Benzyl-Oxygen Functions

Aromatic aldehydes and ketones, ArCOR R = H, alkyl or aryl, like the corresponding benzyl-type alcohols, are readily converted to the corresponding methylene derivatives, ArCH2R, over Pd catalysts in acidic medium, particularly in the presence of 

Catalytic debenzylation is widely utilized for removing a benzyl group introduced in order to protect a reactive function during a series of reactions. An extensive survey of the literature on this reaction is found in a review by Hartung and Simonoff.41 Equation 13.19 illustrates a typical example of such applications.44 

An acetal of benzaldehyde may become a protective group of polyhydroxy compounds. The hydroxyl groups in the 1 and 3 positions of glycerol may form a cyclic acetal with benzaldehyde. The secondary hydroxyl group left intact is available for esterification. Hydrogenolytic removal of the benzal group allows the synthesis of the P-monoglyceride (eq. 13.21).46 

The deprotection of 4-phenyl-1,3-dioxolanes to liberate free carbonyl compounds over Pd-C is possible without affecting acid labile groups such as 0-silyl ether and O-THP (tetrahydropyranyl) ether (eq. 13.22).47 

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 

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Reduction of benzylic oxygen functional groups with Raney nickel has occasionally been reported, but there are very few examples in the recent literature. Hydrogenolysis over W-2 Raney nickel has been used to selectively remove benzyl ether protection in the presence of a 4-methoxybenzyl protecting group (equation 30)." ... 

Benzylic or allylic oxygen functions react with Lewis acids such as trifluoroacetic acid to generate allyl or benzylic cations which abstract a hydride from silanes such as triethylsilane 84 b to result in the removal of the oxygen function in a process which has been called ionic hydrogenation and which has been reviewed [34-38]. 

Arguably the most challenging aspect for the preparation of 1 was construction of the unsymmetrically substituted sec-sec chiral bis(trifluoromethyl)benzylic ether functionality with careful control of the relative and absolute stereochemistry [21], The original chemistry route to ether intermediate 18 involved an unselective etherification of chiral alcohol 10 with racemic imidate 17 and separation of a nearly 1 1 mixture of diastereomers, as shown in Scheme 7.3. Carbon-oxygen single bond forming reactions leading directly to chiral acyclic sec-sec ethers are particularly rare since known reactions are typically nonstereospecific. While notable exceptions have surfaced [22], each method provides ethers with particular substitution patterns which are not broadly applicable. 

The benzyl—nitrogen bond is not so easily cleaved as the benzyl—oxygen bond, unless the O-benzyl group is sterically hindered. This difference in activity allows the selective removal of the O-benzyl function in a molecule containing both N-benzyl and O-benzyl protecting groups. The selectivity can be reversed if the amine is protected by the Cbz group. If a small amount of amine (e g., butylamine) is added, then the selective removal of N-benzyl amines can be achieved.292... 

However, ruthenium, rhodium, and rhodium-platinum catalysts have been found to be highly effective for the selective hydrogenation of these benzyl-oxygen compounds without loss of the oxygen functions. Thus, benzyl alcohol is hydrogenated to cyclohexanemethanol in high yield over ruthenium dioxide with addition of a small amount of acetic acid (eq. 11.35).114... 

An oxygen function in the 4-position of a tetrahydroisoquinoline is benzylic and in a ring. On the basis of its electronic and steric situation, it should be, and is, readily replaced by nucleophiles. The nucleophiles which have been found to be effective thus far are activated (by oxygen) aromatic rings and alcohols. In a related reaction, 4,7-diacetoxytetra-hydroisoquinolines have been shown to undergo a number of base-catalyzed nucleophilic reactions. 

Oxidation of oxygen functions. DDQ is useful for the selective oxidation of allylic " and benzylic alcohols. The reagent has the advantage of not showing the variability encountered with active manganese dioxide. It dehydrogenates 2-hydroxymethylene-3 ketosteroids in about 50% yield. The steroid is treated in dioxane solution at room temperature with 1.1 -1.5 equivalents of DDQ for 1 -5 min.. 

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