Chemoselective vs Regioselective

In this tutorial I want to talk about two terms that a lot of students confuse: chemoselective and regioselective. While they might seem similar, there’s actually an important distinction between the two and what they mean. Let me illustrate with an example.

Let’s start with a reaction between 1-hexene and hydrogen bromide. This is the typical first-semester electrophilic addition to alkenes. There are two possible products here. One, where bromine ends up on the second carbon—the more substituted one. The other, where bromine ends up on the less substituted primary carbon.

If you’re familiar with this reaction, you know the first product is the major product, while the other is unlikely to form in any appreciable amount. So, in theory, both products are possible, but in practice, only one is formed. This is an example of a regioselective reaction.

You might remember terms like Markovnikov product, Anti-Markovnikov product, Zaitsev product, or Hofmann product. These are all examples of regioselectivity. So, if you have one functional group giving multiple similar products—like different halides or alkenes—but one product is major while the others are minor or not formed at all, you’re dealing with a regioselective reaction.

Now, chemoselective is a different classification altogether. For example, imagine a reaction between an unsaturated ketone and sodium borohydride. The starting material has two different functional groups: an alkene and a ketone. Both contain π bonds, but sodium borohydride reacts only with the ketone, producing the corresponding alcohol. The alkene remains unchanged.

So, when you start with two or more functional groups, but only one reacts while the others remain untouched, that’s a chemoselective reaction.

An important thing to remember is that these two terms are not mutually exclusive. A reaction can be both regio- and chemoselective because they describe completely different things.

And that’s the difference between these two terms. EZPZ!