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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)

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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]

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Figure 1