Enantiodivergent reactions

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. 

The relative rates of faster reacting slower reacting amine enantiomers was shown to be 27 1, by a quantitative measure of each rate on pure enantiomers of 2-methylpiperidine. Interestingly, resolution with diastereomeric quinazoline 32b gave as the benzoylamide product the enantiomer of the above experiment, suggesting that the axis of chirality controls the enantiomer selectivity. For the use of similar quinazolines in enantiodivergent reactions, see Scheme 6.28. 

The nitrone 61b underwent stereoselective 1,3-dipolar addition to the sugar-derived racemic lactone 65, to give the adduct 66 (82% de). The unreacted 65 was recovered in 77% ee [60]. See Scheme 6.34 for a similar system used in an enantiodivergent reaction. 

A wide diversity of products may be generated from the transformation of a racemic mixture under the action of an enantiopure reagent. An interesting situation is the preferential formation of two products, one deriving exclusively from the (R)-substrate and the other one deriving from the (S)-substrate (Scheme 2.4a). This is an enantiodivergent reaction - Pjj, Sg -> Pg. The actual situation is... 

Enantiodivergent Reactions Divergent Reactions on a Racemic Mixture and Parallel Kinetic Resolution... 

Introduction The Conceptual Basis for Kinetic Resolution and Enantiodivergent Reactions... 

Introduction The Conceptual Basis for Kinetic Resolution and Enantiodivergent Reactions 221 TCBu = Me2(Cl3C)C Nph = 1-naphthyl C oHiy = fenchyl... 

Chiral organometaUic reagents offer the broadest range of possibilities for enantiodivergent reactions. The oldest and most extensively studied cases involve displacement reactions of allylic C—O bonds to give regioisomeric products under... 

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