Hydrogenation benzyl ether deprotection

Pd/CaC03 is also used for the hydrogenolysis of benzyl-oxygen bonds.152 Hydrogenation and hydrogenolysis of an unsaturated benzyl ether over 5% Pt/ C and Pd(OH)2 gave the saturated and deprotected product.153 In contrast, transfer hydrogenolysis with 1,4-cylohexadiene or ammonium formate failed to provide the product cleanly, rapidly, or dependably. 

Treatment of the 0,0-dibenzyl derivative of norneoenactin with 10% Pd/C in MeOH under hydrogen atmosphere resulted in the rapid deprotection (within 1 h) of the starting material. However, reduction of the benzyl ether functionality, without the concomitant hydrogenolysis of the N-O bond, required fine tuning of the conditions. When the hydrogenolysis was carried out using 20-25 mol % of 10% Pd/C at 20 or 30 mM concentrations for 22-31 hours, a... 

Methoxyphenyl ethers can be cleaved by mild oxidants (Entry 10, Table 7.8). Because many acid-labile linkers are also readily oxidized, care must be taken when applying this deprotection strategy. Benzyl ethers have been removed from Tentagel-or PEGA-bound carbohydrates by catalytic hydrogenation using palladium nanoparticles [112],... 

Step 6. The catecholic and phenolic ethers were removed by treatment with hydrobromic acid. Benzyl ethers are frequently removed by reduction (e.g. hydrogenation) but reduction, of course, would not remove the methyl ether. The mechanism of the deprotection is shown below. 

Direct 2 - or 3 -0-benzylation of nucleosides has been reported,71,95,96 but removal of the benzyl group by catalytic hydrogen-olysis is not straightforward. The deprotection of methyl-substituted-benzyl ethers of nucleosides has been effected by treatment with acid. An improvement here has been the use of the photosensitive o-nitro-... 

In the early 1970s, Barton et al. published the results of their woik on the oxidation of acetals and ethers by hy de transfer. o They observed that substituted benzyl ethers and benzyloxy carbonates, on brief exposure to trityl tetrafluoroborate in dichloromethane at 0 C followed by aqueous work-up, afforded go( yields of the parent alcohols together with the corresponding bennldehydes. Undw the same conditions, the tetrahydropyranyl ether of cholesterol was also efficiently deprotected. A mechanism was proposed which involved an initial hydrogen abstraction, followed by quenching of the resulting stabilized cation by water (Scheme 6). 

Benzyl ethers are Cleaved urider both hydrogenation and Birch reduction conditions. Both methods are used in the deprotection of benzyl-protecteo alcohols. The by-product is toluene ... 

A new cortisone derivative, 3,20-dioxo-lljS,17a,21-trihydroxypregna-l,4,7-triene (298), has been prepared from the intermediate (297) by a classical combination of chemical and microbiological reactions.The chemistry of 17,20-and 20,21-acetonides, epimeric at C(20), has been described. A deprotection of masked steroidal alcohols by hydride transfer has been reported.Several benzyl ethers and bismethylenedioxy-steroids have been prepared and treated with trityl fluoroborate. The results demonstrated that the benzyl hydrogen atoms are sufficiently basic to give a benzyloxonium ion, as shown in the conversion of the 17,20 20,21-bismethylenedioxy-corticoid (299) into its free analogue (302) (see Part II, Chapter 1, refs. 120 and 323). 

Sequential catalytic hydrogenation of the imine bond followed by hydrogenoly-sis of the resultant yV-diphenylmethylamine is an alternative method of deprotection which was used in a solid-phase synthesis of O-glycosyl cyclic Enkephalin analogues [Scheme 8.236]. Note the comprehensive deprotection of 4 benzyl ethers, a diphenylmethyl ester, and an N-diphenylmethyleneamine in a single operation. iV-Diphenylmethyleneamine derivatives of serine have also been applied to the synthesis of Sphingosines. ... 

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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