Synlett 2017; 28(13): 1570-1575
DOI: 10.1055/s-0036-1588502
cluster
© Georg Thieme Verlag Stuttgart · New York

Palladium-Catalyzed Aerobic Oxidative Cyclization of Aliphatic Alkenyl Amides for the Construction of Pyrrolizidine and Indolizidine Derivatives

Kai-Yip Lo
Department of Chemistry, The University of Hong Kong, Pokfulam Road, Hong Kong, P. R. of China   Email: yangdan@hku.hk
,
Liu Ye
Department of Chemistry, The University of Hong Kong, Pokfulam Road, Hong Kong, P. R. of China   Email: yangdan@hku.hk
,
Dan Yang*
Department of Chemistry, The University of Hong Kong, Pokfulam Road, Hong Kong, P. R. of China   Email: yangdan@hku.hk
› Author Affiliations
Financial support was provided by the University of Hong Kong and the Hong Kong Research Grants Council (HKU 706109P and HKU 706112P).
Further Information

Publication History

Received: 26 June 2017

Accepted after revision: 27 June 2017

Publication Date:
13 July 2017 (online)


Published as part of the Cluster Catalytic Aerobic Oxidations

Abstract

An efficient palladium-catalyzed aerobic oxidative cyclization has been developed to synthesize a variety of pyrrolizidine and indolizidine derivatives from simple aliphatic alkenyl amides in moderate to good yields. The reaction features the capability of accessing various N-heterocycles and the use of molecular oxygen (1 atm) as the green oxidant.

Supporting Information

 
  • References and Notes


    • For selected reviews of transition-metal-catalyzed aerobic oxidation, see:
    • 1a Punniyamurthy T. Velusamy S. Iqbal J. Chem. Rev. 2005; 105: 2329
    • 1b Piera J. Bäckvall J.-E. Angew. Chem. Int. Ed. 2008; 47: 3506
    • 1c Shi Z. Zhang C. Tang C. Jiao N. Chem. Soc. Rev. 2012; 41: 3381
    • 1d McCann SD. Stahl SS. Acc. Chem. Res. 2015; 48: 1756

      For selected reviews, see:
    • 2a Stahl SS. Angew. Chem. Int. Ed. 2004; 43: 3400
    • 2b Stahl SS. Science 2005; 309: 1824
    • 2c Sigman MS. Jensen DR. Acc. Chem. Res. 2006; 39: 221
    • 2d Gligorich KM. Sigman MS. Chem. Commun. 2009; 3854

    • For representative examples, see:
    • 2e Nishimura T. Onoue T. Ohe K. Uemura S. J. Org. Chem. 1999; 64: 6750
    • 2f Fix SR. Brice JL. Stahl SS. Angew. Chem. Int. Ed. 2002; 41: 164
    • 2g Andappan MM. S. Nilsson P. Larhed M. Chem. Commun. 2004; 218
    • 2h Mitsudome T. Umetani T. Nosaka N. Mori K. Mizugaki T. Ebitani K. Kaneda K. Angew. Chem. Int. Ed. 2006; 45: 481
    • 2i Zhu J. Liu J. Ma R. Xie H. Li J. Jiang H. Wang W. Adv. Synth. Catal. 2009; 351: 1229
    • 2j Campbell AN. White PB. Guzei IA. Stahl SS. J. Am. Chem. Soc. 2010; 132: 15116
    • 2k Izawa Y. Pun D. Stahl SS. Science 2011; 333: 209
    • 2l White PB. Jaworski JN. Zhu GH. Stahl SS. ACS Catal. 2016; 6: 3340

      For selected reviews, see:
    • 3a McDonald RI. Liu G. Stahl SS. Chem. Rev. 2011; 111: 2981

    • For representative examples, see:
    • 3b Schultz MJ. Sigman MS. J. Am. Chem. Soc. 2006; 128: 1460
    • 3c Zhu M.-K. Zhao J.-F. Loh T.-P. J. Am. Chem. Soc. 2010; 132: 6284
    • 3d Scarborough CC. Stahl SS. Org. Lett. 2006; 8: 3251
    • 3e Wang A. Jiang H. Chen H. J. Am. Chem. Soc. 2009; 131: 3846
    • 3f Shi Z. Ding S. Cui Y. Jiao N. Angew. Chem. Int. Ed. 2009; 48: 7895
    • 3g Ji X. Huang H. Wu W. Jiang H. J. Am. Chem. Soc. 2013; 135: 5286
    • 3h Li J. Grubbs RH. Stoltz BM. Org. Lett. 2016; 18: 5449
    • 5a Larock RC. Hightower TR. Hasvold LA. Peterson KP. J. Org. Chem. 1996; 61: 3584
    • 5b Cacchi S. Fabrizi G. Chem. Rev. 2005; 105: 2873

      The pKaof the anilido proton is about 21.5, see:
    • 6a Bordwell FG. Ji GZ. J. Am. Chem. Soc. 1991; 113: 8398

    • The pK αof the aliphatic amide proton is about 26.5; see:
    • 6b Bordwell FG. Fried HE. J. Org. Chem. 1991; 56: 4218
    • 7a Ramalingan C. Takenaka K. Sasai H. Tetrahedron 2011; 67: 2889
    • 7b Du W. Gu Q. Li Y. Lin Z. Yang D. Org. Lett. 2017; 19: 316
  • 8 Jung ME. Piizzi G. Chem. Rev. 2005; 105: 1735
  • 9 Romanelli MN. Galeotti N. Ghelardini C. Manetti D. Martini E. Gualtieri F. CNS Drug Reviews 2006; 12: 39

    • For examples of cis-aminopalladation, see:
    • 10a Negishi E.-I. Handbook of Organopalladium Chemistry for Organic Synthesis. Wiley; New York: 2002
    • 10b Kočovsy P. Bäckvall J.-E. Chem. Eur. J. 2015; 21: 36
    • 10c Neukom JD. Perch NS. Wolfe JP. J. Am. Chem. Soc. 2010; 132: 6276
    • 10d Neukom JD. Perch NS. Wolfe JP. Organometallics 2011; 30: 1269
    • 10e Liu G. Stahl SS. J. Am. Chem. Soc. 2007; 129: 6328
    • 10f Mai DN. Wolfe JP. J. Am. Chem. Soc. 2010; 132: 12157

      For examples of trans-aminopalladation, see:
    • 11a Weinstein AB. Stahl SS. Angew. Chem. Int. Ed. 2012; 51: 11505
    • 11b Mai DN. Wolfe JP. J. Am. Chem. Soc. 2006; 128: 2893
    • 12a Konnick MM. Gandhi BA. Guzei IA. Stahl SS. Angew. Chem. Int. Ed. 2006; 45: 2904
    • 12b Popp BV. Stahl SS. J. Am. Chem. Soc. 2007; 129: 4410
    • 12c Popp BV. Stahl SS. Chem. Eur. J. 2009; 15: 2915
  • 13 General Procedure To a well-stirred solution of Pd(TFA)2(33.2 mg, 0.1 mmol) in toluene (5 mL) were added pyridine (32.3 μL, 0.4 mmol) and DABCO (44.9 mg, 0.4 mmol). The mixture was stirred continuously until the solid dissolved. The reaction solution was oxygenated for 15 min, then amide 1a (139.2 mg, 1.0 mmol) and toluene (5 mL) were added. The resulting solution was stirred under an O2 atmosphere for 15 min, then heated at 95 °C with an air condenser under an O2 atmosphere for 21 h. The reaction mixture was filtered through a short pad of Celite, then concentrated in vacuo. The residue was purified by flash column chromatography to afford 2a (101.5 mg, 0.74 mmol, 74% yield) as a yellow oil. 2-Methylenehexahydro-3H-pyrrolizin-3-one (2a) Yellow liquid; analytical TLC (silica gel 60), 50% EtOAc in n-hexane, R f = 0.18. 1H NMR (400 MHz, CDCl3): δ = 5.93 (t, J = 2.7 Hz, 1 H), 5.28 (t, J = 2.2 Hz, 1 H), 3.77 (tt, J = 7.2, 4.9 Hz, 1 H), 3.67 (dt, J = 12.0 Hz, 8.1 Hz, 1 H), 3.21 (ddd, J = 12.3, 9.6, 3.0 Hz, 1 H), 3.00 (ddt , J = 17.0 Hz, 7.4 Hz, 2.1 Hz, 1 H), 2.50 (ddd, J = 17.0 Hz, 7.4 Hz, 3.1 Hz, 1 H), 2.26–1.93 (m, 3 H), 1.30–1.21 (m, 1 H). 13C NMR (100 MHz, CDCl3): δ = 168.3 (C), 143.0 (C), 115.2 (CH2), 58.5 (CH), 41.4 (CH2), 31.9 (CH2), 31.4 (CH2), 25.9 (CH2); IR (CH2Cl2) 3048, 2981, 2888, 1692, 1659, 1445, 1244, 1208, 1156 cm–1. LRMS (EI, 20 eV): m/z = 137 (100) [M+]. HRMS (EI): m/z calcd for C8H11NO [M+]: 137.0841; found: 137.0843.