Meso-anhydrides applications

Desymmetrization of prochiral cyclic anhydrides In the presence of the chiral nucleophilic catalyst (e.g. A, Scheme 13.1, top) one of the enantiotopic carbonyl groups of the prochiral (usually meso) cyclic anhydride substrate is selectively converted into an ester. Application of catalyst B (usually the enantiomer or a pseudoenantiomer of A) results in generation of the enantiomeric product ester. Ideally, 100% of one enantiomerically pure product can be generated from the starting anhydride. No reports of desymmetrizing alcoholyses of acyclic meso anhydrides appear to exist in the literature. 

The field of organocatalytic enantioselective anhydride transformations has seen tremendous progress during recent years. For example, the alcoholytic desymmetrization of meso anhydrides, effected by stoichiometric quantities of inexpensive and readily available cinchona alkaloids, has been developed to a very practical level, and several applications, e.g. for the synthesis of enantiomerically pure... 

The cinchona-catalyzed alcoholysis of meso-anhydrides has been successfully applied to the synthesis of key intermediates for a variety of industrially interesting biologically active compounds. Some selected examples are summarized in Scheme 11.13. More detailed information on the synthetic application of this reaction is available in the recent comprehensive review of this topic by Bolm et al. [la]. 

Scheme 11.13 Applications of alcoholytic desymmetrization of meso-anhydrides.

W.-M. Dai, K.K.Y. Yeung, C.W. Chow, I.D. Williams, Study on enantiomerically pure 2-substituted N,N-dialkyl-l-naphthamides resolution, absolute stereochemistry, and application to desymmetrization of cyclic meso anhydrides. Tetrahedron Asymmetry 12 (11) (2001) 1603-1613. 

In this chapter, we attempt to review the current state of the art in the applications of cinchona alkaloids and their derivatives as chiral organocatalysts in these research fields. In the first section, the results obtained using the cinchona-catalyzed desymmetrization of different types of weso-compounds, such as weso-cyclic anhydrides, meso-diols, meso-endoperoxides, weso-phospholene derivatives, and prochiral ketones, as depicted in Scheme 11.1, are reviewed. Then, the cinchona-catalyzed (dynamic) kinetic resolution of racemic anhydrides, azlactones and sulfinyl chlorides affording enantioenriched a-hydroxy esters, and N-protected a-amino esters and sulftnates, respectively, is discussed (Schemes 11.2 and 11.3). 

In 1946, Moses W. Goldberg (1905-1964) and Leo H. Sternbach from Hoffmann-La Roche filed the first of several patent applications relating to the synthesis of biotin (Fig. 7.48). The starting material was fumaric acid, which was tra/is-dibrominated. NucleophEic substitution with benzylamine, cyclisation with phosgene and treatment with acetic anhydride gave the cis-substituted meso-imidazolidinone, which was converted with cydohexanol into the halfester. The enantiomers were then separated with (-)-ephedrine. Alternatively,... 

The most important technical applications of catalytic hydrolysis and acylation involve technical enzymes, as used in food processing, washing powders, or derace-misations. Especially the latter application has also found significant application in chemical synthesis. The kinetic resolution of chiral, racemic esters, anhydrides, or alcohols relies on the faster conversion of only one substrate enantiomer by the chiral catalyst, whereas the other enantiomer ideally remains unchanged. A special case within kinetic resolutions is the desymmetrization of prochiral mexo-compounds like mera-anhydrides (2) or meso-diols, (5) that requires a selective conversion of one of the two enantiotopic functional groups (carbonyl or OH-group, Scheme 7.1). 

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