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Synlett 2011(4): 464-468  
DOI: 10.1055/s-0030-1259528
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© Georg Thieme Verlag Stuttgart ˙ New York

Catalytic Batch and Continuous Flow Production of Highly Enantioenriched Cyclohexane Derivatives with Polymer-Supported Diarylprolinol Silyl Ethers

Esther Alzaa, Sonia Sayaleroa, Xacobe C. Cambeiroa, Rafael Martín-Rapúna, Pedro O. Mirandaa, Miquel A. Pericàs*a,b
a Institute of Chemical Research of Catalonia (ICIQ), Av. Països Catalans 16, 43007 Tarragona, Spain
b Departament de Química Orgànica, Universitat de Barcelona (UB), 08028 Barcelona, Spain
Fax: +34(977)920222; e-Mail: mapericas@iciq.es;
Further Information

Publication History

Received 15 December 2010
Publication Date:
02 February 2011 (online)

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Abstract

Diarylprolinol silyl ethers immobilized onto polystyrene have been employed as catalysts in the enantioselective domino Michael-Knoevenagel reaction of dimethyl 3-oxoglutarate and 3-substituted acrolein derivatives, including aliphatic ones. The best catalyst allows the preparation of highly functionalized cyclohexane derivatives in a straightforward and efficient manner, both under batch and continuous flow conditions.

Key words

asymmetric organocatalysis - domino process - Michael addition - Knoevenagel condensation - flow reactors

    References and Notes

  • 1 Tietze LF. Brasche G. Gericke KM. Domino Reactions in Organic Chemistry   Wiley-VCH; Weinheim: 2006. 
    Google Scholar
  • For selected reviews, see:
  • 2a Enders D. Grondal C. Huettl MRM. Angew. Chem. Int. Ed.  2007,  46:  1570 
    Google Scholar
  • 2b Walji AM. MacMillan DWC. Synlett  2007,  1477 
    Google Scholar
  • 2c Shindoh N. Takemoto Y. Takasu K. Chem. Eur. J.  2009,  15:  12168 
    Google Scholar
  • 2d Grondal C. Jeanty M. Enders D. Nat. Chem.  2010,  2:  167 
    Google Scholar
  • 2e Westermann B. Ayaz M. van Berkel SS. Angew. Chem. Int. Ed.  2010,  49:  846 
    Google Scholar
  • 2f Bonne D. Coquerel Y. Constantieux T. Rodriguez J. Tetrahedron: Asymmetry  2010,  21:  1085 
    Google Scholar
  • For recent reviews on heterogeneized catalysts, see:
  • 3a De Vos DE. Vankelecom IFJ. Jacobs PA. Chiral Catalyst Immobilization and Recycling   Wiley-VCH; Weinheim: 2000. 
    Google Scholar
  • 3b Ding K. Uozumi Y. Handbook of Asymmetric Heterogeneous Catalysis   Wiley-VCH; Weinheim: 2008. 
    Google Scholar
  • 3c Gruttadauria M. Giacalone F. Noto R. Chem. Soc. Rev.  2008,  37:  1666 
    Google Scholar
  • 3d Jimeno C. Sayalero S. Pericàs MA. In Heterogenized Homogeneous Catalysts for Fine Chemicals Production, Catalysis by Metal Complexes Vol. 33   Barbaro P. Liguori F. Springer Science; Berlin: 2010. 
    Google Scholar
  • For recent reviews on flow chemistry, see:
  • 4a Kirschning A. Solodenko W. Mennecke K. Chem. Eur. J.  2006,  12:  5972 
    Google Scholar
  • 4b Cozzi F. Adv. Synth. Catal.  2006,  348:  1367 
    Google Scholar
  • 4c Mason BP. Price KE. Steinbacher JL. Bogdan AR. McQuade DT. Chem. Rev.  2007,  107:  2300 
    Google Scholar
  • 4d Wiles C. Watts P. Eur. J. Org. Chem.  2008,  1655 
    Google Scholar
  • 4e Kirschning A. Beilstein J. Org. Chem.  2009,  5:  No. 15 
    Google Scholar
  • For recent advances in flow chemistry, see:
  • 5a Saaby S. Knudsen KR. Ladlow M. Ley SV. Chem. Commun.  2005,  2909 
    Google Scholar
  • 5b Baxendale IR. Deeley J. Griffiths-Jones CM. Ley SV. Saaby S. Tranmer GK. Chem. Commun.  2006,  2566 
    Google Scholar
  • 5c Bogdan AR. Mason BP. Sylvester KT. MacQuade DT. Angew. Chem. Int. Ed.  2007,  46:  1698 
    Google Scholar
  • 5d Smith CD. Baxendale IR. Lanners S. Hayward JJ. Smith SC. Ley SV. Org. Biomol. Chem.  2007,  5:  1559 
    Google Scholar
  • 6 Little RD. Dawson JR. Tetrahedron Lett.  1980,  21:  2609 
    CrossrefGoogle Scholar
  • 7a Berkessel A. Gröger H. Asymmetric Organocatalysis   Wiley-VCH; Weinheim: 2005. 
    Google Scholar
  • 7b Dalko PI. Enantioselective Organocatalysis   Wiley-VCH; Weinheim: 2007. 
    Google Scholar
  • 7c Melchiorre P. Marigo M. Carlone A. Bartoli G. Angew. Chem. Int. Ed.  2008,  47:  6138 
    Google Scholar
  • 7d Yu X. Wang W. Org. Biomol. Chem.  2008,  6:  2037 
    Google Scholar
  • 7e Marigo M. Melchiorre P. ChemCatChem  2010,  2:  621 
    Google Scholar
  • 8 Hayashi Y. Toyoshima M. Gotoh H. Ishikawa H. Org. Lett.  2009,  11:  45 
    CrossrefPubMedGoogle Scholar
  • 9 Bertelsen S. Johansen RL. Jørgensen KA. Chem. Commun.  2008,  3016 
    Google Scholar
  • For selected examples of enantioselective domino reactions catalyzed by diarylprolinol silyl ethers, see:
  • 10a Marigo M. Schulte T. Franzén J. Jørgensen KA. J. Am. Chem. Soc.  2005,  127:  15710 
    Google Scholar
  • 10b Enders D. Hüttl MRM. Grondal C. Raabe G. Nature (London)  2006,  441:  861 
    Google Scholar
  • 10c Enders D. Hüttl MRM. Runsink J. Raabe G. Wendt B. Angew. Chem. Int. Ed.  2007,  46:  467 
    Google Scholar
  • 10d Enders D. Narine AA. Benninghaus TR. Raabe G. Synlett  2007,  1667 
    Google Scholar
  • 10e Carlone A. Cabrera S. Marigo M. Jørgensen KA. Angew. Chem. Int. Ed.  2007,  46:  1101 
    Google Scholar
  • 10f Hayashi Y. Okano T. Aratake S. Hazelard D. Angew. Chem. Int. Ed.  2007,  46:  4922 
    Google Scholar
  • 10g Enders D. Hüttl MRM. Raabe G. Bats JW. Adv. Synth. Catal.  2008,  350:  267 
    Google Scholar
  • 10h Enders D. Wang C. Bats JW. Angew. Chem. Int. Ed.  2008,  47:  7539 
    Google Scholar
  • 10i Zhao G.-L. Rios R. Vesley J. Eriksson L. Córdova A. Angew. Chem. Int. Ed.  2008,  47:  8468 
    Google Scholar
  • 10j Enders D. Wang C. Bats JW. Synlett  2009,  1777 
    Google Scholar
  • 10k Enders D. Wang C. Raabe G. Synthesis  2009,  4119 
    Google Scholar
  • 10l Kotame P. Hong B.-C. Liao J.-H. Tetrahedron Lett.  2009,  50:  704 
    Google Scholar
  • 10m Zhang F.-L. Xu A.-W. Gong Y.-F. Wei M.-H. Zhang X.-L. Chem. Eur. J.  2009,  15:  6815 
    Google Scholar
  • 10n Franzén J. Fisher A. Angew. Chem. Int. Ed.  2009,  48:  787 
    Google Scholar
  • 10o Rueping M. Kuenkel A. Tato F. Bats JW. Angew. Chem. Int. Ed.  2009,  48:  3699 
    Google Scholar
  • 10p Reyes E. Talavera G. Vicario JL. Badía D. Carrillo L. Angew. Chem. Int. Ed.  2009,  48:  5701 
    Google Scholar
  • 10q Zhu D. Lu M. Dai L. Zhong G. Angew. Chem. Int. Ed.  2009,  48:  6089 
    Google Scholar
  • 10r Hong L. Sun W. Liu C. Wang L. Wang R. Chem. Eur. J.  2010,  16:  440 
    Google Scholar
  • 10s Enders D. Kruell R. Bettray W. Synthesis  2010,  567 
    Google Scholar
  • 10t Enders D. Wang C. Mukanova M. Greb A. Chem. Commun.  2010,  46:  2447 
    Google Scholar
  • 10u Tang J. Xu DQ. Xia AB. Wang YF. Jiang JR. Luo SP. Xu ZY. Adv. Synth. Catal.  2010,  352:  2121 
    Google Scholar
  • 10v Urushima T. Sakamoto D. Ishikawa H. Hayashi Y. Org. Lett.  2010,  12:  4588 
    Google Scholar
  • 11a Font D. Jimeno C. Pericàs MA. Org. Lett.  2006,  8:  4653 
    Google Scholar
  • 11b Font D. Bastero A. Sayalero S. Jimeno C. Pericàs MA. Org. Lett.  2007,  9:  1943 
    Google Scholar
  • 11c Alza E. Cambeiro XC. Jimeno C. Pericàs MA. Org. Lett.  2007,  9:  3717 
    Google Scholar
  • 11d Font D. Sayalero S. Bastero A. Jimeno C. Pericàs MA. Org. Lett.  2008,  10:  337 
    Google Scholar
  • 11e Alza E. Rodriguez-Escrich C. Sayalero S. Bastero A. Pericàs MA. Chem. Eur. J.  2009,  15:  10167 
    Google Scholar
  • 11f Alza E. Pericàs MA. Adv. Synth. Catal.  2009,  351:  3051 
    Google Scholar
  • 12a Tornøe CW. Christensen C. Meldal M. J. Org. Chem.  2002,  67:  3057 
    Google Scholar
  • 12b Sharpless KB. Fokin VV. Green LG. Rostovtsev VV. Angew. Chem. Int. Ed.  2002,  114:  2708 
    Google Scholar
  • 12c Meldal M. Tornøe CW. Chem. Rev.  2008,  108:  2952 
    Google Scholar
  • 13 For a discussion on the suitability of CuAAC reactions as a supporting strategy in catalysis, see: Bastero A. Font D. Pericàs MA. J. Org. Chem.  2007,  72:  2460 
    CrossrefGoogle Scholar
  • 14 Özçubukçu S. Özkal E. Jimeno C. Pericàs MA. Org. Lett.  2009,  11:  4680 
    CrossrefGoogle Scholar
15

See Supporting Information for details.

16

General Procedure for the Domino Michael-Knoevenagel Process of α,β-Unsaturated Aldehydes and Dimethyl 3-Oxopentanedioate: Benzoic acid (0.05 mmol), the corresponding aldehyde (0.25 mmol) and dimethyl 3-oxopentanedioate (0.275 mmol) were added to catalyst 5 (0.025 mmol) previously swollen in CH2Cl2 (1 mL). The suspension was shaken at r.t. for the time indicated in Table  [²] and then directly filtered. The resin was rinsed with CH2Cl2 (3 × 1 mL) and the organic filtrate was concentrated under reduced pressure. MeOH (1 mL) and NaBH4 (0.25 mmol) were added to a solution of the resulting crude in CH2Cl2 (0.5 mL) at 0 ˚C, which was stirred at that temper-ature for 20 min. After addition of the pH 7 phosphate buffer, the organic materials were extracted with CH2Cl2 and the combined organic phase was dried over Na2SO4, and then concentrated under reduced pressure. The residue was purified by flash chromatography on silica gel (CH2Cl2-EtO2) to afford 7.

17

The deposition number at the Cambridge Crystallographyc Data Centre is CCDC 804763.

18

These recycling experiments show the results obtained in six consecutive runs. After each run, the reaction mixture was filtered and the solid-supported catalyst was washed with CH2Cl2 and directly reused.