Direct Deamination of Primary Amines via Isodiazene Intermediates
Kathleen J. Berger, Julia L. Driscoll, Mingbin Yuan, Balu D. Dherange, Osvaldo Gutierrez* and Mark D. Levin*
*Texas A&M University, College Station, Texas 77843; University of Chicago, Chicago, Illinois 60637, United States,
Email: og.labs
tamu.edu, marklevinuchicago.edu
K. J. Berger, J. L. Driscoll, M. Yuan, B. D. Dherange, O. Gutierrez, M. D. Levin, J. Am. Chem. Soc., 2021, 143, 17366-17373.
DOI: 10.1021/jacs.1c09779
see article for more reactions
Abstract
The use of an anomeric amide reagent enables a deamination of primary amines and anilines under mild conditions and with remarkable functional group tolerance including a range of pharmaceutical compounds, amino acids, amino sugars, and natural products via formation of an isodiazene intermediate.
see article for more examples
proposed reaction pathway
General procedure for deamination of primary aliphatic amines
To a round bottom flask equipped with a stir bar under a nitrogen atmosphere was added the anomeric amide reagent (1.2 equiv.) and anhydrous acetonitrile. Under a nitrogen atmosphere, the primary amine (1 equiv.) was dissolved anhydrous acetonitrile and the solution of amine was added dropwise over 10 minutes to the flask containing the anomeric amide reagent. For select reactions, the reverse addition was performed (see supporting information). The total volume of solvent is such that the concentration of anomeric amide in the reaction is 0.1 M. The reaction was stirred at room temperature for 1 hour. The reaction was quenched with saturated aqueous NaHCO3 solution and extracted to DCM. The combined organic layers were washed with brine and dried with sodium sulphate. The volatiles were removed in vacuo and the crude product purified by silica gel chromatography.
General procedure for deamination of anilines
To a 2-dram screw cap vial equipped with a stir bar and PTFE/white silicone septum was added aniline (1 equiv). The anomeric amide (1.5 equiv) and dry CH3CN was added to a second vial under nitrogen atmosphere and this solution was then transferred to the first vial containing aniline and stirred at 45°C for 24 hours. The total volume of solvent is such that the concentration of anomeric amide in the reaction is 0.1 M. The reaction was quenched with saturated aqueous NaHCO3 solution and extracted with EtOAc. The combined organic layers were washed with brine and dried with sodium sulphate. The volatiles were removed in vacuo and the crude product purified by silica gel chromatography.
Direct Deaminative Functionalization
B. D. Dherange, M. Yuan, C. B. Kelly, C. A. Reiher, C. Grosanu, K. J. Berger, O. Gutierrez, M. D. Levin, J. Am. Chem. Soc., 2023, 145, 17-24.
Key Words
ID: J48-Y2021
