Deprotonation of A-Hydrogen

Enantioselective additions of organolithiums to prochiral ketones yield tertiary chiral alcohols, which are a synthetically highly attractive class of substances [85]. The formation of enolates via deprotonation (of a-hydrogens in the sub-... 

Fig. 10. Pharmacophores for angiotension-converting enzyme. Distances in nm. (a) The stmcture of a semirigid inhibitor and distances between essential atoms from which one pharmacophore was derived (79). (b) In another pharmacophore, atom 1 is a potential zinc ligand (sulfhydryl or carboxylate oxygen), atom 2 is a neutral hydrogen bond acceptor, atom 3 is an anion (deprotonated sulfur or charged oxygen), atom 4 indicates the direction of a hydrogen bond to atom two, and atom 5 is the central atom of a carboxylate, sulfate, or phosphate of which atom 3 is an oxygen, or atom 5 is an unsaturated carbon when atom 3 is a deprotonated sulfur. The angle 1- -2- -3- -4 is —135 to —180° or 135 to 180°, and 1- -2- -3- -5 is —90 to 90°.

The hydrogenation of simple alkenes using cationic rhodium precatalysts has been studied by Osborn and Schrock [46-48]. Although kinetic analyses were not performed, their collective studies suggest that both monohydride- and dihydride-based catalytic cycles operate, and may be partitioned by virtue of an acid-base reaction involving deprotonation of a cationic rhodium(III) dihydride to furnish a neutral rhodium(I) monohydride (Eq. 1). This aspect of the mechanism finds precedent in the stoichiometric deprotonation of cationic rhodium(III) dihydrides to furnish neutral rhodium(I) monohydrides (Eq. 2). The net transformation (H2 + M - X - M - H + HX) is equivalent to a formal heterolytic activation of elemental... 

Detailed aspects of the catalytic mechanism remain unclear. However, influence of basic additives on the partitioning of the conventional hydrogenation and reductive cyclization manifolds coupled with the requirement of cationic rhodium pre-catalysts suggests deprotonation of a cationic rhodium(m) dihydride intermediate. Cationic rhodium hydrides are more acidic than their neutral counterparts and, in the context of hydrogenation, their deprotonation is believed to give rise to monohydride-based catalytic cycles.98,98a,98b Predicated on this... 

Scheme 22.2 Formal heterolytic hydrogen activation via deprotonation of a dihydride intermediate.

In order to eliminate the requirement of using at least 2 equivalents of RM (M = Li, MgBr) in their amination with the reagents 3i-o, e.g. 1 equivalent for the deprotonation of amino hydrogen and 1 equivalent for the amination reaction, A-metallated derivatives of 3i-o have been used. The lithium derivative of 31, e.g. A-lithio Af-(f-butoxycar-bonyl) 0-p-tosylhydroxylamine (A-lithio f-butyl A-tosyloxycarbamate), is also known as LiBTOC. 

Nucleophilic attack of the enolate anion to the carhonyl carhon of another ethyl acetate gives an alkoxide tetrahedral intermediate. The resulting alkoxide reforms the carhonyl group hy ejecting the ethoxide anion. This ethoxide anion deprotonates the a-hydrogen, and produces a new enolate anion of the resulting condensed product, which is protonated in the next step upon acidification during work-up and yields the ethyl acetoacetate. 

Mechanism 2 requires deprotonation of a ligand, and dissociation of the hydrogen bound to the C(3) atom was suggested to be the slow step for the reaction of tris(2,2 -bipyridine)ruthenium(III) in base (12). This would require a mechanism for the 1,10-phenanthroline complexes different from that of the 2,2 -bipyridine complexes, but, from the data in Table II as illustrated in Figs. 3-5, this seems unlikely. The requirement of a different mechanism is based upon the significant differences in rates of D/H exchange as measured by 1H NMR for the tris(diimine)... 

When the binding energy of a hydrogen to a heteroatom is weak, heteroatom-centered radicals are readily produced by H-abstraction or one-electron oxidation followed by H+ loss. Typical examples are phenols (e.g vitamin E in non-aqueous media), tryptophan and related compounds and thiols. Deprotonation of radical cations is indeed often a source of heteroatom-centered radicals even if a deprotonation at carbon or OH addition upon reaction with water would be thermodynamically favored. The reason for this is the ready deprotonation at a heteroatom (Chap. 6.2). 

The main direction of decomposition of the cation radical formed at the first stage is a deprotonation leading to a neutral free-radical particle which later oxidizes into a heteroaromatized cation (Scheme 3.90, pathway a). The opposite pathway is rarely observed, i.e., oxidation of the cation radical into a dication foregoing the deprotonation stages (Scheme 3.90, pathway b) [250]. When single-electron transfer occurs along with a cation-radical particle, aromatiza-tion is also observed (Scheme 3.90, pathway c) [292] at the expense of the elimination of a hydrogen atom in the solvent cell , i.e., where repeated collisions of two particles take place. A fourth variation is possible and involves the decomposition of the cation radical and the formation of molecular... 

Nuclear and side chain substitution in aromatics or substitution of a -hydrogen in alkylamines is — in most cases — best rationalized by postulating radical cations as intermediates. For anodic nuclear substitution of aromatics, especially for acyloxylation, cyanation or bromination a ECnECb3 -mechanism is assumed 37,4 9,50,226,227). jc-oxidation of the aromatic to the radical cation 28, which reacts with a nucleophile Nu, e.g., acetate, cyanide, alkoxide, followed by a second electron transfer and deprotonation (Eq. (98) ) ... 

Treatment of hydrogermanium cyclopentadiene transition metal complexes with LDA can lead initially to a competition between the deprotonation of the hydrogen linked to germanium or to the cyclopentadienyl ring, but a migration of the germyl group to cyclopentadiene was actually observed (equation 192)9. 

The applications of PM-IRRAS also include fatty acids, phospholipids, and protein conformations. Desbat and co-workers reported on the variation of the dissociation of a Langmuir monolayer of arachidic acid at the air-water interface as a function of the subphase pH and for several cations (Cd2+, Ca2 +, Mg2 +, and Na+) with the help of the PM-IRRAS method [92]. Fig. 14 shows the PM-IRRAS spectra of Langmuir monolayer of deuterated arachidic acid in the presence of CdCb as a function of the subphase pH. At low subphase pH (pH = 3.5), the spectrum only presents absorption bands related to the acid form, i.e., the C = O stretching vibration (v(C = O)) and the OH bending (<5(0-H)) located at 1720 and 1270 cm respectively. The frequency position of the v(C = O) is characteristic of a hydrogen-bonded carbonyl group. As the subphase pH is increased, the arachidic acid is progressively deprotonated to... 

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