The High Stereoselectivity of the Tandem Sequence Diels-Alder Reaction/Ireland­-Claisen Rearrangement Starting from Substituted O-(E)-Buta-1,3-dienyl Ketene Acetals and Cyclic Dienophiles

Abstract

A new tandem reaction leads to bicyclic cyclohexene derivatives with complete control of the relative configuration of the four chiral centers formed. The high diastereoselectivity is the consequence of an endo-selective Diels-Alder reaction followed by an Ireland-Claisen rearrangement that proceeds via a boat-like transition state.

Key words

cycloaddition - Diels-Alder reaction - rearrangement - stereoselectivity - tandem reaction

References

• 1a Wender PA. Miller BL. In Organic Synthesis: Theory and Applications   Vol. 2:  Hudlicky T. JAI Press; Greenwich: 1993.  p.27 
• 1b Tietze LF. Beifuss U. Angew. Chem., Int. Ed. Engl.  1993,  32:  131 
• 1c Hudlicky T. Chem. Rev.  1996,  96:  3 
• 1d Denmark SE. Thorarensen A. Chem. Rev.  1996,  96:  137 
• 1e Tietze LF. Chem. Rev.  1996,  96:  115 
• 1f Padwa A. Weingarten MD. Chem. Rev.  1996,  96:  223 
• 1g Ho T.-L. Tandem Organic Reactions   John Wiley; New York: 1992. 
• 1h Wender PA. Chem. Rev.  1996,  96:  1 
• 1i Tietze LF. Brasche G. Gericke K. Domino Reactions in Organic Synthesis   Wiley-VCH; Weinheim: 2006. 
• 2 Neuschütz K. Velker J. Neier R. Synthesis  1998,  227 
• 3a Huber S. Stamouli P. Neier R. J. Chem. Soc., Chem. Commun.  1985,  533 
• 3b Huber S. Stamouli P. Jenny T. Neier R. Helv. Chim. Acta  1986,  69:  1898 
• 3c Schoepfer J. Marquis C. Pasquier C. Neier R. J. Chem. Soc., Chem. Commun.  1994,  1001 
• 3d Soldermann N. Velker J. Vallat O. Stoeckli-Evans H. Neier R. Helv. Chim. Acta  2000,  83:  2266 
• 3e Velker J. Roblin J.-P. Neels A. Tesuro A. Stoeckli-Evans H. Klaerner F.-G. Gehrke J.-S. Neier R. Synlett  1999,  925 
• 4a Baak M. Rubin Y. Franz A. Stoeckli-Evans H. Bigler L. Nachbauer J. Neier R. Chimia  1993,  47:  233 
• 4b Franz A. Eschler P.-Y. Tharin M. Stoeckli-Evans H. Neier R. Synthesis  1996,  1239 
• 4c Franz A. Eschler P.-Y. Tharin M. Neier R. Tetrahedron  1996,  52:  11643 
• 4d Franz A. Eschler P.-Y. Tharin M. Neier R. In Electronic Conference on Trends in Organic Chemistry (ECTOC-1) [Online]   Rzepa HS. Goodman JM. Leach C. Royal Society of Chemistry; Cambridge: 1995.  ; See: http://www.ch.ic.ac.uk/ectoc/papers/39/ (accessed 12 April 2007); ISBN 084504899
• 5a Seebach D. Amstutz R. Laube T. Schweizer WB. Dunitz JD. J. Am. Chem. Soc.  1985,  107:  5403 
• 5b Corey EJ. Wright ST. J. Org. Chem.  1990,  55:  1670 
• 6 Corey EJ. Gross AW. Tetrahedron Lett.  1984,  25:  495 
• 8 Pilcher AS. DeShong P. J. Org. Chem.  1993,  58:  5130 
• 9a Lutz RP. Chem. Rev.  1984,  84:  205 
• 9b Wipf P. In Comprehensive Organic Synthesis   Vol. 5:  Trost BM. Fleming I. Pergamon; New York: 1991.  p.827 
• 10a Ireland RE. Wipf P. Xiang J. J. Org. Chem.  1991,  56:  3572 
• 10b Ireland RE. Wipf P. Armstrong JD. J. Org. Chem.  1991,  56:  650 
• 11 Khaledy MM. Kalani MMYS. Khuong KS. Houk KN. Aviyente V. Neier R. Soldermann N. Velker J. J. Org. Chem.  2003,  68:  572 
• 12 Bischofberger N. Waldmann H. Saito T. Simon E. S. Lees W. Bednarski M. D. Whitesides G. M. J. Org. Chem.  1988,  53: 3457

7

Crystal structure analysis of 2f: C₂₀H₂₅NO₄Si, M _r = 371.50, monoclinic, space group P2₁, a = 8.191(1), b = 23.442(2), c = 11.342(1) Å, β = 105.12(1)°, V = 2102.4(3) ų, Z = 4, ρ_calcd = 1.174 g cm^-3, T = 223(2) K, µ = 1.34 cm^-1, λ = 0.71073 Å, 1.65 ≤ θ ≤ 26.05°, Stoe IPDS diffractometer, crystal dimensions 0.65 × 0.40 × 0.15 mm; 7956 independent reflections, 3934 observed reflections with [I > 2σ(I)]; R-values [I > 2σ(I)]: R ₁ = 0.0658, wR ₂ = 0.1409.
Crystal structure analysis of 4: C₂₄H₁₈N₂O₆, M _r = 430.40, triclinic, space group P, a = 7.894(2), b = 11.426(3), c = 12.057(4)Å, α = 101.78(4), β = 97.43(4), χ = 98.91(3)°, V = 1037.2(5) ų, Z = 2, ρ_calcd = 1.378 g cm^-3, T = 293(2) K, µ = 1.01 cm^-1, λ = 0.71073 Å, 1.65 ≤ θ ≤ 26.05°, Stoe IPDS diffractometer, crystal dimensions 0.70 × 0.50 × 0.40 mm; 3738 independent reflections, 2453 observed reflections with [I > 2σ(I)]; R-values [I > 2σ(I)]: R ₁ = 0.0328, wR ₂ = 0.0816.
Crystal structure analysis of 5: C₂₄H₁₈N₂O₆·CHCl₃, M _r = 549.77, triclinic, space group P, a = 10.261(3), b = 11.610(3), c = 11.818(4)Å, α = 76.81(3), β = 67.38(3), χ = 87.40(2)°, V = 1263.9(7) ų, Z = 2, ρ_calcd = 1.445 g cm^-3, µ = 1.34 cm^-1, λ = 0.71073 Å, 2.00 ≤ θ ≤ 25.50°, Stoe AED2 diffractometer, crystal dimensions 0.65 × 0.49 × 0.23 mm; 4709 independent reflections, 3504 observed reflections with [I > 2σ(I)]; R-values [I > 2σ(I)]: R ₁ = 0.0701, wR ₂ = 0.1669.
All three structures were refined with full-matrix block least squares on F ²; all non-hydrogen atoms were anisotropically refined. Crystallographic data (excluding structure factors)for the structures reported in this paper have been deposited with the Cambridge Crystallographic Data Centre as supplementary publication no. CCDC-118778 for 1f, CCDC-629878 for 2f, CCDC-629879 for 3c, CCDC-629880 for 4 and CCDC-629881 for 5. Copies of the data can be obtained free of charge on application to CCDC, 12 Union Road, Cambridge CB2 1EZ, UK [fax: [phone]; e-mail: [e-mail].