Epoxide chiral Lewis bases

Denmark, S. E. Barsanti, P. A. Wong, K.-T. Stavenger, R. A. (1998) Enantioselective ring opening of epoxides with silicon tetrachloride in the presence of a chiral lewis base., J. Org. Chem., 63 2428-2429. 

According to this mechanism (Scheme 15.29), the process is amendable to asymmetric modifications. Among various silicon reagents that were examined, only tetrachlorosilane proved to be suitable for the asymmetric process, while application of other chlorosilanes resulted in the formation of racemic products. Several chiral Lewis bases were investigated in the opening of meso-epoxides 146 and 151 (Scheme 15.30) to produce the corresponding chlorohydrins 150 and 152, respectively. Opening of the norbornene-derived epoxide 153 was found to proceed... 

Table 15.13 Enantioselective ring opening of meso-epoxides catalyzed by chiral Lewis bases (Scheme 15.30 and Figure 15.8).

Other reactions not described here are formal [3 -i- 2] cycloadditions of a,p-unsaturated acyl-fluorides with allylsilanes [116], or the desymmetrization of meso epoxides [117]. For many of the reactions shown above, the planar chiral Fe-sandwich complexes are the first catalysts allowing for broad substrate scope in combination with high enantioselectivities and yields. Clearly, these milestones in asymmetric Lewis-base catalysis are stimulating the still ongoing design of improved catalysts. 

Next to the above presented use of SiCl for the in situ preparation of a Lewis acid catalyst with a Lewis base for the aldol reaction, it is possible to apply this compound as a reagent in the ring opening of epoxides leading to chlorinated alcohols. Denmark [104] reported that the chiral phosphoramide 38 catalyzed the asymmetric ring opening reaction of meso-epoxides in the presence of tetrachlo-rosilane. Similar examples were provided by Hashimoto in 2002 [105], applying the A -oxide 39 as catalyst (Scheme 30). 

Desymmetrization with halogen nucleophiles was effectively demonstrated with two mechanistically-divergent chiral catalysts. Denmark disclosed a Lewis-base activated delivery of chloride that was catalyzed by the enantiopuxe phos-phoramide 16. Binding of the phosphoramide was believed to induce dissociation of SiCl4 into the chiral phosphorus/silicon cation and chloride anion, which subsequently ring-opened the activated epoxide. The best enantioselectivity was observed with cfs-stilbene oxide, which was formed in 94% yield and 87% ee (Scheme 14) [28]. 

There is a frequently noted incompatibility of organoiithiums with many chiral Lewis acids, which are often employed for asymmetric openings of epoxides [99]. Analogous Lewis base-catalyzed reactions are rare [100]. However, activation by Lewis acids, such as BFj OEt2, is necessary for the opening of less reactive epoxides [101]. While organoiithiums are rarely employed, applications of hetero-nucleophiles are well known in enantioselective desymmetrizations of meso-epoxides [102]. 

Thus in the aldol addition, just as in the case of epoxide-opening reactions, the chloride ion, formed as a necessary consequence of the mechanism of Lewis base catalysis with chlorosilanes, is not innocuous. In fact, it is a competent nucleophile that can attack an aldehyde or an epoxide activated by the Lewis base-coordinated silicenium cation in an intermolecular fashion. The desire to understand these two seemingly inconsistent results obtained in our study of the Lewis base-catalyzed reactions of trichlorosilanes presented an opportunity for the development of novel catalytic processes. For example, if a chloride ion can capture these activated electrophiles, could other exogenous nucleophiles be employed to intercept these reactive intermediates If so, a wide variety of bond-forming processes mediated by the phosphoramide-bound chiral Lewis acid [LB SiCls]" would be feasible. At this point it remained unclear if (1) an exogenous nucleophile could compete with the ion-paired chloride and (2) what kinds of nucleophiles could be compatible with the reaction conditions. 

Silyl cyanides react enantioselectively with such electrophiles as aldehydes, ketones, imines, activated azines, or,/ unsaturated carbonyl compounds, epoxides, and aziridines in the presence of chiral Lewis acid catalysts to give functionalized nitriles, versatile synthetic intermediates for hydroxy carboxylic acids, amino acids, and amino alcohols (Tables 3-6, 3-7, 3-8, and 3-9, Figures 3-6, 3-7, and 3-8, and Scheme 3-154). ° Soft Lewis acid catalytst, the reaction of epoxides with trimethylsilyl cyanide often leads to isonitriles, which are derived from silylisonitrile spiecies (Schemes 3-155 and 3-156). Soft Lewis base such as phosphine oxide also catalyzes the reaction and cyanohydrin silyl ethers of high ee s are isolated. 

Although the Sharpless catalyst was extremely useful and efficient for allylic alcohols, the results with ordinary alkenes were very poor. Therefore the search for catalysts that would be enantioselective for non-alcoholic substrates continued. In 1990, the groups of Jacobsen and Katsuki reported on the enantioselective epoxidation of simple alkenes both using catalysts based on chiral manganese salen complexes [8,9], Since then the use of chiral salen complexes has been explored in a large number of reactions, which all utilise the Lewis acid character or the capacity of oxene, nitrene, or carbene transfer of the salen complexes (for a review see [10]). 

Snapper and Hoveyda reported a catalytic enantioselective Strecker reaction of aldimines using peptide-based chiral titanium complex [Eq. (13.11)]. Rapid and combinatorial tuning of the catalyst structure is possible in their approach. Based on kinetic studies, bifunctional transition state model 24 was proposed, in which titanium acts as a Lewis acid to activate an imine and an amide carbonyl oxygen acts as a Bronsted base to deprotonate HCN. Related catalyst is also effective in an enantioselective epoxide opening by cyanide "... 

The authors also investigated the mode of activation of these BINOL-derived catalysts. They proposed an oligomeric structure, in which one Ln-BINOL moiety acts as a Brpnsted base, that deprotonates the hydroperoxide and the other moiety acts as Lewis acid, which activates the enone and controls its orientation towards the oxidant . This model explains the observed chiral amplification effect, that is the ee of the epoxide product exceeds the ee of the catalyst. The stereoselective synthesis of cw-epoxyketones from acyclic cw-enones is difficult due to the tendency of the cw-enones to isomerize to the more stable fraw5-derivatives during the oxidation. In 1998, Shibasaki and coworkers reported that the ytterbium-(f )-3-hydroxymethyl-BINOL system also showed catalytic activity for the oxidation of aliphatic (Z)-enones 129 to cw-epoxides 130 with good yields... 

Asymmetric elimination with high induction has mainly been described for epoxides, halides and alcohols (using chiral bases), for chiral ketals (using achiral Lewis acids), and for chiral sulfoximines (using achiral bases)1 3. For each compound class only a few examples have been examined, thus, the scope of these methods has not yet been fully explored. The literature on asymmetric eliminations up to 1970 has been covered in a review article4. 

It should be noted that addition of DBU (or HMPT) has often - particularly for the catalytic procedures - proven beneficial in terms of enantioselectivity. This effect has been attributed to the breaking-up of active but less enantioselective base aggregates [50, 56, 62-64]. Interestingly, when solid-phase-bound stoichiometric (achiral) bases were used instead of LDA, no addition of DBU was necessary [58, 59]. (An example of the stoichiometric use of a chiral solid-phase bound base is given elsewhere [52].) Both experimental and theoretical investigations [66-68] indicate that the base-induced isomerization of epoxides proceeds as a syn elimination, with the lithium ion of the base acting as a Lewis acid (Scheme 13.31). 

---