Synlett 2008(15): 2331-2333  
DOI: 10.1055/s-2008-1077977
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

Regioselective Synthesis of Functionalized 3-(Methylthio)phenols by the First Formal [3+3] Cyclocondensations of 1,3-Bis(trimethylsilyloxy)-1,3-butadienes with 1,1-Bis(methylthio)-1-en-3-ones

Mathias Lubbea, Renske Klassena, Tiana Trabhardta, Alexander Villingera, Peter Langer*a,b
a Institut für Chemie, Universität Rostock, Albert Einstein Str. 3a, 18059 Rostock, Germany
e-Mail: peter.langer@uni-rostock.de;
b Leibniz-Institut für Katalyse an der Universität Rostock e.V., Albert Einstein Str. 29a, 18059 Rostock, Germany
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Publikationsverlauf

Received 21 April 2008
Publikationsdatum:
15. Juli 2008 (online)

Abstract

The [3+3] cyclocondensation of 1,3-bis(silyl enol ethers) with 1,1-bis(methylthio)-1-en-3-ones results in the regioselective formation of 3-(methylthio)phenols. The products represent useful synthetic building blocks, which are not readily available by other methods.

    References and Notes

  • 1a Campiani G. Nacci V. Bechelli S. Ciani SM. Garofalo A. Fiorini I. Wikström H. de Boer P. Liao Y. Tepper PG. Cagnotto A. Mennini T. J. Med. Chem.  1998,  41:  3763 
  • 2a Cabiddu MG. Cabiddu S. Cadoni E. Demontis S. Fattuoni C. Melis S. Tetrahedron  2002,  58:  4529 
  • 3 Ritchie CD. Hofelich TC. J. Am. Chem. Soc.  1980,  102:  7039 
  • 4 Ohkata K. Takee K. Akiba K.-y. Bull. Chem. Soc. Jpn.  1985,  58:  1946 
  • 5 Cabiddu MG. Cabiddu S. Cadoni E. Demontis S. Fattuoni C. Melis S. Usai M. Synthesis  2002,  875 
  • 6a Mukherjee C. Kamila S. De A. Tetrahedron  2003,  59:  4767 
  • 6b Mukherjee C. De A. Synlett  2002,  325 
  • 6c Kamila S. Mukherjee C. De A. Synlett  2003,  1479 
  • 6d Pradhan TK. De A. Tetrahedron Lett.  2005,  46:  1493 
  • 7 Weber R. J. Heterocycl. Chem.  1978,  15:  865 
  • 8 Dhareshwar GP. Chhaya PN. Hosangadi BD. Indian J. Chem., Sect. B: Org. Chem. Incl. Med. Chem.  1980,  19:  831 
  • 9 Uchida Y. Kozuka S. Bull. Chem. Soc. Jpn.  1982,  55:  1183 
  • 10 Grohe K. Heitzer H. Liebigs Ann. Chem.  1987,  29 
  • 11a Luxen AJ. Christiaens LEE. Renson MJ.
    J. Organomet. Chem.  1985,  287:  81 
  • 11b Zhou C. Dubrovsky AV. Larock RC. J. Org. Chem.  2006,  71:  1626 
  • 12 Ila H. Junjappa H. J. Org. Chem.  1990,  55:  5589 
  • 13 Cipollina JA. Ruediger EH. New JS. Wire ME. Shepherd TA. Smith DW. Yevich JP. J. Med. Chem.  1991,  34:  3316 
  • 14 Cabiddu S. Maccioni A. Piras PP. Plumitallo A. Gazz. Chim. Ital.  1981,  111:  123 
  • 15 Bi X. Dong D. Liu Q. Pan W. Zhao L. Li B. J. Am. Chem. Soc.  2005,  127:  4578 
  • 16 Chan T.-H. Brownbridge P. J. Am. Chem. Soc.  1980,  102:  3534 
  • 17 For a review of 1,3-bis(silyl enol ethers) in general, see: Langer P. Synthesis  2002,  441 
  • 18 For a review of [3+3] cyclocondensations of 1,3-bis(silyl enol ethers) with 1,3-dielectrophiles, see: Feist H. Langer P. Synthesis  2007,  327 
  • 19a Sher M. Ahmed Z. Rashid MA. Fischer C. Langer P. J. Org. Chem.  2007,  72:  6284 
  • 19b Mamat C. Büttner S. Trabhardt T. Fischer C. Langer P. J. Org. Chem.  2007,  72:  6273 
  • 20 Mamat C. Pundt T. Dang THT. Klassen R. Reinke H. Köckerling M. Langer P. Eur. J. Org. Chem.  2008,  492 
  • 21 Sher M. Langer P. Synlett  2008,  1050 
  • 22 Potts KT. Winslow PA. Synthesis  1987,  839 
  • 23 Typical Procedure: Synthesis of Ethyl 4-Ethyl-6-hydroxy-3-methyl-2-(methylthio)benzoate (4b) To a solution of 2b (0.190 g, 1.0 mmol) and 3b (0.549 g, 2.0 mmol) in CH2Cl2 (2 mL) was added TiCl4 (0.11 mL, 1.0 mmol) at -78 ˚C under argon. The temperature of the reaction mixture was allowed to rise to 20 ˚C during 14 h, and an aq HCl solution (10%, 10 mL) was added. The organic layer was separated, and the aqueous layer was extracted with CH2Cl2 (3 × 10 mL). The combined organic layers were dried (Na2SO4), filtered, and concentrated in vacuo. After column chromatography (SiO2, heptane-EtOAc = 10:1), 4b was obtained as a colorless solid (227 mg, 89%); mp 120-121 ˚C; Rf  = 0.39 (heptane-EtOAc = 3:1). ¹H NMR (250 MHz, CDCl3): δ = 9.06 (s, 1 H, OH), 6.78 (s, 1 H, ArH), 4.43 (q, ³ J = 7.1 Hz, 2 H, OCH2), 2.60 (q, ³ J = 7.5 Hz, 2 H, ArCH2), 2.45 (s, 3 H, ArCH3), 2.28 (s, 3 H, SCH3), 1.41 (t, ³ J = 7.1 Hz, 3 H, OCH2CH 3), 1.18 (t, ³ J = 7.5 Hz, 3 H, ArCH2CH 3). ¹³C NMR (300 MHz, CDCl3): δ = 170.2 (C=O), 156.9 (CO), 148.8, 136.2, 132.7, 117.3 (CAr), 116.9 (CHAr), 61.8 (OCH2), 27.6 (ArCH2), 20.0, 16.2, 14.0, 13.8 (CH3). IR (ATR): ν = 3298 (OH), 1699 (C=O) cm. MS (EI, 70 eV): m/z (%) = 254 (39) [M+], 209 (21), 208 (100), 193 (8), 180 (27), 165 (32). Anal. Calcd for C13H18O3S (254.10): C, 61.39; H, 7.13. Found: C, 61.35; H, 7.27
  • 24 CCDC-685823 contains all crystallographic details of this publication and is available free of charge at www.ccdc.cam.ac.uk/conts/retrieving.html or can be ordered from the following address: Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge CB2 1EZ, UK; fax: +44(1223)336033; or deposit@ccdc.cam.ac.uk