Reactivity of Dehydroamino Acids and Dehydrodipeptides TowardsN‐Bromosuccinimide: Synthesis of β‐Bromo‐ and β,β‐Dibromodehydroamino Acid Derivatives and of Substituted 4‐Imidazolidinones

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,NЈ,NЈ-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

Synthesis of Novel Nonproteinogenic Amino Acids: N‐Ethyl‐α,β‐dehydroamino Acid Methyl Esters

“…Dehydration was initially attempted by reaction with 1 equiv. of di‐ tert ‐butyl dicarbonate by using DMAP as catalyst, followed by treatment with TMG 13. However, this method led to complex mixtures resulting from tert ‐butoxycarbonylation of the hydroxy group and also of the sulfonamide function.…”

“…of di‐ tert ‐butyl dicarbonate (Boc 2 O) and 4‐(dimethylamino)pyridine (DMAP) as catalyst in dry acetonitrile 12. For the synthesis of N ‐acyl‐α,β‐dehydroamino acid derivatives, a modification of this method was subsequently reported 13. Thus, by treating β‐hydroxyamino acid derivatives with 1 equiv.…”

“…In this paper we report the use of a combination of the alkylation procedure reported by Liguori et al9b and our dehydration methodologies12,13 to obtain new nonproteinogenic amino acids, namely, N ‐ethyl‐α,β‐dehydroamino acids.…”

Recent progress in the application of N-halo reagents in the synthesis of heterocyclic compounds

“…When the N-protecting group was 4-tolylsulfonyl 41 the reaction of dehydrodipeptides with NBS afforded the 2,2-disubstituted 1-(4-tolylsulfonyl)imidazolidin-4-ones 42 in good-to-high yields (Scheme 33, compounds 42aef). 69 These workers believe that the initial step in the formation of these compounds is the bromination of the dehydroamino acid residue by NBS. This is followed by cyclization, which occurs by nucleophilic attack of the nitrogen atom of the sulfonamide moiety on the a-carbon atom of the second amino acid residue.…”

Copper‐Catalyzed Direct Synthesis of Iodoenamides from Ketoximes

“…One proposed mechanism is reductive acylation of the acetophenone oxime acetate intermediate A by Cu + in a two-step single-electron-transfer reaction to afford enamide intermediate C. [22] Next, oxidative iodination of enamide C occurs through a two-step single-electron-transfer oxidation by Cu 2 + (path a). [24] Another possible mechanism is based on oxidative addition of the N À O bond of acetophenone oxime acetate intermediate A to Cu I to generate Cu III intermediate F. [25] After tautomerization and acylation by anhydride, vinyl C À H activation by Cu III occurs to give intermediate H. Finally, reductive elimination of Cu III intermediate H produces iodoenamide 2 (path c). [24] Another possible mechanism is based on oxidative addition of the N À O bond of acetophenone oxime acetate intermediate A to Cu I to generate Cu III intermediate F. [25] After tautomerization and acylation by anhydride, vinyl C À H activation by Cu III occurs to give intermediate H. Finally, reductive elimination of Cu III intermediate H produces iodoenamide 2 (path c).…”