I have long maintained that a greater mastery of mechanisms aids students in solving synthesis problems. The idea makes sense: the better a student understands how a reaction takes place via the mechanism, the better he or she will be able to incorporate that reaction into a synthesis when a specific modification to a molecule is called for. My textbook, therefore, which is organized to facilitate learning mechanisms, should give students a leg up when it comes to designing syntheses.

Hard evidence to support this claim has been difficult to come by until recently, when Professor Alison Flynn at the University of Ottowa published her research (J. Chem. Educ., 2016, 93, 593-604). In her study, she analyzed the work that students at the University of Ottowa wrote down when solving synthesis problems on one of their Organic II exams (the study involved 494 student exams). Her analysis pointed to “six key problem-solving strategies that were most often associated with successful answers”:

– Identified newly formed bonds in the target molecule
– Identified atoms added to the starting molecule to form the target
– Identified key regiochemical relationships
– Mapped the atoms of the starting material onto the target
– Used a partial or complete retrosynthetic analysis
– Drew reaction mechanisms

Drawing mechanisms to help solve a synthesis problem can be appreciated by taking a look at one student’s work that Professor Flynn calls attention to. The student’s work was from the following synthesis problem on the exam:


The student identified the 1,3-relative positioning of the hydroxyl groups and appropriately decided that an aldol reaction should be used. At first, the student chose a self-aldol reaction involving the starting ketone, but then concluded that it wouldn’t work after having drawn out this mechanistic step:


The student then continued by showing this work:


For many years I have been emphasizing to my students that, when solving synthesis problems, mechanisms help. Until Professor Flynn’s paper, I was emphasizing this to students out of instinct—I just knew it in my gut. Now that it seems my intuition has been justified by Professor Flynn’s research, I feel that much more comfortable keeping significant emphasis on mechanisms when teaching synthesis. Therefore, I feel reassured that my mechanistic organization of reactions, which helps student understand reactions better, also gives students an advantage when it comes to designing multistep syntheses. Thank you Alison!

-Joel Karty, Elon University, Author.

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