Protective Groups Cleavable by Nucleophiles or Other Reagents

2 Protective Groups Cleavable by Nucleophiles or Other Reagents 

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. 

Esters of 4-oxo carboxylic acids, such as levulinic acid (Entry 5, Table 7.8) or 3-ben-zoylpropionic acid [103], can be cleaved under essentially neutral reaction conditions 

Silyl ethers that have been used in solid-phase synthesis include TES, TIPS, TBS, and TBDPS ethers. Polystyrene-bound phenols can be converted into TIPS ethers by treatment with TIPS-OTf/imidazole in DMF for 5 min [105], These silyl ethers are stable towards bases and weak acids, but can be selectively removed by treatment with TBAF (Entries 6 and 8, Table 7.8) or pyridinium hydrofluoride (THF, 25 °C, 15 h [24,75,106]). 

Allyl carbonates can be cleaved by nucleophiles under palladium(O) catalysis. Allyl carbonates have been proposed for side-chain protection of serine and threonine, and their stability under conditions of /VT moc or /V-Boc deprotection has been demonstrated [107]. Prolonged treatment with nucleophiles (e.g., 20% piperidine in DMF, 24 h) can, however, lead to deprotection of Alloc-protected phenols [108,109]. Carbohydrates [110], tyrosine derivatives [107], and other phenols have been protected as allyl ethers, and deprotection could be achieved by palladium-mediated allylic substitution (Entry 9, Table 7.8). 9-Fluorenyl carbonates have been used as protected intermediates for the solid-phase synthesis of oligosaccharides [111]. Deprotection was achieved by treatment with NEt3/DCM (8 2) at room temperature. 

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