Carbon Carbon Bonds

by Kiley Lynch

What are the most important reactions to know?

Unfortunately, there isn’t a Pareto 80/20 rule for synthesis. But there is a next best thing. If I had to advise mastering one type of reaction thoroughly, it would be this:

Thoroughly learn and understand all the reactions that form carbon-carbon bonds. 
The skeleton of all organic molecules is made of carbon-carbon bonds, and the vast majority of synthesis problems will ask you to start with a relatively simple molecule (containing 4 carbons, say) and build it up to something more complex. This will undoubtedly involve carbon-carbon bond formation.

Here are some key carbon-carbon bond forming reactions to know (focusing on the last few chapters)

  • Grignard reaction: Grignard reagents will add to ketones, aldehydes, and esters to form C-C bonds. Very useful.
  • Wittig reaction: Ylides add to aldehydes and ketones to form C-C double bonds. The resulting alkenes can be “decorated” all kinds of ways.
  • Enolate alkylation: enolates are great nucleophiles. Treatment of a ketone or ester with a strong base and then an alkyl halide is a very useful way to form C-C bonds, via an SN2 reaction.
  • Aldol reaction: enolates will react with aldehydes and ketones to form C–C bonds
  • Claisen condensation: similarly, enolates react with esters to form C–C bonds
  • Michael reaction: enolates also react with enones (alpha, beta unsaturated ketones) to form C-C bonds. Also, enones will react with dialkylcuprates (Gilman reagents) that will form carbon-carbon bonds. Also very useful.

If you focus on getting the carbon-carbon bond formation reactions down first, then you can devote later effort to learning how to “decorate” the carbon skeleton with various functional groups, and interconverting esters into carboxylic acids and so on. But get the carbon skeleton formed first.

Thanks for reading! James