Synlett, Table of Contents Synlett 2017; 28(14): 1835-1839DOI: 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 Recommend Article Abstract Buy Article All articles of this category 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. Key words Key wordsoxidative conditions - arylation - tetrahydroisoquinolines - arylzinc reagents - esters Full Text References 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 9a Muramatsu W. Nakano K. Li C.-J. Org. Biomol. Chem. 2014; 12: 2189 9b Muramatsu W. Nakano K. Li C.-J. Org. Lett. 2013; 15: 3650 9c Muramatsu W. Nakano K. Org. Lett. 2014; 16: 2042 9d Muramatsu W. Nakano K. Org. Lett. 2015; 17: 1549 9e Singh KN. Kessar SV. Singh P. Singh P. Kaur M. Batra A. Synthesis 2014; 46: 2644 9f Muramatsu W. Nakano K. Tetrahedron Lett. 2015; 56: 437 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-methyltetrahydrofuran (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]. Supplementary Material Supplementary Material Supporting Information
