Unsaturated carboxylic acids oxidative cleavage

A cursory inspection of key intermediate 8 (see Scheme 1) reveals that it possesses both vicinal and remote stereochemical relationships. To cope with the stereochemical challenge posed by this intermediate and to enhance overall efficiency, a convergent approach featuring the union of optically active intermediates 18 and 19 was adopted. Scheme 5a illustrates the synthesis of intermediate 18. Thus, oxidative cleavage of the trisubstituted olefin of (/ )-citronellic acid benzyl ester (28) with ozone, followed by oxidative workup with Jones reagent, affords a carboxylic acid which can be oxidatively decarboxylated to 29 with lead tetraacetate and copper(n) acetate. Saponification of the benzyl ester in 29 with potassium hydroxide provides an unsaturated carboxylic acid which undergoes smooth conversion to trans iodolactone 30 on treatment with iodine in acetonitrile at -15 °C (89% yield from 29).24 The diastereoselectivity of the thermodynamically controlled iodolacto-nization reaction is approximately 20 1 in favor of the more stable trans iodolactone 30. 

Generally, the yields of the diols are comparable with those obtained by the classical osmium tetroxide procedure, but are lower when the diol has a high degree of solubility in water. Under such circumstances, further oxidative cleavage occurs in the aqueous phase to produce the carboxylic acids [18]. The kinetics and mechanism of the oxidation of a,p-unsaturated carboxylic acids with permanganate in the presence of phase-transfer catalysts has been studied [25]. 

Cleavage of l-trimethyhilyloxybicyclo[n.l.O]alkanes. These cyclopropane derivatives (I) are cleaved by LTA in glacial acetic acid to acyclic oi-unsaturated carboxylic acids (equation I). An intermediate cyclopropanol (o) is formed initially and then two bonds of the cyclopropane ring are cleaved by oxidation. ... 

Nickel(O) complexes of alkjmes in the presence of carbon dioxide undergo oxidative cycli-zation to produce oxametallacycles 51 (Scheme 32).l l Direct cleavage of the oxametal-lacycle in the presence of strong acids affords unsaturated carboxylic acids 52 (Scheme 33). The coupling of di5mes with carbon dioxide leads to an efficient synthesis of bicy-clic a-pyrones such as 53 by a formal [2+2+2] cycloaddition (Scheme 33).l l... 

Zhang et al. effected palladium-catalyzed oxidative C3-vinylations of indol-izine-l-carboxylates 136 with various styrenes (Scheme 10.45)."° Use of the bidentate nitrogen ligand bipy was key to formation of the branched a-product regioisomer 137 over the linear P-product. The authors later demonstrated that the same indolizine-l-carboxylates could be C3-acylated with a variety of a,P-unsaturated carboxylic acids via C—H and C—C double bond cleavage under oxidative conditions (138). "... 

Linkers that enable the preparation of y-lactones by cleavage of hydroxy esters from insoluble supports are discussed in Section 3.5.2. Resin-bound y-lactones have been prepared by Baeyer-Villiger oxidation of cyclobutanones [39], by intramolecular addition of alkyl radicals to oximes [48], by electrophilic addition of resin-bound sele-nenyl cyanide or bromide to 3,y-unsaturated acids (Figure 9.2 [100]), and by palladium-mediated coupling of resin-bound aryl iodides with allenyl carboxylic acids (Entry 10, Table 5.7 [101]). 

Oxidation. Ketones are oxidized with powerful oxidizing agents such as chromic or nitric acid. During oxidation, carbon—carbon bond cleavage occurs to produce carboxylic acids. Ketone oxidation with hydrogen peroxide, or prolonged exposure to air and heat, can produce peroxides. Concentrated solutions of ketone peroxides (>30%) may explode, but dilute solutions are useful in curing unsaturated polyester resin mixtures (see... 

This step leaves two cleavage products. The first, derived from the two carbons at the carboxyl end of the fatty acid, is acetyl-CoA, which can be further metabolized in the TCA cycle. The second cleavage product is a shorter fatty acyl-CoA. Thus, for example, the initial step of digesting a fatty acid with 16 carbons is an acyl-CoA molecule where the acyl group has 14 carbons and a molecule of acetyl-CoA. The P-oxidation scheme may be used to accommodate unsaturated fatty acids also. The reactions occur as described previously for the saturated portions of the molecule. Where a trans carbon-carbon double bond occurs between the %- and p-carbons of the acyl-CoA, the accommodation is fairly simple reaction 1 isn t needed. Where the double bonds are in the cis configuration, or are between the P and y carbons, isomerase enzymes change the location of the double bonds to make recognizable substrates for P-oxidation. 

The physical properties, preparation and reactions of ruthenium tetroxide have been reviewed by Lee and van den Engh, Rylander," Haines and Hetuy and Lange. A more vigorous oxidant than osmium tetroxide, its reaction with double bonds produces only cleavage products. " Under neutral conditions aldehydes are formed from unsaturated secondary carbons while carboxylic acids are obtained under alkaline or acidic conditions. For example, Shalon and Elliott" found that ruthenium tetroxide reacted with compound (11) to give the corresponding aldehyde under neutral conditions, but that a carboxylic acid was formed in acidic or alkaline solvents (equation 23). 

Oxidations with peimanganates are suitable for the preparation of carboxylic acids from saturated and benzylic alcohols. Unsaturated alcohols may suffer cleavage of double bonds. Conventional oxidations are carried out in aqueous media, usually in the presence of alkali hydroxides. Thus... 

Unsaturated halogenated compounds with a central C = C or C = C bond undergo cleavage on oxidation in the middle of the molecule and form two carboxylic acids without loss of a carbon atom. The reaction mechanism of the oxidation of internal fluoroalkenes by potassium permanganate includes hydroxylation of the C = C bond in 2 by permanganate, accompanied by dehydrofluorination of the geminal fluoroalkane-1,2-diol 3 and formation of an intermediate fluorocarbonyl compound 4 oxidative cleavage of the C-C bond in 4 leads to the final products 5.1... 

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