Evans Auxiliaries and a Friend for Aldol Reactions

Using chiral auxiliaries for asymmetric synthesis - diastereoselective aldol reactions with chelating enolates and cyclic transition states. The transition states can be constructed using the Zimmerman-Traxler model.

Motivation in my previous video:

Following selective enolisation, either by hard enolisation with strong bases such as LDA or by soft enolisation methods using a Lewis acid and a weak base, a stereodefined enolate can react with aldehydes in an aldol reaction. Both the nucleophile and electrophile are prochiral and so we form two new stereocentres from this reaction. The reaction is diastereoselective. The diastereoselectivity can be increased by using chelation into a six-membered ring transition state, in which big groups prefer to go equatorial.

A chiral auxiliary can be used to select further for a particular combination of stereocentres that can be formed in this reaction. The chiral auxiliary adds another level of diastereoselectivity and the Evans auxiliary can lead to very high d.r. (diastereomeric ratio). When the aldol reaction is complete, the chiral auxiliary can be cleaved carefully, separate by chromatograhpy, and recycled.

Another type of chiral auxiliary is the lactate auxiliary which uses a stereocentre derived from lactic acid. Both enantiomers of lactic acid are available in the chiral pool. There are similar types of diastereoselectivity observed with these chiral auxiliaries and this topic will be expanded upon in my next video.

REFERENCES

Evans Aldol Reaction:
J. Am. Chem. Soc. 1981, 103, 8, 2127–2129

Lactate Aldol Auxiliaries:
Tet.Letters Vol. 35. No. 48, pp. 9083-9086. 1994

FURTHER DETAIL

Felkin-Anh Model:

Boron aldol reaction:

Another example of use of chiral auxiliaries:

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