Nonstereogenization

In the more successful reagents, the ligands have been selected in such a way that the metal center remains nonstereogenic, this has been achieved mainly by application of chiral diols with C2 symmetry or by introduction of two of the same alkoxy residues. 

P. Beak, Determinations of Transition-State Geometries by the Endocyclic Restriction Test Mechanism of Substitution at Nonstereogenic Atoms, Acc. Chem. Res. 1992, 25, 215-222 P. Beak, Mechanisms of Reactions at Nonstereogenic Heteroatoms Evaluation of Reaction Geometries by the Endocyclic Restriction Test, PureAppl. Chem. 1993, 65, 611-615. 

Recently, the anti-HIV alkaloids michellamines A (4) and B (5) have attracted much attention. The tetraaryl skeleton of the michellamines is constructed by first forming the inner (nonstereogenic) biaryl axis and then adding the two other (stereogenic) axes by means of a double Suzulci-type cross-coupling reaction between binaphthalene ditriflate (2) and iso-quinolineboronic acid (3) (Eq. (13)) [31]. 

P. Beak, Mechanisms of reactions at nonstereogenic heteroatoms evaluation of reaction geometries by the endocyclic restriction test, Pure Appl. Chem. 1993, 65, 611-615. 

This molecule, the most symmetrical of the three, is achiral. The central carbon atom is completely nonstereogenic. Both planes are planes of symmetry and the hydrogens are homotopic. They are chemically and magnetically equivalent. 

Chiral a-methyl aldehydes (43) show exceptional diastereofacial preferences in their Lewis acid mediated reactions with enol silanes (equation i6) 2i 25c-26-64 selected data are reported in Table 8. The reason for this selectivity may be due to an approach trajectory of the nucleophile closer to the stereocenter when the carbonyl group is bound to the Lewis acid. Additions to chiral a-alkoxy aldehyde (48) were studied with both nonstereogenic (equation 17 Table 9) and stereogenic enol silanes (equation 18 Table 10). (Stereogenic and nonstereogenic are defined according to Mislow and Siegel.) ... 

With nonstereogenic enol silanes (Table 9) usually (not always, see entry 2) a single isomer was obtained using tin(IV) chloride or titanium chloride as a promoter (entries 3, 5, 7 and 9). This high facial... 

Table 9 Ratio of Diastereoisomers in the Reactions of Nonstereogenic Enol Silanes with Aldehyde...

Table 21. Pd(0)-Catalyzed Allylations of Nonstereogenic Preformed Ketone Enolates...

Palladium(0)-catalyzed intramolecular reductive coupling of the diacetates 1 and 3 with hexa-methyldistannane leads to tricyclic compounds 2 and 4, respectively, in a completely regioselec-tive manner2. Intermediate formation of a monoallyltin species followed by attack of this allyl tin moiety on the rc-allyl complex generated from the remaining allyl acetate is a likely route to the products. Since a substrate similar to 3 has been shown to isomcrizc to a nonstereogenic terminal diacetate under the conditions listed, the stereochemical results obtained for both 1 and 3 reflect the simple diastereoselectivity of these cyclizations. 

In many cases various proton sources, solvents, auxiliaries, and conditions have been applied in order to obtain different diastereoselectivites from the protonation of nonstereogenic car-banion centers. However, only the tw o extreme diastereomeric product ratios are given in this section. In most experiments kinetically controlled protonation can be assumed. However, since the anionic substrate already carries one (or more) stereogenic center, selective equilibration at the newly formed stereogenic carbon - hydrogen center could increase the diastereoselec-tivity. Indeed, epimerization of this center is a valuable tool for diastereoselective synthesis, provided that the carbon-hydrogen bond is acidic enough (see enolates, Section 2.1.3.1). 

The chiroptical influence of a nonstereogenic sulfonic acid group would be to asymmetrically perturb a UV active chromophore in the molecule in which it is found. 10-Camphorsulfonic acid is an example. However, this type of influence is outside the purview of this chapter. 

Table 16.3. Composite Classification of Destereogenizations/Stereogenizations, Nonstereogenizations and Nonchirononstereogenizations...

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