Nitroaldol Reaction - Stereochemical Course

Stereochemical Course

One of the commonly accepted models for stereoselection without any modification to the Henry reaction is shown below where stereoselectivity is governed by the size of the R groups in the model (ex. carbon chain) as well as a transition state that minimizes dipole by orienting the nitro group and carbonyl oxygen anti (on opposite sides) each other. The R groups play a role in the transition state of the Henry reaction in that the larger the R groups are on each of the substrates, the more they will want to orient themselves away from each other (commonly referred to as steric effects)

Due to a number of factors, including the reversibility of the reaction, as well as the tendency for easy epimerization of the nitro-substituted carbon atom, the Henry Reaction will typically produce a mixture of enantiomers or diastereomers. It is for this reason that explanations for stereoselectivity remain scarce without some modification. In recent years, research focus has shifted toward modifications of the Henry Reaction to overcome this synthetic challenge.

One of the most frequently employed ways to induce enantio- or diastereoselectivity in the Henry Reaction has been through the use of chiral metal catalysts in which the nitro group and carbonyl oxygen coordinate to a metal that is bound to a chiral organic molecule. Some examples of metals that have been used include Zn, Co, Cu, Mg, and Cr. A depiction of this coordination is illustrated above.