Enantioconvergent Transformation

An enantioconvergent transformation leads to a single enantiomeric product from a racemate [51]. Each enantiomer is transformed via independent pathways by the same catalyst or by two different catalysts (Figure 6.6). For example, the hydrolysis of epoxides may proceed with high regio- and stereoselectivity vdth inversion or retention of configuration. Several enantioconvergent transformations of epoxides are reported in the last section of this chapter. 

Langlois JB, Emery D, Mareda J, Alexakis A (2012) Mechanistic identification and improvement of a direct enantioconvergent transformation in copper-catalyzed asymmetric allylic alkylation. Qiem Sci 3 1062-1069... 

Direct Enantioconvergent Transformation of Racemic Allylic Acceptors. 157... 

The direct access to a-chiral allylic boronates and silanes [9] from linear precursors by copper(l)-catalyzed asymmetric allylic displacement with boron and silicon nucleophiles is another major focus of this chapter. A separate section is devoted to direct enantioconvergent transformations of racemic allylic acceptors. 

In an enantioconvergent transformation the diphosphine 296 guided the borocuprate substitution into the anti-Sj direction with the enantiomer 293,... 

Another example of an enantioconvergent transformation of racemic epoxides was reported by Faber and coworkers who employed a chemoenzymatic approach for the synthesis of optically enriched diols. They used an (S)-selective epoxide hydrolase from Nocardia sp. in connection with an add catalyzed hydrolytic step to convergently prepare (S)-diols 41 in good to excellent yields (71-98%) with enantiomeric excess values up to 99% (Scheme 9.13) [75]. 

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). 

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. 

Paedragosa-Moreau, S., Morisseau, C., Baratti, J., Zylber, J., Archelas, A., and Furstoss, R. 1997. Microbiological transformations. 37. An enantioconvergent synthesis of the (l-blocker (R)-Nifenalol using a combined chemoenzymic approach. Tetrahedron, 53(28), 9707-9714. 

The concept of enantioconvergent synthesis has heretofore been virtually restricted to cases in which the chiral center is directly epimerizable such as in a-amino acids. In an alternative view, the separate transformation of two enantiomers via stereochemical 1y complementary pathways into a single enantiomeric series represents a case of enantioconvergence.(D For example, conversion of the enantiomeric alcohols la and lb to Ic via the Z and olefins respectively converge to the same enantiomer of the product derived via a Claisen ortho ester rearrangement (equation 1). (, 3)... 

An enantioconvergent synthesis [64] of (-)-anisomycin (1) has been established starting from both (lt)-(126) and (S)-(134) enantiomers of epichloro-hydrin [65] that could be obtained from o-mannitol (Schemes 15 and 16). The (K)-epichlorohydrin (126) was first transformed to (K)-O-benzylglycidol (128) in 60% overall yield by treatment with benzyl alcohol in the presence... 

The full transformation of a racemic mixture into a chiral product is possible by the combination of formation of a chiral product and a fast racemization of the residual substrate. Dynamic KR is detailed in Chapter 5. There is another strategy for transforming the two enantiomers of a racemic substrate into the same enantiomer of the product (enantioconvergent reactions). Two different types of reactions must concern the two enantiomers. For example, hydrolysis of rac-l-phenyloxirane fuUy converted it into (R)-l-phenyl-l,2-dihydroxyethane in the presence of a biocatalyst [87,88]. The regioselectivity of the reaction is not the same for both enantiomers moreover, hydrolysis at the asymmetric centre occurs with inversion (Scheme 2.8). 

Gutierrez M-C, Furstoss R, Alphand V (2005) Microbiological transformations 60. Enantioconvergent Baeyer-Villiger oxidation via a combined whole cells and ionic exchange resin-catalysed dynamic kinetic resolution process. Adv Synth Catal 347(7-8) 1051-1059. doi 10.1002/adsc.200505048... 

Enantioconvergent biohydrolytic transformation of paraoxide using a bienzymatic process. The sequential use of Solanum tuberosum and Aspergillus niger EHs as biocatalysts led to the formation of enantiopure (/ )-para-chlorophenyl-1,2-diol, a chiral building block for the synthesis of (/ )-eliprodil. 

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... 

Monteide, M.I., Lombard, M., Archelas, A., Cronin, A., Arand, M. and Furstoss, R. (2004) Enzymatic transformations. Part 58 Enantioconvergent biohydrolysis of styrene oxide derivatives catalysed by the Solanum tuberosum epoxide hydrolase. Tetrahedron Asymmetry, 15,2801-2805. 

The process was enantioconvergent. Thus both epoxide enantiomers were transformed to yield the same product enantiomer, and no residual epoxide was obtained, n.d. Not determined. 

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