November 06, 2024, 02:42:16 AM
Forum Rules: Read This Before Posting


Topic: Removing TMS-protection in presence of sensitive groups  (Read 11518 times)

0 Members and 1 Guest are viewing this topic.

Offline asa029

  • Regular Member
  • ***
  • Posts: 64
  • Mole Snacks: +1/-0
Removing TMS-protection in presence of sensitive groups
« on: May 07, 2012, 02:29:46 AM »
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?

Offline discodermolide

  • Chemist
  • Sr. Member
  • *
  • Posts: 5038
  • Mole Snacks: +405/-70
  • Gender: Male
    • My research history
Re: Removing TMS-protection in presence of sensitive groups
« Reply #1 on: May 07, 2012, 05:22:57 AM »
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
Development Chemists do it on Scale, Research Chemists just do it!
My Research History

Offline OC pro

  • Chemist
  • Full Member
  • *
  • Posts: 396
  • Mole Snacks: +36/-15
  • Gender: Male
Re: Removing TMS-protection in presence of sensitive groups
« Reply #2 on: May 07, 2012, 02:23:37 PM »
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.

Offline discodermolide

  • Chemist
  • Sr. Member
  • *
  • Posts: 5038
  • Mole Snacks: +405/-70
  • Gender: Male
    • My research history
Re: Removing TMS-protection in presence of sensitive groups
« Reply #3 on: May 07, 2012, 03:54:35 PM »
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.
Development Chemists do it on Scale, Research Chemists just do it!
My Research History

Offline asa029

  • Regular Member
  • ***
  • Posts: 64
  • Mole Snacks: +1/-0
Re: Removing TMS-protection in presence of sensitive groups
« Reply #4 on: May 09, 2012, 01:24:20 AM »
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.

Offline discodermolide

  • Chemist
  • Sr. Member
  • *
  • Posts: 5038
  • Mole Snacks: +405/-70
  • Gender: Male
    • My research history
Re: Removing TMS-protection in presence of sensitive groups
« Reply #5 on: May 09, 2012, 01:29:29 AM »
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?
Development Chemists do it on Scale, Research Chemists just do it!
My Research History

Sponsored Links