Synlett 2020; 31(05): 492-496
DOI: 10.1055/s-0039-1690718
letter
© Georg Thieme Verlag Stuttgart · New York

Nickel-Catalyzed Amination of α-Aryl Methyl Ethers

Purvish Patel
,
We thank the Natural Sciences and Engineering Research Council of Canada (Grant Number RGPIN-2016-06471), the Ontario Ministry of Research and Innovation, the Canada Research Chairs (Grant Number 950-230945), the Canada Foundation for Innovation (Grant Number 35261), and the University of Toronto for financial support of this work.
Further Information

Publication History

Received: 21 August 2019

Accepted after revision: 01 October 2019

Publication Date:
28 October 2019 (online)


Published as part of the Special Section 11th EuCheMS Organic Division Young Investigator Workshop

Abstract

α-Aryl amines are prevalent in pharmaceutically active compounds and natural products. Herein, we describe a Ni-catalyzed protocol for their synthesis from readily available α-aryl ethers. While α-aryl ethers have been used as electrophiles in Ni-catalyzed C–C bond formations, their use in C–heteroatom bond formation is much less prevalent. Preliminary mechanistic insight suggests that oxidative addition is facilitated by an anionic ligand and that reductive elimination is a reversible process.

Supporting Information

 
  • References and Notes

    • 1a Garg NK, Percec V, Rosen BM, Wilson DA, Quasdorf KW, Resmerita A.-M, Zhang N. Chem. Rev. 2010; 111: 1346
    • 1b Yu DG, Li BJ, Shi ZJ. Acc. Chem. Res. 2010; 43: 1486
    • 1c Tobisu M, Chatani N. Acc. Chem. Res. 2015; 48: 1717
    • 1d Zeng H, Qiu Z, Dominquez-Huerta A, Hearne Z, Chen Z, Li C.-J. ACS Catal. 2017; 7: 510
  • 2 Cornella J, Zarate C, Martin R. Chem. Soc. Rev. 2014; 43: 8081
  • 3 Luo YR. Comprehensive Handbook of Chemical Bond Energies . CRC Press; Boca Raton: 2007: 321-346
  • 4 Ogawa H, Minami H, Ozaki T, Komagawa S, Wang C, Uchiyama M. Chem. Eur. J. 2015; 21: 13904
  • 5 Tobisu M, Takahira T, Morioka T, Chatani N. J. Am. Chem. Soc. 2016; 138: 6711
  • 6 Chen P.-P, Lucas EL, Greene MA, Zhang S.-Q, Tollefson EJ, Erickson LW, Taylor BL. H, Jarvo ER, Hong X. J. Am. Chem. Soc. 2019; 141: 5835
  • 7 Tollefson EJ, Hanna LE, Jarvo ER. Acc. Chem. Res. 2015; 48: 2344
    • 8a Guan BT, Xiang SK, Wang BQ, Sun ZP, Wang Y, Zhao KQ, Shi ZJ. J. Am. Chem. Soc. 2008; 130: 3268
    • 8b Taylor BL. H. H, Swift EC, Waetzig JD, Jarvo ER. J. Am. Chem. Soc. 2011; 133: 389
    • 8c Yonova IM, Johnson AG, Osborne CA, Moore CE, Morrissette NS, Jarvo ER. Angew. Chem. Int. Ed. 2014; 53: 2422
    • 8d Tollefson EJ, Dawson DD, Osborne CA, Jarvo ER. J. Am. Chem. Soc. 2014; 136: 14951
    • 8e Dawson DD, Jarvo ER. Org. Process Res. Dev. 2015; 19: 1356
    • 8f Harris MR, Konev MO, Jarvo ER. J. Am. Chem. Soc. 2014; 136: 7825
    • 8g Tobisu M, Yasutome A, Kinuta H, Nakamura K, Chatani N. Org. Lett. 2014; 16: 5572
  • 9 Zarate C, Manzano R, Martin R. J. Am. Chem. Soc. 2015; 137: 6754
  • 10 Zarate C, Nakajima M, Martin R. J. Am. Chem. Soc. 2017; 139: 1191
  • 11 McGrath NA, Brichacek M, Njardarson JT. J. Chem. Educ. 2010; 87: 1348
  • 12 Corma A, Navas J, Sabater MJ. Chem. Rev. 2018; 118: 1410
  • 13 Marquard SL, Rosenfeld DC, Hartwig JF. Angew. Chem. Int. Ed. 2010; 49: 793
  • 14 General Procedure for the Nickel-Catalyzed Amination of α-Aryl Methyl Ethers To a thick-walled reaction tube was added NiCl2(dppf) (0.02 mmol, 10 mol%), followed by Zn dust (0.10 mmol, 50 mol%) and NaH (0.60 mmol, 3.0 equiv). The reaction tube was evacuated and backfilled with nitrogen 3 times. The reaction tube was taken into the glovebox, where MgCl2 (0.60 mmol, 3.0 equiv) was added. Then, outside the glovebox, the methyl ether 1a (0.20 mmol, 1.0 equiv) was added to the tube as a solution in toluene (0.48 M). Finally, the diphenylamine (0.25 mmol, 1.2 equiv) was added as a solution in THF (1.1 M). After 20 h at 90 °C, the reaction was cooled to room temperature. Methanol was added to the reaction followed by ethyl acetate. The crude mixture was filtered over a plug of Celite and silica using EtOAc and concentrated under reduced pressure to yield a yellow-brown oil. The crude mixture was purified using flash column chromatography on silica gel to yield desired product 2a as yellow flakes; mp 57–59 °C. 1H NMR (400 MHz, CDCl3, 298 K): δ = 7.90–7.74 (m, 4 H), 7.54–7.42 (m, 3 H), 7.34–7.23 (m, 4 H), 7.21–7.13 (m, 4 H), 7.03–6.94 (m, 2 H), 5.19 (s, 2 H) ppm. 13C NMR (100 MHz, CDCl3, 298 K): δ = 148.1, 136.7, 133.5, 132.6, 129.7, 128.3, 127.7, 127.6, 126.0, 125.5, 125.0, 124.9, 121.4, 120.7, 56.5 ppm. IR (neat): 1586, 1491, 1361, 1314, 1255, 1232, 823, 750, 700, 692 cm–1. HRMS (DART-TOF +): m/z [M + H]+ calcd for C23H20N: 310.1551; found: 310.1592.
  • 15 Caubère P. Angew. Chem., Int. Ed. Engl. 1983; 22: 599
  • 16 Guillaumet G, Mordenti L, Caubere P. J. Organomet. Chem. 1975; 92: 43
  • 17 LaBerge NA, Love JA. Top. Organomet. Chem. 2015; 52: 55
  • 18 A reaction with enantioenriched starting material led to a racemic mixture of the desired product 2o.
    • 19a Koo K, Hillhouse GL. Organometallics 1995; 14: 4421
    • 19b Lin BL, Clough CR, Hillhouse GL. J. Am. Chem. Soc. 2002; 124: 2890
    • 19c Tasker SZ, Jamison TF. J. Am. Chem. Soc. 2015; 137: 9531
    • 20a Bajo S, Laidlaw G, Kennedy AR, Sproules S, Nelson DJ. Organometallics 2017; 36: 1662
    • 20b Yin G, Kalvet I, Englert U, Schoenebeck F. J. Am. Chem. Soc. 2015; 137: 4164
  • 21 Bhawal BN, Morandi B. Angew. Chem. Int. Ed. 2019; 58: 10074