Steric effect conformational dependence

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. 

The success of such reactions depends on the intramolecular hydrogen transfer being faster than hydrogen atom abstraction from the stannane reagent. In the example shown, hydrogen transfer is favored by the thermodynamic driving force of radical stabilization, by the intramolecular nature of the hydrogen transfer, and by the steric effects of the central quaternary carbon. This substitution pattern often favors intramolecular reactions as a result of conformational effects. 

The ring size (degree of oligomerization x) and conformation of M-E heterocycles strongly depends on steric effects of the substituents (repulsive interactions), ring strain effects and on entropy factors. This was shown for instance by Beachley and Racette for several heterocyclic aminoalanes [R2A1NR2]X97 and confirmed by our own results. However, predictions whether four- or six-membered heterocycles will be formed are... 

Substituents may be divided into three categories based on the degree of conformational dependence of their steric effects ... 

The Minimal Sterlo iHteraotlon(MSl) Principle. As all sterlo Interactions result In an Increase In the energy of a system, the observed steric effect In the system will be the smallest possible. Thus, when the sterlo effect of a group X depends on Its oonfoiMnatlon, the group will prefer that conformation which results In the smallest possible steric Interaction. This Is the MSI principle. 

Conformational dependence of the sterlo effect. Some groups show little or no conformational dependence of their steric effeots( ). Non-oonformationally dependent groups are monatomic (halogen or hydrogen). HZ symmetric top (M Is hybridized sps), HHg or HZ ,... 

Secondary steric effects on chemical reactivity can result from the shielding of an active site from the attack of a reagent, from solvation, or both. They may also be due to a steric effect that determines the concentration of the reacting conformation of a chemical species. The secondary steric effect of a nonsymmetric group will also depend... 

While the perfluorinated acetates do prefer insertion, they are still capable of forming 1,3-dipoles and have demonstrated interesting effects on the regioselectivity of intramolecular cycloaddition reactions, presumably through Lewis acid-mediated effects on the dipolarophile [83]. Other chemoselectivity effects have been noted in the intramolecular cycloaddition reactions and may or may not be partially induced by conformation and sterics [84]. It was further demonstrated thaL when possible, O-H insertion is the predominant outcome over other types of insertion for rhodium]II)-car-benes, independently of the catalyst. However, cycloaddition reactions have been demonstrated to be hgand-dependent [85]. 

Development of a predictive model for the reactivity of annelated benzenes is facilitated by the partitioning of substituent effects into their steric and electronic parameters. In order for this to be accomplished, reference reactions are needed which depend uniquely on one type of parameter. Typically conformational equilibria serve as good references of steric effects, whereas acid-base equilibria serve as good references of electronic effects. 

Diastereoselectivities in complex systems are determined by conformation of the transition states which are affected by chelation and steric effects of substituents and reaction conditions. For example, the stereochemistry of a hydroxyl group derived from a ketone is determined by coordination of hydroxyl and other functional groups, and depends on the presence or absence of HMPA (Equation (42)). 

In order to investigate the structural requirements for the strong redox dependence, AEia values were also measured for anthraquinone, 12, and benzyl, 13, in the presence of 5 equivalents of diphenylurea in DMF. Under these conditions, phenan-threnequinone gives a shift of 61 mV, whereas anthraquinone gives a shift of only 8 mV and benzil 5 mV. Unlike phenanthrenequinone, the urea can only H-bond to one carbonyl oxygen at a time with anthraquinone. Two bifurcated H-bonds are possible, but these together would be much weaker than the two close to linear H-bonds possible with oquinones. A similar situation arises with benzil, since rotation about the central —C bond will be hindered in the radical anion and the favored conformation will have the oxygens trans due to electrostatic repulsion and steric effects. 

Of the remaining interactions, those which involve the dipole moment of the bas may be subject to an indirect steric effect as the preferred conformation of the bas may depend on steric effects and the dipole moment will depend on the conformation. 

In the second step the bas is recognized by the receptor site and the bas-rep complex forms. As was noted above, the complex is generally bonded by inter-molecular forces. The bas is transferred from an aqueous phase to the receptor site. The receptor site is very much more hydrophobic than is the aqueous phase. It follows, then, that complex formation depends on the difference in intermolecular forces between the bas-aqueous phase and the bas-receptor site. The importance of a good fit between bas and receptor site has been known for many years. The configuration and conformation of the bas can be of enormous importance. Also important is the nature of the receptor. If the receptor is. a cleft, as is the case in some enzymes, steric effects may be maximal as it may not be possible for a substituent to relieve steric strain by rotating into a more favorable conformation. In such a system, more than one steric parameter will very likely be required in order to account for steric effects in different directions. Alternatively, the receptor may resemble a bowl, or a shallow, fairly flat-bottomed dish. Conceivably it may also be a mound. In a bowl or dish, steric effects are likely to be very different from those in a cleft. Possible examples are shown in Fig. 1, 2, and 3. 

IIIc. Groups of the type M(lp)nZ3 n. Examples are OEt, OPh, StBu, NHMe, NEt2. The final category is that of groups which show a strong dependence of their steric effect upon conformation (SCD groups). Among the members of this class are ... 

The dependence of the steric effect of ICD groups on conformation makes it difficult to determine , omx and u for many of these groups. A second problem arises with groups (1) that have a skeleton of 2 or more atoms other than H. Although u, is frequently determined by the first atom of the skeleton, M1, the remaining atoms also contribute to the steric effect of the group. This is not a problem with NCD or MCD groups. For these classes is a valied measure of the stoic effect. 

In order to include an group in a data set in which the substituents exhibit an steric effect it is necessary to know 0 so that the appropriate values of the delocalized electrical effect parameter, ctd and the steric parameter can be used. Values of 0 are usually unavailable. A method has been developed to circumvent this difficulty for chemical reactivities. The procedure is 1) A basis set, which contains only those members of the data set that show minimal dependence of their steric effect on conformation, is correlated with the LDS equation,... 

If the tBu group in 4 and 5 is replaced by the skeletal group, G, we have a system which models that from which the uCh2ch2x constants have been derived. As the steric effect of a CH2CH2X group is conformationally dependent and the conformation is a function at least in part of 2 2 on o, reasonable. 

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