Acceptors, relative reactivities

Mixed condensations of esters are subject to the same general restrictions as outlined for mixed aldol reactions (Section 2.1.2). One reactant must act preferentially as the acceptor and another as the nucleophile for good yields to be obtained. Combinations that work best involve one ester that cannot form an enolate but is relatively reactive as an electrophile. Esters of aromatic acids, formic acid, and oxalic acid are especially useful. Some examples of mixed ester condensations are shown in Section C of Scheme 2.14. Entries 9 and 10 show diethyl oxalate as the acceptor, and aromatic esters function as acceptors in Entries 11 and 12. 

Routes to Relative Reactivity Data Relative reactivity relationships describe the ratio of products between two glycosyl donors for an acceptor. Ley first constructed such relationships for fully protected mannoside and rhamnoside donors to rationalize the results of his one-pot syntheses employing cyclic diketals.16... 

Competition Experiments of Ley Ley examined product distributions to obtain relative reactivity values (RRVs) for both rhamnose and mannose sugars with benzyl, 3,4-cyclic diacetals, and benzoyl groups. Using a limiting amount of acceptor (1 equiv), two donors were added in excess (2 equiv each), followed by the addition of activator (NIS/TfOH, 2 equiv) (Scheme 11.13). After quenching the reaction, the product distribution was analyzed by -NMR. 

In the thiohydroxamate method, activated acceptors are required for successful addition reactions because the thiohydroxamate is relatively reactive towards alkyl radicals. An ingenious method to circumvent this problem has recently been communicated by Zard.160 Photolysis of benzyl xanthate (40) with a UV lamp in the presence of N-methylmaleimide (NMM) provided the adduct (41) in 40% yield, as illustrated in Scheme 50. In this reaction, the competition reaction between the desired addition to the acceptor and the addition to the precursor still exists. However, addition to the precursor is reversible and,... 

For each given acid or Lewis acid (electron acceptor), the capacity of an unsaturated system (electron donor) to form a a-complex is proportional to its basicity (donor force), see series (2). At the same time, the increase in relative reactivity of these compounds with respect to electrophilic attack is observed in the similar sequence [34],... 

Photooxetane formation is quite inefficient, a fact which usually points to the presence of an intermediate which can partially revert to ground state reactants. Cleavage of the diradical must be responsible for some of the inefficiency in oxetane formation 129>. However, in the past few years convincing evidence has appeared that a CT complex precedes the diradical iso.isi). The two most telling pieces of evidence are the relative reactivities of different alkenes 130> and the absence of any measurable secondary deuterium isotope effect on quenching rate constants 131>. Relative quenching rates of sterically un crowded olefins are proportional both to the ionization potentials of the donor olefins 130> and to the reduction potentials of the acceptor ketones 131>, as would be expected for a CT process. Inasmuch as n,n triplets resemble electron-deficient alkoxy radicals, such substituent effects would also be expected on direct radical addition of triplet ketone to olefin. However, radical addition would yield an inverse isotope effect (in, say, 2-butene-2,3-d2) and would be faster to 1,1-dialkylethylenes than to 1,2-dialkylethylenes, in contrast to the actual observations. 

Develop ways to determine the relative reactivity of glycosyl donors by calculation only and similarly to rank the reactivity of the hydroxyl groups of glycosyl acceptors. The ultimate goal would be to find unreactive or misreactive species without performing experiments. 

A disadvantage of this procedure is that it requires long reaction times, and also needs relatively reactive glycosyl acceptors. In such situations, the use of silver triflate as promoter and a glycosyl donor having a benzyl group in the 2-position of the glycosyl donor has been proved to be useful.12,28... 

Much of the relative reactivity data on 1,3-DPCA reactions has been tabulated and discussed in reviews by R. Huisgen, a pioneer researcher in the field.Some representative data are presented in Table 10.3. The dipolarophiles are shown in decreasing order of electrophilicity. The data from these monosubstituted dipolarophiles should be relatively free of steric influences on reactivity. Note that for phenyl azide and benzonitrile oxide, reactivity is at a minimum for unfunctionalized alkenes and is increased by both donor and acceptor substituents. 

Table VI. Relative Reactivities of Acceptors by Acceptor Disappearance"...

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