Deprotection selective

The methods to achieve regioselectively protected derivatives by selective deprotection are less common. However, a few standard methods utilize this approach [52]. The rate difference in 

SCHEME 3.21 Examples of regioselective removal of primary protecting groups. 

SCHEME 3.23 Examples of regioselective removal and opening of acetal protecting groups. 

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Fig. 30. Synthesis of an acid-labile copolymer by radical copolymerization using a latent HOST, followed by selective deprotection (89).

As practiced by Hoffmann-La Roche, the commercial synthesis of vitamin is outlined ia Figure 1. Oxidation of 2-methylnaphthalene (4) yields menadione (3). Catalytic reduction to the naphthohydroquinone (5) is followed by reaction with a ben2oating reagent to yield the bis-benzoate (6). Selective deprotection yields the less hindered ben2oate (7). Condensation of isophytol (8) (see Vitamins, vitamins) with (7) under acid-cataly2ed conditions yields the coupled product (9). Saponification followed by an air oxidation yields vitamin (1) (29). 

T. D. Nelson and R. D. Crouch, Selective Deprotection of Silyl Ethers, Synthesis, 1031 (1996). 

Aryl and alkyl trimethylsilyl ethers can often be cleaved by refluxing in aqueous methanol, an advantage for acid- or base-sensitive substrates. The ethers are stable to Grignard and Wittig reactions and to reduction with lithium aluminum hydride at —15°. Aryl -butyldimethylsilyl ethers and other sterically more demanding silyl ethers require acid- or fluoride ion-catalyzed hydrolysis for removal. Increased steric bulk also improves their stability to a much harsher set of conditions. An excellent review of the selective deprotection of alkyl silyl ethers and aryl silyl ethers has been published. ... 

Silylation of both the primary and secondary hydroxyl groups is followed by selective deprotection to regenerate the primary hydroxyl group. 

An obvious outcome of the Hantzsch synthesis is the symmetrical nature of the dihydropyridines produced. A double protection strategy has been developed to address this issue. The protected chalcone 103 was reacted with an orthogonally protected ketoester to generate dihydropyridine 104. Selective deprotection of the ester at C3 could be accomplished and the resultant acid coupled with the appropriate amine. Iteration of this sequence with the C5 ester substituent ultimately gave rise to the unsymmetrical 1,4-dihydropyridine 105. 

The N(2) atom of l-iminoperhydropyrido[l,2-c]pyrimidine 153 was selectively deprotected by treatment with NaH to yield 1-amino-4,4n,5,6,7,8-hexahydropyrido[l,2-c]pyrimidine 154 (00TL1849). 

Selective Deprotection of Alcoholic and Phenolic TBDMS Ethers (14)... 

Under carefully controlled conditions, TBAF and aqueous HF selectively deprotect phenolic and alcoholic silyl ethers respectively. An excess of either reagent will, of course, ultimately result in complete deprotection. 

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... 

Z)-enolates. The product was subjected to selective deprotection of the C4,C4 -methyl ethers with Mgl2, providing the natural structure of hypocrellin A as the major product. The two newly formed stereocenters in the 7-membered ring were determined to conform to the predicted helical (/ -stereochemistry and the syn-aldol stereochemistry. The minor ( )-enolate afforded the anti aldol product, which matched the diastereomeric natural product shiraiachrome A (8). With this step, the first total syntheses of hypocrellin A and shiraiachrome A (symanti = 10 1 syn diastereomer, 92 % ee) were completed. 

Silica gel-based catalytic systems have been described as efficient promoters for a number of organic reactions.28 Illustrative examples include the oxidative cleavage of double bonds catalyzed by silica-supported KM11O4,29 reaction of epoxides with lithium halides to give /i-halohydrins performed on silica gel,30 selective deprotection of terf-butyldimethylsilyl ethers catalyzed by silica gel-supported phosphomolybdic acid (PMA),31 and synthesis of cyclic carbonates from epoxides and carbon dioxide over silica-supported quaternary ammonium salts.32... 

Scheme 24. Selective deprotection of sugar di-O-isopropylidene acetals using acid zeolites.

Selective removal of one isopropylidene group from a diacetal may be achieved by a variety of procedures, most of them involving protic or Lewis acids.100 Particularly common is the hydrolysis of the acetal engaging of the primary position of di-O-isopropylidene derivatives. Bhaskar et al,101 studied the selective deprotection of di-O-isopropylidene acetals derived from D-glucose, D-xylose, and D-mannose, using acid zeolites and montmorillonite K-10. When 102 was submitted to acid hydrolysis in aqueous methanol, the best yields (85—96%) for the monoacetal 105 were obtained when H-beta and HZSM-5 zeolites were employed as catalysts (Scheme 24, Table IV). HY zeolite proved to be ineffective, whereas the yield obtained for the montmorillonite K-10-catalyzed reaction was low (22%). The zeolites found most effective were then used for the hydrolysis of the diacetal 103 and 104, providing excellent yields for the desired corresponding monoacetals 106 and 107. 

Solid Acid-Catalyzed Selective Deprotection of l,2 5,6-Di-0-isopropylidene-a-D-glucofuranose (102)... 

Furthermore, several functionalities remained unaffected, namely the acid-labile TBDMS or PMB groups.118 Deprotection yields were in the range of 85-95% when methanol was used at room temperature as the solvent, whereas acetonitrile or dichloromethane led to very sluggish or nonexistent reactions, respectively. Cleavage of primary trityl ethers was also accomplished using the same conditions in a very rapid and effective fashion. The trityl pyranosides and furanosides assayed were selectively deprotected in 2-3 h and yields higher than 85% were achieved. This reaction was also more efficient when conducted in methanol, which acts as a nucleophile to trap the generated trityl cation. 

G. D. Kishore Kumar and S. Baskaran, A facile, catalytic, and environmentally benign method for selective deprotection of ferf-butyldimethylsilyl ether mediated by phosphomolybdic acid supported on silica gel, /. Org. Chem., 70 (2005) 4520-4523. 

P. M. Bhaskar, M. Mathiselvam, and D. Loganathan, Zeolite-catalyzed selective deprotection of di- and tri-O-isopropylidene sugar acetals, Carbohydr. Res., 343 (2008) 1801-1807. 

A. Agarwal and Y. D. Vankar, Selective deprotection of terminal isopropylidene acetals and trityl ethers using HCIO4 supported on silica gel, Carbohydr. Res., 340 (2005) 1661-1667. 

Using day supported ammonium nitrate (dayan), selective deprotection of methoxyphenyl methyl (MPM) ether has been achieved recently using microwave irradiation in solvent-free conditions (Scheme 6.15) [56]. The same reagent has been used for the cleavage of tetrahydropyranyl (THP) ethers. A similar selective preparation and deavage of THP ethers has been achieved under microwave irradiation catalyzed by iodine [57] or neat reaction in an ionic liquid [28],... 

This procedure was also compatible with the benzyl ester, as demonstrated in Scheme 8.24 by selective deprotection of compound 66 (67 was isolated in 70% yield by chromatography after 20 min irradiation at 75 °C (30 W) in the Synthewave 402 reactor). 

Compared to the well-known OBO esters [81], the ABO esters are more stable towards protic acids but less stable towards the Lewis acid Cp2ZrCl2/AgC104, which isomerizes the ABO orthoester to a tetrahydrofuranyl ester. Selective deprotection is therefore possible (Scheme 8.41). 

Scheme 8.41. Selective deprotection of ABO and OBO esters from an ABO/OBO mixture.

Acid- and base-sensitive lipidated peptides can be selectively deprotected by enzymatic hydrolysis of choline esters.[13al Choline esters of simple peptides, but also of sensitive peptide conjugates like phos-phorylated and glycosylated peptides,1141 nucleopep-tides1151 and lipidated peptides,113,1631 can be cleaved with acetyl choline esterase (AChE) and butyryl choline esterase (BChE) under virtually neutral conditions with complete chemoselectivity. Acid-labile farnesyl groups and base-sensitive thioesters are not attacked. 

Pd°-catalyzed deprotection of S-palmitoylated dipeptide 9 yielded the corresponding selectively deprotected peptide 10. Condensation of 10 with farnesylated pentapeptide 15, which was readily accessible via the Aloe methodology1201 as depicted in Scheme 10 and alternatively using AcOZ1111 as the protecting group, resulted in the formation of target peptide 16.17251... 

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