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Synlett 2014; 25(20): 2947-2952
DOI: 10.1055/s-0034-1378901
letter
© Georg Thieme Verlag Stuttgart · New York

Direct Organocatalytic Construction of Bicyclo[3.2.1]octanes by Domino Michael/Aldol Reaction with β,γ-Unsaturated 1,2-Keto Amides

Alice Lefranc
a   Department of Organic Chemistry, University of Geneva, Quai Ernest Ansermet 30, 1211 Geneva 4, Switzerland   Fax: +41(22)3793215   eMail: alexandre.alexakis@unige.ch
,
Laure Guénée
b   Laboratory of Crystallography, University of Geneva, Quai Ernest Ansermet 24, 1211 Geneva 4, Switzerland
,
Sylvie Goncalves-Contal
a   Department of Organic Chemistry, University of Geneva, Quai Ernest Ansermet 30, 1211 Geneva 4, Switzerland   Fax: +41(22)3793215   eMail: alexandre.alexakis@unige.ch
,
Alexandre Alexakis*
a   Department of Organic Chemistry, University of Geneva, Quai Ernest Ansermet 30, 1211 Geneva 4, Switzerland   Fax: +41(22)3793215   eMail: alexandre.alexakis@unige.ch
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Publikationsverlauf

Received: 30. Juli 2014

Accepted after revision: 29. September 2014

Publikationsdatum:
06. November 2014 (online)

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Abstract

A direct construction of bicyclo[3.2.1]octanes by an organocatalytic domino Michael/Aldol reaction of cyclic 1,3-keto esters with β,γ-unsaturated 1,2-keto amides is reported. Formation of a precipitate corresponding to the racemic co-crystals of the bicyclic compound was observed in toluene, whereas a homogeneous solution was obtained in dichloromethane. Preliminary mechanistic investigations on the reversibility of the system allowed enhancing the selectivity (>20:1 dr, 73% ee). Relative configuration of the bicyclic compound was determined by X-ray crystal structure analyses.

Key words

domino - organocatalysis - bicyclo[3.2.1]octane - β,γ-unsaturated 1,2-keto amide

Supporting Information

    for this article is available online at http://www.thieme-connect.com/products/ejournals/journal/ 10.1055/s-00000083.
  • Supporting Information
 

  • References and Notes

    • 1a Fujita K, Node M, Sai M, Fujita E, Shingu T, Watson WH, Grossie DA, Zabel V. Chem. Pharm. Bull 1989; 37: 1465
      Crossref
    • 1b Han G, Dai P, Xu L, Wang S, Zheng Q. Chin. Chem. Lett. 1992; 3: 521
    • 1c Li L, Weng Z, Huang S, Pu J, Li S, Huang H, Yang B, Han Y, Xiao W, Li M, Han Q, Sun H. J. Nat. Prod. 2007; 70: 1295
      Crossref
    • 2a Winkelmann K, Heilmann J, Zerbe O, Rali T, Sticher O. Helv. Chim. Acta 2001; 84: 3380
      Crossref
    • 2b Barabé F, Bétournay G, Bellavance G, Barriault L. Org. Lett. 2009; 11: 4236
      Crossref
    • 3a Iida T, Ito K. Phytochemistry 1983; 22: 763
      Crossref
    • 3b For a racemic synthesis of O-methyl liliflodione: Horne DA, Yakushijin K, Büchi G. Tetrahedron Lett. 1999; 40: 5443
      Crossref
  • 4 Huang Y.-L, Tsai W.-J, Shen C.-C, Chen C.-C. J. Nat. Prod. 2005; 68: 217
    CrossrefPubMed
  • 5 Maity P, Lepore SD. J. Am. Chem. Soc. 2009; 131: 4196
    Crossref
    • 6a Presset M, Coquerel Y, Rodriguez J. Chem. Rev. 2013; 113: 525
      Crossref
    • 6b Nicolaou KC, Pappo D, Tsang KY, Gibe R, Chen DY. Angew. Chem. Int. Ed. 2008; 47: 944
  • 7 Tietze LF, Brasche G, Gericke K. Domino Reactions in Organic Synthesis . Wiley-VCH; Weinheim: 2006
    CrossrefGoogle Scholar
    • 8a Grondal C, Jeanty M, Enders D. Nature Chem. 2010; 2: 167
      CrossrefPubMed
    • 8b Enders D, Grondal C, Hüttl MR. M. Angew. Chem. Int. Ed. 2007; 46: 1570
      CrossrefPubMed
    • 8c Volla CM. R, Adotiresei I, Rueping M. Chem. Rev. 2014; 114: 2390
      CrossrefPubMed
    • 8d Tsakos M, Elsegood MR. J, Kokotos CG. Chem. Commun. 2013; 49: 2219
      CrossrefPubMed
    • 9a Lefranc, A.; Gremaud, L.; Alexakis, A. manuscript submitted for publication.
    • 9b For a review on organocatalytic syntheses: Presset M, Coquerel Y, Rodriguez J. ChemCatChem 2012; 4: 172
      Crossref
  • 10 Du H, Rodriguez J, Bugaut X, Constantieux T. Chem. Eur. J. 2014; 20: 8458
    Crossref
  • 11 Desimoni G, Faita G, Quadrelli P. Chem. Rev. 2013; 113: 5924
    Crossref
    • 12a Goncalves-Contal S, Gremaud L, Alexakis A. Angew. Chem. Int. Ed. 2013; 52: 12701
      Crossref
    • 12b Evans DA, Olhava EJ, Johnson JS, Janey JM. Angew. Chem. Int. Ed. 1998; 37: 3372
      Crossref
    • 12c Evans DA, Johnson JS, Olhava EJ. J. Am. Chem. Soc. 2000; 122: 1635
      Crossref
    • 12d Allais C, Constantieux T, Rodriguez J. Chem. Eur. J. 2009; 15: 12945
      CrossrefPubMed
    • 12e Allais C, Liéby-Muller F, Constantieux T, Rodriguez J. Adv. Synth. Catal. 2012; 354: 2537
      Crossref
    • 12f Laras Y, Hugues V, Chandrasekaran Y, Blanchard-Desce M, Acher FC, Pietrancosta N. J. Org. Chem. 2012; 77: 8294
      Crossref
  • 13 Okino T, Hoashi Y, Takemoto Y. J. Am. Chem. Soc. 2003; 125: 12672
    CrossrefPubMed
    • 14a Xi Y, Shi X. Chem. Commun. 2013; 49: 8583
      Crossref
    • 14b Connon SJ. Chem. Commun. 2008; 2499
    • 14c Alemán J, Parra A, Jiang H, Jørgensen KA. Chem. Eur. J. 2011; 17: 6890
      CrossrefPubMed
  • 15 Domino Michael/Aldol Reaction; General Procedure: To a solution of β,γ-unsaturated 1,2-keto amide 1a (26.6 mg, 0.1 mmol, 1 equiv) in the appropriate solvent (0.5 mL) were added successively the catalyst III (11.9 mg, 0.02 mmol, 20 mol%) and 1,3-keto ester 2a (31.2 mg, 0.2 mmol, 2 equiv). The mixture was stirred at the corresponding temperature for the time listed in the Tables. Then the reactive mixture was concentrated under reduced pressure. The crude product was purified by flash chromatography on silica gel (c-hexane–EtOAc, 7:3), affording bicyclo[3.2.1]octanone 3a.
  • 16 Bicyclo[3.2.1]octane 3a: Compound 3a was prepared according to the general procedure previously described. At r.t. after 60 h, 3a was obtained as a white solid. Yield: 75% (30.6 mg, 0.075 mmol); dr >20:1 (determined by 1H NMR of the crude reactive mixture); mp 120–122 °C; Rf 0.3 (silica gel, c-hexane–EtOAc, 7:3). The enantiomeric excess was determined by chiral SFC Chiralpak OD-3 [20% MeOH to 25% MeOH in CO2 (1%/min gradient), 30 °C]: t 1= 11. 3 min, t 2 = 8.8 min; [α]D 22 25.14 (c = 1.0 in CHCl3, 54% ee). 1H NMR (400 MHz, CDCl3): δ = 7.22–7.34 (m, 10 H, CAr–H), 4.41 (m, 2 H, PhCH 2NHCO), 3.94 (dd, J = 13.6, 4.8 Hz, 1 H, CHPhCH2), 3.57 (s, 3 H, Me), 3.00 (t, J = 14.8 Hz, 1 H, CHPhCH 2), 2.84 (1 H, OH), 2.65–2.75 (m, 1 H, CHCH 2CH2), 2.43–2.54 (m, 3 H, CHCH2CH2, CHCH2CH 2), 1.94–2.04 (m, 1 H, CHCH 2CH2), 1.87 (dd, J = 15.1, 4.9 Hz, 1 H, CHPhCH 2). 13C NMR (100 MHz, CDCl3): δ = 209.2 (ketone Cq), 172.2 (amide Cq), 168.8 (ester Cq), 139.0 (Cq), 137.9 (Cq), 128.9 (CAr–H), 128.7 (CAr–H), 128.6 (CAr–H), 127.8 (2 × CAr–H), 127.7 (CAr–H), 80.3 (Cq COHCONHBn), 62.9 (Cq CCO2Me), 54.2 (CHCH2CH2), 52.3 (Me), 47.6 (CHPhCH2), 43.5 (PhCH2NHCO), 34.6 (CHPhCH2), 20.6 (CHCH2 CH2), 18.7 (CHCH2CH2). IR (thin film): 3356, 1755, 1723, 1641, 1451, 1275, 1114, 1026, 908, 695 cm–1. HRMS (ESI): m/z [M + H]+ calcd for C24H26NO5: 408.1806; found: 408.1815.
  • 17 Malerich JP, Hagihara K, Rawal VH. J. Am. Chem. Soc. 2008; 130: 14416
    CrossrefPubMed
  • 18 Substrates with a tert-butyl group or tertiary amide showed no reactivity.
  • 19 Intermediate 4a of the Domino Michael/Aldol Reaction: To a solution of β,γ-unsaturated 1,2-keto amide 1a (26.6 mg, 0.1 mmol, 1 equiv) in CH2Cl2 (0.5 mL) were added successively the catalyst III (11.9 mg, 0.02 mmol, 20 mol%) and 1,3-keto ester 2a (31.2 mg, 0.2 mmol, 2 equiv). The mixture was stirred at r.t. for 1.3 h. Then the reaction mixture was concentrated under reduced pressure. The crude product was purified by flash chromatography on silica gel (c-hexane–EtOAc 8:2), affording the 1,2-keto amide intermediate 4a as a colorless oil. Yield: 74% (30 mg, 0.074 mmol); dr >20:1 (determined by 1H NMR of the crude reaction mixture); Rf 0.2 (silica gel, c-hexane–EtOAc, 7:3). The enantiomeric excess was determined by chiral SFC Chiralpak OJ-3 [10% MeOH to 25% MeOH in CO2 (1%/min gradient), 30 °C]: t 1= 10.1 min, t 2 = 9.5 min; [α]D 22 0.17 (c = 1.0 in CHCl3, 4% ee). 1H NMR (400 MHz, CDCl3): δ = 7.16–7.33 (m, 10 H, CAr–H), 4.35–4.40 (m, 2 H, PhCH 2NHCO), 4.19 (d, J = 10.4, 4.0 Hz, 1 H, CHCH2COCONHBn), 3.78 (dd, J = 18.4, 10.5 Hz, 1 H, CHCH 2COCONHBn), 3.72 (s, 3 H, Me), 3.26 (dd, J = 18.4, 4.0 Hz, 1 H, CHCH 2COCONHBn), 2.57 (m, 1 H, CH2), 2.19–2.26 (m, 1 H, CH2), 2.08–2.15 (m, 1 H, CH2), 1.75–1.87 (m, 1 H, CH2), 1.61–1.69 (m, 1 H, CH2), 1.50–1.60 (m, 1 H, CH2). 13C NMR (100 MHz, CDCl3): δ = 213.5 (ketone Cq), 196.7 (ketone Cq), 170.6 (amide Cq), 159.9 (ester Cq), 138.5 (Cq), 136.9 (Cq), 129.8 (CAr–H), 128.9 (CAr–H), 128.5 (CAr–H), 128.0 (CAr–H), 127.9 (CAr–H), 127.5 (CAr–H), 64.55 (Cq), 53.0 (Me), 43.5 (PhCH2NHCO), 43.2 (CH), 38.8 (CH2), 38.2 (CHCH2COCONHBn), 29.34 (CH2), 19.7 (CH2). IR (thin film): 3322, 2960, 1744, 1676, 1453, 1231, 1149, 702 cm–1. HRMS (ESI): m/z [M + H]+ calcd for C24H26NO5: 408.1806; found: 408.1806.
    • 20a Rueping M, Kuendel A, Tato F, Bats JW. Angew. Chem. Int. Ed. 2009; 48: 3699
      CrossrefPubMed
    • 20b Liu Y, Wang Y, Song H, Zhou Z, Tang C. Adv. Synth. Catal. 2013; 355: 2544
      Crossref
    • 20c Xie H, Zu L, Li H, Wang J, Wang W. J. Am. Chem. Soc. 2007; 129: 10886
      Crossref