[aisha]

Hi All,

I have been given the target molecule 2,3-dimethyl cyclohexanone and i am supposed to give a retrosynthetic analysis and then suggest a synthetic route for this target molecule. I am only allowed to have six carbons in my starting materiall; this would mean that I would have to disconnect at 2 points in the cyclic ring (a few different ways). Does this mean that I will create two synthons (donor and acceptior)with double charges? if so, how do I go about finding a synthetic equivalent for this. I have only encountered synthetic equivalents for synthons with only one charge. I am so confused as to how to disconnect this molecule and then come up with decent starting materials.

Please point me in the right direction. Thanks All.

[sjb]

Well, you don't have to disconnect in the ring, simply removing the 2 alkyl substituents will lead back to a 6-carbon unit that you could make 2,3-dimethylcyclohexanone from. However, you may will probably need different polarities to add the two methyl groups back onto the ring.

Let's see some thoughts en papier, there is not usually just one right answer to retrosynthetic problems.

[aisha]

I'm not sure as to what you mean by needing different polarities...has this something to do with umpolung???

Because after disconnecting the two methyl groups, I have a two charges on the ring, how do I find a synthetic equivalent of a species with two charges?

[sjb]

I wasn't necessarily thinking as far as umpolung, but if you consider alternating the polarities around the ring due to the carbonyl group having an inductive effect you'll see that the carbon next to the carbonyl is possibly slightly electron rich, and the carbon next to that is possibly slightly electron poor.

Can you think of a way to add the methyl group to carbon-2, to get 2-methylcyclohexanone, or alternatively add to carbon-3 to get the regioisomer?

[venkatjohnny]

[quote author=aisha link=topic=25488.msg96211#msg96211


Hi aisha,
your target molecule is 2,3 dimethyl cyclohexanone. You can start from 2-cyclohexenone(conjugated). First u can try (CH3)2CuLi for the conjugate addition to get 3-methyl cyclohexanone. Then u can go for LDA followed by CH3I to get your target molecule, but yield may be low bcz there is a possibility for methylation at 6 position also!!!!! anyway i will try my level best to give some other method for your target molecule.. have a nice time...










Hi All,

I have been given the target molecule 2,3-dimethyl cyclohexanone and i am supposed to give a retrosynthetic analysis and then suggest a synthetic route for this target molecule. I am only allowed to have six carbons in my starting materiall; this would mean that I would have to disconnect at 2 points in the cyclic ring (a few different ways). Does this mean that I will create two synthons (donor and acceptior)with double charges? if so, how do I go about finding a synthetic equivalent for this. I have only encountered synthetic equivalents for synthons with only one charge. I am so confused as to how to disconnect this molecule and then come up with decent starting materials.

Please point me in the right direction. Thanks All.
[/quote]

[sjb]

Hi aisha,
your target molecule is 2,3 dimethyl cyclohexanone. You can start from 2-cyclohexenone(conjugated). First u can try (CH3)2CuLi for the conjugate addition to get 3-methyl cyclohexanone. Then u can go for LDA followed by CH3I to get your target molecule, but yield may be low bcz there is a possibility for methylation at 6 position also!!!!! anyway i will try my level best to give some other method for your target molecule.. have a nice time...

Yes, this was pretty much what I was thinking. I thought about the regiochemistry of the methyl iodide addition, and decided that there was little to choose really between 2,5 and 2,3 addition.

Are you happy on how to make 2-cyclohexenone from cyclohexanone?

It may be possible to do something like 2,3-dibromophenol, protect the phenol, metallate the two bromines and exchange for methyl groups, hydrogenate the aromatic ring, then deprotect and oxidise the alcohol?

(Or even, on further thinking, avoid the protection / deprotection by adding 3 equivalents of BuLi or similar, although this will deprotonate the phenol first, it will also be the last to reprotonate, I think)

Did you have a specific enantiomer or diastereomer in mind?

S