Phenyl esters, to protect carboxyl groups

The SEM ester was used to protect a carboxyl group where DCC-mediated esterification caused destruction of the substrate. It was formed from the acid and SEM chloride (THF, 0°, 80% yield) and was removed solvolytically. The ease of removal in this case was attributed to anchimeric assistance by the phosphate group. Normally SEM groups are cleaved by treatment with fluoride ion. Note that in this case the SEM group is removed considerably faster than the phenyl groups from the phosphate. ... 

Our final example is a base-labile 4-(phenylsulfonyl)methyl-l,3-dioxolane protecting group for aldehydes and ketones.4 Protection is carried out by the reaction of diol 17,1 (obtained by dihydroxylation of ally phenyl sulfone) with a carbonyl compound in the presence of pyridinium p-toluene sulfonate [Scheme 2.17], Cleavage is accomplished by treatment with DBU. /erf-Butyldimethylsilyl ethers, p-toluenesulfonate esters, tetrahydropyranyl ethers, carboxylic esters and benzoates are well tolerated. A disadvantage to the use of 17.1 is the introduc-... 

Like the silyl ethers, the stability of the silyl esters parallels the steric bulk of the substituents on the silicon atom. Tris(2,6-diphenylbenzyl)siiy1 esters confer extraordinary steric protection upon the carboxyl group.234 For example, the tris(2,6-diphenylbenzyl)silyl ester of 4-phenylbutanoic acid 104.1 [Scheme 6.104] does not react with butyllithium (2.5 equiv) after 5 h at -78 °C or methylmag-nesium bromide (2,5 equiv) at room temperature. Nor did it react with lithium aluminium hydride after 30 min at 0 °C l M HC1 in THF at 40 °C, or aqueous sodium hydroxide at 50 °C after 5 h. Ester 104.1 was reduced with diisobutyl-aluminium hydride in 99% yield to give the 4-phenyl-l-butanol (99%) and HF pyridine in THF (1 2) at 50 aC cleaved it back to the acid after 5 h. Unfortunately, the penalty for such unusual stability is high the tris(2 6-diphenyl-... 

The reaction was applied to model dipeptides exemplified by the y-phenyl-hydrazide of N-carbobenzoxy-a-L-glutamyl-L-methionine methyl ester (4) and found to afford the carboxylic acid (S) in good yield without disturbance of the carbo-benzoxy and ester protective groups. The results suggest use of the phenylhydrazide group for protection of carboxyl groups in peptide chemistry. 

The reactivity of ketenimines such as 146 is related to substituent R. Ketenimines were isolable when R was phenyl or alkyl. In contrast, ketenimines wherein R was halogen, thienyl, phenylthio, methylthio, or methylsulfonyl were sufficiently reactive to afford iminoethers (147) at -78°C in the presence of excess lithium methoxide. The trimethyl-chlorosilane-quinoline procedure satisfactorily converted all these substituted iminoethers to amides in good yields. The overall sequence proved amenable for use with cephalosporin acids, by prior protection of the carboxyl group as a silyl ester. Extension of this method to the penicillin series permitted the preparation of 6a-methoxyketenimine 149 and 6a-methoxyimino ether 150 from the corresponding methyl 6p-(2-chlorophenyl)acetamido and fi -dichloroacetamidopenicillanates, respectively. No further transformations of these substances were reported. 

This derivative is prepared from an A-protected amino acid and the anthrylmethyl alcohol in the presence of DCC/hydroxybenzotriazole. It can also be prepared from 2-(bromomethyl)-9,10-anthraquinone (Cs2C03). It is stable to moderately acidic conditions (e.g., CF3COOH, 20°, 1 h HBr/HOAc, / 2 = 65 h HCl/ CH2CI2, 20°, 1 h). Cleavage is effected by reduction of the quinone to the hy-droquinone i in the latter, electron release from the —OH group of the hydroqui-none results in facile cleavage of the methylene-carboxylate bond. The related 2-phenyl-2-(9,10-dioxo)anthrylmethyl ester has also been prepared, but is cleaved by electrolysis (—0.9 V, DMF, 0.1 M LiC104, 80% yield). ... 

In the initial step, the first BOC-protected amino acid is bound to the polymer, e.g. polystyrene in which a proportion of the phenyl rings have chloromethyl substitution. Attachment to these residues is through the carboxyl via an ester linkage. This involves a simple nucleophilic substitution reaction, with the carboxylate as nucleophile and chloride as leaving group (see Section 6.3.2). After each stage, the insoluble polymer-product combination is washed free of impurities. 

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