Students of Organic Chemistry see aromatic chemistry twice, and retrosynthesis is a predominant theme. It is presented the first time as electrophilic aromatic substitution (EAS), and the second time as nucleophilic aromatic substitution (SNAr). Presented alongside SNAr reactions is benzyne chemistry. With benzynes, students are once again exposed to Diels-Alder chemistry. The Claisen Rearrangement is also introduced around this time. Interestingly, many things once thought past come back all of a sudden. What happens when all these tricks are incorporated into one single exam question based upon a Claisen/Diels-Alder sequence? Even more, what happens when the entire final for Organic Chemistry II is made up of combination questions requiring retrosynthesis? Suddenly you feel like your brain is being forced through a wormhole connecting two apparently unrelated areas in space-time.
One of the exercises practiced by distinguished professors of Organic Chemistry at leading universities is having their graduate students propose a multi-step total synthesis for an interesting natural product surfacing in the literature. To date, I’ve never seen a professor do this for an undergraduate class, however I believe it would be a positive exercise in a group environment to facilitate mastery of the principles. Easily assigned as a graded homework assignment, it could be used in place of a midterm to permit students the opportunity of performing without the pressure of a timed exam.
When students study Organic Chemistry via the two semester system, they really don’t get the opportunity to “understand” it until the second semester, when the course takes upon an emphasis of organic reaction mechanisms. The systematic learning Organic Chemistry is very much like learning a language. One first needs to memorize the vocabulary, then comes the proper use of verbs. The third step involves assembling coherent sentences from words. Natural flow of sentences not involving “interpretation” marks the student’s budding ability to “think” in terms of the language. Finally, there is fluency which can also be accompanied by dreaming in the language.
The first really interesting reaction seen by Organic Chemistry students is the Diels-Alder [4+2] cycloaddition, an example of a concerted process where all the bond making and breaking take place concomitantly. The SN2 is also a concerted process, however the Diels-Alder reaction is a gem because of the high density of relative stereochemistry that can be established in a single synthetic step. The most interesting and unique of all organic reactions learned fall within the narrow category of sigmatropic rearrangements, intramolecular pericyclic processes wherein one σ-bond is exchanged for another σ-bond. Example reactions are the Cope and Claisen rearrangements.