Acyl-transfer side reaction

There are only a few examples of low-temperature conditions reported to lead to a species behaving as an o-QM. All of these, except for our O-acyl transfer methods that will be discussed later, use a fluoride ion to trigger the formation of the o-QM in an almost instantaneous manner. In these examples, a high concentration of the intended nucleophile is necessary to prevent any side reactions with the o-QM, because given the low-temperature conditions its formation is usually irreversible. 

A common explanation of the DMAP acceleration suggests that DMAP, as a stronger nucleophile than the alcohol, reacts with the O-acylisourea leading to a reactive amide ( active ester ). This intermediate cannot form intramolecular side products but reacts rapidly with alcohols. DMAP acts as an acyl transfer reagent in this way, and subsequent reaction with the alcohol gives the ester. 

Shi and coworkers found that vinyl acetates 68 are viable acceptors in addition reactions of alkylarenes 67 catalyzed by 10 mol% FeCl2 in the presence of di-tert-butyl peroxide (Fig. 15) [124]. (S-Branched ketones 69 were isolated in 13-94% yield. The reaction proceeded with best yields when the vinyl acetate 68 was more electron deficient, but both donor- and acceptor-substituted 1-arylvinyl acetates underwent the addition reaction. These reactivity patterns and the observation of dibenzyls as side products support a radical mechanism, which starts with a Fenton process as described in Fig. 14. Hydrogen abstraction from 67 forms a benzylic radical, which stabilizes by addition to 68. SET oxidation of the resulting electron-rich a-acyloxy radical by the oxidized iron species leads to reduced iron catalyst and a carbocation, which stabilizes to 69 by acyl transfer to ferf-butanol. However, a second SET oxidation of the benzylic radical to a benzylic cation prior to addition followed by a polar addition to 68 cannot be excluded completely for the most electron-rich substrates. 

With these cyclic peptides it was apparent that no difference of pKa vali s exists between cis and tram isomers and no specific interactions exist between the histidyl and the tyrosyl residues. It was again shown in the hydrolysis of PNPA by these cyclic peptides that the two functional groups do not cooperate for the formation of nitrophenolate ion. On the other hand, for the intramolecular acyl transfer from the acylated imidazole to the phenol group of tyrosine a histidyl side chain in proximity to a tyrosyl side chain facilitated the reaction. This is evident from the fact that the reaction rate was 1,2-cis > 1,2-tram, 1,4-cis > 1,4-trans, and 1,2-cis > 1,4-cis. Thus, a cooperative imidazole function is necessary for the acylation of the tyrosyl phenolic oxygen. Two possibilities illustrated in Fig. 35 a and b are considered... 

The synthesis of histidine-containing peptides without protection of the imidazole side chains is feasible, but it can be inconvenient and unsatisfactory because of the basic, nucleophilic and hydrophihc character of such side chains. /w-Nitrogens can react with electrophilic reagents such as Ar,AT -dicyclohexylcarbodiimide,W catalyze undesirable acyl-transfer reactions,Pl and cause loss of chiral integrity at the histidine a-carbon.t l Side-chain protection has therefore generally been employed. 

Regioselective C-2 amination of 2,3-epoxy alcohols can be realized by intramolecular oxirane ring opening of the carbamates prepared by the reaction of the epoxy alcohols with isocyanates." -" In some cases, however, acyl transfer is a serious side reaction (Scheme 59)." ... 

T. Nukada, A. Berces, and D. M. Whitfield, Acyl transfer as a problematic side reaction in polymer-supported oligosaccharide synthesis,./. Org. Chem., 64 (1999) 9030-9045. 

Polymerization of pPL with a variety of initiators is a terminationless process. Lyudvig a.o. have mostly contributed to our present knowledge of the influence of reaction variables on the rates of polymerization 24 27). They obtained quantitative yields in the polymerization of lactones using bulky complex counterions, like SbClf1. Thus, the decomposition of these anions, leading to transfer and termination in the polymerization of cyclic ethers and acetals, does not lead to side reactions in the polymerization of lactones. This can be ascribed to reversible reactions between acyl halides plus Lewis acids and the acylium cation 28) ... 

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