4- butyl ester protect phosphates

The use of a strong base in the palladium-catalyzed amination of aryl halides precludes the use of many substrates, such as those with aromatic nitro groups or enolizable hydrogens, esters other than tert-butyl esters, and many substrates with base-sensitive stereochemistry such as some protected amino acids and heterocyclic substrates [191]. Thus, conditions that employ milder bases are required. A solution that involves reaction temperatures as low as those used for reactions conducted with sodium tert-butoxide has not been developed. However, carbonate and phosphate bases can be used with certain catalysts at reaction temperatures comparable to those of reactions involving the first- and second-generation catalysts. 

The procedure, based on the phosphoramidite method, is illustrated in Scheme 7.11. Nn-Fmoc-L-tyrosine was temporarily protected as its ferf-butyldimethylsilyl ester (see section 6.6). Phosphitylation with dimethyl tyN-diethylphosphorami-dite followed by in situ oxidation with /erf-butyl hydroperoxide gave the phos-phodiester 11 3 The labile silyl ester hydrolysed during the sodium metabisulfite workup used to destroy excess /erf-butyl hydroperoxide to give 11.4 in 57% overall yield, By the same procedure, the dkerf-butyl phosphate 11.5, dibenzyl phosphate 11.6 and diallyl phosphate (not shown) were prepared. 

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). 

Benzyl-protected amidites generally give better results than f-butyl amidites in the presence of the weakly acidic tetrazole, di-t-butyl phosphite esters have a tendency to lose a t-butyl group, leading to formation of the corresponding iZ-phosphonate 5 (12, 37) (Figure 4). Fortunately, this byproduct can be converted to the desired phosphate by treatment with iodine in pyridine (38). 

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