John F. Hartwig

Research

Our research aims to discover, develop and understand new transition metal-catalyzed reactions. The scope of our studies ranges from catalytic aromatic substitution to the functionalization of alkanes to the enantioselective formation of C-N and C-O bonds in amines and ethers. 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 occurrs 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. Most recently, we have developed a regiospecific functionalization of alkanes using borane or diboron reagents in the presence of a rhodium catalyst and a sterecally 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.

Publications

Liu, Z.; Hartwig, J.F. "Mild, Rhodium-Catalyzed Intramolecular Hydroamination of Unactivated Terminal and Internal Olefins with Primary and Secondary Amines" J. Am. Chem. Soc. 2008, 130, in press.

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

Murphy, J. M.; Liao, X.; Hartwig, J. F. "Meta Halogenation of 1,3-Disubstituted Arenes via Iridium-Catalyzed Arene Borylation" J. Am. Chem. Soc. 2007, 129, 15434-15435.

Stambuli, J.P.; Weng, Z.; Incarvito, C.D.; Hartwig, J.F. "Reductive Elimination of Ether from T-Shaped, Monomeric Arylpalladium Alkoxides" Angew. Chem. Int. Ed. 2007, 46, 7674.

Pouy, M. J.; Leitner, A.; Weix, D. J.; Ueno, S.; Hartwig, J. F. "Enantioselective Iridium-Catalyzed Allylic Amination of Ammonia and Convenient Ammonia Surrogates" Org. Lett. 2007, 9, 3949-3952.

Johns, A. M.; Liu, Z.; Hartwig, J. F. "Primary tert- and sec-Allylamines via Palladium-Catalyzed Hydroamination and Allylic Substitution with Hydrazine and Hydroxylamine Derivatives" Angew. Chem. Int. Ed. 2007, 46, 7259.

Yamashita, Y.; Gopalarathnam, A.; Hartwig, J. F. "Iridium-Catalyzed, Asymmetric Amination of Allylic Alcohols Activated by Lewis Acids" J. Am. Chem. Soc. 2007, 129, 7508-7509.

Herzon, S. B., and J. F. Hartwig, "Direct, Catalytic Hydroaminoalkylation of Unactivated Olefins with N-Alkyl Arylamines". J. Amer. Chem. Soc., 2007. 129(21): p. 6690-6691.

Weix, D. J. and J. F. Hartwig, "Regioselective and Enantioselective Iridium-Catalyzed Allylation of Enamines". J. Amer. Chem. Soc., 2007. 129(25): p. 7720-7721.

Shen, Q. and J. F. Hartwig, "Lewis Acid Acceleration of C-N Bond-Forming Reductive Elimination from Heteroarylpalladium Complexes and Catalytic Amidation of Heteroaryl Bromides". J. Amer. Chem. Soc., 2007. 129(25): p. 7734-7735.

Markovic, D. and J. F. Hartwig, "Resting State and Kinetic Studies on the Asymmetric Allylic Substitutions Catalyzed by Iridium-Phosphoramidite Complexes". J. Am. Chem. Soc., 2007; 129(38); 11680-11681.

Fernandez-Rodríguez, M. A., Shen, Q., and J. F. Hartwig, "A General and Long-Lived Catalyst for the Palladium-Catalyzed Coupling of Aryl Halides with Thiols". J. Am. Chem. Soc., 2006. 128(7): p. 2180-2181.

Hama, T., Culkin, D. A., and J. F. Hartwig, "Palladium-Catalyzed Intermolecular a-Arylation of Zinc Amide Enolates under Mild Conditions". J. Am. Chem. Soc., 2006. 128(15): p. 4976-4985.

Zhao, P., Incarvito, C.D., and J. F. Hartwig, "Carbon-Oxygen Bond Formation between a Terminal Alkoxo Ligand and a Coordinated Olefin. Evidence for Olefin Insertion into a Rhodium-Alkoxide". J. Am. Chem. Soc., 2006. 128(30): p.9642-9643.

Shen, Q., and J. F. Hartwig, "Palladium-Catalyzed Coupling of Ammonia and Lithium Amide with Aryl Halides". J. Am. Chem. Soc., 2006. 128(31): p.10028-10029.

Takemiya, A., and J. F. Hartwig, "Palladium-Catalyzed Synthesis of Aryl Ketones by Coupling of Aryl Bromides with an Acyl Anion Equivalent". J. Am. Chem. Soc., 2006. 128(46): p. 14800-14801.

Awards

• 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