Synthesis: Working Backwards

by James

Let’s start talking about synthesis. Guess where I’m going to start? You might think,  “what bonds form, and what bonds break?”.

Well… yes, but first, let’s start with arithmetic.

Back in first grade, your teacher might have given you questions like this:

4+ 2 = ?

3 + 5 = ?

And you got more and more comfortable with answering those questions. But then, one day, your teacher threw you a curveball.

3 + ? = 9

The first time you saw this it might have looked weird. But then you learned that you could solve them by moving the 3 over to the right hand part of the equation (making it negative) and then solving it that way.

?  = 9 – 3

Believe it or not, we can apply this lesson to organic chemistry questions.

NOW we start with “what bonds break, what bonds form?” (it’s inevitable, I know).

Every time they learn a new reaction, I tell my students to ask themselves  what the “pattern” of bonds forming and bonds breaking for a given reaction is. Here’s the Wittig reaction, for instance. (The same pattern applies for every Wittig reaction)

Now there’s a reason why I tell my students to focus on “bonds formed” and “bonds broken” a lot.   I do it not only because it’s a simplifying way of looking at reactions, but it also works in the reverse direction.

 

So once you’ve learned a reaction in the forward direction, reverse that pattern. This is how you’d go “backwards” from a product, to give you back the starting material. Every “bond formed” becomes a “bond broken” and vice versa.

 

Next, try apply this pattern to different products. In the example of the Wittig reaction provided below, try drawing different alkenes, and applying the “pattern” of the Wittig to give you back different ylides and aldehydes (or ketones).

The more you practice, the better you’ll get.

Getting comfortable with thinking about reactions in the backwards direction is going to be a really valuable skill for doing synthesis.

James

P.S. You might have noticed that there’s more than one way that the alkenes above could be made using the Wittig reaction. Make a note of these reactions for which this is true; it will come in handy when planning a synthesis.

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