Benzyl ethers protecting groups

Selective removal of the benzyl ether-protecting group without hydrogenolysis of the ketal C-O bonds was performed on Ra-Ni in EtOH.154 155 A solution of benzyloxy acetal in MeOH with 5% Pd/C was stirred at room temperature with a H2 pressure from a balloon until the reaction was complete (Scheme 4.30).156... 

In some cases the hydrogenation of the double bond in an unsaturated benzyl ether is necessary without debenzylation. To hydrogenate the carbon-carbon double bond 5% Pd/C in AcOEt was used for 1.5 hours (Scheme 4.40).136 The benzyl ether-protecting group was removed over Pd(OH)2 in AcOEt for 1 hour. 

Selective removal of the benzyl ether-protecting group in compound 9 (Fig. 4.1) was made through both transfer hydrogenolysis and the conventional catalytic hydrogenolysis. 

Scheme 27 Oxidative cleavage of the benzyl ether-protecting group.

A further eight steps were required to convert the cyclopentanone 52 into the sulfone 59 that was deprotonated and treated with an allylic bromide (60) to afford the alkylated sulfone 61 (Scheme 7). The sulfone moiety and the benzyl ether protecting group were reductively removed in a one-pot procedure to afford a mono-protected diol (62). 

The benzyl ether is prepared in a similar manner to the methoxymethyl ether, that is, by reaction of the conjugate base of the alcohol with benzyl bromide in an SN2 reaction. An example of a sequence that employs a benzyl ether protecting group is illustrated in the following sequence ... 

HBr in acetic acid (just the solvent) is used to remove the benzyl ether protecting groups in this example, which forms part of a synthesis of the alkaloid galanthamine. 

The additional presence of a 3-methoxy substituent on the benzyl group confers greater stability on the intermediate cation, and consequently oxidation of DMPM ethers by DDQ is even more facile. Yonemitsu and cowoikers have used this differential reactivity of substituted benzyl ethers to great effect in the total synthesis of the macrolide antibiotics methynolide, tylonolide, (95)-9-dihydroerythro-nolide and pikronolide. The pikronolide synthesis provides an excellent example of the selective, sequential deprotection of DMPM, MPM and benzyl ether protecting groups (Scheme 7). 

Chemical synthesis of oligo-Zpolysaccharides demands the use of orthogonal protecting groups capable of selective removal. Benzyl ether protecting groups have seen widespread use... 

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