Benzyl methyl ether, hydrogenolysis

Hydrogenolysis Benzyl methyl ether Toluene + methanol [157]... 

The oxirane ring in 175 is a valuable function because it provides a means for the introduction of the -disposed C-39 methoxy group of rapamycin. Indeed, addition of CSA (0.2 equivalents) to a solution of epoxy benzyl ether 175 in methanol brings about a completely regioselective and stereospecific solvolysis of the oxirane ring, furnishing the desired hydroxy methyl ether 200 in 90 % yield. After protection of the newly formed C-40 hydroxyl in the form of a tert-butyldimethylsilyl (TBS) ether, hydrogenolysis of the benzyl ether provides alcohol 201 in 89 % overall yield. 

Bamford-Stevens decomposition of tosylhy-drazones, 351 p-Benzoquinone, 308 Benzyl ether hydrogenolysis, 139 Benzyl thioenol ethers, 87 Birch reduction, 11, 49, 50 Birch reduction of estrone methyl ether diethyl ketal, 51... 

Acylation of the amine 35, followed by Odeacetalation, gave 36, which was converted into its dibutyltin derivative.50 This allowed selective acetylation, lactoylation, methylation, and benzylation on 0-6, to give the protected JV-acetylmannosamines, 37,38,39, and 40, respectively. Methylation of 40 gave the 4-methyl ether 41. Catalytic hydrogenolysis led to the free sugars, 16 to 19 (see Scheme 11). 

The 5-methyl ether of V-acetylmannosamine cannot be prepared by this route. The D-glucofuranose 42 was obtained from the 5,6-diol by selective benzylation by way of the dibutyltin derivative, followed by conventional methylation. It was converted into the benzyl glycoside 43 with benzyl alcohol under acidic conditions. Conversion into the amine 44 and amide 45 followed the same path as in the pyranose series. Hydrogenolysis gave20 28 (see Scheme 12). 

Ethers may be removed commonly by acid, with the THE derivative 1.79 reacting more rapidly than the tert-hutyl ether. Benzyl ethers may be removed under a variety of conditions such as hydrogenolysis, dissolving metal reduction (Na in NH3) and HBr (mild). Methyl ethers are cleaved by refluxing with EtSNa and DME tert-Butyl ethers can be cleaved with trifluroacetic acid (CE3COOH) at 25°C. 

Catalytic hydrogenolysis offers the mildest method for deprotecting benzyl ethers. Hydrogenolysis of 2°- and 3°-benzyl ethers may be sluggish. Protection of alcohols using (benzyloxy)methyl chloride produces the corresponding (benzyloxy)methyl ethers (RO-BOM), which are cleaved more readily than the corresponding ROBn ethers. ... 

The method was applied to the synthesis of evodionol (Table 12.1) by the reaction of the methyl ether of phloroacetophenone shown, to give the chromene in 65% yield (95% on the intermediate used). In the much longer synthesis of evodionol (ref. 39), at the initial step by the Hoesch reaction on 2,2-dimethyl-5,7-dihydroxychroman, the desired 6-acetyl product was the minor one and following benzylation to give the 7-benzyloxy compound, methylation, hydrogenolysis and DDQ oxidation were the required remaining steps. 

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