Synthesis of Branched Tryptamines via the Domino Cloke–Stevens/Grandberg Rearrangement

The
rearrangement
of cyclopropylketone arylhydrazones generated in situ from arylhydrazine hydrochlorides and ketones leads
to formation of tryptamine derivatives. The use of (2-aryl­cyclo­propyl)­ethanones
in the reactions with model 4-bromophenylhydrazine hydrochloride gives
branched tryptamines with aryl groups in the α-position to the
amino group, while (2-methylcyclopropyl)­ethanone gives a mixture of
α- and β-substituted products in a ratio of 1:3. The method
was found effective in the synthesis of enantiomerically pure tryptamine.
Thus, (R,R)-(2-phenyl­cyclo­propyl)­ethanone
gives the (S)-α-phenyltryptamine derivative
with an enantiomeric excess over 99%.