Synlett 2011(2): 249-253  
DOI: 10.1055/s-0030-1259296
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

Organocatalyzed Michael Addition Reaction by Novel (2R,3aS,7aS)-Octa-hydroindole-2-carboxylic Acid, a New Fused Proline

David Roca-Lópeza, Pedro Merino*a, Francisco J. Sayagob, Carlos Cativielab, Raquel P. Herrera*a,c
a Laboratorio de Síntesis Asimétrica, Dpto. de Química Orgánica, ICMA (CSIC-UZ), 50009 Zaragoza, Spain
b Laboratorio de Aminoácidos y Péptidos, Dpto. de Química Orgánica, ICMA (CSIC-UZ), 50009 Zaragoza, Spain
c ARAID, Fundación Aragón I+D, 50004 Zaragoza, Spain
Fax: +34(976)762075; e-Mail: raquelph@unizar.es;
Further Information

Publication History

Received 27 November 2010
Publication Date:
04 January 2011 (online)

Abstract

We present here the results obtained in our study on organocatalytic enantioselective Michael addition reaction of acetone to different nitroolefines using (2R,3aS,7aS)-octahydroindole-2-carboxylic acid [(R,S,S)-Oic] as a new and suitable catalyst for this process. Computational calculations support the results obtained with (R,S,S)-Oic versus its diastereomeric form (S,S,S)-Oic. The final products are obtained in good yields and moderate enantioselectivities (up to 58% ee).

    References and Notes

  • 1a Berkessel A. Gröger H. In Asymmetric Organocatalysis   Wiley-VCH; Weinheim: 2004. 
  • 1b Enantioselective Organocatalysis   Dalko PI. Wiley-VCH; Weinheim: 2007. 
  • 1c Organocatalysis   Reetz MT. List B. Jaroch S. Weinmann H. Springer; Berlin: Heidelberg: 2008. 
  • For reviews on asymmetric Michael addition reactions, see:
  • 2a Sibi MP. Manyem S. Tetrahedron  2000,  56:  8033 
  • 2b Krause N. Hoffmann-Röder A. Synthesis  2001,  171 
  • 2c Berner OM. Tedeschi L. Enders D. Eur. J. Org. Chem.  2002,  1877 
  • 2d Christoffers A. Baro A. Angew. Chem. Int. Ed.  2003,  42:  1688 
  • 2e Christoffers J. Koripelly G. Rosiak A. Rössle M. Synthesis  2007,  1279 
  • 2f Enders D. Saint-Dizier A. Lannou MI. Lenzen A. Eur. J. Org. Chem.  2006,  29 
  • 2g Enders D. Luttgen K. Narine AA. Synthesis  2007,  959 
  • For reviews on 1,4-addition reactions catalyzed by organocatalysts, see:
  • 3a Tsogoeva SB. Eur. J. Org. Chem.  2007,  1701 
  • 3b Almaşi D. Alonso DA. Nájera C. Tetrahedron: Asymmetry  2007,  18:  299 
  • 3c Vicario JL. Badía D. Carrillo L. Synthesis  2007,  2065 
  • 3d Sulzer-Mossé S. Alexakis A. Chem. Commun.  2007,  3123 
  • 3e Enders D. Wang C. Liebich JX. Chem. Eur. J.  2009,  15:  11058 
  • 4 For a recent review concerning the organocatalytic addition of ketones to nitroalkenes, see: Roca-López D. Sádaba D. Delso I. Herrera RP. Tejero T. Merino P. Tetrahedron: Asymmetry  2010,  21:  2561 
  • 5a Ono N. The Nitro Group in Organic Synthesis   Wiley-VCH; New York: 2001. 
  • 5b Ballini R. Petrini M. Tetrahedron  2004,  60:  1017 
  • For pioneering examples, see:
  • 6a List B. Pojarliev PH. Martin HJ. Org. Lett.  2001,  3:  2423 
  • 6b Betancort JM. Barbas CF. Org. Lett.  2001,  3:  3737 
  • 6c Enders D. Seki A. Synlett  2002,  26 
  • For selected examples, see:
  • 7a Huang H. Jacobsen EN. J. Am. Chem. Soc.  2006,  128:  7170 
  • 7b Yalalov DA. Tsogoeva SB. Schmatz S. Adv. Synth. Catal.  2006,  348:  826 
  • 7c Gun Q. Guo X.-T. Wu X.-Y. Tetrahedron  2009,  65:  5265 
  • 7d Peng L. Xu X.-Y. Wang L.-L. Huang J. Bai J.-F. Huang Q.-C. Wang L.-X. Eur. J. Org. Chem.  2010,  2978 
  • 8 Sayago FJ. Jiménez AI. Cativiela C. Tetrahedron: Asymmetry  2007,  18:  2358 
  • 9 Sayago FJ. Calaza MI. Jiménez AI. Cativiela C. Tetrahedron  2008,  64:  84 
  • For selected examples, see:
  • 10a Hurst M. Jarvis B. Drugs  2001,  61:  867 
  • 10b Reissmann S. Imhof D. Curr. Med. Chem.  2004,  11:  2823 
  • 10c Gass J. Khosla C. Cell. Mol. Life Sci.  2007,  64:  345 
  • For selected examples, see:
  • 11a Bellemère G. Vaudry H. Morain P. Jégou S. J. Neuroendocrinol.  2005,  17:  306 
  • 11b Curran MP. McCormack PL. Simpson D. Drugs  2006,  66:  235 
  • 11c Bas M. Bier H. Greve J. Kojda G. Hoffmann TK. Allergy  2006,  61:  1490 
  • 11d Sorbera LA. Fernández-Forner D. Bayes M. Drug Future  2006,  31:  101 
  • For reviews on enamine catalysis, see:
  • 12a List B. Synlett  2001,  1675 
  • 12b List B. Tetrahedron  2002,  58:  5573 
  • 12c List B. Chem. Commun.  2006,  819 
  • 12d Marigo M. Jørgensen KA. Chem. Commun.  2006,  2001 
  • 12e Mukherjee S. Yang J.-W. Hoffmann S. List B. Chem. Rev.  2007,  107:  5471 
  • 12f Pihko PM. Majander I. Erkilä A. Top. Curr. Chem.  2010,  291:  29 
  • 13 During the development of our project, a novel application of structure 4 analogue as organocatalyst has been reported: Luo R.-S. Weng J. Ai H.-B. Lu G. Chan ASC. Adv. Synth. Catal.  2009,  351:  2449 
  • 14 For the single reported example of 4 as suitable organocatalyst, see: Tang X. Liégault B. Renaud J.-L. Bruneau C. Tetrahedron: Asymmetry  2006,  17:  2187 
  • 16 For the single reported example of 2 as suitable organocatalyst, see: Vignola N. List B. J. Am. Chem. Soc.  2004,  126:  450 
  • 17 Flores-Ortega A. Jiménez AI. Cativiela C. Nussinov R. Alemán C. Casanovas J. J. Org. Chem.  2008,  73:  3418 
  • For scarce reported examples of 3 as suitable organocatalyst, see:
  • 18a Kunz RK. MacMillan DWC. J. Am. Chem. Soc.  2005,  127:  3240 
  • 18b Hartikka A. Arvidsson PI. J. Org. Chem.  2007,  72:  5874 
  • 19a Mitchell CET. Cobb AJA. Ley SV. Synlett  2005,  611 
  • 19b Huang H. Jacobsen EN. J. Am. Chem. Soc.  2006,  128:  7170 
  • 19c Laars M. Ausmess K. Uudesmaa M. Tamm T. Kanger T. Lopp M. J. Org. Chem.  2009,  74:  3772 
  • 19d Tan B. Zeng X. Lu Y. Chua PJ. Zhong G. Org. Lett.  2009,  11:  1927 
  • 20a Wang J. Li H. Lou B. Zu L. Guo H. Wang W. Chem. Eur. J.  2006,  12:  4321 
  • 20b Arno M. Zaragoza RJ. Domingo LR. Tetrahedron: Asymmetry  2007,  18:  157 
  • 20c Okuyama Y. Nakano H. Watanabe Y. Makabe M. Takeshita M. Uwai K. Kabuto C. Kwon E. Tetrahedron Lett.  2009,  50:  193 
  • 21 Wiesner M. Upert G. Angelici G. Wennemers H. J. Am. Chem. Soc.  2010,  132: 
  • 22 Xue F. Zhang S. Duan W. Wang W. Adv. Synth. Catal.  2008,  250:  2194 
  • 23 Evans DA. Seidel D. J. Am. Chem. Soc.  2005,  127:  9958 
  • 24 All calculations were carried out with the Gaussian 09 suite of programs: Frisch MJ. Trucks GW. Schlegel HB. Scuseria GE. Robb MA. Cheeseman JR. Scalmani G. Barone V. Mennucci B. Petersson GA. Nakatsuji H. Caricato M. Li X. Hratchian HP. Izmaylov AF. Bloino J. Zheng G. Sonnenberg JL. Hada M. Ehara M. Toyota K. Fukuda R. Hasegawa J. Ishida M. Nakajima T. Honda Y. Kitao O. Nakai H. Vreven T. Montgomery JA. Peralta JE. Ogliaro F. Bearpark M. Heyd JJ. Brothers E. Kudin KN. Staroverov VN. Kobayashi R. Normand J. Raghavachari K. Rendell A. Burant JC. Iyengar SS. Tomasi J. Cossi M. Rega N. Millam NJ. Klene M. Knox JE. Cross JB. Bakken V. Adamo C. Jaramillo J. Gomperts R. Stratmann RE. Yazyev O. Austin AJ. Cammi R. Pomelli C. Ochterski JW. Martin RL. Morokuma K. Zakrzewski VG. Voth GA. Salvador P. Dannenberg JJ. Dapprich S. Daniels AD. Farkas . Foresman JB. Ortiz JV. Cioslowski J. Fox DJ. Gaussian 09, Revision A.1   Gaussian, Inc.; Wallingford CT: 2009. 
  • Calculations were carried out by fully optimizing transition structures at the B3LYP/6-31+G(d,p) level and then performing single-point calculations at M062X/6-311+G(d,p) level with correction for solvent using Tomasi’s polarizable continuum model (PCM) for DMSO level. The use of M062X functional was chosen following recent studies carried out by Houk and Papai. See:
  • 26a Rokob TA. Hamza A. Papai I. Org. Lett.  2007,  9:  4279 
  • 26b Wheeler SE. Moran A. Pieniazek SZ. Houk KN. J. Phys. Chem.  2009,  113:  10376 
15

Typical Experimental Procedure To a suspension of catalyst (10 mol%) and nitroalkene (0.5 mmol) in DMF (4 mL), acetone (13.5 mmol, 1 mL) was added, and the resulting mixture was stirred at 25 ˚C for the time indicated in Table  [³] . After that time the reaction was quenched with sat. NH4Cl (2 × 20 mL), the layers were separated and the aqueous layer extracted with EtOAc (3 × 25 mL). The combined organic layers were washed with brine (2 × 20 mL), dried (MgSO4), filtered, and rotatory evaporated to give a residue which was purified by flash chromatography using hexane-EtOAc (7:3) as an eluent.
Selected Spectral Data
Compound 8j: Following the general procedure, compound 8j was obtained after 10 d at r.t. as a white solid in 68% yield; mp 135-136 ˚C. ¹H NMR (400 MHz, CD3OD): δ = 2.05 (s, 3 H), 2.88 (dd, J = 2.6, 7.2 Hz, 2 H), 3.82-3.89 (m, 1 H), 4.57 (dd, J = 9.2, 12.4 Hz, 1 H), 4.70 (dd, J = 6.3, 12.4 Hz, 1 H), 6.70-6.74 (m, 2 H), 7.06-7.10 (m, 2 H). ¹³C NMR (100 MHz, CD3OD): δ = 30.4, 40.0, 47.2, 80.9, 116.5, 129.8, 131.5, 157.9, 208.8. The ee of the product was determined by HPLC using a Daicel Chiralpak IA column (n-hexane-i-PrOH = 90:10, flow rate 1 mL/min, λ = 230 nm): t R(major) = 29.1 min; t R(minor) = 26.9 min. HRMS: m/z calcd for C11H13NNaO4: 246.0737; found: 246.0728 [M+ + Na]. [α]D ²² 7.3 (c 1.0, MeOH, 33% ee).
Compound 8k: Following the general procedure, compound 8k was obtained after 10 d at r.t. as a yellow oil in 74% yield; mp 131-133 ˚C. ¹H NMR (400 MHz, CDCl3): δ = 2.11 (s, 3 H), 2.88 (d, J = 7.1 Hz, 2 H), 3.96 (q, J = 7.1 Hz, 1 H), 4.55 (dd, J = 7.8, 12.2 Hz, 1 H), 4.65 (dd, J = 6.8, 12.2 Hz, 1 H), 5.02 (s, 1 H), 6.91-6.95 (m, 2 H), 7.12-7.15 (m, 2 H), 7.31-7.44 (m, 5 H). ¹³C NMR (100 MHz, CDCl3): δ = 30.3, 38.3, 46.2, 70.0, 79.6, 115.2, 127.4, 128.0, 128.4, 128.5, 130.9, 136.7, 158.3, 205.5. The ee of the product was determined by HPLC using a Daicel Chiralpak IA column (n-hexane-i-PrOH = 97:3, flow rate 1 mL/min, λ = 230 nm): t R(major) = 44.5 min; t R(minor) = 41.1 min. HRMS: m/z calcd for C18H19NNaO4: 336.1206; found: 336.1215 [M+ + Na].
Compound 8l: Following the general procedure, compound 8l was obtained after 2 d at r.t. as a yellow oil in 67% yield. ¹H NMR (300 MHz, CDCl3): δ = 2.13 (s, 3 H), 2.88 (d, J = 6.9 Hz, 2 H), 3.97 (q, J = 6.9 Hz, 1 H), 4.56 (dd, J = 8.1, 12.6 Hz, 1 H), 4.67 (dd, J = 6.3, 12.6 Hz, 1 H), 7.07 (dd, J = 2.1, 8.4 Hz, 1 H), 7.32 (d, J = 2.1 Hz, 1 H), 7.39 (d, J = 8.4 Hz, 1 H). ¹³C NMR (75 MHz, CDCl3): δ = 30.2, 38.0, 45.7, 78.8, 126.9, 129.4, 130.9, 132.0, 133.0, 139.1, 204.6. The ee of the product was determined by HPLC using a Daicel Chiralpak IA column (n-hexane-i-PrOH = 97:3, flow rate 1 mL/min, λ = 230 nm): t R(major) = 29.1 min; t R(minor) = 26.1 min. HRMS: m/z calcd for C11H11Cl2NNaO3: 298.0008; found: 298.0007 [M+ + Na]. [α]D ²² -1.53 (c 1.0, CHCl3, 44% ee).

26

See ref. 25b. Whereas the mean error is estimated of about 2.0 kcal/mol for M062X functional, for B3LYP deviations up to more than 10 kcal/mol could be observed. For this reason, although B3LYP correctly predict the observed enantioselectivity for 4, it cannot be considered representative.