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DOI: 10.1055/s-2004-837237
p-Toluenesulfonylmethyl Isocyanide (TosMIC)
Publikationsverlauf
Publikationsdatum:
20. Januar 2005 (online)
Biographical Sketches
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. |
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(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] |
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(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] |
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(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. |
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(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. |
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(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] |
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(G) Reaction of TosMIC with carbondisulfides under phase transfer conditions provides the tetrabutylammonium salt of thiazole, which can be converted to thiazole. [11] |
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(H) Recently, the synthesis of C-nucleosides by the TosMIC approach from sugar-derived aldehydes and other Michael acceptors was reported. [12] |
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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
References
Figure 1