Protecting groups. Table Acetals

The solid-phase synthesis of oligosaccharides is usually performed using acid-resistant linkers and protective groups, because of the slightly acidic reaction conditions required for glycosylations (Section 16.3). Hydroxyl group protection is conveniently achieved by conversion into carboxylic esters, such as acetates, benzoates, or nitro-benzoates. Support-bound esters of primary or secondary aliphatic alcohols can be cleaved by treatment with alcoholates [97-99] (Table 7.8), with DBU in methanol, with hydrazine in DMF [100] or dioxane [101], or with ethylenediamine [102], provided that a linker resistant towards nucleophiles has been chosen. 

Acetate, chloroacetate, benzoate, p-methoxy benzoate, benzyl carbonate (Cbz), tert-butyl carbonate (Boc) and 9-(fluorenylmethyl) carbonate (Fmoc) are commonly prepared to protect the hydroxyl group (Table 1.3). 

Optically active dialkyl tartrates and (2i ,4/ )-pentane-2,4-diol were used as homochiral protecting groups in a, 6-unsaturated acetals 51 and 52 which were subjected to Simmons-Smith reaction with diethylzinc and diiodomethane to give cyclopropyl derivatives with a de of > 69% (Table 1). The acetal group was readily converted to the aldehyde by acidic hydrolysis or to the acid by ozonolysis. 

It is more surprising that acetals can be used to protect simple alcohols as well as diols. Two of the best are the THP (6) and MEM (7) derivatives. These are often preferred to ethers (Table 9.1) because they can be removed under such mild conditions. The reagent for the MEM protecting group is discussed in Chapter 6. 

B0C2O is a widely used reagent for introducing protecting groups in peptide synthesis [223, 224]. The reaction of substituted anilines with B0C2O in the presence of a stoichiometric amount of 4-dimethylaminopyridine (DMAP) in an inert solvent (acetonitrile, dichloromefhane, ethyl acetate, tetrahydrofuran, toluene) at room temperature leads to aryl isocyanates in almost quantitative yields within 10 min (Table 4.14) [225]. 

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