DOB to DOM/DOPR ?????

[SweetChem]

Hi all!!

Is is just words, but if SWIM has his DOB freebase in hand, has he the possibility to make DOM and DOPR with MeI and PrBr using the Grignard reaction ?  Has anyone do the try ?
... crazy synth for sweet dreams ...

[PrimoPyro]

No one here has done that, but I'm not sure if you can. The reason being that for a good yield, I think you may have to make the grignard reagent of the DOB, not the aliphatic chain, like MeMgI or PrMgI.

I personally think this because the grignard attacks positive centers, and the benzene ring is so very negative. When the grignard is made of the ring, it attacks the alpha carbon to the aliphatic halide, and couples just dandy. But I don't think the benzene ring (especially the activated ring in the 2,5-DiMeO version) is significantly positive to be attacked by a grignard in good yield.

This means that it would only work if you made DO-MgBr. But this is not possible with DOB freebase, as grignards won't form of amines. If you had the full ketal of the preceeding ketone of DOB, it would work. You would couple your alkane, quench the reaction, hydrolyze your ketal, and then add your amine.

But with the amine there, no way to form the grignard. Too reactive. You might want a second opinion on the ring grignard necessity, as it is just my personal theory.

                                                     PrimoPyro
Vivent Longtemps la Ruche!

[SweetChem]

Merci Men!!

But is it possible at the aldehyde or nitropropene state???
... crazy synth for sweet dreams ...

[PrimoPyro]

The aldehyde would also have to be made into the acetal (versus the ketal I spoke of before).

The carbonyl group on the aldehyde will react with your grignard, forming an alcohol. You prevent this by condensing the aldehyde with an alcohol to change it into an acetal, which is a gem diol diether. Ethers are unreactive to grignards.

This is easily accomplished. Acetals are prepared from the aldehyde, an alcohol (methyl or ethyl for instance) and small amounts of acid, say HCl in EtOH would do. But the acetal route really is too difficult.

The acetal cannot be used as is. During the formation, water is produced, which must be removed for the grignard to proceed, and the acid traces will quench the grignard as well. So the acetal must be purified.

As for the nitropropene, Im sorry to say, I really have no idea. Aren't nitropropenes very picky, condition-wise? They seem to be little bitches when people speak of them as far as stability, but I could be wrong. I seriously don't know if they are stable in grignard reactions.

                                                  PrimoPyro
Vivent Longtemps la Ruche!

[yellium]

You might want a second opinion on the ring grignardnecessity, as it is just my personal theory.

BTDT, grignard is very difficult to start. BuLi/MeI works better.

[PrimoPyro]

BTDT, grignard is very difficult to start. BuLi/MeI works better.

Dearest hest: What does BTDT mean? And I am unaware of how MeI would produce DOM. Could you tell me, please.  

I just had an idea:
Could one react acetone enolate with the bromine to get the phenylacetone derivative, then reduce the carbonyl with LAH to get DOPr?

                                                   PrimoPyro

Vivent Longtemps la Ruche!

[Acme]

What you are proposing is called a Wurtz coupling, not a Grignard

[hest]

PrimoPyro, where doo I come into all this ??

[PrimoPyro]

Im sorry yellium and hest. I dont know why, but I thought hest had posted what yellium did. Sorry for the error.

Correction: Yellium, how does Bu/Li couple MeI with DOB?

                                                   PrimoPyro
Vivent Longtemps la Ruche!

[slappy]

Correction: Yellium, how does Bu/Li couple MeI with DOB?

It doesn't. You can't prepare a Lithium/Gringnard reagent in the presence of an amine. But, here's the route I would take:

2,5-Dimethoxybenzaldehyde -> 2-(2,5-dimethoxyphenyl)-[1,3]dioxolane -> 2-(4-Bromo-2,5-dimethoxyphenyl)-[1,3]dioxolane -> 2-(2,5-Dimethoxy-4-Phenyllithium)-[1,3]dioxolane -> -> 4-Methyl-2,5-Dimethoxybenzaldehyde -> -> DOM

Start with 2,5-Dimethoxybenzaldehyde, react that with Ethylene Glycol and catalytic p-Toluenesulfonic Acid to get your dioxolane acetal. Then run that with N-Bromosuccinimde in Acetonitrile for 4 hours at 20°C to get 2-(4-Bromo-2,5-Dimethoxyphenyl)-[1,3]dioxolane. Lithiate that in THF with n-Butyllithium, then add MeI or PrI dropwise to the solution. Then you can get your aldehyde back by treating it with 5%HCl in THF. Whalah!