Alcohols acetate protecting groups

One way of making the alcohol we want is to protect the ketone as an acetal. An acetal-protecting group (shown in black) is used. 

The stability of ethers and mixed acetals as protecting groups for alcohols varies from the very stable methyl ether to the highly acid-labile trityl ether. However, all ethers are stable to basic reaction conditions. Hence, ether or mixed acetal protecting groups specifically tolerate... 

The acetal protective group is introduced by treating the carbonyl compound with an alcohol, an orthoester, or a diol in the presence of a Lewis acid catalyst. In recent years, several transition metal catalysts such as TiCl4 have been shown to offer major advantage over general Brpnsted acid catalysts. ... 

Phthalyl alcohol, HOCH2CeH4CH20H-o. Mol. wt. 138.16, m.p. 64°. Prepared by reduction of phthalic anhydride with lithium aluminum hydride in ether (87% yield). In a novel and efficient synthesis of cyclopropanone hydrate, Grewe and Struve used the o-xylylene acetal protective group (1) and, after elimination of... 

Bromination might well oxidise the reactive benzylic alcohol in (5) so an acetal protecting group is added. This could be removed to give (4), but as a protecting group was needed later in the synthesis, it was left in place. 

A.I. Ether and Acetal Protecting Groups. A simple way to protect the OH of an alcohol is as its methyl ether (-OMe). Reaction of an alcohol with a base [often sodium hydride (NaH) in THF or DMF] gives an alkoxide. Subsequent reaction with iodomethane gives the methyl ether via an Sn2 reaction (sec. 2.7.A.i). Formation of dialkyl ethers via reaction of an alkoxide with an alkyl halide is called the Williamson ether... 

UAIH4 to give a mixture ( 4 1) in favour of the syn amino alcohol 197 (3.133). Hydrolysis of the acetal protecting groups led to the desired glycoside. 

Protection of an alcohol function by esterification sometimes offers advantages over acetal protecting groups such as the tetrahydropyranyl ethers. Generally, acetals are stable in base and labile in acid, while esters are more stable in acid than acetals and are readily hydrolyzed in base. Esters are notably useful in reactions such as oxidations, but are not satisfactory in organometallic reactions. Acetates and benzoates are the most common ester protecting groups they can be conveniently prepared by reaction of unhindered alcohols with acetic anhydride or benzoyl chloride, respectively, in the presence of pyridine or other tertiary amine. The use of reactive amides such as N-acylimidazoles (imidazolides) allows the reaction to be carried out in the absence of added bases ... 

Six protective groups for alcohols, which may be removed successively and selectively, have been listed by E.J. Corey (1972B). A hypothetical hexahydroxy compound with hydroxy groups 1 to 6 protected as (1) acetate, (2) 2,2,2-trichloroethyl carbonate, (3) benzyl ether, (4) dimethyl-t-butylsilyl ether, (5) 2-tetrahydropyranyl ether, and (6) methyl ether may be unmasked in that order by the reagents (1) KjCO, or NH, in CHjOH, (2) Zn in CHjOH or AcOH, (3) over Pd, (4) F", (5) wet acetic acid, and (6) BBrj. The groups may also be exposed to the same reagents in the order A 5, 2, 1, 3, 6. The (4-methoxyphenyl)methyl group (=MPM = p-methoxybenzyl, PMB) can be oxidized to a benzaldehyde derivative and thereby be removed at room temperature under neutral conditions (Y- Oikawa, 1982 R. Johansson, 1984 T. Fukuyama, 1985). 

Since (A) does not contain any other functional group in addition to the formyl group, one may predict that suitable reaction conditions could be found for all conversions into (A). Many other alternative target molecules can, of course, be formulated. The reduction of (H), for example, may require introduction of a protecting group, e.g. acetal formation. The industrial synthesis of (A) is based upon the oxidation of (E) since 3-methylbutanol (isoamyl alcohol) is a cheap distillation product from alcoholic fermentation ( fusel oils ). The second step of our simple antithetic analysis — systematic disconnection — will now be exemplified with all target molecules of the scheme above. For the sake of brevity we shall omit the syn-thons and indicate only the reagents and reaction conditions. 

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