What do rock climbing and synthetic organic chemistry have in common?

During a bouldering session last fall, I found myself talking to some fellow climbers about a tool we use in organic chemistry called “retrosynthetic analysis.” My climbing buddy, a coworker from the lab, mentioned the term as he was coaching me through visualization for a route that I’d attempted a few times but hadn’t yet been able to finish. Another climber nearby asked, “what’s that science word you just used?” and we enthusiastically explained: retrosynthetic analysis is a method of thinking in reverse.

You see the end goal in front of you, and visualize how to work backward from there, one step at a time. I was struggling to complete the climb because I wasn’t getting myself into the right spot to execute the last two critical moves, and my friend was encouraging me to work backwards from those last steps to see what I position I’d need to be in to implement them. Then, I could focus on how to approach the early part of the route so I could get there.

If you distill synthetic organic chemistry, one of the fundamental elements it breaks down to is creative problem solving. Thinking about how to make complex molecules has taught me a lot about this, not only in the specific sense (how to strategically design a synthetic route to a target structure), but also in the general sense—how to approach a problem from multiple angles and what to do when you keep hitting dead ends.

There are two primary ways to think about how to synthesize a complex molecule. The first is to consider the finished product and try to imagine what starting materials it could originate from, thinking about constructing the molecule from the ground up. This is thinking about the synthesis in the forward direction. But looking at a complex structure and trying to envision what simple building blocks to start with can be pretty difficult, sort of like looking at a fully assembled piece of furniture and trying to figure out (without the instructions) which two components should be joined together first.

The other strategy is to consider the target molecule and imagine what it might look like one step before completion, thinking about what final reaction or series of reactions (or moves in the case of rock climbing) could get you across the finish line. Then, you visualize what the penultimate structure would have to look like to facilitate that final transformation (or in the climbing analogy, where/how you’d need to be positioned in order to make that last move). The idea is you are working backward instead of forward. This is the essence of retrosynthetic analysis: thinking in reverse.

There are advantages to both approaches, and chemists must consider each when developing a synthetic route, but retrosynthetic analysis (or “retrosynthesis”) offers some unique benefits. Retrosynthetic analysis helps you identify where you want to be right before you complete the route (on the wall or in the synthesis). Thinking this way allows you to focus on what the problem looks like when it’s nearly solved, rather than starting all the way back at the beginning where things are nowhere near finished.

The fundamental concept of retrosynthetic analysis—working backward instead of forward—can be applied to problem-solving scenarios beyond the lab. Even though I no longer do complex molecule synthesis, I still find myself applying what I’ve learned in other ways. So next time you’re faced with a challenging task and find yourself stuck, try thinking in reverse.