In planning a synthesis, it's as important to know what not to do as to know what to do. As writ

In planning a synthesis, it's as important to know what not...

Key Concepts

Retrosynthetic Analysis

This is the process of deconstructing a target molecule into simpler precursor structures and planning a sequence of reactions to synthesize it. In synthesis planning, identifying potential disconnections and working backwards helps recognize pitfalls such as incompatible functional groups or inefficient transformations. It is crucial to foresee issues before executing the synthesis in order to avoid unproductive or problematic reaction steps.

Reaction Sequence Planning

The order in which reactions are performed in a synthesis can significantly affect the outcome. A poorly ordered reaction sequence might lead to functional group interference, reagent incompatibility, or the need for redundant steps. Careful planning ensures that intermediate functionalities are either protected or unreactive under subsequent conditions, preventing unwanted side reactions.

Functional Group Compatibility

Understanding how different functional groups interact under certain conditions is essential in multi-step syntheses. Incompatible groups may undergo unwanted side reactions or decompositions if exposed to harsh reagents or reaction conditions. Selecting reaction conditions that are gentle on sensitive functionalities or using strategies to mask reactive sites can prevent these issues.

Protecting Group Strategy

In cases where a functional group is reactive under planned conditions, the employment of protecting groups is crucial. They temporarily 'mask' reactive sites so that other transformations can proceed selectively. A well-planned synthesis considers when and how to introduce and subsequently remove protecting groups without interfering with the overall synthetic route.

Chemoselectivity

Chemoselectivity refers to the preferential reaction of one functional group over another when multiple reactive sites are present. In synthesis design, selecting reagents and conditions that provide selective reactivity minimizes side reactions and leads to higher yields and cleaner product profiles. Recognizing potential selectivity issues in a synthesis plan is key to constructing an efficient and reliable pathway.

Transcript

00:01 Okay, so we're given these schemes here and we have to figure out what is wrong with them and say why it's not possible, the way that it's drawn as is.

00:10 Right.

00:11 So i say just do the chemistry and then figure out what, figure out if the product that you get at the end matches the product that's drawn in the scheme.

00:22 I would say that's my first, that's my first inkling here.

00:25 So let's do step one first, right? so we're going to do frito crafts a salation of the siano.

00:30 Benzene here.

00:32 So i'm just going to do it, right? just for just to do it.

00:39 So, right? so remember that this cyanide group is a deactivating species.

00:44 It deactivates the ring, and that's important for this.

00:47 So those groups are generally meta -directors.

00:50 So we're going to put that three -carbon aso group in the meta position, just as is in the product.

00:55 And then we're going to do step two, which is a nitration.

00:59 And then now we have two electron withdrawing groups, the siano and the aso group are both electron withdrawings.

01:06 So they're both meta -directors, which will both favor position substitution at that, at the meta, the position that's meta to both of those.

01:17 And that's actually going to give you the product that is drawn here.

01:19 So you might have gone through that entire thing and been like, i don't understand what's wrong.

01:23 So this is one of those caveats that you have to remember.

01:26 So the chemistry on paper looks fine, right? in terms of directing, you did fine.

01:32 The thing is, you can't do fidel crafts with a deactivated benzene ring.

01:37 And that's a big caveat, right? so the first step is what's wrong here.

01:42 You won't be able to add that aiso group because you have a cyanol group that's deactivating the ring.

01:49 So that's what's wrong with the chemistry in step a.

01:52 Let's just follow the same kind of chemistry in b here.

01:55 So we have chlorobenzene, and we're going to start by adding, a three carbon, three carbon, uh, apropo group.

02:07 Yeah, we're going to add a proper group.

02:09 So, um, let's do one.

02:12 So, um, chlorine is an ortho power director, right? so, um, the product, it puts it in the power position.

02:19 So we're just going to, um, it probably would favor the power position to the sterix anyway.

02:23 Um, so let's put the propo group in the power position...

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