Meso cinchona-catalyzed

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). 

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]. 

Enantioselective alcoholysis of racemic, prochiral, or meso cyclic anhydrides can be catalyzed by hydrolases, yielding the corresponding monoesters (Eigure 6.25). In most cases, the enantioselectivity was moderate ]75-77]. Organometallic catalysts or organocatalysts such as cinchona alkaloids are often more efficient than enzymes for the stereoselective ring opening of cyclic anhydrides. 

The catalytic efficiency of the diamines, 24 and 25, derived from the truncated cinchona alkaloids, quincorine and quincoridine, respectively, for the desymmetrization of meso- 1,4-diols was also investigated by Kiindig and coworkers [31a, b[. Both pseudoenantiomers 24 and 25 efficiently catalyzed the desymmetrization of the meso-complex 26 with benzoyl chloride, giving the enantiopure monobenzoylated Cr (CO)3 complexes, 27 and ent-27, respectively, with up to 99% ee (Scheme 11.17). This process will provide easy access to new planar chiral complexes. 

Deng reported the cinchona alkaloid-catalyzed desymmetrization of meso and achiral cyclic anhydrides by alcoholysis [26]. 

Cinchona alkaloid derivatives are rarely applied in large-scale preparations of enantioenriched compounds. One example, though, is the large-scale enantiose-lective desymmetrization of meso-anhydrides (Scheme 6.16) as catalyzed by the C9 O-propargyl ethers of 1 and 4 [38]. 

Song and coworkers further utilized squaramide 33 for methanolytic desym-metrization of meso-glutaric anhydrides (Scheme 10.35) [113, 114]. The authors attributed the high enantioselectivity to the fact that the cinchona-derived dimeric squaramide catalyst does not self-associate. The catalyst can be easily recovered from the reaction mixture after extractive acid/base work up. A thiourea-catalyzed version of this process had been reported by the same authors in 2008 [115]. 

In 2003, Fujimoto et al. reported the asymmetric desymmetrization of meso-1,2-diols with benzoylbromide catalyzed by phosphinite derivatives of cinchona alkaloids 85 (Table 7.6) [109]. The phosphinite derivative 85a of cinchonidme which was generated in situ by using Hiinig s base. 

Table 7.6 Desymmetrization of meso-diol 88 catalyzed by phosphinite derivatives of cinchona alkaloids 85 and 86...

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