Abstract
Several new β,β-dihalo and β-halo-β-substituted dehydroalanines and dehydrodipeptides were synthesized by reacting the corresponding dehydroamino acid derivative with a N-halosuccinimide or in the case of β,β-di-iododehydroalanines with iodine. The results obtained confirmed that the stereochemical outcome of the halogenation reaction with β-substituted dehydroamino acids depends on the substrate. Thus, an increase Z-stereoselectivity was found when the β-phenyldehydroalanines were used as substrates and when these compounds were N-protected with 4-tolylsulfonyl or with carbamates. From this study, it is also possible to conclude that when N-iodosuccinimide was used as reagent a much higher Z-stereoselectivity is found. The electrochemical behaviour of the halogenated dehydroamino acids was studied by cyclic voltammetry. The results show a shift in the reduction peak to higher potentials of the β-halogenated dehydroamino acids when compared with the corresponding non-halogenated derivatives. As expected, the β,β-dihalodehydroalanines exhibit higher peak potentials than β-halo-β-substituted dehydroalanines and the bromo derivatives have lower peak potentials when compared with the corresponding iododehydroamino acids. Controlled potential electrolysis of several β-halo-β-substituted dehydroamino acids afforded the corresponding dehalogenated dehydroamino acids as mixtures of their E and Z-isomers. In all cases, the major isomer isolated results from dehalogenation without isomerization. These new results show that electrochemical reduction constitutes a valuable method for the synthesis of the E-isomer of β-substituted dehydroalanines.
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Acknowledgments
Foundation for the Science and Technology (FCT)–Portugal and FEDER (Fundo Europeu de Desenvolvimento Regional) for financial support to Centro de Química (CQ-UM) The NMR spectrometer Bruker Avance II 400 is part of the National NMR Network and was acquired with funds from FCT and FEDER. G.P. acknowledges FCT for a PhD grant SFRH/BD/38766/2007.
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Ferreira, P.M.T., Monteiro, L.S. & Pereira, G. Synthesis and electrochemical behaviour of β-halodehydroamino acid derivatives. Amino Acids 39, 499–513 (2010). https://doi.org/10.1007/s00726-009-0466-x
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DOI: https://doi.org/10.1007/s00726-009-0466-x