Allylic halogenation of unsaturated amino acids

Abstract

A range of dehydro amino acid derivatives has been prepared and subjected to halogenation using either molecular bromine or chlorine, or NBS. Allylic halogenation of the unsaturated amino acid side chains occurs through radical bromination with NBS. The procedure is complementary to treatment with chlorine, which also affords allyl halides. This latter and unusual reaction is shown through a deuterium labelling study to proceed via an ionic mechanism. The choice of NBS or chlorine for allyl halide synthesis is shown to depend on the potential to avoid competing reactions, such as halolactonization of leucine derivatives with chlorine, and hydrogen abstraction and bromine incorporation at multiple sites on treatment of isoleucine derivatives with NBS. The synthetic utility of the allyl halides prepared in this study is indicated through the synthesis of a cyclopropyl amino acid derivative and the extension of the carbon skeleton of an amino acid side chain.

[3,3]‐Sigmatropic Rearrangement of Cyclopropenylcarbinyl Cyanates: Access to Alkylidene(aminocyclopropane) Derivatives

“…So far, these latter compounds have essentially been prepared by Curtius rearrangement of alkylidene cyclopropanecarboxylic acids B (Scheme , route a) and elimination reactions (of HBr, ArSeOH or Br 2 ) applied to substituted (aminocyclopropyl)methyl compounds C (Scheme , route b) . One example of construction of the three‐membered ring by intramolecular nucleophilic substitution, involving an α‐amino acid derivative D , has also been disclosed (Scheme , route c) . It is worth noting that most of the aforementioned methods were used to prepare methylene(aminocyclopropanes) lacking substituents on the olefin…”

“…[23] One example of construction of the three-membered ring by intramolecular nucleophilic substitution, involving an a-aminoa cid derivative D,h as also been disclosed( Scheme 1, route c). [24] It is worth noting that mosto ft he aforementioned methods were used to preparem ethylene(aminocyclopropanes) lacking substituents on the olefin. [25] Sigmatropicr earrangements involvingc yclopropenylcarbinol derivatives constitute an interesting entry to diversely substituted alkylidene cyclopropanes.…”

Allylic chlorination of terpenic olefins using a combination of MoCl5 and NaOCl

“…[5][6][7] Chlorination represents a valuable pathway to produce versatile starting materials that are widely used in synthetic organic chemistry. [8][9][10][11] Chloride compounds can be prepared directly by bubbling molecular chlorine, but the difficulty of handling chlorine gas limits this procedure. 12 Other authors have shown a convenient method for this transformation using solid CO 2 and calcium hypochlorite 13,14 or a combination of Vilsmeier reagent and H 2 O 2 .…”

In Situ Deprotection and Incorporation of Unnatural Amino Acids during Cell‐Free Protein Synthesis

“…[45] Hydrazide 9 a was prepared from (S)lysine by esterification with thionyl chloride in methanol, followed by treatment of the corresponding ester with hydrazine hydrate. [20] (S)-4,5-Dehydroleucine hydrazide (25) was prepared from N-phthaloyl-4,5dehydroleucine methyl ester (22) [49] by reaction with hydrazine hydrate. [48] (S)-4-Fluoroleucine hydrazide (23) was prepared by the protection of (S)-leucine, bromination of phthalimide 19, treatment of bromide 20 with silver fluoride, and reaction of fluoride 21 with hydrazine hydrate.…”