Carbon rearrangements

Early Synthesis. Reported by Kolbe in 1859, the synthetic route for preparing the acid was by treating phenol with carbon dioxide in the presence of metallic sodium (6). During this early period, the only practical route for large quantities of sahcyhc acid was the saponification of methyl sahcylate obtained from the leaves of wintergreen or the bark of sweet bitch. The first suitable commercial synthetic process was introduced by Kolbe 15 years later in 1874 and is the route most commonly used in the 1990s. In this process, dry sodium phenate reacts with carbon dioxide under pressure at elevated (180—200°C) temperature (7). There were limitations, however not only was the reaction reversible, but the best possible yield of sahcyhc acid was 50%. An improvement by Schmitt was the control of temperature, and the separation of the reaction into two parts. At lower (120—140°C) temperatures and under pressures of 500—700 kPa (5—7 atm), the absorption of carbon dioxide forms the intermediate phenyl carbonate almost quantitatively (8,9). The sodium phenyl carbonate rearranges predominately to the ortho-isomer. sodium sahcylate (eq. 8). 

When carbon rearrangements are balanced to account for net hexose synthesis, five of the glyceraldehyde-3-phosphate molecules are converted to dihy-droxyacetone phosphate (DHAP). Three of these DHAPs then condense with three glyceraldehyde-3-P via the aldolase reaction to yield 3 hexoses in the form... 

The subjects of this section are two reactions that do not actually involve carbo-cation intermediates. They do, however, result in carbon to carbon rearrangements that are structurally similar to the pinacol rearrangement. In both reactions cyclic intermediates are formed, at least under some circumstances. In the Favorskii rearrangement, an a-halo ketone rearranges to a carboxylic acid or ester. In the Ramberg-Backlund reaction, an a-halo sulfone gives an alkene. 

Different rearrangements were observed in other cases. Thus, Maas22 reported that when photolyzed in benzene the polysilyldiazoketone 180 gave the isomeric ketene 181, the product of a Wolff rearrangement (a 1,2 carbon-to-carbon rearrangement) of the initially formed carbene 182 (Eq. 57). The isomeric bis-silylketene 183 was not observed, but the siloxa-tene 184 was also a product of the reaction. 

Aryl migrations are not confined to carbon/carbon rearrangements, as is seen in the behaviour of (Ph3CO)2 (120, cf. p. 300) on heating ... 

Recently, the hydroxy derivatives of furan, thiophene, and selenophene have been studied with regard to their physical properties and reactions. These compounds are tautomeric and if the oxygen function is placed in the 2-position they exist as unsaturated lactones and undergo carbon-carbon rearrangement, whereas the 3-hydroxy derivatives form oxo-enol tautomeric systems. By NMR the structures of the different tautomeric forms have been determined as well as the position of the tautomeric equilibrium and the rate of isomerization. 

Figure 6.25 Oxygen-to-carbon rearrangement at vinylic carbon.

The reactivity of alkynylstannanes toward electrophiles is one element in the oxygen-to-carbon rearrangement of alkynylstannane derivatives of furanyl and pyranyl lactols (e.g., Equation (85)). The cleavage of the anomeric C-O bond is assisted by the Lewis acid to give an oxonium ion, which is trapped in situ by the nucleophilic stannylalkyne. The utility of this process has been demonstrated in the synthesis of the natural product muricatetrocin C, and the drug substance CMI-977.246... 

Treatment of 4-hydroxy-l-(2-pyridyl)quinolin-2-one (442) with sulfuryl chloride gave 3,3-dichloro-l-(2-pyridyl)quinoline-2, 4-dione (443) which, upon treatment with sodium carbonate, rearranged to pyrido[2,l- >]quinazolin-l 1-one (440) (79CB3424). 

Relatively few data and no systematic studies of the halogenation of dienes have been reported. Monoaddition products are usually formed through the attack on the more substituted double bond. Interhalogens add to allenes to give products in which the positive part of the reagent is attached to the central allenic carbon. Rearrangements, however, may affect product distributions. Ionic mechanisms are usually established, but very few details are available. 

A 1,2-hydride shift has been invoked399 to account for the formation of p-methoxyphenylbutyraldehyde derivatives (337) during the treatment of />methoxy-benzyl-protected allylic alcohols (336) with zeolites. A similar C-glycosidation procedure involving Lewis acid-catalysed anomeric oxygen to carbon rearrangement of tetrahydropyranyl ether derivatives has been reported400 (see Scheme 82). It has been... 

The product of acetyl-CoA carboxylase reaction, malonyl-CoA, is reduced via malonate semialdehyde to 3-hydroxypropionate, which is further reductively converted to propionyl-CoA. Propionyl-CoA is carboxylated to (S)-methylmalonyl-CoA by the same carboxylase. (S)-Methylmalonyl-CoA is isomerized to (R)-methylmal-onyl-CoA, followed by carbon rearrangement to succinyl-CoA by coenzyme B 12-dependent methylmalonyl-CoA mutase. Succinyl-CoA is further reduced to succinate semialdehyde and then to 4-hydroxybutyrate. The latter compound is converted into two acetyl-CoA molecules via 4-hydroxybutyryl-CoA dehydratase, a key enzyme of the pathway. 4-Hydroxybutyryl-CoA dehydratase is a [4Fe-4S] cluster and FAD-containing enzyme that catalyzes the elimination of water from 4-hydroxybutyryl-CoA by a ketyl radical mechanism to yield crotonyl-CoA [34]. Conversion of the latter into two molecules of acetyl-CoA proceeds via normal P-oxidation steps. Hence, the 3-hydroxypropionate/4-hydroxybutyrate cycle (as illustrated in Figure 3.5) can be divided into two parts. In the first part, acetyl-CoA and two bicarbonate molecules are transformed to succinyl-CoA, while in the second part succinyl-CoA is converted to two acetyl-CoA molecules. 

Berson and Willcott (1966) have used the all-carbon rearrangement of an optically active trisubstituted tropilidene (11) to formulate the... 

Treatment of alkynyl tri- -butyltin tetrahydropyranyl ether derivatives with BF3-OEt2 effects an anomeric oxygen to carbon rearrangement, furnishing the corresponding carbon-linked alkynol products (Equation (64)).218... 

Cyclopentenes Vinylcyclopropanes (1) when pyrolyzed at 500 through a glass column coated with lead carbonate rearrange to annulated cyclopentenes (2). In the absence of the salt, the yields are lowered to 15-20%. 

In order to establish definitely the structure of streptomycin, it was required to show that no carbon to carbon rearrangement occurred during the acid degradation of streptomycin to the various streptobiosamine derivatives. The formation of maltol (XIV, page 357) in 17% yield from methyl streptobiosaminide dimethyl acetal provided some evidence that the streptose portion in this derivative was of identical structure with that in streptomycin, which likewise yielded maltol with alkali. However, maltol possesses a linear carbon skeleton, while the streptose portion of the various streptobiosamine derivatives was shown to contain a branched carbon skeleton. It was therefore evident that a carbon to carbon rearrangement occurred during the formation of maltol by alkali. 

This reaction does not proceed via a Whitmore 1,2-shift, but instead is a concerted pericyclic [3,3] sigmatropic rearrangement that results in a cyclic ketone, which after tautomerisation, gives the phenol. Furthermore, in this reaction a C-0 bond is broken, rather than made, and a C-C bond is formed thus, it could have been considered under carbon/carbon rearrangements. 

Thus, the total syntheses of the racemic aflatoxins B, (/), B2 (5) [since this can be prepared by the controlled catalytic hydrogenation of aflatoxin B, (l)51,63)], and B2a (11) were accomplished in a rather elegant carbon rearrangement fashion. 

New mercaptoaryl- and mercaptoheteroaryl-phosphonates (139) have been prepared by or /io-lithiation of the corresponding O, O-diisopropyl S -aryl/hetero-aryl phosphorothioates 138 followed by sulfur to carbon rearrangement. A simple and efficient synthesis of the 2-substituted 3-diethylphosphono 5-methyl-furans 141 from the ketal phosphonate 140 has been reported. Acylation of a-... 

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