Furans and Thiophenes 101C-Metallated thiophenes and furans
In thiophene and furan chemistry, there is, of course, no equivalent to the acidic N-hydrogen of pyrrole. Thus, we
can compare strong base metallation of thiophene or furan to the deprotonation of N-substituted pyrroles, and in
the absence of other infl uences, exactly comparable selectivity is observed – exclusive deprotonation at the -position,
adjacent to the heteroatom. The selectivity is further illustrated by the isomerisation of the 3-lithiated heterocycles
(generated from the 3-halides by exchange reactions), to the 2-lithio-heterocycles at temperatures above about 40 °C.
The 2-lithio- and the 3-lithio-species (at low temperature) behave as normal carbon organometallic nucleophiles
and will react with the full range of electrophilic reagents. Grignard reagents can be formed easily from bromo- and
iodothiophenes and, signifi cantly, the 3-isomer does not isomerise to its 2-isomer, even at room temperature.
Lithio-reagents formed by deprotonations under the infl uence of an ortho-directing group (DOM) also feature widely
in the chemistry of thiophene and furan. A nice and illustrative example is the deprotonation of 3-bromothiophene
with LDA: ortho-assistance from the electronegative halogen substituent guides deprotonation to the 2-position, rather
than the other -position (C-5). In contrast, reaction with n-butyllithium brings about a metal–halogen exchange
process and gives 3-lithiothiophene.