Enantioselective opening of meso epoxides

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... 

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.

One of the earliest useful methods for asymmetric opening of meso-epoxides with sulfur-centered nucleophiles was reported by Yamashita and Mukaiyama, who employed a heterogeneous zinc tartrate catalyst (Scheme 7.10) [20]. Epoxides other than cydohexene oxide were not investigated, and the enantioselectivity depended strongly on the identity of the thiol. 

Our hypothesis of steric factors dominating the stability of the emerging radical centers in the transition states readily explains the enantioselective epoxide opening of meso-epoxide 35 to 36 that is shown in Fig. 3 [59,60]. In the case of a reversible epoxide opening, a stability difference of at least 3 kcalmol 1 between the two radicals 37 and 38 is necessary to explain the observed selectivity. According to the calculations this seems highly unlikely. A thermodynamically controlled epoxide opening can therefore be ruled out. 

Reymond, S. Brunei, J. M. Buono, G. (2000) New development in the enantioselective ring opening of meso-epoxides by various ion silicon sources catalyzed by an o-methoxyaryldiazaphosphonamide Lewis base., Tetrahedron Asymmetry, 11 4441-4445. 

Nakajima, M. Saito, M. Uemura, M. Hashimoto, S. (2002) Enantioselective ring opening of meso-epoxides with tetrachlorosilane catalyzed by chiral bipyridine N,N -dioxide derivatives.. Tetrahedron Lett., 43 8827-8829. 

Carree, F. Gil, R. Collin, J. (2005) Enantioselective ring opening of meso-epoxides by aromatic amines catalyzed by lanthanide iodo binaphtholates., Org. Lett., 7 1023-1026. 

The enantioselective ring opening of meso-epoxides such as cyclohexene oxide, which uses benzoic acid as the nucleophile, was also investigated (see Scheme... 

Scheme 2.1.6.6 Enantioselective ring opening of meso-epoxides with benzoic acid.

Jacobsen s cobalt and chromium salen complexes 69 and 70 have proven extremely successful in the enantioselective ring opening of meso-epoxides (and kinetic resolution of racemic epoxides). Recent accounts of these most efficient and practical catalysts can be found elsewhere [71-73]. 

The first attempt at enantioselective ring opening of meso-epoxides by using a chiral selenolate was reported in 1988 [90]. Enantiomerically pure seleno-binaphthyl compounds 65-67 were synthesized and applied to the asymmetric ring opening of cyclohexene oxide (Scheme 47). 

Enolboration of Ketones and Opening of meso-Epoxides. Methyl alkyl ketones have been successfully enolized by IpciBX (X = OTf or Cl) in the presence of a tertiary amine. The corresponding enolborinates have been used in asymmetric aldol condensations (eq 5). The reagent has also been applied to the enantioselective opening of mcj o-epoxides to form the corresponding nonracemic chlorohydrins (eq 6). ... 

Enantioselective ring opening of meso-epoxides catalysed by an o-methoxyaryldiaza-phosphonamide Lewis base (374) has been achieved using various chloride ion silicon sources. The use of TMSCl leads to enantioselectivi-ties varying from 6 to 98% ee depending on the nature of the epoxide. ... 

Denmark et al. have extended this study to the enantioselective ring opening of meso-epoxides with silicon tetrachloride catalyzed by chiral phosphoramide 71 (Table 11). In this case, enantiomerically enriched chlorohydrins have been synthesized in enantiomeric excesses varying from 7 to 87 depending on the structure of the considered substrate [68]. 

Catalysts formed from Me2Zn and binaphthol 3.7 (R = H) have been used for asymmetric ene-reactions [778]. Enantioselective ring opening of meso-epoxides by n-BuSH is catalyzed by a potassium tartrate/ZnCl2 complex [559, 778, 805]. Mukaiyama and coworkers have shown that reaction of Et2Zn with chiral sulfamides 3.15 (R = PI1CH2, r-Pr) generates Lewis acids [806] that catalyze asymmetric reactions of aldehydes with ketene acetals. 

Scheme 8.11. (a) Group-selective ring-opening of meso epoxides by nucleophiles leads to enantioselective syntheses of 1,2-difunctionalized compounds, (b) Azido alcohol synthesis from epoxides and trimethylsilyl azide as catalyzed by (salen)CrCl complexes (see Scheme 8.6a for general structures of salen catalysts)... 

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