[xshadow]

Have to describe this sequence but I have no idea!!

What   reaction is it?
 

It has been added a carbont atom and also the cyclic oxygen trnasformed in a C=O

[rolnor]

To form a ketone from a phenol it seems you need to make a triflate and use Pd(0)/CO. This is just a part of the synthesis, this seems  complicated. Or is it some clever way to do it??

[xshadow]

To form a ketone from a phenol it seems you need to make a triflate and use Pd(0)/CO. This is just a part of the synthesis, this seems  complicated. Or is it some clever way to do it??

could be!!...We have done organometallic reaction infact

Do you mean Stille reaction  + CO ??
Here at starting I don't have a phenol (but a cyclic ""anisole "" derivative... am I miss something??
THanks

[rolnor]

You need to open the ring with HBr first, then make triflate and somehow transform the formed bromide to boronic acid or stannane. Then ringclose with Pd(0)/CO.
This is a complicated synthesis, it feels backwards.

[xshadow]

You need to open the ring with HBr first, then make triflate and somehow transform the formed bromide to boronic acid or stannane. Then ringclose with Pd(0)/CO.
This is a complicated synthesis, it feels backwards.

Hi
I've tried to do the first step:



Is this  what have you thought before?

Now If I have understood I need to convert  the -Br to a -SnMe3  group

But in order to do then the stille reaction with Pd +CO should the Sn(Me)₃ be bonded to a vinylic/arylic carbon??

Because in all reactions ( with Pd + CO)that  I see in my textbook is alwayas bondes to a sp2/sp carbon...

Ps: bit with the ringlcosing I'll get a "5 atom" cycle...not 6?!
Am I missing  something?


Thanks

[rolnor]

I am sorry, it seems like you will get a five-membered ketone with my method. You can make a acetyl group with Me4Sn/Pd(0)/CO and then ringclose this with the bromide with base. I feel that all this chemistry is not very good, it would be nice if someone could suggest something else.

[xshadow]

I am sorry, it seems like you will get a five-membered ketone with my method. You can make a acetyl group with Me4Sn/Pd(0)/CO and then ringclose this with the bromide with base. I feel that all this chemistry is not very good, it would be nice if someone could suggest something else.

I'm sure that  is an exercise where  I have to use organometallic reactions!!

Anyway I've tried another solutuon:




Where I add the missing carbon + cSn" through a Sn2 reaction with organocuprated on the alkyl halide

I know that organocuprates are very good in Sn2 reaction...than I use Pd + CO
Coul it be?


Thanks

[rolnor]

Thats an interesting solution, maybe it could work. There is a problem when you open the ring with HBr you will hydrolyse the methyl group.

[xshadow]

Thats an interesting solution, maybe it could work. There is a problem when you open the ring with HBr you will hydrolyse the methyl group.

Do you mean that the organucuprate can react with water (in an acidic environment) in an acid-base reaction and so it could be destroyed  before  giving the sn2 reaction...?
thanks

[rolnor]

No, you have a methoxy group and when you open the ring with HBr this will be cleaved.

[xshadow]

No, you have a methoxy group and when you open the ring with HBr this will be cleaved.

so do we have to protect it?!
...But  SiMe3Cl or THP are not stable in acid environment....perhaps benzylether?

PS: the -OMe is bonded to a sp2 aromatic carbon....if I use HBr I don't think Br^- can give a Sn2 substitution on an Aromatic carbon giving the cleavage..or I am wrong??

[rolnor]

No, Br- attacks the methyl group and you get ArOH+MeBr. I think if you get this you can protect this with t-BuDiphenylsilyl without affecting the other hydroxy group because the other has a o-substituent and this bulky protecting group is probable selective for the one without o-substituent. Then when the ketone is finnished you can deprotect it with TBAF and methylate it. Do you know that this cuprate you want to use is known?

[xshadow]

No, Br- attacks the methyl group and you get ArOH+MeBr. I think if you get this you can protect this with t-BuDiphenylsilyl without affecting the other hydroxy group because the other has a o-substituent and this bulky protecting group is probable selective for the one without o-substituent. Then when the ketone is finnished you can deprotect it with TBAF and methylate it. Do you know that this cuprate you want to use is known?

Have to search if it's known!!

But  is SiMe3 (and that derivate)  stable in acidic condition (HBr)??

Because I know that there are two way to cleavage it:
Hydrolisis in Acidic environment
Salt of F-


Here we are in an acidic environment...no?
Thanks

[rolnor]

Yoy first boil with HBr and open the ring+hydrolyse the methyl ether, then you selectively protect the hydroxy that has no ortho-substituent with tBuDPhSiCl

[xshadow]

Yoy first boil with HBr and open the ring+hydrolyse the methyl ether, then you selectively protect the hydroxy that has no ortho-substituent with tBuDPhSiCl

Thankss