Substitutions general concepts

Initially, chiral stationary phases for chiral liquid chromatography were designed for preparative purposes, mostly based on the concept of three-point recognition .47 Pirkle and other scientists48 developed a series of chiral stationary phases that usually contain an aryl-substituted chiral compound connected to silica gel through a spacer. Figure 1-14 depicts the general concept and an actual example of such a chiral stationary phase. 

In this chapter, the porphyrazines are named in one of two ways. For simple substitution patterns, substituents will be denoted directly for example, Cu(II) oc-taethylporphyrazine can be written Cu[pz(Et)g], When the pattern is more complex, or general concepts are discussed, the porphyrazines are systematically named based on the nature of their substituents, using the general formula, M[pz (AmB4 ), where M represents the metal ion and its axial ligands (or two hydro-... 

Lewis Acid Sites. Many other mechanisms (66, 85) are best described in terms of the more general concept of aprotic, or Lewis acidity which is defined in terms of the capacity to donate or share pairs of electrons. Aprotic acid sites are commonly derived from the coordinatively unsaturated cations at crystal edges or adsorbed on crystal faces, from deydration of hydroxylated surfaces, and from deamination or deamination and dehydration of silica-aluminum catalysts or similarly treated clays having extensive tetrahedral substitution (130, 132). Formation of Lewis acid sites by deamination or deamination-dehydration is dependent on inversion of the basal oxygens of the aluminum-substituted tetrahedron away from the surface, in order to expose the aluminum (131). 

Hence, the first clearcut evidence for the involvement of enol radical cations in ketone oxidation reactions was provided by Henry [109] and Littler [110,112]. From kinetic results and product studies it was concluded that in the oxidation of cyclohexanone using the outer-sphere one-electron oxidants, tris-substituted 2,2 -bipyridyl or 1,10-phenanthroline complexes of iron(III) and ruthenium(III) or sodium hexachloroiridate(IV) (IrCI), the cyclohexenol radical cation (65" ) is formed, which rapidly deprotonates to the a-carbonyl radical 66. An upper limit for the deuterium isotope effect in the oxidation step (k /kjy < 2) suggests that electron transfer from the enol to the metal complex occurs prior to the loss of the proton [109]. In the reaction with the ruthenium(III) salt, four main products were formed 2-hydroxycyclohexanone (67), cyclohexenone, cyclopen tanecarboxylic acid and 1,2-cyclohexanedione, whereas oxidation with IrCl afforded 2-chlorocyclohexanone in almost quantitative yield. Similarly, enol radical cations can be invoked in the oxidation reactions of aliphatic ketones with the substitution inert dodecatungstocobaltate(III), CoW,20 o complex [169]. Unfortunately, these results have never been linked to the general concept of inversion of stability order of enol/ketone systems (Sect. 2) and thus have never received wide attention. 

Fig. 4. A general concept for solubilizing catalyticaUy relevant ligands for the use m SCCO2, exemplified for a bidentate aryl phosphine ligand. Perfluoroalkyl chains or other solubitoers waved line) are fixed at the periphery of the ligand. The position of the substitution and the use of appropriate spacers bold line) are used to tune the stereo-electronic properties of the ligand...

A detailed study of the nucleophilic aromatic substitution of hydrogen has been initiated at the Urals State Technical University (Russia) in the 1970s. In the first review on this topic, it was suggested to use the symbol Sjj in order to distinguish these reactions from the classical nucleophilic ipso-substitution Ar [8]. Later, a number of special reviews [9-38] and also the book Nucleophilic Aromatic Substitution of Hydrogen [39], which accumulated a considerable body of data on conditions, kinetics, structure of intermediates, electrochemical and mathematic modeling, as well as plausible mechanisms and the general concept of the 5 -reactions, have also been published. 

When used with diphenyliodonium salts in the presence of a metal and an organocatalyst the enantioselective introduction of a phenyl group at the a-position of aldehydes can be accompUshed [42]. This transformation can be extended to a more general concept of enantioselective a-arylation of aldehydes by deployment of different substituted diaryl-iodonium salts. In these reactions CuBr was used as Lewis acid (Scheme 4.12). Based on these findings the authors were able to develop a rapid asymmetric synthesis of the anti-inflammatory drug (S)-ketoprofen. 

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