Protection and Deprotection of Alcohols

Protection and deprotection of alcohols are important steps in organic synthesis and can be used to obtain selectivity - particularly in the chemistry of carbohydrates (for extended considerations, see Chapter 12), where the presence of several hydroxyl groups makes it difficult to obtain the desired selectivity. Microwave irradiation has been used for selective protection and deprotection of alcohols in several systems. 

Herradon [39] conducted a study on the selective benzoylation of polyols by microwave irradiation and excellent results were obtained. In the example shown, the reaction conducted under the action of radiation and in the presence of dibutyltin oxide led exclusively to product 10, which is benzoylated in the 2-position. This product is formed via a dibutyltin acetal, which catalyzes and controls the direction 

A similar strategy was used by Ballel [40] in the tin-mediated regioselective 3-0-alkylation of lactose and galabiose derivatives. The corresponding reactions under conventional heating did not yield any product. 

More recently, Caddick et al. [43] studied the selective benzoylation of primary hydroxyl groups using dibutyltin oxide as a catalyst and triethylamine as the base. These experiments again show that the stoichiometry and the mode of heating have a significant effect on the selectivity of the reaction. 

Lardy [45] studied the selective acetylation of sterols in the semi-solid state. It was found that the reaction is both chemoselective and regioselective under the action of microwave irradiation. For example, thermal heating of progesterone 

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Torii S, Inokuchi T, Kondo K, Ito H (1985) Electrogenerated acid as an efficient catalyst for the protection and deprotection of alcohols with dihydropyran and transesterification of glyceride. Bull Chem Soc Jpn 58 1347-1348. doi 10.1246/ bcsj.58.1347... 

In addition to the preparation of l-alkenes, the hydrogenolysis of allylic compounds with formate is used for the protection and deprotection of carboxylic acids, alcohols, and amines as allyl derivatives (see Section 2.9). 

In general, the methods for protection and deprotection of carboxylic acids and esters are not as convenient as for alcohols, aldehydes, and ketones. It is therefore common to carry potential carboxylic acids through synthetic schemes in the form of protected primary alcohols or aldehydes. The carboxylic acid can then be formed at a late stage in the synthesis by an appropriate oxidation. This strategy allows one to utilize the wider variety of alcohol and aldehyde protective groups indirectly for carboxylic acid protection. 

Tetrahydropyranilation of alcohols is an important process for the protection of hydroxyl groups. For this purpose pyridinium p-toluenesulfonate and bis(trimethyl-silyl) sulfonate have been frequently employed as mild catalysts. The apphcation of EGA catalysis is an effective alternative to protection and deprotection of hydroxyl groups The combinations, CH2CI2—LiClO4—Et4NC104 and MeOH—LiClO4 are applicable for the protection and deprotection step, respectively (34 35). 

Siletane oxidation can be used as a trigger to promote cleavage of/>-siletanylbenzyl (PSB) ethers <2005TL3283>. Mild oxidation of the arylsiletane yields the />-hydroxybenzyl ether, which can be easily hydrolyzed to release the alcohol. This methodology appears to be most efficient for the protection and deprotection of phenols and primary alcohols (Scheme 28). 

The enantioselective synthesis (51) of the side chain 30 of taxol had been achieved by way of stereospecific Sharpless epoxidation of cij-cinnamyl alcohol (29a), giving 29b (see Scheme 6). Following oxidation of the alcohol group, protection of the resulting carboxylic acid, regioselective opening of the epoxide with azide, benzoylation, and reduction, a suitably substituted moiety (28) was available which, after protection and deprotection of the acid function to form 30, was coupled to baccatin III. 

Protection and deprotection of functional groups. Alcohols and their tetrahydro-pyranyl ethers are interconverted with iodine as catalyst. Etherfication is done in a nonhydroxylic solvent, whereas the ether cleavage is achieved in MeOH. 

Protection and Deprotection of Pendent Amino Groups. Scheme V illustrates a method used recently for the preparation of polyphosphazenes with i ndent all lamino groups (76). 2-Aminoethanol was first amino-protected by reaction with di-t-butyl dicarbonate to yield a"BOC"unit. The alcohol function was then converted to the alkoxide salt by treatment with sodium hydride, and this reagent was used for halogen replacement with poly(dichlorophosphazene). Subsequent deprotection of the amino unit then took place following exposure of the polymer to acid. 

Protection and deprotection of functional groups is an important strategy in organic S3Tithesis. Particularly, trimethylsilyl ether (TMS), methotymethyl acetal (MOM) and tert-butoty carbamate (Boc) are three frequently used effective reagents in the protection of alcohols, phenols, amines, carbotylic... 

Two new sections on the protection of phosphates and the alkyne-CH are included. All other sections of the book have been expanded, some more than others. The section on the protection of alcohols has increased substantially, reflecting the trend of the nineties to synthesize acetate- and propionate-derived natural products. An effort was made to include many more enzymatic methods of protection and deprotection. Most of these are associated with the protection of alcohols as esters and the protection of carboxylic acids. Here we have not attempted to be exhaustive, but hopefully, a sufficient number of cases are provided that illustrate the true power of this technology, so that the reader will examine some of the excellent monographs and review articles cited in the references. The Reactivity Charts in Chapter 10 are identical to those in the first edition. The chart number appears beside the name of each protective group when it is first introduced. No attempt was made to update these Charts, not only because of the sheer magnitude of the task, but because it is nearly impossible in... 

The diol was protected and the C-terminal group converted to a methyl ester in sequence B. A phosphonate group was installed at C(7) via an acylation reaction in Step C-5. Successive oxidations of the primary and deprotected secondary alcohol gave the C(l)-C(8) intermediate. 

Selective protection of the primary alcohol gave 138 (P=TBDMS), which was then esterified with ( )-3-hexenoic acid to produce the key intermediate 139 for cyclization. Ireland ester-enolate Claisen rearrangement and hydrolysis produced a protected hydroxyacid, which, after reduction of the acid and deprotection of the alcohol, yielded meso diol 128 more quickly and efficiently than in the previous synthesis. The meso diol was then converted to the racemate of the lactol pheromone 130 as previously described. 

Finally, achiral phosphonium salts have been applied as Lewis acid catalysts in some other reactions. The examples will be listed here but not discussed in more detail. Phosphonium salts have been used as catalysts for the A,A-dimethylation of primary aromatic amines with methyl alkyl carbonates giving the products in good yields [123]. In addition acetonyltriphenylphosphonium bromide has been found to be a catalyst for the cyclotrimerization of aldehydes [124] and for the protection/ deprotection of alcohols with alkyl vinyl ethers [125, 126]. Since the pK of the salt is 6.6 [127-130], the authors proposed that, next to the activation of the phosphonium center, a Brpnsted acid catalyzed pathway is possible. 

Dicarboxypyridinium chlorochromate (2,6-DCPCC)392 possesses an acidic character that allows the in situ deprotection and oxidation of alcohols, protected as tetrahydropyranyl and trimethylsilyl ethers. 2,2 -Bipyridinium chlorochromate (BPCC)393 contains a ligand that complexes efficiently with the reduced chromium species, generated during the oxidation of alcohols, allowing for a substantial simplification of the work-ups. For this reason, it enjoys a popularity among chlorochromates surpassed by only PCC. 

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