The α-Alkylation of Methyl Ketones with Primary Alcohols Promoted by Nickel Nanoparticles under Mild and Ligandless Conditions

Abstract

Nickel nanoparticles have been found to promote the α-alkylation of ketones with primary alcohols in the absence of any added ligand or base, under mild reaction conditions.

Key words

α-alkylation - ketones - primary alcohols - nickel - nanoparticles

References and Notes

• 1a Caine D. In Comprehensive Organic Synthesis   Vol. 3:  Trost BM. Fleming I. Pattenden G. Pergamon; Oxford: 1991.  p.1-63  
• 1b Modern Carbonyl Chemistry   Otera J. Wiley-VCH; Weinheim: 2000. 
• 2 For a recent review, see: Guillena G. Ramón DJ. Yus M. Angew. Chem. Int. Ed.  2007,  46:  2358 
• 3a Cho CS. Kim BT. Kim T.-J. Shim SC. Tetrahedron Lett.  2002,  43:  7987 
• 3b Cho CS. J. Mol. Catal. A: Chem.  2005,  240:  55 
• 4a Martínez R. Brand GJ. Ramón DJ. Yus M. Tetrahedron Lett.  2005,  46:  3683 
• 4b Martínez R. Ramón DJ. Yus M. Tetrahedron  2006,  62:  8988 
• 5 Kwon MS. Kim N. Seo SH. Park IS. Cheedrala RK. Park J. Angew. Chem. Int. Ed.  2005,  44:  6913 
• 6 Yamada YMA. Uozumi Y. Org. Lett.  2006,  8:  1375 
• 7 Taguchi K. Nakagawa H. Hirabayashi T. Sakaguchi S. Ishii Y. J. Am. Chem. Soc.  2004,  126:  72 
• 8a Alonso F. Calvino JJ. Osante I. Yus M. Chem. Lett.  2005,  34:  1262 
• 8b Alonso F. Calvino JJ. Osante I. Yus M. J. Exp. Nanosci.  2006,  1:  419 
• 9 Alonso F. Yus M. Chem. Soc. Rev.  2004,  33:  284 
• 10a Alonso F. Osante I. Yus M. Adv. Synth. Catal.  2006,  348:  305 
• 10b Alonso F. Osante I. Yus M. Tetrahedron  2007,  63:  93 
• 11 Alonso F. Osante I. Yus M. Synlett  2006,  3017 
• 12 Hisamura K, Yamanaka N, and Sugitani T. inventors; JP  2002173460.  ; Chem. Abstr. 2002, 137, 33075
• 15 Cho CS. Shim SC. J. Organomet. Chem.  2006,  691:  4329 
• 16 Goosen LJ. Ghosh K. Eur. J. Org. Chem.  2002,  3254 
• 17 Spogliarich R. Farnetti E. Graziani M. Tetrahedron  1991,  47:  1965 
• 18 Cabello JA. Campelo JM. García A. Luna D. Marinas JM. J. Org. Chem.  1986,  51:  1786 
• 19 Hayes JF. Shipman M. Twin H. J. Org. Chem.  2002,  67:  935 
• 20 Hattori K. Sajiki H. Hirota K. Tetrahedron  2001,  57:  4817 

13

It must be pointed out that the alkylated ketone in entry 7 was not obtained (0% yield) by using the complex [RuCl₂(dmso)₄]. [4]

14

General Procedure for the α-Alkylation of Ketones with Primary Alcohols
Nickel(II) chloride (130 mg, 1 mmol) was added over a suspension of lithium (14 mg, 2 mmol) and DTBB (13 mg, 0.05 mmol) in THF (2 mL) at r.t. under argon. The reaction mixture, which was initially dark blue, changed to black indicating that nickel(0) was formed. After 10 min, the corresponding alcohol (4 mmol for benzyl alcohols, 4 mL for EtOH and n-PrOH) and the ketone (1 mmol) were consecutively added. The reaction mixture was warmed to 76 °C and monitored by GLC-MS until total or steady conversion of the starting material. The resulting suspension was filtered through a pad containing Celite^®, the filtrate was washed with 2 M HCl (2 × 20 mL) and dried over MgSO₄. The residue obtained after removal of the solvent (15 torr) was purified by column chromatography (silica gel, hexane-EtOAc) to give the pure alkylated ketone.
Butyrophenone and valerophenone were characterized by comparison of their physical and spectroscopic data with those of commercially available samples (Aldrich). 3-(4-Methoxyphenyl)-1-phenylpropan-1-one, [15] (4-chloro-phenyl)-1-phenylpropan-1-one, [15] 1-(4-methoxyphenyl)-3-phenylpropan-1-one, [16] 1-(4-trifluoromethylphenyl)-3-phenylpropan-1-one, [17] 1-phenylhexan-3-one, [18] 1-phenyl-octan-3-one, [19] and 1-phenyl-4,4-dimethylpentan-3-one²⁰ were characterized by comparison of their physical and spectroscopic data with those described in the literature.