Chemistry at Illinois University of Illinois at Urbana-Champaign

John F. Hartwig

Kenneth L. Rinehart Professor of Chemistry

Professor Hartwig received his A. B. degree from Princeton, in 1986 and his Ph.D. from the University of California, Berkeley in 1990. Subsequently, he was an American Cancer Society Postdoctoral Fellow at the Massachusetts Institute of Technology and joined the Yale University faculty in 1992. Dr. Hartwig joined the University of Illinois chemistry faculty in July 2006.

Research

Our research aims to discover, develop, and understand new organic reactions catalyzed by transition-metal complexes. The scope of our studies includes catalytic aromatic substitution, the functionalization of alkanes and arenes, enantioselective formation of C-N and C-O bonds in amines and ethers, and the cleavage of C-O bonds in bio-feedstocks. The discovery of fundamentally new transition-metal chemistry and its development into practical, catalytic synthetic methods is a theme of our research. We reach these goals by obtaining insight from detailed mechanistic studies. The following classes of metal-catalyzed reactions are currently being investigated in my group:

Catalytic Formation of Amines, Ethers and Sulfides. Chemical Formulas

We developed a palladium-catalyzed process that forms arylamines, aryl sulfides, and arylethers. The catalytic chemistry resulted from our detailed mechanistic experiments on transition-metal amide, alkoxo, and thiolato complexes. Our most recently developed catalyst leads to the formation of arylamines and aryl sulfides with turnover numbers exceeding 10,000 in many cases and ppm levels of palladium in others.

This catalysis is useful for total synthesis, combinatorial synthesis, and the preparation of electronically important organic materials. At the same time, the catalysis involves unprecedented reactions of transition-metal compounds. Thus, some students focus on novel inorganic chemistry, while others use this reaction as a modular route to nitrogen heterocycles and polyanilines.

Catalytic Alpha Arylation of Carbonyl Compounds

We have developed a simple method to convert aryl halides and ketones, esters, amides, cyanoesters, malonates, nitriles, and related compounds to alpha aryl carbonyl compounds and nitriles in the presence of base and a palladium catalyst. Familiar compounds that can be generated from these products include Ibuprofen, Naproxin, and Tamoxifen. The reaction occurs in a general fashion and in many cases with low catalyst loadings.

As part of our studies to understand this process, we have generated both O-bound and C-bound palladium enolate complexes. These complexes undergo reductive elimination of the alpha-aryl ketone, ester, or amide product in good yields. Studies on the effects of changing the enolate electronics on reductive elimination rate are in progress.

Transition-Metal Boryl- and Borane Complexes. Catalytic, Regiospecific Functionalization of Alkanes

The chemistry of compounds with covalent transition metals and main group bonds is unexplored. While studying this fundamental reactivity, we discovered that metal boryl compounds react with arenes and alkanes to form functionalized products. We have developed a regiospecific functionalization of alkanes using borane or diboron reagents in the presence of a rhodium catalyst and a sterically controlled, iridium-catalyzed functionalization of arenes using the same boron reagents. We are currently exploring improved catalysts, as well as the scope and applications of the functionalization process.

Our mechanistic work on this process has intersected with our fundamental work in the group on borane sigma complexes. These complexes have unusual bonding between a metal hydride and the boryl ligand. In these complexes a partial, intact B-H bond accompanies an M-H and M-B bond. Recently, we have found that complexes of this type are similar to those involved in the alkane functionalization process.

Iridium-Catalyzed Asymmetric Allylic Substitution

Asymmetric allylic substitution is a widely utilized reaction catalyzed by complexes of transition metals, but the majority of studies have focused on palladium complexes. We have discovered an iridium complex that catalyzes allylic substitution with site selectivity that contrasts that of palladium complexes. Iridium-catalyzed reactions of allylic esters form products in which the new bond is formed at the more hindered end of the allyl intermediate. As a result, chiral allylic amines, ethers, and alkylation products, as well as a variety of N-allyl heterocycles, form by this process. These products are bifunctional compounds that serve as fundamental chiral building blocks. We are currently expanding the scope of this process and envision using this reaction as a means to generate new three-dimensional architectures for the discovery of medicinally important compounds.

New Catalytic Reactions of Bio-feedstocks

As part of the Energy Biosciences Institute at Illinois, we have sought new catalytic reactions that will enable the conversion of the components of lignocellulose to chemicals and fuels. In our first efforts toward this goal, we have identified a nickel complex that catalyzes the first hydrogenolyses of C-O bonds in the aryl ether units found in lignin to form arenes. Prior catalysts for these transformations lead to the reduction of arenes in concert with C-O bond cleavage, and this competing process prevents the use of lignin as a source of arene feedstocks. Current studies are directed toward understanding the mechanism of this reaction to increase the efficiency of the C-O bond cleavage and to use these results as a starting point for the discovery of further catalytic reactions that will stimulate work on the conversion of lignocellulose and its fermentation products to fuels and chemical feedstocks.

Publications

Textbook

Hartwig, J.F. Organotransition Metal Chemistry: From Bonding to Catalysis, University Science Books, Sausalito, CA, 2010.

Articles

Huang, D. S.; Hartwig, J. F. "Palladium-Catalyzed γ-Arylation of α,β-Unsaturated Esters from Silyl Ketene Acetals" Angew. Chem. Int. Ed. 2010, 49, 5757-5761.

Stanley, L. M.; Hartwig, J. F. "Mechanistically Driven Development of Iridium Catalysts for Asymmetric Allylic Substitution" Acc. Chem. Res. 2010 ASAP.

Simmons, E. M.; Hartwig, J. F. "Iridium-Catalyzed Arene ortho-Silylation by Formal Hydroxyl-Directed C-H Activation" J. Am. Chem. Soc. 2010 132, 17092-17095.

Giri, R.: Hartwig, J. F. "Cu(I) Amido Complexes in the Ullmann Reaction. Reactions of Cu(I)-Amido Complexes with Iodoarenes with and without Autocatalysis by CuI" J. Am. Chem. Soc. 2010 132, 15860-15863.

Klinkenberg, J. L.; Hartwig, J. F. "Catalytic Organometallic Reactions of Ammonia" Angew. Chem. Int. Ed. 2010, early view.

Julian, J. D.; Hartwig, J. F. "Intramolecular Hydroamination of Unbiased and Functionalized Primary Aminoalkenes Catalyzed by a Rhodium Aminophosphine Complex" J. Am. Chem. Soc. 2010 132, 13813-13822.

Klinkenberg, J. L.; Hartwig, J. F. "Slow Reductive Elimination from Arylpalladium Parent Amido Complexes" J. Am. Chem. Soc. 2010 132, 11830-11833.

Liskey, C. W.; Liao, X.; Hartwig, J. F. "Cyanation of Arenes via Iridium-Catalyzed Borylation" J. Am. Chem. Soc. 2010 132, 11389-11391.

Huang, Z.; Zhou, J. Hartwig, J. F. "N-H Activation of Hydrazines by Iridium(I). Double N-H Activation to Form Iridium Aminonitrene Complexes" J. Am. Chem. Soc. 2010 132, 11458-11460.

Stanley, L. M.; Bai, C.; Ueda, M.; Hartwig, J. F. "Iridium-Catalyzed Kinetic Asymmetric Transformations of Racemic Allylic Benzoates" J. Am. Chem. Soc. 2010, 132, 8918-8920.

Fernández-Rodríguez, M. A.; Hartwig, J. F. "One-Pot Synthesis of Unsymmetrical Diaryl Thioethers by Palladium-Catalyzed Coupling of Two Aryl Bromides and a Thiol Surrogate" Chem.—Eur. J. 2010, 16, 2355-2359.

Hanley, P. S.; Markovic, D.; Hartwig, J. F. "Intermolecular Insertion of Ethylene and Octene into a Palladium-Amide Bond. Spectroscopic Evidence for an Ethylene Amido Intermediate" J. Am. Chem. Soc. 2010, 132, 6302-6303.

Tye, J. W.; Weng, Z.; Giri, R.; Hartwig J. F. "Copper(I) Phenoxide Complexes in the Etherification of Aryl Halides" Angew. Chem. Int. Ed. 2010, 49, 2185-2189.

Tan, Y.; Hartwig, J. F. "Palladium-Catalyzed Amination of Aromatic C–H Bonds with Oxime Esters" J. Am. Chem. Soc. 2010, 132, 3676-3677.

Robbins, D. W.; Boebel, T. A.; Hartwig, J. F. "Iridium-Catalyzed, Silyl-Directed Borylation of Nitrogen-Containing Heterocycles" J. Am. Chem. Soc. 2010, 132, 4068-4069.

Sawyer, K. R., Cahoon, J. F., Shanoski, J. E., Glascoe, E. A., Kling, M. F., Schlegel, J. P., Zoerb, M. C., Hapke, M., Hartwig, J. F., Webster, C. E., Harris, C. B. "Time-resolved IR Studies on the Mechanism for the Functionalization of Primary C−H Bonds by Photoactivated Cp*W(CO)3(Bpin)" J. Am. Chem. Soc. 2010, 132, 1848-1859.

Wei, C. S.; Jimenez-Hoyos, C. A.; Videa, M. F.; Hartwig, J. F.; Hall, M. B. "Origins of the Selectivity for Borylation of Primary over Secondary C–H Bonds Catalyzed by Cp*-Rhodium Complexes" J. Am. Chem. Soc. 2010, 132, 3078-3091.

Carrow, B. P.; Hartwig, J. F. "Ligandless, Anionic, Arylpalladium Halide Intermediates in the Heck Reaction" J. Am. Chem. Soc. 2010, 132, 79-81.

Marquard, S. L.; Rosenfeld, D. C.; Hartwig, J. F. "C(sp3)-N Bond-Forming Reductive Elimination of Amines: Reactions of Bisphosphine-Ligated Benzylpalladium(II) Diarylamido Complexes" Angew. Chem. Int. Ed. 2010, 49, 793-796.

Mkhalid, I. A. I.; Barnard, J. H.; Marder, T. B.; Murphy, J. M.; Hartwig, J. F. "C-H Activation for the Construction of C-B Bonds" Chem. Rev. 2010, 110, 890-931.

Previous Publications

See the Hartwig Group website for a full list of Prof. Hartwig's publications.

Awards

  • GlaxoSmithKline Scholars Award, 2010
  • National Institutes of Health MERIT Award, 2009
  • Royal Society of Chemistry Joseph Chatt Award, 2009
  • Edward Mack Jr. Memorial Award, Ohio State University, 2009
  • Mitsui Chemicals Catalysis Science Award, 2009
  • International Catalysis Award (International Association of Catalysis Societies)
  • RSC Joseph Chatt Lectureship, 2008
  • Paul N. Rylander Award of the Organic Reactions Catalysis Society, 2008
  • Tetrahedron Young Investigator Award in Organic Synthesis, 2007
  • Mukaiyama Award from the Society of Synthetic Organic Chemistry of Japan, 2007
  • Raymond and Beverly Sackler Prize in the Physical Sciences, 2007
  • ACS Award in Organometallic Chemistry, 2006
  • Thieme-IUPAC Prize in Synthetic Organic Chemistry, 2004
  • Leo Hendrik Baekeland Award, 2003
  • A. C. Cope Scholar, 1997
  • Eli Lilly Grantee, 1997
  • Camille Dreyfus Teacher-Scholar Award, 1997
  • Alfred P. Sloan Research Fellow, 1996-1998
  • Union Carbide Innovative Recognition Award, 1995-1996
  • NSF Young Investigator Award, 1994
  • DuPont Young Professor Award, 1993
  • Dreyfus Foundation New Faculty Award, 1992

Highlights

Recent Publication Highlights

Many of the papers published by the Hartwig group have been highlighted in the secondary literature and are among the most downloaded and cited papers in their respective journals. In the last survey by the ISI citation service, Prof. Hartwig was among the 50 most cited chemists in any field and the most cited of any synthetic chemist in the world his age or younger.

A few of the places that regularly highlight his group's work are work are shown below.

Thieme Chemistry Synfacts
A large fraction of the papers published by Prof. Hartwig's group on synthetic methodology are highlighted in Synfacts. These highlights and the corresponding original papers are listed below.

Knochel, P.; Thaler, T. "Mild Pd-Catalyzed Amination of Aryl and Heteroaryl Tosylates" Synfacts 2009, 1, 84.

Corresponding original paper:
Ogata, T.; Hartwig, J. F. "Palladium-Catalyzed Amination of Aryl and Heteroaryl Tosylates at Room Temperature" J. Am. Chem. Soc. (Communication), 2008, 130, 13848-13849.

Knochel, P.; Thaler, T. "A Highly Efficient Catalyst for Pd-Catalyzed Amination of Aryl Halides" Synfacts 2008, 8, 859.

Corresponding original paper:
Shen, Q.; Ogata, T.; Hartwig, J. F. "Highly Reactive, General and Long-Lived Catalysts for Palladium-Catalyzed Amination of Heteroaryl and Aryl Chlorides, Bromides and Iodides: Scope and Structure-Activity Relationships" J. Am. Chem. Soc 2008, 130, 6586-6596.

Knochel, P.; Gavryushin, A. "Palladium-Catalyzed α-Arylation of Esters" Synfacts 2008, 7, 750.

Corresponding original paper:
Hama, T.; Hartwig, J. F. "Palladium-Catalyzed α-Arylation of Esters with Chloroarenes" Org. Lett. 2008, 10, 1549-1552.

Lautens, M.; Aureggi, V. "Iridium-Catalyzed Asymmetric Allylic Etherification" Synfacts 2008, 5, 500.

Corresponding original paper:
Ueno, S.; Hartwig, J. F. "Direct, Iridium-Catalyzed Asymmetric Allylic Etherification with Aliphatic Alcohols" Angew. Chem. Int. Ed. 2008, 47, 1928-1931.

Yamamoto, H.; Cheon, C. H. "Difluorphos Complexes of Palladium and Nickel-Catalyzed α-Arylation of Ketones" Synfacts 2008, 4, 385.

Corresponding original paper:
Liao, X.; Weng, Z.; Hartwig J. F. "Enantioselective α-Arylation of Ketones with Aryl Triflates Catalyzed by Difluorphos Complexes of Palladium and Nickel" J. Am. Chem. Soc. 2008, 130, 195-200.

Chemical & Engineering News
Publications from the Hartwig Group have also frequently been highlighted in stories in Chemical & Engineering News. A sample of these is listed below:

Steve Ritter, "Expanding on Hydroaminations" Chem. Eng. News 2008, 86, 12.

Steve Ritter, "Amine Synthesis Gains Utility" Chem. Eng. News 2007, 85, 9.

Steve Ritter, "Ammonia Is Ready for a Transfer" Chem. Eng. News 2005, 83, 12.

"Pd Dimers Let Aryl Halides React Fast Under Mild Conditions" Chem. Eng. News 2002, 80, 31.

"ACS News: Most Requested Article, Journal from 2003" Chem. Eng. News 2004, 82, 39.

Stu Borman "Pin the Tail on the Olefin" Chem. Eng. News 2004, 82, 42-43.

Announcements of recent awards in Chemical & Engineering News include:

"Sackler Prize Winners Announced" Chem. Eng. News 2007, 85, 75-76.

"2007 and 2008 Rylander Award Winners Announced" Chem. Eng. News 2007, 85, 75.

"ACS Award in Organometallic Chemistry" Chem. Eng. News 2006, 84, 50-54.

Angewandte Chemie International Edition
Angewandte Chemie includes articles that highlight papers chosen by other chemists to be particularly noteworthy. Many of these articles highlight work from Prof. Hartwig's Group, and a selection of such recent highlights include:

Willis, M. C. "Palladium-Catalyzed Coupling of Ammonia and Hydroxide with Aryl Halides: The Direct Synthesis of Primary Anilines and Phenols" Angew. Chem., Int. Ed. 2007, 46, 3402-3404.

Christmann, U.; Vilar, R. "Monoligated Palladium Species as Catalysts in Cross-Coupling Reactions" Angew. Chem., Int. Ed. 2005, 44, 366-374.

Braun, T. "Oxidative Addition of NH3 to a Transition-Metal Complex: A Key Step for the Metal-Mediated Derivatization of Ammonia?" Angew. Chem., Int. Ed. 2005, 44, 5012-5014.

Lloyd-Jones, G. C. "Palladium-Catalyzed α-Arylation of Esters: Ideal New Methodology for Discovery Chemistry" Angew. Chem., Int. Ed. 2002, 41, 953-956.

Other Highlights

Organic Chemistry Portal Highlights

Buchwald-Hartwig Reaction on Wikipedia

Professor John Hartwig Joins Cambridge Major Lab's Scientific Advisory Team

Patents

Photo of John F. Hartwig