Electronic effects, steric control

The majority of asymmetric dipolar cycloadditions have been investigated in the context of the tandem [4 + 2]/[3 + 2]-nitroalkene cycloaddition. The chiral nitronate is prepared by using either a chiral nitroalkene, vinyl ether, or Lewis acid in the hrst cycloaddition. The acetal center at C(6) of the nitronate provides important steric and electronic effects that control the subsequent dipolar cycloaddition. Subsequently, in the cycloadditions of the chiral nitroalkenes 281 and 284, the dipolarophile approaches from the side distal to that of the substituent at C(4) and the acetal center at C(6) (Eq. 2.27 and Table 2.53) (90,215). 

Key to these applications has been the control of selectivity-chemoselectivity, regioselectivity, diastereoselectivity, and, especially, enantioselectivity. Here the design of chiral catalysts, begun already in the 1960s, has allowed access to one product when multiple products would, in the past, have been expected. Both electronic and steric control are important, and different metal ions with their associated chiral ligands can have unexpected effects. 

Reaction of p-nitrobenzenesulfonyl azide with alkylidenecycloalkanes 22-25187 does not yield isolable triazolines as expected, but the reaction products derived from alkenes 22 and 23 suggest a single triazoline intermediate, whereas in the case of tetrasubstituted derivative 24 both possible reaction modes are present,187 owing to weak double bond dissymmetry. Product analysis from 25 indicates some conflict between electronic and steric control in the addition, but provides evidence that electronic factors are much more important than steric effects in controlling regioselectivity.187 Reaction of the exocyclic olefins 22 and 23 appears to be controlled more by the interaction of the LUMO of the azide and the HOMO of the alkene.187 p-Nitrobenzenesulfonyl azide is reported to react with members of the novel... 

Table 17 3 compares the equilibrium constants for hydration of some simple aldehydes and ketones The position of equilibrium depends on what groups are attached to C=0 and how they affect its steric and electronic environment Both effects con tribute but the electronic effect controls A hydr more than the steric effect... 

Taft began the LFER attack on steric effects as part of his separation of electronic and steric effects in aliphatic compounds, which is discussed in Section 7.3. For our present purposes we abstract from that treatment the portion relevant to aromatic substrates. Hammett p values for alkaline ester hydrolysis are in the range +2.2 to +2.8, whereas for acid ester hydrolysis p is close to zero (see Table 7-2). Taft, therefore, concluded that electronic effects of substituents are much greater in the alkaline than in the acid series and. in fact, that they are negligible in the acid series. This left the steric effect alone controlling relative reactivity in the acid series. A steric substituent constant was defined [by analogy with the definition of cr in Eq. (7-22)] by Eq. (7-43), where k is the rate constant for acid-catalyzed hydrolysis of an orr/to-substituted benzoate ester and k is the corresponding rate constant for the on/to-methyl ester note that CH3, not H, is the reference substituent. ... 

Silyl ethers are among the most frequently used protective groups for the alcohol function. This stems largely from the fact that their reactivity (both formation and cleavage) can be modulated by a suitable choice of substituents on the silicon atom. Both steric and electronic effects are the basic controlling elements that regulate the ease of cleavage in multiply functionalized substrates. In plan-... 

In a recent study, we showed that the more flexible pyrido[l,2-a]indole-based cyclopropyl quinone methide is not subject to the stereoelectronic effect.47 Scheme 7.17 shows an electrostatic potential map of the protonated cyclopropyl quinone methide with arrows indicating the two possible nucleophilic attack sites on the electron-deficient (blue-colored) cyclopropyl ring. The 13C label allows both nucleophile attack products, the pyrido[l,2-a]indole and azepino [l,2-a]indole, to be distinguished without isolation. The site of nucleophilic is under steric control with pyrido [1,2-a]indole ring formation favored by large nucleophiles. 

It can be seen that a large variety of 9-substituted anthracenes dimerize upon irradiation. There are a few, however, from which no dimers have yet been isolated. Although at this point it is difficult to say what determines whether a particular derivative will dimerize or not, it would appear from the above lists that the controlling factor cannot be steric in nature since the relatively crowded 9-cyclohexyl anthracene dimerizes whereas 9-phenyl-anthracene does not. This result would tend to indicate that electronic effects of the substituents may influence the dimerization. 

In many cases it is all but impossible to distinguish, separately, the operation of electronic and steric effects, as they often both operate towards the same end result. Except where crowding becomes extreme, however, it seems likely that the electronic effects are commonly in control. 

N-heterocycles are a class of neutral ligands with strong coordination affinity to many metal ions. Since a number of neutral N-donors ligands are available, a wide range of oxo-centered triruthenium complexes with various N-heterocyclic ligands have been prepared through axial ligand substitution. By judicious selection of the N-heterocyclic type and modification of the substituents with different electronic and steric effects, the electronic, redox, and spectroscopic properties in these oxo-centered triruthenium derivatives are controllable. 

These observations suggest that bond dissociation reactions, occurring in a homolytic fashion for this family of complexes, are controlled largely, if not entirely, by steric factors, provided that one stays within a family of complexes in which special electronic effects, such as might be found in the benzyl chromium ion, do not play an important role. 

The foregoing examples of differential reactivities of rotamers may be summarized by saying that the reactivity is controlled by the steric factor. The difference in the reactivities of rotamers of 9-(2-bromomethyl-6-methyl-phenyl)fluorene (56) in SN2 type reactions falls in the same category (176). However, the substituent effect is not limited to a steric one there can be conformation-dependent electronic effects of substituents as well. A pertinent example is found in the reactivity of the bromomethyl compound (56) when the rotamers are heated in a trifluoroacetic acid solution (Scheme 10). The ap form gives rise to a cyclized product, whereas the sp form remains intact (176). The former must be reacting by participation of the it system of the fluorene ring. 

Although the intermolecular selectivity of the nitration of alkylbenzenes by nitric acid in trifluoroacetic acid is controlled by both electronic and steric factors, it is argued that intramolecular selectivity is controlled by steric effects on transition state solvation. 

Crotti and co-workers work on regiochemical control of ring opening of epoxides by means of chelating agents has continued. Under standard conditions the regio-isomeric C(l) derivatives are the sole products from the trans epoxides (22a) and (22b) and are the predominant products from the cis epoxides (23a) and (23b). Under chelating conditions the cis epoxides unexpectedly show a consistent increase in C(2) selectivity. The results are discussed in terms of electronic and steric effects. 

---