Chapter 14: Organometallic Compounds

How to Plan a Synthesis.....(part 2)

Throughout this page we will collect some simple ideas to keep in mind:

• Most reactions occur at or adjacent to FUNCTIONAL GROUPS.
• FUNCTIONAL GROUPS characterise the reactivity of molecules.

• functional group interconversions (e.g. R-Br to R-OH)
• carbon-carbon bond forming reactions (e.g. reactions of Grignard reagents)

• Recognise the FUNCTIONAL GROUPS in the TARGET.
• Ask yourself how you could make this functional group.
• Use disconnections that correspond to known and reliable reactions.
• Repeat steps these steps to reach available starting materials.

• Write out the plan according to the analysis adding reagents and conditions
• refine plan based on practical results and or a rationale order

• Make synthesis as short as possible.
• Use disconnections that correspond to known and reliable reactions.
• Disconnect C-X or C-C bonds.
• The reactions of alcohols, aldehydes / ketones and carboxylic acids are some of the most important.
• If possible aim for the greatest simplification by disconnecting at the middle of molecules, at branch points or rings from chains or use symmetry (if there is any)
• There are rarely unique solutions, but some are better than others
• As simple as it sounds COUNT CARBONS !

Scenario 1 Lets first consider "disconnecting" the R group by breaking the C-C bond at the functional group.
This would correspond to the reaction of an organometallic reagent (which is equivalent to the carbanion, R-) with methanal (which has an electrophilic C)
Scenario 2 Alternatively we could "disconnect" an H atom by breaking a C-H bond at the functional group.
This would correspond to the reaction of a reducing agent such as lithium aluminum hydride with an aldehyde:

Let's think about disconnections in general. When we break a bond, most likely we will be considering heterolytic reactions involving nucleophiles and electrophiles, so we need to "consider" which fragment is the nucleophile and which is the electrophile. Consider both options, but typically one will make much more sense than the others provided you know how to recognise nucleophilic and electrophilic centers.

© Dr. Ian Hunt, Department of Chemistry