Enantioconvergent Processes

A number of previous reviews [2-6] have dealt with both deracemization and enantioconvergent processes and hence this chapter will focus primarily on the recent literature. 

Figure 5.1 Schematic illustration of (a) dynamic kinetic resolution, (b) deracemization, and (c) enantioconvergent processes.

As outlined above, enantioconvergent processes require two separate reaction pathways in order to transform a racemic substrate into a single product enantiomer. This is accomplished by employing a catalyst, which transforms one of the substrate enantiomers to the product with retention of configuration. Concurrently, another catalyst, with opposite enantioselectivity and opposite regioselectivity, transforms the other substrate enantiomer with inversion of configuration (Figure 5.24). 

Figure 6.72 An enantioconvergent process leading to an enantiopure epoxide.

Biocatalytic Deracemization Dynamic Resolution, Stereoinversion, Enantioconvergent Processes and Cyclic Deracemization, in Biocatalysts in the Pharmaceutical and Biotechnology industries, (ed. R.N. Patel), CRC Press, Boca Raton, pp. 27-51. 

The above procedure can be exploited for the asymmetric oxidation of racemic sulfoxide1 1, and high stereoselection can be frequently observed. Moreover unreacted / -sulfoxides were always recovered as the most abundant enantiomers, kinetic resolution and asymmetric oxidation being two enantioconvergent processes. Thus, by the combined routes, higher enantioselectivity can be observed with dialkyl sulfoxides, usually obtained with poor to moderate e.e.s. 

Thus, racemic 62 can be resolved enzymatically to give either C15 diaste-reomer of 61, simply by using the appropriate enzyme. Because it was observed that the C15 stereocenter of 62 epimerizes faster in the presence of base [87, 88] (e.g., EtsN) than that of 61, even an enantioconvergent process is possible, where 62a and 62b are in constant equilibrium, but only 62a is converted to the corresponding acetate. Enantiomerically pure 61a is then readily converted to 64. 

Enamel, percarbamide safety, 623 Enantioconvergent processes, metal-catalyzed sulfoxidations, 490 Enantiomers... 

Importantly, mixtures of E- and Z-olefin substrates could be hydrogenated with comparable enantioselectivities, providing an enantioconvergent process a highly desirable yet rare feature of a catalytic asymmetric reaction. In addition, this transformation effectively differentiates between />,/>-olefin substituents of similar steric demand (e.g., Me/Et, Ar/c-hex), furnishing hydrogenated products with very high enantioselectivity. 

Another strategy for the achievement of an enantioconvergent process was set up using the combination of bio- and chemo-catalysis[107, 109, 121> 122). For instance, 2,2-disubstituted epoxides were selectively resolved by lyophilized whole cells of Nocardia sp. The biohydrolysis proceeds via attack at the less substituted C-atom with excellent regioselectivity thus leading to retention of configuration at the stereogenic center. On the other hand, acid-catalyzed hydrolysis of such epoxides usually proceeds at the more substituted oxirane carbon with inversion. Careful... 

Simeo Y, KrontU W, Paber K. Biocatalytic deracemization dynamic resolution, stereoinversion, enantioconvergent processes, and cyclic deracemization. In Biocatalysis in the Pharmaceutical and Biotechnology Industries, Ed. Patel RN. CRC Press, Boca Raton, PL, 2007, p. 27. 

Furstoss and collaborators have shown that the partially purified recombinant EH from A. niger LCP 521 efficiently catalyzes the kinetic resolution of l-chloro-2-(2,4-difluorophenyl)-2,3-epoxypropane at a very high substrate concentration of 500 g/1 using a biphasic process [5]. The unreacted (S)-chloro-epoxide and the formed (R)-chloro-diol were obtained in nearly enantiopure form and nearly quantitative 5tield. Due to tiie fact that the formed (R)-chloro-diol was easily chemically transformed into tile (S)-chloro-epoxide, an enantioconvergent process could be set up. Using the difference in chemical reactivity between the oxirane ring and the chlorine... 

Karboune, S., Archelas, A., Fiustoss, R. and Baratti, J. (2005) Immobilization of the Solanum tuberosum epoxide hydrolase and its ap>plication in an enantioconvergent process. Biocatal. Biotransformation, 23,397—105. 

Kroutil, W., Mischitz, M. and Faber, K. (1997) Deracemisation of ( )-2,3-disubstituted oxiranes via biocatalytic hydrolysis using bacterial epoxide hydrolases kinetics of an enantioconvergent process. /. Chem. Soc. Perkin Trans. 1, 3629-3636. 

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