Each year, after I teach my class the overview of the ten most-common elementary steps, I feel a great sense of satisfaction because I begin to see students mastering two critical aspects of elementary steps: Drawing curved arrows in the correct way, and correctly predicting products when they are told which step occurs. But after that, there is still another hill to climb: Getting students to draw multistep mechanisms correctly. I tell my students that for any overall reaction that occurs, I can draw curved arrows in such a way as to show the reaction taking place in a single step, and I even show a couple crazy examples with half a dozen curved arrows on a single structure. But that doesn’t make it right. Rather, each overall reaction proceeds by a relatively well-defined set of elementary steps. I expect my students to know that sequence of steps for each reaction—not because they have memorized the mechanism, but rather because the mechanism makes sense. For this to work, I need my students to understand why steps in one order make sense, but in a different order don’t. In other words, I need my students to gain a certain “chemical intuition” about mechanisms, and this is not something I can/should expect students to pick up on their own—I feel it is up to me to teach certain aspects of it to them.

In the context of multistep mechanisms, I teach students four major rules of thumb to help understand why a certain sequence of elementary steps is the way it is, and to further help students devise mechanisms for reactions they have not explicitly seen before.  I refer to these as rules of thumb for the “reasonableness of mechanisms.” These rules are:

  1. Under acidic conditions, strong bases should not appear anywhere in the mechanism; under basic conditions, no strong acids should appear.
  2. Intramolecular proton transfers are usually unreasonable.
  3. Termolecular steps are unreasonable.
  4. Carbocation rearrangements are fast.

These rules are easy to state succinctly like this, and students have no problem accepting them. It takes a little discussion to explain the reasoning for each step, and then only two challenges remain. One challenge is for students to recognize when these rules are (or are not) broken, particularly for Rules 2 and 4. For Rule 2, students need to know that the references for strong acids and bases are H3O+ and HO⁻, respectively. For Rule 4, students need to know that a 1,2-hydride or 1,2-methyl shift that produces a significantly more stable carbocation will beat out other elementary steps. Students just need to be reminded of these things every now and again.

The second, tougher challenge is for students to find an alternate arrangement of steps once they realize that a particular rule has been broken. If Rule 1 is broken, the typical fix is to add a proton transfer step immediately before or immediately after the problematic step. If Rule 2 is broken, the fix is a solvent-mediated proton transfer. If Step 3 is broken, the termolecular step can often be split into two bimolecular steps. If Rule 4 is broken, students need to test for possible carbocation rearrangements to see which one leads to a significant increase in stability.

With these rules in hand, students are much better poised to master multistep mechanisms. But, like anything else, it’s still a matter of practice.

— Joel Karty

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