Allyl phosphates, deprotection

Allyl phosphates 332 are deprotectd using HCO2H amine [146] or HSnBu3 [147], The method is applied to the protection and deprotection of the amino and phosphate groups in nucleotides synthesized in the solid phase [148],... 

A mild and efficient deprotection of phosphate triesters involves nucleophilic attack by weakly basic nucleophiles such as iodide, thiolate and amines at the O-C bond with synchronous expulsion of a phosphate diester as the leaving group [Scheme 7.6]. The reaction is especially useful for the deprotection of methyl, benzyl and allyl phosphates as in Scheme 7.8 shown below. An analogous reaction occurs with carboxylic esters but the conditions required are more stringent because the carboxylate anion is a poorer leaving group (see section 6.3.1),... 

Proteases, such as thermitase,papain,f " l and subtilisinf have been employed for the deprotection of tert-butyl and methyl esters from various glycopeptides. More interestingly, the C-terminus of a nucleopeptide methyl ester 8 was deprotected selectively and in very high yield by papain.l Neither the acetate, the N-terminal urethane, the allyl phosphate, nor the phenylacetamide protection of the nucleobase were attacked (Scheme 17). 

Allyl-based protection for the phosphate group in phosphoserine-containing peptides has also been employed. In this case, the Af-alloc-bis(allyl)phosphate of serine was incorporated into a resin-bonnd peptide using standard solid phase peptide synthesis methodology and deprotected nsing trimethylsilyl azide and tetrabutylammonium flnoride as the nucleophile (Scheme 10). 

The NSEC group is stable to glycosylation conditions using glycosyl phosphates, and it is not affected under deprotection conditions that facilitate the removal of Lev, Fmoc, allyl, and PMB groups. For ester-type protecting groups selective deprotection in the presence of NSEC derivatives is not possible. 

When Pd-catalyzed deprotection of an allyl ester is conducted in the presence of external carboxylic acid nucleophile, an equilibrium between two different allyl esters is established. Several strategies have been developed to perturb this equilibrium far enough to ensure complete deprotection. Use of a large excess of acetic acid has been shown to effect the deprotection of allyl carbonates and aUyl phosphates. Another approach employs the soluble carboxylate salt potassium 2-ethylhexanoate (Scheme 3) for the deprotection of allyl carboxylic esters. Precipitation of the desired potassium carboxylate is used to perturb the equihbrium in the direction of products. Because these deprotection conditions are essentially neutral, they have been employed in the deprotection of particularly sensitive allyl esters. ... 

The Pd(Ph3P)4-catalyzed removal of the 0-allyl protecting group has been described for a number of systems. For example, allyl esters are efficiently cleaved to the parent acid in chemically sensitive systems such as penicillins and glycopeptides. The internucleotide phosphate linkage, protected as the allyl phos-pho(III)triester, remains intact upon deprotection under Pd(Ph3P)4 catalysis. Allyl ethers that protect the anomeric hydroxy in carbohydrates (mono- and disaccharides) are efficiently removed under Pd(Ph3P)4 catalysis in hot (80 °C) HOAc. ... 

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