Alcohol protecting group for

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). 

Acetals are useful because they can act as protecting groups for aldehydes and ketones in the same way that trimethylsilyl ethers act as protecting groups for alcohols (Section 17.8). As we saw previously, it sometimes happens that one functional group interferes with intended chemistry elsewhere... 

Silyl Ethers as Protective Groups for Alcohols. Oxidative Deprotection and Stability Under Alcohol Oxidation Conditions, Muzart. J. Synthesis. 1993, 11... 

Thermolytic Cleavage of Allvlic and Benzvlic Ethers and Polvethers. The thermal lability of the types of ethers which are of interest in the context of this study was discovered during a thorough study of the application of certain benzylic carbonates as labile protecting groups for alcohols and phenols [IS]. It was observed that, under acid catalysis, the bis-methylcarbonate derivative of l-(4-hydroxyphenyl)ethanol (4, in Equation 1) was transformed into the benzylic ether (5) which then underwent clean acid-catalyzed thermolysis to the corresponding styrene (6) in very high yield [14]. 

Silyl protecting groups are the gold standard for the protection of alcohols.234 Novel photochemically removable protection groups for alcohols have been developed by Brook et a/.23S and Pirrung et al,236 For instance, cyclo-pentanol can be reacted with tris(trimethylsilyl)chlorosilane 53 in the presence of a mild base to yield the protected silyl ether 54. The protection group can be removed conveniently upon UV irradiation or by the use of Bu4NF (Scheme 12). 

Scheme 55 Photolabile protecting groups for alcohols and thiols.

Tetrahydropyranyl (TUP) and tetrahydrofuranyl ethers are important protecting groups for alcohols and phenols in organic synthesis, but they can also be converted to other useful functional groups [8, 118]. For example, allylation of a TUP ether should yield a highly functionalized molecule (Scheme 15). 

Benzyl ethers are among the most commonly used protecting groups for alcohols. Usually, these are prepared using an excess of NaH and benzyl bromide. Okan Sirkecioglu of Istanbul Technical University has found (Tetrahedron Lett. 44 8483,2003) that heating a primary or secondary alcohol neat with benzyl chloride and a catalytic amount of Cu(acac>2 smoothly yields the benzyl ether, with evolution of HC1. The reaction can also be run in solvent THF, but it proceeds more slowly. Note that primary alcohols react more quickly than secondary alcohols. 

Notes This is often used as a protecting group for alcohols, where it is observed that primary alcohols form more readily than secondary hydroxy groups, which in turn are more reactive than tertiary alcohols. As with most benzylic ethers, this protecting group can be removed by hydrogenolysis over Pd or by metal-ammonia reduction.1 Examples ... 

T. Mukaiyama, M. Ohshima, and M. Murakami, 2-Benzyloxy-propene A novel protective reagent of hydroxyl groups, Chem Lett 265 (1984) T. Mukaiyama, M. Ohshima, H. Nagaoka, and M. Murakami, A novel acid-resistant acetal-type protective group for alcohols, Chem. Lett 615 (1984). 

Dihydropyran is of value as a protecting group for alcohols and phenols, and to a lesser extent amines, carboxylic acids and thiols (B-67MI22403, B-81MI22404). The resulting tetrahydropyranyl ethers (736) are stable to base, but are readily cleaved under acidic conditions (Scheme 284). 

The alkenic bond in dihydrothiopyrans in one case is a thioenol system in the other it is effectively an isolated double bond. The thioenol readily adds alcohols or thiols (c/. dihydropyran) it has been suggested as a protecting group for alcohols, and is readily removable with Ag+ under neutral conditions (66JOC2333). If conjugated with a carbonyl function, thiols will add under basic conditions (equation 34) (81JA4597). 

Table 7.7. Acid-labile protective groups for alcohols.

Table 7.8. Protective groups for alcohols cleavable by nucleophiles and oxidants.

Allyl carbonates can function as protecting groups for alcohols, with removal of the protecting group being effected by R3SnH and Pd° (equation 101).299... 

Sulfonates with a sulfur-bound C,H group can also eliminate alkoxide when treated with a strong base [82]. Phenylmethanesulfonic esters, for instance, are sufficiently base-labile to be useful protective groups for alcohols (Scheme 4.17). 

The 4-ethoxy-l-naphthyloxycarbonyl group is a valuable electrochemically labile protecting group for alcohols and amines. The deprotection of bomeol 105 and gerani-... 

Furuta, T., Hirayama, Y. and Iwamura, M. (2001) Anthraquinone-2-ylmethoxy-carbonyl (Aqmoc) a new photochemically removable protecting group for alcohols. Organic Letters, 3, 1809-1812. 

Literak, J., Wirz, J. and Klan, P. (2005) 2,5-Dimethylphenacyl carbonates A photoremovable protecting group for alcohols and phenols. Photochemical el... 

An ether of formula R -0-SiR3 with a substituted silicon atom replacing one of the alkyl groups of an ether. Used as protecting groups for alcohols, (p. 642)... 

We can also easily convert hydroxyl groups to silyl ethers. Section 14-10B covered the use of the triisopropylsilyl (TIPS) protecting group for alcohols. Similarly, sugars can be converted to their silyl ethers by treatment with a silyl chloride, such as chlorotrimethylsilane (TMSC1), and a tertiary amine, such as triethylamine. 

Q Additional coverage on silyl ethers addresses their use as protecting groups for alcohols and carbohydrates. 

Silyl ethers are versatile protecting groups for alcohols... 

---