Synlett 2006(9): 1283-1294  
DOI: 10.1055/s-2006-939728
ACCOUNT
© Georg Thieme Verlag Stuttgart · New York

Discovery and Understanding of Transition-Metal-Catalyzed Aromatic Substitution Reactions

John F. Hartwig*
Department of Chemistry, Yale University, P.O. Box 208107, New Haven, CT 06520-8107, USA
Fax: +1(203)4326144; e-Mail: john.hartwig@yale.edu;
Further Information

Publication History

Received 5 January 2006
Publication Date:
22 May 2006 (online)

Abstract

This article presents studies on the development of cross-coupling reactions of aryl halides and sulfonates with amines, alkoxides, and various enolates. Emphasis is placed on the process of developing new catalysts with mechanistic information gained in the author’s laboratory.

  • 1 Introduction

  • 2 Early Reaction Development

  • 3 New Catalyst Developments

  • 4 Mechanism of the Cross-Coupling Processes

  • 5 Mechanism of Oxidative Addition

  • 6 Reductive Elimination of Amines

  • 7 Stable Palladium Catalysts for Coupling of Primary Amines

  • 8 Guidelines for Catalyst Selection

    References and Notes

  • 1 Heaney H. Chem. Rev.  1962,  62:  81 
  • 2 Rossi RA. Bunnett JF. J. Org. Chem.  1973,  38:  1407 
  • 3 Rossi R. de Rossi RH. Aromatic Substitution by the S RN 1 Mechanism   ACS Monograph Series No. 178:  American Chemical Society; Washington D.C.: 1983. 
  • 4 Hartwig JF. In Handbook of Organopalladium Chemistry for Organic Synthesis   Vol. 1:  Negishi EI. Wiley-Interscience; New York: 2002.  p.1051 
  • 5 Hartwig JF. In Handbook of Organopalladium Chemistry for Organic Synthesis   Vol. 1:  Negishi EI. Wiley-Interscience; New York: 2002.  p.1097 
  • 6 Culkin DA. Hartwig JF. Acc. Chem. Res.  2003,  36:  234 
  • 7 Kosugi M. Kameyama M. Migita T. Chem. Lett.  1983,  927 
  • 8 Kosugi M. Kameyama M. Sano H. Migita T. Nippon Kagaku Kaishi  1985,  3:  547 
  • 10 Hartwig JF. Acc. Chem. Res.  1998,  31:  852 
  • 11 Wolfe JP. Wagaw S. Marcoux J.-F. Buchwald SL. Acc. Chem. Res.  1998,  31:  805 
  • 12 Muci AR. Buchwald SL. Top. Curr. Chem.  2002,  219:  131 
  • 13 Guram AS. Rennels RA. Buchwald SL. Angew. Chem., Int. Ed. Engl.  1995,  34:  1348 
  • 14 Louie J. Hartwig JF. Tetrahedron Lett.  1995,  36:  3609 
  • 15 Wolfe JP. Åhman J. Sadighi JP. Singer RA. Buchwald SL. Tetrahedron Lett.  1997,  38:  6367 
  • 16 Mann G. Hartwig JF. Driver MS. Fernandez-Rivas C. J. Am. Chem. Soc.  1998,  120:  827 
  • 17 Lee S. Jorgensen M. Hartwig JF. Org. Lett.  2001,  3:  2729 
  • 18 Huang XH. Buchwald SL. Org. Lett.  2001,  3:  3417 
  • 19 Hartwig JF. Angew. Chem., Int. Ed. Engl.  1998,  37:  2090 
  • 20 Wagaw S. Yang BH. Buchwald SL. J. Am. Chem. Soc.  1998,  120:  6621 
  • 21 Wagaw S. Yang B. Buchwald SL. J. Am. Chem. Soc.  1999,  121:  10251 
  • 22 Haddad N. Baron J. Tetrahedron Lett.  2002,  43:  2171 
  • 23 Mann G. Hartwig JF. J. Org. Chem.  1997,  62:  5413 
  • 24 Mann G. Hartwig JF. Tetrahedron Lett.  1997,  38:  8005 
  • 25 Mann G. Hartwig JF. J. Am. Chem. Soc.  1996,  118:  13109 
  • 26 Palucki M. Wolfe JP. Buchwald SL. J. Am. Chem. Soc.  1997,  119:  3395 
  • 27 Palucki M. Wolfe JP. Buchwald SL. J. Am. Chem. Soc.  1996,  118:  10333 
  • 28 Mann G. Incarvito C. Rheingold AL. Hartwig JF. J. Am. Chem. Soc.  1999,  121:  3224 
  • 29 Shelby Q. Kataoka N. Mann G. Hartwig JF. J. Am. Chem. Soc.  2000,  122:  10718 
  • 30 Kataoka N. Shelby Q. Stambuli JP. Hartwig JF. J. Org. Chem.  2002,  67:  5553 
  • 31 Aranyos A. Old DW. Kiyomori A. Wolfe JP. Sadighi JP. Buchwald SL. J. Am. Chem. Soc.  1999,  121:  4369 
  • 32 Torraca K. Kuwabe S. Buchwald S. J. Am. Chem. Soc.  2000,  122:  12907 
  • 33 Kuwabe S. Torraca KE. Buchwald SL. J. Am. Chem. Soc.  2001,  123:  12202 
  • 34 Parrish CA. Buchwald SL. J. Org. Chem.  2001,  66:  2498 
  • 35 Torraca KE. Huang XH. Parrish CA. Buchwald SL. J. Am. Chem. Soc.  2001,  123:  10770 
  • 36 Hamann BC. Hartwig JF. J. Am. Chem. Soc.  1997,  119:  12382 
  • 37 Palucki M. Buchwald SL. J. Am. Chem. Soc.  1997,  119:  11108 
  • 38 Ehrentraut A. Zapf A. Beller M. Adv. Synth. Catal.  2002,  344:  209 
  • 39 Viciu MS. Germaneau RF. Nolan SP. Org. Lett.  2002,  4:  4053 
  • 40 Fox JM. Huang XH. Chieffi A. Buchwald SL. J. Am. Chem. Soc.  2000,  122:  1360 
  • 41 Kawatsura M. Hartwig JF. J. Am. Chem. Soc.  1999,  121:  1473 
  • 42 Driver MS. Hartwig JF. J. Am. Chem. Soc.  1996,  118:  7217 
  • 43 Nishiyama M. Yamamoto T. Koie Y. Tetrahedron Lett.  1998,  39:  617 
  • 44 Hartwig JF. Kawatsura M. Hauck SI. Shaughnessy KH. Alcazar-Roman LM. J. Org. Chem.  1999,  64:  5575 
  • 45 Stambuli JP. Kuwano R. Hartwig JF. Angew. Chem. Int. Ed.  2002,  41:  4746 
  • 46 Shen Q. Shekhar S. Stambuli JP. Hartwig JF. Angew. Chem. Int. Ed.  2004,  44:  1371 
  • 47 Roy AH. Hartwig JF. J. Am. Chem. Soc.  2003,  125:  8704 
  • 48 Rathke MW. Lindert A. J. Am. Chem. Soc.  1971,  93:  2318 
  • 49 Rathke MW. Sullivan DF. J. Am. Chem. Soc.  1973,  95:  3050 
  • 50 Jørgensen M. Liu X. Wolkowski JP. Hartwig JF. J. Am. Chem. Soc.  2002,  124:  12557 
  • 51 Hama T. Liu X. Culkin D. Hartwig JF. J. Am. Chem. Soc.  2003,  125:  11176 
  • 52 Shaughnessy KH. Hamann BC. Hartwig JF. J. Org. Chem.  1998,  63:  6546 
  • 53 Liu X. Hartwig JF. J. Am. Chem. Soc.  2004,  126:  5182 
  • 55 Fauvarque J.-F. Pflüger F. J. Organomet. Chem.  1981,  208:  419 
  • 56 Amatore C. Pfluger F. Organometallics  1990,  9:  2276 
  • 57 Hartwig JF. Paul F. J. Am. Chem. Soc.  1995,  117:  5373 
  • 58 Barios-Landeros F. Hartwig JF. J. Am. Chem. Soc.  2005,  127:  6944 
  • 59 Alcazar-Roman LM. Hartwig JF. Rheingold AL. Liable-Sands LM. Guzei IA. J. Am. Chem. Soc.  2000,  122:  4618 
  • 60 Singh UK. Strieter ER. Blackmond DG. Buchwald SL. J. Am. Chem. Soc.  2002,  124:  14104 
  • 61 Shekhar S. Ryberg P. Hartwig JF. Org. Lett.  2006,  8:  851 
  • 62 Shekhar S. Ryberg P. Hartwig JF. Mathew JS. Blackmond DG. Strieter ER. Buchwald SL. J. Am. Chem. Soc.  2006,  128:  3584 
  • 63 Stambuli JP. Bühl M. Hartwig JF. J. Am. Chem. Soc.  2002,  124:  9346 
  • 64 Stambuli JP. Incarvito CD. Buhl M. Hartwig JF. J. Am. Chem. Soc.  2004,  126:  1184 
  • 65 Barrios-Landeros F. Hartwig JF. J. Am. Chem. Soc.  2005,  127:  6944 
  • 66 Roy AH. Hartwig JF. Organometallics  2004,  23:  194 
  • 67 Driver MS. Hartwig JF. J. Am. Chem. Soc.  1995,  117:  4708 
  • 68 Driver MS. Hartwig JF. J. Am. Chem. Soc.  1997,  119:  8232 
  • 69 Hartwig JF. J. Am. Chem. Soc.  1996,  118:  7010 
  • 70 Zhao J. Hesslink H. Hartwig JF. J. Am. Chem. Soc.  2001,  123:  7220 
  • 71 Hartwig JF. Richards S. Barañano D. Paul F. J. Am. Chem. Soc.  1996,  118:  3626 
  • 72 Yamashita M. Hartwig JF. J. Am. Chem. Soc.  2004,  126:  5344 
  • 73 Culkin DA. Hartwig JF. J. Am. Chem. Soc.  2001,  123:  5816 
  • 74 Culkin DA. Hartwig JF. Organometallics  2004,  23:  3398 
  • 75 Huang XH. Anderson KW. Zim D. Jiang L. Klapars A. Buchwald SL. J. Am. Chem. Soc.  2003,  125:  6653 
  • 76 Harris MC. Huang X. Buchwald SL. Org. Lett.  2002,  4:  288 
9

For a review of our work on the reductive elimination to form carbon-nitrogen and carbon-oxygen bonds, see reference 10.

54

Our original work on the catalytic process led to the conclusion that the immediate product of the C-N bond-forming step [Pd(BINAP)(NArRR")], reacts with free ligand to regenerate [Pd(BINAP)2] faster than the amine dissociates to generate [Pd(BINAP)] and that [Pd(BINAP)2] lies directly on the catalytic cycle. We recently remeasured kinetic data on the order of the catalytic process in bromoarene and ligand and our corrected data imply that [Pd(BINAP)(NArRR")] dissociates the amine to form [Pd(BINAP)] faster than it reacts with the free ligand and that [Pd(BINAP)2] lies off the cycle as shown in Scheme [4] . These data are presented in reference 62.