Quinoxaline Synthesis from α-Hydroxy Ketones via a Tandem Oxidation Process Using Catalysed Aerobic Oxidation

Abstract

The direct conversion of α-hydroxy ketones into quinoxalines via metal-catalysed aerobic oxidation followed by in situ trapping with aromatic 1,2-diamines is reported. Catalyst screening indicated that these transformations could be carried out efficiently using 2 mol% Pd(OAc)₂ or RuCl₂(PPh₃)₃-TEMPO; the palladium system was utilised for a range of transformations.

Key words

direct conversion - α-hydroxy ketones - quinoxalines

References

• 1a Raw SA. Wilfred CD. Taylor RJK. Org. Biomol. Chem.  2004,  2:  788 
• 1b Raw SA. Wilfred CD. Taylor RJK. Chem. Commun.  2003,  2286 
• 2 Ireland RE. Norbeck DW. J. Org. Chem.  1985,  50:  2198 
• For reviews see:
• 3a Sakata G. Makino K. Kurasawa Y. Heterocycles  1988,  27:  2481 
• 3b Sato N. In Comprehensive Heterocyclic Chemistry II   Katritzky AR. Rees CW. Scriven EFV. Elsevier Science Ltd.; Oxford: 1996.  Vol. 6:  Chap. 6.03.
• For more recent references see:
• 4a Aguirre G. Cerecetto H. Di Maio R. González M. Alfaro MEM. Jaso A. Zarranz B. Ortega MA. Aldana I. Monge-Vega A. Bioorg. Med. Chem. Lett.  2004,  14:  3835 
• 4b Zarranz B. Jaso A. Aldana I. Monge A. Bioorg. Med. Chem.  2004,  12:  3711 
• 4c Kim JH. Kim JH. Lee GE. Kim SW. Chung IK. Biochem. J.  2003,  373:  523 
• 4d Seitz LE. Suling WJ. Reynolds RC. J. Med. Chem.  2002,  45:  5604 
• For recent reviews see:
• 5a Zhan B.-Z. Thompson A. Tetrahedron  2004,  60:  2917 
• 5b Muzart J. Tetrahedron  2003,  59:  5789 
• 6 Lee M. Chang S. Tetrahedron Lett.  2000,  41:  7507 
• 7 Dijksman A. Marino-González A. Payeras AM. Arends IWCE. Sheldon RA. J. Am. Chem. Soc.  2001,  123:  6826 
• 8a Schultz MJ. Park CC. Sigman MS. Chem. Commun.  2002,  3034 
• 8b See also: Mueller JA. Goller CP. Sigman MS. J. Am. Chem. Soc.  2004,  126:  9725 
• 10a Ihmels H. Maggini M. Prato M. Scorrano G. Tetrahedron Lett.  1991,  32:  6215 
• 10b Fürstner A. Leitner A. Méndez M. Jrause H. J. Am. Chem. Soc.  2002,  124:  13856 

a

Permanent address: Department of Chemistry, University of KwaZulu-Natal , Private Bag XO1, Scottsville, Pieter­maritzburg, South Africa, 3209.

9

2-Hydroxyacetophenone 1a (0.136 g, 1 mmol) was added to a 25 mL round bottomed flask containing toluene (4 mL, dried over activated 3 Å MS), Et₃N (0.01 mL) and dry THF (0.6 mL). This solution was stirred and o-phenylenediamine (0.108 g, 1 mmol) was added followed by Pd(OAc)₂ (4.5 mg, 2 mol%) and the mixture was boiled under reflux for 3 h. The mixture was then filtered through a silica plug and the solvent removed in vacuo to afford a crude product which was purified using column chromatography (petroleum ether-EtOAc, 3:1) to afford 2-phenylquinoxaline 4a (0.1703 g, 83%) as an orange solid: R _f = 0.35 (petroleum ether-EtOAc, 2:1); mp 79-80 °C (lit.^11a) mp 79-80 °C); spectroscopic data consistent with those published (ref. 10b).