During total synthesis of a natural product, I am facing problem during final step where I need to de-protect around 4 phenolic protections. I tried TBS but it did not last till the final steps. THP didn't cleave. I tried iPrO protection and it did last till final step, but during de-protection with AlCl3, it gave multiple spots. Please give some good suggestions. The protecting group must be stable to mild acids/bases to LDA and to reducing agents like LAH or DIBAL. Also, during deprotection must not lead to racemization.
TBPTS is less labile than TBS. You may try that if you feel that the protecting groups (TBPTS) are tolerant to the subsequent steps. Otherwise Me can also be used which can be taken off by either BBr3 or TMSI.
when using more bulky silyl protections, it was affecting the chiral outcome of the subsequent reaction. I am thinking to use TIPS now.
Regarding PMB protection, I have not tried it. Looking for some literature. Is it easier to introduce?
Yes indeed PMB protection is easier for phenols compared to alcohols.
Try using isopropyl as protecting group and de-protect with borontrifluoride etherate complex at 0 degrees
I already tried isopropyl. But it gave multiple spots. My moiety has iPrO- as well as -OMe groups, and I don't want to lose those OMe groups. BF3 doesn't selectively cleave iPrO, but BCl3 and AlCl3 were reported, but it didn't work out.
t-Butyl ether or Trityl ether may work for you..Considering theri steric effects, they may also assist in the stereo-outcome you are looking for.
These protecting groups can be installed and deprotected under very mild conditions like aqueous H3PO4 or ZnBr2 for the deprotection of t-butyl groups or any mild acidic conditions for deprotection of both groups
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