Natural Science Forum / Chemistry / Organic Synthesis / May 2005

It is one of the systems that works well, it was one of the first good
ones in the literature and it came from Corey group.

You get silylated imidazole in mix with imidazole hydrochloride (source
of protons to activate silylated imidazole) and if you use concentrated
DMF solution the mix turns out to be quite powerful but mild.

NE3 instead of imidazole often works, especialy for TMS-Cl, but you may
need to add something like DMAP.
I have been also using stronger bases like DBU in acetonitrile - it
works even faster but base-sensitive substrates may not like it.

In the classical paper by Corey et al about the protection of alcohol
with TBS- (JACS, 6190 (1972), they mentioned that TBSCl/Py/THF leads to
a very slow reaction specially on hindered alcohols, and they proposed
the use of TBSCl/Im/DMF that, according to them, "proved very
effective."
This must be the origin for the general preference for imidazole.

I am not aware of any detalied analysis of the mechanism of the
silylation of alcohols. I suspect than imidazol works via a very
effective nucleophylic catalysis, but sound experimental data is
lacking as long as I know.

Somebody must perform these kinetic analyses...pleeease.

Best regards.

Gabriel Tojo