[orgo814]

Hello,

I would like to get some input on this. I am adding a thiolate to my compound. My compound has both TBS and PNB groups. I am seeing some deprotection of these groups on my compound if reaction is left overnight (which in general is needed for this type of reaction). I can't find much information on this- are TBS and PNB groups unstable to thiolates? I am surprised to see such quick deprotection of these groups.

[phth]

The silyl ether can accept a nucleophile to form a trigonal bypyrimidal geometry, so I don't see why a great nucleophile like a thiolate could react.  I would try changing the solvent and possibly running the reaction at a colder temperature.  If you were running the rxn at room temperature, then I would try -5º in MeOH or MeOH/Acetone, or DMF/water because if you can't get the reaction to go under kinetic conditions then it will not work.

[Dan]

TBS is known to have some sensitivity to nucleophiles (e.g. hydroxide). You could switch to TBDPS, it should be more stable.

For the PNB I guess it is theoretically feasible that your thiol might be able to reduce the nitro group, triggering deprotection. You should be able to isolate the aromatic side product of deprotection and check the oxidation state of N to verify this.