Desymmetrizations meso-epoxides

Chromium(salen) catalysts (e.g., 69) are also useM in desymmetrizing meso epoxides. Thus, c/5-stilbene oxide 70 is converted to the (5 ,iS)-aminoalcohol 71 in the presence of eatalytic quantities of 69 in methylene ehloride solution open to the atmosphere. The addition of small quantities of triethylamine was found to dramatically increase enantioseleetivities (by almost 25%). This catalytic system also promotes an efficient aminolytic kinetie resolution (AKR) of raeemie epoxides with C2-type symmetry <04OL2173>. 

NOL-based systems for addition of (substituted) anilines to meso epoxides. Hou found that a ytterbium-BI NO L complex catalyzed desymmetrization of cyclohexene oxide in up to 80% ee [15], Shibasaki demonstrated that a praseodymium-BINOL complex could promote addition of p-anisidine to several epoxides in moderate yields with modest enantioselectivities (Scheme 7.7) [16]. 

Subsequent to the development of the (salen)Cr-catalyzed desymmetrization of meso-epoxides with azide (Scheme 7.3), Jacobsen discovered that the analogous (salen)Co(n) complex 6 promoted the enantioselective addition of benzoic acids to meso-epoxides to afford valuable monoprotected C2-symmetric diols (Scheme 7.15) [26], Under the reaction conditions, complex 6 served as a precatalyst for the (salen) Co(iii)-OBz complex, which was fonned in situ by aerobic oxidation. While the enantioselectivity was moderate for certain substrates, the high crystallinity of the products allowed access to enantiopure materials by simple recrystallization. 

The only notable success to date in the use of (salen)metal systems in catalysis of asymmetric cyanide addition to epoxides was achieved by Pietrusiewicz, who reported the aluminium-catalyzed desymmetrization of phospholene meso-epoxide (Scheme 7.23) in moderate ee [47]. Despite these significant efforts, a truly prac-... 

The principle cost determinant in typical hydrolytic or phenolic resolutions is the cobalt catalyst, despite the relatively low catalyst loadings used in most cases and the demonstrated recyclability with key substrates. From this standpoint, recently developed oligomeric (salen)Co complexes, discussed earlier in this chapter in the context of the hydrolytic desymmetrization of meso-epoxides (Scheme 7.16), offer significant advantages for kinetic resolutions of racemic terminal epoxides (Table 7.3) [29-31]. For the hydrolytic and phenolic kinetic resolutions, the oligo-... 

Figure 6.73 EH-catalyzed desymmetrization of cyclic meso-epoxides.

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. 

An elegant application of this protocol has recently been reported, which relied on the desymmetrization of a meso-epoxide to produce a key intermediate for the synthesis of merrilactone A (Equation (76)).275... 

Related catalytic enantioselective processes [115] Two catalytic procedures for asymmetric addition of cyanides to meso epoxides have been reported [116]. One is the result of work carried out in these laboratories, shown in Eq. 6.24, promoted by Ti-peptide chiral complexes, while the other, developed by Jacobsen and Schaus, is a Yb-catalyzed enantioselective reaction that is effected in the presence of pybox ligands (Eq. 6.25) [117]. Although the Shibasaki method (Eq. 6.21) is not as enantioselective as these latter methods, it has the advantage that it accomplishes both the epoxidation and subsequent desymmetrization in a single vessel. 

Scheme 6.37. Zr-catalyzed enantioselective desymmetrization of meso epoxides proceeds efficiently and with high levels of asymmetric induction.

To avoid the inherent limitations of a kinetic resolution process, the reaction was extended to desymmetrization of prochiral meso epoxides. A number of cyclic di-methylidene epoxides were synthesized and subjected to treatment with Et2Zn in the presence of Cu(OTf)2 and ligands 42 or 43. As in the case mentioned above, ligand 42 was superior in terms of selectivity. Cydohexane derivative 46 gave the ring-opened product with a 97% ee and in a 90% isolated yield, with a y/a ratio of 98 2 (Scheme 8.28). The other substrates investigated produced sigmficantly lower ees of between 66% and 85%. 

Kassab, D. J. Ganem, B., (1999) An enantioselective synthesis of (-)-Allosamidin by asymmetric desymmetrization of a highly functionalized meso-epoxide. J. Org. Chem., 64 1782-1783. 

Pakulskia, Z. Pietrusiewicz, K. M. (2004) Enantioselective desymmetrization of phospholene meso-epoxide by nucleophilic opening of the epoxide.. Tetrahedron ... 

Nugent, W. A. (1998) Desymmetrization of meso-epoxides with halides A new catalytic reaction based on mechanistic insight, J. Am. Chem. Soc., 120 7139-7140. Bruns, S. Haufe, G. (1999) Catalytic asymmetric ring opening of epoxides to chlorohydrins with mild chloride donors and enantiopure titanium complexes.. 

Shibasaki and coworkers have applied heterobimetalhc gallium complexes to the desymmetrization of meso epoxides using phenolic nucleophiles. Complex 35 is... 

In addition, new some epoxide hydrolases have also shown a great utility for the desymmetrization of meso-epoxides. An interesting example is the synthesis of nelfinavir-the active pharmaceutical ingredient (API) of the anti-human immunodeficiency virus drug Viracept-where the (R,R)-diol obtained by opening the meso-epoxide is a suitable starting material. Scheme 10.6 shows a synthetic route to nehinavir [14]. 

Desymmetrization and Kinetic Resolution of Anhydrides Desymmetrization of meso-Epoxides and other Prochiral Substrates... 

It should finally be mentioned that chiral base methodology is not limited to the desymmetrization of meso-epoxides but also enables kinetic resolution of racemic epoxides [57, 63, 65], This (organocatalytic) type of reaction seems, however, to be less prominent than the desymmetrization of meso-epoxides. Some examples of kinetic resolution of chiral epoxides are summarized in Scheme 13.35. 

Cycloadditions [8.2] Desymmetrization of meso-diols [13.3] Desymmetrization of meso-epoxides [13.4]... 

---