Alkene addition reactions asymmetric centers

These chains are depicted in their Fischer projections rather than as conformational representations for the specific reason that the planar zigzag orientation of the chain is clearly favored only in chains having the arabino stereochemistry ( ) For the other configurations, the conformational preference is for non-extended conformations that may be conformational mixtures separated by low energy-barriers. It is clearly naive to depict exact molecular orientations for putative transition states in such reactions. Nevertheless, the model depicted here for interpreting the course of the reaction, which is in accord with the general model proposed by Trost (10) for diastereofacial selectivity in additions to alkenes having an adjacent asymmetric center, has predictive utility in these reactions. 

This gives control over the stereochemistry of the product, because 8.14 can be resolved, thanks to the presence of the optically active group (R ) on the Cp ring, in which case carrying out the addition with one enantiomer of the metal complex means that the new asymmetric center on the ligand is formed with very high asymmetric induction. This reaction therefore constitutes a chiral synthesis of the alkenes shown. 

Synthesis of a chiral compormd from an achiral compound requires a prochiral substrate that is selectively transformed into one of the possible stereoisomers. Important prochiral substrates are, for example, alkenes with two different substituents at one of the two C-atoms forming the double bond. Electrophilic addition of a substitutent different from the three existing ones (the two different ones above and the double bond) creates a fourth different substituent and, thus, an asymmetric carbon atom. Another class of important prochiral substrates is carbonyl compounds, which form asymmetric compounds in nucleophilic addition reactions. As exemplified in Scheme 2.2.13, prochiral compounds are characterized by a plane of symmetry that divides the molecule into two enantiotopic halves that behave like mirror images. The side from which the fourth substituent is introduced determines which enantiomer is formed. In cases where the prochiral molecule already contains a center of chirality, the plane of symmetry in the prochiral molecules creates two diastereotopic halves. By introducing the additional substituent diasterom-ers are formed. 

We have seen that when an alkene reacts with an electrophilic reagent such as HBr, the major product of the addition reaction is the one obtained by adding the electrophile (H ) to the sp carbon bonded to the most hydrogens and adding the nucleophile (Br ) to the other sp carbon (Section 6.4). Thus, the major product obtained from the following reaction is 2-bromopropane. This product does not have an asymmetric center, so it does not have stereoisomers. Therefore, we do not have to be concerned with the stereochemistry of the reaction. 

If two asymmetric centers are created from an addition reaction that forms a bromonium (or chloronium) ion intermediate, only one pair of enantiomers will be formed. For example, the addition of Br2 to the cis alkene forms only the threo enantiomers. 

The high levels of enantioselectivity obtained in the asymmetric catalytic carbomagnesa-tion reactions (Tables 6.1 and 6.2) imply an organized (ebthi)Zr—alkene complex interaction with the heterocyclic alkene substrates. When chiral unsaturated pyrans or furans are employed, the resident center of asymmetry may induce differential rates of reaction, such that after -50 % conversion one enantiomer of the chiral alkene can be recovered in high enantiomeric purity. As an example, molecular models indicate that with a 2-substituted pyran, as shown in Fig. 6.2, the mode of addition labeled as I should be significantly favored over II or III, where unfavorable steric interactions between the (ebthi)Zr complex and the olefmic substrate would lead to significant catalyst—substrate complex destabilization. 

In an attempt to rationalize the factors that control selectivity in the Rh- and Ir-catalyzed hydroboration reactions, Fernandez and Bo [35] carried out experimental and theoretical studies on the H—B addition of catecholborane to vinylarenes with [M(C0D)(R-QUINAP)]BF4, (QUINAP = l-(2-diphenylphosphino-l-naphthyl) isoquinoHne). A considerable difference was found in the stability of the isomers when the substrate was coordinated to the iridium(I) or rhodium(I) complexes. In particular, the difference between pro-R B1 and pro-S B2 isomers was not so great when the metal center was iridium and not rhodium (Figure 7.1), which explains the low ee-values observed experimentally when asymmetric iridium-catalyzed hydroboration was performed. Structurally, the energy analysis of the n2 and Tti interactions [36] seems to be responsible for the extra stabilization of the B2 isomer in the iridium intermediates (Figure 7.1). The coordination and insertion of alkenes, then, could be considered key steps in the enantiodifferentiation pathway. 

Quite recently it was reported that in addition to hydrogen peroxide, periodate or hexacyanoferrat(III), molecular oxygen21,31-34 can be used to reoxidize these metal-oxo compounds. New chiral centers in the products can be created with high enantioselectivity in the dihydroxylation reactions of prochiral alkenes. The development of the catalytic asymmetric version of the alkene dihydroxylation was recognized by Sharpless receipt of the 2001 Nobel prize in Chemistry. 

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