Benzyl deprotection with liquid

FIGURE 3.4 Deprotection of functional groups by reduction with sodium in liquid ammonia [du Vigneaud et al., 1930]. As in Figure 3.3, except reduction is effected by solvated electrons and protons are provided by water at the end of the reaction. Excess sodium is destroyed by NH4C1. This is a simplified presentation of the reaction. AH benzyl-based protectors as well as -Arg(N02)-, -Arg(Tos)-, and -His(Tos)- are sensitive to sodium in liquid ammonia. 

The coupling led to the intermediate phosphite (step a) which was oxidized by TBHP (step b). The phosphate formed containing eight ethoxy groups was deprotected by trans-esterification using trimethylbromosilane and subsequent hydrolysis by water (step c). Two benzoyl groups were removed by basic hydrolysis (step d). The same tetrakis phosphate was prepared by phosphitylation with dibenzyl-h/,iSr-diisopropylphosphoroamidite in the presence of tetrazole (step c) followed by oxidation with CPBA (step f). The removal of all benzyl and benzoyl groups was achieved in one step by sodium in liquid ammonia (step g). 

The benzylated polymers have been deprotected, to give the free polysaccharides, by treatment with sodium in liquid ammonia. A few... 

The A chain was synthesized by the automated solid-phase procedure (94). Three grams of A -Boc-Asn resin was carried through 20 reaction cycles as described for the B chain except that the reagents used for all deprotection and neutralization steps were 4M HCl in dry dioxane and triethylamine in CHCI3, respectively (95). The peptide was cleaved from the resin as described above (yield, 69%). The total time required was 8 days. The S-benzyl protecting groups were removed by treatment with sodium in liquid ammonia (96), and the four cysteine residues were converted to the S-sulfonates (ASSOB) (over all yield, 37%). 

In some instances an allylic oxygen bond can undergo reductive cleavage. For example, in a synthesis of Allopumiliotoxin 339A, Overman and co-workers showed that the reductive cleavage product 1403 was the major product on attempted deprotection of the two benzyl ethers in 140.1 with lithium in liquid ammonia at -78 C for more than 5 minutes [Scheme 4.140]. However, by terminating the reaction after 2 minutes, the desired triol 1403 was obtained in 86% yield. 

Glycopeptides. — Treatment with sodium in liquid ammonia has been used as a novel method of benzyl- and benzylidene-group deprotection in glycopeptide synthesis. ... 

The auxiliary was designed in such a way that it contains a substituted benzyl ether, and therefore should be removable by catalytic hydrogenation over Pd/C or Birch reduction. Indeed, saponification of the benzoyl ester of 17S(a) by treatment with NaOMe in methanol followed by removal of the benzyl ethers and chiral auxiliary using sodium in liquid ammonia led to a clean formation of the deprotected compound 25 (Scheme 4). On the other hand, catalytic hydrogenation over Pd/C was sluggish probably due to steric hindrance at the benzylic carbon. 

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