Low Catalyst Loadings for Copper-Catalyzed O-Arylation of Phenols with Aryl and Heteroaryl Halides under Mild Conditions

Abstract

A practical and mild strategy has been developed for the cross-coupling of O-arylation of phenol with differently substituted aryl halides and heteroaryl iodides using low catalyst loading of copper iodide under low operating temperature in DMF with TMHD as the ligand and Cs₂CO₃ as the base. This method tolerates a variety of functional groups including sterically hindered phenols and heteroaryl iodides to afford products in good to excellent yields (up to 95%).

cross-coupling - mild conditions - low catalyst loading - copper-catalyzed - O-arylations - phenol

References and Notes

For representative papers on pharmaceutical compounds, see:

<A NAME="RD29711ST-1A">1a</A> Evans DA. Devries KM. In Glycopeptide Antibiotics, Drugs and the Pharmaceutical Sciences   Vol. 63:  Nagarajan R. Marcel Decker, Inc.; New York: 1994.  p.63-104  

<A NAME="RD29711ST-1B">1b</A> Rao AV. Rama Gurjar MK. Reddy L. Rao AS. Chem. Rev.  1995,  95:  2135 

<A NAME="RD29711ST-1C">1c</A> Wada CK. Holms JH. Curtin ML. Dai Y. Florjancic AS. Garland RB. Guo Y. Heyman HR. Stacey JR. Steinman DH. Albert DH. Bouska JJ. Elmore IN. Goodfellow CL. Marcotte PA. Tapang P. Morgan DW. Michaelides MR. Davidsen SK. J. Med. Chem.  2002,  45:  219 

<A NAME="RD29711ST-1D">1d</A> Hodous BL. Feuns-Meyer SD. Hughes PE. Albrecht BK. Bellon S. Bready J. Caenepeel S. Cee VJ. Chaffee SC. Coxon A. Emery M. Fretland J. Gallant P. Gu Y. Hoffman D. Johnson RE. Kendall R. Kim JL. Long AM. Morrison M. Olivieri PR. Patel VF. Polverino A. Rose P. Tempest P. Wang L. Whittington DA. Zhao HL. J. Med. Chem.  2007,  50:  611 

<A NAME="RD29711ST-1E">1e</A> Liu LB. Siegmund A. Xi N. Kaplan-Lefko P. Rex K. Cheti A. Lin J. Moriguchi J. Berry L. Huang L. Teffera Y. Yang YI. Zhang YH. Bellon SF. Lee M. Shimanovich R. Bak A. Dominguez C. Norman MH. Harmange JC. Dussault I. Kimt TS. J. Med. Chem.  2008,  51:  3688 

<A NAME="RD29711ST-1F">1f</A> Caron S. Do NM. Sieser JE. Whritenour DC. Hill PD. Org. Process Res. Dev.  2009,  13:  324 

For representative papers on agricultural compounds, see:

<A NAME="RD29711ST-1G">1g</A> Draper WM. Casida JE. J. Agric. Food Chem.  1983,  31:  1201 

<A NAME="RD29711ST-1H">1h</A> The Pesticide Manual   10th ed.:  Tomlin C. British Crop Protection Council; Farnham: 1994. 

<A NAME="RD29711ST-1I">1i</A> Scrano L. Bufo SA. D’Auria M. Meallier P. Behechti A. Shramm KW. J. Environ. Qual.  2002,  31:  268 

For representative papers on polymer industries, see:

<A NAME="RD29711ST-1J">1j</A> Labadie JW. Hedrick JL. Ueda M. Am. Chem. Soc. Symp. Ser.  1996,  624:  210 

<A NAME="RD29711ST-1K">1k</A> Theil F. Angew. Chem. Int. Ed.  1999,  38:  2345 

<A NAME="RD29711ST-1L">1l</A> Laskoski M. Dominguez DD. Keller TM. J. Polym. Sci., Part A: Polym. Chem.  2006,  44:  4559 

<A NAME="RD29711ST-2">2</A> Ullmann F. Chem. Ber.  1904,  37:  853 

<A NAME="RD29711ST-3A">3a</A> Lindley J. Tetrahedron  1984,  40:  1433 

<A NAME="RD29711ST-3B">3b</A> Paul S. Gupta M. Tetrahedron Lett.  2004,  45:  8825 

<A NAME="RD29711ST-4A">4a</A> Marcoux J.-F. Doye S. Buchwald SL. J. Am. Chem. Soc.  1997,  119:  10539 

<A NAME="RD29711ST-4B">4b</A> Fagan PF. Hauptman E. Shapiro R. Casalnuovo A. J. Am. Chem. Soc.  2000,  122:  5043 

<A NAME="RD29711ST-4C">4c</A> Gujadhur R. Venkataraman D. Synth. Commun.  2001,  31:  2865 

<A NAME="RD29711ST-4D">4d</A> Gujadhur RK. Bates CG. Venkataraman D. Org. Lett.  2001,  3:  4315 

<A NAME="RD29711ST-4E">4e</A> Ma D. Cai Q. Org. Lett.  2003,  5:  3799 

<A NAME="RD29711ST-4F">4f</A> Cai Q. Zou B. Ma D. Angew. Chem. Int. Ed.  2006,  45:  1276 

<A NAME="RD29711ST-4G">4g</A> Chen Y.-J. Chen H.-H. Org. Lett.  2006,  8:  5609 

<A NAME="RD29711ST-4H">4h</A> Ouali A. Spindler JF. Cristau HJ. Taillefer M. Adv. Synth. Catal.  2006,  348:  499 

<A NAME="RD29711ST-4I">4i</A> Rao H. Jin Y. Fu H. Jiang Y. Zhao Y. Chem. Eur. J.  2006,  12:  3636 

<A NAME="RD29711ST-4J">4j</A> Lv X. Bao W. J. Org. Chem.  2007,  72:  3863 

<A NAME="RD29711ST-4K">4k</A> Naidu AB. Raghunath OR. Prasad DJC. Sekar G. Tetrahedron Lett.  2008,  49:  1057 

<A NAME="RD29711ST-4L">4l</A> Niu J. Zhou H. Li Z. Xu J. Hu S. J. Org. Chem.  2008,  73:  7814 

<A NAME="RD29711ST-4M">4m</A> Liu Y.-H. Li G. Yang L.-M. Tetrahedron Lett.  2009,  50:  343 

<A NAME="RD29711ST-4N">4n</A> Maiti D. Buchwald SL. J. Am. Chem. Soc.  2009,  131:  17423 

<A NAME="RD29711ST-4O">4o</A> Zhang Q. Wang D. Wang X. Ding K. J. Org. Chem.  2009,  74:  7187 

<A NAME="RD29711ST-4P">4p</A> Maiti D. Buchwald SL. J. Org. Chem.  2010,  75:  1791 

<A NAME="RD29711ST-5">5</A> Marcoux J.-F. Doye S. Buchwald SL. J. Am. Chem. Soc.  1997,  119:  10539 

<A NAME="RD29711ST-6">6</A> Buck E. Song ZJ. Tschaen D. Dormer PG. Volante RP. Reider PJ. Org. Lett.  2002,  4:  1623 

<A NAME="RD29711ST-7">7</A> Larsson P.-F. Correa A. Carril M. Norrby P.-O. Bolm C. Angew. Chem. Int. Ed.  2009,  48:  5691 

<A NAME="RD29711ST-8">8</A>

Representative Procedure for O-Arylation of Phenols: A mixture of CuI (Sigma-Aldrich, 99.99% purity, 0.0147 mmol), TMHD (0.147 mmol), Cs₂CO₃ (2.94 mmol) was dissolved in DMF (0.3 mL). Subsequently, the aryl halide (1.47 mmol) and the phenol (2.21 mmol) were added to the reaction vial and a screw cap was fitted to it. The reaction mixture was stirred under air in a closed system at 60 ˚C for 24 h and the heterogeneous mixture was then cooled to r.t. and diluted with EtOAc. The resulting solution was directly filtered through a pad of Celite. The organic extracts were washed with H₂O twice. The combined organic extracts were dried with anhyd Na₂SO₄ and the solvent was removed under reduced pressure. The crude product was purified by silica gel column chromatography to afford the O-arylated product. The identity and purity of known products were confirmed by ^¹H NMR and ^¹³C NMR spectroscopic analysis.