Enantioselective opening of meso

Using the catalytic system described above, the enantioselective opening of meso epoxides could also be pursued. Although many excellent examples of ring-opening of meso epoxides by Sn2 reactions have recently been reported, the reaction planned here is conceptually different [40]. In the SN2 reaction, the path of the incoming nucleophile has to be controlled. In the titanocene-catalyzed reaction, the intermediate radical has to be formed selectively. If an intermediate similar to that invoked in the Bartmann ring-open-... 

In recent years there has been considerable progress both in the base-catalyzed isomerization of meso-epoxides and in the metal-free catalysis of enantioselective opening of meso epoxides. The former approach has proven its potential in sev-... 

Conceptually new multifunctional asymmetric two-center catalysts, such as the Ln-BINOL derivative, LnMB, AMB, and GaMB have been developed. These catalysts function both as Brpnsted bases and as Lewis acids, making possible various catalytic, asymmetric reactions in a manner analogous to enzyme catalysis. Several such catalytic asymmetric reactions are now being investigated for potential industrial applications. Recently, the catalytic enantioselective opening of meso epoxides with thiols in the presence of a heterobimetallic complex has... 

This titanocene-catalyzed procedure was immediately extended by Gansauer et al. to the enantioselective opening of meso-epoxides by employing substoichiometric quantities of titanocene complexes with chiral hgands [58-60]. It has also been applied by this group in racemic form not only for reductive epoxide openings and intermolecular additions to a,P-unsaturated carbonyl compounds, but also to achieve 3-exo, 4-exo, and 5-exo cycliza-tions, as well as tandem cyclization addition reactions featuring vinyl radicals (Scheme 9) [8,9,44,46,57,61-65]. 

Enantiomerically pure bis-Gp derivatives with chiral Gp ligands have been used with success in the catalytic enantioselective opening of meso-epoxides via electron transfer (see Section 4.05.8). The structural features are of relevance for the understanding of activity and selectivity of these complexes in diastereoselective reactions and for the design of novel catalysts. A comparison of the structure of three of these bis-Gp Ti derivatives (Scheme 481) in the solid state and in solution determined by X-ray crystallography and NMR methods indicated that the structures in the crystal and in solution are the same, and that applications of these complexes in catalysis can de discussed on the basis of crystallographic data.1114 In a similar study, the 1-methylcyclohexyl-Cp, 1-butyl-1-methylbutyl-Cp, and cyclohexyl-Cp titanocene dichlorides (Scheme 481) have been prepared and their molecular structures compared. The use of these three compounds in radical addition reactions has been studied.1115... 

The enantioselective opening of meso compounds is a highly efficient entry to optically active cyclic and acyclic compounds and is an area awaiting further breakthroughs. Transition-metal catalyzed processes may lead to milder and more selective reactions on increasingly complex substrates. 

A less common strategy for asymmetric synthesis, but one with considerable merit, is the enantioselective opening of meso epoxides (Fig. la) by achiral nucleophiles in the presence of a chiral catalyst. [5] Similarly, the kinetic resolution of racemic epoxides (Fig. lb), in the best cases, can deliver high enantiomeric excesses in the unreacted epoxide and ring-opened product. 

Enantioselective opening of meso epoxides by heteroatom nucleophiles [6-11] has been... 

Figure 1. Enantioselective opening of meso epoxides (a) and racemic epoxides (b) by achiral nucleophiles.

Figure 2. Enantioselective opening of meso epoxides. Pathway a activation of the epoxide by the chiral Lewis acid (M XL 2). Pathway b activation of the stoichiometric nucleophile (NuM ) by metathesis with the chiral complex.

Scheme 5. Combinatorial screening of ligands for Ti-catalysed enantioselective opening of meso epoxides by trimethylsilyl cyanide.

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