|Organic Chemistry 4e Carey|
|Online Learning Center
How to Plan a Synthesis
Chapter 14: Organometallic Compounds
How to Plan a Synthesis.....(part 1)
The ideas collected here
are based on the work of E.J.Corey (Nobel Prize 1990) who was one of the
pioneers at trying to design strategies for the synthesis of complex organic
means planning a synthesis backwards, by starting at the product, the
"target" and taking it back a step at a time to simple, available starting
materials or precursors.
In general students dislike these problems because it requires "thinking backwards", good problem solving skills, and a good knowledge of their organic reactions.
In order to "plan" a synthesis, we can break the target down by making a series of "disconnections" - these steps are the reverse of synthetic steps or reactions.
Why do you think most students struggle with synthesis questions ?
By now you will probably have written at least one exam that had a lot of reactions on it.... and many of you will have gone into the exam thinking you knew your reactions, but still got a grade you were less than happy with.
Part of the reason for this is shown by the following cartoon that depicts a typical student response to various organic question types......
|Fill the gap, forwards or backwards|
|Think backwards, but lots of help|
|Think backwards with no help !|
The MORAL ?
KNOW YOUR REACTIONS !
|An instructor will probably expect that you know your reactions inside out and literally back to front. An idea that may help you to prepare for this is treating reactions as a "triangle" of information that connects the starting material, the product and the reagent.|
so "x" = 4
|R-Br + "x"
How to Plan a Synthesis.....(part 2)
Throughout this page we will collect some simple ideas to keep in mind:
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)
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 recognize nucleophilic and electrophilic centers.
In order to become good
at synthesis problems practice
is the best tactic. (it
also helps you learn your reactions)