[asa029]

Hello!

I have a tosylate protected N-heterocycle containing a TMS-protected terminal alkyne. I want to selectively deprotect the TMS and leave the tosylate untouched.

I tried TBAF in dry THF but found that both groups fell off (and I was actually able to isolate TosF from the reaction mixture). I also tried K2CO3 in boiling methanol, but found the same result.

Does anyone have any suggestions to other (milder) methods?

[discodermolide]

Hello!

I have a tosylate protected N-heterocycle containing a TMS-protected terminal alkyne. I want to selectively deprotect the TMS and leave the tosylate untouched.

I tried TBAF in dry THF but found that both groups fell off (and I was actually able to isolate TosF from the reaction mixture). I also tried K2CO3 in boiling methanol, but found the same result.

Does anyone have any suggestions to other (milder) methods?

Try HF/MeCN or acetic acid /methanol at RT or below

[OC pro]

1.0 equiv. TBAF in THF (it is available as stock solution) at 0°C should cleave the TMS-alkyne within minutes without affecting the tosylate. In contrast, you could also try dilute HCl in methanol at room temperature.

[discodermolide]

1.0 equiv. TBAF in THF (it is available as stock solution) at 0°C should cleave the TMS-alkyne within minutes without affecting the tosylate. In contrast, you could also try dilute HCl in methanol at room temperature.

TBAF sometimes contains significant amounts of TBA-OH depending upon its age so it's worth getting a new bottle analysed.

[asa029]

1.0 equiv. TBAF in THF (it is available as stock solution) at 0°C should cleave the TMS-alkyne within minutes without affecting the tosylate. In contrast, you could also try dilute HCl in methanol at room temperature.

As stated in the first post, I allready tried TBAF in THF and it cleaved both the tosylate and the silane. HCl in methanol also cleaved the tosylate.

[discodermolide]

1.0 equiv. TBAF in THF (it is available as stock solution) at 0°C should cleave the TMS-alkyne within minutes without affecting the tosylate. In contrast, you could also try dilute HCl in methanol at room temperature.

As stated in the first post, I allready tried TBAF in THF and it cleaved both the tosylate and the silane. HCl in methanol also cleaved the tosylate.

Did you try the HF/acetonitrile yet?