Axial reactivity

The incorporation of pendant Pcs to a polymeric backbone via the grafting of a suitable Pc molecule to a preformed polymer containing appropriate functional groups has been accomplished by Chen and co-workers [163], These authors exploited the axial reactivity of some metalloPcs (namely, In(III)Pcs) to prepare an In(III)Pc-polystyrene copolymer. The most remarkable feature of this material is that cofacial association between the macrocycles is fully prevented. For some applications of the Pcs, such as optical limiting or photodynamic therapy (PDT), aggregation should be avoided because it produces the quenching of the excited-states. 

Li Z, Lieberman M (2001) Axial reactivity of soluble silicon(IV) phthalocyanines. Inorg Chem 40(5) 932-939... 

Later, Furusaki et al. (F17) studied the hydrogenation of ethylene by fluidized Ni catalyst to obtain the axial reactivity distribution. Here the samples of bed gas were removed by a traveling sampler placed at the center of the bed during steady reaction, so that the sample taken in the dense phase shows an average of the concentration in the bubble and emulsion phase. Figure 74 shows an example of the axial concentration profile. 

Apparently the reaction seems to have almost ended near the distributor this is because the sample has been mostly taken from the emulsion phase. The calculated concentration profile, assuming (eb)sampie = 0.2, is close to the observed profile. However, the axial reactivity distribution inside the bed is not always clear, although this kind of experiment does give useful information. A similar experimental approach has been utilized by other investigators (C7a, F12). 

Keywords Acceptorless alcohol dehydrogenatiOTi AUylic C-H activation Axial reactivity Carbenoid C-H insertion C-H activation Cycloprpanation Diruthenium compounds Metal nitride Metal-ligand cooperation Metal-metal bond... 

The third chapter, entitled Reactivity and Catalysis at Sites Trans to the [Ru-Ru] Bond is from Jitendra K. Bera and two co-workers. After analyzing the effects of the various axial donors on the paddlewheel [Ru2(CO)4] core of electronic configuration, the authors exploit the axial reactivity for stoichiometric C-H bond activation and C-C bond formation. 

The physical, chemical cind biological properties of a molecule often depend critically upo the three-dimensional structures, or conformations, that it can adopt. Conformational analysi is the study of the conformations of a molecule and their influence on its properties. Th development of modem conformational analysis is often attributed to D H R Bcirton, wh showed in 1950 that the reactivity of substituted cyclohexanes wcis influenced by th equatoricil or axial nature of the substituents [Beirton 1950]. An equcilly important reaso for the development of conformatiorml analysis at that time Wcis the introduction c analytic il techniques such as infreired spectroscopy, NMR and X-ray crystaillograph] which actucilly enabled the conformation to be determined. 

An interesting aspect of this reaction is the contrasting stereoselective behaviour of the dimethyisulfonium and dimethyloxosuifonium methylides in reactions with cyclic ketones (E.J. Corey, 1963 B, 1965 A C.E. Cook, 1968). The small, reactive dimethyisulfonium ylide prefers axial attack, but with the larger, less reactive oxosulfonium ylide only the thermodynamically favored equatorial addition is observed. 

We shall describe a specific synthetic example for each protective group given above. Regiosdective proteaion is generally only possible if there are hydroxyl groups of different sterical hindrance (prim < sec < tert equatorial < axial). Acetylation has usually been effected with acetic anhydride. The acetylation of less reactive hydroxyl groups is catalyzed by DMAP (see p.l44f.). Acetates are stable toward oxidation with chromium trioxide in pyridine and have been used, for example, for protection of steroids (H.J.E. Loewenthal, 1959), carbohydrates (M.L. Wolfrom, 1963 J.M. Williams, 1967), and nucleosides (A.M. Micbelson, 1963). The most common deacetylation procedures are ammonolysis with NH in CH OH and methanolysis with KjCO, or sodium methoxide. 

Me3SiNEt2- Trimethylsilyldiethylamine selectively silylates equatorial hydroxyl groups in quantitative yield (4-10 h, 25°). The report indicated no reaction at axial hydroxyl groups. In the prostaglandin series the order of reactivity of trimethylsilyldiethylamine is Cii > Ci5 C9 (no reaction). These trimethylsilyl ethers are readily hydrolyzed in aqueous methanol containing a trace of acetic acid. The reagent is also useful for the silylation of amino-acids. ... 

The incorporation of heteroatoms can result in stereoelectronic effects that have a pronounced effect on conformation and, ultimately, on reactivity. It is known from numerous examples in carbohydrate chemistry that pyranose sugars substituted with an electron-withdrawing group such as halogen or alkoxy at C-1 are often more stable when the substituent has an axial, rather than an equatorial, orientation. This tendency is not limited to carbohydrates but carries over to simpler ring systems such as 2-substituted tetrahydropyrans. The phenomenon is known as the anomeric ect, because it involves a substituent at the anomeric position in carbohydrate pyranose rings. Scheme 3.1 lists... 

Scheme 3.2 gives some data that illustrate the differences in reactivity between groups in axial and equatorial positions. It should be noted that a group can be either more or less reactive in an axial position as compared to the corresponding equatorial position. 

Extensive research has established that axial cyclohexanols are more reactive than equatorial alcohols toward chromic acid oxidation. The basis for this effect can be seen... 

Isomers with equatorial 2-alkoxy groups are more reactive than those with axial 2-alkoxy groiqis. The greater reactivity of the equatorial isomers is the result of the alignment of... 

There is another aspect to the question of the reactivity of the carbonyl group in r ck)hexanone. This has to do with the preference for approach of reactants from the axial ir equatorial direction. The chair conformation of cyclohexanone places the carbonyl coup in an unsynunetrical environment. It is observed that small nucleophiles prefer to roach the carbonyl group of cyclohexanone from the axial direction even though this is 1 more sterically restricted approach than from the equatorial side." How do the ctfcnaices in the C—C bonds (on the axial side) as opposed to the C—H bonds (on the equatorial side) influence the reactivity of cyclohexanone ... 

The reactivity of various steroid alcohols decreases in the order primary > secondary (equatorial) > secondary (axial) > tertiary. The only systematic investigation relating to the selective protection of steroidal hydroxyl functions has been carried out with the cathylate (ethyl carbonate) group. Since only equatorial hydroxyl groups form cathylates this ester has been used as a diagnostic tool to elucidate the configuration of secondary alcohols. 

Strong 1 3 interactions between the axial substituent at C-6 with 8j5- and 2ji (5a-series) hydrogens and 10 -substituents decrease the reactivity of the 6-ketone as compared to saturated 3-ketones. The 6-ketone does not react with methanol to give a dimethyl ketal, even in the absence of the C-19 methyl group. Thus the 19-nor-5a-3,6-dione (75) gives selectively the 3,3-dimethyl-ketal (76). ... 

Tetrahydropyranyl ethers have been prepared from the quasi-axial 7a-hydroxyl in a 3)5-acetoxy-A -7a-ol, but in this case enhanced reactivity is due to the adjacent double bond. °... 

The tetrasubstituted isomer of the morpholine enamine of 2-methyl-cyclohexanone (20) because cf the diminished electronic overlap should be expected to exhibit lower degree of enamine-type reactivity toward electrophilic agents than the trisubstituted isomer. This was demonstrated to be the case when the treatment of the enamine with dilute acetic acid at room temperature resulted in the completely selective hydrolysis of the trisubstituted isomer within 5 min. The tetrasubstituted isomer was rather slow to react and was 96% hydrolyzed after 22 hr (77). The slowness might also be due to the intermediacy of quaternary iminium ion 23, which suffers from a severe. 4< strain 7,7a) between the equatorial C-2 methyl group and the methylene group adjacent to the nitrogen atom, 23 being formed by the stereoelectronically controlled axial protonation of 20. 

Stereoselective epoxidation can be realized through either substrate-controlled (e.g. 35 —> 36) or reagent-controlled approaches. A classic example is the epoxidation of 4-t-butylcyclohexanone. When sulfonium ylide 2 was utilized, the more reactive ylide irreversibly attacked the carbonyl from the axial direction to offer predominantly epoxide 37. When the less reactive sulfoxonium ylide 1 was used, the nucleophilic addition to the carbonyl was reversible, giving rise to the thermodynamically more stable, equatorially coupled betaine, which subsequently eliminated to deliver epoxide 38. Thus, stereoselective epoxidation was achieved from different mechanistic pathways taken by different sulfur ylides. In another case, reaction of aldehyde 38 with sulfonium ylide 2 only gave moderate stereoselectivity (41 40 = 1.5/1), whereas employment of sulfoxonium ylide 1 led to a ratio of 41 40 = 13/1. The best stereoselectivity was accomplished using aminosulfoxonium ylide 25, leading to a ratio of 41 40 = 30/1. For ketone 42, a complete reversal of stereochemistry was observed when it was treated with sulfoxonium ylide 1 and sulfonium ylide 2, respectively. ... 

A chiral titanium complex with 3-cinnamoyl-l,3-oxazolidin-2-one was isolated by Jagensen et al. from a mixture of TiCl 2(0-i-Pr)2 with (2R,31 )-2,3-0-isopropyli-dene-l,l,4,4-tetraphenyl-l,2,3,4-butanetetrol, which is an isopropylidene acetal analog of Narasaka s TADDOL [48]. The structure of this complex was determined by X-ray structure analysis. It has the isopropylidene diol and the cinnamoyloxazolidi-none in the equatorial plane, with the two chloride ligands in apical (trans) position as depicted in the structure A, It seems from this structure that a pseudo-axial phenyl group of the chiral ligand seems to block one face of the coordinated cinnamoyloxazolidinone. On the other hand, after an NMR study of the complex in solution, Di Mare et al, and Seebach et al, reported that the above trans di-chloro complex A is a major component in the solution but went on to propose another minor complex B, with the two chlorides cis to each other, as the most reactive intermediate in this chiral titanium-catalyzed reaction [41b, 49], It has not yet been clearly confirmed whether or not the trans and/or the cis complex are real reactive intermediates (Scheme 1.60). 

Alcohols undergo an oxidation reaction to yield carbonyl compounds on treatment with CrO. Forexample, 2-ftvt-butylcyclohexanol gives 2-terT-butylcyclo-hexanone. If axial -OH groups are generally more reactive than their equatorial isomers, which do you think would react faster, the cis isomer of 2-ferf-butylcyclohexanol or the trans isomer Explain. 

The difference in reactivity between the isomeric menthyl chlorides is due to the difference in their conformations. Neomenthyl chloride has the conformation shown in Figure 11.20a, with the methyl ancl isopropyl groups equatorial and the chlorine axial—a perfect geometry for L2 elimination. Loss of the hydrogen atom at C4 occurs easily to yield the more substituted alkene product, 3-menthene, as predicted by Zaitsev s rule. 

The stereochemistry of this reaction is consistent with transition state 2 in which the ethoxycar-bonyl unit adopts an equatorial position. The same result could occur, however, via boat-like transition state 3 with an axial ethoxycarbonyl group47. The reactions of 2-oxopropanoate esters and 9-(2-butenyl)-9-borabicyclo[3.3.1]nonane occur at — 78°C, reflecting the greater reactivity, but stereoselectivity is generally poor except in cases where a very hindered ester is employed3811. 

The stereoselectivity of these reactions has been interpreted in terms of chair-like six-membered ring transition states in which the substituents a to tin adopt an axial position, possibly because of steric and anomeric effects. The cc-substituted (Z)-isomers are less reactive because the axial preference of the a-substituent would lead to severe 1,3-diaxial interactions17. 

The most direct evidence that stereoelectronic effects are also important in these reactions follows from the specificity observed in hydrogen atom abstraction from conformationally constrained compounds,18 60 C-H bonds adjacent to oxygen113"118 or nitrogen110 and which subtend a small dihedral angle with a lone pair orbital (<30°) are considerably activated in relation to those where the dihedral angle is or approaches 90°. Thus, the equatorial H in 20 is reported to be 12 times more reactive towards /-butoxy radicals than the axial 11 in 21.115... 

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