Highly Efficient Copper-Catalyzed Formation of N-Aryl Diazoles Using KF/Al₂O₃

Abstract

A simple and efficient method for the coupling of aryl ­iodides with heterocyclic compounds such as diazoles that does not require the use of alkoxide bases is described. The C-N bond forming procedure shows that the combination of air stable CuI and 1,10-phenanthroline in the presence of KF/Al₂O₃ comprises an extremely efficient and general catalyst system for the N-arylation of aryl ­iodides. Different functionalized aryl iodides were coupled with ­diazoles using this method.

diazole - aryl iodides - copper iodide - coupling reaction - potassium fluoride on alumina

References and Notes

<A NAME="RD06206ST-1A">1a</A> Craig PN. In Comprehensive Medicinal Chemistry   Drayton CJ. Pergamon Press; New York: 1991.  p.8 

<A NAME="RD06206ST-1B">1b</A> Southon IW. Buckingham J. In Dictionary of Alkaloids   Saxton JE. Chapman and Hall; London: 1989. 

<A NAME="RD06206ST-1C">1c</A> Negwer M. In Organic-Chemical Drugs and their Synonyms: An International Survey   7th ed.:  Akademie Verlag GmbH; Berlin: 1994. 

<A NAME="RD06206ST-2A">2a</A> Venuti MC. Stephenson RA. Alvarez R. Bruno JJ. Strosberg AM. J. Med. Chem.  1988,  31:  2136 

<A NAME="RD06206ST-2B">2b</A> Cozzi P. Carganico G. Fusar D. Grossoni M. Menichincheri M. Pinciroli V. Tonani R. Vaghi F. Salvati P. J. Med. Chem.  1993,  36:  2964 

<A NAME="RD06206ST-2C">2c</A> Qiao JX. Cheng X. Modi DP. Rossi KA. Luettgen JM. Knabb RM. Jadhav PK. Wexler RR. Bioorg. Med. Chem. Lett.  2005,  15:  29 

<A NAME="RD06206ST-2D">2d</A> Ohmori J. Shimizu-Sasamata M. Okada M. Sakamoto S. J. Med. Chem.  1996,  39:  3971 

<A NAME="RD06206ST-3A">3a</A> Yoshikawa S. Shinzawa-Itoh K. Nakashima R. Yaono R. Yamashita E. Inoue N. Yao M. Fei MJ. Libeu CP. Mizushima T. Yamaguchi H. Tomizaki T. Tsukihara T. Science  1998,  280:  1723 

<A NAME="RD06206ST-3B">3b</A> Bambal RB. Hanzlik RP. Chem. Res. Toxicol.  1995,  8:  729 

<A NAME="RD06206ST-4">4</A> Herrmann WA. Angew. Chem. Int. Ed.  2002,  41:  1290 

<A NAME="RD06206ST-5A">5a</A> Sircar I. Duell BL. Bobowski G. Bristol JA. Evans DB. J. Med. Chem.  1985,  28:  1405 

<A NAME="RD06206ST-5B">5b</A> Gungor T. Fouquet A. Teulon JM. Provost D. Cazes M. Cloarec A. J. Med. Chem.  1992,  35:  4455 

<A NAME="RD06206ST-5C">5c</A> Hu NX. Xie S. Popovic Z. Ong B. Hor AM. Wang S. J. Am. Chem. Soc.  1999,  121:  5097 

<A NAME="RD06206ST-5D">5d</A> Thomas KRJ. Lin JT. Tao YT. Ko CW. J. Am. Chem. Soc.  2001,  123:  9404 

<A NAME="RD06206ST-5E">5e</A> Yu S. Saenz J. Srirangam JK. J. Org. Chem.  2002,  67:  1699 

<A NAME="RD06206ST-6A">6a</A> Brickner SJ. Hutchinson DK. Barbachyn MR. Manninen PR. Ulanowicz DA. Garmon SA. Grega KC. Hendges SK. Toops DS. Ford CW. Zurenko GE. J. Med. Chem.  1996,  39:  673 

<A NAME="RD06206ST-6B">6b</A> Gallego J. Varani G. Acc. Chem. Res.  2001,  34:  836 

<A NAME="RD06206ST-7">7</A> Moureau F. Wouters J. Vercauteren DP. Collin S. Evrard G. Durant F. Ducrey F. Koenig JJ. Jarreau FX. Eur. J. Med. Chem.  1994,  29:  269 

<A NAME="RD06206ST-8A">8a</A> Harbert CA. Plattner JJ. Welch WM. Weissman A. Koe BK. J. Med. Chem.  1980,  23:  635 

<A NAME="RD06206ST-8B">8b</A> Lexy H. Kauffmann T. Chem. Ber.  1980,  113:  2755 

<A NAME="RD06206ST-8C">8c</A> Unangst PC. Connor DT. Stabler SR. Weikert RJ. J. Heterocycl. Chem.  1987,  24:  811 

<A NAME="RD06206ST-8D">8d</A> Kato Y. Conn MM. Rebek J. J. Am. Chem. Soc.  1994,  116:  3279 

<A NAME="RD06206ST-8E">8e</A> Murakami Y. Watnabe T. Hagiwara T. Akiyama Y. Ishii H. Chem. Pharm. Bull.  1995,  43:  1281 

<A NAME="RD06206ST-8F">8f</A> Mederski WWKR. Lefort M. Germann M. Kux D. Tetrahedron  1999,  55:  12757 

<A NAME="RD06206ST-8G">8g</A> Collman JP. Zhong M. Org. Lett.  2000,  2:  1233 

<A NAME="RD06206ST-9A">9a</A> Lopez-Alvarado P. Avendano C. Menendez JC. J. Org. Chem.  1995,  60:  5678 

<A NAME="RD06206ST-9B">9b</A> Cristau H.-J. Cellier PP. Spindler J.-F. Taillefer M. Chem. Eur. J.  2004,  10:  5607 

<A NAME="RD06206ST-9C">9c</A> Ma D. Cai Q. Synlett  2004,  128 

<A NAME="RD06206ST-10A">10a</A> Ullmann F. Ber. Dtsch. Chem. Ges.  1903,  36:  2382 

<A NAME="RD06206ST-10B">10b</A> Lindley J. Tetrahedron  1984,  40:  1433 

<A NAME="RD06206ST-10C">10c</A> Hassan J. Sevignon M. Gozzi C. Schulz E. Lemaire M. Chem. Rev.  2002,  102:  1359 

<A NAME="RD06206ST-11A">11a</A> Sezen B. Sames D. J. Am. Chem. Soc.  2003,  125:  5274 

<A NAME="RD06206ST-11B">11b</A> Sezen B. Sames D. J. Am. Chem. Soc.  2003,  125:  10580 

<A NAME="RD06206ST-12">12</A> Zhang H. Cai Q. Ma D. J. Org. Chem.  2005,  70:  5164 

<A NAME="RD06206ST-13">13</A> Antilla JC. Baskin JM. Barder TE. Buchwald SL. J. Org. Chem.  2004,  69:  5578 

<A NAME="RD06206ST-14">14</A> Kiyomori A. Marcoux JF. Buchwald SL. Tetrahedron Lett.  1999,  40:  2657 

<A NAME="RD06206ST-15">15</A> Blass BE. Tetrahedron  2002,  58:  9301 

<A NAME="RD06206ST-16A">16a</A> Yamawaki J. Ando T. Hanafusa T. Chem. Lett.  1981,  1143 

<A NAME="RD06206ST-16B">16b</A> Yadav VK. Kapoor KK. Tetrahedron  1996,  52:  3659 

<A NAME="RD06206ST-16C">16c</A> Alloum BA. Villemin D. Synth. Commun.  1989,  19:  2567 

<A NAME="RD06206ST-16D">16d</A> Kabalka GW. Wang L. Namboodiri V. Pagni RM. Tetrahedron Lett.  2000,  41:  5151 

<A NAME="RD06206ST-16E">16e</A> Kabalka GW. Pagni RM. Hair CM. Org. Lett.  1999,  1:  1423 

<A NAME="RD06206ST-17">17</A> Hosseinzadeh R. Tajbakhsh M. Mohadjerani M. Mehdinejad H. Synlett  2004,  1517 

<A NAME="RD06206ST-18">18</A> Hosseinzadeh R. Tajbakhsh M. Mohadjerani M. Alikarami M. Synlett  2005,  1101 

<A NAME="RD06206ST-19">19</A>

Satisfactory physical and spectral data were obtained in accordance with the structure. Selected physical and spectral data are as follows.
Entry 3: colorless solid; mp 96-98 °C (Lit. [21] 98 °C). ¹H NMR (90 MHz, CDCl₃): δ = 8.1 (1 H, s), 7.8 (1 H, m), 7.6-7.3 (8 H, m). Anal. Calcd for C₁₃H₁₀N₂: C, 80.38; H, 5.20; N, 14.42. Found: C, 80.43; H, 5.14; N, 14.41.
Entry 5: brown solid; mp 60-62 °C (Lit. [9b] 60-61 °C). ¹H NMR (90 MHz, CDCl₃): δ = 7.7 (1 H, br s), 7.3-7.1 (4 H, m), 7.12 (1 H, s), 6.8 (1 H, s), 3.9 (3 H, s). Anal. Calcd for C₁₀H₁₀N₂O: C, 68.94; H, 5.78; N, 16.08. Found: C, 68.71; H, 5.67; N, 16.01. Entry 6: liquid. ¹H NMR (90 MHz, CDCl₃): δ = 7.8-7.5 (4 H, m), 7.2-6.9 (2 H, m), 6.5 (1 H, s), 3.9 (3 H, s). Anal. Calcd for C₁₀H₁₀N₂O: C, 68.94; H, 5.78; N, 16.08. Found: C, 68.81; H, 5.56; N, 16.19.
Entry 10: yellow oil. ¹H NMR (90 MHz, CDCl_3:) δ = 7.5 (1 H, s), 7.4-7.1 (5 H, m), 7.1 (1 H, s), 2.2 (3 H, s). Anal. Calcd for C₁₀H₁₀N₂: C, 75.73; H, 6.47; N, 17.70. Found: C, 75.91; H, 6.35; N, 17.80.

<A NAME="RD06206ST-20">20</A> Schmittling EA. Sawyer JS. Tetrahedron Lett.  1991,  32:  7207 

<A NAME="RD06206ST-21">21</A> Phillips AM. J. Chem. Soc.  1929,  2820