Stereoselective ligand exchange

Racemate separation by stereoselective ligand exchange occurs when a chiral matrix complex has additional coordination sites which are capable of readily exchanging a racemic substrate ligand. The chiral induction, i. e., the efficiency of die matrix complex, is related to the product distribution, which depends on the stability of the complexes with the two enantiomers of the racemic substrate (Fig. 7.1). The problem to be solved in the design of effective chiral matrix complexes for specific racemic substrates is therefore related to conformational analyses of the type discussed above. 

Table 7.2. Racemate separation by stereoselective ligand exchange.

The hydroxide-promoted exchange of the a-proton of amino acids is catalyzed by metal ions [326]. If the amino acid is coordinated to a chiral complex fragment, the ratio of the two enantiomeric forms of the amino acid is controlled by a chiral intermediate [3]. One of the chiral fragments presented above in the discussion of the stereoselective ligand exchange reactions, [Co(S),(S)-ppm)j (see Table 8.2), was used to promote the epimerization of optically pure a-alanine [327]. The proposed mechanism is shown in Figure 8.10. 

Treatment of P-hydroxy ketones with tetramethylammonium triacetoxyborohy-dride [Me4NHB(OAc)3] complements the chelation approach described above by affording the corresponding 1,3-trans diols. Acetic acid-promoted ligand exchange provides an alkoxydiacetoxyborohydride intermediate in which the proximal ketone is stereoselectively reduced by intramolecular hydride transfer. Alkyl substituents in the a-position do not diminish the 1,3-asymmetric induction. 

Stereoselective Associative Ligand Exchange of 4-coordinate Square Planar Complex... 

Detailed studies from these laboratories shed light on the mechanistic intricacies of asymmetric catalytic carbomagnesations, allowing for an understanding of the above trends in regio- and stereoselectivity [6]. Importantly, our mechanistic studies indicate that there is no preference for the formation of either the anti or the syn (EBTHI)Zr-olefin isomers (e.g.,8 anti vs 8 syn) it is only that one metallocene-alkene diastereomer (syn) is more reactive. Our mechanistic studies also indicate that zirconacyclopentane intermediates (i in Scheme 3) do not spontaneously eliminate to the derived zirconocene-alkoxide Zr-Mg ligand exchange is likely a prerequisite for the alkoxide elimination and formation of the terminal alkene. 

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