Enantiotopic sites

The Cossee-Arlman mechanism as originally proposed has a weakness—the back-flip is required to explain isoselective placement since the two active (coordination) sites are assumed to be enantiotopic. However, the structure of the traditional Ziegler-Natta heterogeneous initiators is not sufficently understood to either support or reject the assumption of enantiotopic sites. Further, even if the sites are enantiotopic, there is no overwhelming reason why the polymer chain is more stable at one site than the other—which is the rationale for the back-flip. The mechanism of isoselectivity with various metallocene initiators is much better understood since these are initiators whose molecular structures are well-established [Busico and Cipullo, 2001 Busico et al., 1997, 1999 Cavallo et al., 1998 Ewen, 1999 Rappe et al., 2000 Resconi et al., 2000], Considerable advancements in understanding heterogeneous Ziegler-Natta initiators occur if one assumes that the active sites in these initiators mimic those in metallocene initiators. Two types of metallocene initiators offer possible models... 

Asymmetric addition of PhLi, coordinated by the chiral ligand 200, to the prochiral imine complex 199 generates 201. Discrimination between enantiotopic sites at C(2) and C(6) occurs. Then the 5,6-mmv-disubstituted 1,3-cyclohexadienal 202 was prepared with 93% ee by electrophilic attack of propargyl bromide [50],... 

Syndiotactic polymer Cs-symmetric, prochiral Enantiotopic sites... 

A and B are the two enantiotopic sites subscripts c and w indicate correct (c) and wrong (w) insertions, according to the given enantioselectivity of each site. 

In a chemical transformation of a molecule with two reactive sites (or subsites) tj and t2, it is the topic relationship between the two sites (or subsites) (Volume 1, Chapter 3, p. 35) that determines the exact type of situselectivity (vide infra). If tj and t2 are stereotopic with respect to each other, then the process is characterized by stereosituselectivity (stereotopic site selectivity) if the sites are nonstereotopic, then one has nonstereosituselectivity (nonstereotopic site selectivity). Stereosituselectivity is subclassified into enantiosituselectivity (enantiotopic site selectivity) or diastereosituselectivity (diastereotopic site selectivity), if ti and t2 are enantiotopic, or, diastereotopic with respect to each other, respectively.On the other hand, nonstereosituselectivity is subclassified into astereosituelectivity (nonstereotopic site selectivity) or nonequisituselectivity (nonstereotopic site selectivity), depending on whether ti and t2 are astereotopic, or, nonequitopic with respect to each other, respectively. Figures 11.5 and 11.6 illustrate select examples of stereosituselectivity and nonstereosituselectivity. 

Busico, V. CipuUo, R. Cutillo, R Talarico, G Razavi, A. Syndiotactic poly(propylene) from [Me2Si(3,6-di-fert-butyl-9-fluorenyl)(N-fert-butyl)]TiCl2-based catalysts Chain-end or enantiotopic-sites stereocontrol Macrc>/nc>/. Chem. Phys. 2003, 204, 1269-1274. 

The classical topism concepts are directly applicable to predict the number of distinct environments, and the largest number of distinguishable nuclei. Nuclei in homotopic sites, related by proper symmetry axes, have necessarily the same chemical shifts. Those situated in enantiotopic sites, related by improper, Sn, axes (e.g., inversion centers or symmetry planes) also show identical chemical shifts. However, interactions with chiral entities or the formation of chiral supramolecular complexes (e.g., a helical structure) may destroy preexisting elements, render the sites diastereotopic, and result in the observation of distinct chemical shifts. 

Fig. 8. The process of fc fc interconversion 11, leading to enantiomerization. The different methylene protons are denoted by letters (a-e). Homotopic sites are denoted by identical letters, enantiotopic sites are denoted by the same letter with a bar. As a result of the dynamic process the following exchanges take place a f, e b, a f and e b. Note that the two protons within a given methylene group do not mutually exchange.

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