Synlett 2005(2): 363-364  
DOI: 10.1055/s-2004-837237
SPOTLIGHT
© Georg Thieme Verlag Stuttgart · New York

p-Toluenesulfonylmethyl Isocyanide (TosMIC)

V. V. Ramana Reddy*
D-206, Discovery Laboratory, Organic Chemistry Division-III, ­Indian Institute of Chemical Technology, Tarnaka, Hyderabad-500 007, India
e-Mail: ramanareddyvv@yahoo.co.in;

Further Information

Publication History

Publication Date:
20 January 2005 (online)

Biographical Sketches

V. V. Ramana Reddy was born in Tenali, Andhra Pradesh, India. He obtained his MSc in 1999 from Pondicherry University, Pondicherry, India. He is currently working as a senior research ­fellow towards his PhD under the supervision of Dr. P. Radha Krishna at the Indian Institute of Chemical Technology, in ­Hyderabad, India. His research interests include the total synthesis of bioactive natural products and C-nucleosides.

Introduction

p-Toluenesulfonylmethyl isocyanide (TosMIC) is one of the most versatile and widely applicable reagents in organic synthesis. The methylene group of TosMIC is highly activated (pKa = 14) by the two electron-withdrawing substituents. Deprotonation of TosMIC has been achieved with an array of bases ranging from K2CO3 in MeOH to n-BuLi in THF. TosMIC is considered as a formaldehyde equivalent with reversible polarity. The reagent is a stable solid (mp 116-117 °C) that is commercially available, or can be prepared from p-toluenesulfonic acid [1] in a two-step process. Many heterocycles, such as oxazole, pyrrole, ­imidazole, thiazole and 1,3,4-triazole, can be synthesized from TosMIC.

Figure 1

Abstracts

(A) Most ketones are converted in one operation into cyanides with TosMIC in the presence of potassium tert-butoxide in non-protic solvents (DME, DMSO). [2] The reductive cyanation of some aldehyde [3] was carried out at low temperature and needs addition of methanol.

(B) TosMIC on reaction with aldehyde in methanol at room ­temperature leads to oxazolene, where as oxazoles were formed at reflux temperature. [4] The addition of TosMIC to the aldehyde is ­followed by cyclization and subsequent elimination of the tosyl group to afford oxazole. Dhar et al. reported a modified oxazole synthesis using DBU in DME at 80 °C. [4b]

(C) Base-induced addition of TosMIC to aldimines in protic medium occurs with concomitant cyclization followed by elimination of p-toluenesulfonic acid to result in imidazoles. [5]

(D) Pyrroles [6] are obtained by base-induced addition of TosMIC to Michael acceptors. The ring closure between the isocyano and ­enolate carbons is followed by aromatization.

(E) TosMIC, on reaction with diazonium salts, results in 1,2,4-triazoles. [7] The TosMIC anion attacks the electrophilic b-nitrogen of the diazonium ion, then ring closure occurs.

(F) Mono- and dialkylated TosMIC [8] were formed from corresponding alkyl halides under phase transfer conditions. Hydrolysis of dialkylated TosMIC leads to symmetrical and unsymmetrical ketones. [9] The reduction of mono and dialkylated TosMIC with Li in liquid NH3 afforded the corresponding hydrocarbons. [10]

(G) Reaction of TosMIC with carbondisulfides under phase transfer conditions provides the tetrabutylammonium salt of thiazole, which can be converted to thiazole. [11]

(H) Recently, the synthesis of C-nucleosides by the TosMIC approach from sugar-derived aldehydes and other Michael acceptors was reported. [12]

    References

  • 1a Hoogenboom BE. Oldenzil OH. van Leusen AM. Org. Synth. Coll. Vol. VI  1988,  987 
  • 1b Obrecht R. Herrmann R. Ugi I. Synthesis  1985,  400 
  • 2 Oldenziel OH. van Leusen D. van Leusen AM. J. Org. Chem.  1977,  42:  3114 
  • 3a van Leusen AM. Oomkes PG. Synth. Commun.  1980,  10:  399 
  • 3b Oldenzil OH. Wildeman J. van Leusen AM. Org. Synth. Coll. Vol. VI  1988,  41 
  • 4a van Leusen AM. Hoogenboom BE. Siderius HL. Tetrahedron Lett.  1972,  13:  2369 
  • 4b Murali DharTG. Shen Z. Fleener CA. Rouleau KA. Barrish JC. Hollenbaug DL. Iwanowicz EJ. Bioorg. Med. Chem. Lett.  2002,  12:  3305 
  • 5 van Leusen AM. Wildeman J. Oldenziel OH. J. Org. Chem.  1977,  42:  1153 
  • 6a van Leusen AM. Siderius H. Hoogenboom BE. van Lesen D. Tetrahedron Lett.  1972,  52:  5337 
  • 6b van Lesen D. Flentge E. van Leusen AM. Tetrahedron  1991,  47:  4639 
  • 7 van Leusen AM. Hoogenboom BE. Houuling HA. J. Org. Chem.  1976,  41:  711 
  • 8 van Leusen AM. J. Heterocycl. Chem., Suppl. 5  1980,  17:  111 
  • 9 Possel O. van Leussen AM. Tetrahedron Lett.  1977,  48:  4229 
  • 10 Yadav JS. Reddy PS. Joshi BV. Tetrahedron  1988,  44:  7243 
  • 11 van Leusen AM. Wildeman J. Synthesis  1977,  501 
  • 12 Radha Krishna P. Ramana Reddy VV. Sharma GVM. Synlett  2003,  1619 

    References

  • 1a Hoogenboom BE. Oldenzil OH. van Leusen AM. Org. Synth. Coll. Vol. VI  1988,  987 
  • 1b Obrecht R. Herrmann R. Ugi I. Synthesis  1985,  400 
  • 2 Oldenziel OH. van Leusen D. van Leusen AM. J. Org. Chem.  1977,  42:  3114 
  • 3a van Leusen AM. Oomkes PG. Synth. Commun.  1980,  10:  399 
  • 3b Oldenzil OH. Wildeman J. van Leusen AM. Org. Synth. Coll. Vol. VI  1988,  41 
  • 4a van Leusen AM. Hoogenboom BE. Siderius HL. Tetrahedron Lett.  1972,  13:  2369 
  • 4b Murali DharTG. Shen Z. Fleener CA. Rouleau KA. Barrish JC. Hollenbaug DL. Iwanowicz EJ. Bioorg. Med. Chem. Lett.  2002,  12:  3305 
  • 5 van Leusen AM. Wildeman J. Oldenziel OH. J. Org. Chem.  1977,  42:  1153 
  • 6a van Leusen AM. Siderius H. Hoogenboom BE. van Lesen D. Tetrahedron Lett.  1972,  52:  5337 
  • 6b van Lesen D. Flentge E. van Leusen AM. Tetrahedron  1991,  47:  4639 
  • 7 van Leusen AM. Hoogenboom BE. Houuling HA. J. Org. Chem.  1976,  41:  711 
  • 8 van Leusen AM. J. Heterocycl. Chem., Suppl. 5  1980,  17:  111 
  • 9 Possel O. van Leussen AM. Tetrahedron Lett.  1977,  48:  4229 
  • 10 Yadav JS. Reddy PS. Joshi BV. Tetrahedron  1988,  44:  7243 
  • 11 van Leusen AM. Wildeman J. Synthesis  1977,  501 
  • 12 Radha Krishna P. Ramana Reddy VV. Sharma GVM. Synlett  2003,  1619 

Figure 1