Benzylation and Debenzylation

Benzylation of a carboxylic acid is a key step in the synthesis of depsides and is carried out using a) benzylbromide (BnBr) and 

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N-debenzylation was achieved with Pd black in AcOH-H20 (4 1) at 50 psi hydrogen for 2-3 days. Removing of O-benzyl, N-benzyl, and N-Boc protecting groups was also achieved under these circumstances (Scheme 4.89).337... 

This method has been extended to include 1,3-diarylthioureas which are benzylated and then treated with phenylisocyanate to give S-benzylisothiobiurets (252). Oxidative debenzylation with... 

Treatment of tertiary benzylamines with acylating agents can lead to debenzylation. If the benzyl group is linked to an insoluble polymer, acylation and debenzylation will lead to the release of an acylated amine into solution (Entry 6, Table 3.9). These cleavage reactions generally yield products that are contaminated with acylating agent and so require further purification. 

This interesting transformation from a readily available 6-deoxyhexose forms the basis for the synthesis231 of 6-deoxy-2,3-di-0-methyl-D-allose (mycinose),168 one of the carbohydrate moieties of the antibiotic chalco-mycin. The synthesis merely involves the protection of the C-5 hydroxyl group in (41) by benzylation, followed by partial hydrolysis with acid, methylation of the product at the C-2 and C-3 hydroxyl groups, and debenzylation. 

Debenzylation of the benzyl esters of phosphoric acid has been employed in the synthesis of phosphorylated alcohols. Examples are shown in eqs. 13.2348 and 13.24.49 Tener and Khorana synthesized a-D-ribofuranose 1,5-diphosphate (36) by hydrogenolysis of the benzyl phenyl phosphate 35, first, in the presence of 5% Pd-C, and then in the presence of Adams platinum to remove, respectively, the benzyl and the phenyl groups (eq. 13.25).50... 

The selective reduction of nitroarenes containing benzyl-protected phenolic groups without concomitant hydrogenolysis has also been achieved using hydrazine hydrate and Raney nickel. This procedure avoids strongly acidic conditions. The reaction is selective and a variety of (V-benzyl- and chloro-sub-stituted nitroarenes are reduced to the corresponding anilines without dehalogenation or debenzylation. 

Use of the Wittig reaction on a reducing sugar is a handy method to generate a double bond, which can then be used as aradical acceptor. As shown in Scheme 8.18, D-galactose was classically transformed into a selectively protected hemiacetal 60 by benzyl alcohol glycosylation, protection of the primary hydroxyl, 3,4-acetonide formation and debenzylation. The Wittig reaction followed by desilylation afforded the triol 61, which was then selectively tosylated on the primary hydroxyl... 

TBHP yielded an allylic alcohol, which was benzylated to provide 97. This highly functionalized diene underwent RCM with Schrock s catalyst affording cyclopentene 98 in a yield of 91%. Under the action of hydrogen and Pd/C, hnal reduction and debenzylation were performed simultaneously to give 5a-carba-(3-D-fmctofuranose [54]. 

The classical permanent protecting group of carbohydrate hydroxyl functions is probably the benzyl ether. It is very stable and can be readily removed under essentially neutral conditions. For this reason, numerous benzylation and 0-debenzylation procedures have been described. Benzyl ether formation is usually achieved by the reaction of alcohols and benzyl halides in the presence of a base such as sodium hydride in anhydrous DMF (O Scheme 2) [11], or a mild base (Ag20) in THF using a phase-transfer catalyst [12]. Benzylation can also be accomplished by the use of an acidic catalyst with benzyltrichloroacetimidate as the reagent [13]. A method using the reductive etherification of TMS ethers under non-basic conditions has also been reported [14]. 

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