Steric Control of Ring Conformation

A typical example of steric control over spin delocalization has been described for the cation-radical of 3,4-bis(thioisopropyl)-2,5-dimethyl-l-phenylpyrrole (Domingo et al. 2001). Scheme 3.15 depicts this sitnation. In this cation-radical, one thioisopropyl group is almost coplanar with the pyrrole ring, whereas the other one occupies an orthogonal position. Accordingly, the ESR spectra established an eqnilibrinm between the symmetrical and asymmetrical conformations of the cation-radical. This equi-librinm is shifted toward the asymmetrical form at low temperatmes. The main feature of the equilibrium is the widening of spin delocalization, which includes not only the pyrrole ring but also one donor sulfur atom at the expense of the other sulfur atom. The steric control predetermines the discrimination of the other sulfur atom in the spin-delocalization process. 

Steric control elements are also important for the diastereoselectivity in alkylations of mono-cyclic cyclohexanone enolates. However, electronic control becomes more evident in these systems compared to monocyclic cyclopentanone enolates The flexibility of the six-membered ring system, and the large number of possible ring conformations, makes predictions of the diastereoselectivity difficult. In general, one may conclude that the diastereoselectivity in alkylations of enolates derived from monocyclic cyclohexanones is not as high as in alkylations of cyclopentanone enolates. The syntheses of compounds 21-27 demonstrate the effect of substitution in each position of the six-membered ring49,61 -7°. 

These steric interactions become more pronounced when we consider the introduction of an additional chelate ring in those complexes containing three didentate en ligands. The A XkX form of an [M(en)3]n+ cation is estimated to be 7-8 kJ mol-1 more stable than the A 888 diastereomer. This becomes particularly important when we consider kinetically inert complex cations, such as [Co(en)3]3+, where there is a significant barrier to the interconversion of the diastereomers. In practice, the conformation of the chelate rings in [Co(en)3]3+ salts depends upon the nature of both the anions and any additional solvent molecules in the lattice which can form hydrogen bonds with the en ligands. We will return to this topic in Chapter 7, where we discuss some reactions of [Co(en)3]3+ salts in which an extraordinary steric control is exerted. 

Factors analogous to those just discussed have been reported to explain the striking differences in stereochemistry of the alkaline hydrolysis of 22 and 23 the former is hydrolyzed with predominant retention 0)- and the latter with nearly complete inversion of configuration at phosphorus In 22, the steric effect of the f-butyl group replaces ring constraint as the key factor controlling the conformation of intermediate phosphoranes, and hence the overall stereochemistry of displacement 2), Similar steric-bulk effects have been discussed with regard to the stereochemistry and product distribution of the alkaline hydrolysis of 24... 

This can be done by conformational and steric effects, which have to serve two objectives. Firstly, as in the previous section, a defined reactive conformation has to be fixed by substituent effects and, secondly, one of the two diastereofaces has to be shielded by the steric repulsion of the substituents.These effects are different in cyclic and acyclic systems as in the former ones the conformation is normally controlled by the more or less rigid geometry of the ring. 

It appeared more attractive to carry out a Diels-Alder reaction with control of both, its regio- and stereo-chemistry. In 1975, Corey published a diastereose-lective Diels-Alder reaction with the use of 8-phenylmenthol as a chiral auxiliary. The Lewis acid fulfils two tasks on the one hand, it increases the reactivity by lowering the LUMO of the dienophile [219] on the other hand, it stabilises the s-trans conformation for steric reasons. The attack of the diene on the s-cis-dienophUe would lead to the opposite absolute stereochemistry in the product. The Diels-Alder reaction occurs diastereoselectively, because the Si-facial half of the prochiral double bond is effectively shielded by 7t-stacking with the phenyl ring of the auxiliary. In this reaction, four new stereogenic centres are generated all at once. The yield of the desired diastereomer amounts to 89 %. 

Based on experimental evidence obtained with the above catalysts, it was concluded by Miyake et al., that the isotactic propylene polymerization with zirconium catalysts takes place by a regiose-lective 1,2-insertion of the propylene monomer into the metal-polymer bond [294]. Monomer insertion is believed to take place at two active sites on the metal center in an alternating manner. In addition, it was shown [295] that the substituents on the cyclopentadiene rings determine the conformatiOTi of the polymer chain end, and the fixed polymer chain end conformation in turn determines the stereochemistry of olefin insertion in the transitimi state as a form of indirect steric control. 

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