Reactivity of dehydroamino acids and dehydrodipeptides towards N- bromosuccinimide: Synthesis of β-bromo- and β,β- dibromodehydroamino acid derivatives and of substituted 4-imidazolidinones

Article abstract of DOI:10.1002/ejoc.200700669

We have developed a modification of our previously reported high-yielding method for the synthesis of N,N-diacyldehydroamino acid derivatives to prepare N-monoprotected dehydroamino acids and dehydrodipeptides. Thus, several dehydroalanine, dehydroaminobutyric acid and dehydrophenylalanine derivatives have been prepared by treating the corresponding L-serine, L-threonine and D,L-3-phenylserine (threo-type) derivatives with 1 equiv. of di-tert-butyl dicarbonate and 4-(dimethylamino)pyridine. The reaction proceeded with the initial formation of an O-tert-butyl carbonate which, by treament with N,N,N′,N′-tetramethylguanidine, underwent β elimination to give the corresponding dehydroamino acid derivative. This two-step method can be carried out as a one-pot procedure and is stereoselective, giving only the Z isomer. The N-monoprotected dehydroamino acids were treated with N-bromosuccinimide and thereafter with triethylamine to afford several β,β-dibromodehydroalanines or β-bromo-, β-alkyl- or β-aryldehydroalanines. The latter were obtained as mixtures of E and Z isomers. An increased stereoselectivity towards the formation of the Z isomer was observed with dehydrophenylalanine and when 4-tolylsulfonyl was used as the N-protecting group. In the case of dehydrodipeptides, the reaction with NBS and triethylamine afforded the corresponding brominated dehydrodipeptides when the N-protecting group was other than 4-tolylsulfonyl. However, when the reagent was a peptide with a dehydroamino acid as the second residue and an N-(4-tolylsulfonyl) group the corresponding 2,2-disubstituted 1-(4-tolylsulfonyl)imidazolidin-4-ones were obtained in good-to-high yields. Wiley-VCH Verlag GmbH & Co. KGaA, 2007.