Synlett 2009(13): 2201-2202  
DOI: 10.1055/s-0029-1217607
SPOTLIGHT
© Georg Thieme Verlag Stuttgart ˙ New York

Dimethylsulfonium Methylide: A Versatile Reagent

Huankai Yao*
School of Pharmaceutical Science and Technology, Tianjin University, Tianjin, 300072, P. R. of China
e-Mail: hkyao@tju.edu.cn;

Further Information

Publication History

Publication Date:
23 July 2009 (online)

Biographical Sketches

Huankai Yao was born in Hebei Province, P. R. of China, in 1979. He received his B.Sc. in Pharmacy from Shandong University in 2004 and M.Sc. in Medicinal Chemistry from Shandong Academy of Medical Sciences in 2007. Presently he is working toward his Ph.D. under the supervision of Prof. Shende Jiang and Prof. Hongquan Duan at Tianjin University. His research interests include isolation, structure elucidation and synthesis of bioactive natural products.

Introduction

Dimethylsulfonium methylide, Me2SCH2, was reported by Corey and Chaykovsky for the first time in 1962. [¹] It is a versatile nucleophile which can insert the methylene unit into certain unsaturated linkages, such as C=O and C=C, to form epoxides and cyclopropanes, respectively. [²] Utilization of this reagent is a reliable method in many synthetic applications and it has been well-utilized in the synthesis of functional molecules, especially bioactive natural products.

Preparation

In general, Me2SCH2 is prepared from trimethylsulfonium iodide. Addition of a DMSO solution of trimethylsulfonium iodide to an equivalent solution of methylsulfinyl carbanion in THF-DMSO under nitrogen afforded Me2SCH2 successfully. [²] This reagent is decomposable at room temperature with a half-life of a few minutes. [²] In practice trimethylsulfonium iodide and a strong base are employed directly to produce Me2SCH2.

Scheme 1

Abstracts

(A) Carbonyl groups of aromatic and nonconjugated aldehydes and ketones can react with dimethylsulfonium methylide to generate corresponding epoxides. Toward the synthesis of quassinoid, the nonconjugated aldehyde was treated with Me2SCH2 to give a separable 2:1 mixture of epoxide and its C7 diastereomer in 85% combined yield, respectively. [³] In the (S)-ibuprofen synthesis the aromatic epoxide can be synthesized from the corresponding acetophenone precursor by the reaction with Me2SCH2. [4]

(B) When α,β-unsaturated carbonyl compounds react with dimethylsulfonium methylide, epoxide or cyclopropane derivatives are generated as major products. By the reaction with Me2SCH2, α,β-keto unsaturated C-glycosides can be converted into α,β-unsaturated epoxy-C-glycosides. [5] But in the synthesis of d-homo analogues of the natural neurosteroid, cyclopropylketone was obtained by reaction of 16-dehydropregnenolone with Me2SCH2. [6]

(C) The reaction of benzyl tert-butylsulfinyl imine with Me2SCH2 led to an aziridine in good yield and with excellent diastereoselectivity. [7]

(D) Epoxides and aziridines, when subjected to dimethylsulfonium methylide, can provide corresponding allyl alcohols and allylic amines. In the asymmetric synthesis of (S)-vigabatrin Sudalai and co-workers used this regiospecific ring opening of an epoxide with Me2SCH2 to produce the allyl alcohol in good yield. [8] Using Me2SCH2, one-carbon homologation of N-sulfonylaziridine to allylic amine could be carried out successfully. [9]

(E) Treating tetralone with dimethylsulfonium methylide, Plumet and co-workers afforded the corresponding aldehyde toward the synthesis of hydrophenalene ring system of pseudopterosins. [¹0]

(F) When silylalkylidene malonate was added to Me2SCH2 and then quenched with benzyl bromide the desired vinylsilane was provided in high yield. [¹¹]

(G) Oxoketene dithioacetal was exposed to Me2SCH2 followed by acid workup, which gave rise to 7-(methythio)acenaphtho[1,2-c]furan in good yield. [¹²] If the treatment of ketene dithioacetal with Me2SCH2 was followed by acid workup, cyclocondensation led to the formation of an unexpected lactone. [¹³]

(H) A THF solution of the iminophosphane was added to an equimolar quantity of Me2SCH2 to produce methylenephosphorane. [¹4]

    References

  • 1 Corey EJ. Chaykovsky M. J. Am. Chem. Soc.  1962,  84:  3782 
  • 2 Corey EJ. Chaykovsky M. J. Am. Chem. Soc.  1965,  87:  1353 
  • 3 Cwynar V. Donahue MG. Hart DJ. Yang D. Org. Lett.  2006,  8:  4577 
  • 4 Cleij M. Archelas A. Furstoss R. J. Org. Chem.  1999,  64:  5029 
  • 5 Herscovici J. Uriel C. Uriel J. Antonakis K. Bioorg. Med. Chem. Lett.  1994,  4:  421 
  • 6 Di Chenna P. Ghini AA. Burton G. Molecules  2000,  5:  447 
  • 7 Morton D. Pearson D. Field RA. Stockman RA. Synlett  2003,  1985 
  • 8 Raj IVP. Sudalai A. Tetrahedron Lett.  2008,  49:  2646 
  • 9 Hodgson DM. Fleming MJ. Stanway SJ. Org. Lett.  2005,  7:  3295 
  • 10 Benoit-Marquie F. Csákÿ AG. Esteban G. Martínez ME. Plumet J. Tetrahedron Lett.  2000,  41:  3355 
  • 11 Singh R. Singh GC. Ghosh SK. Eur. J. Org. Chem.  2007,  5376 
  • 12 Panda K. Venkatesh C. Ila H. Junjappa H. Eur. J. Org. Chem.  2005,  2045 
  • 13 Kumar S. Ila H. Junjappa H. Tetrahedron  2007,  63:  10067 
  • 14 Schinkels B. Ruban A. Nieger M. Niecke E. J. Chem. Soc., Chem. Commun.  1997,  293 

    References

  • 1 Corey EJ. Chaykovsky M. J. Am. Chem. Soc.  1962,  84:  3782 
  • 2 Corey EJ. Chaykovsky M. J. Am. Chem. Soc.  1965,  87:  1353 
  • 3 Cwynar V. Donahue MG. Hart DJ. Yang D. Org. Lett.  2006,  8:  4577 
  • 4 Cleij M. Archelas A. Furstoss R. J. Org. Chem.  1999,  64:  5029 
  • 5 Herscovici J. Uriel C. Uriel J. Antonakis K. Bioorg. Med. Chem. Lett.  1994,  4:  421 
  • 6 Di Chenna P. Ghini AA. Burton G. Molecules  2000,  5:  447 
  • 7 Morton D. Pearson D. Field RA. Stockman RA. Synlett  2003,  1985 
  • 8 Raj IVP. Sudalai A. Tetrahedron Lett.  2008,  49:  2646 
  • 9 Hodgson DM. Fleming MJ. Stanway SJ. Org. Lett.  2005,  7:  3295 
  • 10 Benoit-Marquie F. Csákÿ AG. Esteban G. Martínez ME. Plumet J. Tetrahedron Lett.  2000,  41:  3355 
  • 11 Singh R. Singh GC. Ghosh SK. Eur. J. Org. Chem.  2007,  5376 
  • 12 Panda K. Venkatesh C. Ila H. Junjappa H. Eur. J. Org. Chem.  2005,  2045 
  • 13 Kumar S. Ila H. Junjappa H. Tetrahedron  2007,  63:  10067 
  • 14 Schinkels B. Ruban A. Nieger M. Niecke E. J. Chem. Soc., Chem. Commun.  1997,  293 

Scheme 1