Research Interests: Organic Chemistry, from antisense
oligonucleotides to transition metal heteronuclear clusters, NMR, DFT
calculations, and X-ray crystallography. Current projects include
helical disulfide polymers and mechanisms of phosphoramidite activation
for oligonucleotide synthesis.
Phosphites and Disulfides NMR Electron-Withdrawing Phosphines Noncoordinating Anions and Diels-Alder Catalysis
Organometallic Carbyne, Carbene, and Acyl
Clusters
X-ray Crystal Structures Back to Top
Current Publication List (NCBI Website)
1. Chiral phosphites and disulfides - connections to oligonucleotide synthesis (papers A1-7). Starting with N-sulfonyl amino acids, we showed that P-chiral trivalent phosphorus compounds such as 1
were readily accessible, and that they do not undergo inversion at
phosphorus (A1, A2, A3, A7). The inversion barrier in phosphite
triesters similarly appears to be high, as evidenced by sulfurization
of chiral phosphites during the synthesis of chiral phosphorothioates
for antisense oligonucleotides, where a sulfur atom replaces an oxygen
on the phosphodiester backbone. We showed that the barrier is
virtually the same as that for phosphines, with inversion occurring
slowly at 150 °C, as shown for the equilibrium between 2 and 3 (A4). We synthesized chiral disulfides (for instance 4 and 5)
as a potential route to chiral sulfurization of phosphorus for chiral
phosphorothioate synthesis (A5, A6).
We recently found the novel route from H-phosphonodiamidite 6 and acid chlorides to give acylphosphonites such as 7, and coupling to give acyl dinucleosides such as 8. While 8
was expected to epimerize readily by analogy to acyl phosphines, it
does not, and the calculated inversion barrier is over 40 kcal/mol (A8).
Current work is continuing
in two directions, namely, activation of the phosphoramidites used in
oligonucleotide synthesis in order to understand the epimerization at
phosphorus that occurs as well as the alcohol coupling reaction, and the possibility of using chiral disulfides
to create novel helical polymers.
(A8) Hersh, W. H., “Synthesis of dinucleoside acylphosphonites by phosphonodiamidite chemistry and investigation of phosphorus epimerization,” Beilstein J.Org. Chem. 2015, 11, 184-191. (Thematic Issue on Nucleic Acid Chemistry)
(A7) Hersh, W. H.; Lam, S. T.; Moskovic, D. J.; Panagiotakis, A. J.
“A Non-Karplus Effect: Evidence from Phosphorus Heterocycles and DFT
Calculations of the Dependence of Vicinal Phosphorus-Hydrogen NMR
Coupling Constants on Lone-Pair Conformation,” J. Org. Chem. 2012, 77,
4968-4979.
(A6) Mukhlall, J. A.; Hersh, W. H. “Sulfurization of Dinucleoside
Phosphite Triesters with Chiral Disulfides,” Nucleosides, Nucleotides
& Nucleic Acids 2011, 30, 706-725.
(A5) Mukhlall, J. A.; Noll, B. C.; Hersh, W. H. “Synthesis of Chiral
Disulfides: Potential Reagents for Enantioselective Sulfurization,” J.
Sulfur Chem. 2011, 32, 199-212.
(A4) Mukhlall, J. A.; Hersh, W. H. “Measurement of the Barrier to
Inversion of Configuration in Acyclic Phosphite Triesters,” Inorg.
Chim. Acta 2011, 369, 62-70. (special R. G. Bergman issue)
(A3) 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.
(A2) Hersh, W. H.; Xu, P.; Simpson, C. K.; Grob, J.; Bickford, B.;
Hamdani, M. S.; T., W.; Rheingold, A. L. “Synthesis and Structural
Characterization of Trivalent Amino Acid Derived Chiral Phosphorus
Compounds,” J. Org. Chem. 2004, 69, 2153-2163.
(A1) 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.
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2. 31P NMR and spin-spin coupling - experiment and theory (papers A7, B1-3).
We have a long-standing interest in unusual NMR spectra, such as that
seen in anion "spinning" in phosphine-tungsten complexes where all six
fluorine atoms of SbF6- couple to phosphorus
(B2), and more recently in the observation of vastly different vicinal
phosphorus-hydrogen coupling constants as a function of lone-pair
conformation as shown for calculations on CH3OPH2 below (A7). We use Gaussian
DFT calculations to minimize structures, analyze chemical shifts and
coupling constants, and currently to develop a scale to accurately
predict 31P chemical shifts for novel species.
(A7) Hersh, W. H.; Lam, S. T.; Moskovic, D. J.; Panagiotakis, A. J.
“A Non-Karplus Effect: Evidence from Phosphorus Heterocycles and DFT
Calculations of the Dependence of Vicinal Phosphorus-Hydrogen NMR
Coupling Constants on Lone-Pair Conformation,” J. Org. Chem. 2012, 77,
4968-4979.
(B3) 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.
(B2) 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.
(B1) Honeychuck, R. V.; Hersh, W. H. “Observation of a Novel 31P NMR
Cis-Influence Series: Implications for the Relative Basicity of PPh3
and PMe3 in Tungsten Carbonyl Complexes,” Inorg. Chem. 1987, 26,
1826-1828.
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3. Electron-withdrawing phosphines and hydroformylation (papers A1, C1-3). Typical
triaryl or trialkyl phosphorus ligands in organometallic compounds are
relatively electron-rich. We showed that
N-sulfonyl phosphoramides such as
TosL and diTosL and 1 above (C1, A1) are comparable to fluorinated phosphines
in electron-withdrawing ability. Rhodium-catalyzed
hydroformylation generally gives better results when relatively
electron-poor
phosphines are used, and we examined a variety of these ligands; results for diTosL are shown (C2, C3).
(C3) Magee, M. P.; Li, H. Q.; Morgan, O.; Hersh, W. H. “Synthesis of
Electron-withdrawing Butane- and Arenesulfonylamino Phosphines and use
in Rhodium-catalyzed Hydroformylation,” Dalton Transactions 2003,
387-394.
(C2) 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,”
Organometallics 2002, 21, 362-372.
(A1) 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.
(C1) 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 Ligand. Comparative IR and 13C
and 31P NMR Study of Related Phosphorus Complexes,” Inorg. Chem. 1996,
35, 5453-5459.
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4. Coordination of "noncoordinating" anions and Diels-Alder catalysis (papers B2, D1-5).
In the 1980's we discovered a group of tungsten carbonyl nitrosyl Lewis
acids that would reversibly bind the so-called "noncoordinating" anions
SbF6-, PF6-, and BF4-
via a bridging fluorine atom (D1, D4). X-ray structures showed that
tungsten coordination stretched the Sb-F, P-F, or B-F bond but did not
cleave it from the inorganic Lewis acids SbF5, PF5, and BF3 (see SbF6- adduct 1 with a Cy3P ligand below). 31P and 19F
NMR spectra exhibited P-F coupling indicating anion coordination at low
temperature, but at higher temperatures anion "spinning" via
dissociation to tight ion pairs occurred followed by dissociation to
free ions (D1, B2, D5).
The Me3P analogue of 1
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 2 (D2) with acrolein coordinated to the tungsten cation. We examined chiral analogues such as 3 and 4 but have not achieved high yields with high enantioselectivity (D3).
(D5) Hersh, W. H. “Synthesis and Characterization by 1H, 13C, and
19F NMR of (CH3CN)n(CO)4-n(NO)W(μ-F)BF3 and
[(CH3CN)n+1(CO)4-n(NO)W][BF4] (n=0-2), Tungsten Mononitrosyl Carbonyl
Cations with Labile Acetonitrile and [(μ-F)BF3]¯ Ligands,” Inorg. Chem.
1990, 29, 713-722.
(B2) 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.
(D4) 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.
(D3) 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.
(D2) 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 η1-Acrolein Complex (cis-Me3P)(trans-NO)(CO)3W-O=C(H)-C(H)=CH2,” J.
Org. Chem. 1987, 52, 5293-5296.
(D1) Hersh, W. H. “Coordination of a "Noncoordinating" Anion: X-Ray
Crystal Structure and 31P NMR Characterization of a Tungsten Nitrosyl
Cation Ligated to SbF6¯,” J. Am. Chem. Soc. 1985, 107, 4599-4601.
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5. Organometallic carbynes, alkylidenes, and acyls (papers E1-12).
Metal clusters have long been used to model the behavior of simple
organic fragments on a metal surface in order to better understand
complex reactions such as the Fisher-Tropsch conversion of CO and H2
to hydrocarbons. We found a general method for the synthesis of
heterodinuclear alkoxycarbynes and discovered a novel oxygen to metal
methyl migration reaction (E1, E6, E8, E9, E11), prepared a related μ-acyl (E2, E3),
converted the carbynes to "difunctional clusters" containing both a
carbyne and alkylidene ligand that couple to give a vinyl ligand (E4, E5), and
examined the kinetics and crossover reactions of these processes (E7, E10, E12).
(E12) Hersh, W. H.; Fong, R. H., “Crossover Studies of Methyl
Migration from Oxygen to Iron in the Iron-Manganese Methoxycarbyne
Complex Cp(CO)Fe(μ-COCH3)(μ-CO)Mn(CO)MeCp,” Organometallics 2005, 24,
4179-4189.
(E11) Luo, W.; Fong, R. H.; Hersh, W. H. “Synthesis and Oxygen to
Iron Methyl Migration Reaction of the Heterodinuclear Methoxycarbyne
Complex Cp(CO)Fe(μ-COCH3)(μ-CO)Cr(CO)(η6-C6H6),” Organometallics 1997,
16, 4192-4199.
(E10) Idmoumaz, H.; Lin, C. H.; Hersh, W. H. “Mechanism of Alkyl
Migration from Oxygen to Metal in Iron-Manganese Ethoxycarbyne
Complexes. Induction of Postcleavage Intermolecular Ethyl Exchange by
Hydride Bridging of Mononuclear Iron Species,” Organometallics 1995,
14, 4051-4063.
(E9) Wang, B.; Hersh, W. H.; Rheingold, A. L. “Synthesis and X-Ray
Crystal Structure of the Heterodinuclear Iron-Chromium Carbonyl
Nitrosyl Anion Complex [trans-(η5-MeCp) (CO)
Fe(μ-CO)2Cr(NO)(η5-Cp)][Ph3PCH3], Conversion to a Heterodinuclear
Methoxycarbyne Complex, and Kinetics of Thermally-Induced Oxygen to
Iron Methyl Migration,” Organometallics 1993, 12, 1319-1330.
(E8) Hersh, W. H. “Syntheses and Reactions of Heterodinuclear
Alkoxycarbyne Complexes,” In Transition Metal Carbyne Complexes; F. R.
Kreissl, Ed.; Nato ASI Series C: Mathematical and Physical Sciences,
Vol. 392; Kluwer Academic Publishers: Dordrecht, 1993; pp 149-150.
(E7) Hersh, W. H.; Hunte, F.; Siegel, S. “Kinetic Investigation of
Phosphine Exchange in CpFe(CO)(L)CH3 (L = PPh3, PPh2Me) - Rate of
Thermal Formation of the 16-Electron Species CpFe(CO)CH3,” Inorg. Chem.
1993, 32, 2968-2971.
(E6) Fong, R. H.; Lin, C. H.; Idmoumaz, H.; Hersh, W. H. “Synthesis,
Structure, Cis-Trans Isomerization, and Reactions of Heterodinuclear
Iron Manganese Anion and Alkoxycarbyne Complexes. X-Ray Crystal
Structure of cis-(η5-Cp)(CO)Fe(μ-COCH2CH3)(μ-CO)Mn(CO)(η5-MeCp),”
Organometallics 1993, 12, 503-516.
(E5) Fong, R. H.; Hersh, W. H. “Stereospecific Synthesis of
(μ3-COCH3)(μ2-C(H)CH3)(Cp)(MeCp)Fe2Mn(CO)5, the First
Carbyne-Ethylidene Cluster, and Intramolecular Hydrogen Migration to
Give (μ2-C(H)OCH3)(μ3-CCH3)(Cp)(MeCp)Fe2Mn(CO)5, the First
Carbene-Ethylidyne Cluster,” Organometallics 1988, 7, 794-796.
((E4) Fong, R. H.; Hersh, W. H. “Synthesis and X-Ray Crystal
Structure of (μ3-COCH3)(μ2-CH2)(Cp)(MeCp)Fe2Mn(CO)5, the First
Carbyne-Methylene Cluster. Carbon-Carbon Coupling to Give a
Methoxyvinyl Cluster,” J. Am. Chem. Soc. 1987, 109, 2843-2845.
(E3) Bonnesen, P. V.; Yau, P. K. L.; Hersh, W. H. “Oxidative
Syntheses of Cyclopentadienyl η2-Acyl Complexes and Stereospecific
Conversion to an η2-Ylide Complex. X-Ray Crystal Structures of
Cp(NO)(I)Mo(η2-C(O)-p-tol) and Cp(NO)(I)Mo(η2-C(O)(PMe3)-p-tol),”
Organometallics 1987, 6, 1587-1590.
(E2) Bonnesen, P. V.; Baker, A. T.; Hersh, W. H. “A New Metal-Metal
Bond-Forming Reaction: Synthesis, Structure, and Mechanism of Formation
of (η5-C5H5)(CO)Fe(μ-C(O)-p-tolyl)(μ-CO)Mo(NO)(η5-C5H5), a Rare π-Bound
μ-Acyl Compound,” J. Am. Chem. Soc. 1986, 108, 8304-8305.
(E1) Fong, R. H.; Hersh, W. H. “Synthesis and Reactions of the First
Heterodinuclear Methoxycarbyne Complex
(η5-C5H5)(CO)Fe(μ-COCH3)(μ-CO)Mn(CO)(η5-CH3C5H4),” Organometallics
1985, 4, 1468-1470.
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6. X-ray structures (F1-3). With
the acquisition of a new X-ray diffractometer in 2011, we have carried
out a series of structures on our own compounds and as collaborations
with colleagues. These structures are just now starting to be
published, with more than 10 structures currently in the pipeline.
(F3) Chen, Y.; Liu, X.; Lee, M.; Huang, C.; Inoyatov, I.; Chen, Z.;
Perl, A. C.; Hersh, W. H., “ICl-Induced Intramolecular Electrophilic
Cyclization of 1-[4-Methoxy(1,1-biphenyl)2-yl]alkynones—A Facile
Approach to Spiroconjugated Molecules,” Chemistry – A European Journal
2013, 19, 9795-9799.
(F2) Dana, D.; Davalos, A. R.; Subramaniam, G.; Afzal, N.; Hersh, W.
H.; Kumar, S., “A Base-Controlled Regioselective Synthesis of Allyl and
Vinyl Phenyl Sulfones,” Tetrahedron Lett. 2013, 54, 2717-2721.
(F1) She, Z.; Niu, D.; Chen, L.; Gunawan, M. A.; Shanja, X.; Hersh,
W. H.; Chen, Y. “Synthesis of Trisubstituted Isoxazoles by
Palladium(II)-Catalyzed Cascade Cyclization–Alkenylation of
2-Alkyn-1-one O-Methyl Oximes,” J. Org. Chem. 2012, 77, 3627-3633.
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7. Miscellaneous and early papers.
(6) Kane, S.; Hersh, W. H. “Periplanar or Coplanar?,” J. Chem. Educ. 2000, 77, 1366.
(5) Hersh, W. H.; Bergman, R. G. “Kinetics and Mechanism of
Decomposition of a Benzodicobaltacyclohexene: Reversible Dinuclear
Elimination of o-Xylylene via a Dimetalla-Diels-Alder Reaction,” J. Am.
Chem. Soc. 1983, 105, 5846-5859.
(4) Hersh, W. H.; Hollander, F. J.; Bergman, R. G. “Synthesis,
Crystal and Molecular Structures, and Reactions of a
Benzodicobaltacyclohexene, a Thermally-Derived Mononuclear o-Xylylene
Complex, and an Unsymmetrical Phosphine-Derived Dinuclear Complex,” J.
Am. Chem. Soc. 1983, 105, 5834-5846.
(3) Theopold, K. H.; Hersh, W. H.; Bergman, R. G. “Binuclear
Metallacycles: Organometallic Ring Systems Containing Two Metal
Centers,” Israel J. Chem. 1982, 22, 27-29.
(2) Hersh, W. H.; Bergman, R. G. “Synthesis and Reactions of a
Dimetallacyclohexene. Thermal Conversion to an o-Xylylene Complex and
Phosphine-Induced Conversion to Free o-Xylylene and a New Reactive Dinuclear Cobalt Complex,” J. Am. Chem. Soc. 1981, 103, 6992-6994.
(1) Katz, T. J.; Hersh, W. H. “The Stereochemistry
of the Olefin Metathesis Reaction,” Tetrahedron Lett. 1977, 585-588.
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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, Biotage flash chromatography, departmental Bruker DPX400 MHz NMR equipped with a
1H/13C/19F/31P
QNP probe, VT device, and 60-sample sample-changer and Bruker Avance500
MHz NMR, and a Bruker Smart Breeze X-ray diffractometer with Oxford
cryoprobe.
A
perspective
on undergraduate research - in the Queens College
undergraduate
science journal Nucleus
Current
group members:
Eric Chan (Ph.D.)
Antoaneta Tarpanova (BA/MA)
Former
group members:
Postdoctorals:
Robert V. Honeychuck (George
Mason University, Fairfax, VA)
Hamid Idmoumaz
Matthew P. Magee (Transportation
Security Administration)
Oma Morgan (Davis
& Elkins College)
V. Dayal Reddy (Kingsborough
Community College, CUNY)
Ph.D. students:
Peter V. Bonnesen (Oak
Ridge National Laboratories)
Raymond H. Fong (City
College of San Francisco)
Wei Luo (Barr Laboratories, Plainsboro, NJ)
Joshua Mukhlall (Ph.D., 2010)
Ping Xu
Masters students:
Sara Burgdorf
Muhammad Jamil
Huan-Qiu Li (Abbott Laboratories, Chicago, IL)
Chien-Hsing Lin
Daniel Madden
Evelyn Teran
Anh Tran
Bing Wang (DuPont Merck Pharmaceuticals,
Garden
City, NY)
Undergraduates:
Daniel Ahn
Azriel Avezbadalov
Sallyanna Bazelais
Brian Bickford (Syosset High School)
Liliana Bordeianou
Sara Burgdorf
Alfred Chiang
Stella Chow
Mark Chua
Joshua Dunn
Achini Elayaperuma
Ginn Fang
Judah Farahi
Andrew Fortney
Edgar Garcia
Joseph Gera
Jonathan Grob (Novartis)
Ani Hamdani (M.D.)
M.
Salman
Hamdani (deceased September 11, 2001, World Trade Center)
Frederick Hunte
(Stony Brook
University Medical Center)
Michael Ihde
David Janash
Joseph Kaplovitz
Jeremy Kiffel
Lauren Klein (Oceanside High
School)
King Kwong
Sherrell Lam (M.D., Walter Reed National Military Medical Center)
Dennis Lee
Devora Lichtman
Sarwar Malik
Benjamin Marcune (Pharmaceuticals Consulting)
Daniel Moskovic (Baylor
College of Medicine - student)
Menachem Moskowitz (Chemistry Ph.D. student, Georgetown University)
Dawit Negussie
Ezra Orlofsky
Steven Nadler
Tony Panagiotakis
(D.O., Stamford Hospital, CT)
Saketu Patel
William Pineros
Libby Pollack
Craig Puckett (Kenyon
& Kenyon)
Jerry Remy
Steven Rodriguez (Genetics Ph.D., Cornell
University)
Omid Rofeim
(M.D.)
Eli Ron (Chemistry Ph.D., SUNY Stony Brook, postdoctoral, Florida State University)
Sondra Siegel
Cheslan Simpson (Ph.D., University of Chicago;
currently: Los Alamos National
Laboratories - Port Security staff)
Rebecca Singh
Mahamud Subir
(Assistant Professor, Ball State University)
John Walzer
(Senior Scientist, ExxonMobil Chemical Co.)
Yisrael Wallach
Paul Yau
Phillip Jong Won Yom (D.C., Flushing, NY)
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Last modified February 2015
