Diastereotopic sites

Togni s [38] approach was therefore to test the ability of sparteine to act as an ancillary ligand in Pd(II)-allyl complexes—susceptible to nucleophilic attack by stabihzed anions such as Na[CH(COOMe)2]—which could be employed as catalyst precursors. In addition he speculated that the rather rigid and bulky sparteine would be able to induce significant differentiation between the two diastereotopic sites of 1,3-disubstituted allyl hgand, thus leading to enantioselection upon nucleophilic attack. 

The substrate-controlled reaction is often called the first generation of asymmetric synthesis (Fig. 1-30, 1). It is based on intramolecular contact with a stereogenic unit that already exists in the chiral substrate. Formation of the new stereogenic unit most often occurs by reaction of the substrate with an achiral reagent at a diastereotopic site controlled by a nearby stereogenic unit. 

In removing the oxazoline auxiliary from the products, Richards and coworkers have demonstrated the use of the diastereoselective ferrocenyloxazoline lithiation in the synthesis of conformationally constrained amino acid derivatives (Scheme 146) °. Amination of 305 was achieved by nitration, reducing to the amino group after removal of the oxazoline under standard conditions. Using the trick of silylating the more reactive diastereotopic site, it was possible to make either enantiomer of 321 from the same oxazoline starting material. 

Metallocenes with diastereotopic sites for monomer coordination show quite an interesting polymerization behavior introduction of a methyl group in position 3 of the cyclopentadienyl ring in (21) disturbs the stereospecificity at this site, giving rise to hemiisotactic polypropylene [53], while a f-butyl group at the same position inverts the preferred mode of coordination (22) thus an isotactic polymer is generated [54]. Metallocene (8) has one nonspecific and one stereo-specific site, too at low temperature, hemiisotactic polypropylene is produced while at high temperatures site isomerization without insertion facilitates the formation of isoblock polypropylene. 

Asymmetric Catalysts. The control of polymer stereochemistry using asymmetric C point group) catalysts is conceptually more complicated than using C2-symmetric variants that contain homotopic coordination sites. Since C catalysts have inequivalent, diastereotopic sites (A, B) for olefin coordination, several stereochemical scenarios are possible (Figure... 

The Cs-symmetric meso ansa-metallocenes have two diastereotopic sites, both being achiral, hence the lack of enantioselectivity in propene polymerization. However, from a mechanistic standpoint, these as-pecific catalysts can be interesting and instructive as well. 

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. 

The Cl-symmetric active cation derived from 3 has two diastereotopic sites. To explain their observations, the authors postulated that propylene insertion is enantioselective at only one of the sites, and isotactic/atactic stereoblock chain propagation results from long sequences of monomer insertions at the two sites feolCsH ] 2> feinv and feaspCCsH ] < inv in Scheme 8.4). 

If the amount of the sample is sufficient, then the carbon skeleton is best traced out from the two-dimensional INADEQUATE experiment. If the absolute configuration of particular C atoms is needed, the empirical applications of diastereotopism and chiral shift reagents are useful (Section 2.4). Anisotropic and ring current effects supply information about conformation and aromaticity (Section 2.5), and pH effects can indicate the site of protonation (problem 24). Temperature-dependent NMR spectra and C spin-lattice relaxation times (Section 2.6) provide insight into molecular dynamics (problems 13 and 14). 

The idea of determining the site of initiation via the substitution pattern of the olefin has also been used by Blechert et al. during the course of a stereocon-trolled RCM process (Scheme 10). Again, the reaction starts most likely at the terminal olefin site in 33 independent of whether 1 or 24 is used as catalyst however, due to the different coordination geometries of ruthenium and molybdenum, the evolving carbene reacts with either diastereotopic olefin attached to... 

Case 3. (90°) = s (0°). Now the minima are found near 45° and 135° twist angles, and appreciable maxima exist both near 0° (180°) and 90° (270°). At slow exchange, a donor group A has two sites corresponding to the above minima, and prochiral nuclei in A are diastereotopic in both sites. The exchange system can thus be depicted as a four-site case, and a complete analysis can give both the steric barrier and the tt barrier. 

An extensive review appeared on the configurational stability of enantiomeric organolithium reagents and the transfer of the steric information in their reactions. From the point of view of the present chapter an important factor that can be evaluated is the ease by which an inversion of configuration takes place at the metallation site. It happens that H, Li, C and P NMR spectra of diastereotopic species have been central to our understanding of the epimerization mechanism depicted in equation 26, where C and epi-C represent the solvated complex of one chiral species and its epimer, respectively. It has been postulated that inversion of configuration at the Li attachment site takes place when a solvent-separated ion pair is formed. This leads to planarization of the carbanion, its rotation and recombination to form the C—Li bond, as shown in equation 27, where Li+-L is the solvated lithium cation. An alternative route for epimerization is a series of... 

C -symmetric initiators have a pair of diastereotopic (nonequivalent) sites one site is sterically crowded and enantioselective, and the other site is less crowded and nonselective. The propagating polymer chain always prefers the less crowded site, but monomer coordination and migratory insertion occur at the more crowded enantioselective site. The polymer chain then back-flips to the less crowded site. This model offers a rationale for the back-flip of the polymer chain—the polymer chain is less stable at the more crowded site. 

The two coordination (active) sites of a meso Cs metallocene are diastereotopic and nonequivalent, but achirotopic. Each site resides in an achiral environment and polymerization produces a highly atactic polymer, although the regioselectivity is very high, even higher than the best C2 metallocenes. Unlike some C2v metallocenes, there are no reported cases of even modest stereoselective polymerization, either syndioselective or isoselective, due to chain end control. 

The two coordination sites are chirotopic—each site is in a chiral environment. The two sites are diastereotopic, not enantiotopic. Thus, one might expect both sites to be... 

Stereoselectivity is also induced by the zeolite framework surrounding the active site in the oxidation of norbornane and methyl cyclohexane by PhIO [49-50,63-64]. The zeolite orientates the incoming substrate in such a way that one of the two diastereotopic C-H bonds has a greater chance to be oxidized. 

The anion crystallizes as a dimer with bonding occurring via a Li20, four-membered ring. Two further coordination sites on each Li4 arc occupied by the TMF.DA N-atoms. This result is fully consistent with the four-center chelate structure which was proposed before for a-lithio sulfoxides 39- 40 and believed to be responsible for the planar configuration of the anionic carbon atom, This chelation discriminates between the two diastereotopic faces and for this reason a-sulfinyl carbanions react with electrophiles in a highly stereoselective manner (see the following section). 

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