Synthesis and electrochemical behaviour of β-halodehydroamino acid derivatives

Abstract

Several new beta,beta-dihalo and beta-halo-beta-substituted dehydroalanines and dehydrodipeptides were synthesized by reacting the corresponding dehydroamino acid derivative with a N-halosuccinimide or in the case of beta,beta-di-iododehydroalanines with iodine. The results obtained confirmed that the stereochemical outcome of the halogenation reaction with beta-substituted dehydroamino acids depends on the substrate. Thus, an increase Z-stereoselectivity was found when the beta-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 beta-halogenated dehydroamino acids when compared with the corresponding non-halogenated derivatives. As expected, the beta,beta-dihalodehydroalanines exhibit higher peak potentials than beta-halo-beta-substituted dehydroalanines and the bromo derivatives have lower peak potentials when compared with the corresponding iododehydroamino acids. Controlled potential electrolysis of several beta-halo-beta-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 beta-substituted dehydroalanines.