Combining steric and electronic effects

We have already seen that a -methyl group slightly increases the stability of acetylcholine analogues through steric effects and also has the advantage of introducing some selectivity. 

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A kinetically stabilized diarylgermylene, Tb(Tip)Ge, is also stable in hexane solution with no tendency to dimerize. The structure has not yet been measured but it was characterized as the base-free mononuclear transition metal complex formed with the reactive M(CO)s. THF adduct (M = Mo,W). The crystal structure of the W complex466 shows Ge=W = 259.3 pm, Ge-Tb = 198.8 pm, Ge-Tip = 199.9 pm, CGeC = 108.4°, TbGeW = 138.9° and TipGeW = 112.2°. Thus the Ge is pyramidal and the structure is obviously the result of a balance of steric repulsions between the carbonyls, Tb, and Tip. Older work on similar Ge=W compounds, RR,Ge=W(CO)5 with RR = Cp (Cl) or (Bsi)2467, show Ge=W lengths of 251.1 and 263.2 pm, respectively, indicating the combined steric and electronic effects. 

Fig. 12.46 Structures of four palladium complexes illustrating combined steric and electronic effects on bonding of the thiocyanate ligand. [From Palenik, G. J. Steffen, W. L. Mathew, M. Li, M. Meek, D. W. Inorg. Nucl. Chem. Leu. 1974. 10, 125-128. Reproduced with permission.]...

Cycloaddition reactions of (E)-l-acetoxybutadiene (18a) and (E)-l-methoxy-butadiene (18b) with the acrylic and crotonic dienophiles 19 were studied under high pressure conditions [9] (Table 5.1). Whereas the reactions of 18a with acrylic dienophiles regioselectively and stereoselectively afforded only ortho-enJo-adducts 20 in fair to good yields, those with crotonic dienophiles did not work. Similar results were obtained in the reactions with diene 18b. The loss of reactivity of the crotonic dienophiles has been ascribed to the combination of steric and electronic effects due to the methyl group at the )S-carbon of the olefinic double bond. 

Hydroboration is highly regioselective and stereospecific. The boron becomes bonded primarily to the less-substituted carbon atom of the alkene. A combination of steric and electronic effects works to favor this orientation. Borane is an electrophilic reagent. The reaction with substituted styrenes exhibits a weakly negative p value (-0.5).156 Compared with bromination (p+ = -4.3),157 this is a small substituent effect, but it does favor addition of the electrophilic boron at the less-substituted end of the double bond. In contrast to the case of addition of protic acids to alkenes, it is the boron, not the hydrogen, that is the more electrophilic atom. This electronic effect is reinforced by steric factors. Hydroboration is usually done under conditions in which the borane eventually reacts with three alkene molecules to give a trialkylborane. The... 

This reaction is first-order with respect to each rate constant, the values of which reflect a combination of steric and electronic effects. The values are summarized in Table III. The values can be interpreted in terms of Giering s QALE procedure (59). 

Two separate computational investigations of the Rh/dppms catalyst and related systems have appeared in the literature. One study [40] concluded that steric effects were important in promoting migratory CO insertion in [Rh(CO)(dppms)l2Me], while the other [41] proposed that an electronic effect, arising from the sulfur donor atom of dppms, was responsible. It is likely that a combination of steric and electronic effects result in the observed reactivity. 

Hydroboration is highly regioselective and is stereospecilic. The boron becomes bonded primarily to the less substituted carbon atom of the alkene. A combination of steric and electronic effects work together to favor this orientation. Borane is an electrophilic reagent. The reaction with substituted styrenes exhibits a weakly negative p value... 

Benzotriazine (8, R = H), for example, can be isolated as a reasonably stable, colorless crystalline solid, but it reacts rapidly in solution with water to give o-aminobenzaldehyde, presumably by initial covalent hydration to give 98, which decomposes to o-aminobenzaldehyde via the triazene 99. Reaction of 8, R = H, with other nucleophiles also occurs readily, while 4-substituted 1,2,3-benzo-triazines react similarly but more slowly, as expected, owing to a combination of steric and electronic effects. 

Structure analysis has shifted completely from intramolecular to intermolecular structure. Distributions of intermolecular distances can be statistically analyzed over hundreds of thousands of reliable data these distributions should be properly normalized to be statistically significant. The chemical interpretation must, however, take into account the unavoidable fact that intermolecular separations are a combination of steric and electronic effects, and that near to does not always mean bound to . 

Because the electronic nature of substituents has little effect on the rate of acid-catalyzed hydrolysis of meta- or para-substituted benzoates (e.g., p for the acid hydrolysis of XC6H4COOR esters is close to zero), Taft suggested that the electronic nature of substituents will also have little effect on acid-catalyzed hydrolysis of aliphatic esters (Lowry and Richardson, 1987). Nevertheless, a strong electronic effect occurs in basic hydrolysis, as can be examined from the large p values for base-catalyzed hydrolysis of meta- or para-substituented benzoates. Hence, the effect of X on acid hydrolysis is purely steric but is a combination of steric and electronic effects in basic hydrolysis. Taft defined Es, a steric substituent constant, by Equation (5.11) ... 

The lithium benzamidinates 8 can be obtained analytically pure by recrystallization from hexane. Unsolvated 8 (R = CF3) is especially remarkable in that it sublimes readily at room temperature and dissolves freely in nonpolar solvents such as toluene or even hexane. Although the molecular structures of 8 (R = CF3) has not been determined by X-ray diffraction, it is highly likely that the 2,4,6-tris(trifluoromethyl)phenyl substituent is responsible for the remarkable properties of this particular lithium benzamidinate. It has been demonstrated that the stabilizing influence of the 2,4,6-tris(trifluoromethyl)phenyl substituent can be traced back to a combination of steric and electronic effects [42]. In addition, this ligand allows the characterization of its derivatives by 19F NMR spectroscopy. 

The steric and electronic effects which seem independent can be interrelated as follows. As X and Y leave the alkane, the n orbital begins to form X and Y move away from the carbon atoms in directions indicated X - X, Y -> Y in 104 and 105. Except for a few XY pairs, e.g. the lower hydrides, most XY distances exceed the carbon-carbon double bond distance, even when the atoms are bonded. Moreover, since X and Y are generally not bonded to one another, the syn transition state will have a large nonbonded interaction. If 105 were an alkene or cyclohexane, the repulsions would be even larger in the planar form. We would also guess that in 105, the necessary reduction in the size of the solvation sheaths of X and Y in solution would be energetically costly (Amis, 1966). Therefore, the incursion of nonbonded effects both in the ground state and in the transition state of process (198) combines... 

Methyl, ethyl, isopropyl, and r-butyl magnesium bromides were compared in enolization reactions [Eq. (11)]. The relative rates were Et>/-Pr> Me>f-Bu, which reflects a combination of steric and electronic effects. The bulkier Grignard reagents react slower, whereas the more substituted Grignard reagents are stronger bases. With more-hindered ketones, steric effects predominate over electronic. The structures of magnesium enoiates were confirmed by reaction with benzoyl chloride to form enol-benzoates [14,15]. 

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