Synlett 2015; 26(08): 1026-1030
DOI: 10.1055/s-0034-1380411
letter
© Georg Thieme Verlag Stuttgart · New York

Copper-Catalyzed γ-Cyanation of Aza-Baylis–Hillman Adducts Using Trimethylsilyl Cyanide

Arvind K. Yadav
Green Synthesis Lab, Department of Chemistry, University of Allahabad, Allahabad 211002, India   Email: ldsyadav@hotmail.com
,
Lal Dhar S. Yadav*
Green Synthesis Lab, Department of Chemistry, University of Allahabad, Allahabad 211002, India   Email: ldsyadav@hotmail.com
› Author Affiliations
Further Information

Publication History

Received: 04 January 2015

Accepted after revision: 16 February 2015

Publication Date:
16 March 2015 (online)


Abstract

A copper-catalyzed γ-cyanation of aza-Baylis–Hillman adducts via iminium ion formation adjacent to benzylic tertiary amines has been developed using tert-butyl hydroperoxide (TBHP) as the external oxidant. The protocol involves in situ formation of 4π-conjugated iminium ion intermediates that undergo nucleophilic attack by cyanide to provide valuable γ-cyanated α,β-unsaturated amines.

 
  • References and Notes


    • For recent articles, see:
    • 1a Li C.-J, Li Z. Pure Appl. Chem. 2006; 78: 935
    • 1b Li C.-J. Acc. Chem. Res. 2009; 42: 335
    • 1c Shu X.-Z, Xia X.-F, Yang Y.-F, Ji K.-G, Liu X.-Y, Liang Y.-M. J. Org. Chem. 2009; 74: 7464
    • 1d Scheuermann CJ. Chem. Asian J. 2010; 5: 436
    • 1e Yeung CS, Dong VM. Chem. Rev. 2011; 111: 1215
    • 1f Sun C.-L, Li B.-J, Shi Z.-J. Chem. Rev. 2011; 111: 1293
    • 1g Hirano K, Miura M. Chem. Commun. 2012; 48: 10704
    • 1h Kozhushkov SI, Ackermann L. Chem. Sci. 2013; 4: 886
    • 1i Dev ML, Dey SS, Bento I, Barros MT, Maycock CD. Angew. Chem. Int. Ed. 2013; 52: 9791
    • 1j Liu D, Liu C, Li H, Lei A. Chem. Commun. 2014; 50: 3623
    • 1k Wu XF, Gong J.-L, Qi X. Org. Biomol. Chem. 2014; 12: 5807
    • 1l Muramatsu W, Nakano K. Tetrahedron Lett. 2015; 56: 437
    • 1m Shang X.-J, Liu Z.-Q. Tetrahedron Lett. 2015; 56: 482

      For selected examples, see:
    • 2a Li Z, Li C.-J. J. Am. Chem. Soc. 2004; 126: 11810
    • 2b Li Z, Li C.-J. J. Am. Chem. Soc. 2005; 127: 6968
    • 2c Li Z, Li C.-J. J. Am. Chem. Soc. 2005; 127: 3672
    • 2d Zhang Y, Li C.-J. J. Am. Chem. Soc. 2006; 128: 4242
    • 2e Li Z, Bohle DS, Li C.-J. Proc. Natl. Acad. Sci. U.S.A. 2006; 103: 8928
    • 2f Li Z, Li H, Guo X, Cao L, Yu R, Li H, Pan S. Org. Lett. 2008; 10: 803
    • 2g Shen Y, Li M, Wang S, Zhan T, Tan Z, Guo C.-C. Chem. Commun. 2009; 953
    • 2h Sugiishi T, Nakamura H. J. Am. Chem. Soc. 2012; 134: 2504
    • 2i Zhang G, Ma Y, Cheng G, Liu D, Wang R. Org. Lett. 2014; 16: 656
    • 3a Srivastava VP, Yadav AK, Yadav LD. S. Tetrahedron Lett. 2014; 55: 1788
    • 3b Yadav AK, Yadav LD. S. Tetrahedron Lett. 2015; 56: 686

      For selected articles on Baylis–Hillman reaction, see:
    • 4a Basavaiah D, Rao PD, Hyma RS. Tetrahedron 1996; 52: 8001
    • 4b Kotti SR. S. S, Xu X, Li G, Headley AD. Tetrahedron Lett. 2004; 45: 1427
    • 4c Yadav JS, Gupta MK, Pandey SK, Reddy BV. S, Sharma AV. S. Tetrahedron Lett. 2005; 46: 2761
    • 4d Basavaiah D, Kalapala Rao V, Reddy RJ. Chem. Soc. Rev. 2007; 36: 1581
    • 4e Singh V, Pathak R, Batra S. Catal. Commun. 2007; 8: 2048
    • 4f Shi Y.-L, Shi M. Eur. J. Org. Chem. 2007; 2905
    • 4g Singh V, Batra S. Tetrahedron 2008; 64: 4511
    • 4h Ma G.-N, Jiang J.-J, Shi M, Wei Y. Chem. Commun. 2009; 5496
    • 4i Basavaiah D, Reddy BS, Badsara SS. Chem. Rev. 2010; 110: 5447
    • 4j Basavaiah D, Veeraraghavaiah G. Chem. Soc. Rev. 2012; 41: 68
    • 5a Yadav LD. S, Patel R, Srivastava VP. Synlett 2008; 1789
    • 5b Yadav LD. S, Srivastava VP, Patel R. Tetrahedron Lett. 2008; 49: 3142
    • 5c Yadav LD. S, Patel R, Srivastava VP. Tetrahedron Lett. 2009; 50: 1335
    • 5d Yadav LD. S, Rai VK, Singh S. Synlett 2009; 1423
    • 5e Yadav LD. S, Awasthi C. Tetrahedron Lett. 2009; 50: 3801
    • 5f Patel R, Srivastava VP, Yadav LD. S. Synlett 2011; 1261
    • 6a Srivastava VP, Yadav AK, Yadav LD. S. Synlett 2013; 24: 465
    • 6b Yadav AK, Yadav LD. S. RSC Adv. 2014; 4: 34764
    • 6c Yadav AK, Yadav LD. S. Org. Biomol. Chem. 2015; 13: 2606

      For recent developments in nitrogen radical cation chemistry, see:
    • 7a Condie AG, González-Gómez JC, Stephenson CR. J. J. Am. Chem. Soc. 2010; 132: 1464
    • 7b Rueping M, Leonori D, Poisson T. Chem. Commun. 2011; 47: 9615
    • 7c Rueping M, Zhu S, Kόnigs RM. Chem. Commun. 2011; 47: 12709
    • 7d Xuan J, Cheng Y, An J, Lu L.-Q, Zhang X.-X, Xiao W.-J. Chem. Commun. 2011; 47: 8337
    • 7e Pan Y, Wang S, Kee CW, Dubuisson E, Yang Y, Loh KP, Tan C.-H. Green Chem. 2011; 13: 3341
    • 7f Rueping M, Zhu S, Koenigs RM. Chem. Commun. 2011; 47: 8679
    • 7g Zhao G, Yang C, Guo L, Sun H, Chen C, Xia W. Chem. Commun. 2012; 48: 2337
    • 7h Fu W, Guo W, Zou G, Xu C. J. Fluorine Chem. 2012; 140: 88
    • 7i Freeman DB, Furst L, Condie AG, Stephenson CR. J. Org. Lett. 2012; 14: 94
    • 7j DiRocco DA, Rovis T. J. Am. Chem. Soc. 2012; 134: 8094
    • 7k Rueping M, Koenigs RM, Poscharny K, Fabry DC, Leonori D, Vila C. Chem. Eur. J. 2012; 18: 5170
    • 7l Zhu S, Rueping M. Chem. Commun. 2012; 48: 11960
    • 7m Mathis CL, Gist BM, Frederickson CK, Midkiff KM, Marvin CC. Tetrahedron Lett. 2013; 54: 2101
    • 7n Feng Z.-J, Xuan J, Xia X.-D, Ding W, Guo W, Chen J.-R, Zou Y.-Q, Lu L.-Q, Xiao W.-J. Org. Biomol. Chem. 2014; 12: 2037
  • 8 Nobuta T, Tada N, Fujiya A, Kariya A, Miura T, Itoh A. Org. Lett. 2013; 15: 574
  • 9 Allen JM, Lambert TH. J. Am. Chem. Soc. 2011; 133: 1260

    • For selected articles on electrochemical cyanation of amines, see:
    • 10a Andreades S, Zahnow E.-W. J. Am. Chem. Soc. 1969; 91: 4181
    • 10b Le Gall E, Hurvois J.-P, Sinbanbhit S. Eur. J. Org. Chem. 1999; 2645
    • 10c Le E, Malassene G, Toupet RL, Hurvois J.-P, Moinet C. Synlett 1999; 1383
    • 10d Tajima T. Nakajima A. 2008; 130: 10496
    • 10e Libendi SS, Demizu Y, Onomura O. Org. Biomol. Chem. 2009; 7: 351
    • 10f Louafi F, Hurvois J.-P, Chibani A, Roisnel T. J. Org. Chem. 2010; 75: 5721
  • 11 General Procedure for the Copper-Catalyzed γ-Cyanation of Aza-Baylis–Hillman Adducts (Table 3) A round-bottom flask was charged with aza-Baylis–Hillman adduct 1 (1.0 mmol), MeCN (3 mL), CuI (10 mol%), TBHP (2.0 equiv), and TMSCN (1.5 equiv). The flask was stoppered, and the reaction mixture was stirred at r.t. for 6–12 h (Table 3). After completion of the reaction (as monitored by TLC), H2O (5 mL) was added, and the mixture was extracted with EtOAc (3 × 5 mL). The combined organic phases were dried over MgSO4, filtered, and evaporated under reduced pressure. The resulting product was purified by silica gel column chromatography using a gradient mixture of hexane–EtOAc as eluent to afford an analytically pure sample of 2. All the compounds were characterized by NMR, IR, and MS analysis. The characterization data of representative compounds 2a, 2h, and 2k are given below. Compound 2a: yellow oily liquid. IR (neat liquid): νmax = 3053, 3021, 2235, 2950, 2925, 2850, 2710, 1962, 1727, 1624, 1575, 1492, 1435, 1378, 1260, 1013, 767, 705 cm–1. 1H NMR (400 MHz, CDCl3): δ = 7.34–7.26 (m, 5 H), 3.76 (s, 3 H), 3.07 (s, 2 H), 2.35–2.33 (m, 4 H), 1.36–1.34 (m, 4 H). 13C NMR (100 MHz, CDCl3): δ = 166.1, 156.2, 133.4, 128.3, 127.1, 126.9, 116.2, 95.9, 54.1, 52.3, 26.5, 13.1. HRMS (EI): m/z calcd for C16H18N2O2: 270.1368; found: 270.1365. Compound 2h: yellow oily liquid. IR (neat liquid): νmax = 3023, 3067, 3023, 2957, 2923, 2858, 2713, 2232, 1693, 1632, 1572, 1497, 1437, 1379, 1264, 1197, 1148, 1013, 753, 715 cm–1. 1H NMR (400 MHz, CDCl3): δ = 9.56 (s, 1 H), 7.27–7.14 (m, 4 H), 7.08–6.76 (m, 5 H), 3.17 (t, J = 6.4 Hz, 2 H), 3.08 (t, J = 6.4 Hz, 2 H), 3.05 (s, 2 H). 13C NMR (100 MHz, CDCl3): δ = 187.7, 168.4, 144.1, 138.0, 134.3, 129.1, 127.6, 127.0, 125.3, 120.7, 118.8, 116.3, 109.2, 74.5, 51.7, 27.6, 12.3. HRMS (EI): m/z calcd for C19H16N2O: 288.1263; found: 288.1261. Compound 2k: yellow oily liquid. IR (neat liquid): νmax = 3107, 3064, 3020, 2963, 2920, 2854, 2713, 2237, 1722, 1621, 1572, 1495, 1434, 1370, 1263, 1197, 1148, 1012, 762, 711 cm–1. 1H NMR (400 MHz, CDCl3): δ = 7.32–7.24 (m, 4 H), 7.12–6.69 (m, 5 H), 3.66 (s, 3 H), 3.19 (t, J = 6.4 Hz, 2 H), 3.03 (t, J = 6.4 Hz, 2 H), 2.93 (s, 2 H). 13C NMR (100 MHz, CDCl3): δ = 168.5, 144.3, 137.6, 133.7, 126.2, 125.0, 124.7, 120.3, 118.3, 117.5, 115.2, 72.5, 52.3, 50.3, 42.7, 27.1, 24.5, 12.9. HRMS (EI): m/z calcd for C20H18N2O2: 318.1368; found: 318.1370.
    • 12a Lee KY, Kim TH, Kim JN. Bull. Korean Chem. Soc. 2004; 25: 1966
    • 12b Kim SJ, Lee HS, Kim JM, Kim JN. Bull. Korean Chem. Soc. 2008; 29: 265