[OrganicDan96]

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?

[AWK]

For terminal alkynes, chloroboration occurs about 0°C

[rolnor]

TMSI in DCM at 0°C is effective, I dont know if alkynes survive these conditions but I think its OK.

[clarkstill]

Some options:

Lewis acid
BCl3 : https://www.thieme-connect.com/products/ejournals/abstract/10.1055/s-2001-16782
BF3, EtSH: https://pubs.acs.org/doi/abs/10.1021/ja00215a058
BBr3: https://pubs.acs.org/doi/pdf/10.1021/ol0489898

Single electron reduction
Li, naphthalene: https://pubs.acs.org/doi/10.1021/acs.orglett.8b01894

Oxidative
DDQ: https://pubs.acs.org/doi/10.1021/ol034923l

[clarkstill]

(all example of OBn deprotection in the presence of a terminal alkyne that remains unreacted)

[rolnor]

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?

[OrganicDan96]

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

[hollytara]

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. 

[rolnor]

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.

[OrganicDan96]

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

[OrganicDan96]

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?

[rolnor]

Thats suprising, is really TFA strong enough acid to cleave a regular benzyl? A p-MeObenzyl for shure but not regular??

[OrganicDan96]

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.

[hollytara]

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.

[OrganicDan96]

update: since the step this was required was right at the end of a long synthesis and material was precious i made a model substrate to screen conditions. i tested the BCl3/ pentamethyl benzene at -78°C on this and it worked a charm and did not touch the alkynes. so i used it on my real substrate and it seemed  to work well.