Ozonolysis is one of the simplest of all organic reactions to perform, yet the ozonolysis mechanism often leads to confusion when presented in undergraduate Organic Chemistry. If the reaction is so simple, then why is the ozonolysis mechanism so challenging? Well, there’s the 1,3-dipolar cycloaddition followed by a retro 1,3-cycloaddition and recombination via a second 1,3-cycloaddition leading to an intermediate with an electrophilic oxygen that gets attacked by a sulfur nucleophile. Sounds kinda like listening to someone’s story of getting from point A to point Z via a tour through La La Land, huh?
In Part I, there was an example of a crossed Aldol Condensation leading to a mixture of products where only one may have been desired. The question was raised, how might one implement control over this reaction? It’s important to note the conditions for the reaction between acetaldehyde (Acet) and propionaldehyde (Prop) utilized NaOEt and EtOH as reagents. This particular choice of reagents leads to “thermodynamic control” over the reaction. The greatest synthetic utility of the Aldol Condensation is realized through carefully implemented kinetic control of the reaction conditions at low temperature using lithium diisopropylamide (LDA) or a comparable base for deprotonation.
Electronegativity, designated by the Greek letter χ, is a property that is also a measure of an atom’s or functional group’s tendency to draw electron density to itself. The Pauling scale of electronegativty ranges from 0.7 to 4.0, with fluorine being the most electronegative element on the periodic table. Aldehydes are endowed with certain special properties due to the dipole existing between carbon ( χ = 2.5) and oxygen ( χ = 3.5). The Δ χ = 1.0, resulting in aldehydes having a polar nature. One such property is increased acidity of α-protons relative to alkanes, thereby permitting a particularly useful carbon-carbon bond forming reaction known as the Aldol Condensation.