Download PDF
Synlett 2017; 28(14): 1771-1774
DOI: 10.1055/s-0036-1588831
letter
© Georg Thieme Verlag Stuttgart · New York

Chemo- and Regioselective Asymmetric Friedel–Crafts Reaction of Furans and Thiophenes with α,β-Unsaturated Aldehydes through Dual Activation

Xiao-Ru Zhang
a   Department of Medicinal Chemistry, West China School of Pharmacy, Sichuan University, Chengdu 610041, P. R. of China
,
Su-Lan Zhou
a   Department of Medicinal Chemistry, West China School of Pharmacy, Sichuan University, Chengdu 610041, P. R. of China
,
Yi Yuan
b   College of Pharmacy, Third Military Medical University, Shapingba, Chongqing 400038, P. R. of China   Email: ycchen@scu.edu.cn
,
Wei Du
a   Department of Medicinal Chemistry, West China School of Pharmacy, Sichuan University, Chengdu 610041, P. R. of China
,
Ying-Chun Chen  *
a   Department of Medicinal Chemistry, West China School of Pharmacy, Sichuan University, Chengdu 610041, P. R. of China
b   College of Pharmacy, Third Military Medical University, Shapingba, Chongqing 400038, P. R. of China   Email: ycchen@scu.edu.cn
› Author AffiliationsWe are grateful for the financial support from the NSFC (21372160 and 21125206).
Further Information

Publication History

Received: 09 March 2017

Accepted after revision: 18 April 2017

Publication Date:
10 May 2017 (online)

    Permissions and Reprints All articles of this category


Abstract

A highly chemo- and regioselective Friedel–Crafts alkylation reaction of furans and thiophenes has been developed, which relies on the activation from the remote conjugated Mukaiyama silyl enol ether motif. Excellent enantioslectivity is generally obtained in reactions with α,β-unsaturated aldehydes under the well-established iminium ion catalysis of a chiral secondary amine.

Key words

Friedel–Crafts alkylation - furans - thiophenes - iminium ion catalysis - α,β-unsaturated aldehydes - dual activation

Supporting Information

    Supporting information for this article is available online at https://doi.org/10.1055/s-0036-1588831.
  • Supporting Information
 

  • References and Notes


      • For selected reviews on asymmetric Friedel–Crafts reaction, see:
    • 1a Bolm C. Hildebrand JP. Muñiz K. Hermanns N. Angew. Chem. Int. Ed. 2001; 40: 3284
      CrossrefPubMed
    • 1b Bandini M. Melloni A. Umani-Ronchi A. Angew. Chem. Int. Ed. 2004; 43: 550
      CrossrefPubMed
    • 1c Poulsen TB. Jørgensen KA. Chem. Rev. 2008; 108: 2903
      CrossrefPubMed
    • 1d You S.-L. Cai Q. Zeng M. Chem. Soc. Rev. 2009; 38: 2190
      CrossrefPubMed
  • 2 Paras NA. MacMillan DW. C. J. Am. Chem. Soc. 2001; 123: 4370
    CrossrefPubMed

      • For selected examples, see:
    • 3a Jensen KB. Thorbauge J. Hazell RG. Jørgensen KA. Angew. Chem. Int. Ed. 2001; 40: 160
      CrossrefPubMed
    • 3b Austin JF. MacMillan DW. C. J. Am. Chem. Soc. 2002; 124: 1172
      CrossrefPubMed
    • 3c Evans DA. Scheidt KA. Frandrick KR. Lam HW. Wu J. J. Am. Chem. Soc. 2003; 125: 10780
      CrossrefPubMed
    • 3d Blay G. Fernandez I. Pedro JR. Vila C. Org. Lett. 2007; 9: 2601
      CrossrefPubMed
    • 3e Chen W. Du W. Yue L. Li R. Wu Y. Ding L.-S. Chen Y.-C. Org. Biomol. Chem. 2007; 5: 816
      CrossrefPubMed
    • 3f Bartoli G. Bosco M. Carlone A. Pesciaioli F. Sambri L. Melchiorre P. Org. Lett. 2007; 9: 1403
      CrossrefPubMed
    • 3g Sibi MP. Coulomb J. Stanley LM. Angew. Chem. Int. Ed. 2008; 47: 9913
      CrossrefPubMed
    • 3h He Y. Lin M. Li Z. Liang X. Li G. Antilla JC. Org. Lett. 2011; 13: 4490
      CrossrefPubMed
    • 3i Wang S.-G. Zhang W. You S.-L. Org. Lett. 2013; 15: 1488
      CrossrefPubMed
    • 3j Mori K. Wakazawa M. Akiyama T. Chem. Sci. 2014; 5: 1799
      Crossref
    • 3k Zhang J.-W. Liu X.-W. Gu Q. Shi X.-X. You S.-L. Org. Chem. Front. 2015; 2: 476
      Crossref
    • 3l Nakamura S. Matsuda N. Ohara M. Chem. Eur. J. 2016; 22: 9478
      CrossrefPubMed
    • 3m García-García C. Ortiz-Rojano L. Álvarez S. Álvarez R. Ribagorda M. Carreño MC. Org. Lett. 2016; 18: 2224
      CrossrefPubMed
    • 3n Zhao Y. Wang L. Zhao J. Tetrahedron Lett. 2017; 58: 213
      Crossref
    • 4a Uraguchi D. Sorimachi K. Terada M. J. Am. Chem. Soc. 2004; 126: 11804
      CrossrefPubMed
    • 4b Liu H. Xu J. Du D.-M. Org. Lett. 2007; 9: 4725
      CrossrefPubMed
    • 4c Majer J. Kwiatkowski P. Jurczak J. Org. Lett. 2008; 10: 2955
      CrossrefPubMed
    • 4d Adachi S. Tanaka F. Watanabe K. Harada T. Org. Lett. 2009; 11: 5206
      CrossrefPubMed
    • 4e Adachi S. Tanaka F. Watanabe K. Watada A. Harada T. Synthesis 2010; 2652
      Article in Thieme Connect
    • 4f Kondoh A. Ota Y. Komuro T. Egawa F. Kanomata K. Terada M. Chem. Sci. 2016; 7: 1057
      CrossrefPubMed
    • 4g Wang Y. Jiang L. Li L. Dai J. Xiong D. Shao Z. Angew. Chem. Int. Ed. 2016; 55: 15142
      CrossrefPubMed
    • 5a Zhuang W. Gathergood N. Hazell RG. Jørgensen KA. J. Org. Chem. 2001; 66: 1009
      CrossrefPubMed
    • 5b Saaby S. Bayón P. Aburel PS. Jørgensen KA. J. Org. Chem. 2002; 67: 4352
      CrossrefPubMed
    • 5c Shirakawa S. Berger R. Leighton JL. J. Am. Chem. Soc. 2005; 127: 2858
      CrossrefPubMed
    • 5d Majer J. Kwiatkowski P. Jurczak J. Org. Lett. 2009; 11: 4636
      CrossrefPubMed
    • 5e Aikawa K. Asai Y. Hioki Y. Mikami K. Tetrahedron: Asymmetry 2014; 25: 1104
      Crossref
  • 6 Brown SP. Goodwin NC. MacMillan DW. C. J. Am. Chem. Soc. 2003; 125: 1192
    CrossrefPubMed
    • 7a Li J.-L. Yue C.-Z. Chen P.-Q. Xiao Y.-C. Chen Y.-C. Angew. Chem. Int. Ed. 2014; 53: 5449
      CrossrefPubMed
    • 7b Yang G.-J. Du W. Chen Y.-C. J. Org. Chem. 2016; 81: 10056
      CrossrefPubMed

      • For HOMO activation of arene systems for [4+2] cycloadditions, see:
    • 7c Jiang H. Rodríguez-Escrich C. Johansen TK. Davis RL. Jørgensen KA. Angew. Chem. Int. Ed. 2012; 51: 10271
      CrossrefPubMed
    • 7d Rodríguez-Escrich C. Davis RL. Jiang H. Stiller J. Johansen TK. Jørgensen KA. Chem. Eur. J. 2013; 19: 2932
      CrossrefPubMed
    • 7e Xiao Y.-C. Yue C.-Z. Chen P.-Q. Chen Y.-C. Org. Lett. 2014; 16: 3208
      CrossrefPubMed
    • 7f Xiao B.-X. Du W. Chen Y.-C. Adv. Synth. Catal. 2017; 359: 1018
      Crossref
    • 8a Wang W. Li H. Wang J. Org. Lett. 2005; 7: 1637
      CrossrefPubMed
    • 8b Gupta V. Sudhir S. Mandal VT. Schneider C. Angew. Chem. Int. Ed. 2012; 51: 12609
      CrossrefPubMed
    • 9a Saraber FC. E. Dratch S. Bosselaar G. Jansen BJ. M. de Groot A. Tetrahedron 2006; 62: 1717
      Crossref
    • 9b Hashmi AS. K. Wölfle M. Tetrahedron 2009; 65: 9021
      Crossref
    • 9c Kang BC. Shim SY. Ryu DH. Org. Lett. 2014; 16: 2077
      CrossrefPubMed
    • 9d The configuration of the O-TBS enol ether is confirmed by NOEDS analysis. See the Supporting Information.
  • 10 Donslund BS. Johansen TK. Poulsen PH. Halskov KS. Jørgensen KA. Angew. Chem. Int. Ed. 2015; 54: 13860
    CrossrefPubMed
  • 11 Lelais G. MacMillan DW. C. Aldrichimica Acta 2006; 39: 79
    CrossrefPubMed
  • 12 The reaction was carried out with α,β-unsaturated aldehyde 3 (0.15 mmol) and silyl enol ether 2 (0.1 mmol) in CHCl3 (1.0 mL) in the presence of secondary amine catalyst C4 (4.9 mg, 0.02 mmol) and TFA (2.2 mg, 0.02 mmol) at –20 °C. After completion, the solution was concentrated, and the residue was dissolved in MeOH (2 mL), then NaBH4 (5.7 mg, 0.15 mmol) was added in one portion at r.t. After completion, the solution was concentrated and purified by flash chromatography on silica gel (PE–EtOAc) to afford the chiral product 4. Isolated products have been fully characterized by 1H NMR and 13C NMR spectroscopy (see the Supporting Information). (S,Z)-3-(5-{2-[(tert-Butyldimethylsilyl)oxy]prop-1-en-1-yl}furan-2-yl)-3-(4-nitrophenyl)propan-1-ol (4d) Yield: 35.0 mg (84%), yellow oil; the enantiomeric excess was determined to be 95% by HPLC analysis [Chiralpak AD-H column (5% 2-PrOH–n-hexane, 1.0 mL/min), UV (220 nm), t R (minor) = 11.32 min, t R (major) = 13.22 min]; [α]D 20 = +13.5 (c 0.80 in CHCl3). 1H NMR (400 MHz, CDCl3): δ = 8.14 (d, J = 8.8 Hz, 2 H), 7.41 (d, J = 8.8 Hz, 2 H), 6.35 (d, J = 3.2 Hz, 1 H), 6.13 (d, J = 3.2 Hz, 1 H), 5.34 (s, 1 H), 4.29 (t, J = 7.8 Hz, 1 H), 3.66–3.57 (m, 2 H), 2.39–2.33 (m, 1 H), 2.12–2.07 (m, 1 H), 1.95 (s, 3 H), 1.40 (s, 1 H), 0.95 (s, 9 H), 0.21–0.20 (m, 6 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 151.7, 151.6, 150.4, 148.9, 128.7, 123.8, 108.0, 106.6, 98.7, 60.1, 41.2, 37.1, 25.9, 23.4, 18.4, -3.1 ppm. ESI-HRMS: m/z calcd for C22H31NO5Si + Na+: 440.1864; found: 440.1868.
  • 13 To the best of our knowledge, there is only one example involving the Friedel–Crafts reaction of 2-methoxythiophene under aminocatalytic conditions, see: Huang Y. Walji AM. Larsen CH. MacMillan DW. C. J. Am. Chem. Soc. 2005; 127: 15051
    CrossrefPubMed
    • 14a Freedman TB. Cao X. Dukor RK. Nafie LA. Chirality 2003; 15: 743
      CrossrefPubMed
    • 14b Stephens PJ. Harada N. Chirality 2010; 22: 229
      PubMed
    • 14c Kong F.-D. Ma Q.-Y. Huang S.-Z. Wang P. Wang J.-F. Zhou L.-M. Yuan J.-Z. Dai H.-F. Zhao Y.-X. J. Nat. Prod. 2017; 80: 1039
      CrossrefPubMed
  • 15 Wang M. Han F. Yuan HJ. Liu Q. Chem. Commun. 2010; 46: 2247
    CrossrefPubMed