Alkylation of acylmetalates with alkyl halides to prepare Fischer carbene complexes: an improved protocol Bappaditya Nandi, Surajit Sinha * Department of Organic Chemistry, Indian Association for the Cultivation of Science, Kolkata 700032, West Bengal, India article info Article history: Received in revised form 2 November 2010 Accepted 2 November 2010 Available online 6 November 2010 Keywords: Fischer carbene complex Alkylation Cesium carbonate Mechanistic study abstract Alkoxy Fischer carbene complexes have been synthesized by alkylation of lithium acylmetalates with alkyl halides in the presence of catalytic amount (5e10 mol %) of n-tetrabutylammonium bromide (n- Bu 4 NBr) restricting the temperature below 55  C to minimize decomposition of the product. The reaction occurs in a biphasic condition involving water and alkyl halide. The effect of cesium on this alkylation reaction has been studied. The presence of a radical quencher, di-tert-butyl phenol, neither affects the yield nor leads to the formation of dimer of di-tert-butyl phenol, which rules out the possibility of radical pathway mechanism. The kinetic study and the 1 H NMR spectra of products suggest an S N 2 pathway particularly involving alkyl halides. Ó 2010 Elsevier Ltd. All rights reserved. 1. Introduction Fischer carbene complexes have proven to be useful in the synthesis of a range of interesting and useful organic compounds 1 and suitably substituted alkoxy Fischer carbene complexes of chromium, tungsten or molybdenum are normally used as syn- thons. These complexes are usually prepared by the treatment of M (CO) 6 with organolithium reagents followed by alkylation. Simple alkyl groups such as methyl and ethyl are introduced using Meer- wein oxonium salts 2 or methyl fluorosulfate or methyl triflate 3 but these methods are not useful for the incorporation of more complex alkyl groups. Fischer carbene complexes with complex alkoxy groups are synthesized by treating the tetraalkylammonium acyl- metalate with different acyl halides like acetyl chloride, acetyl bromide or pivaloyl chloride at low temperature, followed by ad- dition of alcohol. 4 Chromium Fischer carbene complexes are obtained in good yield, but tungsten carbene complexes give moderate yield in this procedure. Direct incorporation of alkyl groups using alkyl halides have been reported earlier 5 but this method is limited to the preparation of only chromium carbene complexes. Moreover the reaction was done in large scale (20 mmol) and variable yields were reported. 5c In this direction, Matsuyama’s method 6 is more general and has covered a wide range of substrates. 2. Results and discussion 2.1. Preparation of Fischer carbene complexes During the course of our work on the application of metal- locarbenes in the synthesis of organic compounds, we wanted to make the Fischer carbene complex 1 using Hoye’s 5a method as it appeared to be simple and straightforward. Unfortunately, we isolated the desired complex 1 in very poor yield (20%) using methyl iodide as an alkylating agent. However, the reaction was performed in 2 mmol scale, which was much lower than the reported scale (30 mmol). The reaction was even tried at elevated temperature (65e70  C) in aqueous medium according to their procedure, yet the yield was same. Moreover, methyl iodide es- caped during heating. Carrying out the reaction in various solvents like DCM, DMF or THF, did not improve the yield. When the reaction was performed in these organic solvents, we observed that the reaction mixture turned green and significant amount of un- identified byproducts were formed. Based on our extensive in- vestigation and guided by earlier reports, 5a,c we found the optimum condition which involved (a) filtering the aqueous solution of the lithio salt of the transition metalecarbene complex for removing decomposed acylmetalate impurity and unreacted metal hex- acarbonyl prior to the addition of the alkyl halides, (b) restricting the temperature below 55  C to minimize decomposition of the product, (c) performing the reaction in biphasic condition of neat alkyl halides (no organic solvent for dilution) and water to make the reaction faster and move to forward direction. * Corresponding author. Tel.: þ91 33 2473 4971; fax: þ91 33 2473 2805; e-mail address: ocss5@iacs.res.in (S. Sinha). Contents lists available at ScienceDirect Tetrahedron journal homepage: www.elsevier.com/locate/tet 0040-4020/$ e see front matter Ó 2010 Elsevier Ltd. All rights reserved. doi:10.1016/j.tet.2010.11.016 Tetrahedron 67 (2011) 106e113