Cyclic alcohol esters

Chapter VIII. Polyhydroxylic Branched-Chain and Cyclic Alcohol Esters... 

Another method for the hydroxylation of the etliylenic linkage consists in treatment of the alkene with osmium tetroxide in an inert solvent (ether or dioxan) at room temperature for several days an osmic ester is formed which either precipitates from the reaction mixture or may be isolated by evaporation of the solvent. Hydrolysis of the osmic ester in a reducing medium (in the presence of alkaline formaldehyde or of aqueous-alcoholic sodium sulphite) gives the 1 2-glycol and osmium. The glycol has the cis structure it is probably derived from the cyclic osmic ester ... 

Compounds which dissolve in concentrated sulphuric acid may be further subdivided into those which are soluble in syrupy phosphoric acid (A) and those which are insoluble in this solvent (B) in general, dissolution takes place without the production of appreciable heat or colour. Those in class A include alcohols, esters, aldehydes, methyl ketones and cyclic ketones provided that they contain less than nine carbon atoms. The solubility limit is somewhat lower than this for ethers thus re-propyl ether dissolves in 85 per cent, phosphoric acid but re-butyl ether and anisole do not. Ethyl benzoate and ethyl malonate are insoluble. 

Alcohols, esters (but not ethyl benzoate, ethyl malonate or ethyl oxalate), aldehydes, methyl ketones and cyclic ketones containing less than nine carbon atoms as well as ethers containing less than seven carbon atoms are soluble in 85 p>er cent, phosphoric acid. 

Myrtenol, CjpHjgO, is a primary cyclic alcohol, which was isolated from essential oil of myrtle, in which it occurs principally in the form of its acetic ester, by von Soden and Elze. It is separated from geraniol, with which it is found, by fractional distillation, and by the crystallisa-... 

Li et al. (1997) have discussed the use of catalytic antibodies to control the reactivity of carbocations. At an entry level, the acyclic olefinic sulfonate ester [72] is converted into the cyclic alcohol [73] (98%) using antibody 4C6 raised to hapten [73] with only 2% of cyclohexene produced (Appendix entry 15.1) (Li et al, 1994). 

Esters are difficult to reduce, and are inert to many of the conditions used in electroreductive processes. A recent investigation has demonstrated that they can easily be reduced at a magnesium cathode in the presence of t-BuOH [52,53]. When tethered to an alkene, cyclization occurs to afford a cyclic alcohol. Two examples are illustrated, the second being a key step in a synthesis of racemic muscone [53]. 

Quinolinium dichromate (QDC) oxidations of primary and secondary alcohols both proceed via a cyclic chromate ester. Acrylonitrile polymerization was observed in the oxidation of several para- and meffl-substituted benzaldehydes to the corresponding benzoic acids by quinolinium chlorochromate (QCC). QCC oxidations of diphenacyl sulfide and of aromatic anils have been studied. 

Oxidation of primary, secondary and benzylic alcohols with TBHP or CHP, mainly catalyzed by Mo and Zr derivatives, were performed by different authors. As an example, Ishii, Ogawa and coworkers reported the conversion of secondary alcohols such as 2-octanol to ketones mediated by catalyst 39 and TBHP. The oxidation of cyclic alcohols depended on steric factors. Zirconium alkoxides may act as catalysts in the conversion of different alcohol typologies with alkyl hydroperoxides . Secondary alcohols, if not severely hindered, are quantitatively converted to the corresponding ketones. The selectivity for equatorial alcohols is a general feature of the system, as confirmed by the oxidation of the sole cis isomer 103 of a mixture 103-bl04 (equation 68). Esters and acids could be the by-products in the oxidation of primary alcohols. 

BINAP-ruthcnium(II)-catalyzed hydrogenation of the racemic cyclic / -oxo ester, methyl 2-ox-ocyclopentanecarboxylate, was found to lead to alcohol 3, one of the four possible stereoisomers135. The reaction is both enantioselective (kinetic resolution) and diastereoselective. Since racemization of the substrate is sufficiently faster than hydrogenation, the yield of the hydroxy ester was almost quantitative. Whereas the relative configuration was probably clear from NMR spectra (not reported), the absolute configuration of 3 had to be determined (see p 438)135. 

A rule, similar to Prelog s rule, has been proposed for the enzyme-mediated hydrolysis of the esters of secondary alcohols. Esters of the enantiomers 31 usually react faster. This rule correctly predicted the configuration of 14 out of 15 substrates when cholesterol esterase was used, 63 out of 64 substrates with a lipase from Pseudomonas cepacia, and of 51 out of 55 cyclic substrates using a lipase from Candida rugosa24°. 

Konovalova and Orekhov103 demonstrated that the primary hydroxyl group in platynecine is more reactive to acylation than the secondary. For example, use of more or less drastic conditions yields platynecine di- or mono-benzoate, respectively. Pyrrolizidine alcohols can be esterified with inorganic acids e.g., mild treatment of platynecine with thionyl chloride yields the cyclic sulfite ester hydrochloride79 (see Section III, A). 

Inositol hexanitrate ( nitroinosite , nitroinositol ), a solid melting at 132.5°C, and quebrachitol hexanitrate ( nitroquebrachite ), an oily liquid, are esters of isomeric cyclic alcohols. Their common constitutional formula is ... 

Hudson et a/.156 have shown that N,N-dialkylcarbamates decompose in strongly acidic media to carbon dioxide, olefin, alkyl halide and alcohol, the rate of reaction of the secondary esters closely following h0. This fact, together with the variation in the rate of hydrolysis of carbamates of cyclic alcohols with the ring size154, shows that these reactions involve the intermediate formation of carbonium ions. 

Cyclic alcohols are excellent targets for enantioselective enzymatic acylations. For example, acylation of (65) with vinyl acetate catalyzed by Upase SAM-II gives the (R),(5)-ester with 95% ee (81). Similarly (66), which is a precursor for seratonin uptake inhibitor, is resolved in a high yield and selectivity with Amano Upase P (82). The prostaglandin synthon (67) is resolved by the same method into the optically pure alcohol in 35% yield (83). 

The at complex from DIB AH and butyllithium is a selective reducing agent.16 It is used tor the 1,2-reduction of acyclic and cyclic enones. Esters and lactones are reduced at room temperature to alcohols, and at -78 C to alcohols and aldehydes. Acid chlorides are rapidly reduced with excess reagent at -78 C to alcohols, but a mixture of alcohols, aldehydes, and acid chlorides results from use of an equimolar amount of reagent at -78 C. Acid anhydrides are reduced at -78 C to alcohols and carboxylic acids. Carboxylic acids and both primary and secondary amides are inert at room temperature, whereas tertiary amides (as in the present case) are reduced between 0 C and room temperature to aldehydes. The at complex rapidly reduces primary alkyl, benzylic, and allylic bromides, while tertiary alkyl and aryl halides are inert. Epoxides are reduced exclusively to the more highly substituted alcohols. Disulfides lead to thiols, but both sulfoxides and sulfones are inert. Moreover, this at complex from DIBAH and butyllithium is able to reduce ketones selectively in the presence of esters. 

Sometimes, alcohols can direct the oxidation of alkenes, resulting in highly stereoselective formation of tetrahydrofurans by the action of Collins reagent. Thus, 1,2-diols can form cyclic chromate esters that can intramole-cularly oxidize alkenes, positioned so as to allow the operation of five-membered cyclic transition states.119... 

Chromium coordinates selectively with the 1,2-diol, forming a stable cyclic chromate ester that evolves producing the formation of a tetrahydrofuran. Observe that no formation of tetrahydrofuran from the alcohol on the left occurs, for this would involve the intermediacy of a less stable simple chromate ester (vide infra). The experimental conditions are so mild that no direct oxidation of the secondary alcohol to ketone is observed, either on the starting compound or in the product. 

However, as the formation of an intermediate simple chromate ester is not as favorable as the generation of the cyclic chromate ester, involved in the oxidation of 5,6-dihydroxyalkenes, this reaction, demands harsher conditions. Therefore, only tertiary 5-hydroxyalkenes may be normally used as starting compounds, otherwise a direct oxidation of the alcohol to an aldehyde or ketone would occur.287 Because of the harsher conditions involved, very often the resulting 1-hydroxyalkyltetrahydrofuran is further oxidized to a y-lactone or to a ketone.288... 

This mechanistically fascinating product can be explained by the initial formation of a cyclic chromate ester, facilitated by the formation of a five-membered ling and the (cis) relationship in the 1,2-diol. Interestingly, this stable chromate does not evolve resulting in the oxidation of the secondary alcohol, but it suffers elimination producing a very electron-rich benzyloxy alkene that is easily epoxidized intramolecularly by chromium. Observe that the epoxide oxygen enters from the same face than the secondary alcohol. 

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