Zinc Bromide deprotection

Notes This alcohol protecting is easily attached and readily removed by Lewis acids such as zinc bromide and titanium tetrachloride. Phenols can be protected (reaction of the sodium salt with MEMC1) and deprotected with TFA. More easily removed than the MOM group. 

These ethers are stable to reducing and oxidising agents, to organometallic reagents, and to mildly acidic conditions that deprotect tetrahydropyranyl and silyl ethers (see below). They are deprotected by the action of either anhydrous zinc bromide or titanium(iv) chloride in dichloromethane solution.80... 

Deprotection of a dimethyl acetal at a late stage in a synthesis of the unusual diterpenoid tropone Hainanolido was not a problem.123 What was a problem was the fate of the aldehyde released because under most conditions, the aide-hyde underwent a very easy Prins-like reaction with the cycloheptatriene ring to give the tetracyclic product 573 [Scheme 2.57], This reaction could not be suppressed completely, but it was minimised by using zinc bromide to deprotect the dimethyl acetal 57.1. The desired aldehyde 573 was obtained in 61 % yield together with 16% of the unwanted 573. 

The cyclohexylidene protecting group has been employed in several syntheses. A preparation of 2,3-0-cyclohexylidene-4-deoxy-L-threose (445) fi om L-( + )-diethyltartrate (lb) in seven steps illustrates one synthetic application (Scheme 99). Conversion of the monobenzyl protected alcohol 443 to its tosylate followed by reduction with sodium borohydride provides the deoxy intermediate 444, which is reductively deprotected and Swem oxidized to 445 in good overall yield. Treatment with benzylamine provides an imine that undergoes a stereoselective carbon-carbon bond forming reaction with a-lithio-A, A -dimethylacetamide in the presence of the Lewis acid zinc bromide to furnish, after Cbz-amine protection, the j9-aminoamide 446. This is converted in four steps to A -acetyl-L-daunosamine (447), a sugar moiety particularly important as the carbohydrate constituent of the anthracycline antibiotics [149]. 

Deprotection can be effected with zinc bromide (CH2CI2, 25°) or with TiCU (0°, 20 minutes). 

Protection and Deprotection.—In a substantial paper, Barton and co-workers have discussed in detail the protection of carboxylic acid functions in penicillin derivatives by conversion into the corresponding acylhydrazines, acylhydrazones, and dihydro-heteroaromatic amides. An alternative method for the methoxymethyl-ation of free acids, which avoids the use of toxic chloromethyl methyl ether, is by prior conversion into the zinc bromide salt followed by reaction with acetyl chloride and methylaP (Scheme 14). 

An attractive feature of the MEM group is the ease with which it can be removed under nonaqueous conditions. Lewis acids such as zinc bromide, titanium tetrachloride, dimethylboron bromide, or trimethylsilyl iodide permit its removal. The MEM group is cleaved in preference to the MOM or THP groups under these conditions. Conversely, the MEM group is more stable to acidic aqueous hydrolysis than the THP group. These relative reactivity relationships allow the THP and MEM groups to be used in a complementary fashion when two hydroxyl groups must be deprotected at different points in a synthetic sequence. 

Construction of the azepine ring by C-N bond formation. Aranapakam et al. synthesized 5,10-dihydro-4H-benzo[l7]thieno[2,3-e]azepine 111 and 4H-benzo[ 7]thieno[3,2-e]azepin-10(9H)-one 113 (X = CO) starting from the corresponding tributylstannyl derivatives 110 and 112, which react with 2-nitrobenzyl bromide and [(Ph)3P]4Pd. Sequential deprotection and reductive cyclization were carried out in one step with zinc and aqueous acetic acid (Scheme 22 (1999BMCL1733)). 

Methoxyphenacyl esters were first described by Sheehan and Umezawa in 1973.They studied the deprotection of a series of amino acids and found that the best yields were obtained when the photolysis was carried out in ethanol. The 4-methoxyphenacyl esters were formed by the reaction of the free acid with 4-methoxyphenacyl bromide in DMF containing triethylamine. Photolyses were carried out with a 450-W Hanovia mercury immersion lamp fitted with a Pyrex filter. The 4-methoxyphenacyl group was used in a synthesis of thymo-pentin analogues.The authors used zinc dust as the standard deprotection procedure for cleavage of phenacyl esters (see Section 2.2). 

Nitrophenyl-a-L-fuco/galacto/rhamno/manno-pyranosides can be made by the reaction of the acetate protected sugar with p-nitrophenol and zinc chloride at 120 °C under vacuum [7]. p-Nitrophenyl-p-D-gluco/galactopyranoside can be generated from the reaction of the acetylated hexopyranosyl bromides with sodium p-nitrophenoxide in DMF [8], followed by deprotection, and /7-nitrophenyl-(3-D-mannopyranoside can be synthesised from mannose via 2,3 4,6-di-0-cyclohex-ylidene-a-D-mannopyranose [9]. 

Subsequently, compound 91 was elaborated to primary alcohol 92 with the H-ring functionality in a similar manner to the Sasaki synthesis (Scheme 11). For the introduction of the triene side chain, a simple and practical method for the stereoselective synthesis of (Z)-vinyl iodide, which is expected to be more reactive than the bromide counterpart, was developed [105]. Thus, PCC oxidation of alcohol 92 followed by treatment of the resultant aldehyde with tetraiodomethane and triphenylphosphine gave diiodoalkene 93. Reduction of 93 with the zinc-copper couple in the presence of acetic acid provided (Z)-vinyl iodide 94 in high yield. Since deprotection of the fully protected... 

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