Mechanistic Studies. The Hoffmann Test

In 1987, Hoffinann introduced a new method for investigating configurational stability [109]. It is particularly usefiil for the investigation of the optical stabihty of organometals, as it does not require the use of these enantiomerically enriched reagents. Furthermore, no enantiomeric excess measurement is necessary. It thus appears as completely different to that of the classical methods run to investigate configurational stability. 

Two separate experiments are necessary, as described below on organolithium compounds [110]. The first experiment involves the reaction of the racemic organolithium with a racemic electrophile, an a-aminoaldehyde, and the determination of the ratio of the diastereomeric products formed. The same experiment is repeated under the same conditions but with an enantiomerically enriched electrophile and the ratio of diastereomers measured as well. The validity of the test requires that these reactions reach completion. 

The comparison of the figures obtained allow to say whether the organometal is configurationally stable or not in the reaction conditions used and on the time scale of the rate of its reaction with the electrophile. If the rate of interconversion of the enantiomeric organometals is much higher than their rate of reaction with the electrophile, then the ratio of diastereomeric products would be the diastereoselectivity (s) measured in the mutual KR experiment, and should be constant all over the reaction. Conversely, if there is no interconversion, the enantiomerically enriched electrophile effects a KR of the organometal and the diastereomeric excess in the product would decrease with the conversion, from a (s — l)/(s -I-1) value to a zero value. 

First experiment racemic organometai R-M + S-M) with racemic eiectrophiie E-R + E-S ) 

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