conjugated glucuronic acid in biological fluids presents special problems. Since small quantities are usually involved, and interfering substances are present, decarboxylation procedures are at a disadvantage. Some methods employ a reduc-timetric determination after hydrolysis. 

A number of materials,10 water, certain organic acids, the most important of which is citric acid, and certain inorganic salts, interfere with the determination. The decarboxylation cannot be conducted in the presence of nitrates and when carbonates are present two separate determinations of carbon dioxide are necessary. The procedure is also inapplicable when oxidizing compounds which are soluble in the hot reagent are present. Another interfering substance, sulfur dioxide,01 can be eliminated by the use of a saturated, acidified (sulfuric acid) solution of potassium dichromate to wash the gases evolved by the decarboxylation procedure. 

Decarboxylation procedures, which have been discussed by Schipper and Day,2 require fairly high temperatures. 

Acetate esters are common by-products of LTA decarboxylation procedures. The yield of diese products, derived from further oxidation of the alkyl radical and quenching of the subsequent carbocation by acetate ions, can be improved by working in acetic acid in die presence of potassium acetate. Selective monodecarboxylation of 1,3- and 1,4-dicarboxyIic acids leads, via an analogous mechanism, to y- and 8-lactones in mo rate to good yields, as illustrate in equation (39). 

It is found that decarboxylation of dichlorofluoroacetate [49] gives about 70% of CCI2FH via competitive abstraction of a proton from solvent by the intermediate CCl2F anion, whereas chlorodifluoroacetate [50] gives very little CCIF2H, suggesting either that chloride ion loss in this case is faster than protonation, or that the process is concerted. Decarboxylation procedures have been widely used, mainly for the preparation of fluorocyclopropyl derivatives as illustrated in Figure 6.36 [51, 52]. 

Perfluoroarylzinc derivatives may be obtained directly from the corresponding iodide and, sometimes, the chloride they are also sufficiently stable to be produced by decarboxylation procedures (Figure 10.15). 

Unsymmetrical phenylpentafluorophenyl and methylpentafluorophenyl compounds are obtained from the appropriate mercury(ll) halide [45], or by decarboxylation procedures [69], and these mixed derivatives are particularly susceptible to attack. Nevertheless, bis(pentafluorophenyl)mercury is very resistant to acid cleavage for example, it can be recrystallised from concentrated sulphuric acid, but the well-known ligand-exchange process, e.g. with mercury(ll) chloride, occurs very rapidly and presumably by a four-centre process [45] (Figure 10.23). 

In the absence of the activating second carbonyl functionality, it is necessary to use more ingenious methods to produce the same net effect. These procedures more often than not involve radical reactions. Among them is the thermolysis of tert-butyl esters of peroxyacids 437, which are readily synthesized in a standard esterification of tert-butyl hydroperoxide with an acid chloride. Decarboxylation proceeds via an initial homolytic cleavage of the 0-0 bond, elimination of CO2, and reduction of the incipient alkyl radical by an added hydrogen atom donor such as 438 (Scheme 2.143). Examples showing the exceptional synthetic importance of this decarboxylation procedure will be presented later. 

Another widely used decarboxylation procedure involves the use of lead tetraacetate. Depending on the nature of the substrate and the reaction conditions, this reagent may transform a carboxylic acid into an alkane or alkene, or into the respective acetoxy derivative (Scheme 2.144). The most favorable conditions for alkane formation utilize a good hydrogen donor as the solvent. Usually this transformation is carried out as a photochemically induced oxidative decarboxylation in chloroform solution, as is exemplified in the conversion of cyclobutanecarboxylic acid in cyclobutane.In contrast, the predominant formation of alkenes occurs in the presence of co-oxidants such as copper acetate. ... 

Since (2) is readily hydrolyzed to the ester (3), the two-step process provides a convenient decarboxylation procedure. 

The Barton decarboxylation procedure was used in the total synthesis of (-)-verrucarol by K. Tadano et al. The initially formed thiohydroxamic ester was decarboxylated to leave a methylene radical on the cyclopentyl ring, which was then trapped by molecular oxygen. Reductive work-up in the presence of f-BuSH finally provided the hydroxylated product. ... 

C.H. Heathcock and co-workers devised a highly convergent asymmetric total synthesis of (-)-secodaphniphylline, where the key step was a mixed Claisen condensation. In the final stage of the total synthesis, the two major fragments were coupled using the mixed Claisen condensation] the lithium enolate of (-)-methyl homosecodaphniphyllate was reacted with the 2,8-dioxabicyclo[3.2.1]octane acid chloride. The resulting crude mixture of (3-keto esters was subjected to the Krapcho decarboxylation procedure to afford the natural product in 43% yield for two steps. 

Decarboxylation. Cohen and Schambach1 report that the usual copper metal-quinoline decarboxylation procedure is much slower than that using the cupric or cuprous salt of the acid (N2,180-200°). They also note that the rate is increased markedly by certain chelating agents such as 2,2 -dipyridyl (Eastman, Aldrich) and 1,10-phenanthroline (Eastman, Aldrich). The latter is more effective, but about twice as expensive. 

A mild decarboxylation procedure was developed by Krapcho.223 When methyl ester 256 was treated with LiCl in DMSO, decarboxylation occurred to give a 78% yield of 257 in the Molander and Hass synthesis of davanone.224 xhis mild procedure is referred to as Krapcho decarboxylation. 

A very interesting development in this area is an application of crown chemistry to the malonic ester synthesis. A one-pot hydrolysis and decarboxylation procedure, using 18-crown-6 and potassium hydroxide in an organic solvent system, has been developed for esters with activating groups (Scheme 52). This procedure, which relies on the ability of 18-crown-6 both to catalyse ester hydrolysis and to facilitate decarboxylation under mild conditions, offers a simplification of what is often the yield-determining part of conventional malonate syntheses. 

Through the carboxyl-directed alkenylation/decarboxylation procedure, a series of meta-substituted stilbenes can be synthesized from ortho-substituted benzoic acids (Scheme 18.13). 

N-(D-Threo- and racemic erythro-3-amino-2-hydroxy-butanoyl)-2, 3 -dideoxykanamycin A has been prepared using a standard esterification procedure with the corresponding azido-hydroxy-butanoic acid. Glucuronide saponins have been used to furnish paromamine and ribostamycin by means of lead tetraacetate or anodic oxidative decarboxylation procedures. Phase-sensitive 2D COSY spectra... 

This degradation procedure would not be applicable for determining the relative incorporation of isotope into the carbonyl and carboxyl moieties of acetoacetate labeled in the a- and 7-carbons (C HjCOC H2-COOH). The simplicity of the decarboxylation procedure no doubt accounts for the popularity of the use of fatty acids labeled in an odd carbon. 

Figure 10.19 Variants of the classical Hunsdiecker halo-decarboxylation procedure...

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