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

• Published in: Journal of organic chemistry 2017-01, Vol.82 (1), p.790-795
• Main Authors: Salikov, Rinat F, Trainov, Konstantin P, Levina, Anastasia A, Belousova, Irina K, Medvedev, Michael G, Tomilov, Yury V
• Format: Article
• Language: English
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/acs.joc.6b02578

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%.