A Tandem Oxidation Procedure for the Conversion of Alcohols into 1,1-Dibromoalkenes

Abstract

A practical and concise route to dibromoalkenes directly from activated alcohols in good to excellent yields using a new Tandem Oxidation Procedure (TOP) is reported. We also describe the use of these dibromoalkenes as intermediates in a one-pot route to 4,5-dihydro-1H-imidazoles and in the synthesis of bromoalkynes through MTBD-induced elimination.

Key words

dibromoalkenes - tandem oxidation procedure - one-pot - MTBD

References

• 1 Huh DH. Jeong JS. Lee HB. Ryu H. Kim YG. Tetrahedron  2002,  58:  9925 
• For some noteworthy examples in natural product synthesis see:
• 2a Roush WR. Brown BB. J. Org. Chem.  1993,  58:  2162 
• 2b Meyers AG. Hogan PC. Hurd AR. Goldberg SD. Angew. Chem. Int. Ed.  2002,  41:  1104 
• 2c Evans DA. Starr JT. Angew. Chem. Int. Ed.  2002,  41:  1865 
• 2d Mergott DJ. Frank SA. Roush WR. Org. Lett.  2002,  4:  3157 
• 3 Uenishi J. Kawahama R. Yonemitsu O. J. Org. Chem.  1998,  63:  8965 
• 4 Kuang C. Senboku H. Tokuda M. Tetrahedron  2002,  58:  1491 
• 5 Lee HB. Huh DH. Oh JS. Min G.-H. Kim BH. Lee DH. Hwang JK. Kim YG. Tetrahedron  2001,  57:  8283 
• 6 Corey EJ. Fuchs PL. Tetrahedron Lett.  1972,  13:  3769 
• 7 Lin S.-T. Lee C.-C. Liang DW. Tetrahedron  2000,  56:  9619 
• 8 Ramirez F. Desai NB. McKelvie N. J. Am. Chem. Soc.  1962,  84:  1745 
• 10 Patrick M. Gennet D. Rassat A. Tetrahedron Lett.  1999,  40:  8575 
• 11 Dolhem F. Lièvre C. Demailly G. Tetrahedron Lett.  2002,  43:  1847 
• 12 Korotchenko VN. Shastin AV. Nenajdenko VG. Balenkova ES. Org. Biomol. Chem.  2003,  1:  1906 
• 13 Baxendale IR. Ley SV. Sneddon HF. Synlett  2002,  775 
• 14a Blackburn L. Wei X. Taylor RJK. Chem. Commun.  1999,  1337 
• 14b Wei X. Taylor RJK. J. Org. Chem.  2000,  65:  616 
• 14c Blackburn L. Kanno H. Taylor RJK. Tetrahedron Lett.  2003,  44:  115 
• 14d Outram HS. Raw SA. Taylor RJK. Tetrahedron Lett.  2002,  43:  6185 
• 15a Blackburn L. Pei C. Taylor RJK. Synlett  2002,  215 
• 15b Reid M. Rowe D. Taylor RJK. Chem. Commun.  2003,  2284 
• 16a Davies SB. McKervey MA. Tetrahedron Lett.  1999,  40:  1229 
• 16b Nicolaou KC. Li Y. Fylaktakidou KC. Mitchell HJ. Wei H.-X. Weyershausen B. Angew. Chem. Int. Ed.  2001,  40:  3849 
• 16c Mladenova M. Tavlinova M. Momchev M. Alami M. Ourévitch M. Brion JD. Eur. J. Org. Chem.  2003,  2713 
• 16d Nicolaou KC. Li Y. Fylaktakidou KC. Monenschein H. Li Y. Weyershausen B. Mitchell HJ. Wei H.-X. Guntupalli P. Hepworth D. Sugita K. J. Am. Chem. Soc.  2003,  125:  15433 
• 17 Simoni D. Rossi M. Rondanin R. Mazzani A. Baruchello C. Malagutti C. Roberti M. Indiviata FP. Org. Lett.  2000,  2:  3765 
• 19 Bestmann HJ. Frey H. Liebigs Ann. Chem.  1980,  12:  2061 
• 20 Lok WN. Ward AD. Aust. J. Chem.  1978,  31:  617 

9

Phosphonium salt 2 was prepared from triphenylphosphine and carbon tetrabromide according to the procedure reported by Dolhem et al. [11] and could be stored on the bench for several months without any noticeable degradation, either by NMR spectroscopy or in its reactivity.

18

Representative Procedure. To a suspension of activated manganese dioxide (Aldrich, 21764-6; 867 mg, 9.97 mmol), phosphonium salt 2 (1.80 g, 3.50 mmol) and ground 4Å molecular sieves (100 mg) in solvent (CH₂Cl₂ or chloroform; 10 mL) was added MTBD 3 (0.22 mL, 1.50 mmol). The reaction mixture was heated at reflux for 30 min, cooled to r.t., then a solution of alcohol (1 mmol) in solvent (5 mL) added. The reaction mixture was then heated at reflux for the time specified, cooled to r.t. and filtered through Celite^®. The resulting filtrate was then pre-loaded on to silica and the dibromoalkenes purified by silica chromatography, eluting with EtOAc/petroleum ether.

21

Synthesis of 2-(4-Nitrobenzyl)-4,5-dihydro-1 H -imidazole(7). To a suspension of activated manganese dioxide (Aldrich, 21764-6; 867 mg, 9.97 mmol), phosphonium salt 2 (1.80 g, 3.50 mmol) and ground 4 Å molecular sieves (100 mg) in CH₂Cl₂ (10 mL) was added MTBD 3 (0.22 mL, 1.50 mmol). The reaction mixture was heated at reflux for 30 min, cooled to r.t., then a solution of p-nitrobenzyl alcohol (153 mg, 1 mmol) in CH₂Cl₂ (5 mL) was added. The reaction mixture was then heated at reflux for 17 h, cooled to r.t. and filtered through Celite^®. Ethylenediamine (10 mL) was added and the reaction mixture concentrated in vacuo to afford a purple oil which was partitioned between conc. aq NH₃ solution (40 mL) and CH₂Cl₂ (40 mL). The NH₃ solution was further extracted with CH₂Cl₂ (2 × 20 mL). The combined organics were then concentrated in vacuo then redissolved in CH₂Cl₂ (20 mL) and extracted with 10% aq HCl (20 mL). The aqueous extracts were then basified to pH 12 with 10 M NaOH solution and extracted with CH₂Cl₂ (4 × 10 mL) and the combined organics were dried over Na₂SO₄ and concentrated in vacuo to afford the title compound 7 (166 mg, 81%) as a purple solid (mp 124-126 °C, lit. [1] 135-137 °C). ¹H NMR data were consistent with those reported in the literature. [1]