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. 2023 Sep 22;25(37):6791-6795.
doi: 10.1021/acs.orglett.3c02153. Epub 2023 Sep 8.

Iron-Catalyzed Synthesis of α-Azido α-Amino Esters via the Alkylazidation of Alkenes

Pierre Palamini  1 , Emmanuelle M D Allouche  1 , Jerome Waser  1
Affiliations

Iron-Catalyzed Synthesis of α-Azido α-Amino Esters via the Alkylazidation of Alkenes

Pierre Palamini et al. Org Lett. .

Abstract

An iron-catalyzed alkylazidation of dehydroamino acids using peroxides as alkyl radical precursors is described. Non-natural azidated amino esters bearing an α-alkyl chain could be obtained in 18-94% yields using TMSN3 as an azide source. The obtained α-alkyl-α-azide α-amino esters could be further functionalized through cycloaddition or azide reduction with amide couplings to afford aminal-type peptides, α-triazolo amino acids, and tetrahydro-triazolopyridine, showing the great versatility of this now easily accessible class of amino acids.

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Conflict of interest statement

The authors declare no competing financial interest.

Figures

Scheme 1
Scheme 1. (a) α-Heteroatom-Substituted Amino Acids, (b) Azidation of α-Hydroxy Glycines, (c) Azidation of Glycine and Alanine Derivatives, (d) Alkylazidation of Electron-Deficient Alkenes, and (e) Carboazidation of Dehydroamino Acids on the Way to New Peptide Building Blocks
Scheme 2
Scheme 2. Scope of Amino and Ester Groups
Reaction conditions: Dha 1 (1.0 equiv), TMSN3 (2.0 equiv), peroxide 2 (2.0 equiv), and DME (0.25 M) at 21 °C for 2 h. Reactions were carried out under a N2 atmosphere on a 0.25 mmol scale. At 0 °C. With 1.5 mmol.
Scheme 3
Scheme 3. Scope of Alkyl Groups
Reaction conditions: Dha 1 (1.0 equiv), TMSN3 (2.0 equiv), peroxide 2 (2.0 equiv), and DME (0.25 M) at 21 °C for 2 h. Reactions were carried out under a N2 atmosphere on a 0.25 mmol scale. At 0 °C. For 6 h. For 4 h. At 40 °C using Togni II reagent. With 7 mmol.
Scheme 4
Scheme 4. Product Modifications
See the Supporting Information for experimental details.
See this image and copyright information in PMC

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