Trimethylsilyl Cyanide (TMSCN)

Biographical Sketches

Ebrahim Soleimani was born in 1979 in Kermanshah, Iran. He ­obtained his B.Sc. in applied chemistry from Razi University, ­Kermanshah and his M.Sc. in organic chemistry from Shahid ­Beheshti University under the guidance of Professor Javad Azizian. Presently he is working towards his Ph.D. at Shahid Beheshti ­University, Tehran under the supervision of Professor Ahmad ­Shaabani. His research field is isocyanide-based multi-component reactions (MCRs).

Introduction

Cyanation of carbonyl compounds is one of the most ­powerful procedures for the synthesis of polyfunctionalized molecules. Compared to various cyanating reagents such as KCN, NaCN, and HCN, trimethylsilyl cyanide (TMSCN) is a safer and more effective cyanide source for nucleophilic addition to carbonyl compounds under mild conditions. [1] [2] Asymmetric addition of TMSCN to carbonyl compounds and subsequent hydrolysis produces chiral cyanohydrins. [3] The reaction of an epoxide with TMSCN leads to formation of either trimethylsilyloxy ­nitrile (C-nucleophilic attack) or trimethylsiloxy iso­cyanide (N-nucleophilic attack) depending on the nature of the catalyst, due to the ambident nucleophilic character of TMSCN. [4] Cyanation of nucleophilic alkynes as an easy approach to substituted α-cyanoenamines is another ­ability of TMSCN. [5] Recently, TMSCN was used as a functional, yet non-classical isonitrile, for the synthesis of 3-aminoimidazo[1,2-a]pyridines. [6]

Abstracts

(A) The addition of TMSCN to carbonyl compounds is an area of active study due to the synthetic versatility of cyanohydrins. The reaction of TMSCN with benzaldehyde at -20 °C in the presence of proline-based N,N′-dioxides as catalyst afforded enantioselective cyanosilylation. [7]
(B) There are few reports on the preparation of cyanohydrin tri­methylsilyl ethers of acylferrocenes except for formylferrocene. Bian et al. described the synthesis of cyanohydrin trimethylsilyl ethers of acylferrocenes via the addition of TMSCN to various acylferrocenes in the presence of ZnI2 in dichloromethane. [8]
(C) TMSCN is a very effective cyanide anion source for the synthesis of α-amino nitriles. The reaction of aldehydes and amines with TMSCN in the presence of a catalytic amount of H14[NaP5W30O110] afforded α-amino nitrile derivatives. [9]
(D) Recently, Schwerkoske et al. reported a novel one-step three-component procedure for the synthesis of 3-iminoarylimidazo[1,2-a]pyridines via the unique application of TMSCN as a functional, yet non-classical isonitrile. Reactions are performed under microwave irradiation in methanol by simply mixing α-amino-pyridines, aldehydes, and TMSCN in the presence of scandium triflate to ­afford the products. [10]
(E) β-Hydroxynitriles are useful synthetic intermediates in organic synthesis and versatile moieties for the synthesis of 1,3-amino ­alcohols. The ring opening reaction of epoxides with TMSCN is the most direct method for the preparation of these compounds. An asymmetric ring opening of meso epoxides with TMSCN in the presence of catalytic amounts of (pybox)YbCl3 complexes, yielding the β-trimethylsilyloxy nitrile ring-opened products with good enantioselectivities (83-92% ee) is reported. [11]
(F) The addition of TMSCN to a wide range of electron-rich heteroaromatic compounds such as pyrroles, thiophenes, and indoles in the presence of phenyliodine bis(trifluoroacetate) (PIFA) under mild conditions produced the selective cyanation products. [12]

References

• 1a Sigman MS. Jacobsen EN. J. Am. Chem. Soc.  1998,  120:  4901 
• 1b Vallee Y. Chavant PY. Byrne JJ. Chavarot M. Tetrahedron: Asymmetry  2001,  12:  1147 
• 1c Vachal P. Jacobsen EN. J. Am. Chem. Soc.  2002,  12:  10012 
• 1d Keith JM. Jacobsen EN. Org. Lett.  2004,  6:  153 
• 1e Chakraborty TK. Reddy GV. Hussain KA. Tetrahedron Lett.  1991,  32:  7597 
• 1f Leblanc J. Gibson HW. Tetrahedron Lett.  1992,  33:  6295 
• 1g Heydari A. Fatemi P. Alizadeh AA. Tetrahedron Lett.  1998,  39:  3049 
• 2 Groutas WC. Felker D. Synthesis  1980,  861 
• 3a Gregory RJH. Chem. Rev.  1999,  99:  3649 
• 3b North M. Tetrahedron: Asymmetry  2003,  14:  147 
• 3c Brunel JM. Holmes IP. Angew. Chem. Int. Ed.  2004,  43:  2752 
• 3d Córdoba R. Plumet J. Tetrahedron Lett.  2003,  44:  6157 
• 4a Imi K. Yanagihara N. Utimoto K. J. Org. Chem.  1987,  52:  1013 
• 4b Konno H. Toshiro E. Hinoda N. Synthesis  2003,  2161 
• 5 Lukashev NV. Kazantsev AV. Borisenko AA. Beletskaya LP. Tetrahedron  2001,  57:  10309 
• 6 Masquelin T. Bui H. Brickley B. Stephenson G. Schwerkoske J. Hulme C. Tetrahedron Lett.  2006,  47:  2989 
• 7 Wen Y. Huang X. Huang J. Xiong Y. Qin B. Feng X. Synlett  2005,  2445 
• 8 Bian ZX. Zhao HY. Li BG. Polyhedron  2003,  22:  1523 
• 9 Oskooie HA. Heravi MM. Bakhtiari K. Zadsirjan V. Bamoharram FF. Synlett  2006,  1768 
• 10 Schwerkoske J. Masquelin T. Perun T. Hulme C. Tetrahedron Lett.  2005,  46:  8355 
• 11 Schaus SE. Jacobsen EN. Org. Lett.  2000,  2:  1001 
• 12 Dohi T. Morimoto K. Kiyono Y. Tohma H. Kita Y. Org. Lett  2005,  7:  537