4 continued... Adding carbon-carbon forming reactions into
You've learned your reactions and organized them into (at
least) two categories: functional group conversions and carbon-carbon
bond forming reactions. You've got a fresh synthetic problem
in front of you. So now what?
want to think of which carbon-carbon bonds you have to form
to take the starting material into the product.
example, you can think, "well, if I'm starting with cyclohexane,
the carbon-carbon bond I'm going to have to make connects
the cyclohexane ring to the chain containing the carbonyl
can think "which of the carbon-carbon forming reactions
would be useful to make this carbon-carbon bond?" Then
check off the list to see which ones might be used and which
can be eliminated from consideration.
chemistry: This reaction won't work to make this bond.
Acetylide reactions work well only with primary halides.
The acetylide chain would have to attack a ring carbon which
would be a secondary carbon. Also, it's not clear how to
selectively take the resulting alkyne to the ketone since
it would be an internal alkyne.
addition: This won't work. Cyanides add only one carbon.
You need to add three carbons.
reaction: This one might work. Of course, Wittig reactions
form a carbon-carbon double bond and you want a carbon-carbon
single bond. Probably it's best to see if there's a better
route to go before trying this one.
You don't have an aromatic ring in this problem, so this
reaction's out of the question.
reaction. This won't work. The Diels-Alder reaction
forms rings and bicyclic compounds. You already have the
ring in the starting material.
reagents. This reaction should work. Of course, a Grignard
reagent reacts with a carbonyl compound to make an alcohol,
not a ketone. Fortunately, since you've learned all of your
functional group transformations, you know that it's a straightforward
task to take a secondary alcohol into a ketone. This reaction
looks the most promising so try this carbon-carbon bond
you've chosen the carbon-carbon forming reaction, notice how
all the other functional group conversions required to complete
the synthesis seem to fall neatly into place. It's usually
best to work backwards (using the retrosynthesis approach
I discussed in a previous tip), so do that for this problem.
you know the carbon-carbon bond-forming reaction forms
an alcohol, the last step must convert that alcohol to
the ketone in the product. In this case, a number of oxidizing
reagents could be used. PCC or Jones' reagent would work
just fine here. (You could use other chromium reagents
make this alcohol you use the Grignard reagent in the
carbon-carbon bond-making step that you decided upon earlier.
To make a secondary alcohol, you must react the Grignard
reagent with an aldehyde. I chose cyclohexyl magnesium
chloride here as the starting material, but you could
just as easily have gone with cyclohexyl magnesium bromide
(either works fine)
make Grignard reagents you add magnesium turnings to an
alkyl halide. Since I chose in the previous reaction to
make a chloride Grignard reagent, the starting material
I choose in this case is chlorocyclohexane (it would be
bromocyclohexane if you went with the bromo Grignard reagent).
way to add a chlorine to an alkane is to chlorinate
using free-radical chemistry in the presence of light.
the retrosynthesis for this molecule. Notice how the steps
all seemed to be logical once the carbon-carbon bond forming
reaction was chosen.