Improvements on Retrosynthetic Analysis

Success in organic chemistry is heavily reliant on a student’s ability to identify patterns. Until recently, I organized my course by functional group. It was only after I adopted Joel Karty’s approach that I recognized that the variety of reactions used to synthesize each functional group can vary widely and that this variance makes it difficult for a student to connect patterns in order to complete a synthetic analysis or determine a mechanism. Organizing the course by reaction type gives students a better chance to see patterns and more immediately apply their knowledge to solve new problems. After organizing the course by mechanism, I have observed that students are now less likely to see organic chemistry as an exercise in memorization and more likely to treat it as an exercise for practicing complex problem solving skills.

Karty’s book does an excellent job organizing molecular reactivity by introducing a general mechanism and continually using this mechanism to synthesize a variety of functional groups. After an overview of all elementary steps in Chapter 7, subsequent chapters are paired and devoted to individual steps like nucleophilic addition reactions, nucleophilic addition/elimination reactions, electrophilic addition reactions, and electrophilic aromatic substitution. By focusing intensely on particular elementary steps, each chapter forces students to repeatedly practice using a specific sequence of mechanistic arrows. As students see this pattern develop though a chapter, they are more readily able to apply it to new organic reactions. For example, in Chapter 15, Karty covers nucleophilic addition using strong nucleophiles, and in Chapter 16 he immediately extends the same principals to weak nucleophiles. Since students are so familiar with the mechanistic patterns of nucleophilic addition from Chapter 15, a significant amount class time is saved when it is covered again in Chapter 16. This allows more lecture time to compare the differences between reactions and for reviewing problem sets.

Once a general mechanism is reviewed in lecture, I often use class time to allow students to draw mechanisms for new reactions that have not been formally taught. By focusing on the mechanistic theme to the chapter, students are able to correctly propose new mechanisms more successfully than I have seen in the past. For example, last week after reviewing the general mechanism for electrophilic aromatic substitution of benzene with Br2, students were able to draw the mechanisms for Friedel-Crafts alkylation and acylation without additional instruction. Students were so used to recognizing patters that it was easy for them to solve mechanisms with slight modifications. As students are able to solve new problems on their own, it imparts higher levels of self-confidence that increase later success and improve a student’s overall attitude toward organic chemistry.

As my students are becoming comfortable with a mechanistic pattern, they relay this knowledge into which functional groups can be synthesized. This has allowed them to complete more complex retrosynthetic analysis problems like the creation of polysubstituted aryl rings. I am now able to gradually amp up the retrosynthetic questions in order to review reactions taught earlier in the course. Recognizing patterns along the way to key intermediates aids a student’s ability in breaking apart routes to complex molecules. While students still grumble at the difficulty of multistep retrosynthetic analysis, I feel they are more likely to critically think about pathways to synthesize more complex molecular targets.

— James Wollack, St. Catherine University

James Wollack teaches at St. Catherine University and is currently class-testing the Preliminary Edition of Joel Karty’s forthcoming textbook. Click here to learn more about Prof. Wollack.

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