Rearrangement ester derivatives

Esters derived from the primary alcohols are the most stable and those derived from the tertiary alcohols are the least stable. The decomposition temperature is lower in polar solvents, eg, dimethyl sulfoxide (DMSO), with decomposition occurring at 20°C for esters derived from the tertiary alcohols (38). Esters of benzyl xanthic acid yield stilbenes on heating, and those from neopentyl alcohols thermally rearrange to the corresponding dithiol esters (39,40). The dialkyl xanthate esters catalytically rearrange to the dithiol esters with conventional Lewis acids or trifluoroacetic acid (41,42). The esters are also catalytically rearranged to the dithiolesters by pyridine Ai-oxide catalysts (43) ... 

Other methods for the preparation of cyclohexanecarboxaldehyde include the catalytic hydrogenation of 3-cyclohexene-1-carboxaldehyde, available from the Diels-Alder reaction of butadiene and acrolein, the reduction of cyclohexanecarbonyl chloride by lithium tri-tcrt-butoxy-aluminum hydride,the reduction of iV,A -dimethylcyclohexane-carboxamide with lithium diethoxyaluminum hydride, and the oxidation of the methane-sulfonate of cyclohexylmethanol with dimethyl sulfoxide. The hydrolysis, with simultaneous decarboxylation and rearrangement, of glycidic esters derived from cyclohexanone gives cyclohexanecarboxaldehyde. 

Lormetazepam (84) is readily synthesized by Polonovski rearrangement of benzodiazepine oxide derivative by heating with acetic anhydride followed by saponification of the resulting rearranged ester.The mechanism of this rearrangement to... 

Figure 3.11 Woodward s reagent K undergoes a rearrangement in alkaline solution to form a reactive ketoket-enimine. This active species can react with a carboxylate group to create another active group, an enol ester derivative. In the presence of amine nucleophiles, amide bond formation takes place.

Only limited precedent exists for the stereoselective enolization and subsequent condensation of a-heteroatom-substituted esters 48a and 48b (eq. [29]). Ireland has examined the enolization process for a-amino ester derivatives where the Claisen rearrangement (chair-preferred transition states) was employed to ascertain enolate geometry (Scheme 10) (43). These results imply that 48a [X = N(CH2Ph)2 ] exhibits only modest selectivity for ( )-enoIate formation under the... 

Apart from the reaction of cyclohexanecarboxylic acid with methyllithium, cyclohexyl methyl ketone has been prepared by the reaction of cyclohexylmagnesium halides with acetyl chloride or acetic anhydride and by the reaction of methylmagnesium iodide with cyclohexanecarboxylic acid chloride. Other preparative methods include the aluminum chloride-catalyzed acetylation of cyclohexene in the presence of cyclohexane, the oxidation of cyclohexylmethylcarbinol, " the decarboxylation and rearrangement of the glycidic ester derived from cyclohexanone and M)utyl a-chloroj)ropionate, and the catalytic hydrogenation of 1-acetylcycIohexene. "... 

Carboxylic acids can also be protected as ortho esters. Ortho esters derived from simple alcohols are very easily hydrolyzed, and a more useful ortho ester protecting group is the 4-methyl-2,6,7-trioxabicyclo[2.2.2]octane structure. These bicyclic orthoesters can be prepared by exchange with other ortho esters, by reaction with iminoethers, or by rearrangement of the ester derived from 3-hydroxymethyl-3-methyloxetane. 

In a related type of reaction, the styryl isocyanates, readily available by Curtius rearrangement of cinnamoyl azides, undergo thermal cyclization to l-isoquinolones in good yield (equation 34) the reaction can also be carrried out using Friedel-Crafts catalysts. 2,3-Dihydro-4( 1//)- isoquinolones are obtained by Dieckmann cyclization of N- (o- carbalkoxy-benzyl)glycine ester derivatives (equation 35). The same reaction has been used for the synthesis of a range of non-aromatic heterocycles (equations 36 and 37). 

The mechanism of Scheme 34 quantitatively explains the yields of rearrangement, solvent-derived and N3-derived products of hydrolysis of hydroxylamine or hydroxamic acid esters that yield selective nitrenium ions (log 5 One of the characteristics of these hydrolysis reactions is the... 

A farther example of the same type of rearrangement is provided by the observation of Komfeld and oo-workers,888 drawn durim lla-ir synthesis of lysergic acid, that treatment of the 0,y-epoxy ester derivative shown in Eq. (509) with the base saroosine (tbe ethyl ester of A -methylglydue) led to a lactone instead of the desired nucleophilic addition product. 

Krespan also found that allyl alcohol added to 1-mcthoxy-2-(trifluoromethyl)tetrafluoro-propcnc, derived from perfluoro(2-mclhylpropene). to give the rearranged ester 5. a presage of the Johnson Claiscn rearrangement. Reactions of allylic alcohols with vinyl ethers derived from perfluoro(2-methylpropene) were subsequently studied by Andreev and co-workers11 and are discussed below. 

P,y-Unsaturated a-amino esters. y-Phenylseleno-a, (3-unsaturated esters on treatment with NCS (3 equiv.), N,N-diisopropylethylamine (6 equiv.), and an alkyl carbamate (3 equiv.) in methanol at 25° rearrange to derivatives of p,y-unsaturated a-amino acids, generally in 60-80% yield.2... 

Other simple alkenois (enols) also rearrange to carbonyl compounds. However, ether and ester derivatives of enols are known and can be prepared by... 

Ester derivatives, RCH=CH—CH2COOR, and the corresponding unsaturated aldehydes and ketones, RCH=CH—CH2COR, are much more prone to this type of rearrangement than are the acids. 

The rearrangement is of interest because the corresponding enzymatic interconversion of aldoses and ketoses is an important part of the biosynthetic, photosynthetic, and metabolic pathways, as we shall see in Section 20-9. Although the biochemical rearrangement also may proceed by way of enediol intermediates, it is highly stereospecific and yields only one of two possible stereoisomeric aldoses. For example, glucose, but not mannose, can be enzymatically interconverted with fructose as the 6-phosphate ester derivative ... 

The first nonambiguous report of rearrangement of esters derived from propargyl alcohols promoted by silver salts was due to Saucy and coworkers at Hoffmann-La Roche.50 Their observations on the transformation of acetate derived from... 

A Ciba-Geigy group used the Carroll reaction for the synthesis of hydroxyethylene dipeptide iso-steres. Alcohol (80) was converted with diethyl isopropylmalonate to the mixed malonic ester derivative (81) by Ti(OEt)4 catalysis. Subsequent sigmatropic rearrangement of (81) was also effectively catalyzed by Ti(OEt)4, thereby allowing a one-step conversion of the allylic alcohol (80) to ester (82) (Scheme 13). 

The rearrangement products derived from aromatic and non-aromatic heterocyclic amines crystallize readily from the lower alcohols. Unlike those of many of the A-substituted glycosylamines, the crystals are not solvated. On the other hand, the ketose derivatives of aralkyl- and alkyl-amines, such as 2-phenylethylamine, ethanolamine, diethanolamine, glycine ethyl ester, and phenylalanine (see Table II), are hydrated or alcoholated, or both, and are difficult to isolate in pure crystalline form. The crystals which have been isolated were hygroscopic. Alcohols, aqueous alcohols, and water are the most commonly used solvents for crystallization. Acetone, ether, or benzene have been added to the alcoholic media in order to increase the yield of crystalline compound. The use of solvents that contain peroxides promotes decomposition of the crystals during storage. ... 

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