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Topic: deprotection of benzyl groups in the presence of alkynes  (Read 714 times)

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Offline OrganicDan96

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deprotection of benzyl groups in the presence of alkynes
« on: November 08, 2019, 06:12:03 AM »
hello everyone, i have a bit of a synthetic problem, I have a molecule with several terminal alkynes and some benzyl ethers i need to be able to deprotect the benzyl ethers leaving the alkynes intact. obviously the standard hydrogenation conditions would hydrogenate the alkynes. I have found conditions using BCl3 and pentamethyl benzene (https://www.organic-chemistry.org/abstracts/lit2/213.shtm) has anyone had any luck with these conditions? or does anyone know of any reliable conditions for such a transformation?

Offline AWK

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Re: deprotection of benzyl groups in the presence of alkynes
« Reply #1 on: November 08, 2019, 07:28:33 AM »
For terminal alkynes, chloroboration occurs about 0°C
« Last Edit: November 08, 2019, 07:59:00 AM by AWK »
AWK

Online rolnor

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Re: deprotection of benzyl groups in the presence of alkynes
« Reply #2 on: November 08, 2019, 07:36:28 AM »
TMSI in DCM at 0°C is effective, I dont know if alkynes survive these conditions but I think its OK.


Offline clarkstill

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Re: deprotection of benzyl groups in the presence of alkynes
« Reply #4 on: November 08, 2019, 08:17:58 AM »
(all example of OBn deprotection in the presence of a terminal alkyne that remains unreacted)

Online rolnor

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Re: deprotection of benzyl groups in the presence of alkynes
« Reply #5 on: November 08, 2019, 08:30:30 AM »
You can also use triflic acid/thioanisol, this works for methyl-aryl ethers and probably for benzyl ethers. Do you have Greenś book on protectinggroups?

Offline OrganicDan96

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Re: deprotection of benzyl groups in the presence of alkynes
« Reply #6 on: November 08, 2019, 05:01:39 PM »
You can also use triflic acid/thioanisol, this works for methyl-aryl ethers and probably for benzyl ethers. Do you have Greenś book on protectinggroups?

i have seen TFA/thioanisole in my reading i think i will try this as i know my molecule is stable to TFA

Offline hollytara

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Re: deprotection of benzyl groups in the presence of alkynes
« Reply #7 on: November 08, 2019, 11:29:21 PM »
What is on the other side of the benzyl ether - aryl or alkyl?  It can make a difference. 

If you are using a boron based agent, BI3 is pretty Hot - The B-I bonds are weak and the I- is more nucleophilic.  On a project where you are frequently deprotecting ethers it can be useful to set up a glove box to handle BI3. 

Online rolnor

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Re: deprotection of benzyl groups in the presence of alkynes
« Reply #8 on: November 09, 2019, 04:46:19 AM »
You can also use triflic acid/thioanisol, this works for methyl-aryl ethers and probably for benzyl ethers. Do you have Greenś book on protectinggroups?

i have seen TFA/thioanisole in my reading i think i will try this as i know my molecule is stable to TFA

Obs! Triflic acid is trifluoromethanesulphonic acid, not TFA.

Offline OrganicDan96

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Re: deprotection of benzyl groups in the presence of alkynes
« Reply #9 on: November 09, 2019, 06:10:08 AM »
You can also use triflic acid/thioanisol, this works for methyl-aryl ethers and probably for benzyl ethers. Do you have Greenś book on protectinggroups?

i have seen TFA/thioanisole in my reading i think i will try this as i know my molecule is stable to TFA

Obs! Triflic acid is trifluoromethanesulphonic acid, not TFA.

I know that but i saw TFA in the literature not triflic acid

Offline OrganicDan96

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Re: deprotection of benzyl groups in the presence of alkynes
« Reply #10 on: November 09, 2019, 06:12:46 AM »
What is on the other side of the benzyl ether - aryl or alkyl?  It can make a difference. 

If you are using a boron based agent, BI3 is pretty Hot - The B-I bonds are weak and the I- is more nucleophilic.  On a project where you are frequently deprotecting ethers it can be useful to set up a glove box to handle BI3.

its aryl, how compatible is BI3 with other functional groups?

Online rolnor

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Re: deprotection of benzyl groups in the presence of alkynes
« Reply #11 on: November 09, 2019, 11:37:56 AM »
Thats suprising, is really TFA strong enough acid to cleave a regular benzyl? A p-MeObenzyl for shure but not regular??

Offline OrganicDan96

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Re: deprotection of benzyl groups in the presence of alkynes
« Reply #12 on: November 24, 2019, 11:07:09 AM »
i think i will try a few conditions, triflic acid/thioanisole, BCl3 and pentamethyl benzene or EtSH at -78C. if no luck I may need to look at different protecting groups (PG). the PG needs to survive TFA, NH3, TFA, hydrogenation (raney Ni, OBn seems to stay on), DIPEA. looked at PMB group but probably won't survive TFA.

Offline hollytara

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Re: deprotection of benzyl groups in the presence of alkynes
« Reply #13 on: November 24, 2019, 01:30:28 PM »
The compounds I used BI3 on were dimethoxybenzenes, they also contained alkyl, aryl, and aromatic amine groups.  I can't find any references where BI3 and alkynes react, but BCl3 is used to couple alkynes and aldehydes:

https://pubs.acs.org/doi/10.1021/jo702493j

These workers use a Boron Tris(trifluoroacetate) which is apparently pretty good

http://reag.paperplane.io/00000360.htm

The procedure we used was to dissolve our protected compound in CH2Cl2, cool to 0 C under inert atmosphere.
Add an excess of BI3 in CH2Cl2 via syringe (the syringes used get corroded pretty quickly since BI3 and H2O give HI)
Stir for an hour at 0 under inert atmosphere
Pour into an equal volume of dilute ammonium hydroxide
Separate organic layer, wash with Na2CO3 (to remove HI) and water
At this point we removed CH2Cl2 and either purified by chromatography or did further deprotections.


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