Olefin addition, face preference

Figure 29. A schematic illustration of the face preference for addition of olefins to a steroidal enone in solution and on silica surface. In solution the less-hindered a face is preferred. On silica surface the molecule adsorbs from the less-hindered face exposing the more-hindered face for attack by an olefin.

Simple stereoinduction in the Diels-Alder reaction typically follows a number of general guidelines. Two of these are well known to the student of organic chemistry, namely the notable preference for endo selectivity, as a consequence of secondary orbital overlap, and regioselectivity consistent with the optimal interactions of the frontier molecular orbitals [38]. Additional stereochemical preferences may also be observed for chiral reacting partners. In a study by Overman with cyclic dienes such as 30, cycloaddition was observed to occur on the olefin face anti to the allylic substituent in 30 (Scheme 17.7) [39]. The superimposition of the basic stereochemical features of the Diels-Alder reaction (i.e., endo selectivity cf 32) on the steric differentiation of the olefin faces leads to the preferential formation of 33-35 with increasing diastereoselectivity as a function of the size of the substituent X. 

The theoretical study by Khan et al. [13] on the stereochemistry of nucleophilic addition of organometallics to unsaturated substrates can also be applied to conjugated systems. Of the three major factors affecting the orientation of the nucleophile to the substrate (see Chapter 16), the ability of the substrate to discriminate between the nucleophilic and electrophilic character of the Grignard reagent is the one most susceptible to influence by conjugation with an adjacent 7r-system. They concluded that the accessible electrophilic site (the metal) is the source of the stereochemical preference for the electron-rich olefin face. 

The two olefins carry a total of two enantiomeric pairs of diastereotopic faces. When a tartrate-titanium epoxidation system is allowed to react with this substrate, approach to only one of these four faces simultaneously satisfies the requirements of both the catalyst (which prefers the Re face) and the substrate (which prefers 1,2-anti addition). To the extent that the rate of epoxidation at this face exceeds that of the others (ki in Scheme 8.10), one product predominates. Minor diastereomers result from pathways k2 and k4. However, note that the pathway with a rate of ky (mismatched 1,2-anti diastereoselectivity combined with disfavored Si enantiofacial attack) affords the enantiomer of the major isomer. 

Then, the hydride ion is selectively transferred to the f-olefin from the least sterically hindered face to produce the corresponding isomer of the product. Furthermore, although a kinetic preference for (he (Z)-iminium ion formation has been demonstrated, the ( )-iminium ion intermediates, which dominate the equilibrium ratio, react with nucleophiles faster than the ( -isomers when diarylprolinol and imidazohnone-based chiral catalysts are anployed in conjugate additions to a,P-unsaturated aldehydes [20]. 

The ion pair mechanism would not be expected to be stereospecific, since the carbonium ion intermediate permits loss of the stereochemistry relative to the initial olefin. It might be expected that the ion pair mechanism could lead to a preference for syn addition, since at the instant of formation of the ion pair, the halide ion is necessarily on the same side of the multiple bond from which hydrogen was added. On the other hand, the termolecular mechanism would be expected to give anti addition. Concerted attack by the nucleophile would occur at the face opposite from proton addition ... 

---