Substituents rational selection

The stereochemistry of the reactions catalyzed by 269c may be rationalized by invoking the model advanced by Evans in relation to the Diels-Alder studies, Fig. 26. However, an adequate stereochemical model that rationalizes selectivities observed with catalyst 269d/271d and accounts for the turnover in selectivities between the two systems remains elusive. The effect of the vinyl ether substituent on... 

Wootton, R., Cranfield, R., Sheppey, G.C. and Goodford, P.J. (1975). Physicochemical-Activity Relationships in Practice. 2. Rational Selection of Benzenoid Substituents. LMetLChem., 18, 607-613. 

Physicochemical-Aaivity Relationships in Practice. 2. Rational Selection of Benzenoid Substituents. 

A mechanism has been proposed to rationalize the results shown in Figure 23. The relative proportion of the A -pyrazolines obtained by the reduction of pyrazolium salts depends on steric and electronic effects. When all the substituents are alkyl groups, the hydride ion attacks the less hindered carbon atom for example when = Bu only C-5 is attacked. The smaller deuterohydride ion is less sensitive to steric effects and consequently the reaction is less selective (73BSF288). Phenyl substituents, both on the nitrogen atom and on the carbon atoms, direct the hydride attack selectively to one carbon atom and the isolated A -pyrazoline has the C—C double bond conjugated with the phenyl (328 R or R = Ph). Open-chain compounds are always formed during the reduction of pyrazolium salts, becoming predominant in the reduction of amino substituted pyrazoliums. 

The reaction is less selective than the related benzoylation reaction (/pMe = 30.2, cf. 626), thereby indicating a greater charge on the electrophile this is in complete agreement with the greater ease of nuclophilic substitution of sulphonic acids and derivatives compared to carboxylic acids and derivatives and may be rationalized from a consideration of resonance structures. The effect of substituents on the reactivity of the sulphonyl chloride follows from the effect of stabilizing the aryl-sulphonium ion formed in the ionisation step (81) or from the effect on the preequilibrium step (79). 

The high enantioselectivity again can be rationalized by enantioface-selective alkene coordination in 63 (Fig. 35). The olefin moiety is expected to bind trans to the upper imidazoline moiety [70,73] thereby releasing the catalyst strain. Coordination at this position may, in principal, afford four different isomers assuming the stereoelectronically preferred perpendicular orientation of the alkene and the Pt(II) square plane. In the coordination mode shown, steric repulsion between both olefin substituents and the ferrocene moiety is minimized. Outer-sphere attack of the indole core results in the formation of the product s stereocenter. 

It was rationalized that one could gain control of the disassembly rate by changing the substituent R on the aromatic ring. Electron-withdrawing substituents should accelerate the cyclization step since phenol 7 will become a better leaving group in the acyl substitution of 6 to 7. Four dendrons were selected for this study (Fig. 5.5) two (9 and 11) with a methyl substituent and two others... 

As observed in runs 3-5 (Table 6) the reaction shows poor diastereofa-cial selectivity. For example, the reaction with 4-substituted cyclohexanone provides a mixture of an equatorial approach product 52eq and an axial approach product 52ax in a ration of ca. 6 1, irrespective of the steric size of the substituents... 

The Z selectivity increases with the electron-withdrawing properties of the p-substituent of the aryldiazomethane. In the light of the assumed mechanistic scheme, this fact may be rationalized by a more selective formation of 385a, as the diazo carbon becomes less nucleophilic 357 K... 

In the hydrogenation of 1, catalysts 31 a—j gave 87-97% ee, whereas catalyst 31 k, with the very bulky trityl substituent on the alkyl backbone, only gave 38% ee. The silyl substituent was found to have a significant effect on selectivity catalyst 311 gave 88% ee, while catalyst 31 n gave only 4% ee with substrate 1 [35]. This remarkable effect was rationalized based on X-ray structural data. 

Pyridine formation, by the reaction of a metallacyclopentadiene with a nitrile, has been extensively investigated in the case of cobalt [If]. When pyridine derivatives are prepared from two different alkynes and a nitrile, specific substituents are needed for the selective coupling reactions. In most cases, a mixture of two isomers (91 and 92) is obtained, the formation of which can be rationalized as shown in Eq. 2.61 [If,27a,44]. 

The reasons for the ewrfo-selectivity of Diels-Alder reactions are only useful for the reactions of dienophiles bearing substituents with lone pairs without a Lewis basic site no secondary orbital interactions are possible. But even in reactions of pure hydrocarbons the ewrfo-selectivity is observed, requiring alternative explanations. For example, the ewrfo-preference of the reactions of cyclopropene with substituted butadienes have been rationalized on the basis of a special type of secondary orbital interactions70. Apart from secondary orbital interactions which are probably the most important reason for the selec-tivities of Diels-Alder reactions, recent literature also advocates other interpretations. 

Diastereoface selection has been investigated in the addition of enolates to a-alkoxy aldehydes (93). In the absence of chelation phenomena, transition states A and B (Scheme 19), with the OR substituent aligned perpendicular to the carbonyl a plane (Rl = OR), are considered (Oc-or c-r transition state R2 Nu steric parameters dictate that predoniinant diastereoface selection from A will occur. In the presence of strongly chelating metals, the cyclic transition states C and D can be invoked (85), and the same R2 Nu control element predicts the opposite diastereoface selection via transition state D (98). The aldol diastereoface selection that has been observed for aldehydes 111 and 112 with lithium enolates 99, 100, and 101 (eqs. [81-84]) (93) can generally be rationalized by a consideration of the Felkin transition states A and B (88) illustrated in Scheme 19, where A is preferred on steric grounds. 

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