Ultrafast spectroscopy and computational study of the photochemistry of diphenylphosphoryl azide: Direct spectroscopic observation of a singlet phosphorylnitrene

Article abstract of DOI:10.1021/ja909327z

The photochemistry of diphenylphosphoryl azide was studied by femtosecond transient absorption spectroscopy, by chemical analysis of light-induced reaction products, and by RI-CC2/TZVP and TD-B3LYP/TZVP computational methods. Theoretical methods predicted two possible mechanisms for singlet diphenylphosphorylnitrene formation from the photoexcited phosphoryl azide. (i) Energy transfer from the (π,π*) singlet excited state, localized on a phenyl ring, to the azide moiety, thereby leading to the formation of the singlet excited azide, which subsequently loses molecular nitrogen to form the singlet diphenylphosphorylnitrene. (ii) Direct irradiation of the azide moiety to form an excited singlet state of the azide, which in turn loses molecular nitrogen to form the singlet diphenylphosphorylnitrene. Two transient species were observed upon ultrafast photolysis (260 nm) of diphenylphosphoryl azide. The first transient absorption, centered at 430 nm (lifetime (τ) ～ 28 ps), was assigned to a (π,π*) singlet S₁ excited state localized on a phenyl ring, and the second transient observed at 525 nm (τ ～ 480 ps) was assigned to singlet diphenylphosphorylnitrene. Experimental and computational results obtained from the study of diphenyl phosphoramidate, along with the results obtained with diphenylphosphoryl azide, supported the mechanism of energy transfer from the singlet excited phenyl ring to the azide moiety, followed by nitrogen extrusion to form the singlet phosphorylnitrene. Ultrafast time-resolved studies performed on diphenylphosphoryl azide with the singlet nitrene quencher, tris(trimethylsilyl)silane, confirmed the spectroscopic assignment of singlet diphenylphosphorylnitrene to the 525 nm absorption band.

Full text of DOI:10.1021/ja909327z

Published on Web 11/04/2010
Ultrafast Spectroscopy and Computational Study of the
Photochemistry of Diphenylphosphoryl Azide: Direct
Spectroscopic Observation of a Singlet Phosphorylnitrene
†
†
†
Shubham Vyas, Sivaramakrishnan Muthukrishnan, Jacek Kubicki,
†
†
§
,†
Ryan D. McCulla, Gotard Burdzinski, Michel Sliwa, Matthew S. Platz,* and
,
†
Christopher M. Hadad*
Department of Chemistry, The Ohio State UniVersity, 100 West 18th AVenue, Columbus,
Ohio 43210, United States, Quantum Electronics Laboratory, Faculty of Physics, Adam
Mickiewicz UniVersity, Umultowska 85, 61-614 Pozna n´ , Poland, and LASIR, CNRS UMR 8516,
UniVersit e´ Lille 1 Sciences et Technologies, 59655 VilleneuVe d’Ascq cedex, France
Received November 3, 2009; E-mail: platz.1@osu.edu; hadad.1@osu.edu
Abstract: The photochemistry of diphenylphosphoryl azide was studied by femtosecond transient absorption
spectroscopy, by chemical analysis of light-induced reaction products, and by RI-CC2/TZVP and TD-B3LYP/
TZVP computational methods. Theoretical methods predicted two possible mechanisms for singlet
diphenylphosphorylnitrene formation from the photoexcited phosphoryl azide. (i) Energy transfer from the
(π,π*) singlet excited state, localized on a phenyl ring, to the azide moiety, thereby leading to the formation
of the singlet excited azide, which subsequently loses molecular nitrogen to form the singlet diphenylphos-
phorylnitrene. (ii) Direct irradiation of the azide moiety to form an excited singlet state of the azide, which
in turn loses molecular nitrogen to form the singlet diphenylphosphorylnitrene. Two transient species were
observed upon ultrafast photolysis (260 nm) of diphenylphosphoryl azide. The first transient absorption,
centered at 430 nm (lifetime (τ) ∼ 28 ps), was assigned to a (π,π*) singlet S
1
excited state localized on a
phenyl ring, and the second transient observed at 525 nm (τ ∼ 480 ps) was assigned to singlet
diphenylphosphorylnitrene. Experimental and computational results obtained from the study of diphenyl
phosphoramidate, along with the results obtained with diphenylphosphoryl azide, supported the mechanism
of energy transfer from the singlet excited phenyl ring to the azide moiety, followed by nitrogen extrusion
to form the singlet phosphorylnitrene. Ultrafast time-resolved studies performed on diphenylphosphoryl
azide with the singlet nitrene quencher, tris(trimethylsilyl)silane, confirmed the spectroscopic assignment
of singlet diphenylphosphorylnitrene to the 525 nm absorption band.
1
. Introduction
Several organophosphorus (OP) compounds (Scheme 1) are
Scheme 1. Some Organophosphorus (OP) Nerve Agents: The
Leaving Group Is Oriented to the Right
chemical warfare agents, which are potential threats to human
1
society. These chemical agents inhibit acetylcholinesterase
(AChE) in the human body, and this efficient enzyme is a serine
hydrolase which is responsible for the hydrolysis of the
2
neurotransmitter, acetylcholine. The mechanism of OP binding
to AChE is a two-step process (Figure 1) and has been3
extensively studied both experimentally and computationally.
In the first step of the reaction, which is reversible, the serine’s
oxygen in the active site attacks the phosphorus center of the
OP compound. In the forward direction, this results in covalent
bond formation between the catalytic serine and the OP, along
with departure of the leaving group (L). However, a better
leaving group makes this step almost irreversible by favoring
†
The Ohio State University.
Adam Mickiewicz University.
Universit e´ Lille 1 Sciences et Technologies.
†
§
(
(
1) Bartels, C. F.; James, K.; La Du, B. N. Am. J. Hum. Genet. 1992, 50,
1
104–1114.
2) (a) Main, A. R. Pharmacol. Ther. 1979, 6, 579–628. (b) Rozenbeny,
T. L. AdV. Enzymol. 1975, 43, 103. (c) Quinn, D. M. Chem. ReV.
1
987, 87, 955–979.
1
6796 9 J. AM. CHEM. SOC. 2010, 132, 16796–16804
10.1021/ja909327z  2010 American Chemical Society

Photochemistry of Diphenylphosphoryl Azide
A R T I C L E S
Figure 1. Inhibition of cholinesterase by an OP compound and the aging process. The OP compound is highlighted in blue, and the S198-H438-E325
triad is the catalytic active site of AChE. Also, for AChE, the oxyanion hole is another important structural motif which helps to stabilize the phosphoryl
oxygen.
the forward reaction. In the second step, which is also called
the “aging process”, one of the P-OR bonds of the organo-
phosphorus agent breaks due to the attack of a water molecule,
leaving a totally inactivated AChE bound by a stable phosphate
can catalyze the hydrolysis of many OP compounds. However,
the catalytic efficiency of HuPON1 is not sufficient to offer
complete protection against OP nerve agents. Furthermore,
6
there is no crystal structure of the homoenzyme available and
the only crystal structure available is that of a chimeric protein,
(
or phosphonate) ligand. Once the AChE is inhibited, acetyl-
7
choline concentration in the brain surges, causing neuromuscular
failure and ultimately leading to death.
referred to as G2E6 by Tawfik and co-workers, and this
chimeric isoform only has about 80% sequence homology with
the human enzyme. Hence, the exact mechanism of OP
hydrolysis by HuPON1 is not completely understood. Conse-
quently, an efficient, catalytic bioscavenger for OPs has not yet
been developed. With the goal of improving the catalytic
Two different approaches have been used in order to protect
humans from OP exposure: (a) postexposure treatment with
4
powerful nucleophiles, such as pyridinium oximes, that can
reactivate AChE; or (b) a pre-exposure with a prophylactic
8
5
efficiency, several mutants of PON1 have been prepared, albeit
enzyme (bioscavenger) that either catalytically hydrolyzes the
with little success. Presumably, the limited understanding of
the active site structure and mechanism of hydrolysis are the
most important reasons why an efficient catalytic PON1 variant
has not been developed. Thus, a more detailed understanding
of the critical active site residues will aid in the design of
mutants with the desired catalytic properties.
lethal OP compounds or at least competes with AChE for
reaction with the OP. The latter method is of obvious advantage
due to the short time available for first-responders to treat
6
patients with an OP exposure. Recently, human paraoxonase
1
(HuPON1) was recognized as a potential catalytic bioscav-
enger to hydrolyze OPs prior to the inhibition of AChE.
HuPON1 is a natural human enzyme, which is normally
associated with high density lipoprotein (HDL), and this enzyme
A commonly employed method used to obtain structural
9
information about an active site is photoaffinity labeling. An
ideal photoaffinity label (PAL) is similar in structure to a
substrate of an enzyme and has a strong affinity to bind at the
active site of the enzyme. However, the PAL contains a
photoreactive group which, upon irradiation, produces a highly
(
3) (a) Michel, H. O.; Hackley, B. E., Jr.; Berkowitz, L.; List, G.; Hackley,
E. B.; Gilliam, W.; Paukan, M. Arch. Biochem. Biophys. 1967, 121,
2
9–34. (b) Bennet, A. J.; Kovach, I. M.; Schowen, R. L. J. Am. Chem.
Soc. 1988, 110, 7892–7893. (c) Bencsura, A.; Enyedy, I.; Kovach,
I. M. Biochemistry 1995, 34, 8989–8999. (d) Bencsura, A.; Enyedy,
I. Y.; Kovach, I. M. J. Am. Chem. Soc. 1996, 118, 8531–8541. (e)
Millard, C. B.; Kryger, G.; Ordentlich, A.; Greenblatt, H. M.; Harel,
M.; Raves, M. L.; Segall, Y.; Barak, D.; Shafferman, A.; Silman, I.;
Sussman, J. L. Biochemistry 1999, 38, 7032–7039. (f) Viragh, C.;
Kovach, I. M.; Pannell, L. Biochemistry 1999, 38, 9557–9561. (g)
Elhanany, E.; Ordentlich, A.; Dgany, O.; Kaplan, D.; Segall, Y.; Barak,
R.; Velan, B.; Shafferman, A. Chem. Res. Toxicol. 2001, 14, 912–
(6) (a) Josse, D.; Xie, W.; Renault, F.; Rochu, D.; Schopfer, L. M.;
Masson, P.; Lockridge, O. Biochemistry 1999, 38, 2816–2825. (b)
Harel, M.; Aharoni, A.; Gaidukov, L.; Brumshtein, B.; Khersonsky,
O.; Meged, R.; Dvir, H.; Ravelli, R. B.; McCarthy, A.; Toker, L.;
Silman, I.; Sussman, J. L.; Tawfik, D. S. Nat. Struct. Mol. Biol. 2004,
11, 412–419. (c) Khersonsky, O.; Tawfik, D. S. Biochemistry 2005,
44, 6371–6382. (d) Khersonsky, O.; Tawfik, D. S. J. Biol. Chem. 2006,
281, 7649–7656.
9
18. (h) George, K. M.; Schule, T.; Sandoval, L. E.; Jennings, L. L.;
Taylor, P.; Thompson, C. M. J. Biol. Chem. 2003, 278, 45512–45518.
i) Nachon, F.; Asojo, O. A.; Borgstahl, G. E. O.; Masson, P.;
(7) Harel, M.; Aharoni, A.; Gaidukov, L.; Brumshtein, B.; Khersonsky,
O.; Meged, R.; Dvir, H.; Ravelli, R.; Mccarthy, A.; Toker, L.; Silman,
I.; Sussman, J.; Tawfik, D. Nat. Struct. Mol. Biol. 2004, 11, 412–419.
(8) (a) Yueng, D. T.; Lenz, D. E.; Cerasoli, D. M. FEBS J. 2005, 272,
2225–2230. (b) Yeung, D. T.; Josse, D.; Nicholson, J. D.; Khanal,
A.; McAndrew, C. W.; Bahnson, B. J.; Lenz, D. E.; Cerasoli, D. M.
Biochim. Biophys. Acta 2004, 1702, 67–77.
(
Lockridge, O. Biochemistry 2005, 44, 1154–1162.
(4) (a) Clement, J. G. Arch. Toxicol. 1992, 66, 143–144. (b) Lundy, P. M.;
Hansen, A. S.; Hand, B. T.; Boulet, C. A. Toxicology 1992, 72, 99–
1
5
05. (c) Worek, F.; Eyer, P.; Szinicz, L. Arch. Toxicol. 1998, 72, 580–
87.
(
5) (a) Raveh, L.; Grauer, E.; Grunwald, J.; Cohen, E.; Ashani, Y. Toxicol.
Appl. Pharmacol. 1997, 145, 43–53. (b) Cerasoli, D. M.; Griffiths,
E. M.; Doctor, B. P.; Saxena, A.; Fedorko, J. M.; Greig, N. H.; Yu,
Q. S.; Huang, Y.; Wilgus, H.; Karatzas, C. N.; Koplovitz, I.; Lenz,
D. E. Chem. Biol. Int. 2005, 157, 362–365.
(9) (a) Staros, J. V. Trends Biochem. Sci (Pers. Ed.) 1980, 5, 320–322.
(b) BayLey, H. Photogenerated Reagent in Biochemistry and Molec-
ular Biology; Elsevier: New York, 1983. (c) Bayley, H.; Straos, J. In
Azides and Nitrenes; ReactiVity and Utility; Academic Press: New
York, 1984; p 434.
J. AM. CHEM. SOC. 9 VOL. 132, NO. 47, 2010 16797

A R T I C L E S
Vyas et al.
N, along with N
2
extrusion. Our femtosecond spectroscopic
results favored the mechanism involving energy transfer.
2. Results and Discussion
A. Computational Chemistry: Ground-State Geometries and
Figure 2. Structures of (a) paraoxon which is a substrate for HuPON1
and, (b) a proposed photoaffinity label for HuPON1, diphenylphosphoryl
azide.
Vertical Excitations. We optimized the geometry of DPP-N
using the second-order coupled-cluster method with the resolu-
3
1
7
tion-of-the-identity approximation (RI-CC2) and Becke’s
1
8
reactive intermediate that can randomly and rapidly insert into
the amino acids present in the vicinity of the binding site. The
most frequently employed PALs are azides which, upon
irradiation, generate short-lived singlet nitrenes that can insert
three-parameter hybrid exchange functional combined with
1
9
the Lee-Yang-Parr correlation functional (B3LYP) meth-
odology with the triple-ꢀ valence polarized basis set (TZVP),
2
0
as implemented in the Turbomole-5.80 suite of programs.
Optimized geometries of DPP-N at the RI-CC2/TZVP and
1
0
into nearby C-H bonds of the amino acids. Following the
PAL insertion, mass spectrometric and proteomic analysis of
the PAL-enzyme complex provides important structural infor-
mation about the active site.
3
B3LYP/TZVP levels of theory are shown in Figure 3. The view
shown in the figure is along the OdP bond, as viewed from
oxygen to phosphorus. Both of the phenyl rings are in a ‘geared’
conformation, and each ring has a 50-60° torsion angle with
respect to the OdP bond. The azide unit is found to be almost
parallel to the OdP bond and has a typical geometry, as
Since many OP compounds are substrates with PON1, we
designed a structurally similar PAL. Diphenylphosphoryl azide
(
3
DPP-N ) is an OP compound in which one of the bonds at the
2
1,22
17
phosphorus center is replaced with an azide group as shown in
Figure 2. It is known that upon photolysis, phosphoryl azides
can generate phosphorylnitrenes which can insert into unacti-
described in the literature.
Using a coupled cluster and a
23
time-dependent density functional theory (TD-DFT) approach,
we calculated the vertical excitations using these optimized
1
1-13
vated C-H bonds.
DPP-N was studied by laser flash photolysis (LFP) and electron
paramagnetic resonance (EPR) methods.
Subsequently, the photochemistry of
geometries for the S
The RI-CC2/TZVP level of theory predicts that S
0
ground state, which are listed in Table 1.
and S states
3
1
2
1
4,15
Although triplet
are degenerate, whereas TD-B3LYP/TZVP calculations separate
these two excited singlet states by a small energetic difference.
However, the energy difference between the S and S states is
1 2
very small, and both of these states have low oscillator strengths.
Each of these Franck-Condon states is a combination of many
orbital-to-orbital transitions; therefore, a single orbital-to-orbital
transition cannot be assigned. Consequently, it is very difficult
to predict the photochemical behavior of a particular excited
state by visualizing the molecular orbitals involved in the
formation of that singlet excited state.
15
phosphorylnitrene has been detected by Gohar and Platz using
nanosecond LFP techniques, the shorter lived reactive singlet
1
(
DPP-N) analogue has not been spectroscopically observed.
3
The lifetime of triplet diphenylphosphorylnitrene ( DPP-N) is
on the order of microseconds in various solvents, while the
lifetime of singlet diphenylphosphorylnitrene ( DPP-N), which
1
was not observed, was estimated to be on the order of 1 ns (ns)
in 1,2-dichloroethane and methanol. Hence, confirming the
1
formation of DPP-N and directly measuring its lifetime would
be a significant step toward the development of a PAL for
PON1.
B. Computational Chemistry: Difference Density Plots. To
address the challenge of the multiconfigurational nature of the
excited states, we obtained electron density difference plots for
Earlier, we reported a computational investigation concerning
the potential of phosphoryl azides to function as precursors to
3
the four lowest energy singlet excited states of DPP-N . We
1
6
phosphorylnitrenes. Herein, we report the first experimental
observation of a singlet phosphorylnitrene. We investigated the
have recently applied this methodology to different photochemi-
cal problems such as predicting the photochemistry of aryl
2
1,22
24
25
photochemistry of DPP-N
3
by computational approaches, chemi-
azides,
naphthylimides, and inorganic complexes, in-
cal analysis of light-induced products (in acetonitrile and
cyclohexane), and femtosecond ultrafast UV-vis transient
absorption spectroscopic methods in acetonitrile. Computational
vestigating the photochemical mechanism of nitro-substituted
(17) (a) H a¨ ttig, C.; Weigend, F. J. Chem. Phys. 2000, 113, 5154–5161.
(b) H a¨ ttig, C.; K o˜ hn, A.; Hald, K. J. Chem. Phys. 2002, 116, 5401–
1
studies predicted the formation of DPP-N via two plausible
5
410. (c) H a¨ ttig, C. J. Chem. Phys. 2003, 118, 7751–7761.
mechanisms, namely: (a) energy transfer that can occur from
(
(
18) Becke, A. D. J. Chem. Phys. 1993, 98, 5648–5652.
1
the (π,π*) S excited state of the phenyl rings to the azide group,
19) Lee, C.; Yang, W.; Parr, R. G. Phys. ReV. B 1988, 37, 785–789.
1
which forms DPP-N and an N
2
molecule; and (b) the direct
(20) (a) Ahlrichs, R.; B a¨ r, M.; H a¨ ser, M.; Horn, H.; K o¨ lmel, C. Chem.
Phys. Lett. 1989, 162, 165. (b) For the current version of TURBO-
MOLE, see http://www.turbomole.de. (c) Treutler, O.; Ahlrichs, R.
J. Chem. Phys. 1995, 102, 346.
1
excitation of the azide moiety leading to the formation of DPP-
(
10) (a) Torres, M. J.; Zayas, J.; Platz, M. S. Tetrahedron Lett. 1986, 27,
91–794. (b) Leyva, E.; Chang, D. H. S.; Platz, M. S.; Watt, D. S.;
Crocker, P. J.; Kawada, K. Photochem. Photobiol. 1991, 54, 329–
33. (c) Pandurangi, R. S.; Katti, K. V.; Barnes, C. L.; Volkert, W. A.;
(21) (a) Burdzinski, G.; Gustafson, T. L.; Hackett, J. C.; Hadad, C. M.;
Platz, M. S. J. Am. Chem. Soc. 2005, 127, 13764–13765. (b)
Burdzinski, G.; Hackett, J. C.; Wang, J.; Gustafson, T. L.; Hadad,
C. M.; Platz, M. S. J. Am. Chem. Soc. 2006, 128, 13402–13411. (c)
Wang, J.; Kubicki, J.; Burdzinski, G.; Hackett, J. C.; Gustafson, T. L.;
Hadad, C. M.; Platz, M. S. J. Org. Chem. 2007, 72, 7581–7586. (d)
Sliwa, M.; Mouton, N.; Ruckebusch, C.; Poisson, L.; Idrissi, A.; Aloise,
S.; Potier, L.; Poizat, O.; Buntinx, G. Photochem. Photobiol. Sci. 2010,
9, 661–669.
7
3
Kuntz, R. R. J. Chem. Commun. 1994, 16, 1841–1842. (d) Mueller,
P.; Fruit, C. Chem. ReV. 2003, 103, 2905–2919.
(
(
11) Shioiri, T.; Ninomiya, K.; Yamada, S. J. Am. Chem. Soc. 1972, 94,
6
203–6205.
12) Breslow, R.; Feiring, A.; Herman, F. J. Am. Chem. Soc. 1974, 96,
5
937–5939.
(22) Voskresenska, V.; Wilson, R. M.; Panov, M.; Tarnovsky, A. N.;
Krause, J. A.; Vyas, S.; Winter, A. H.; Hadad, C. M. J. Am. Chem.
Soc. 2009, 131, 11535–11547.
(
(
13) Maslak, P. J. Am. Chem. Soc. 1989, 111, 8201–8207.
14) Houser, M.; Kelley, S.; Maloney, V.; Marlow, M.; Steininger, K.;
Zhou, H. J. Phys. Chem. 1995, 99, 7946–7950.
(23) Olivucci, M. Computational Photochemistry; Elsevier: Amsterdam,
2005; pp 92-128.
(
(
15) Gohar, G. A.; Platz, M. S. J. Phys. Chem. A 2003, 107, 3704–3707.
16) McCulla, R. D.; Gohar, G. A.; Hadad, C. M.; Platz, M. S. J. Org.
Chem. 2007, 72, 9426–9438.
(24) Kucheryvavy, P.; Li, G.; Vyas, S.; Hadad, C. M.; Glusac, K. D. J.
Phys. Chem. A 2009, 113, 6453–6461.
1
6798 J. AM. CHEM. SOC. 9 VOL. 132, NO. 47, 2010

Photochemistry of Diphenylphosphoryl Azide
A R T I C L E S
3
Figure 3. Optimized geometries of diphenylphosphoryl azide (DPP-N ) at the RI-CC2/TZVP (left) and TD-B3LYP/TZVP (right) levels of theory. (Selected
distances are shown in angstroms, and dihedral angles are measured with respect to the OdP bond.)
Table 1. Calculated Vertical Excitations for Diphenylphosphoryl
a
3
Azide (DPP-N )
RI-CC2/TZVP
TD-B3LYP/TZVP
excited state wavelength (nm) oscillator strength wavelength (nm) oscillator strength
-
-
-
-
3
3
4
2
-2
-3
-3
-3
S
S
S
S
1
2
3
4
237
237
230
205
1.0 × 10
1.0 × 10
3.7 × 10
3.0 × 10
249
242
238
233
1.8 × 10
6.2 × 10
5.3 × 10
8.8 × 10
a
The optimized geometry for the S
0
ground state of DPP-N
3
was
computed at the same level of theory as the excitation energies.
26
polycyclic aromatic hydrocarbons, and predicting the character
2
7
of the excited states of N-confused porphyrins. This strategy
2
8
has also been used earlier with other ab initio methods. To
obtain the difference density plots, we calculated the electronic
density for the Franck-Condon singlet excited state, followed
by subtraction of the ground state’s electron density at the same
geometry. Such plots show the overall change in the electron
density upon vertical excitation wherein the green contours
depict the accumulation of electron density in the excited state
and the red contours illustrate the loss of electron density from
Figure 4. Difference density plots for S
n
3
(n ) 1 to 4) of DPP-N at the
the S
0
ground state at some contour value.
RI-CC2/TZVP level of theory. The energy of the excitation is provided as
well as the oscillator strength. The green contours depict the accumulation
of electron density in the excited state, and the red contours illustrate the
loss of electron density from the S ground state. The isocontour values
0
are -0.005 and +0.0005 au.
3
For DPP-N , the calculated difference density plots are shown
in Figures 4 and 5 at the RI-CC2/TZVP and TD-B3LYP/TZVP
levels of theory, respectively. Interestingly, the calculated difference
density plots for the S
methods show different photochemical consequences. The RI-CC2
calculations predicted the S and S states to possess (π,π*)
character localized on the phenyl rings. On the other hand, the
TD-B3LYP method predicted that the S and S states are primarily
localized on the azide group having (π,π*in-plane) character, which
1 2
and S states by the two different theoretical
level and (π,π*) characteristics (of the phenyl rings) at the TD-
B3LYP level. The dramatic changes involving the azide unit
of these states would suggest that the proximal N-N bond
would be weakened upon excitation to these excited states and
thus lead to phosphorylnitrene formation after extrusion of
molecular nitrogen. However, the computational results sug-
1
2
1
2
21,22
was also reported previously
Furthermore, the difference density plots for S
π,π*in-plane) characteristics (of the azide moiety) at the RI-CC2
for various aryl azides.
and S
4
showed
1
3
gested two different pathways for DPP-N formation as shown
(
in Scheme 2. While TD-B3LYP predicted direct formation of
1
DPP-N via the azide excited state, the RI-CC2 results suggested
(
(
(
(
25) Li, G.; Parimal, K.; Vyas, S.; Hadad, C. M.; Flood, A. H.; Glusac,
K. D. J. Am. Chem. Soc. 2009, 131, 1156–11657.
energy transfer from the phenyl (π,π*) excited state to eventu-
1
ally form the DPP-N.
26) Vyas, S.; Onchoke, K. K.; Hadad, C. M.; Dutta, P. K. J. Phys. Chem.
A 2009, 113, 12558–12565.
21,22
To our knowledge,
such a discrepancy between these two
27) Vyas, S.; Hadad, C. M.; Modarelli, D. A. J. Phys. Chem. A 2008,
levels of theory has not been previously noted for azides. Both
theoretical methods provided remarkably similar predictions in
the past that were comparable to the experimental observa-
1
12, 6533–6549.
28) (a) Wiberg, K. B.; Hadad, C. M.; Breneman, C. M.; Laidig, K. E.;
Murcko, M. A.; LePage, T. J. Science 1991, 252, 1266–1272. (b)
Wiberg, K. B.; Hadad, C. M.; LePage, T. J.; Breneman, C. M.; Frisch,
M. J. J. Phys. Chem. 1992, 96, 671–679. (c) Wiberg, K. B.; Hadad,
C. M.; Foresman, J. B.; Chupka, W. A. J. Phys. Chem. 1992, 96,
2
1,22,26,27
tions.
However, the preceding computations were
performed on aryl azides, for which the lowest excited singlet
state always had (π,π*in-plane) characteristics of the azide moiety,
thereby leading to singlet nitrene formation. On the basis of
these computational results, we predict that photolysis of
1
0756–10768. (d) Hadad, C. M.; Foresman, J. B.; Wiberg, K. B. J.
Phys. Chem. 1993, 97, 4293–4312. (e) Wiberg, K. B.; Hadad, C. M.;
Ellison, G. B.; Foresman, J. B. J. Phys. Chem. 1993, 97, 13586–13597.
J. AM. CHEM. SOC. 9 VOL. 132, NO. 47, 2010 16799

A R T I C L E S
Vyas et al.
Figure 5. Difference density plots for S
n
3
(n ) 1 to 4) of DPP-N at the
TD-B3LYP/TZVP level of theory. The energy of the excitation is provided
as well as the oscillator strength. The green contours depict the accumulation
of electron density in the excited state, and the red contours illustrate the
0
loss of electron density from the S ground state. The isocontour values
are (0.003 au.
3
DPP-N at about 250 nm will result in pumping the precursor
Figure 6. Femtosecond UV-vis transient absorption spectra obtained with
molecule to either a singlet azide excited state or a singlet (π,π*)
excited state of the phenyl ring, which will then transfer its
energy to the azide unit. In either case, the singlet nitrene will
then be formed, which may be observed using ultrafast
absorption spectroscopic measurements.
2
60 nm pulsed photolysis of ∼16-18 mM DPP-N
3
in acetonitrile: (a) rise
of a (π,π*) excited state, intermediate A; (b) decay of the (π,π*) intermediate
1
1
and rise of DPP-N, intermediate B; (c) decay of DPP-N. (For detailed
absorption spectra at early time scales, see Supporting Information, Figures
S1 and S5.) At about 520 nm, the probe wavelength data are not shown
because of a strong contribution from the scattered excitation light (260
nm).
C. Ultrafast Spectroscopic Studies of Diphenylphosphoryl
Azide. The singlet state of diphenylphosphorylnitrene
1
(
DPP-N) has never been observed previously, although triplet
observed immediately after the sample is exposed to the laser
pulse. On the basis of our calculations, this species could be
assigned either to the azide (π,π*in-plane) excited state or a (π,π*)
phosphorylnitrenes have been observed by LFP and EPR
methods.
spectroscopy experiments for DPP-N
1
4,15
The results of ultrafast time-resolved absorption
are shown in Figure 6
3
3
excited state of the phenyl rings of DPP-N (Figures 4 and 5).
after 260 nm photolysis of a ∼16-18 mM solution of the azide
The decay of this species is observed at about 1 ps after
photolysis, and a new species (B) then grows in the spectral
range 450-550 nm over 80 ps (Figure 6b); species B then
decays after 150 ps and almost completely disappears at about
in acetonitrile. At ambient temperature, the excited state of
DPP-N
3
, species A, is observed at about 370 and 430 nm with
a less intense band at 640 nm (Figure 6a). This excited state is
a
3
Scheme 2. The Photochemistry of DPP-N As Predicted by the RI-CC2/TZVP (top) and TD-B3LYP/TZVP (bottom) Levels of Theory
a
The initially photoexcited unit of the molecule is depicted in bold.
1
6800 J. AM. CHEM. SOC. 9 VOL. 132, NO. 47, 2010

Photochemistry of Diphenylphosphoryl Azide
A R T I C L E S
1
500 ps (Figure 6c) after the initial laser pulse. A possibility is
that species B could be the ylide formed from coordination of
a molecule of acetonitrile to the nitrogen of the singlet
phosphorylnitrene. However, similar experiments conducted in
methanol show the same transients with approximately same
lifetimes; thus, we can rule out the possibility of B being the
ylide (see Supporting Information). We propose that species B
1
is the singlet diphenylphosphorylnitrene, DPP-N. It is important
to note that vibrational cooling or band narrowing was not observed
for the 525 nm band; the time constant for evolution of the 370,
4
30, and 640 nm bands is about 20-30 ps, which is on the same
time scale for which vibrational cooling typically occurs.
Because the predicted singlet nitrene and the second short-
lived, promptly formed species absorbing at around 440 nm have
an overlapping absorption band, we performed global fitting of
the data to determine the lifetimes of the intermediates.
Deconvolution of the data was achieved by fitting to the
expression:
Figure 7. A plot of the observed pseudo-first-order rate constant (1/τ) of
decay of singlet nitrene versus tris(trimethylsilyl)silane concentration. The
3
nitrene was produced after 260 nm excitation of DPP-N . A single
exponential equation was fit to the data obtained from kinetic traces
monitored at 550 nm after photolysis.
f(x) ) A exp(-x/τ ) + A exp(-x/τ ) + A
3
1
1
2
2
1
supports our assignment of species B as DPP-N. Moreover, if
we recalculate the lifetime using a second-order rate constant
in which the first and second time-constants correspond to the
lifetimes of the excited state of the precursor and the singlet
nitrene, respectively, and the third term is the offset (residual
absorption) remaining after 3 ns. The residual at about 360 nm
remained steady even after 3000 ps, which is the limit of our
ultrafast absorption experiments. Gohar and Platz observed
the triplet ylide in acetonitrile at 340 nm with a predicted lifetime
larger than 200 µs, while the triplet nitrene was not observed.
In our experiments, as the singlet nitrene is decaying, the triplet
nitrene should rise or immediately form triplet ylide in aceto-
nitrile. Hence, we assign the residual peak to the triplet nitrene
or the triplet ylide. The global fitting procedure yielded the
10
-1 -1
of 1 × 10
M
s , their data predict a lifetime of 500 ps, in
excellent accord with this study.
E. Ultrafast Spectroscopic Studies of Diphenyl Phosphora-
midate. The short-lived species (28 ( 9 ps) observed at about
430 nm in our ultrafast experiments can, in principle, be assigned
to either the (π,π*in-plane) excited state localized on the azide
unit or a (π,π*) excited state localized at the phenyl rings as
predicted by our calculations. In order to rule out one of the
two possibilities, we performed similar calculations and ultrafast
1
5
UV-vis experiments on diphenyl phosphoramidate (DPP-NH
2
),
in which the azide group of DPP-N
moiety.
3
is replaced by an amine
lifetime of the excited state of DPP-N to be 28 ( 9 ps (species
3
1
2 3
The geometries of DPP-NH are similar to that of DPP-N at
A), and the lifetime of DPP-N to be about 480 ( 50 ps (species
both levels of theory (Supporting Information). The calculated
electron density difference plots for the S and S states at the
RI-CC2/TZVP and TD-B3LYP/TZVP levels of theory are
shown in Figure 8. Both the S and S states are localized on
one of the phenyl rings and with a (π,π*) character. These plots
indicated that the ultrafast UV-vis measurements for DPP-NH
B).
D. Ultrafast Time-Resolved Spectroscopic Studies on Quench-
1
2
ing of the Singlet Nitrene. Tris(trimethylsilyl)silane, ((H
3 3
C) -
Si) Si-H (TRIS), is known to quench singlet nitrenes, presum-
3
1
2
1
5
ably by insertion into the Si-H bond. In order to verify that
the relatively long-lived (∼0.5 ns) species in our ultrafast
2
1
will probably show either a short-lived singlet excited state
localized on the phenyl rings if the intersystem crossing rate is
very fast or a long-lived species if the intersystem crossing rate
is slow. Consequently, the observed absorption, and its lifetime,
will rule out either azide excited state formation or a (π,π*)
UV-vis experiments is DPP-N, we performed ultrafast time-
resolved experiments in the presence of various concentrations
of the silane. Similar to the experiments discussed above, two
species were observed at 430 and 525 nm, respectively.
However, the lifetime of the 525 nm species was observed to
decrease with the increasing concentration of TRIS. Upon single
exponential fitting of the data at 550 nm, we obtained the
lifetimes (τ) of the second species at different concentrations
of TRIS. A plot of 1/τ versus TRIS concentration is roughly
3
excited state of the phenyl ring in the case of the DPP-N .
Ultrafast transient absorption experiments were performed in
acetonitrile with an absorption of ∼1.0 at 260 nm, and the results
are shown in Figure 9. We detected the growth of a species at
490 nm immediately after the first laser pulse. This intermediate
A decayed after about 7 ps, and a new species B was found to
grow as a broad peak at 550 nm. The intermediate B was formed
over 500 ps, followed by an extremely slow decay. Since, the
decay of intermediate B is very slow, its lifetime could not be
determined by ultrafast spectroscopy. We estimate the lifetime
of B to be on the order of several nanoseconds. The intermediate
A is predicted to be a singlet (π,π*) excited state localized on
the phenyl ring, a result that is consistent with the computational
results. This singlet excited state rapidly intersystem crosses to
form a triplet, presumably a (n,π*), excited state, as intermediate
B has no obvious competing photochemical pathway (Scheme
3). While studying the ultrafast photolysis of aryl azides, Platz
1
0
-1 -1
linear (Figure 7). The slope of this plot is 1.13 × 10
which is the absolute, second-order rate constant for reaction
of the nitrene with the silane. The y (1/τ ) intercept corresponds
to a value of τ
M
s ,
0
0
∼ 900 ps. This lifetime determined from the
intercept is larger than the 480 ( 50 ps measured by a direct
measurement of the decay in the absence of silane. As there is
a greater error in the extrapolation to the y intercept, the directly
measured value is deemed more accurate. Gohar and Platz
assumed that the second-order rate constant for reaction of the
9
-1 -1
nitrene with silane was 5.0 × 10 M
s
and, on the basis of
this assumption, also deduced that the singlet nitrene lifetime
1
5
was 1 ns in 1,2-dichloroethane and methanol. This is in
reasonable agreement with the results of this work and further
J. AM. CHEM. SOC. 9 VOL. 132, NO. 47, 2010 16801

A R T I C L E S
Vyas et al.
1 2 2
Figure 8. Difference density plots for the S and S states of DPP-NH at
the TD-B3LYP/TZVP (top) and RI-CC2/TZVP (bottom) level of theory.
The green contours depict the accumulation of electron density in the excited
state, and the red contours illustrate the loss of electron density from the S
0
ground state. The isocontour values are -0.005 and +0.0001 au (RI-CC2/
TZVP) and (0.001 au (TD-B3LYP/TZVP).
21
and co-workers observed a similar singlet (π,π*) excited state
localized on the aryl ring at a similar wavelength, ∼480 nm.
Because there is an overlap region for A and B in the transient
spectra, global fitting was attempted to deconvolute the areas
under the two overlapping curves. However, the growth of B
completely obscured the spectral region corresponding to A.
Moreover, B has almost no decay within the time scale used in
the experiments; therefore, a global fit would not yield results
with reliable accuracy. However, as A decayed, the second
species B rose, suggesting that the excited state of DPP-NH
i.e., A) transforms into species B. Therefore, the growth lifetime
of B should correspond to the lifetime of intermediate A. Thus,
we monitored the kinetic traces at 550, 560, 570, 580, 590, 600,
and 610 nm at which the spectral signature of A is negligible
in order to monitor the formation of B. The kinetic traces from
2
(
Figure 9. Femtosecond UV-vis transient absorption spectra produced by
2
60 nm photolysis of ∼12 mM DPP-NH
2
in acetonitrile: (a) evolution of
a (π,π*) excited state, intermediate A; (b) decay of the (π,π*) excited state
and rise of triplet (n,π*) excited state, intermediate B, and (c) decay of the
triplet intermediate.
0
to 500 ps were fitted to a single exponential function to
phenyl ring) rather than the (π,π*in-plane) excited state (of the
calculate the growth of the intermediate B. For DPP-NH , the
2
azide group). Inspection of the geometry of DPP-N
showed that the phenyl rings were oriented toward the azide
group, thereby favoring fast energy transfer. Since DPP-NH
does not have a competing energy transfer decay pathway (such
as to the azide group of DPP-N ), we posit that the excited state
of DPP-NH should be longer lived than the DPP-N excited
3
(Figure 3)
rise
average τ
B
was determined to be 33 ( 8 ps, which is also
the lifetime of the intermediate A. This lifetime is comparable
2
to, but slightly longer than, the deduced lifetime for the singlet
excited state of DPP-N
3
(Figure 5, intermediate A) obtained by
3
global fitting (28 ( 9 ps), as predicted by the mechanistic
scheme. Global fitting analysis of the ultrafast experimental data
2
3
state, which is in good agreement with the aforementioned
observations. The slower, competing decay pathway of DPP-
of DPP-NH
00 ps (although with a large error). This species, attributed
to the singlet excited state localized on the phenyl ring of
DPP-NH , has a longer lifetime than the corresponding singlet
exited phenyl ring observed for DPP-N at 430 nm. The relatively
longer lifetime of the phenyl excited state of DPP-NH
2
established the lifetime of species A to be about
1
NH
2
is intersystem crossing to the triplet manifold. Thus, we
to a triplet state, a species which
assign species B in DPP-NH
2
2
is formed from the (A) singlet (π,π*) phenyl excited state with
a time constant of 33 ( 8 ps. This conclusion was confirmed
by nanosecond LFP studies with DPP-NH in which the 550
2
nm band was again observed and which had a lifetime of 9.1
( 0.1 ns. The lifetime of this transient species was sensitive to
oxygen concentration and found to have a shorter lifetime (∼5
ns) for air-saturated solutions, consistent with its assignment
as a triplet species. These results also confirmed that the RI-
CC2/TZVP calculations predicted the correct photochemistry
3
2
is reasonable
(or species A) can only decay through intersystem
1
since DPP-NH
2
crossing, while the singlet excited state of DPP-N
possibilities, including energy transfer to the azide moiety.
Thus, from the DPP-NH spectral analysis, we conclude that
the short-lived intermediate observed in the ultrafast UV-vis
absorption spectra of DPP-N is a (π,π*) excited state (of the
3
has several other
2
3
1
6802 J. AM. CHEM. SOC. 9 VOL. 132, NO. 47, 2010

Photochemistry of Diphenylphosphoryl Azide
A R T I C L E S
a
Scheme 3. Ultrafast UV-vis Photochemistry of Diphenyl Phosphoramidate
a
Note that the lowest energy excited state is localized on the aromatic moiety of this compound.
for DPP-N
less consistent with experiment in this system.
In our ultrafast experiments with DPP-N , similar to the
3
, whereas the TD-B3LYP/TZVP calculations were
3. Conclusions
3
We investigated the photochemistry of DPP-N by compu-
3
tational and experimental methods. Our computational results
at the RI-CC2/TZVP and TD-B3LYP/TZVP levels of theory
were not in agreement with each other; however, we do note
that the excitation energies are very similar (within 30 nm) for
the first few excited states. The experimental results are clearly
in better agreement with the RI-CC2 results. We established
the formation of two transient species with a lifetime of about
2
1
ultrafast studies on aryl azides, we could not observe the
intermediate azide dissociative state which can be formed
following energy transfer from the initially generated (π,π*)
singlet excited state of the phenyl ring. Furthermore, vibrational
cooling (band narrowing) of the 525 nm absorption was not
21
observed. In the case of naphthyl azide, the azide dissociative
state, which was not observed, was predicted to have a lifetime
shorter than 1 ps. In general, the barrier for the loss of molecular
nitrogen from the azide dissociative state is very small (<1-2
2
8 and 480 ps, respectively, using ultrafast UV-vis transient
absorption measurements for DPP-N . These transient absorp-
tions were assigned to the singlet excited state of the azide
3
2
1
kcal/mol); hence, nitrene formation can be expected to occur
almost instantaneously upon populating the dissociative excited
state of the azide. The rate of growth of the 525 nm band was
the same as the rate of decay of the 440 nm band, which is
about 20 ps. As these time scales are similar to that of vibrational
cooling, we are not surprised that we did not observe any band-
narrowing at 525 nm.
1
(
3
DPP-N *), localized on the phenyl ring, and the direct
1
observation of the singlet diphenylphosphorylnitrene ( DPP-N),
respectively. We confirmed our assignments using quenching
studies by tris(trimethylsilyl)silane and by the ultrafast UV-vis
2
analysis of DPP-NH .
This is the first spectroscopic observation of a singlet
phosphorylnitrene, and this reactive intermediate has a lifetime
of ∼0.5 ns in solution at ambient temperature. The singlet
phosphorylnitrene is generated by initial excitation of the (π,π*)
phenyl ring of the azide precursor, energy transfer from the
phenyl moiety to the azide unit, and subsequent extrusion of
F. Chemical Analysis of Reaction Products. As the photo-
products of DPP-N
3
have not been completely characterized,
we decided to isolate the photoproducts following preparative
scale photolysis of DPP-N
as solvents.
3
, using acetonitrile and cyclohexane
in acetonitrile using a high-
1
molecular nitrogen to form DPP-N. From the product studies,
we predict that DPP-N can serve as an effective reagent for
3
Steady-state photolysis of DPP-N
3
pressure mercury lamp primarily formed an uncharacterizable
brown polymer presumably due to several reactions including
ylide formation, nitrene-dimerization, and hydrogen-atom ab-
straction reactions. Nevertheless, analysis of the mixture of
volatile products in acetonitrile and cyclohexane by GC-MS and
ESI-MS confirmed the singlet nitrene insertion into the solvent
photoaffinity labeling, as upon photolysis it will produce a short-
lived singlet nitrene that should react rapidly and indiscrimi-
nately with C-H bonds within a nanosecond to form robust
11-13
adducts.
Further work for binding and photoaffinity labeling
with HuPON1 is ongoing and will provide
studies of DPP-N
3
further insight into developing a catalytic bioscavenger as a
therapeutic against nerve agent poisoning.
(
see Supporting Information for details) as reported earlier in
refs 11-13. In order to understand if the product formation was
due to secondary photochemistry, DPP-N was dissolved in
3
4. Experimental and Computational Methods
acetonitrile and photolyzed at 260 nm using the femtosecond
absorption setup for about 1-2 h(s). Although the precipitates
were not formed initially in the femtosecond apparatus, the
solution turned yellow-brown in color and began to form a small
amount of a visible precipitate over time.
A. Computational Methods. All calculations were performed
2
0
with the Turbomole-5.80 suite of programs at the Ohio Super-
computer Center. The ground-state geometries were optimized with
second-order coupled cluster methods using the resolution-of-the-
identity approximation for the electron-electron repulsion integrals
1
7
We carried out the preparative scale, steady-state photolysis
(RI-CC2) and with Becke’s three-parameter hybrid exchange
18
of DPP-N
3
in cyclohexane at >254 nm, and isolated two
functional in combination with the Lee-Yang-Parr correlation
19
functional (B3LYP). The triple-ꢀ valence polarized (TZVP) basis
sets ([14s9p1d]/[5s4p1d] for P; [11s6p1d]/[5s3p1d] for C, N, and
O; and [5s1p]/[3s/1p] for H), as developed by Ahlrichs and co-
products; formation of DPP-CH was observed due to the singlet
nitrene insertion reaction into a C-H bond of the solvent (see
Scheme S1, Supporting Information). The photoproduct was
2
9
workers, were used for all of these calculations. To calculate the
vertical excitations and to obtain the difference density plots, the
1
isolated by silica gel chromatography and characterized by H
NMR, 13C NMR, IR, and MS techniques (see Supporting
Information for experimental details). We performed similar
studies with tris(trimethylsilyl)silane as a quenching agent in
acetonitrile. From characterization of those mixtures, we also
detect a small peak in the mass spectra consistent with trapping
of the nitrene with the silane (see Supporting Information). All
of these reactions are consistent with formation of a very reactive
singlet diphenylphosphorylnitrene.
23
time-dependent B3LYP (TD-B3LYP) methodology was used as
1
7
well as the RI-CC2 methodology. All of the stationary points
were confirmed to be minima by calculating vibrational frequencies
analytically with the AOFORCE module, as implemented in
Turbomole.
(
29) Weigend, F.; H a¨ ser, F.; Patzelt, H.; Ahlrichs, R. Chem. Phys. Lett.
1998, 294, 143–152.
J. AM. CHEM. SOC. 9 VOL. 132, NO. 47, 2010 16803

A R T I C L E S
Vyas et al.
Scheme 4. Synthesis of DPP-NH
2
of LiCl (0.13 g, 3.6 mmol) and NaBH
in dry THF (35 mL) with
4
stirring at 0 °C for 30 min. Then, the mixture was allowed to warm
to room temperature. Upon completion (as analyzed by thin-layer
chromatography), 5% aqueous HCl was added (20 mL) and the
mixture was extracted with diethyl ether. The organic layer was
dried with anhydrous sodium sulfate and evaporated. THF was then
removed in vacuo, and the product was purified by silica gel column
chromatography with ethyl acetate:hexane (1:4) along with a few
drops of triethylamine. The pure product was obtained as colorless
B. Femtosecond Broadband UV-vis Transient Absorption
Spectrometer. The measurements discussed in the paper were
performed using the nanosecond and femtosecond time-resolved
2
1,30
1
absorption spectrometers described elsewhere.
The excitation
crystals and was characterized by H NMR and mass spectrometry
3
1
wavelength used in the ultrafast experiments was 260 nm. (The
nanosecond LFP measurements were carried out using 266 nm
excitation, while a 254 nm light source was used for preparative-
scale product analyses.) The concentrations of the photolytic
precursors were adjusted in each case so that all samples used for
spectroscopic studies would have an absorption of ∼1.0 at 260 nm.
All of the curve fittings were performed with the Igor Pro 6.0
software.
and confirmed with data published in the literature.
Acknowledgment. We acknowledge financial support from the
National Institutes of Health (U54-NS058183). We also acknowl-
edge the National Science Foundation for funding the femtosecond
transient absorption UV-vis apparatus. S.V. acknowledges a
Presidential Fellowship by The Ohio State University. Generous
computational resources from the Ohio Supercomputer Center are
also gratefully acknowledged.
C. Materials. Diphenylphosphoryl azide (DPP-N
purchased from Aldrich. Spectroscopic grade acetonitrile was used
as purchased from Fisher Scientific Inc. DPP-NH was synthesized
3
) was used as
2
Supporting Information Available: Coordinates of all opti-
according to the procedure published in the literature (Scheme 4).
Commercially available diphenylphosphoryl azide (1.0 g, 3.6
mmol) was dissolved in 15 mL of dry THF and added to a mixture
mized geometries, calculated vibrational frequencies, and
detailed figures of the ultrafast measurements for DPP-N
3
and
DPP-NH . This material is available free of charge via the
2
Internet at http://pubs.acs.org.
JA909327Z
(
30) (a) Gritsan, N. P.; Zhai, H. B.; Yuzawa, T.; Karweik, D.; Brooke, J.;
Platz, M. S. J. Phys. Chem. A 1997, 101, 2833–2840. (b) Martin, C. B.;
Shi, X.; Tsao, M.-L.; Karweik, D.; Brooke, J.; Hadad, C. M.; Platz,
M. S. J. Phys. Chem. B 2002, 106, 10263–10271. (c) Tsao, M.-L.;
Gritsan, N.; James, T. R.; Platz, M. S.; Hrovat, D. A.; Borden, W. T.
J. Am. Chem. Soc. 2003, 125, 9343–9358.
(31) Rajaram, S.; Chary, K. P.; Iyengar, D. S. Synth. Commun. 2000, 30,
4495–4500.
1
6804 J. AM. CHEM. SOC. 9 VOL. 132, NO. 47, 2010