Synthesis and Retrosynthesis Strategies | Organic Chemistry 1

The strategies in retrosynthesis are studied in this chapter: the protection/deprotection of chemical function groups, the retrosynthetic analysis, the summary of the chemical transformations seen so far.

Protecting Groups

A molecule usually has more than one chemical function.
In order to get chemoselectivity, we sometimes have to protect one of the chemical functions.
At the end of the specific reaction, a deprotection step gives back the original function.

Alcohol Protection:

 

Without Protection/Deprotection:


 

With Protection/Deprotection:

Retrosynthetic Analysis

Always work backwards (retrosynthetic direction).
Look at the final product and find the immediate precursor(s), keeping in mind the compounds you have in your toolbox ⇒ Count the number of carbons and determine the disconnections you need.

At this point you have two different types of goals:

- modification or formation of a chemical function.
You can use deprotonation, substitution, elimination, oxidation or reduction reactions.

- formation of carbon-carbon bond.
We have seen so far only one possibility: the reaction between organometallics and carbonyls.
 

Do the same with the precursors until you arrive at the starting material.

 

Propose a strategy to synthesize heptan-3-ol, using propanal, butan-1-ol and any inorganic reagents:

 

1st goal: C-C bond formation
⇒ organometallics + carbonyls

 

2nd goal: chemical function modification
⇒ alkyl halide to alkyl lithium

 

3rd goal: chemical function modification
⇒ alcohol to alkyl halide

 

Proposed Synthesis:

Retrosynthesis Strategies

Carbon-Carbon bond formation:

- Organometallics + Carbonyls (chapter 8)
- Organometallics + Epoxides (chapter 9)
 

Chemical Function formation/modification:

- Alkene formation (chapter 7) - Elimination reaction
- Aldehyde to Alcohol (chapter 8) - NaBH4 or LiAlH4
- Ketone to Alcohol (chapter 8) - LiAlH4
- Alcohol to Ketone (chapter 8) - Na2Cr2O7 or PCC
- Alcohol to Aldehyde (chapter 8) - PCC
- Alcohol to Carboxylic acid (chapter 8) - Na2Cr2O7
- Alcohol to Alkyl Halide (chapter 9) - PBr3, SOCl2, HBr
- Alcohol to Ether (chapter 9) - NaOR
- Alcohol to Epoxide (chapter 9) - NaOH
- Alkyl Halide to Ether (chapter 9) - NaOR