37. Tricky Alcohol Synthesis

In this tutorial, we’re going to look at a transformation where we start from 1-pentene and convert it into 1,4-heptanediol.

The first thing that jumps out is the difference in carbon count between the starting material and the product. We begin with a five-carbon chain and end up with a seven-carbon molecule. That clearly means we’ll need to form a new carbon–carbon bond somewhere along the way.

Looking closer at the structure, I notice that one portion of the molecule is a two-carbon segment with an alcohol sitting two carbons away from the bond-forming position. That setup is a classic hallmark of epoxide opening chemistry. It suggests that the diol we’re trying to make could come from attacking an epoxide with a Grignard reagent.

But here’s the catch: if we were to use a Grignard reagent that contains an alcohol elsewhere in the molecule, that wouldn’t work. Alcohols are not compatible with Grignards. So to get around that, we’d have to protect the alcohol—probably with something like a TMS group—to keep it safe during the reaction. That protection step, though, adds complexity and extra steps to the synthesis. And as a general rule, long, winding synthetic routes are something we want to avoid whenever possible.

So instead of following that tricky path, let’s try looking at the problem from a different angle. We still need to form the same carbon–carbon bond, but this time we’ll build the epoxide from the side that comes directly from our starting material. That approach immediately makes more sense—it’s simple and direct.

Here’s how we’ll put it all together. We start by redrawing 1-pentene and treating it with mCPBA to form the epoxide. Then, we react that epoxide with vinyl magnesium bromide—a Grignard reagent. This opens the epoxide, giving us an alcohol with a terminal double bond. Finally, we carry out a hydroboration–oxidation to convert that terminal alkene into the second alcohol, giving us our target diol.

If you’re wondering why I didn’t suggest the more efficient route from the very beginning, it’s because I wanted to illustrate something important: sometimes your initial instinct in retrosynthetic analysis can lead you in the wrong direction. Retrosynthesis is part science, part art. You have to be willing to backtrack and rethink your plan when it starts feeling too convoluted. That kind of flexibility is how you grow and improve as a problem solver in organic synthesis. You’ll only get better by making mistakes, re-evaluating your strategies, and pushing through the challenge.

Let me know what you thought of this synthesis and if you’d have taken a different approach.