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%.