Methyl ether, hydrogenolysis

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. 

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

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). 

Fig (13) The adduct (103) prepared from (96) is converted to diketone (104) by Pvmunerer rearrangement. Treatment of (104) with p-TsOH and methanol affords enol ether (105) which on treatment with sodium methoxide in methanol yields the catechol (106) which was converted to ethyl (+)-camosate dimethylether (101) by methylation and hydrogenolysis respectively. 

Palladium was about half as active as rhodium, and platinum and ruthenium were almost inactive for the hydrogenation of isopropenyl methyl ether. Since these metals showed the same order of activity for the hydrogenolysis of acetone diisopropyl acetal, it has been suggested that the dissociation of the acetal to unsaturated ether and alcohol to form an equilibrium mixture (eq. 13.2) constitutes the first step in the hydrogenolysis of acetals. Hydrogenation then removes the unsaturated ether and allows further conversion of the acetal to the unsaturated ether. 

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 3-methyl ethers of the 4,6-0-benzylidene and 4,6-0-ethylidene derivatives of methyl 2-(A-benzyloxycarbonyl)amino-2-deoxy-a-n-gluco-pyranoside have been prepared by a sequence of reactions paralleling Neuberger s synthesis. The d anomer of the latter compound was obtained directly by methylation of 2-(A-benzyloxycarbonyl)amino-2-deoxy-4,6-0-ethylidene-D-glucose with dimethyl sulfate and alkali. Both anomers were transformed into the free amines by catalytic hydrogenolysis. ... 

Post and Anderson prepared the (+)-(13/24) stereoisomer (61) by hydrogenolysis and demethylation of an active inosose methyl ether (65) obtamed by catalytic oxidation of (+)-pinitol (66). The (—) enantiomorph was similarly prepared from (—)-quebrachitol (93, 2-methyl ether). 

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