Desymmetrization of meso-epoxides

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 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-... 

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. 

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

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]... 

Nugent, W. A. Lucini, G. Bonchio, M. Bortolini, O. Finn, M. G. McCleland, B. W., Homogeneous catalysis as a tool for organic synthesis Pure Appl. Chem. 1998, 70, 1041 Nugent, W. A., Desymmetrization of Meso Epoxides with Halides A New Catalytic Reaction Based on Mechanistic Insight J.Am. Chem. Soc. 1998, 120,7139. 

Fig. 2.11 Enzyme-catalyzed desymmetrization of meso-epoxides using epoxide hydrolases of microbial origin that were screened for maximum activity. Note that the relative rate (measured as the turnover frequency, TOE) offormingthe (R,R)-stereoisomer is about 250 times higher than for the (S,S) one.

Highly enantioselective catalytic desymmetrization of meso-epoxides through nucleophihc ring opening was first effectively demonstrated by Nugent, who found that a zirconium trialkanolamine complex catalyzed the addition of azi-dosilanes to meso-epoxides (Scheme 1) [3]. Azide has been the most widely explored nitrogen nucleophile [4,5,6,7], in part due to its utiHty as an amine sur-... 

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]. 

Recent review on enantioselective desymmetrization of meso-epoxides C. Weng, H. Zhang, X. Xiong, X. Lu and Y. Zhou, Asian J. Chem., 2014, 26, 3761-3768... 

The use of amine as the nucleophile for desymmetrization of meso epoxides to provide optically active amino alcohols has been developed by Inaba using BINOL-Ti catalyst [236]. Excellent stereoselectivity and yields were observed... 

Desymmetrization of meso epoxides by ring-opening reaction using thiol as nucleophile catalyzed by chiral salen-Ti Lewis acid was first reported by Hou [238]. Under the optimized conditions, the reaction of meso epoxides in the presence of 5 mol% of catalyst gave the corresponding -hydroxy sulfide compounds in good yields (86-93%) with moderate enantiomeric excesses (46-63%) (Scheme 14.101). The use of BINOL-Ti or salen-Ti catalyst for the same type of reaction afforded the corresponding chiral P-hydroxysulfides in moderate yield and enantiomeric excess values (<73%) [239]. 

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