Formal Synthesis of Linderone and Lucidone Based on One-Pot Cyclizations of 1,3-Bis-Silyl Enol Ethers with Oxalyl Chloride

Abstract

A formal synthesis of the acylcyclopentenediones linderone and lucidone is reported which is based on the cyclization of 2,4-bis(trimethylsilyloxy)-1,3,5-hexatrienes with oxalyl chloride and on the synthesis and functionalization of γ-(2-silyloxypropenylidene)butenolides.

Key words

acylcyclopentenediones - butenolides - cyclizations - natural products - silyl enol ethers

References

• 1 Kiang AK. Lee HH. Sim KY. J. Chem. Soc.  1962,  4338 
• 2 Lee HH. Tetrahedron Lett.  1968,  4243 
• 3a Takai M. Liu SY. Ogihara Y. Iitaka Y. Chem. Pharm. Bull.  1977,  25:  1404 
• 3b Leong Y.-W. Harrison LJ. Bennett GJ. Kadir AA. Connolly JD. Phytochemistry  1998,  47:  891 
• 4 Li X.-C. Ferreira D. Jacob MR. Zhang Q. Khan SI. ElSohly HN. Nagle DG. Smillie TJ. Khan IA. Walker LA. Clark AM. J. Am. Chem. Soc.  2004,  126:  6872 
• 5 Aoyama Y. Konoike T. Kanda A. Naya N. Nakajima M. Bioorg. Med. Chem. Lett.  2001,  11:  1695 
• 6 Clemo NG. Gedge DR. Pattenden G. J. Chem. Soc., Perkin Trans. 1  1981,  1448 
• 7 Birch AJ. Elliot P. Aust. J. Chem.  1956,  9:  95 
• For the synthesis of linderones from phloroglucinols, see:
• 8a Lee H.-H. Tan CH. J. Chem. Soc.  1967,  1583 
• 8b For lucidones, see: Lee H.-H. Que Y.-T. J. Chem. Soc., Perkin Trans. 1  1985,  453 
• 9 Römpp Lexikon Naturstoffe   Fugmann B. Lane-Fugmann S. Steglich W. Thieme; Stuttgart: 1997. 
• 10 For a review of 1,3-bis-silyl enol ethers, see: Langer P. Synthesis  2002,  441 
• Reviews:
• 11a Brückner R. Chem. Commun.  2001,  141 
• 11b Brückner R. Curr. Org. Chem.  2001,  5:  679 
• 12a Langer P. Schneider T. Stoll M. Chem.-Eur. J.  2000,  6:  3204 
• 12b For 1-alkoxy-1,5-bis(trimethylsilyloxy)-1,3,5-hexatrienes, see: Langer P. Freifeld I. Synlett  2001,  523 
• 12c For applications to the synthesis of pulvinic acids, see: Ahmed Z. Langer P. J. Org. Chem.  2004,  69:  3753 
• 12d See also: Desage-El Murr M. Nowaczyk S. Le Gall T. Mioskowski C. Amekraz B. Moulin C. Angew. Chem. Int. Ed.  2003,  42:  1289 ; Angew. Chem. 2003, 115, 1327
• For reactions of 1,3-bis-silyl enol ethers with α,β-unsaturated aldehydes, see:
• 13a Staunton J. Sutkowski AC. J. Chem. Soc., Chem. Commun.  1991,  1108 
• 13b Soriente A. De Rosa M. Stanzione M. Villano R. Scettri A. Tetrahedron: Asymmetry  2001,  12:  959 

14

Synthesis of 5a.
To a CH₂Cl₂ solution (10 mL) of oxalyl chloride (0.090 mL, 1.03 mmol) and 4a (0.332 g, 1.00 mmol) was added a CH₂Cl₂ solution (5 mL) of Me₃SiOTf (0.09 mL, 0.50 mmol) at -78 °C. The temperature of the reaction mixture was allowed to rise to 20 °C over 12 h. After stirring for 2 h at 20 °C, brine (50 mL) was added. The aqueous layer was separated and extracted with CH₂Cl₂ (2 × 50 mL). The combined organic layers were washed with an aq solution of HCl (10%, 50 mL), dried over anhyd Na₂SO₄ and filtered. The solvent of the filtrate was removed in vacuo and the residue was purified by column chromatography (silica gel, hexane-EtOAc) to give 5a (0.155 g, 64%) as a yellow solid; mp 128-129 °C; R _f = 0.27 (hexane-EtOAc = 1:1). IR (KBr): 3002 (br), 1800 (s), 1628 (s), 1612 (s), 1552 (s), 1398 (m), 1267 (s), 1213 (m), 1045 (s), 979 (m), 767 (w) cm^-1. ¹H NMR (300 MHz, CDCl₃): δ = 7.74-7.67 (m, 3 H, ArH, =CH), 7.46-7.42 (m, 3 H, ArH), 7.12-7.03 (m, 2 H, =CH), 6.59 (s, 1 H, =CH). ¹³C NMR (75 MHz, CDCl₃): δ = 188.3, 163.7, 159.3, 151.4 (C), 152.3 (CH), 134.4 (C), 130.5, 128.9 (2 C), 128.5 (2 C), 128.2, 107.7, 103.6 (CH). MS (EI, 70 eV): m/z (%) = 241.9 (1) [M⁺], 225.9 (2), 213.9 (3), 131.1 (1), 102.8 (1), 77.3 (1), 44.0 (7), 28.0 (100). Anal. Calcd for C₁₄H₁₀O₄ (%): C, 69.41; H, 4.16. Found: C, 69.17; H, 4.49.