Synlett 2017; 28(14): 1835-1839
DOI: 10.1055/s-0036-1589029
letter
© Georg Thieme Verlag Stuttgart · New York

Efficient C(sp3)–H Bond Arylation of Tetrahydroisoquinolines with Knochel-Type Arylzinc Reagents under Oxidative Conditions

Zhihua Peng*
Department of Chemistry, China University of Petroleum, Qingdao, 266580, P. R. of China   Email: zpech@upc.edu.cn
,
Zhi Yu
Department of Chemistry, China University of Petroleum, Qingdao, 266580, P. R. of China   Email: zpech@upc.edu.cn
,
Dong-Huang Chen
Department of Chemistry, China University of Petroleum, Qingdao, 266580, P. R. of China   Email: zpech@upc.edu.cn
,
Shuyuan Liang
Department of Chemistry, China University of Petroleum, Qingdao, 266580, P. R. of China   Email: zpech@upc.edu.cn
,
Liwei Zhang
Department of Chemistry, China University of Petroleum, Qingdao, 266580, P. R. of China   Email: zpech@upc.edu.cn
,
Dezhi Zhao
Department of Chemistry, China University of Petroleum, Qingdao, 266580, P. R. of China   Email: zpech@upc.edu.cn
,
Linhua Song
Department of Chemistry, China University of Petroleum, Qingdao, 266580, P. R. of China   Email: zpech@upc.edu.cn
,
Cuiyu Jiang
Department of Chemistry, China University of Petroleum, Qingdao, 266580, P. R. of China   Email: zpech@upc.edu.cn
› Author Affiliations
Supported by: Shandong Provincial Natural Science Foundation ZR2012BQ006
Supported by: National Natural Science Foundation of China 21202205
Supported by: Fundamental Research Funds for the Central Universities 15CX02059A
Further Information

Publication History

Received: 16 February 2017

Accepted after revision: 18 April 2014

Publication Date:
04 May 2017 (online)


Abstract

A novel C(sp3)–H bond arylation of tetrahydroisoquinoline (THIQ) derivatives with Knochel-type arylzinc reagents has been developed. In the presence of MgCl2, arylzinc reagents readily reacted with THIQ derivatives under oxidative conditions, affording a wide range of potentially biologically active compounds in good yields. Moreover, the developed method can tolerate a variety of sensitive functional groups such as an ester group.

Supporting Information

 
  • References and Notes

    • 1a Yu J.-Q. Shi Z.-J. C–H Activation . Springer; Berlin: 2010
    • 1b Li JJ. C–H Bond Activation in Organic Synthesis. CRC Press; New York: 2015
    • 1c Dixneuf PH. Doucet H. C–H Bond Activation and Catalytic Functionalization I. Springer; Berlin: 2016
    • 1d Dixneuf PH. Doucet H. C–H Bond Activation and Catalytic Functionalization II. Springer; Berlin: 2016

      For selected reviews, see:
    • 2a Wasa M. Engle KM. Yu J.-Q. Isr. J. Chem. 2010; 50: 605
    • 2b Sun C.-L. Li B.-J. Shi Z.-J. Chem. Commun. 2010; 46: 677

      For selected examples, see:
    • 3a Sun C.-L. Liu N. Li B.-J. Yu D.-G. Wang Y. Shi Z.-J. Org. Lett. 2010; 12: 184
    • 3b Wang D.-H. Mei T.-S. Yu J.-Q. J. Am. Chem. Soc. 2008; 130: 17676
    • 3c Wang D.-H. Wasa M. Giri R. Yu J.-Q. J. Am. Chem. Soc. 2008; 130: 7190
    • 3d Yang S.-D. Sun C.-L. Fang Z. Li B.-J. Li Y.-Z. Shi Z.-J. Angew. Chem. Int. Ed. 2008; 47: 1473
  • 4 Yang S. Li B.-J. Wan X. Shi Z.-J. J. Am. Chem. Soc. 2007; 129: 6066
    • 5a Chen X. Li J.-J. Hao X.-S. Goodhue CE. Yu J.-Q. J. Am. Chem. Soc. 2006; 128: 78
    • 5b Kawai H. Kobayashi Y. Oi S. Inoue Y. Chem. Commun. 2008; 1464

      Fe-catalyzed C–H functionalizations with organometallic reagents:
    • 6a Norinder J. Matsumoto A. Yoshikai N. Nakamura E. J. Am. Chem. Soc. 2008; 130: 5858
    • 6b Yoshikai N. Matsumoto A. Norinder J. Nakamura E. Angew. Chem. Int. Ed. 2009; 48: 2925
    • 6c Yoshikai N. Matsumoto A. Norinder J. Nakamura E. Synlett 2010; 313
  • 7 Co-catalyzed C–H functionalizations with organometallic reagents: Li B. Wu Z.-H. Gu Y.-F. Sun C.-L. Wang B.-Q. Shi Z.-J. Angew. Chem. Int. Ed. 2011; 50: 1109
  • 8 Cr-catalyzed C–H functionalizations with organometallic reagents: Kuzmina OM. Knochel P. Org. Lett. 2014; 16: 5208
  • 10 Wang T. Schrempp M. Berndhäuser A. Schiemann O. Menche D. Org. Lett. 2015; 17: 3982
  • 11 Benischke AD. Ellwart M. Becker MR. Knochel P. Synthesis 2016; 48: 1101
  • 12 Krasovskiy A. Malakhov V. Gavryushin A. Knochel P. Angew. Chem. Int. Ed. 2006; 45: 6040
    • 13a Piller FM. Appukkuttan P. Gavryushin A. Helm M. Knochel P. Angew. Chem. Int. Ed. 2008; 47: 6802
    • 13b Metzger A. Bernhardt S. Manolikakes G. Knochel P. Angew. Chem. Int. Ed. 2010; 49: 4665
  • 14 The effect of MgCl2 on the addition of organozinc reagents was explained in ref. 13b. In addition, the Ellman group reported MgCl2-enhanced addition of Knochel-type benzyl zinc reagents to N-tert-butanesulfinyl aldimines: Buesking AW. Baguley TD. Ellman JA. Org. Lett. 2011; 13: 964
  • 15 General Procedure for the Reaction of 1,2,3,4-Tetrahydroisoquinoline Derivatives with Aryl Zinc Reagents A clean Schlenk tube was dried for 5 min at 380 °C (heat gun) under high vacuum (1 mbar). After cooling to r.t., the tube was evacuated and backfilled with nitrogen three times. To the mixture of PIFA (0.5 mmol) and 2-​methyltetrahydrofura​n (2.5 mL) was added the starting material N-substituted 1,2,3,4-tetrahydroisoquinoline (0.5 mmol). The reaction mixture was stirred for 1 h. The corresponding aromatic Zn reagent was added dropwise at r.t. After 12–16 h, water (20 mL) was then added to the reaction mixture. The organic layer was extracted with EtOAc (3 × 20 mL). The combined organic phases were washed with brine and dried over MgSO4. The solvent was removed by rotary evaporation. Purification by flash column chromatography on silica gel using PE–EtOAc as an eluent gave the expected products. Compound 3a: white solid; yield 78% (112 mg); mp 63.1–65.0 °C. 1H NMR (400 MHz, CDCl3): δ = 7.25–7.04 (m, 11 H), 6.77 (d, J = 8.1 Hz, 2 H), 6.67 (t, J = 7.3 Hz, 1 H), 5.76 (s, 1 H), 3.65 (ddd, J = 11.2, 5.5, 5.3 Hz, 1 H), 3.43 (ddd, J = 11.2, 8.7, 5.3 Hz, 1 H), 2.93–2.78 (m, 2 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 149.5, 143.1, 137.9, 135.7, 129.1, 128.2, 128.1, 127.8, 127.3, 127.0, 126.8, 126.1, 117.4, 113.8, 62.8, 43.8, 28.0 ppm. IR (diamond-ATR, neat): 3019.4, 2915.6, 1591.9, 1504.0, 1324.5, 745.8. HRMS: m/z calcd [C21H19N + H]: 286.1596; found: 286.1590 [M+ + H].