Enantiodivergent process

In a more recent study, the same organism (R. rubra) was used in an attempt to obtain enantiomerically enriched cyclopentanone alcohol (R)-20 by simple KR (Scheme 6.4) [13]. Although KR did occur under conditions of >50% conversion, the products contained a saturated cyclopentanone (R)-21 (>99% ee) as well as the expected unsaturated diol (S)-22 (>99% ee) and recovered slow-reacting enantiomer (R)-20 (>99% ee). This is a rare example where an enantiodivergent process affords products that differ in functionality rather than just stereochemistry. Although the reaction was not taken to 100% conversion, this modification would allow near-total recovery of individual enantiomers by separating the products (R)-21 and (S)-22. 

The nature of the organometal compound can of course only influence the diastereoselectivity of an addition reaction. If enantiocontrol is desired a chiral ligand is required. Here complementary stereoselectivity can be accomplished via the type of coordination of the metal atom, hence the influence of hi- versus tridentate ligands. Organozinc additions to aldehydes provide an illustrative example for such an enantiodivergent process. 

Vedejs and Chen [39] described an efficient non-enzymatic system able to approach the efficiency of some of the lipase methods in enantioselectivity. The reaction was carried out in a 2 1 ratio racemic secondary alcohol acylating agent, in contrast to Evans procedure. The pyridinium salt 8 was prepared by reaction of the chiral 4-dimethylaminopyridine (DMAP) 6 with the commercially available chloroformate 7. This pyridinium salt proved to be unreactive to secondary alcohols. The reactivity was found only upon strict experimental conditions addition of a Lewis acid, then the racemic alcohol, followed by addition of a tertiary amine gave the carbonate 9. Under these conditions (using MgBr2 and triethylamine), (2-naphthyl)- -ethanol was converted (room temperature, 20 h and 54% conversion) into the (S)-carbonate (82% ee). The recovered alcohol showed 83% ee, revealing a stereoselectivity s=39 for the process. A number of 1-arylalkanols have been resolved by this procedure in 20-44% yield (based on the racemic material) and 80-94% ee. For the use of this system in enantiodivergent reactions, see Schemes 6.1 and 6.32. 

Several other PKR experiments are shown in Scheme 6.41. Enantiodivergent derivatization of nitrone enantiomers 196 and mM96 was achieved by cycloaddition with quaxi-enantiomeric alkenes 197 and 198 [64]. The process affords separable adducts 199 and 200, a result that could be useful if both substitution patterns are desired. A more flexible process is the Michael addition of quaxi-enantiomeric hthium amides (S)-202 and (R)-203 to the racemic enoate (R,S)-201 [65]. The... 

An alternative process to the use of enantiodivergent ligands and applicable to add more functionalized organozinc species is the use of reagents 25a and 25b in a catalytic form [11]. This reaction is enantioselectively catalyzed in the addition process of organozinc compounds to generate 1,3-diols. 

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