Enabling Reductive C-N Cross-Coupling of Nitroalkanes and Boronic Acids by Steric Design of P(III)/P(V)=O Catalysts
Gen Li, Yuzuru Kanda, Seung Youn Hong and Alexander T. Radosevich*
*Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, United States,
Email: radosevich
mit.edu
G. Li, Y. Kanda, S. Y. Hong, A. T. Radosevich, J. Am. Chem. Soc., 2022, 144, 8242-8248.
DOI: 10.1021/jacs.2c01487
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Abstract
An organophosphorus-catalyzed C-N bond-forming reductive coupling of nitroalkanes with arylboronic acids and esters shows excellent chemoselectivity for the nitro/boronic acid substrate pair, allowing the synthesis of N-(hetero)arylamines rich in functionalization.
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proposed mechanism
General Procedure A (For primary nitroalkanes):
An oven-dried reaction tube described in the general material equipped with a magnetic stir bar was charged with boronic acid (0.30 mmol, 1.5 equiv), nitroalkane (0.20 mmol, 1.0 equiv) and P4•[O] (4.4 mg, 0.03 mmol, 15 mol%). The tube was capped with a septa cap, and then placed under N2 atmosphere and evacuated/backfilled 3x with N2. CPME (0.66 mL, 0.3 M) was added by syringe, followed by Ph2SiH2 (149 μL, 0.80 mmol, 4.0 equiv). The N2 inlet needle was removed and the septum was quickly replaced with a new septum cap. The reaction mixture was heated to 120 °C and stirred for the indicated time. Upon completion, the reaction was cooled to room temperature. The resulting crude was loaded on a pad of SiO2 and eluted with CHCl3/acetone to obtain a crude solution. The filtrate was concentrated under reduced pressure. The crude residues were purified by column chromatography to yield pure coupling products. Columns were primarily slurry packed with hexanes and mobile phase polarity was increased gradually to the mixture indicated. Note: hexanes = Hex, dichloromethane = DCM, ethyl acetate = EA.
General Procedure B (For secondary nitroalkanes):
An oven-dried reaction tube described in the general material equipped with a magnetic stir bar was charged with boronic acid (0.30 mmol, 1.5 equiv), MgO (40 mg, 1.0 mmol, 5.0 equiv), nitroalkane (0.20 mmol, 1.0 equiv) and P4•[O] (4.4 mg, 0.03 mmol, 15 mol%). The tube was capped with a septa cap, and then placed under N2 atmosphere and evacuated/backfilled 3x with N2. CPME (0.4 mL) and PivCN (0.27 mL) were added by syringe, followed by Ph2SiH2 (149 μL, 0.80 mmol, 4.0 equiv). The N2 inlet needle was removed and the septum was quickly replaced with a new septum cap. The reaction mixture was heated to 120 °C and stirred for the indicated time. Upon completion, the reaction was cooled to room temperature. The resulting crude was loaded on a pad of SiO2 and eluted with CHCl3/acetone to obtain a crude solution. The filtrate was concentrated under reduced pressure. The crude residues were purified by either column chromatography or preparative TLC (SiO2) to yield pure coupling products. Columns were primarily slurry packed with hexanes and mobile phase polarity was increased gradually to the mixture indicated. Note: hexanes = Hex, dichloromethane = DCM, ethyl acetate = EA.
Intermolecular Reductive C-N Cross Coupling of Nitroarenes and Boronic Acids by PIII/PV=O Catalysis
T. V. Nykaza, J. C. Cooper, G. Li, N. Mahieu, A. Ramirez, M. R. Luzung, A. T. Radosevich, J. Am. Chem. Soc., 2018, 140, 15200-15205.
G. Li, Z. Qin, A. T. Radosevich, J. Am. Chem. Soc., 2020, 142, 16205-16210.
S. Y. Hong, A. T. Radosevich, J. Am. Chem. Soc., 2022, 144, 8902-8907.
Key Words
arylamines, organocatalysis, diphenylsilane
ID: J48-Y2022
