Paul J Chirik

Princeton University, Princeton, New Jersey, United States

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Publications (166)1411.72 Total impact

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    ABSTRACT: The asymmetric hydrogenation of cyclic alkenes lacking coordinating functionality with a C1-symmetric bis(imino)pyridine cobalt catalyst is described and has been applied to the synthesis of important substructures found in natural products and biologically active compounds. High activities and enantioselectivities were observed with substituted benzo-fused 5-, 6- and 7-membered alkenes. The stereochemical outcome was dependent on both the ring size and exo/endo disposition. Deuterium labeling experiments and computational studies support rapid and reversible 2,1-insertion that is unproductive for generating alkane product but accounts for unusual isotopic distribution in deuterated alkanes. Analysis of the stereochemical outcome of the hydrogenated products coupled with isotopic labeling, stoichiometric, kinetic and computational studies established 1,2-alkene insertion as both turnover limiting and enantiodetermining with no evidence for erosion of cobalt alkyl stereochemistry by competing β-hydrogen elimination processes. A stereochemical model accounting for the preferred antipodes of the alkanes is proposed and relies on the subtle influence of the achiral aryl imine substituent on the cobalt catalyst.
    No preview · Article · Feb 2016 · Journal of the American Chemical Society
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    ABSTRACT: A thorough understanding of the pharmacokinetic and pharmacodynamic properties of a drug in animal models is a critical component of drug discovery and development(1-6). Such studies are performed in vivo and in vitro at various stages of the development process-ranging from preclinical absorption, distribution, metabolism and excretion (ADME) studies to late-stage human clinical trials-to elucidate a drug molecule's metabolic profile and to assess its toxicity(2). Radiolabelled compounds, typically those that contain C-14 or H-3 isotopes, are one of the most powerful and widely deployed diagnostics for these studies(4,5). The introduction of radiolabels using synthetic chemistry enables the direct tracing of the drug molecule without substantially altering its structure or function. The ubiquity of C-H bonds in drugs and the relative ease and low cost associated with tritium (H-3) make it an ideal radioisotope with which to conduct ADME studies early in the drug development process(2,4,6). Here we describe an iron-catalysed method for the direct H-3 labelling of pharmaceuticals by hydrogen isotope exchange, using tritium gas as the source of the radioisotope. The site selectivity of the iron catalyst is orthogonal to currently used iridium catalysts and allows isotopic labelling of complementary positions in drug molecules, providing a new diagnostic tool in drug development.
    No preview · Article · Jan 2016 · Nature
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    ABSTRACT: Cobalt dialkyl and bis(carboxylate) complexes bearing α-diimine ligands have been synthesized and demonstrated as active for the C(sp3)-H borylation of a range of substituted alkyl arenes using B2Pin2 (Pin = pinacolate) as the boron source. At longer reaction times, rare examples of polyborylation were observed and in the case of toluene all three benzylic C-H positions were functionalized. Coupling benzylic C-H activation with alkyl isomerization enabled a base metal catalyzed method for the C(sp3)-H borylation of remote, unactivated C-H bonds.
    No preview · Article · Dec 2015 · Journal of the American Chemical Society
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    ABSTRACT: A new route to single-component iron ethylene oligomerization and polymerization catalysts is described. Treatment of readily synthesized iron butadiene complexes with B(C6F5)3 generated the corresponding betaine compounds, active catalysts for the oligomerization and polymerization of ethylene. The electronic structures of a family of iron compounds bearing tridentate, α-diimine phosphine ligands have been determined, including cases where the neutral donor has dissociated from the metal. In iron-catalyzed ethylene oligomerization with these compounds, the hemilability of the chelate has been identified as a catalyst deactiviation pathway.
    No preview · Article · Dec 2015 · Organometallics
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    Paul J. Chirik

    Preview · Article · Oct 2015 · Organometallics
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    ABSTRACT: Cycloadditions, such as the [4+2] Diels-Alder reaction to form six-membered rings, are among the most powerful and widely used methods in synthetic chemistry. The analogous [2+2] alkene cycloaddition to synthesize cyclobutanes is kinetically accessible by photochemical methods, but the substrate scope and functional group tolerance are limited. Here, we report iron-catalyzed intermolecular [2+2] cycloaddition of unactivated alkenes and cross cycloaddition of alkenes and dienes as regio- and stereoselective routes to cyclobutanes. Through rational ligand design, development of this base metal-catalyzed method expands the chemical space accessible from abundant hydrocarbon feedstocks. Copyright © 2015, American Association for the Advancement of Science.
    No preview · Article · Aug 2015 · Science
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    Paul J. Chirik

    Preview · Article · Jul 2015 · Organometallics
  • Paul J Chirik
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    ABSTRACT: The hydrogenation of alkenes is one of the most impactful reactions catalyzed by homogeneous transition metal complexes finding application in the pharmaceutical, agrochemical, and commodity chemical industries. For decades, catalyst technology has relied on precious metal catalysts supported by strong field ligands to enable highly predictable two-electron redox chemistry that constitutes key bond breaking and forming steps during turnover. Alternative catalysts based on earth abundant transition metals such as iron and cobalt not only offer potential environmental and economic advantages but also provide an opportunity to explore catalysis in a new chemical space. The kinetically and thermodynamically accessible oxidation and spin states may enable new mechanistic pathways, unique substrate scope, or altogether new reactivity. This Account describes my group's efforts over the past decade to develop iron and cobalt catalysts for alkene hydrogenation. Particular emphasis is devoted to the interplay of the electronic structure of the base metal compounds and their catalytic performance. First generation, aryl-substituted pyridine(diimine) iron dinitrogen catalysts exhibited high turnover frequencies at low catalyst loadings and hydrogen pressures for the hydrogenation of unactivated terminal and disubstituted alkenes. Exploration of structure-reactivity relationships established smaller aryl substituents and more electron donating ligands resulted in improved performance. Second generation iron and cobalt catalysts where the imine donors were replaced by N-heterocyclic carbenes resulted in dramatically improved activity and enabled hydrogenation of more challenging unactivated, tri- and tetrasubstituted alkenes. Optimized cobalt catalysts have been discovered that are among the most active homogeneous hydrogenation catalysts known. Synthesis of enantiopure, C1 symmetric pyridine(diimine) cobalt complexes have enabled rare examples of highly enantioselective hydrogenation of a family of substituted styrene derivatives. Because improved hydrogenation performance was observed with more electron rich supporting ligands, phosphine cobalt(II) dialkyl complexes were synthesized and found to be active for the diastereoselective hydrogenation of various substituted alkenes. Notably, this class of catalysts was activated by hydroxyl functionality, representing a significant advance in the functional group tolerance of base metal hydrogenation catalysts. Through collaboration with Merck, enantioselective variants of these catalysts were discovered by high throughput experimentation. Catalysts for the hydrogenation of functionalized and essentially unfunctionalized alkenes have been discovered using this approach. Development of reliable, readily accessible cobalt precursors facilitated catalyst discovery and may, along with lessons learned from electronic structure studies, provide fundamental design principles for catalysis with earth abundant transition metals beyond alkene hydrogenation.
    No preview · Article · Jun 2015 · Accounts of Chemical Research
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    ABSTRACT: Aryl-substituted bis(imino)pyridine cobalt dinitrogen compounds, (RPDI)CoN2 are effective pre-catalysts for the intramolecular [2π+2π] cycloaddition of α,ω-dienes to yield the corresponding bicyclo [3.2.0]heptane derivatives. The reactions proceed under mild thermal conditions with unactivated alkenes, tolerating both amine and ether functional groups. The overall second order rate law for the reaction, first order with respect to both cobalt pre-catalyst and substrate, in combination with EPR spectroscopic studies established the catalyst resting state as the starting cobalt dinitrogen compounds. Planar, S = ½ κ3-bis(imino)pyridine cobalt alkene and tetrahedral κ2-bis(imino)pyridine cobalt diene complexes were observed by EPR spectroscopy and in the latter case, structurally characterized. The electronic structure of these intermediates highlights the role of metal-ligand cooperativity during catalytic turnover. The hemilabile chelate facilitates conversion of a principally ligand-based SOMO in the cobalt dinitrogen and alkene compounds to a metal-based SOMO in the diene intermediates, generating a sufficiently reducing metal center to promote C-C bond forming oxidative cyclization. Structure-activity relationships on bis(imino)pyridine substitution were also established with 2,4,6-tricyclopentyl aryl groups, resulting in optimized catalytic [2π+2π] cycloaddition. The cyclopentyl groups provide a sufficiently open metal coordination sphere that encourages substrate coordination while remaining large enough to promote a challenging, turnover limiting C(sp3)-C(sp3) reductive elimination.
    No preview · Article · Jun 2015 · Journal of the American Chemical Society
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    ABSTRACT: Generated in situ from air-stable cobalt precursors or readily synthesized using NaHBEt3, (PPh3)3CoH(N2) was found to be an effective catalyst for the hydroboration of alkenes. Unlike previous base-metal catalysts for alkene isomerization-hydroboration which favor the incorporation of boron at terminal positions, (PPh3)3CoH(N2) promotes boron incorporation adjacent to π-systems even in substrates where the alkene is at a remote position, enabling a unique route to 1,1-diboron compounds from α,ω-dienes.
    No preview · Article · May 2015 · Organic Letters
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    ABSTRACT: A bis(imino)pyridine cobalt-catalyzed hydroboration of terminal alkynes with HBPin (Pin = pinacolate) with high yield and (Z)-selectivity for synthetically valuable vinylboronates is described. Deuterium labeling studies, stoichiometric experiments and isolation of catalytically relevant intermediates support a mechanism involving selective insertion of an alkynylboronate ester into a Co-H bond, a pathway distinct from known precious metal catalysts where metal vinylidene intermediates have been proposed to account for the observed (Z)-selectivity.
    No preview · Article · Apr 2015 · Journal of the American Chemical Society
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    ABSTRACT: Cobalt(II) dichloride complexes supported by a variety of neutral, tridentate pincer ligands have been prepared and, following in situ activation with NaBEt3H, evaluated for the catalytic borylation of 2-methylfuran, 2,6-lutidine, and benzene using both HBPin and B2Pin2 (Pin = pinacolate) as boron sources. Preparation of well-defined organometallic compounds in combination with stoichiometric experiments with HBPin and B2Pin2 provided insight into the nature and kinetic stability of the catalytically relevant species. In cases where sufficiently electron donating pincers are present, such as with bis(phosphino)pyridine chelates, Co(III) resting states are preferred and catalytic C-H borylation is efficient. Introduction of a redox-active subunit into the pincer reduces its donating ability and, as a consequence, the accessibility of a Co(III) resting state. In these cases, unusual mixed-valent μ-hydride cobalt complexes have been crystallographically and spectroscopically characterized. These studies have also shed light on the active species formed during in situ activated cobalt alkene hydroboration catalysis and provide important design criteria in base metal catalyzed C-B bond forming reactions.
    No preview · Article · Apr 2015 · Organometallics
  • Iraklis Pappas · Paul J Chirik
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    ABSTRACT: The catalytic hydrogenolysis of the titanium-amide bond in (η5-C5Me4SiMe3)2Ti(Cl)NH2 to yield free ammonia is described. The rhodium hydride, (η5-C5Me5)(py-Ph)RhH (py-Ph = 2-phenylpyridine), serves as the catalyst and promotes N-H bond formation via hydrogen atom transfer. The N-H bond dissociation free energies of ammonia ligands have also been determined for titanocene and zirconocene complexes and reveal a stark dependence on metal identity and oxidation state. In all cases, the N-H BDFEs of coordinated NH3 decreases by >40 kcal/mol from the value in the free gas phase molecule.
    No preview · Article · Feb 2015 · Journal of the American Chemical Society
  • Peter T Wolczanski · Paul J. Chirik
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    ABSTRACT: On the occasion of Professor John Bercaw’s 70th birthday, we reflect and highlight his distinguished career in organometallic chemistry and homogeneous catalysis. What began as a fundamental interest in the chemistry bis(cyclopentadienyl)titanium compounds and their interaction with molecular nitrogen evolved into a vibrant and di-verse program tackling some of the most important problems in catalysis. Using well-defined organometallic compounds, fundamental insights were gained in the mechanism of CO reduction, basic transformations of organometallic chemistry such as alkene insertion and alkyl β-hydrogen elimination, the origin of stereocontrol in metallocene-catalyzed polymeri-zation and in the activation of hydrocarbons by electrophilic late transition metals.
    No preview · Article · Feb 2015 · ACS Catalysis
  • W. Neil Palmer · Tianning Diao · Iraklis Pappas · Paul J. Chirik
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    ABSTRACT: Cobalt alkyl complexes bearing readily available and redox-active 2,2′:6′,2″-terpyridine and α-diimine ligands have been synthesized, and their electronic structures have been elucidated. In each case, the supporting chelate is reduced to the monoanionic, radical form that is engaged in antiferromagnetic coupling with the cobalt(II) center. Both classes of cobalt alkyls proved to be effective for the isomerization-hydroboration of sterically hindered alkenes. An α-diimine-substituted cobalt allyl complex proved exceptionally active for the reduction of hindered tri-, tetra-, and geminally substituted alkenes, representing one of the most active homogeneous catalysts known for hydroboration. With limonene, formation of an η3-allyl complex with a C-H agostic interaction was identified and accounts for the sluggish reactivity observed with diene substrates. For the terpyridine derivative, unique Markovnikov selectivity with styrene was also observed with HBPin.Keywords: cobalt; hydroboration; catalysis; redox-active ligands; boronates
    No preview · Article · Feb 2015 · ACS Catalysis
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    Paul J. Chirik

    Preview · Article · Jan 2015 · Organometallics
  • Iraklis Pappas · Paul J. Chirik
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    ABSTRACT: Cycloaddition of monosubstituted allenes with a monomeric, base free titanocene oxide resulted in isolation and crystallographic characterization of the corresponding oxatitanacyclobutanes. In solution these compounds are a mixture of (E) and (Z) isomers and interconvert by mechanisms that are dependent on the specific substitution of the allene. Facile carbonylation of the oxatitanacyclobutanes was also observed to yield rare examples of structurally characterized oxatitanacyclopentanones. Isomerization of these species was observed in the presence of proton sources. These studies highlight the new chemistry available from synthesis of base free titanocene oxide compounds enabled by appropriate cyclopentadienyl substitution.
    No preview · Article · Dec 2014 · Polyhedron
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    ABSTRACT: The activity of bis(phosphine) iron dialkyl complexes for the asymmetric hydrogenation of alkenes has been evaluated. High-throughput experimentation was used to identify suitable ironphosphine combinations using the displacement of pyridine from py(2)Fe(CH2SiMe3)(2) for precatalyst formation. Preparative-scale synthesis of a family of bis(phosphine) iron dialkyl complexes was also achieved using both ligand substitution and salt metathesis methods. Each of the isolated organometallic iron complexes was established as a tetrahedral and hence high-spin ferrous compound, as determined by Mossbauer spectroscopy, magnetic measurements, and, in many cases, X-ray diffraction. One example containing a Josiphos-type ligand, (SL-J212-1)Fe(CH2SiMe3)(2), proved more active than other isolated iron dialkyl precatalysts. Filtration experiments and the lack of observed enantioselectivity support dissociation of the phosphine ligand upon activation with dihydrogen and formation of catalytically active heterogeneous iron. The larger six-membered chelate is believed to reduce the coordination affinity of the phosphine for the iron center, enabling metal particle formation.
    No preview · Article · Oct 2014 · Organometallics

  • No preview · Article · Oct 2014 · ChemInform
  • Grant W. Margulieux · Zoë R. Turner · Paul J. Chirik
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    ABSTRACT: The bis(imino)pyridine 2,6-(2,6-iPr2-C6H3NCPh)2-C5H3N (iPrBPDI) molybdenum dinitrogen complex, [{(iPrBPDI)Mo(N2)}2(μ2,η1,η1-N2)] has been prepared and contains both weakly (terminal) and modestly (bridging) activated N2 ligands. Addition of ammonia resulted in sequential NH bond activations, thus forming bridging parent imido (μ-NH) ligands with concomitant reduction of one of the imines of the supporting chelate. Using primary and secondary amines, model intermediates have been isolated that highlight the role of metal–ligand cooperativity in NH3 oxidation.
    No preview · Article · Oct 2014 · Angewandte Chemie

Publication Stats

7k Citations
1,411.72 Total Impact Points

Institutions

  • 2011-2016
    • Princeton University
      • Department of Chemistry
      Princeton, New Jersey, United States
  • 2002-2012
    • Cornell University
      • Department of Chemistry and Chemical Biology
      Итак, New York, United States
  • 1999-2005
    • California Institute of Technology
      • Division of Chemistry and Chemical Engineering
      Pasadena, California, United States