P-methoxybenzyl groups

The p-methoxybenzylidene ketal can be prepared by DDQ oxidation of a p-methoxybenzyl group that has a neighboring hydroxyl. This methodology has been used to advantage in a number of syntheses. " In one case, to prevent an unwanted acid-catalyzed acetal isomerization, it was necessary to recrystallize the DDQ and use molecular sieves. The following examples serve to illustrate the reaction " ... 

Removal of the p-methoxybenzyl group is accomplished by treatment with dichloro-dicyanoquinone (DDQ), which forms quantitatively aminal 17 in an 11.5 1 diastereomeric ratio (Yu and Levy, 1984). The solution is treated with sodium methoxide in methanol, which decomposes the aminal into the desired amine 18 and p-methoxybenzaldehyde. Due to the difficulties in separating the p-methoxybenzaldehyde from amino alcohol 18, the aldehyde is reduced in situ with sodium borohydride. The amino alcohol 18 is crystallized from the reaction mixture after neutralization with acetic acid. Additional recrystallization provides the desired amino alcohol 18 in 94% yield. 

Yoshimura has introduced the p-methoxybenzyl group for N-protection in piperazine-2,5-diones (83CL1001 85BCJ1413). The N-alkylation is carried out with sodium hydride and p-methoxybenzyl bromide in DMF at room temperature. Deprotection is achieved by ceric ammonium nitrate (CAN) in acetonitrile-water. 

The p-methoxybenzyl group has also been recommended as an N-protecting group. In this use, it is cleaved by trifluoroacetic acid at 65°, conditions to which an N-benzyl group is stable.3... 

The extended cyclic enolate derived from a simple pyrrol-3-en-2-one (butenolac-tam) has been deuterated at the 5-position with very high diastereoselectivity if the (g) nitrogen atom carries a a-methyl-p-methoxybenzyl group (de > 99 l).27 A similar diastereoselective protonation has been observed in a pyrrol-3-en-2-one formed by dearomatizing cyclization of a pyrrole. 

NH4)2Ce(N03)6, MeCN—112(), 20°C, 2 h 96% note selective removal of the p-methoxybenzyl group, leaving the /V-bcnzyl (or in other examples, an /V-mcthyl) group intact.576... 

An excerpt of a synthesis of the potent antitumour agent FR-900482 [Scheme 3.126] illustrates the use of an N, O-acetal with additional Af-protection in the form of a 2,2,2-trichloroethoxycarbonyl (TVoc) group (see section 8.3.7) in a multifunctional environment.244 245 The A 0-acetal survived the mildly acidic conditions required to deprotect the p-methoxybenzyl group that preceded the formation of the triflate 1263. Later, reductive cleavage of the Troc group and simultaneous hydrolysis of the oxazolidine ring was accomplished in a single... 

Protic acids will also cleave p-methoxy benzyl ethers under comparatively mild conditions. At 90 cC, acetic acid is sufficient352 but the reaction works at room temperature with as little as 0.5% trifluoroacetic acid in dichloromethane.353 p-Methoxybenzyl groups can be removed selectively with trifluoroacetic acid in the presence of secondary glycosidic linkages, azides, or phenylthio glycosides [Scheme 4.189],354 The survival of a trisaccharide under the deprotection conditions indicates that p-methoxybenzyl groups may be useful in oligosaccharide synthesis. 

Strong acidolytic conditions were precluded by the presence of an N-Boc group and an activated secondary benzylic alcohol in a synthesis of the Ecteinasddin fragment depicted in Scheme 5.7. Hence, the S-p-methoxybenzyl group was excised with mercury(II) trifluoroacetate in acetic acid and the liberated thiol then cydised onto a benzylic centre under the aegis of trifiuoroacetic acid.20 21... 

During a synthesis of the antibiotic Micacocidin, a p-methoxybenzyl group was used to protect the thiol function in intermediate 8.1 [Scheme 5.8].22 The 5-p-methoxybenzyl group was cleaved in two steps by first reacting 8.1 with 3-nitro-2-pyridinesulfenyl chloride (83) to give the disulfide intermediate 83 which was then treated with tributylphosphine in aqueous acetone to afford the thiol 8.4 in 69% overall yield for the two steps 2324... 

The benzyl (Bn) or p-methoxybenzyl groups (PMB) can be removed under reducing cleavage conditions (Scheme 1.20). 

Removal of protective groups in peptide synthesis. The reagent, dis.solved in tri-fluoroacetiu acid, removes various acid-Iabiie N-protecting groups (Cb, BOC, etc.) at 0°. It also removes nitro, tosyl, or p-methoxybenzyl groups used for protection of side-chain groups. 

DMTST-promoted coupling of donor 25 with the earlier used 3-OH acceptor 10 gave the heptoside disaccharide 26, from which the p-methoxybenzyl group... 

Similarly, DDQ oxidation of the p-methoxybenzyl group of 269 in the presence of alcohol 270, a strategy reported by Ito and Ogawa [119] in O-glycoside s)uithesis, provides benzylidene acetal 271 [120] (O Scheme 57). 

Red-Al) or the Z-olefin 341 after benzylation. Stereoselective dihydroxylation and regiose-lective protection of the diol provides protected polyol 342 that is transformed in three steps to terminal epoxide 343. Removal of the p-methoxybenzyl group followed by acid-catalyzed epoxide opening yields exclusively tetrahydropyran 344 after protection of the primary alcohol and deacetylation. Inversion of the C2 stereocenter by an oxidation-reduction sequence and deprotection furnishes the C-mimic of a,a-trehalose 345. 

Peptide synthesis. The p-methoxybenzyl group is regarded as superior to the benzyl group for S-protection. It is readily cleaved from the final peptide either by sodium in liquid ammonia or by boiling with trifluoroacetic acid or with anhydrous hydrogen fluoride. ... 

Lithium di-terf-butylbiphenyl (LiDBB), THF, -78°C, 3 h, 95% yield. LiDBB has been found to cleave THF upon sonication. A p-methoxybenzyl group is retained during benzyl cleavage with this reagent. ... 

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