Hydroxy anions

Stereoinversion Stereoinversion can be achieved either using a chemoenzymatic approach or a purely biocatalytic method. As an example of the former case, deracemization of secondary alcohols via enzymatic hydrolysis of their acetates may be mentioned. Thus, after the first step, kinetic resolution of a racemate, the enantiomeric alcohol resulting from hydrolysis of the fast reacting enantiomer of the substrate is chemically transformed into an activated ester, for example, by mesylation. The mixture of both esters is then subjected to basic hydrolysis. Each hydrolysis proceeds with different stereochemistry - the acetate is hydrolyzed with retention of configuration due to the attack of the hydroxy anion on the carbonyl carbon, and the mesylate - with inversion as a result of the attack of the hydroxy anion on the stereogenic carbon atom. As a result, a single enantiomer of the secondary alcohol is obtained (Scheme 5.12) [8, 50a]. 

Stabilization by a solvent can often determine the very initial step consists of ion-radical generation. Hence, alkali metal hydroxides are highly stabilized in water and in aqueous organic solvents, and therefore, their reactivities in simple one-electron processes are either very low or practically nonexistent. Alkali-metal hydroxides are at least somewhat soluble, particularly in the presence of water traces, in polar solvents (DMSO, HMPA, THF). In these solvents, the HO solvation is drastically diminished (Popovich and Tomkins 1981). As a result, reactions of one-electron transfer from the hydroxy anion to the substrate take place (Ballester and Pascual 1991). 

The conversion of 3-chloropentafluoropropene to 2-(chlorodifluoromethyI)-2,3,3-trifluoro-oxirane (33) can be carried out64 by heating the mixture of the alkene and oxygen in 1,1,2-trichlorotrifluoroethane (CFC-113) in an autoclave.64 The oxidation with hydrogen peroxide in alkaline solution is negatively influenced by the high nucleophilic reactivity of allylic chlorine.65 66 The reaction is performed at very low temperatures that favor the attack of the hydroperoxy anion in competition with the hydroxy anion. Acceptable yields of 31 -38 % are obtained in the presence of a phase-transfer catalyst.66... 

More recently, Houk and coworkers have tried to address the problem of the selectivity of the deprotonation of bridged (camphor-type) or cyclic (cyclohexanone) ketones using quantum mechanical methods22. Using a water-hydroxy anion complex to model the solvated base, they established that the overlap effect is essential to the deprotonation, but cannot account for the selectivity in favor of the axial proton observed experimentally. 

Figure 1. Valence of core cations in their aquo complexes plotted against crystal radii of the cations. The radii are mostly from Shannon and Prewitt (22). (0) Cations (O) hydroxy cations and hydroxy anions (X) oxy cations oxy anions.

Figure 1 Chemical mechanism of DNA polymerase and 3 -5 exonuclease, (a) DNA polymerase reaction. The enzyme chelates two metal Ions using three aspartic acid residues (only two are shown). Metal ion A abstracts the 3 hydroxyl proton of the primer terminus to generate a nucleophile that attacks the a-phosphate of an incoming dNTP substrate. The phosphoryl transfer results In production of a pyrophosphate leaving group, which is stabilized by metal Ion B. (b) The 3 -5 exonuclease proofreading activity is located in a site that is distinct from the polymerase site yet it uses two-metal-ion chemistry similar to DNA synthesis. The reaction type is hydrolysis in which metal ion A activates water to form the hydroxy anion nucleophile. Nucleophile attack on the phosphate of the mismatched nucleotide releases it as dNMP (dGMP in the case shown).

An (allyl)silylcuprate, [(2-methyl-2-butenyl)diphenylsilyl]cuprate, is also a hydroxy anion equivalent. The 2-methyl-2-butenyl group can easily be removed selectively in the presence of other allyl or vinyl groups by protodesilylation under mild conditions (Scheme 31) (13). 

The most important reason why chlorodifluoromethane does not react with alkenes to give 1,1-difluorocyclopropanes under phase-transfer conditions is due to its synchronous, rather than stepwise, cleavage to difluorocarbene. The difluorocarbene thus generated at the interface of the two-phase system (without formation of the intermediate chlorodifluoromethyl anion) reacts quickly with the hydroxy anion and/or water, instead of the alkene. 

The successful preparation of 1,1-difluorocyclopropanes under phase-transfer catalysis conditions would therefore be possible if difluorocarbene were to be generated within the organic phase where the concentration of hydroxy anions and water is negligible. 

Elimination of a hydroxy anion to form a cyclopropyliminium ion is a typical reaction when 1-aminocyclopropanols are treated with acid. In the presence of carbon nucleophiles, trapping of the cyclopropiminium ion occurs (Table 14, entries 1-4). The overall transformation is substitution of the hydroxy group, hence providing a useful entry to a variety of 1-substituted aminocyclopropanes. Alkoxy- and (siloxy)aminocyclopropanes can also be used as substrates for this type of transformation (Table 14, entries 5 and 6). ... 

Aryl iodides can also be carboxylated with NaOH and CO at atmospheric pressure in the presence of 2 under biphasic conditions, and give aryl carboxylic acids in high isolated yields [16] (Eq. (6) and Table 5). The normal PTCs are not very effective in accelerating the carboxylation [23]. This may be ascribable to the poor ex-tractability of hydroxy anion [24]. 

No difference was found between the values for the La " and for the Ce " reactions, indicating that the polymerization process is primarily a property of the hydroxy anion but relatively independent of the identity of the cation. This cationic independence is unlikely to be valid over a wider range of the lanthanide series. Although there have been some attempts to account for the polymeric species formed, at present it would seem more important to seek firmer evidence for the species which are formed than to propose explanations for those which have been reported but whose existence is open to question. 

Fig. 58. Two possible orientations of the C-4 Schiff base with respect to various substituents in the pyridine ring. Note that only in strcture 1 is the protonated Schiff base able to hydrogen bond with the 3-hydroxy anion.

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