Nucleophilic hydroxylations

AC2O, BF3 Et20, THE, 0°. These conditions give good chemoselectivity for the most nucleophilic hydroxyl group. Alcohols are acetylated in the presence of phenols. 

Oxygen nucleophiles (hydroxyl or nitrite) readily replace fluonne mperfluor-inated systems [10, II] (equations 6 and 7). 

Figure 15.2 Reaction mechanism of urease. Ni 1 binds urea and acts as a Lewis acid to polarise the carbonyl group, making its carbon more electrophilic, while Ni 2 facilitates deprotonation of a bound water molecule to generate a nucleophilic hydroxyl species. (From Ragsdale, 1998. Copyright 1998, with permission from Elsevier.)...

The proposed mechanism involves the usual oxidative addition of the aryl halide to the Pd(0) complex affording a Pd(II) intermediate (Ar-Pd-Hal), subsequent coordination of allene 8 and migratory insertion of the allene into the Pd-C bond to form the jt-allylpalladium(II) species 123. A remarkable C-C bond cleavage of 123 leads by decarbopalladation to 1,3-diene 120 and a-hydroxyalkylpalladium species 124. /8-H elimination of 124 affords aldehyde 121 and the H-Pd-Hal species, which delivers Pd(0) again by reaction with base (Scheme 14.29). The originally expected cyclization of intermediate 123 by employment of the internal nucleophilic hydroxyl group to form a pyran derivative 122 was observed in a single case only (Scheme 14.29). 

One of the consequences of forming a cyclic hemi-acetal or hemiketal is that the nucleophilic hydroxyl adds to the carbonyl group and forms a new hydroxyl. This new group is susceptible to many normal chemical reactions of hydroxyls, e.g. esterification, and this type of reaction effectively freezes the carbohydrate into one anomeric form, since the ringopening and equilibration can now no longer take place. Consider esterification of glucose with acetic anhydride (see Section 7.9.1). P-o-Glucose will be... 

A key point should be to identify the rate-limiting step of the polymerization. Several studies indicate that the formation of the activated open monomer is the rate-limiting step. The kinetics of polymerization obey the usual Michaelis-Menten equation. Nevertheless, all experimental data cannot be accounted for by this theory. Other studies suggest that the nature of the rate-limiting step depends upon the structure of the lactone. Indeed, the reaction of nucleophilic hydroxyl-functionalized compounds with activated opened monomers can become the rate-limiting step, especially if stericaUy hindered nucleophilic species are involved. 

Even if the anomeric hydroxyl group is the most reactive, the presence of five nucleophilic hydroxyl groups in these substrates can lead to the formation of various mono- and polyethers. Moreover, these ethers can be pyranose or furanose derivatives with linear and branched octadienyl tethers (Fig. 9). 

The Mitsunobu reaction has been successfully applied to the synthesis of carbohydrate epoxides directly from diols (Scheme 3.15c).84 The more accessible and nucleophilic hydroxyl is converted into an alkoxyphos-phonium ion, which in turn is intramolecularly displaced by a hydroxyl to give an epoxide. Again it is of critical importance that a coplanar SN2 transition state be attained. 

Displacement Reactions. Cyclopentadienyltitanium halides undergo displacements with a wide variety of nucleophiles. Hydroxylic reagents cleave Ti—R bonds... 

Another example of nucleophilic hydroxylation of nitro compounds is the formation of nitrophenols by the action on nitrobenzene with aqueous ferrous sulphate in the presence of hydrogen peroxide in a yield of ca. 3% [46a] (Fenton s reagent) [46b] Weiss et al. [46]) and by the action of ionizing radiations on aqueous solution (Weiss and Stein [46c]) ... 

To control the equilibrium position of the rearrangement, Overman and others introduced a nucleophilic hydroxyl group at the C2 position to capture the rearranged iminium ion2 (Scheme 1.6b). Although the levels of diastereoselecti-vity for the formation of pyrrolidines 6a and 6b are low, the tandem cationic aza-Cope-Mannich cyclization provides a variety of substituted 3-acylpyrrolidines in high yields under mild reaction conditions. The first step in the reaction is the... 

After protonation of the acetic anhydride the electrophilic carbonium ion formed is added to a nucleophilic hydroxyl oxygen atom of the cellulose. This intermediate is then decomposed into cellulose acetate and acetic acid with liberation of a proton. 

Two nucleophiles, hydroxyl ion and cyanide, can bleach the visible absorption at higher concentrations. The product in the cyanide reaction is presumed to be rhodanate. Although cyanide can attack not only persulfide bond but also the iron atom, a possible site reacting with cyanide would be the persulfide bond. 

Reactive betaine intermediates are almost certainly involved in many reactions of imidazoles, e.g. base catalyzed deuterium exchange, acylation at C-2, etc. Begtrup (B-76MI40600, p. 143) has implicated betaines in his studies of the nucleophilic hydroxylation of triazolium salts, and one might expect an extension of these researches into the imidazolium series. 

This Fischer esterification reaction reaches equilibrium after a few hours of refluxing. The position of the equilibrium can be shifted by adding more of the acid or of the alcohol, depending on cost or availability. The mechanism of the reaction involves initial protonation of the carboxyl group, attack by the nucleophilic hydroxyl, a proton transfer, and loss of water followed by loss of the catalyzing proton to give the ester. Because each of these steps is completely reversible, this process is also, in reverse, the mechanism for the hydrolysis of an ester ... 

The methyl ester is stable under these conditions as there is no nucleophilic hydroxyl function. The Cbz deprotection is initialized by protonation of the carbamate s carbonyl oxygen. Br is a good nucleophile it attacks the benzylic methylene carbon, and cleavage of the benzylic C-0 bond follows. The unsubstituted hydrogen carbamate is not stable carbon dioxide is lost, delivering the driving force of this reaction. 

Why, then, does water not attack the neutral aquo n complex, a route that is not consistent with the kinetics The answer could simply be that once the aquo tt complex is formed, the lower-energy route is to lose a proton to give the better nucleophile, hydroxyl, which then attacks the olefin from the coordination sphere. However, the important point is that in the light of recent studies, trans attack still does not appear likely. 

Scheme 5. Examples of nucleophiles often present in glycosylation reactions that can compete with the nucleophilic hydroxyl group (A) 1,6-anhydro formation, (B) thio exchange, (C) leaving-group return, (D) promoter-derived components such as triflate anions, (E) additives such as added bases, (F) solvents.

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