Synthesis and Retrosynthesis Strategies | Organic Chemistry 1
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.
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
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