Carbon acetolysis

Conversely, processes which convert carbons to sfp- carbons are more favorable for five-membered than for six-membered rings. This can be illustrated by the data for acetolysis of cyclopentyl versus cyclohexyl tosylate. The former proceeds with an enthalpy of activation about 3kcal/mol less than the latter." A molecular mechanics analysis found that the difference was largely accounted for by the relief of torsional strain in the cyclopentyl case." Notice that there is an angle-strain effect which is operating in the opposite direction, since there will be some resistance to the expansion of the bond angle at the reaction center to 120° in the cyclopentyl ring. 

Methoxy-7)5-hydroxy-B-homo-estr-5(10)-en-17-one (70a) ° The buffered acetolysis solution is prepared by heating at reflux overnight a solution prepared from anhydrous potassium carbonate (3.5 g), acetic anhydride (5 ml) and glacial acetic acid (250 ml). 

Hardy effect.248-249 The internal return part of the ionization equilibrium is particularly hard to detect since it is almost completely independent of the concentration of anything in the bulk of the solution outside of the solvent cage. The extent of internal return will depend on the reactivity of the cage walls and their resistance to the escape of either ion. Unless internal return has been eliminated by the use of an extremely reactive cage wall, the measured rate is not that of the ionization but the lesser rate of ion pair dissociation. In the case of the acetolysis of a, a-dimethylallyl chloride (XXXIX), internal return is detectable by virtue of the fact that the chloride ion can return to either of two allylic carbon atoms.248... 

Here we have a c = c group attached to a carbon atom which is adjacent to be carbon atom where nucleophilic substitution can occur and during the course of the reaction becomes bonded of partially bonded to the reaction centre to form a non-classical or bridged ion (Fig. 1 to 1(c)). Thus the rate and/or the stereochemistry may be affected. This explains why the acetolysis of 5 is 1011 times faster than that of 5(a), because it involves the formation of a non-classical carbocation... 

In contrast, the results obtained in the methanolysis, acetolysis, and trifluoroacetolysis of the tosylate 91 were not the expected ones. Cram obtained the methyl ether 93, the acetate 94 and the trifluoro-acetate 95 with the same configuration and optical purity as in the direct synthesis from the alcohol 92. These solvolyses at the bridge carbon atom of [2.2]paracyclophane therefore proceed with complete retention of configuration. The rate of acetolysis of the tosylate 91 also deviates considerably from that of aliphatic secondary tosylates it is some 100 times faster than that of 2-butyl tosylate and about the same as that of a-phenylneopentyl tosylate, acetolysis of which is only slightly stereospecific. 

A long series on stereochemistry has continued in a smdy of the acetolysis of triterpenoid / -toluenesulfonates in the presence of NaOAc. Both substitution and elimination products were formed. Substitution could be accounted for by bimolecular processes (5 n2 on carbon, SaN on sulfur). Some confirmation of this was obtained by kinetic studies. 

Formolysis and acetolysis are not common methods for cleavage of glycosidic linkages. They do have some unique applications, however. For instance, methylated polysaccharides are not generally soluble in hot water, and consequently, hydrolysis is best preceded by formolysis under these circumstances. For example, 5 mg of methylated polysaccharide is dissolved in 3 mL of 90% formic acid, and the solution is kept for 2 h at 100°. The formic acid is removed by evaporation at 40°. The residue is dissolved in 1 mL of 250 mM sulfuric acid and the solution is heated for 12 h at 100°, cooled, the acid neutralized with barium carbonate, the... 

Byproducts of this rearrangement are cyclobutenes, cyclopropane derivatives and allenic alcohols. The ratio of these products depends on the substitution of the substrate and on the reaction conditions. For example, 3-methyl-5-tosyloxypenta-l,2-diene (3) gives 75% of 1-methyl-2-methylenecyclobutanol (4) upon hydrolysis with water and calcium carbonate at 100 °C, while acetolysis with acetic acid/sodium acetate at 80 °C, and subsequent treatment with lithium aluminum hydride, provides only 37% of the cyclobutanol.12... 

Efforts to cause the carbon nucleophile available at C-2 (carbohydrate numbering) of the osulose derivative 66 to displace the methoxy group with allylic rearrangement and with consequent formation of a tricyclic product by use of Pd(0) catalysts [34] were unsuccessful, but the intended reaction proceeds "smoothly when tin(IV) chloride is used together with acetic anhydride in dichloromethane. Clearly, the Lewis acid activates the allylic ether group, and the C-2 nucleophile effects its displacement. Concurrently, acetolysis of the benzylidene ring occurs and the product isolated is the cu-decalin analogue 67 [33],... 

The possibility of electrophilic substitution at saturated carbon as an independent mechanism was considered by Hughes and Ingold2 in 1935, but this mechanism was not kinetically demonstrated with metal alkyls as substrates until 1955, when Winstein and Traylor3 published their results on the acetolysis of dialkylmercurys. At about the same time, stereochemical studies on electrophilic substitutions at saturated carbon were commenced by Winstein and by Reutov, again using alkylmercury compounds as substrates. Notable studies on the kinetics and stereochemistry of substitution at saturated carbon have been carried out by Ingold and his co-workers and by Reutov and his co-workers. Ingold4... 

The fact that di-4-camphyImercury (VII) is not especially unreactive (see sequence (20)) indicates that the acetolysis involves retention of configuration at the carbon atom undergoing substitution. If inversion of configuration was the preferred mode, (VII) would be expected to be extremely unreactive. 

In early work [165] on the synthesis of the pentasaccharide (236), the azide (237) was condensed with (238) [an intermediate in the preparation of (237)]in the presence of silver perchlorate and polyvinylpyridine to give the a-linked disaccharide (239) in 60 % yield and this on acetolysis gave the disaccharide (240) which contains the potential terminal disaccharide unit of the Forssman antigen. Compound (240) was converted into the glycosyl bromide with titanium(IV) bromide under carefully controlled conditions [182] and condensed with l,6-anhydro-2,4-di-0-benzyl-D-galacto-pyranose in the presence of silver carbonate to give the potential terminal trisaccharide (241) of the Forssman antigen. 

Acetolysis of (241) and subsequent treatment of the 1,6-di-O-acetate produced with titanium(IV) bromide gave the a-glycosyl bromide (247). This was condensed with the lactose derivative (248) (substitution with deuterated benzyl groups made it possible to interpret the NMR spectra [185]) in the presence of silver carbonate — silver perchlorate to give the a-linked pentasaccharide (249) in 38 % yield, and this was deprotected to give (236). 

One difficulty we encountered in the approach described above was liberation of the 3-carbon fragment from the auxiliary. The glycosidic linkage resisted acid hydrolysis and a rather severe acetolysis followed by basic peroxide oxidation to degrade the carbohydrate moiety had to be performed. A second approach to the use of glucose as an auxiliary is illustrated in scheme 11. 

Finally, when the triple bond is three carbon atoms removed from the reaction centre, participation effects are apparently much less important, as is indicated by the fact that 4-pentyn-l-yl tosylate does not cyclize on acetolysis (Kwiatkowski, as reported by Closson and Roman, 1966). 

Methyl 4,6-0-benzylidene-3-deoxy-a-D-ribo-hexopyranoside (56) was benzoylated, debenzylidenated, and partially p-toluenesulfon-ylated to 57 this was converted into 58 by reaction with sodium iodide, followed by catalytic reduction. The methanesulfonate of 58 was converted into 59 by reaction with sodium azide in N,N-dimethylformamide, and 59 was converted into 4-azido-3,4,6-trideoxy-a-D-xylo-hexose (60) by acetolysis followed by alkaline hydrolysis. Reduction of 60 with borohydride in methanol afforded 61, which was converted into 62 by successive condensation with acetone, meth-anesulfonylation, and azide exchange. The 4,5-diazido-3,4,5,6-tetra-deoxy-l,2-0-isopropylidene-L-ara/uno-hexitol (62) was reduced with hydrogen in the presence of Raney nickel, the resultant diamine was treated with phosgene in the presence of sodium carbonate, and the product was hydrolyzed under acidic conditions to give 63. The overall yield of 63 from 56 was 4%. The next three reactions (with sodium periodate, the Wittig reaction, and catalytic reduction) were performed without characterization of the intermediate products, and gave (+)-dethiobiotin methyl ester indistinguishable from an authentic sample thereof prepared from (+)-biotin methyl ester. 

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