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Synlett 2024; 35(08): 935-939
DOI: 10.1055/s-0043-1763656
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Special Issue dedicated to Keith Fagnou

Nickel-Catalyzed Synthesis of Benzylamines from (Hetero)aryl Halides and Glycine-Derived N-Hydroxyphthalimide Esters

Eun Seo Choi
a   Discovery Chemistry, Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, USA
b   Davenport Research Laboratories, Department of Chemistry, University of Toronto, 80 St. George Street, Toronto, Ontario, M5S 3H6, Canada
,
Sophie A. L. Rousseaux 
b   Davenport Research Laboratories, Department of Chemistry, University of Toronto, 80 St. George Street, Toronto, Ontario, M5S 3H6, Canada
,
Malcolm P. Huestis  ∗
a   Discovery Chemistry, Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, USA
› Author AffiliationsS.A.L.R. thanks NSERC (Discovery Grant and Canada Research Chair programs) and the University of Toronto for financial support.
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Dedicated to the late Prof. Keith Fagnou on the 20th anniversary of the start of his academic career.

Abstract

A nickel-catalyzed aminomethylation of aryl or heteroaryl iodides or bromides for the preparation of protected primary benzylamines is reported. This cross-electrophile reductive protocol engages carbamate-protected, glycine-derived N-hydroxyphthalimide (NHP) esters in an efficient decarboxylative cross-coupling in only two hours. The catalyst and NHP ester reagents are commercially available or can be synthesized in one step on a decagram scale with no chromatography.

Key words

cross-electrophile - glycine - hydroxyphthalimide esters - decarboxylative cross-coupling - aminomethylation - benzylamines

Supporting Information

    Supporting information for this article is available online at https://doi.org/10.1055/s-0043-1763656.
  • Supporting Information


Publication History

Received: 27 September 2023

Accepted after revision: 21 November 2023

Article published online:
12 January 2024

© 2023. Thieme. All rights reserved

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

  • References and Notes

  • 1 Anbarasan P, Schareina T, Beller M. Chem. Soc. Rev. 2011; 40: 5049
    CrossrefPubMed
  • 2 Another useful method of reducing benzonitriles to benzylamines when conventional hydrogenation routes fail is CoCl2/NaBH4; see: Satoh T, Suzuki S, Suzuki Y, Miyaji Y, Imai Z. Tetrahedron Lett. 1969; 4555
    Crossref
  • 4 Zuo Z, Ahneman DT, Chu L, Terrett JA, Doyle AG, MacMillan DW. C. Science 2014; 345: 437
    CrossrefPubMed

      • Dual photoredox/Ni-catalyzed alkylations of aryl halides using aminomethyl silanes and potassium aminomethyl trifluoroborate salts function with tertiary N-Boc-amines and thus cannot afford primary benzyl amines, see:
    • 5a El Khatib M, Massarico Serafim RA, Molander GA. Angew. Chem. Int. Ed. 2016; 55: 254
      CrossrefPubMed
    • 5b Remeur C, Kelly CB, Patel NR, Molander GA. ACS Catal. 2017; 7: 6065
      CrossrefPubMed
    • 5c Badir SO, Sim J, Billings K, Csakai A, Zhang X, Dong W, Molander GA. Org. Lett. 2020; 22: 1046
      CrossrefPubMed
    • 5d Thierry T, Pfund E, Lequeux T. Chem. Eur. J. 2021; 27: 14826
      CrossrefPubMed
    • 5e Dong W, Badir SO, Zhang X, Molander GA. Org. Lett. 2021; 23: 4250
      CrossrefPubMed
  • 6 Jung J, Kinoshita T, Makihara Y, Sakakibara Y, Amaike K, Murakami K, Itami K. Synlett 2023; in press DOI: 10.1055/s-0041-1738444.
    Article in Thieme Connect
    • 7a Huihui KM. M, Caputo JA, Melchor Z, Olivares AM, Spiewak AM, Johnson KA, DiBenedetto TA, Kim S, Ackerman LK. G, Weix DJ. J. Am. Chem. Soc. 2016; 138: 5016
      CrossrefPubMed
    • 7b Salgueiro DC, Chi BK, Gezei IA, García-Reynaga P, Weix DJ. Angew. Chem. Int. Ed. 2022; 61: e202205673
      CrossrefPubMed
  • 8 The Ni-catalyzed coupling of N-Boc-glycine NHP ester 1 with 2-chloro-5-iodopyridine was reported by Ley in 86% yield using a flow apparatus fitted with a Zn column. Applying those conditions to 4-iodoanisole in a batch reaction with Zn flake (8.0 equiv, –325 mesh) afforded a 49% isolated yield; see: Watanabe E, Chen Y, May O, Ley SV. Chem. Eur. J. 2020; 26: 186
    CrossrefPubMed
  • 9 A dual electrochemical/Ni-catalyzed coupling of N-Boc-glycine NHP ester 1 with 7-chloro-4-iodoquinoline in 44% yield was reported by the Baran group. Applying those conditions to 4-iodoanisole afforded 66% isolated yield; see: Palkowitz MD, Laudadio G, Kolb S, Choi J, Oderinde MS, Ewing TE.-H, Bolduc PN, Chen T, Zhang H, Cheng PT. W, Zhang B, Mandler MD, Blasczak VD, Richter JM, Collins MR, Schioldager RL, Bravo M, Dhar TG. M, Vokits B, Zhu Y, Echeverria P.-G, Poss MA, Shaw SA, Clementson S, Petersen NN, Mykhailiuk PK, Baran PS. J. Am. Chem. Soc. 2022; 144: 17709
    CrossrefPubMed
  • 10 West MS, Gabbey AL, Huestis MP, Rousseaux SA. L. Org. Lett. 2022; 24: 8441
    CrossrefPubMed
  • 11 Murakami and Itami’s conditions afforded less than 30% conversion of 4-iodoanisole to the corresponding benzylamine (see ref. 6).
  • 12 N-Boc Benzylamines 2–25; General Procedure A 16 mL threaded reaction tube containing a stirrer bar was capped with a septum, flame-dried under vacuum, and cooled under an inert atmosphere. The tube was charged with the appropriate NHP ester (0.75 mmol, 1.5 equiv), aryl iodide or bromide (0.50 mmol, 1.0 equiv, if solid), [(bipy)2Ni2(μ-Cl)2Cl2(H2O)2] (0.025 mmol, 5.0 mol%), nonactivated Zn flake [4.0 mmol, 8.0 equiv, (–325 mesh)], and 3 Å molecular sieves (20 wt%). The tube was refitted with the septum, evacuated, and backfilled with N2 (×3), then placed in an ice bath to chill at 0 °C (for aryl iodides). Anhyd DMA (2.5 mL, 0.2 M; cooled to 0 °C for aryl iodides) was added to the reaction tube, followed by Me3SiCl (1.5 mmol, 3.0 equiv). If the aryl iodide or bromide was a liquid, it was added as a solution during the DMA addition. The mixture was stirred (500 rpm) at 0 °C for 2 h (rt for aryl bromides). The reaction was then quenched with 10% aq K2CO3 at 0 °C and the mixture was diluted with CH2Cl2 and brine. After extraction, the organics were dried (MgSO4) and concentrated, and the residue was purified by chromatography. See the Supporting Information for detailed procedures and NMR spectra.
  • 13 tert-Butyl (4-Methoxybenzyl)carbamate (2a) Following the general procedure, 1-iodo-4-methoxybenzene (117 mg, 0.500 mmol), [(bipy)2Ni2(μ-Cl)2Cl2(H2O)2] (15.2 mg, 0.0250 mmol), 1,3-dioxoisoindolin-2-yl N-(tert-butoxycarbonyl)glycinate (240 mg, 0.750 mmol), Zn flake (262 mg, 4.00 mmol), and Me3SiCl (191 μL, 1.50 mmol) were reacted in anhyd DMA (2.50 mL) containing 3 Å MS (23 mg). Purification by flash chromatography [silica gel, heptane–i-PrOAc (100:0 to 60:40)] gave a white solid; yield: 92.2 mg (78%). 1H NMR (400 MHz, CDCl3): δ = 7.21 (d, J = 7.9 Hz, 2 H), 6.86 (d, J = 7.9 Hz, 2 H), 4.75 (br s, 1 H), 4.24 (br s, 2 H), 3.80 (s, 3 H), 1.46 (s, 9 H). 13C{1H} NMR (101 MHz, CDCl3): δ = 158.9, 155.9, 131.0, 128.8, 114.0, 79.4, 55.3, 44.2, 28.4. HRMS: m/z [M + Na]+ calcd for C13H19NNaO3: 260.1257; found: 260.1259.
    • 14a Biswas S, Weix DJ. J. Am. Chem. Soc. 2013; 135: 16192
      CrossrefPubMed
    • 14b Lin Q, Fu Y, Liu P, Diao T. J. Am. Chem. Soc. 2021; 143: 14196
      CrossrefPubMed
    • 14c Duan A, Xiao F, Lan Y, Niu L. Chem. Soc. Rev. 2022; 51: 9986
      CrossrefPubMed
    • 14d Day CS, Rentería-Gómez Á, Ton SJ, Gogoi AR, Gutierrez O, Martin R. Nat. Catal. 2023; 6: 244
      Crossref
    • 15a Turro RF, Wahlman JL. H, Tong ZJ, Chen X, Yang M, Chen EP, Hong X, Hadt RG, Houk KN, Yang Y.-F, Reisman SE. J. Am. Chem. Soc. 2023; 145: 14705
      CrossrefPubMed
    • 15b Michel NW. M, Gabbey AL, Edjoc RK, Fagbola E, Hughes JM. E, Campeau L.-C, Rousseaux SA. L. J. Org. Chem. 2023; in press; DOI: DOI: 10.1021/acs.joc.3c02354.
      CrossrefPubMed
  • 16 The majority of mass balance in most cases was dehalogenation.
  • 17 Following the conclusion of our work, a complimentary reaction manifold was reported by Dowling (Pfizer), synthesizing tert-butyl {[1-(tetrahydro-2H-pyranyl)-1H-indazol-6-yl]methyl}carbamate (68% yield), tert-butyl (quinolin-3-ylmethyl)carbamate (84% yield), and tert-butyl [4-(morpholinomethyl)benzyl]carbamate (55% yield); see: DeCicco E. M.; Berritt S.; Knauber T.; Coffey S. B.; Hou J.; Dowling M. S. J. Org. Chem. 2023, 88, 12329.