Synlett 2021; 32(16): 1665-1669
DOI: 10.1055/a-1337-6459
cluster
Modern Nickel-Catalyzed Reactions

Nickel-Catalyzed N-Arylation of Amides with (Hetero)aryl Electrophiles by Using a DBU/NaTFA Dual-Base System

Travis Lundrigan
,
Joseph P. Tassone
,
Mark Stradiotto  ∗
We are grateful to the NSERC of Canada (Discovery Grant RGPIN-2019-04288 for M.S.), the Government of Canada (Vanier-CGS for J.P.T.), the Killam Trusts, the Province of Nova Scotia, and Dalhousie University for their support of this work.
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Abstract

The first nickel-catalyzed N-arylation of amides with (hetero)aryl (pseudo)halides employing an organic amine base is described. By using a bis(cyclooctadienyl)nickel/8-[2-(dicyclohexylphosphinyl)phenyl]-1,3,5,7-tetramethyl-2,4,6-trioxa-8-phosphaadamantane catalyst mixture in combination with DBU/NaTFA as a dual-base system, a diversity of (hetero)aryl chloride, bromide, tosylate, and mesylate electrophiles were successfully cross-coupled with structurally diverse primary amides, as well as a selection of secondary amide, lac­tam, and oxazolidone nucleophiles.

Key words

nickel catalysis - C–N cross-coupling - amides - arylation

Supporting Information

    Supporting information for this article is available online at https://doi.org/10.1055/a-1337-6459.
  • Supporting Information


Publication History

Received: 19 November 2020

Accepted after revision: 15 December 2020

Accepted Manuscript online:
15 December 2020

Article published online:
13 January 2021

© 2020. Thieme. All rights reserved

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  • References and Notes

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  • 19 N-Arylation of Amides with Aryl Electrophiles (Figures 3 and 4); General Procedure In a N2-filled glovebox, a screw-capped vial containing a magnetic stirrer bar was charged with Ni(COD)2 (5 mol%), CyPAd-DalPhos (5 mol%), the appropriate aryl (pseudo)halide (0.45 mmol, 1.0 equiv, 0.12 M), DBU (2.0 equiv), NaTFA (2.0 equiv), and the appropriate amide (1.1 equiv), followed by the addition of toluene (3.75 mL). The vial was sealed with a cap containing a PTFE septum, removed from the glovebox, and placed in a temperature-controlled aluminum heating block set to 100 °C for 18 h, with magnetic stirring. The vial was then removed from the heating block and left to cool to rt. The crude reaction mixture was filtered through a short plug of Celite and silica gel (3:1 v/v), eluting with EtOAc. The volatile materials were evaporated in vacuo, and the crude product was purified by flash-column chromatography. N-(2-Methylquinolin-4-yl)-2-furamide (2a) Synthesized according to the general procedure and purified by flash column chromatography (silica gel; 30% EtOAc–hexanes) to give a pale-yellow solid; yield: 100 mg (0.40 mmol, 88%). 1H NMR (500 MHz, CDCl3): δ = 8.87 (s, 1 H), 8.34 (s, 1 H), 8.08 (d, J = 8.4 Hz, 1 H), 7.87 (d, J = 8.3 Hz, 1 H), 7.71 (ddd, J = 8.3, 7.1, 1.2 Hz, 1 H), 7.62–7.61 (m, 1 H), 7.57–7.54 (m, 1 H), 7.36–7.35 (m, 1 H), 6.64 (dd, J = 3.5, 1.8 Hz, 1 H), 2.76 (s, 3 H). 13C{1H} UDEFT NMR (125.8 MHz, CDCl3): δ = 160.2, 156.3, 148.3, 147.5, 145.0, 140.1, 129.8, 125.9, 118.8, 118.4, 116.7, 113.2, 111.3, 25.8. HRMS-ESI: m/z [M + H]+ calcd for C15H13N2O2: 253.0972; found: 253.0980. N-(4-Benzoylphenyl)-2-furamide (3a) Synthesized according to the general procedure and purified by flash column chromatography (silica gel; 20% EtOAc–hexanes) to give a colorless solid; yield: 100 mg (0.38 mmol, 84%). 1H NMR (500 MHz, CDCl3): δ = 7.87–7.84 (m, 2 H), 7.79–7.76 (m, 4 H), 7.60–7.56 (m, 1 H), 7.49–7.46 (m, 2 H), 3.93 (t, J = 7.1 Hz, 2 H), 2.66 (t, J = 8.1 Hz, 2 H), 2.21 (quintet, J = 7.6 Hz, 2 H). 13C{1H} UDEFT NMR (125.8 MHz, CDCl3): δ = 195.8, 174.8, 143.2, 138.0, 133.1, 132.3, 131.4, 130.0, 128.4, 118.8, 48.7, 33.0, 18.1. HRMS-ESI: m/z [M + Na]+ calcd for C17H15NNaO2: 288.0995; found: 288.0998.
  • 20 N-(4-Cyanophenyl)benzamide (2f); Gram-Scale Synthesis In a N2-filled glovebox, an oven-dried 250 mL round-bottomed Schlenk flask was charged with Ni(COD)2 (100 mg, 0.363 mmol), CyPAd-DalPhos (178 mg, 0.363 mmol), 4-chlorobenzonitrile (1.0 g, 7.27 mmol), benzamide (0.969 g, 8.00 mmol), NaTFA (1.98 g, 14.5 mmol), DBU (2.17 mL, 14.5 mmol), and toluene (60 mL). A magnetic stirrer bar was added and the flask was sealed with a rubber septum, removed from the glovebox, and placed in an oil bath preheated to 100 °C. A reflux condenser was attached to the reaction vessel under a positive pressure of N2, and magnetic stirring was initiated. After 18 h (unoptimized), the crude reaction mixture was cooled to rt and filtered through a short plug of Celite and silica gel (3:1 v/v), eluting with EtOAc. Volatile materials were evaporated in vacuo, and the crude product was purified by flash-column chromatography (silica gel, 20% EtOAc–hexanes) to give a pale-yellow solid; yield: 1.37 g (6.18 mmol, 85%). 1H NMR (500 MHz, CDCl3): δ = 8.01 (s, 1 H), 7.88–7.86 (m, 2 H), 7.81–7.79 (m, 2 H), 7.67–7.64 (m, 2 H), 7.61–7.58 (m, 1 H), 7.53–7.50 (m, 2 H). 13C{1H} UDEFT NMR (125.8 MHz, CDCl3): δ = 166.0, 142.2, 134.3, 133.5, 132.7, 129.2, 127.3, 120.1, 118.9, 107.6. HRMS-ESI: m/z [M + Na]+ calcd for C14H10N2NaO: 245.0685; found: 245.0686.