Reactivity of Dehydroamino Acids and Dehydrodipeptides Towards <i>N</i>‐Bromosuccinimide: Synthesis of β‐Bromo‐ and β,β‐Dibromodehydroamino Acid Derivatives and of Substituted 4‐Imidazolidinones

Abstract

Abstract 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 &amp; Co. KGaA, 69451 Weinheim, Germany, 2007)