Iron-Catalyzed Synthesis of α-Azido α-Amino Esters via the Alkylazidation of Alkenes
Pierre Palamini, Emmanuelle M. D. Allouche and Jerome Waser*
*Laboratory of Catalysis and Organic Synthesis, Institut des
Sciences et Ingénierie Chimique, Ecole Polytechnique Fédérale de Lausanne,
CH-1015 Lausanne, Switzerland, Email: jerome.waser
epfl.ch
P. Palamini, E. M. D. Allouche, J. Waser, Org. Lett., 2023, 25, 6791-6795.
DOI: 10.1021/acs.orglett.3c02153
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Abstract
An iron-catalyzed alkylazidation of dehydroamino acids using peroxides as alkyl radical precursors provides α-alkyl-α-azide α-amino esters in good yields using TMSN3 as an azide source. The products could be further functionalized through cycloaddition or azide reduction with amide couplings to afford aminal-type peptides, α-triazolo amino acids, and a tetrahydro-triazolopyridine.
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proposed mechanism
General Procedure for solid peroxides
To an oven-dried vial, Fe(OTf)2 (5 mol%) was added in a glovebox. The vial was removed from the glovebox and placed under nitrogen. To another oven-dried vial, dehydroamino acid (1.0 equiv.) and solid peroxide (2.0 equiv.) were dissolved in DME (0.25 M) under nitrogen atmosphere. TMSN3 (2.00 equiv.) was then added. The solution was added to the catalyst vial via syringe and the deep purple mixture was stirred vigorously for 2 hours at 21 °C. The reaction mixture was diluted with EtOAc and filtered through celite/silica. Flash chromatography afforded the desired alkylazidated product.
General Procedure for liquid peroxides
To an oven-dried vial, Fe(OTf)2 (5 mol%) was added in a glovebox. The vial was removed from the glovebox and placed under nitrogen. To two different oven-dried vial, dehydroamino acid (1.0 equiv.) and liquid peroxide (2.0 equiv.) were added under nitrogen atmosphere. DME was added to the peroxide vial and it was transferred to the dehydroamino acid vial via syringe. TMSN3 (2.00 equiv.) was then added. The solution was added to the catalyst vial via syringe and the deep purple mixture was stirred vigorously for 2 hours at 21 °C. The reaction mixture was diluted with EtOAc and filtered through celite/silica (1:1). Flash chromatography afforded the desired alkylazidated product.
Key Words
azidation, alkylation, multicomponent reactions
ID: J54-Y2023
