Professor and Chair
Ph.D. Columbia University (1980)
Office: Remsen 109B
E-Mail: william.hersh@qc.cuny.edu
Phone: (718) 997-4144
FAX: (718) 997-5531
Current and former group members
Research Interests: Organic/Organometallic; uses of novel phosphorus chemistry in organometallic catalysis, antisense oligonucleotide synthesis, and enantioselective catalysis.
[Phosphorus Chemistry] [Hydroformylation] [Antisense Oligonucleotides] [Diels-Alder Catalysis] [Back to top]
Phosphorus Chemistry. Typical triaryl or trialkyl phosphorus ligands in organometallic compounds are relatively electron-rich. We have begun investigating novel electron-withdrawing phosphines possessing N-sulfonyl moieties, the first two of which we have named TosL and diTosL(5, 7). We have shown these ligands to be comparable to fluorinated phosphines in electron-withdrawing ability. Compound 1 is a chiral analog, and is easy to prepare in enantiomerically pure form from the amino acid valine (8, 12). We are pursuing the many opportunities for steric and electronic tuning of analogues of these phosphoramides.
The figure below is a movie of the X-ray structure of 1 above, rotating about the center of the heterocycle ring, and it allows the stereochemistry to be visualized.
Hydroformylation. Rhodium-catalyzed hydroformylation generally gives better results when relatively electron-poor phosphines are used. While monodentate TosL gives poor regioselectivity and reactivity compared to PPh3 for the hydroformylation of 1-hexene, use of chelating diTosL is clearly superior (10). We are presently examining the scope of this reaction in the presence of a variety of N-sulfonyl phosphoramides (11).
Antisense Oligonucleotides. Phosphorothioates are useful antisense oligonucleotides with enhanced resisistance to nucleases. Current syntheses give mixtures of configuration at phosphorus. We are examining chemistry related to that used for 1 above to synthesize chiral phosphorothioates; some initial preliminary results are shown.
Diels-Alder Catalysis. Several years ago we discovered the tungsten nitrosyl Lewis acid 2, in which the so-called "noncoordinating" anion SbF6¯ is bound via a fluorine atom to tungsten (4). We reported X-ray crystal structures of related analogues and 31P and 19F NMR spectra detailing the anion coordination at low temperature, and at higher temperatures anion "spinning" via dissociation to tight ion pairs and finally dissociation to free ions (3, 4).
Compound 2 is an efficient Diels-Alder catalyst, activating enones such as acrolein and methyl vinyl ketone by Lewis acid coordination of tungsten to the carbonyl oxygen as seen in the X-ray structure of 3 (1, 2). Compound 4a is a chiral catalyst that we have prepared (2), shown with a molecule of acrolein coordinated to the metal. Attack by a diene on the front face of acrolein (away from the phenyl ring as shown for 5 below) will give a chiral product. While 4a is racemic, stoichiometric reaction gives a 55:45 mixture of coordinated diastereomeric Diels-Alder adducts of acrolein and isoprene, suggesting that a pure enantiomer of 4a would give a 10% e.e. Using the bulkier t-butyl group was expected to improve the selectivity, and the diphenyl/di-t-butyl analog 4b is an excellent catalyst. The enantiomerically pure compound 5 incorporates a chiral-at-phosphorus chelating ligand with phenyl and t-butyl groups, and catalyzes the reaction of acrolein and isoprene to give the Diels-Alder adduct with 36% e.e. However, subtle conformational or electronic differences from 4b result in surprisingly low yields using 5, so this means of introducing enantioselectivity fails.
Group resources: Major equipment includes a Vacuum/Atmospheres double station glove box equipped with a -35 °C freezer and a mini antechamber for fast pumping, vacuum lines, Mattson FTIR, Macintosh computers, and a departmental Bruker 400 MHz NMR equipped with a 1H/13C/19F/31P QNP probe, VT device, and 60-sample sample-changer.
A perspective on undergraduate research - in the Queens College undergraduate science journal Nucleus
Representative Publications:
(14) Hersh, W. H.; Fong, R. H. "Crossover Studies of Methyl Migration from Oxygen to Iron in the Iron-Manganese Methoxycarbyne Complex Cp(CO)Fe(m-COCH3)(m-CO)Mn(CO)MeCp, Organometallics 2005, 24, 4179-4189. (13) Hersh, W. H.; Klein, L.; Todaro, L. J. "Stereoselective Synthesis of P-Chiral Phosphorus Compounds from N-tert-Butoxycarbonyl Amino Acids," J. Org. Chem. 2004, 69, 7355-7358.
(12) Hersh, W. H.; Xu, P.; Simpson, C. K.; Grob, J.; Bickford, B.; Hamdani, M. S.; Wood, T.; Rheingold, A. L. "Synthesis and Structural Characterization of Trivalent Amino Acid Derived Chiral Phosphorus Compounds," J. Org. Chem. 2004, 69, 2153-2163.
(11) Magee, M. P.; Li, H.-Q.; Morgan, O.; Hersh, W. H. "Synthesis of Electron-Withdrawing Butane- and Arene-sulfonylamino Phosphines and Use in Rhodium-Catalyzed Hydroformylation," Dalton Transactions, 2003, 387-394.
(10) Magee, M. P.; Luo, W.; Hersh, W. H. "Electron-Withdrawing Phosphine Compounds in Hydroformylation Reactions. 1. Syntheses and Reactions Using Mono and Bis(p-toluenesulfonylamino) Phosphines," Organometallics2002, 21, 362-372.
(9) Kane, S.; Hersh, W. H. "Periplanar or Coplanar?," J. Chem. Educ. 2000, 77, 1366.
(8) Hersh, W. H.; Xu, P.; Simpson, C. K.; ,Wood, T.; Rheingold, A. L. "A Chiral N-Sulfonylphosphoramide: Synthesis and X-Ray Crystal Structure of a 1,3,2-Oxazaphospholidin-5-one, a Trivalent Electron-Withdrawing Amino Acid-Derived Phosphorus Compound, and Synthesis of Its W(CO)5 Adduct," Inorg. Chem. 1998, 37, 384-385.
(7) Hersh, W. H. "False AA'X Spin-Spin Coupling Systems in 13C NMR: Examples Involving Phosphorus and a 20-Year-Old Mystery in Off-Resonance Decoupling," J. Chem. Educ. 1997, 74, 1485-1489.
(6) Luo, W.; Fong, R. H.; Hersh, W. H. "Synthesis and Oxygen to Iron Methyl Migration Reaction of the Heterodinuclear Methoxycarbyne Complex Cp(CO)Fe(m-COCH3)(m-CO)Cr(CO)(h6-C6H6)," Organometallics, 1997, 16, 4192-4199.
(5) Hersh, W. H.; Xu, P.;Wang, B.; Yom, J. W.; Simpson, C. K. "Synthesis of Tungsten Carbonyl and Nitrosyl Complexes of Monodentate and Chelating Aryl-N-sulfonylphosphoramides, the First Members of a New Class of Electron-Withdrawing Phosphine Ligands. Comparative IR and 13C and 31P NMR Study of Related Phosphorus Complexes," Inorg. Chem.1996, 35, 5453-5459.
(4) Honeychuck, R. V.; Hersh, W. H. "Coordination of "Noncoordinating" Anions: Synthesis, Characterization, and X-ray Crystal Structures of Fluorine-Bridged [SbF6]¯, [BF4]¯, and [PF6]¯ Adducts of [R3P(CO)3(NO)W]+. An Unconventional Order of Anion Donor Strength," Inorg. Chem. 1989, 28, 2869-2886.
(3) Honeychuck, R. V.; Hersh, W. H. "Observation of Anion Spinning in the Dynamic 31P NMR Spectra of Fluorine-Bridged SbF6¯, BF4¯, and PF6¯ Adducts of R3P(CO)3(NO)W+. Implications for Barriers to Ionization and the Formation of Ion Pairs and Free Ions in Methylene Chloride and Hexane Solution," J. Am. Chem. Soc. 1989, 111, 6056-6070.
(2) Bonnesen, P. V.; Puckett, C. L.; Honeychuck, R. V.; Hersh, W. H. "Catalysis of Diels-Alder Reactions by Low Oxidation State Transition Metal Lewis Acids: Fact and Fiction," J. Am. Chem. Soc. 1989, 111, 6070-6081.
(1) Honeychuck, R. V.; Bonnesen, P. V.; Farahi, J.; Hersh, W. H. "Catalysis of Diene Polymerization and Diels-Alder Reactions by an Octahedral Tungsten Nitrosyl Lewis Acid. X-ray Crystal Structure of the h1-Acrolein Complex (cis-Me3P)(trans-NO)(CO)3W-O=C(H)-C(H)=CH2," J. Org. Chem. 1987, 52, 5293-5296.
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Current group members: Joshua Mukhlall (Ph.D.) Eric Chan (Ph.D.) Sara Burgdorf (undergrad) Menachem Moskowitz (undergrad)
Last modified April 29, 2007
