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Synlett 2011(12): 1717-1722  
DOI: 10.1055/s-0030-1260824
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

Trapping of Oxonium Ylides with Michael Acceptors: Highly Diastereoselective Three-Component Reactions of Diazo Compounds with Alcohols and Benzylidene Meldrum’s Acids/4-Oxo-enoates

Xingchun Han, Minghua Gan, Huang Qiu, Jingjing Ji, Xia Zhang, Liqing Jiang*, Wenhao Hu*
Institute of Drug Discovery and Development, and Department of Chemistry, East China Normal University, 3663 North Zhongshan Road, Shanghai 200062, P. R. of China
Fax: +86(21)62232487; e-Mail: lqjiang@sat.ecnu.edu.cn; e-Mail: whu@chem.ecnu.edu.cn;
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Publication History

Received 26 February 2011
Publication Date:
29 June 2011 (online)

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Abstract

Trapping of oxonium ylides with a number of Michael acceptors via a 1,4-addition fashion has been investigated. Benzylidene Meldrum’s acids and 4-oxo-enoates have been found to be matched components as suitable Michael acceptors for the transformation. Thus, Rh2(OAc)4-catalyzed three-component reactions of diazo compounds, alcohols, and benzylidene Meldrum’s acids/4-oxo-enoates gave corresponding α-hydroxyesters in good yield with high to excellent diastereoselectivity. Synthetic utility of this efficient method was demonstrated by conversion of the addition product to a γ-butyrolactone through simple procedures.

Key words

oxonium ylide - multicomponent reaction - benzylidene Meldrum’s acid - 4-oxo-enoates - 1,4-addition

    References and Notes

  • For reviews on MCR, see:
  • 1a Dömling A. Chem. Rev.  2006,  106:  17 
    Google Scholar
  • 1b Zhu J. Bienaymé H. Multicomponent Reactions   Wiley-VCH; Weinheim: 2005. 
    Google Scholar
  • 1c Wipf P. Stephenson CRJ. Okumura K. J. Am. Chem. Soc.  2003,  125:  14694 
    Google Scholar
  • 1d Dömling A. Ugi I. Angew. Chem. Int. Ed.  2000,  39:  3168 
    Google Scholar
  • For recent progress in multicomponent reactions, see:
  • 2a Ramón DJ. Yus M. Angew. Chem. Int. Ed.  2005,  44:  1602 
    Google Scholar
  • 2b Nicolaou KC. Edmonds DJ. Bulger PG. Angew. Chem. Int. Ed.  2006,  45:  7134 
    Google Scholar
  • 2c Enders D. Grondal C. Hüttl MRM. Angew. Chem. Int. Ed.  2007,  46:  1570 
    Google Scholar
  • 2d Zhu W. Mena M. Jnoff E. Sun N. Patrick P. Ghosez L. Angew. Chem. Int. Ed.  2009,  48:  5880 
    Google Scholar
  • 2e Sunderhaus JD. Martin SF. Chem. Eur. J.  2009,  15:  1300 
    Google Scholar
  • 2f Enders D. Hüttl MRM. Grondal C. Raabe G. Nature (London)  2006,  441:  861 
    Google Scholar
  • 2g Liu H. Dagousset G. Masson G. Retailleau P. Zhu JP. J. Am. Chem. Soc.  2009,  131:  4598 
    Google Scholar
  • 2h Arndtsen BA. Chem. Eur. J.  2009,  15:  302 
    Google Scholar
  • 3a Lu C. Liu H. Chen Z. Hu W. Mi A. Org. Lett.  2005,  7:  83 
    Google Scholar
  • 3b Wang Y. Zhu Y. Chen Z. Mi A. Hu W. Doyle MP. Org. Lett.  2003,  5:  3923 
    Google Scholar
  • 3c Zhu Y. Zai C. Yue Y. Yang L. Hu W. Chem. Commun.  2009,  1362 
    Google Scholar
  • 3d Lu C. Chen Z. Hu W. Mi A. Org. Lett.  2004,  6:  3071 
    Google Scholar
  • 3e Lu C. Liu H. Chen Z. Hu W. Mi A. Chem. Commun.  2005,  2624 
    Google Scholar
  • 3f Wang Y. Chen Z. Mi A. Hu W. Chem. Commun.  2004,  2486 
    Google Scholar
  • 4 Zhang X. Huang H. Guo X. Guan X. Yang L. Hu W. Angew. Chem. Int. Ed.  2008,  47:  6647 
    CrossrefGoogle Scholar
  • 5 Guo X. Huang H. Yang L. Hu W. Org. Lett.  2007,  9:  4721 
    CrossrefGoogle Scholar
  • 6a Huang H. Guo X. Hu W. Angew. Chem. Int. Ed.  2007,  46:  1337 
    Google Scholar
  • 6b Hu W. Xu X. Zhou J. Liu W. Huang H. Hu J. Yang L. Gong L. J. Am. Chem. Soc.  2008,  130:  7782 
    Google Scholar
  • 6c Xu X. Zhou J. Yang L. Hu W. Chem. Commun.  2008,  6564 
    Google Scholar
  • 7a Guan X. Yang L. Hu W. Angew. Chem. Int. Ed.  2010,  49:  2190 
    Google Scholar
  • 7b Zhu Y. Zhai C. Yang L. Hu W. Chem. Commun.  2010,  46:  2865 
    Google Scholar
  • 9a Dumas AM. Fillion E. Acc. Chem. Res.  2010,  43:  440 
    Google Scholar
  • 9b Fillion E. Fishlock D. Wilsily A. Goll JM. J. Org. Chem.  2005,  70:  1316 
    Google Scholar
  • 9c Fillion E. Fishlock D. Org. Lett.  2003,  5:  4653 
    Google Scholar
  • 9d Frost CG. Hartley BC. J. Org. Chem.  2009,  74:  3599 
    Google Scholar
  • 9e Lipson V. Gorobets NY. Mol. Diversity  2009,  13:  399 
    Google Scholar
  • 9f Chen B.-C. Heterocycles  1991,  32:  529 
    Google Scholar
  • 10a Ivanov AS. Chem. Soc. Rev.  2008,  37:  789 
    Google Scholar
  • 10b Adams TE. Sous ME. Hawkins BC. Hirner S. Holloway G. Khoo ML. Owen DJ. Savage GP. Scammells PJ. Rizzacasa MA. J. Am. Chem. Soc.  2009,  131:  1607 
    Google Scholar
  • 10c Kim S. Chin Y.-W. Su B.-N. Riswan S. Kardono LBS. Afriastini JJ. Chai H. Farnsworth NR. Cordell GA. Swanson SM. Kinghorn AD. J. Nat. Prod.  2006,  69:  1769 
    Google Scholar
  • 10d Desaubry H, Desaubry GC, Cresteil T, and Tuerkeri G. inventors; Preparation of rocaghaol derivatives as cardioprotectants. PCT Int. Appl. 2010, 93pp. CODEN: PIXXD2 WO 2010060891 A1  20100603. 
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General Procedure for Trapping Oxonium Ylides with Michael Acceptors
A suspension of Rh2(OAc)4 (8.8 mg, 1 mmol%), alcohols 3 (0.24 mmol, 1.2 equiv), Michael acceptors 1 (0.2 mmol, 1 equiv) in CH2Cl2 (3 mL) under argon atmosphere was stirred at r.t., and then diazo compound 2 (0.24 mmol, 1.2 equiv) in CH2Cl2 (4 mL) was added over 2 h via a syringe pump. After completion of the addition, the reaction was stirred for another 0.5 h. The crude product was subjected to ¹H NMR spectroscopy analysis for the determination of diastereo-selectivity. The reaction mixture was purified by flash chromatography on silica gel (eluent: EtOAc-light PE = 1:20 to ca. 1:10) to give pure products.

11

Analytical Data for (2 S *,3 R *)-Methyl 2-(Benzyloxy)-3-(2,2-dimethyl-4,6-dioxo-1,3-dioxan-5-yl)-3-(4-methoxy-phenyl)-2-phenylpropanoate (4gf)
¹H NMR (400 MHz, CDCl3): δ = 7.42-6.64 (m, 14 H), 5.08 (s, 1 H), 4.60-4.58 (d, 1 H), 4.09-4.06 (d, 1 H), 4.04 (s, 1 H), 3.78 (s, 3 H), 3.73 (s, 3 H), 1.66 (s, 3 H), 1.30 (s, 3 H). ¹³C NMR (100 MHz, CDCl3): δ = 170.32, 165.78, 165.70, 158.51, 138.00, 137.74, 131.32, 129.80, 129.73, 129.07, 128.92, 128.66, 128.61, 128.56, 128.50, 128.14, 127.46, 126.60, 112.80, 104.40, 86.33, 68.97, 56.08, 55.01, 51.61, 48.64, 27.50, 27.42. ESI-HRMS: m/z calcd for C30H30NaO8 [M + Na]+: 541.1838; found: 541.1800.

12

Crystallographic Data for Compound 4gb Empirical formula: C29H27NO9, CCl4; formula weight: 685.04; bond precision: C-C = 0.0040 Å; λ = 0.71073 Å; unit cell dimensions: a = 14.3476 (4) Å, α = 90˚, b = 10.1897 (3) Å, β = 94.419 (1)˚, c = 20.8480 (5) Å, γ = 90˚; temp: 296 K; volume: 3038.87 (14) A³, space group: P2 (1)/c; Z = 4; F(000) = 1280.0; h,k,l max = 17, 12, 24; N ref = 5339; T min, T max = 0.881, 1.000; correction method: MULTI-SCAN; data completeness = 0.997; θ max = 25.010; R(reflections) = 0.0466 (3695); wR2 = 0.1310 (5339); S = 1.034; N par = 398. CCDC 822168 contains the supplementary crystallographic data for this structure. These data can be obtained free of charge from the Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_request/cif.

13

Analytical Data for (2R*,3S*)-2-Benzyloxy-3-(2-oxo-2-phenyl-ethyl)-2-phenyl-succinic Acid Dimethyl Ester (4ha)
¹H NMR (400 MHz, CDCl3): δ = 7.92-7.85 (m, 2 H), 7.58-7.50 (m, 3 H), 7.48-7.24 (m, 10 H), 4.57 (d, J = 11.9 Hz, 1 H), 4.33 (d, J = 11.9 Hz, 1 H), 4.26 (dd, J = 10.7, 2.7 Hz, 1 H), 3.93 (s, 3 H), 3.67 (s, 3 H), 3.55 (dd, J = 18.1, 10.7 Hz, 1 H), 3.15 (dd, J = 18.1, 2.7 Hz, 1 H). ¹³C NMR (100 MHz, CDCl3): δ = 197.74, 172.32, 171.10, 138.30, 136.52, 135.41, 133.15, 128.75, 128.49, 128.45, 128.24, 128.08, 127.76, 127.30, 126.88, 85.84, 67.83, 52.45, 52.09, 50.69, 37.02. ESI-HRMS: m/z calcd for C27H26NaO6 [M + Na]+: 469.1627; found: 469.1611.

14

Crystallographic Data for Compound 4ha Empirical formula: C27H26O6; formula weight: 446.48; temp: 293 (2) K; λ = 0.71073 Å; crystal system space group: monoclinic, P2 (1)/c; unit cell dimensions: a = 11.0595 (9) Å, α = 90˚, b = 12.4819 (10) Å, β = 106.3950 (10)˚, c = 17.3890 (14) Å, γ = 90˚; volume: 2302.8 (3) A³, Z = 4; calcd density = 1.288 mg/m³; absorption coefficient = 0.091 mm-¹, F(000) 472; crystal size = 0.385 × 0.316 × 0.257 mm; θ range for data collection: 1.96-26.00˚; limiting indices, -13 ≤ h ≤ 13, -11 ≤ k ≤ 15, -17 ≤ l ≤ 21, reflections collected/unique: 12323/4530 [R(int) = 0.0223]; completeness to = 26.00, 100.0%; absorption correction: empirical; max. and min. transmission =: 1.00000 and 0.75342; refinement method, full-matrix least-squares on F²; data/restraints/parameters, 4530/0/300; goodness-of-fit on F2, 1.020; final R indices [I > 2σ(I)], R1 = 0.0439, wR2 = 0.1097, R indices (all data), R1 = 0.0554, wR2 = 0.1171; largest diff. peak and hole, 0.180 and -0.151 e A-³. CCDC 812578 contains the supplementary crystallographic data for this structure. These data can be obtained free of charge from the Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_request/cif.