4- Methoxybenzyl ether cleaved

NBS, CH3CN, H2O, 62-90% yield.The POM group has been selectively removed in the presence of an ethoxy ethyl ether, TBDMS ether, benzyl ether, p-methoxybenzyl ether, an acetate, and an allyl ether. Because the hydrolysis of a pentenyl 2-acetoxyglycoside was so much slower than a pentenyl 2-benzyloxyglycoside, the 2-benzyl derivative could be cleaved selectively in the presence of the 2-acetoxy derivative. The POM group is stable to 75% AcOH, but is cleaved by 5% HCl. 

These reaction conditions do not affect most of the other common hydroxy-protecting groups and the methoxybenzyl group is therefore useful in synthetic sequences that require selective deprotection of different hydroxy groups. 4-Methoxybenzyl ethers can also be selectively cleaved by dimethylboron bromide.182... 

DDQ. a reagent typically used to deprotect p-methoxybenzyl ethers (see section 4.3 4), has been used for the deprotection of acetals19 and thioacetals.20 The use of 0.1 -0.4 equivalents of DDQ in acetonitrile-H20 (9 1) cleaves isopropylidene groups at room temperature to 80 C without affecting p-toluenesulfonyl, benzoyl, benzyl, or acetate groups. Monosubstituted dioxolanes [Scheme 3.17]21 are more readily hydrolysed than bicyclic, spirocyclic, and disubstituted systems and 1,3-dioxanes are more labile than 1,3-dioxolanes. Removal of dithioacetals requires 2 equivalents of DDQ at 80 °C... 

The regiochemistry of reductive cleavage of p-methoxybenzylidene acetals depends on the substrate and the reaction conditions. By suitable choice of solvent and electrophile, the distribution of regioisomers can be controlled in some cases. For example, sodium cyanoborohydride cleaved glucose derivative 66.1 [Scheme 3.66] selectively to the 6-0-p-methoxybenzyl ether 663 using trifluoro-acetic add as electrophile and DMF as solvent whereas the 4-Op-methoxy-benzyl ether 663 predominated when chlorotrimethylsilane was used as electrophile in acetonitrile as solvent.115 Note, however, that application of the latter conditions to the p-methoxybenzylidene acetal 67,1 [Scheme 3.67] gave the p-methoxybenzyl ether of the less hindered primary hydroxyl as well as rearrangement of the isopropylidene acetal,116... 

More specific anomeric protecting groups are the 2-trimethylsilylethyl (TMSE) [25] and p-methoxyphenyl glycosides [26], both introduced by glycosylation reactions on protected derivatives (Scheme 3.5). The former is cleaved by treatment with BF3-etherate conditions in which TBDMS ethers survive. p-Methoxyphenyl glycosides are cleaved by CAN-oxidation similarly to p-methoxybenzyl ethers. 

Ether cleavage. 4-Methoxybenzyl ethers are cleaved with clay-supported ammonium nitrate on microwave irradiation (13 examples, 70-88%). No solvent is used. 

Pd/C, H2, EtOAc, >52% yield. Thep-phenylbenzyl ether is more easily cleaved by hydrogenolysis than normal benzyl ethers. This was used to great advantage in the deprotection of the vineomycinone intermediate shown below. The use of the p-methoxybenzyl ether proved unsuccessful in this application because it could not be removed by either hydrogenolysis or oxidatively with DDQ. 

Ether cleavage. An allylicp-methoxybenzyl ether is selectively cleaved with DDQ in a buffer solution, thereby facilitating the progress in a synthesis of multipolide-A. ... 

Transetherification and transesterification. Tin(II) bromide is a catalyst for converting p-methoxybenzyl ethers into methoxymethyl ethers by CH2(OMe)2 and MeOCH2Br. Benzyl ethers and trimethylsilyl ethers are cleaved and acetylated in one operation by the action of SnBr2-AcBr in CH2CI2 at room temperature. 

De-O-protection. Both tetrahydropyranyl ethers and p-methoxybenzyl ethers are said to be cleaved with this reagent. However, the method does not seem to have any advantage over existing procedures. 

Lewis acids can also be exploited for the cleavage of isopropylidene derivatives. One of the mildest examples comes from a synthesis of Lankacidin in which cleavage of an isopropylidene acetal without harm to a p-methoxybenzyl ether was effected with copper(Il) chloride dihydrate in methanol at reflux [Scheme 3.11]. Alternatively, zinc(II) nitrate hexahydrate in acetonitrile at SO C can be used in which case even a primary te/t-butyldimethylsilyl ether survives [Scheme 3.12]. During a synthesis of Quinocarin, Katoh and co-workers cleaved an isopropylidene group using iron(III) chloride adsorbed onto silica gel [Scheme 3.13]. 

Diisobutylalane is both a Lewis acid and a reducing agent that selectively cleaves arylmethylene acetals. The reaction conditions are compatible with the presence of rm-butyldiphenylsilyl ethers [Scheme 3.63] and p-methoxybenzyl ethers [Scheme 3.64]. - The high regioselectivity in the latter case is at first surprising but an X-ray structure of the substrate shows that the bond selectively cleaved is longer in the ground state and therefore weaker. 

Scavengers are usually added to arrest the p-methoxybenzyl carbocation before it can do any collateral damage. Typical combinations of Lewis acid and scavenger are trifluoroborane and triethylsilane tin(IV) chloride and benzene-thiol - catalytic amounts of tin(II) chloride dihydrate and ethanelhiol - catalytic amounts of trichloroalane and ethanethiol magnesium bromide etherate and dimethyl sulfide and trichloroborane and dimethyl sulfide [Scheme 4.188]. Cerium(III) chloride heptahydrate together with sodium iodide cleaves p-methoxybenzyl ethers in refluxing acetonitrile- as does iodine in refluxing methanol but in the latter case, isopropylidene acetals do not survive. ... 

Protic acids will also cleave p-methoxybenzyl ethers under comparatively mild conditions. At 90 °C, acetic acid is sufficient- but the reaction works at room temperature with as little as 0.5% trifluoroacetic acid in dichloromethane. p-Methoxybenzyl groups can be removed selectively with trifluoroacetic acid in the presence of secondary glycosidic linkages, azides, or phenylthio glycosides [Scheme 4.189]. The survival of a trisaccharide under the deprotection conditions indicates that p-methoxybenzyl groups may be useful in oligosaccharide synthesis. 

Another useful strategy for the activation of an amide towards hydrolysis involves intramolecular 0-alkylation of the amide carbonyl. An early rendition of this strategy entailed the use of 4-chlorobutanamides in which cleavage was initiated by treatment with silver(I) perchlorate in aqueous acetone. More re-cently the Fraser-Reid group showed that N-pent-4-enoyl derivatives are rapidly and efficiently cleaved under mild conditions by brief treatment with 3 equivalents of iodine in aqueous THF [Scheme 8.29]. These deprotection conditions do not affect oxidisable functionalities including p-methoxybenzyl ethers and alkyl sulfides though allyloxycarbonyl groups appear to be incompatible. Primary and secondary amines are readily protected as N-pent-4-enoyl derivatives by reaction with pent-4-enoic anhydride. 

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