When students of general chemistry are taught periodic trends and stoichiometry, they require use of the entire periodic table for the purpose of learning. Most of general chemistry consists of inorganic chemistry and basic physical chemistry. Organic Chemistry, on the other hand, is quite different, and so are Organic Chemist’s. We like to simplify things – that’s the stuff of “lightbulb” moments. There are 41 elements used most frequently on the Organic Chemist Periodic Table. What is the Organic Chemist Periodic Table you might ask? Well, I’m glad you asked that question!
The Art of Retrosynthetic Analysis represents a very powerful tool in synthetic Organic Chemistry, one indispensible in the assembly of complex natural products such as Forskolin and Rhizoxin D (two of my PhD research projects), Taxol and Brevetoxin. Even if one were gifted with the combined brain power of Sir Isaac Newton, Albert Einstein and Stephen Hawking, I guarantee that no chemist would ever be able to synthesize complex natural products without the application of retrosynthetic analysis.
Thus far we’ve looked at both thermodynamic and kinetic control in the Aldol Condensation. This is typically where most undergraduate Organic Chemistry professors conclude discussing the reaction. The topic of stereochemistry, however, is left mostly unexamined due to time constraints. The man pictured to the right, Professor Howard Zimmerman (1926-2012), University of Wisconsin – Madison was an exception to this rule. This article takes the Aldol Condensation one step further by discussing one of the most interesting aspects of the reaction. The article is dedicated to Professor Howard Zimmerman, one of my former mentors who helped shape me as a both a scientist and a teacher, and as a person who pursues the meaning in everything through deductive reasoning.
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.