Aromatics to Diquinanes: An Expeditious Synthesis of Tetramethyl­bicyclo[3.3.0]octane Framework of Ptychanolide

Abstract

An expeditious route to methyl-7-oxo-1,4,5,8-tetra­methylbicyclo[3.3.0]octane-3-carboxylate from a simple aromatic precursor is described. Oxidative dearomatization of 2-hydroxy­methyl-3,4,6-trimethylphenol into spiroepoxycyclohexa-2,4-dienone, its cycloaddition and triplet-sensitized 1,2-acyl shift, and stereochemical inversion are the key features of our methodology.

cycloaddition - oxa-di-π-methane rearrangement - diquinanes - Diels-Alder reaction

References and Notes

1a Chanon M. Barone R. Baralotto C. Julliard M. Hendrickson JB. Synthesis  1998,  1559 

1b Corey EJ. Cheng X.-M. The Logic of Chemical Synthesis   John Wiley & Sons; New York: 1989. 

2 Tietze LF. Brasche G. Gericke KM. Domino Reactions in Organic Synthesis   Wiley-VCH; Weinheim: 2006. 

3a Ugi I. Pure Appl. Chem.  2001,  73:  187 

3b Bertozzi F. Gundersen BV. Gustafsson M. Olsson R. Org. Lett.  2003,  5:  1551 

4a Magdziak D. Meek SJ. Pettus TRR. Chem. Rev.  2004,  104:  1383 ; and references therein

4b Liao CC. Peddinti RK. Acc. Chem. Res.  2002,  35:  856 

4c Gagnepain J. Castel F. Quideau S. Angew. Chem. Int. Ed.  2007,  46:  1533 

4d Quideau S. Pouysegu L. Org. Prep. Proc. Int.  1999,  31:  617 

4e Bonnarme V. Mondon M. Gesson J.-P. Cousson A. Chem. Commun.  1999,  1143 

5a Takeda R. Naoki H. Iwashita T. Hirose Y. Tetrahedron Lett.  1981,  22:  5307 

5b Takeda R. Naoki H. Iwashita T. Mizukawa K. Hirose Y. Isida T. Inoue M. Bull. Chem. Soc. Jpn.  1983,  56:  1125 

5c Tori M. Arbiyanti H. Taira Z. Asakawa Y. Tetrahedron Lett.  1992,  33:  4011 

5d Tori M. Arbiyanti Z. Taira Z. Asakawa Y. Phytochemistry  1993,  32:  335 

5e Tang Y.-Q. Sattler I. Thiericke R. Grabley S. Feng S.-Z. Eur. J. Org. Chem.  2000,  2401 

6a Mehta G. Srikrishna A. Chem. Rev.  1997,  97:  671 

6b Paquette LA. Doherty AM. Polyquinane Chemistry   Vol. 26:  Hafner K. Rees CW. Trost BM. Lehn J.-M. Schleyer PvR. Zahradnik R. Springer; Berlin: 1987. 

7a Mehmoud B. West FG. Tetrahedron Lett.  2007,  48:  5051 

7b Srikrishna A. Gowri V. Tetrahedron: Asymmetry  2007,  18:  1663 

7c Tzvetkov NT. Neumann B. Stammler H.-G. Mattay J. Eur. J. Org. Chem.  2006,  351 

7d Khan FA. Rao CN. Tetrahedron Lett.  2006,  47:  7567 

7e Wu YT. Vidovic D. Magull J. De Meijere A. Eur. J. Org. Chem.  2005,  1625 

7f Srikrishna A. Dethe DH. Org. Lett.  2003,  5:  2295 

7g Dhimane A. Aissa C. Malacria M. Angew. Chem. Int. Ed.  2002,  41:  3284 

7h Shino M. Sato Y. Shisido K. Tetrahedron Lett.  2002,  43:  5039 

7i Harrowven DC. Lucas MC. Howes PD. Tetrahedron  2001,  57:  9157 

8a Hashimoto H. Abe Y. Mayuzumi Y. Karikomi M. Seki K. Haga K. Uyehara T. Tetrahedron Lett.  2002,  43:  265 

8b Solaja B. Huguet J. Karpf M. Dreiding AS. Tetrahedron  1987,  43:  4875 

8c Huguet J. Karpf M. Dreiding AS. Tetrahedron Lett.  1983,  24:  4177 

9a Singh V. Acc. Chem. Res.  1999,  31:  324 

9b Singh V. Sahu PK. Singh RB. Mobin SM. J. Org. Chem.  2007,  72:  10155 

9c Singh V. Chandra G. Mobin SM. Synlett  2008,  2267 

10 Andreetti GD. Böhmer V. Jordon JG. Tabatabai M. Ugozzoli F. Vogt W. Wolff A. J. Org. Chem.  1993,  58:  4023 

11a Adler E. Brasen S. Miyake H. Acta Chem. Scand.  1971,  25:  2055 

11b Becker H.-D. Bremholt T. Adler E. Tetrahedron Lett.  1972,  13:  4205 

11c Singh V. Porinchu M. Vedantham P. Sahu PK. Org. Synth.  2005,  81:  171 

12

All the compounds gave satisfactory spectral data.
Data of Compound 6
IR (neat): 1735 (br) cm^-¹. ^¹H NMR (400 MHz, CDCl₃): δ = 5.55 (br s, 1 H), 3.68 (s, 3 H), 3.06 (part of an AB system, J = 5.86 Hz, 1 H), 2.92 (part of an AB system, J = 5.86 Hz, 1 H), 2.77 (dd, J ₁ = 10.26 Hz, J ₂ = 5.87 Hz, 1 H), 2.15 (dd, J ₁ = 13.19 Hz, J ₂ = 10.26 Hz, 1 H), 1.87 (d, J = 1.46 Hz, 3 H), 1.74 (dd, J ₁ = 12.83 Hz, J ₂ = 5.87 Hz, 1 H), 1.26 (s, 3 H), 1.04 (s, 3 H). ^¹³C NMR (100 MHz, CDCl₃): δ = 204.3, 173.8, 146.2, 124.9, 59.1, 51.9, 50.6, 49.6, 45.2, 40.9, 36.7, 17.9, 15.7, 14.4. ESI-HRMS: m/z calcd for C₁₄H₁₉O₄: 251.1283 [M + H]⁺; found: 251.1277 [M + H]⁺.

13a Demuth M. Hisken W. Angew. Chem., Int. Ed. Engl.  1985,  24:  973 

13b Demuth M. Schaffner K. Angew. Chem., Int. Ed. Engl.  1982,  21:  820 

14a Zimmerman H. E., Armesto D.; Chem. Rev.; 1996, 96: 3065

14b Armesto D. Ortiz MJ. Agarrabeitia AR. CRC Handbook of Organic Photochemistry and Photobiology   Horspool W. Lenci F. CRC; Boca Raton: 2004.  p.95.1 

14c Singh V. In CRC Handbook of Organic Photochemistry and Photobiology   Horspool W. Lenci F. CRC; Boca Raton: 2004.  p.78.1 

15 Austin KAB. Banwell MG. Harfoot GJ. Willis AC. Tetrahedron Lett.  2006,  47:  7381 

16 Enholm EJ. Jia ZJ. J. Org. Chem.  1997,  62:  174 

17

Data of Compound 14
IR (neat): 1735 cm^-¹. ^¹H NMR (400 MHz, CDCl₃): δ = 3.68 (s, 3 H), 2.44-2.36 (m, 1 H), 2.32-2.15 (m, 2 H), 2.01 (d of AB pattern, J = 19.42 Hz, 1 H), 1.92 (d of AB pattern, J = 19.42 Hz, 1 H), 1.76-1.62 (m, 2 H), 1.09 (s, 3 H), 1.04-0.98 (m, 9 H). ^¹³C NMR (100 MHz, CDCl₃): δ = 219.0, 176.6, 53.2, 52.0, 50.7, 48.1, 45.6, 45.1, 36.4, 23.5, 21.4, 20.7, 14.2, 8.8. ESI-HRMS: m/z calcd for C₁₄H₂₃O₃: 239.1647 [M + H]⁺; found: 239.1655 [M + H]⁺.

18

Data for Hydrazone Derivative 15 IR (neat): 1731 cm^-¹. ^¹H NMR (400 MHz, CDCl₃): δ = 10.82 (br s, 1 H), 9.13 (d, J = 2.44 Hz, 1 H), 8.30 (dd, J ₁ = 8.85 Hz, J ₂ = 1.83 Hz, 1 H), 7.97 (d, J = 9.47 Hz, 1 H), 3.69 (s, 3 H), 2.67-2.45 (m, 1 H), 2.41-2.31 (m, 1 H), 2.30-2.25 (m, 2 H), 2.10 (d, J = 18.32 Hz, 1 H), 1.74-1.62 (m, 2 H), 1.19 (d, J = 6.72 Hz, 3 H), 1.10-1.09 (m, 6 H), 1.03 (s, 3 H). ^¹³C NMR (100 MHz, CDCl₃): δ = 176.6, 167.7, 145.2, 137.8, 130.1, 129.0, 123.7, 116.5, 53.4, 53.4, 52.0, 48.3, 47.9, 45.7, 35.8, 35.4, 20.9, 20.8, 14.3, 11.1. ESI-HRMS: m/z calcd for C₂₀H₂₇O₆N₄: 419.1931 [M + H]⁺; found: 419.1939 [M + H]⁺.
Crystal Data of Hydrazone Derivative 15
C₂₀H₂₆N₄O₆, M 418.45, space group, monoclinic, P 21/c, a = 20.475 (4), b = 14.245 (2), c = 7.3712 (12) Å, α = 90, β = 99.326 (19), γ = 90.0, U = 2121.5 (6)A^³, Z = 4, D _c  = 1.310 g/m^³, T = 150 (2) K, F(000) = 888, size = 0.21 × 0.18 × 0.15 mm. Reflections/collected/unique 10087/3694 [R(int) = 0.1809], final R indices [I > 2σ(I)] = R ₁ =  = 0.0732, wR ₂ = 0.1210 R indices (all data) R ₁ = 0.2346, wR ₂ = 0.1622. The complete crystal data can be obtained free of charge from The Cambridge Crystallographic data Centre via www.ccdc.cam.ac.uk/data_request/cif quoting the CCDC number 694681.

19

Data of Compound 18 IR (neat): 1736 (br) cm^-¹. ^¹H NMR (400 MHz, CDCl₃): δ = 3.70 (s, 3 H), 2.58-2.50 (dd with structure, J ₁ = 18 Hz, J ₂ = 9 Hz, 1 H), 2.41-2.34 (d with structure, J = 9 Hz, 1 H), 2.24-2.16 (m, 2 H), 2.00-1.86 (m, 3 H), 1.03 (d, partly merged with a s, J = 7.33 Hz, 3 H), 1.02 (s, 3 H), 1.00 (s, 3 H), 0.99 (d, partly merged with s, J = 6.72 Hz, 3 H). ^¹³C NMR (100 MHz, CDCl₃): δ = 220.3, 176.3, 53.2, 51.9, 50.9, 50.6, 49.0, 47.3, 46.1, 44.2, 23.7, 18.9, 15.2, 11.9. ESI-HRMS: m/z calcd for C₁₄H₂₃O₃: 239.1647 [M + H]⁺; found: 239.1655 [M + H]⁺.