Phenyl esters cleavage

V. Luzhkov, J. Aqvist, Computer Simulation of Phenyl Ester Cleavage by fi-Cyclodextrin in Solution , J. Am. Chem. Soc., 120,6131 (1998)... 

A photochemical variant, the so-called photo-Fries rearrangement, proceeds via intermediate formation of radical species. Upon irradiation the phenyl ester molecules (1) are promoted into an excited state 11. By homolytic bond cleavage the radical-pair 12 is formed that reacts to the semiquinone 13, which in turn tautomerizes to the p-acylphenol 3. The corresponding ort/zo-derivative is formed in an analogous way ... 

An additional example is the observed moderate acceleration in the cleavage of particular phenyl esters in the presence of a cyclodextrin. In such cases, the bound ester is attacked by an hydroxyl group on the cyclodextrin to yield a new ester. There was found to be a significant enhancement of phenol release from meta-substituted phenyl acetate on interaction with cyclodextrin (relative to other esters which do not fit the cavity so well) (Van Etten, Clowes, Sebastian Bender, 1967). During the reaction, the acyl moiety transfers to an hydroxyl group on the... 

The hydrolysis of sulfate monoesters has been studied increasingly in relation to sulfate group transfer in vivo. In general, the rate-enhancing effect on the sulfate cleavage is small even with hydroxamate- or imidazole-functionalized cationic micelles which are extremely effective for the hydrolysis of phenyl esters. Recently, Kunitake and Sakamoto (1979a) found that zwitterionic hydroxamate [47] cleaved 2,4-dinitrophenyl sulfate effectively in cationic and... 

Some phenyl esters give rise to photodecarbonylation as a side reaction [37], This is also the case for certain phenylpropionamides, which implies cleavage of the CO—C bond in the acyl radical, after the breaking of the N—CO bond [99], If CO—C cleavage occurs prior to N—CO cleavage, then an isocyanate is formed (Scheme 38) and PFR does not occur. 

Immobilized, highly reactive phenyl esters can be prepared by acylating resin-bound 4-acyl-2-nitrophenol (Entry 4, Table 3.13 [285-288]) or 4-(aminocarbonyl)-2,3,5,6-tetrafluorophenol (Entries 7 and 8, Table 3.13). These esters are similar to oxime esters (see Section 3.3.3.3), and even react with weak nucleophiles such as anilines or alcohols. This type of linker is not, therefore, well suited for long synthetic sequences on insoluble supports, but only for the preparation of simple acid derivatives. Because cleavage yields the unchanged phenol, these resins can be reused several times, which renders this strategy of preparing acid derivatives quite cost-effective. 

Entry 9 in Table 3.13 is an example of a safety-catch linker, which requires activation by TFA-mediated cleavage of a tert-butyl ether. The unactivated 2-(tm-butoxyj-phenyl esters are cleaved by amines 700 times more slowly than the corresponding 2-hydroxyphenyl esters [289]. A similar linker has been described [290], in which a benzyl ether is used instead of a ferf-butyl ether. Activation of this linker by debenzy-lation was achieved by treatment with HF or HBr/TFA [290]. 

Different solid-phase techniques for the synthesis of C-terminal peptide aldehydes have gained much attention and allowed greater accessibility to such compounds. Solid-phase techniques have been used to synthesize peptide aldehydes from semicarbazones, Weinreb amides, phenyl esters, acetals, and a, 3-unsaturated y-amino acids)47-50,60 63 The examples presented below use unique linkers to enhance the automated efficiency of C-terminal peptide aldehyde synthesis)47 For instance, the reduction of phenyl esters led to the aldehyde as the major product, but also a small amount of alcohol)50 The cleavage of u,p-unsaturated y-amino acids via ozonolysis yielded enantiomeric pure C-terminal peptides)49,61 The semicarbazone from reduction of peptide esters technique laid the initial foundation for solid-phase synthesis. Overall, Weinreb reduction is an ideal choice due to its high yields, optical purity, and its adaptability to a solid-phase platform)47 ... 

Phenyl trimethylsilyl tellurium reacted under mild conditions with cyclic and linear ethers and with carboxylic acid esters. Cleavage of the C — O bonds produced C-tellurated and O-silylated products in yields ranging from 15 to 98%2. 

This naked selenolate is more reactive than the one complexed with borane 1 [1]. For example, in the presence of HMPA, 4 undergoes an SN2-type ester cleavage to produce the corresponding acids and alkyl phenyl selenides (Sect. 3.3) [6 a]. Uncomplexed selenolate 4 can also be prepared by the reduction of benzeneselenol (PhSeH) with sodium hydride (NaH) (Scheme 4b) [6aj. 

The addition of ethyl sodiomalonate to olefinic ketones followed by ring closure and /3-keto ester cleavage leads to 1,3-cyclohexanediones. The reaction has been applied to the formation of 2-alkyl-5-phenyl-1,3-cyclohexanediones and is typified by the preparation of 5,5-dimethyl-1,3-cyclohexanedione (85%). Other cyclizations for formation of four-and five-membered rings have been described. ... 

The best way to prepare peptide aldehydes from the corresponding N -protected amino acids is by using a handle based on the Weinreb amide.f This commercial handle allows classical solid-phase elongation of peptides using protected Boc or Fmoc amino adds and, at the end of the synthesis, the peptide aldehyde is formed by reduction and concomitant cleavage from the resin with lithium aluminum hydride. Although the 4-hydro-xybenzoic acid handle also allows the preparation of peptide aldehydes by reduction of the resin-bound phenyl ester with lithium tri-tert-butoxyaluminum hydride, a noixture of the aldehyde and the alcohol is always formed. 

The cleavage of esters in basic medium, mediated by CDs, is the system most studied. In some cases, such as that with meta-substituted phenyl acetates, cleavage is strongly accelerated on the contrary, the reaction of para-substituted isomers is accelerated only modestly. The observed effects depend on the chain length of the ester, the CD, and the position of the substituent on the phenyl group. The mechanism typically involves nucleophilic attack by the ionized secondary hydroxyl groups of CD, but in other cases, general base catalysis competes with nucleophile catalysis. 

In homogeneous solvent, the initial cleavage of the phenyl esters produces phenoxyl and acyl radical fragments which recombine in the solvent cage to give a mixture of o- and p-hydroxyketones and phenol as result of radical escape (Scheme 16). The overall quantum yield of the reaction and the product distribution is highly dependent on the H-bonding ability and polarity of the solvent [266]. 

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