Decarboxylation radical-based

Decarboxylation. - Barton s group has further extended their studies of radical-based decarboxylations in a number of ways (Scheme 10). One-carbon degradations of acids, RCO2H, to alkanes, RH, can be simply achieved by conversion into the thiohydroxamic esters derived from N-hydroxypyridine-2-thione followed by heating in benzene or toluene in the presence of t-butyl thiol.This avoids the use of more expensive tin hydrides which produce organostannane by-products which can be difficult to remove. By changing the traps available to the... 

The reaction fails if the decarboxylation produces a radical that is easily oxidized, such as an a-hydroxyalkyl radical.2 In intermediate cases, such as tert-alkyl or a-alkoxyalkyl radicals,2 the yield based on the parent quinono is usually improved by using an excess of persulfate and carboxylic acid to compensate for the loss of radicals due to oxidation (footnote b, Table I). 

Rychnovsky et al. considered the formation of achiral conformers from chiral molecules and trapping the prochiral radical with a hydrogen atom donor based on memory of chirality (Scheme 12) [41], The photo-decarboxylation of optically active tetrahydropyran 40 leads to an intermediate 43, which now does not contain a stereocenter. If the intermediate 43 can be trapped by some hydrogen atom source before ring inversion takes place, then an optically active product 41 will be formed. This is an example of conformational memory effect in a radical reaction. It was reported that the radical inversion barrier is low (< 0.5 kcal/mol) while the energy for chair flip 43 44 is higher (5 to... 

Addition of P—H bonds to unsaturated systems also continues to be used as a route to heterocyclic systems. Thus base-catalysed cyclization of the phosphine (32) [prepared by the addition of methyl methacrylate (2 moles) to phenylphosphine], followed by subsequent hydrolysis and decarboxylation, affords the phosphorinanone (33). The phosphorinanone system is also directly accessible by the addition of phenylphosphine to divinyl ketones.28 The radical-initiated addition of phenylphosphine to dialkynyl systems (34) gives the heterocyclohexadienes (35).29 80 The stereochemistry of the addition of phenylphosphine to cyclo-octa-2,7-dienone to give... 

This reaction resembles decarboxylation of carboxylates during electrode one-electron oxidation (Kolbe reaction). Kolbe reaction also consists of one-electron oxidation, decarboxylation, and culminates in dimerization of alkyl radicals just after their formation at the electrode surface. When the sulfate radical acts as a one-electron oxidant, the caboradical dimerization is hampered. The radicals can be used in preparative procedures. One typical example is alkylation of heterocyclic nitrogen bases (Minisci et al. 1983). This difference between Kolbe reaction and the reaction with the help of a dissolved electrode (the sulfate radical) deserves some explanation. The concentration of the one-electron oxidation products in the electrode vicinity is significantly higher than that in the bulk of the solution. Therefore, in the case of anode-impelled reactions, the dimerization of radicals produced from carboxylates proceeds easily. Noticeably, 864 secures the single electron nature of oxidation more strictly than an anode. In electrode reactions, radical intermediates can... 

In this type of spin traps, 5,5-dimethyl-l-pyrroline-Af-oxide (DMPO) deserves particular mention. DMPO is widely employed as a spin trap in the detection of transient radicals or ion-radicals in chemical and biological systems (see, e.g., Siraki et al. 2007). Characteristic ESR spectra arising from the formation of spin adducts are used for identification of specific spin species. In common opinion, such identification is unambiguous. However, in reactions with superoxide ion (Villamena et al. 2004, 2007b), carbon dioxide anion-radical (Villamena et al. 2006), or carbonate anion-radical (Villamena et al. 2007a), this spin trap gives rise to two adducts. Let us consider the case of carbonate anion-radical. The first trapped product arises from direct addition of carbonate anion-radical, second adduct arises from partial decarboxylation of the first one. Scheme 4.25 illustrates such reactions based on the example of carbonate anion-radical. 

The oxidative decarboxylation of carboxylic acids is the most convenient source for the alkylation of protonated heteroaromatic bases owing to their easy availability and the high versatility of the reaction, which permits methyl, primary, secondary, and tertiary alkyl radicals to be obtained under very simple experimental conditions. The following methods have been utilized. 

Two sources of acyl radicals have proved to be useful for the homolytic acylation of protonated heteroaromatic bases the oxidation of aldehydes and the oxidative decarboxylation of a-keto acids. The oxidation... 

The usual sources used for the homolytic aromatic arylation have been utilized also in the heterocyclic series. They are essentially azo- and diazocompounds, aroyl peroxides, and sometimes pyrolysis and photolysis of a variety of aryl derivatives. Most of these radical sources have been described in the previous review concerning this subject, and in other reviews concerning the general aspects of homolytic aromatic arylation. A new source of aryl radicals is the silver-catalyzed decarboxylation of carboxylic acids by peroxydisulfate, which allows to work in aqueous solution of protonated heteroaromatic bases, as for the alkyl radicals. 

Reaction of 1,2 -dicarboxylic acids has been used for the formation of a number of strained alkenes and also applied to the Diels-Alder addition products from maleic anhydride (Table 9.5). Both cis- and tr s-diacids take part in the process. Aqueous pyridine containing, triethylamine as a strong base, is considered the best solvent and higher yields are obtained at temperatures of around 80 "C [130]. Use of a divided cell avoids a possibility of electrocatalytic hydrogenation of the product at the cathode. The addition of /a/-butylhydroquinone as a radical scavenger prevents polymerization of the product [127], An alternative chemical decarboxylation process is available which uses lead tetraacetate [131] but problems can arise because of reaction between the alkene and lead tetraacetate. 

Thiepane (35) has been synthesized by an intramolecular radical addition of the thiyl radical (equation 59) which was generated by photolysis of a thiol (71TL2025). Similarly, C—S bond formation has been achieved (equation 60) by an intramolecular condensation of 6-mercaptohexanoic acid to give the thiolactone, thiepan-2-one (135) (64MI51700). A Dieckmann-type base-catalyzed cyclization of a diester precursor followed by acid-catalyzed hydrolysis and decarboxylation has been used in the synthesis of thiepan-3-one (41) as indicated in equation (61) (52JA917). 

Oxidative cleavage by means of electrochemically generated cation-radicals is also possible thus benzyl ethers may be cleaved and carboxylates decarboxylated using cation-radicals of brominated triphenylamines in acetonitrile containing a weak base.34 35 Such as indirect reaction makes it... 

Loss of a carbon atom from the precursor need not always result. Barton and Crich have introduced a related procedure based on the chemistry of mixed oxalates, an example of which is provided in Scheme 49.159 Double decarboxylation is involved in the decomposition of oxalate precursors, such as (39). Unfortunately, there are indications that this method may to be limited to tertiary alcohols one secondary alcohol derived mixed oxylate did not fragment completely to the alkyl radical. 

The use of the hypervalent iodine reagent [bis(trifluoroacetoxy)iodo]benzene has been reported to be effective in the synthesis of C-nucleoside-like compounds. Radical decarboxylation of a suitably protected uronic acid, initiated photochem-ically, followed by addition of a heterocyclic base provided the C-nucleoside in high yield.154 The mode of action involves initial radical formation of 122 (Scheme 33), followed by introduction of the base and radical coupling.155 The anomeric selectivity was high in some examples, and low in others—lepidine gave the highest proportion of the ( anomer. Isolated yields were poor to moderate. 

Photoinduced electron transfer from the carboxylate ion to the excited triplet phthalimide (fcT = 293-300 kj mol-1) appears to be followed by a rapid protonation of the radical anion and cyclization via a biradical recombination reaction (Scheme 9.1). Acetone (which also acts as photosensitizer) containing a small amount of water is the solvent of choice, whereas potassium carbonate is the ideal base to enhance cyclization versus simple decarboxylation and ring opening of the phthalimide [4]. 

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