90 Indoles
C-Metallated indoles
N-Substituted indoles can be C-deprotonated, with very strong bases, selectively at the -position (2-position), producing
organometallic intermediates, which can react with even weak electrophiles, for example carbonyl compounds, giving
-substituted products. This can be carried out using appropriate removable N-protecting groups. Several of the com-
monN-protecting groups also assist the regioselective -lithiation via intramolecular co-ordination and electron with-
drawal, for example phenylsulfonyl. Amongst other useful removable indole-N-protecting groups are t-butoxycarbonyl
and diethoxymethyl. The examples below illustrate the importance of this lithiation methodology in indole chemistry.
Another elegant device for N-protection involves indole-N-carboxylation (base and CO 2 ) before -lithiation, that is, for-
mation of the lithium salt of a carbamic acid. (A carbamic acid has the general formula R^1 R^2 NCO 2 H; a carbamate ester
is R^1 R^2 NCO 2 R^3 .)N-Lithiation, addition of CO 2 , then reaction with an electrophile at C-2 and N-deprotection are carried
out all in one pot, without isolation of intermediates – the scheme shows how this works for a synthesis of 2-iodoindole.