Protective groups 4-methoxyphenyl

Six protective groups for alcohols, which may be removed successively and selectively, have been listed by E.J. Corey (1972B). A hypothetical hexahydroxy compound with hydroxy groups 1 to 6 protected as (1) acetate, (2) 2,2,2-trichloroethyl carbonate, (3) benzyl ether, (4) dimethyl-t-butylsilyl ether, (5) 2-tetrahydropyranyl ether, and (6) methyl ether may be unmasked in that order by the reagents (1) KjCO, or NH, in CHjOH, (2) Zn in CHjOH or AcOH, (3) over Pd, (4) F", (5) wet acetic acid, and (6) BBrj. The groups may also be exposed to the same reagents in the order A 5, 2, 1, 3, 6. The (4-methoxyphenyl)methyl group (=MPM = p-methoxybenzyl, PMB) can be oxidized to a benzaldehyde derivative and thereby be removed at room temperature under neutral conditions (Y- Oikawa, 1982 R. Johansson, 1984 T. Fukuyama, 1985). 

Methoxyphenyl (PMP) ethers find occasional use as hydroxy protecting groups. Unlike benzylic groups, they cannot be made directly from the alcohol. Instead, the phenoxy group must be introduced by a nucleophilic substitution.185 Mitsunobu conditions are frequently used.186 The PMP group can be cleaved by oxidation with CAN. 

It is synthesized by the reaction of 3,4-dimethoxyphenyl-2-amine and l-(4-methoxyphenyl)-3-butanone with a simultaneous reduction of formed imine, giving the product (11.1.30), the methoxyl-protecting groups of which are cleaved by hydrogen bromide, giving dobutamine (11.1.31) [32,33]. 

Hexestrol Hexestrol, 4,4 -(l,2-diethylethylene)diphenol (28.1.29), is a derivative of a,j3-diphenylethane, and it is a synthetic estrogen. Hexestrol is made in a Wurtz dimerization reaction of l-bromo-l-(4-methoxyphenyl)propane (28.1.27) in the presence of sodium, magnesium, aluminum, or iron. The initial l-bromo-l-(4-methoxyphenyl)propane (28.1.27) is made in turn by addition reaction of hydrogen bromide to 4-methoxy-l-propenylbenzene. Subsequent removal of the methoxy protective groups from the resulting dimerization product (28.1.28) using hydroiodic acid gives hexestrol (28.1.29) [37-43]. 

Methoxyphenyl (PMP) ethers find occasional use as hydroxyl-protecting groups. 

Amide nitrogens can be protected by 4-methoxyphenyl or 2,4-dimethoxyphenyl groups. The protective group can be removed by oxidation with ceric ammonium nitrate.79... 

In a synthetic application of this double inversion sequence, tris(benzyloxy)bromo boronic ester 6 obtained in the ribose sequence (Section 1.1.2.1.3.2.) is converted to the 4-methoxyphenyl-methoxy derivative 7 in the usual way. 2,3-Dichloro-5,6-dicyano-l,4-benzoquinone cleaves the protecting group to furnish the a-hydroxy boronic ester 8. Conversion of the a-hydroxy boronic ester 8 to the methanesulfonate 9 followed by displacement of the sulfonate by phenylmethoxide yields a-benzyloxy boronic ester 10, which is a diastereomer of one of the ribose intermediates37. 

Boc,245 /-butyl ester,246 trityl ether247 and even tris(p-methoxyphenyl)methyl ether.248 The oxidation-sensitive PMB normally resists the action of PCC,249 as well as the sulfur-containing protecting groups dithioacetals250 and mono-thioacetals.251... 

The chloro moiety of thieno[3,4-d]pyrimidine 383 was displaced by 4-(2-methoxyphenyl)piperazine or 4-(4-fluorobenzoyl)piperidine in refluxing propan-2-ol containing sodium bicarbonate and a catalytic amount of sodium iodide. The N-3 protecting group of the resulting derivatives 384 was... 

FIGURE 10.1 Some monosaccharide building blocks used in the assembly of (a) HA, (b) CS, and (c) heparin/HS showing the array of protecting groups. All, allyl Bn, benzyl Bz, benzoyl Fmoc, 9-fluorenylmethoxycarbonyl Lev, levulinyl NAP, 2-naphthylmethyl PBB, p-bromobenzyl Phth, phthaloyl PMB, / -methoxybenzyl PMP, p-methoxyphenyl TBDPS, ferf-butyldiphenylsilyl TBS, ferf-butyldimethylsilyl TCA, trichloroacetyl TDS, dimethylthexylsilyl Tol, 4-tolyl. 

An excerpt from a synthesis of the phytosiderophore Nicotianamine illustrates the formation and cleavage of the 2,2,2-trichloroethyl carbonate protecting group [Scheme 4.357].676 Reaction of alcohol 357,1 with 2,2,2-trichloroethyl chloroformate and a catalytic amount of DMAP in pyridine gave the 2,2>2-tri-chloroethyl carbonate 357 2 in 98% yield. After oxidative destruction of the two p-methoxyphenyl rings to carboxylic acids and esterification, the 2224ri-chloroethyl carbonate 3573 was cleaved with zinc and acetic acid in 97% yield. 

A good example of the useful participation of a protecting group in a chemical transformation is shown in the following scheme. Suggest a mechanism for the conversion of 2-bromo-4-methoxyphenyl ether 2.1 to the bicyclic derivative 2.2 as well as a mechanism for the oxidative deprotection of 2.2 to 23 using ceriu-m(lV) ammonium nitrate. 

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. 

This strategy was followed in the example shown in Scheme 5.5, Scheme 5.6 and Scheme 5.7 using the tert-butyldimethylsilyl ether as the temporary protecting group. Silyl ethers, allyl, p-methoxyphenyl and 2-(trimethylsilyl)ethyl groups are all commonly used for temporary protection of the anomeric position. 

The PMB ether, also referred to as an MPM ether [(4-methoxyphenyl)methyl], is less stable to acids than a benzyl ether. Its utility as a protecting group stems from the fact that it can be removed oxidatively with DDQ (2,3-dichloro-5,6-dicyano-l,4-benzo-quinone) under conditions that do not affect protecting groups such as acetals, RO-Bn (or RO-BOM), RO-MOM, RO-MEM, RO-THP, RO-TBS, benzoyl, tosyl, or acetate groups, nor do they affect epoxides or ketones. Alternatively, RO-PMB ethers can be cleaved with (NH4)2Ce(N03)6. ... 

In the synthesis of Aristotelia-type alkaloids, Burkard and Borschberg [13] found that the best method for elimination of the 2,6-difluorobenzyl group of the indole derivative Ila was a procedure involving calcium in ammonia. This led to the desired indolyl alcohol 12 in 74% yield (Scheme 4.3). Use of excess dissolved calcium also enabled simultaneous removal of both the (4-methoxyphenyl)sulfonyl and the 2,6-difluorobenzyl protecting groups from 11b to give 12 in 62% yield [14]. 

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