Synthetic and mechanistic studies on Pd(0)-catalyzed diamination of conjugated dienes

Article abstract of DOI:10.1021/ja909459h

Various dienes and a triene can be regioselectively diaminated at the internal double bond with good yields and high diastereoselectivity using di-tert-butyldiaziridinone (5) as the nitrogen source and Pd(PPh ₃)₄ (1-10 mol %) as the catalyst. Kinetic studies with ¹H NMR spectroscopy show that the diamination is first-order in total Pd catalyst and inverse first-order in PPh₃. For reactive dienes, such as 1-methoxybutadiene (6g) and alkyl 1,3-butadienes (6a, 6j), the diamination is first-order in di-tert-butyldiaziridinone (5) and zero-order in the olefin. For olefins with relatively low reactivity, such as (E)-1-phenylbutadiene (6b) and (3E,5E)-1,3,5-decatriene (6i), similar diamination rates were observed when 3.5 equiv of olefins were used. Pd(PPh ₃)₂ is likely to be the active species for the insertion of Pd(O) into the N-N bond of di-ferf-butyldiaziridinone (5) to form a four-membered Pd(II) complex (A), which can be detected by NMR spectroscopy. The olefin complex (B),. formed from intermediate A via ligand exchange between the olefin substrate and the PPh₃, undergoes migratory insertion and reductive elimination to give the diamination product and regenerate the Pd(O) catalyst.

Full text of DOI:10.1021/ja909459h

Published on Web 02/18/2010
Synthetic and Mechanistic Studies on Pd(0)-Catalyzed
Diamination of Conjugated Dienes
Baoguo Zhao, Haifeng Du, Sunliang Cui, and Yian Shi*
Department of Chemistry, Colorado State UniVersity, Fort Collins, Colorado 80523
Received November 7, 2009; E-mail: yian@lamar.colostate.edu
Abstract: Various dienes and a triene can be regioselectively diaminated at the internal double bond with
good yields and high diastereoselectivity using di-tert-butyldiaziridinone (5) as the nitrogen source and
Pd(PPh3)4 (1-10 mol %) as the catalyst. Kinetic studies with 1H NMR spectroscopy show that the diamination
is first-order in total Pd catalyst and inverse first-order in PPh3. For reactive dienes, such as 1-methoxy-
butadiene (6g) and alkyl 1,3-butadienes (6a, 6j), the diamination is first-order in di-tert-butyldiaziridinone
(5) and zero-order in the olefin. For olefins with relatively low reactivity, such as (E)-1-phenylbutadiene
(6b) and (3E,5E)-1,3,5-decatriene (6i), similar diamination rates were observed when 3.5 equiv of olefins
were used. Pd(PPh3)2 is likely to be the active species for the insertion of Pd(0) into the N-N bond of
di-tert-butyldiaziridinone (5) to form a four-membered Pd(II) complex (A), which can be detected by NMR
spectroscopy. The olefin complex (B), formed from intermediate A via ligand exchange between the olefin
substrate and the PPh3, undergoes migratory insertion and reductive elimination to give the diamination
product and regenerate the Pd(0) catalyst.
Scheme 1
Introduction
Vicinal diamines are very important functional moieties that
are present in various biologically active compounds, chemical
materials, and chiral catalysts.1 Diamination of olefins presents
an attractive strategy to introduce vicinal nitrogen atoms.
Various metal-free,1,2 metal-mediated,1,3,4 or metal-catalyzed5,6
processes have been developed. Palladium has been one of the
most important metals explored for the diamination process. In
(1) For leading reviews, see: (a) Lucet, D.; Gall, T. L.; Mioskowski, C.
Angew. Chem., Int. Ed. 1998, 37, 2580. (b) Mortensen, M. S.;
O’Doherty, G. A. Chemtracts: Org. Chem. 2005, 18, 555. (c) Kotti,
S. R. S. S.; Timmons, C.; Li, G. Chem. Biol. Drug Des. 2006, 67,
101. (d) Kizirian, J.-C. Chem. ReV. 2008, 108, 140. (e) Lin, G.-Q.;
Xu, M.-H.; Zhong, Y.-W.; Sun, X.-W. Acc. Chem. Res. 2008, 41, 831.
(f) de Figueiredo, R. M. Angew. Chem., Int. Ed. 2009, 48, 1190. (g)
Cardona, F.; Goti, A. Nat. Chem. 2009, 1, 269.
a pioneering study, Ba¨ckvall reported stereospecific diamination
of olefins via trans-aminopalladation, oxidation of Pd(II) to
possible Pd(IV) with oxidants such as mCPBA, and subsequent
nucleophilic displacement of Pd by an amine (Scheme 1).7 In
2005, Lloyd-Jones, Booker-Milburn, and co-workers reported
a Pd(II)-catalyzed intermolecular diamination of conjugated
dienes with ureas (Scheme 2).8 The diamination occurred
regioselectively at the less-substituted double bond of dienes.
The reaction is likely to proceed via a Pd(II)-promoted aza-
Wacker-type process (trans-aminopalladation)9 to form a π-allyl
Pd complex, followed by the displacement of Pd with N. The
resulting Pd(0) is oxidized by O2 or benzoquinone to regenerate
the Pd(II) catalyst. In 2005, Mun˜iz and co-workers reported a
Pd(II)-catalyzed intramolecular diamination of olefins tethered
(2) For leading references on recent Ritter-type diamination see: (a) Li,
G.; Kim, S. H.; Wei, H.-X. Tetrahedron Lett. 2000, 41, 8699. (b)
Booker-Milburn, K. I.; Guly, D. J.; Cox, B.; Procopiou, P. A. Org.
Lett. 2003, 5, 3313.
(3) For examples of metal-mediated diaminations, see Tl: (a) Aranda,
V. G.; Barluenga, J.; Aznar, F. Synthesis 1974, 504. Os: (b) Chong,
A. O.; Oshima, K.; Sharpless, K. B. J. Am. Chem. Soc. 1977, 99,
3420. (c) Mun˜iz, K. Eur. J. Org. Chem. 2004, 2243. Hg: (d) Barluenga,
J.; Alonso-Cires, L.; Asensio, G. Synthesis 1979, 962. Co: (e) Becker,
P. N.; White, M. A.; Bergman, R. G. J. Am. Chem. Soc. 1980, 102,
5676. Mn: (f) Fristad, W. E.; Brandvold, T. A.; Peterson, J. R.;
Thompson, S. R. J. Org. Chem. 1985, 50, 3647.
(4) For recent Cu(II)-mediated intramolecular diamination, see: (a)
Zabawa, T. P.; Kasi, D.; Chemler, S. R. J. Am. Chem. Soc. 2005,
127, 11250. (b) Zabawa, T. P.; Chemler, S. R. Org. Lett. 2007, 9,
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(5) For Rh(II), Cu(I), and Fe(III)-catalyzed diamination with TsNCl2 or
TsNBr2, see: (a) Li, G.; Wei, H.-X.; Kim, S. H.; Carducci, M. D.
Angew. Chem., Int. Ed. 2001, 40, 4277. (b) Wei, H.-X.; Kim, S. H.;
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11, 2671.
(7) Ba¨ckvall, J.-E. Tetrahedron Lett. 1978, 163.
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Soc. 2005, 127, 7308.
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9
10.1021/ja909459h  2010 American Chemical Society
J. AM. CHEM. SOC. 2010, 132, 3523–3532 3523

A R T I C L E S
Zhao et al.
Scheme 2
Scheme 4
Scheme 3
Scheme 5
with ureas (Scheme 3).10 The reaction was proposed to proceed
via aminopalladation to form a Pd(II) intermediate, which is
oxidized to Pd(IV) species, followed by the replacement of the
C-Pd(IV) bond with a C-N bond to give the diamination
product and regenerate the Pd(II) catalyst.10c,11-13 Very recently,
Michael and co-workers reported the diamination of olefins
tethered with amide groups using N-fluorobenzenesulfonimide
as electrophilic nitrogen source (Scheme 4).14 The diamination
is proposed to proceed via a Pd(II)-promoted aminopalladation,
oxidative addition of N-fluorobenzenesulfonimide to the Pd(II)
species, and subsequent reductive elimination.
As part of our general interest in the oxidation of olefins,15
we have explored a possible diamination of olefins via the
activation of a N-N bond (Scheme 5). It was hoped that a
suitable metal catalyst could oxidatively insert into the N-N
bond of dinitrogen compound 1 (cyclic or acylic) to form
diamido species 2, which would then undergo migratory
insertion into a double bond to form 3,16 followed by reductive
elimination to give diamination product 4. Our studies started
with the investigation of the feasibility of diaziridines and related
analogues as nitrogen source and various metals as catalyst. It
was found that conjugated dienes can be effectively diaminated
at the internal double bond with di-tert-butyldiaziridinone (5)17,18
as nitrogen source and Pd(PPh3)4 as catalyst (Scheme 6).19 In
subsequent studies, the reaction parameters such as ligand and
solvent have been examined to improve the reaction process.
The catalyst loading can be reduced to 1-2 mol % from the
original 10 mol % (Scheme 6).17b The reaction mechanism has
also been investigated via NMR spectroscopy and kinetic
studies, providing a better understanding of the reaction
(10) (a) Streuff, J.; Ho¨velmann, C. H.; Nieger, M.; Mun˜iz, K. J. Am. Chem.
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C. H.; Campos-Go´mez, E.; Barluenga, J.; Gonza´lez, J. M.; Streuff,
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Cha´vez, P.; Ho¨velmann, C. H. Chem. Asian J. 2008, 3, 1248.
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Li, M. J. Phys. Org. Chem. 2008, 21, 979. (b) Yu, H.; Fu, Y.; Guo,
Q.; Lin, Z. Organometallics 2009, 28, 4507.
(12) For related Ni(II)-catalyzed diaminations, see: (a) Mun˜iz, K.; Streuff,
J.; Ho¨velmann, C. H.; Nu´n˜ez, A. Angew. Chem., Int. Ed. 2007, 46,
7125. (b) Mun˜iz, K.; Ho¨velmann, C. H.; Streuff, J.; Campos-Go´mez,
E. Pure Appl. Chem. 2008, 80, 1089.
(13) For additional leading references on oxidation of Pd(II) to Pd(IV) and
subsequent displacement of Pd with heteroatom nucleophiles, see: (a)
Ba¨ckvall, J.-E. Acc. Chem. Res. 1983, 16, 335. (b) Yoneyama, T.;
Crabtree, R. H. J. Mol. Catal. A 1996, 108, 35. (c) Dick, A. R.; Hull,
K. L.; Sanford, M. S. J. Am. Chem. Soc. 2004, 126, 2300. (d) Desai,
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Chem., Int. Ed. 2005, 44, 7420. (g) Dick, A. R.; Kampf, J. W.; Sanford,
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Chem. ReV. 2008, 108, 3958.
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385. (b) Ney, J. E.; Wolfe, J. P. Angew. Chem., Int. Ed. 2004, 43,
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F. D.; Stowell, J. C.; Bergmark, W. R. J. Org. Chem. 1969, 34, 2254.
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& Sons, Inc: New York, 1983; p 547.
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(14) Sibbald, P. A.; Michael, F. E. Org. Lett. 2009, 11, 1147.
9
3524 J. AM. CHEM. SOC. VOL. 132, NO. 10, 2010

Pd(0)-Catalyzed Diamination of Conjugated Dienes
A R T I C L E S
Scheme 6
Table 1. Solvent Study on the Pd(PPh3)4-Catalyzed Diaminationa
entry
solvent
conv. (%)b
process.20-22 Herein, we wish to report our detailed studies on
this subject.23-26
1
2
3
4
5
6
7
CDCl3
C6D6
toluene
THF
hexanes
DCM
CH3CN
0
100
100
100
100
100
0
Results and Discussion
1. Reaction Condition Studies. Several solvents were screened
for the diamination using (E)-1,3-decadiene (6a) as substrate,
a All reactions were carried out with olefin 6a (0.20 mmol),
di-tert-butyldiaziridinone (5) (0.24 mmol), Pd(PPh3)4 (0.020 mmol) at 65
°C in dry solvent (0.60 mL) with stirring under argon for 1.5 h.
b Conversion was determined by crude 1H NMR spectroscopy based on
the olefin.
(20) For leading reviews on mechanistic studies on transition-metal
catalysis, see: (a) Masel, R. I. Chemical Kinetics and Catalysis; Wiley-
Interscience: New York, 2001. (b) Bhaduri, S.; Mukesh, D. Homo-
geneous Catalysis: Mechanisms and Industrial Applications; Wiley-
Interscience: New York, 2000. (c) Heaton, B. Mechanisms in
Homogeneous Catalysis: a Spectroscopic Approach; Wiley-VCH:
Weinheim, 2005. (d) Blackmond, D. G. Angew. Chem., Int. Ed. 2005,
44, 4302.
Table 2. Ligand Study on the Pd(0)-Catalyzed Diaminationa
entry
ligand
conv. (%)b
entry
ligand
conv. (%)b
(21) For a leading review on mechanistic studies of Pd-catalyzed reactions,
see: Amatore, C.; Jutand, A. Acc. Chem. Res. 2000, 33, 314.
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(b) Goodson, F. E.; Wallow, T. I.; Novak, B. M. J. Am. Chem. Soc.
1997, 119, 12441. (c) Marcone, J. E.; Moloy, K. G. J. Am. Chem.
Soc. 1998, 120, 8527. (d) Alcazar-Roman, L. M.; Hartwig, J. F.;
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Brookhart, M. J. Am. Chem. Soc. 2000, 122, 6351. (f) Rosner, T.;
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Blackmond, D. G. J. Am. Chem. Soc. 2001, 123, 4621. (i) Stambuli,
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Singh, U. K.; Strieter, E. R.; Blackmond, D. G.; Buchwald, S. L. J. Am.
Chem. Soc. 2002, 124, 14104. (k) de K. Lewis, A. K.; Caddick, S.;
Cloke, F. G. N.; Billingham, N. C.; Hitchcock, P. B.; Leonard, J. J. Am.
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Buchwald, S. L. J. Am. Chem. Soc. 2003, 125, 13978. (m) Steinhoff,
B. A.; Guzei, I. A.; Stahl, S. S. J. Am. Chem. Soc. 2004, 126, 11268.
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V. J. Am. Chem. Soc. 2006, 128, 5818. (r) Shekhar, S.; Ryberg, P.;
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Buchwald, S. L. J. Am. Chem. Soc. 2006, 128, 3584. (s) Cochran,
B. M.; Michael, F. E. J. Am. Chem. Soc. 2008, 130, 2786. (t) Erhardt,
S.; Grushin, V. V.; Kilpatrick, A. H.; Macgregor, S. A.; Marshall,
W. J.; Roe, D. C. J. Am. Chem. Soc. 2008, 130, 4828. (u) Desai, L. V.;
Stowers, K. J.; Sanford, M. S. J. Am. Chem. Soc. 2008, 130, 13285.
1
2
3
4
5
6
7
8
9
PPh3
P(4-tolyl)3
P(4-MeOC6H4)3
P(4-CF3C6H4)3
P(3-tolyl)3
P(2-furyl)3
P(2-tolyl)3
P[3,5-(CF3)2C6H3]3
P[2,6-(MeO)2C6H3]3
P(2,4,6-Me3C6H2)3
100
100
100
91
100
92
15
3
11
12
13
14
PPh2Me
PMe2Ph
0
0
0
10
0
0
0
4
18
P(n-Bu)3
P(c-hexyl)3
15c dppe
16c dppb
17
18
19
P(OMe)3
P(OEt)3
P(OPh)3
0
0
10
a All reactions were carried out with olefin (6a) (0.20 mmol),
di-tert-butyldiaziridinone (5) (0.25 mmol), and Pd catalyst (0.020 mmol)
[prepared in situ from Pd(OAc)2 (0.020 mmol), phosphorus ligand
(0.080 mmol), n-butyllithium (0.040 mmol, 0.025 mL, 1.6
M in
hexanes) at room temperature] in benzene-d6 (0.20 mL) at 65 °C under
argon for 2 h unless otherwise stated. b Conversion was determined by
crude H NMR spectroscopy based on olefin. c Phosphorus ligand (0.040
1
mmol).
10 mol % Pd(PPh3)4 as catalyst, and di-tert-butyldiaziridinone
(5) as nitrogen source at 65 °C. As shown in Table 1, a number
of solvents27 are suitable for the diamination except CDCl3 and
CH3CN. Since Pd(PPh3)4 was found to be less soluble in solvents
such as hexanes or toluene, benzene was then typically used
for the diamination study.
A series of phosphorus ligands were examined for the
diamination of (E)-1,3-decadiene (6a) at 65 °C in dry benzene-
d6 using 10 mol % Pd complex as catalyst. Catalysts were
prepared in situ by treating Pd(OAc)2 with n-BuLi and
phosphorus ligands at room temperature.28 Studies showed that
monodentate triarylphosphines with exception of bulkier ones,
were effective ligands for the diamination (Table 2, entries 1-6
vs entries 7-10). However, phosphines containing one or more
alkyl groups, bidentate phosphine ligands, and phosphites were
found to be poor ligands for this diamination (Table 2, entries
11-19). Overall, PPh3 became the ligand of choice for the
diamination due to its effectiveness and low cost.
´
(v) Gordillo, A.; de Jesu´s, E.; Lo´pez-Mardomingo, C. J. Am. Chem.
Soc. 2009, 131, 4584. (w) Alvaro, E.; Hartwig, J. F. J. Am. Chem.
Soc. 2009, 131, 7858. (x) Barrios-Landeros, F.; Carrow, B. P.; Hartwig,
J. F. J. Am. Chem. Soc. 2009, 131, 8141.
(23) For asymmetric process of this diamination, see: (a) Du, H.; Yuan,
W.; Zhao, B.; Shi, Y. J. Am. Chem. Soc. 2007, 129, 11688. (b) Xu,
L.; Shi, Y. J. Org. Chem. 2008, 73, 749.
(24) For related Pd(0)-catalyzed intermolecular allylic and homoallylic C-
H diamination of terminal olefins using di-tert-butyldiaziridinone, see:
(a) Du, H.; Yuan, W.; Zhao, B.; Shi, Y. J. Am. Chem. Soc. 2007, 129,
7496. (b) Du, H.; Zhao, B.; Shi, Y. J. Am. Chem. Soc. 2008, 130,
8590.
(25) For Pd(0)-catalyzed dehydrogenative diamination of terminal olefins
using di-tert-butylthiadiaziridine 1,1-dioxide, see: Wang, B.; Du, H.;
Shi, Y. Angew. Chem., Int. Ed. 2008, 47, 8224.
The previously reported diamination procedure requires 10
mol % Pd(PPh3)4.19 Only 20% conversion was obtained for (E)-
(26) For Cu(I)-catalyzed intermolecular diamination with di-tert-butyldiaz-
iridinone and related compounds, see: (a) Yuan, W.; Du, H.; Zhao,
B.; Shi, Y. Org. Lett. 2007, 9, 2589. (b) Zhao, B.; Yuan, W.; Du, H.;
Shi, Y. Org. Lett. 2007, 9, 4943. (c) Zhao, B.; Du, H.; Shi, Y. Org.
Lett. 2008, 10, 1087. (d) Du, H.; Zhao, B.; Yuan, W.; Shi, Y. Org.
Lett. 2008, 10, 4231. (e) Wen, Y.; Zhao, B.; Shi, Y. Org. Lett. 2009,
11, 2365.
(27) All the solvents were dried according to standard drying procedures.
It was found that moisture in the solvent could lead to the decomposi-
tion of di-tert-butyldiaziridinone (5) and deactivation of the Pd catalyst.
(28) Trost, B. M.; Mignani, S. J. Org. Chem. 1986, 51, 3435.
9
J. AM. CHEM. SOC. VOL. 132, NO. 10, 2010 3525

A R T I C L E S
Zhao et al.
2. Monitoring the Diamination Reaction by 1H, 13C, and
31P NMR Spectroscopy. In an effort to gain a better understand-
ing of the diamination, the reaction was monitored by 1H NMR
spectroscopy. As shown in Figure 1, a new singlet peak at 1.59
ppm appeared when di-tert-butyldiaziridinone (5) was treated
with Pd(PPh3)4 in dry benzene-d6 at 40 °C. This singlet peak
(1.59 ppm) is corresponding to the signal of the tert-butyl groups
of intermediate A [the signal of the tert-butyl groups of di-tert-
butyldiaziridinone (5) appeared as a singlet at 1.05 ppm (Figure
1)]. After 85 min at 40 °C, all the di-tert-butyldiaziridinone (5)
was consumed, and the singlet peak at 1.59 ppm reached its
highest point. At that point, (E)-1-phenylbutadiene (6b) was
added, the signals of the tert-butyl groups of diamination product
7b appeared immediately as two singlet peaks at 1.32 and 1.36
ppm and gradually increased while the singlet peak at 1.59 ppm
gradually decreased. The diamination was practically complete
40 min after the addition of diene substrate 6b. As shown in
Figure 2, more electron-rich 1-methoxybutadiene (6g) was much
more reactive toward this diamination. The reaction between
intermediate A and the diene was finished in less than one
minute. These results indicate a two-step mechanism for the
Pd(PPh3)4-catalyzed diamination. Di-tert-butyldiaziridinone (5)
first reacts with Pd(PPh3)4 to form an active intermediate with
a singlet peak at 1.59 ppm (corresponding to the signal of its
tert-butyl groups), which subsequently reacts with the olefin
substrate to give the diamination product. The singlet peak at
1.59 ppm is consistent with the symmetry of four-membered
Pd(II) species A, whose structure is also supported by its 13C
NMR spectrum (177.3 ppm for CdO, 58.1 ppm for CMe3, and
33.6 ppm for Me, see Supporting Information).
Table 3. Diamination of Conjugated Dienes and a Triene with
Pd(PPh3)4
The reaction between Pd(PPh3)4 and di-tert-butyldiaziridinone
(5) (Scheme 7) was also monitored in situ by 31P NMR
spectroscopy. The reaction was carried out in benzene-d6 at 40
°C in an NMR tube, and 31P NMR spectra were collected at
room temperature for higher quality spectra. As shown in Figure
3, a new singlet at 19.8 ppm appeared and increased gradually
as more di-tert-butyldiaziridinone (5) was consumed. A broad
singlet between -4.3 pm and 17.1 ppm appeared as an averaged
spectrum of Pd(PPh3)m and PPh3 as a result of rapid ligand
exchange between Pd(PPh3)m and free PPh3 [PPh3 at -4.3 ppm,
Pd(PPh3)4 at 17.1 ppm)].29 As the reaction proceeded, and more
free PPh3 was released, the broad singlet moved upfield in the
direction of PPh3, and its intensity decreased gradually. After
85 min, di-tert-butyldiaziridinone (5) was completely consumed
as judged by 1H NMR spectroscopy, and the new singlet at 19.8
ppm in the 31P NMR spectrum reached the highest intensity.
The integration ratio of the singlet at 19.8 ppm to the broad
singlet at 7.2 ppm is 1:1.65 as shown in Figure 3, which is
smaller than the theoretical value (1:1). A possible reason is
that the partial decomposition of di-tert-butyldiaziridinone (5)
under the reaction conditions led to incomplete conversion of
Pd(PPh3)4 to intermediate A when 5 was consumed. At that
point, additional PPh3 or Pd(PPh3)4 was added to the reaction
mixture to monitor any changes of the signals. It was observed
that the broad 31P NMR singlet moved further upfield in the
direction of PPh3 upon addition of PPh3 and moved downfield
in the direction of Pd(PPh3)4 upon addition of Pd(PPh3)4. The
signal intensity increased in similar magnitude in both of the
cases as expected. The singlet at 19.8 ppm is consistent with
a Method
A (ref 19): All reactions were carried out with
di-tert-butyldiaziridinone (5) (0.20 mmol), olefin (E isomer, 0.24 mmol),
and Pd(PPh3)4 (0.02 mmol) in benzene-d6 (0.6 mL) in an NMR tube at
65 °C under argon for 0.25-5 h unless otherwise stated. For entry 3,
diene (E/Z ) 1/1, E isomer: 0.24 mmol). For more examples, see ref 19.
Method B: All reactions were carried out with olefin (0.80 mmol),
di-tert-butyldiaziridinone (5) (0.90 mmol, slow addition at a rate of 0.3
mmol/h), Pd(PPh3)4 (0.016 mmol) at 65 °C under solvent-free conditions
and argon for 4 h unless otherwise stated. For entry 2, benzene-d6 (0.10
mL) was used to dissolve diene. b Isolated yield based on 5 for Method
A and based on olefin for Method B. c Containing <10% Z isomer,
diamination product 7g is acid sensitive and was purified on less acidic
silica gel (Iatrobeads 6RS-8060, Mitsubishi Kagaku Iatron, Inc. Japan).
d Pd(PPh3)4 (1 mol %, 0.008 mmol) was used.
1-phenylbutadiene (6b) when the catalyst loading was reduced
to 5 mol %. It was surmised that the relatively high concentration
of di-tert-butyldiaziridinone (5) in the reaction system might
cause the deactivation of the Pd catalyst, and that slow addition
of 5 could lower its concentration and might be beneficial for
this diamination. It was indeed the case. As shown in Table 3,
the catalyst could be reduced to 2 mol % (even to 1 mol % as
illustrated in entry 7)17b when di-tert-butyldiaziridinone (5) was
added slowly via syringe pump (Method B). Various dienes and
a triene can be efficiently diaminated at 65 °C to give
diamination products with good to excellent yields (79-95%)
in high regio- and diastereoselectivity. Essentially only one
regio- and stereoisomer was obtained. Other regio- and stereo-
1
isomers were barely detectable by H NMR spectroscopy of
the crude reaction mixture if there was any. The yields obtained
with 2 mol % Pd(PPh3)4 (Method B) are comparable to the ones
obtained with the previous conditions (Method A) in most cases.
However, electron-deficient diene 6h, was not an effective
substrate for Method B (Table 3, entry 8).
(29) (a) Tolman, C. A.; Seidel, W. C.; Gerlach, D. H. J. Am. Chem. Soc.
1972, 94, 2669. (b) Mann, B. E.; Musco, A. J. Chem. Soc., Dalton
Trans. 1975, 1673.
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Pd(0)-Catalyzed Diamination of Conjugated Dienes
A R T I C L E S
1
Figure 1. Monitoring of the reaction of Pd(PPh3)4 with di-tert-butyldiaziridinone (5) and the subsequent diamination of (E)-1-phenylbutadiene (6b) by H
NMR spectroscopy. Pd(PPh3)4 (0.030 mmol) reacted with di-tert-butyldiaziridinone (5) (0.020 mmol) in dry benzene-d6 (0.6 mL) in an NMR tube under
argon atmosphere at 40 °C for 85 min, followed by the addition of (E)-1-phenylbutadiene (6b) (0.040 mmol). The NMR spectra were recorded at 40 °C.
Figure 2. Monitoring of the reaction of Pd(PPh3)4 with di-tert-butyldiaziridinone (5) and the subsequent diamination of (E)-1-methoxybutadiene (6g) by1H
NMR spectroscopy. Pd(PPh3)4 (0.030 mmol) reacted with di-tert-butyldiaziridinone (5) (0.02 mmol) in dry benzene-d6 (0.6 mL) in an NMR tube under
argon atmosphere at 40 °C for 85 min, followed by the addition of (E)-1-methoxybutadiene (6g) (E:Z ) 15.7:1, E isomer: 0.040 mmol). The NMR spectra
were recorded at 40 °C.
Scheme 7
ligand exchange between olefin 6 and the PPh3, then undergoes
migratory insertion to form π-allyl Pd intermediate C,33-35
(31) For leading references on metal insertion into N-N bonds, see: (a)
Erker, G.; Froemberg, W.; Krueger, C.; Raabe, E. J. Am. Chem. Soc.
1988, 110, 2400. (b) Kitamura, M.; Yanagisawa, H.; Yamane, M.;
the PPh3 signal of symmetric four-membered Pd(II) intermediate
A, generated from Pd(PPh3)4 and di-tert-butyldiaziridinone (5).
3. Kinetic Model for the Diamination. Based on the above
NMR spectroscopy studies, a detailed catalytic cycle for the
Pd(PPh3)4-catalyzed diamination is proposed in Scheme 8. The
14e species Pd(PPh3)2, generated from Pd(PPh3)4 by loss of two
PPh3 ligands,29,30 inserts into the N-N bond of di-tert-
butyldiaziridinone (5), giving four-membered Pd(II) species
A.31,32 Olefin-complex B, resulting from intermediate A via the
Narasaka, K. Heterocycles 2005, 65, 273. (c) Hoover, J. M.; DiPas-
quale, A.; Mayer, J. M.; Michael, F. E. Organometallics 2007, 26,
3297. (d) Hoover, J. M.; Freudenthal, J.; Michael, F. E.; Mayer, J. M.
Organometallics 2008, 27, 2238.
(32) The insertion of Ni and Pd to the N-N bond of diaziridinone has
been reported, see: Komatsu, M.; Tamabuchi, S.; Minakata, S.;
Ohshiro, Y. Heterocycles 1999, 50, 67. However, to the best of our
knowledge, the reaction of the resulting complex with an olefin has
not been reported.
(33) For a recent leading review on π-allyl Pd chemistry, see: Trost, B. M.
J. Org. Chem. 2004, 69, 5813.
(34) For a recent book on Pd, see: Tsuji, J. Palladium Reagents and
Catalysts: New PerspectiVe for the 21st Century: John Wiley & Sons
Ltd: New York, 2004.
(30) (a) Fauvarque, J.-F.; Pflu¨ger, F.; Troupel, M. J. Organomet. Chem.
1981, 208, 419. (b) Amatore, C.; Pflu¨ger, F. Organometallics 1990,
9, 2276.
(35) The precise understanding for the first C-N formation and the origin
of the observed high regioselectivity awaits further studies.
9
J. AM. CHEM. SOC. VOL. 132, NO. 10, 2010 3527

A R T I C L E S
Zhao et al.
Figure 3. Monitoring of the reaction between di-tert-butyldiaziridinone (5) (0.030 mmol) and Pd(PPh3)4 (0.030 mmol) by 31P NMR spectroscopy. The
reaction was carried out at 40 °C, and 31P NMR spectra were collected at room temperature (for higher quality spectra). “reaction mixture + PPh3”: additional
PPh3 (0.040 mmol) was added to the reaction mixture after 85 min. “reaction mixture + Pd(PPh3)4”: additional Pd(PPh3)4 (0.010 mmol) was added to the
reaction mixture after 85 min in a separate experiment.
Scheme 8. Proposed Catalytic Cycle for Pd(0)-Catalyzed
Diamination of Olefin
Scheme 9
diamination is first-order in total Pd(PPh3)4 and inverse first-
order in PPh3 (for derivation of eq 1, see Supporting Informa-
tion). If the Pd(0) insertion into the N-N bond of di-tert-
butyldiaziridinone (5) is the rate-determining step, the reaction
rate can be expressed with [Pd(PPh3)2] and [5] (eq 2). Based
on the quick pre-equilibria among Pd(PPh3)2, Pd(PPh3)3, and
Pd(PPh3)4, [Pd(PPh3)2] can be expressed with [Pd(PPh3)4]0 and
[PPh3]. Therefore, the reaction rate can be further expressed
with [Pd(PPh3)4]0, [PPh3], and [5] (eq 2) (for detailed derivation,
see Supporting Information), indicating first-order in total
Pd(PPh3)4 and di-tert-butyldiaziridinone (5) respectively, zero-
order in olefin 6, and inverse first-order in PPh3.
K2k1k2k3
[Pd(PPh3)4]0[5][6]
rate )
·
(1)
k2k3[6] + K2k1k-2[5]
[PPh3]
K2k1[Pd(PPh3)4]0[5]
rate ) k1[Pd(PPh3)2][5] )
) kobs[5]
(2)
[PPh3]
followed by reductive elimination to give diamination product
736 and regenerate the active catalyst Pd(PPh3)2.
4. Kinetic Studies for the Pd(PPh3)4-Catalyzed Diamination
with 1-Methoxybutadiene (6g). Using H NMR spectroscopy,
Ligand exchange between the Pd(PPh3)m and free PPh3 in
solution is very fast even at room temperature.29 Therefore, it
is reasonable to assume that there are two fast pre-equilibria
among Pd(PPh3)4, Pd(PPh3)3, and Pd(PPh3)2.30 According to the
literature, Pd(PPh3)4 in solution mainly exists as Pd(PPh3)3.29,30
Using steady-state approximation, the reaction rate for the
diamination can be expressed as eq 1, which indicates that the
1
kinetics studies of the diamination were carried out in benzene-
d6 with 10 mol % Pd(PPh3)4 as catalyst using Si(SiMe3)4 as
internal standard (Scheme 9). The diamination was run at 40
°C so that the reaction was slow enough to allow the data
collection. 1-Methoxybutadiene (6g) was chosen as substrate
for the kinetic experiment to avoid any interference with the
tert-butyl signals of di-tert-butyldiaziridinone (5) and the di-
amination product (7g) in the 1.0-2.0 ppm region. The
(36) It appears that the cyclization for the five-membered ring is kinetically
favored with no seven-membered ureas being observed.
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Pd(0)-Catalyzed Diamination of Conjugated Dienes
A R T I C L E S
Figure 4. Plots of concentrations of di-tert-butyldiaziridinone (5), diami-
nation product (7g), and their sum (5 + 7g) against the reaction time (min)
for the diamination of 1-methoxybutadiene (6g) (E:Z ) 15.7:1, E isomer:
0.24 mmol) with 5 (0.20 mmol) and Pd(PPh3)4 (0.020 mmol) in dry benzene-
d6 (1.2 mL) at 40 °C in an NMR tube.
Figure 5. Plot of ln([5]0/[5]) against the reaction time for the diamination
of 1-methoxybutadiene (6 g) (E:Z ) 15.7:1, E isomer: 0.24 mmol) with 5
(0.20 mmol) and Pd(PPh3)4 (0.020 mmol) in dry benzene-d6 (1.2 mL) in an
NMR tube at 40 °C. [5]0 stands for the initial concentration of 5 in M and
[5] stands for the concentration of 5 in M at a particular reaction time.
concentrations of 5 and diamination product 7g were determined
by integration of the signals corresponding to the respective
1
tert-butyl groups. As judged by H NMR spectroscopy, this
diamination was very clean and no side-reaction was observed
under the reaction conditions.
(a) Reaction Order in Di-tert-Butyldiaziridinone (5) for the
Diaminations. The diamination of 1-methoxybutadiene (6g) was
1
monitored by H NMR spectroscopy at 40 °C. The concentra-
tions of di-tert-butyldiaziridinone (5) and diamination product
(7g) at different reaction times were obtained via integration of
the signals corresponding to the respective tert-butyl groups.
The plots of the concentrations of 5 and 7g against the reaction
time are shown in Figure 4. No induction period was observed
for this reaction, suggesting that the active catalyst species
Pd(PPh3)2 is generated very quickly, then enters the catalytic
cycle. The sum of the concentrations of 5 and 7g remained
almost constant over the reaction time (Figure 4), indicating
that di-tert-butyldiaziridinone (5) was quantitatively converted
to diamination product 7g. The 31P NMR spectrum of the
reaction mixture is similar to that of Pd(PPh3)4, and no reaction
intermediates were observed from the 1H NMR spectrum,
indicating that the concentrations of Pd intermediates in the
catalytic cycle were very low during the reaction. A plot of
ln([5]0/[5]) against the reaction time gives a straight line with a
slope, kobs ) 8.2 × 10-4 s-1 (Figure 5), indicating first-order
kinetics in di-tert-butyldiaziridinone (5) for the diamination of
1-methoxybutadiene (6g).
(b) Effect of 1-Methoxybutadiene (6g) Concentration. Di-
aminations with different amounts of 6g were investigated with
10 mol % Pd(PPh3)4 at 40 °C. As shown in Figure 6, these
diaminations have similar reaction rates, indicating zero-order
kinetics in olefin 6g. All these results show that the diamination
is first-order in di-tert-butyldiaziridinone (5) and zero-order in
diene 6g as expressed in eq 2, which indicates that the Pd(0)
insertion into the N-N bond of di-tert-butyldiaziridinone (5)
is the rate-determining step for the diamination of 1-methoxy-
butadiene (6g).
Figure 6. Plots of the conversion of di-tert-butyldiaziridinone (5) against
the reaction time (min) for the diamination of 1-methoxybutadiene (6g)
with different initial olefin concentrations. The diaminations were carried
out with 6g (E:Z ) 15.7:1, E isomer: 0.12 mmol, 0.24 mmol, 0.47 mmol,
0.62 mmol, 0.94 mmol, or 1.25 mmol), di-tert-butyldiaziridinone (5) (0.40
mmol), and Pd(PPh3)4 (0.040 mmol) in dry benzene-d6 (1.2 mL) in an NMR
tube at 40 °C.
mixture should approximately equal to the sum of the initial
[Pd(PPh3)4] and [PPh3] added.30a The plot of 1/kobs against the
concentration of PPh3 was found to be a straight line as shown
in Figure 7, indicating the diamination is inverse first-order in
PPh3 ligand and also validating the approximation of the value
of [PPh3]free. This result is consistent with eq 2, which further
supports the reaction mechanism proposed in Scheme 8.
(d) Effect of Total Pd Concentration. Equation 2 indicates
that the diamination should be first-order in the total Pd catalyst.
In order to investigate the influence of Pd catalyst, the
diamination of 1-methoxybutadiene (6g) was investigated with
different amounts of Pd(PPh3)4 and fixed concentration of free
PPh3. The plot of kobs against [Pd(PPh3)4]0 was found to be a
straight line as shown in Figure 8, indicating the diamination is
first-order in total Pd catalyst as expressed in eq 2.
(c) Effect of PPh3 Concentration. According to eq 2, the
observed rate constant of the diamination (kobs) would be
inversely proportional to [PPh3]. The diaminations were carried
out at 40 °C with 10 mol % Pd(PPh3)4 and varying amounts of
PPh3. Since Pd(PPh3)3 is the main Pd species in the solution of
Pd(PPh3)4,29,30 the concentration of free PPh3 in the reaction
5. Effect of Olefin Structure. Thus far, studies have been
mainly focused on the diamination of 1-methoxybutadiene (6g),
which is zero-order in 6g under the diamination conditions.
Several other dienes and a triene were also examined, and the
results are shown in Figure 9. Alkyl diene 6a has a diamination
rate similar to that of 6g. The diamination was found to also be
9
J. AM. CHEM. SOC. VOL. 132, NO. 10, 2010 3529

A R T I C L E S
Zhao et al.
Scheme 10
the same reaction conditions. The reaction was no longer first
order in di-tert-butyldiaziridinone (5) possibly due to the side
reaction(s) and/or lower substrate reactivity. When more
substrate was used (3.5 equiv), the diamination rate of 6i was
similar to that of 6g. Significantly slower diamination was
observed for electron-deficient olefin 6h.
6. Studies on the Reaction of Olefins with Pd(II) Intermediate
A. To investigate the olefin reactivity toward intermediate A
(Scheme 8), the diaminations of various olefins were carried
out with preformed Pd(II) species A by treating di-tert-
butyldiaziridinone (5) with Pd(PPh3)4 (1.5 equiv) in dry benzene-
d6 in an NMR tube at 40 °C under argon atmosphere for 85
Figure 7. Plot of 1/kobs against the concentration of free PPh3 for the
diamination of 1-methoxybutadiene (6g) (E:Z ) 15.7:1, E isomer: 0.12
mmol) with di-tert-butyldiaziridinone (5) (0.10 mmol), Pd(PPh3)4 (0.010
mmol), and added PPh3 (0, 0.010, 0.030, 0.070, and 0.10 mmol, respectively)
in dry benzene-d6 (1.2 mL) in an NMR tube at 40 °C. The value of [PPh3]free
is corresponding to [PPh3]added + [Pd(PPh3)4]0.
1
min (Scheme 10). The reaction was monitored by H NMR
spectroscopy at 40 °C upon addition of olefins (2.0 equiv). As
shown in Figure 10, the reaction was influenced significantly
by the electronic and steric properties of the olefin. Electron-
rich olefins were more reactive toward complex A. 1-Methoxy-
butadiene (6g) was the most reactive for the diamination and
the reaction was finished in several seconds at 40 °C. Alkyl
dienes such as 6j and 6a were more reactive than aryl dienes
such as 6b and aliphatic triene 6i.
In the aforementioned kinetic studies with 1-methoxybuta-
diene (6g), little information was obtained about the details for
the reaction between the four-membered Pd(II) species A and
olefins because the rate-determining step was the insertion of
Pd(0) into the N-N bond of di-tert-butyldiaziridinone (5) and
the C-N bond formation occurred after the rate-determining
step. In order to get some insight into C-N bond formation, an
olefin with relatively low activity was needed for the kinetic
studies so that the rate of C-N bond formation is slower than
or competitive to the rate of the insertion of Pd into the N-N
bond of 5. (3E,5E)-Undeca-1,3,5-triene (6i) showed a relatively
low activity in the reaction with intermediate A (Figure 10).
Figure 8. Plot of kobs against [Pd(PPh3)4]0 for the diamination of
1-methoxybutadiene (6g) (E:Z ) 15.7:1, E isomer: 0.12 mmol) with di-
tert-butyldiaziridinone (5) (0.10 mmol), various amounts of Pd(PPh3)4
(0.010-0.030 mmol), and fixed amount of free PPh3 (0.040 mmol) in dry
benzene-d6 (1.2 mL) in an NMR tube at 40 °C. Additional PPh3
(0.030-0.010 mmol) was added to maintain the amount of PPh3 (0.040
mmol) in each reaction [PPh3 (added) ) 0.040 mmol - Pd(PPh3)4 (added)].
1
Intermediate A could be detected by H NMR spectroscopy
Figure 9. Plots of [7] against the reaction time for the diaminations of
different dienes or triene with di-tert-butyldiaziridinone (5) (0.20 mmol),
Pd(PPh3)4 (0.020 mmol) in dry benzene-d6 (1.2 mL) in an NMR tube at 40
°C. For 1-methoxybutadiene (6g): E:Z ) 15.7:1, E isomer: 0.24 mmol; for
(E)-1,3-decadiene (6a): 0.24 mmol; for (3E,5E)-undeca-1,3,5-triene (6i):
3.5 equiv (0.70 mmol), 1.2 equiv (0.24 mmol); for methyl 1,3-butadiene-
1-carboxylate (6h): E:Z ) 8.3:1, E isomer: 0.24 mmol.
Figure 10. Plots of [7] against the reaction time for the reactions between
Pd(II) intermediate A and different dienes or triene (6) (E isomer: 0.040
mmol) in dry benzene-d6 (0.6 mL) at 40 °C in an NMR tube. For
1-methoxybutadiene (6g): E:Z ) 15.7:1, E isomer: 0.040 mmol; for (E)-
1,3-pentadiene (6j): 0.040 mmol; for (E)-1,3-decadiene (6a): 0.040 mmol;
for (E)-1-phenylbutadiene (6b): 0.040 mmol; for (3E,5E)-undeca-1,3,5-triene
(6i): 0.040 mmol; for methyl 1,3-butadiene-1-carboxylate (6h): E:Z ) 8.3:
1, E isomer: 0.040 mmol. Compound A was prepared by reacting di-tert-
butyldiaziridinone (5) (0.020 mmol) with Pd(PPh3)4 (0.030 mmol) in dry
benzene-d6 (0.6 mL) at 40 °C in an NMR tube for 85 min.
first-order in 5. The diamination of triene 6i was found to be a
little slower but with some unidentified side reaction(s) under
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3530 J. AM. CHEM. SOC. VOL. 132, NO. 10, 2010

Pd(0)-Catalyzed Diamination of Conjugated Dienes
A R T I C L E S
Scheme 11
diamination. The dilithium salt 8 generated from di-tert-
butylurea and n-BuLi was treated with a mixture of Pd(OAc)2-
PPh3 (1:2) and diene 6j (Scheme 11). At the end of the reaction,
the palladium complex was removed by filtration, and diami-
nation product 7j was isolated by flash chromatography on silica
gel in 38% yield. The diamination occurred regioselectively at
the internal double bond, suggesting that the reaction proceeded
via four-membered Pd(II) intermediate A. The regioselectivity
obtained in this case is different from the Pd(II)-catalyzed
terminal diamination of diene with urea as previously reported
by Lloyd-Jones, Booker-Milburn, and co-workers,8 illustrating
that the current diamination proceeds via a completely different
reaction mechanism. While the reaction efficiency needs to be
improved and a catalytic process needs to be developed, the
diamination process using a urea salt described in Scheme 11
is very encouraging, which could open up a new approach to
the diamination. Further study on this subject is in progress.
Figure 11. Plots of 1/[A] against [6i]/[5] for the diaminations of (3E,5E)-
undeca-1,3,5-triene (6i) (0.20 mmol) with di-tert-butyldiaziridinone (5) (0.10
mmol), Pd(PPh3)4 (0.020 mmol), and different amounts of PPh3 added (0
mmol; 0.020 mmol; 0.050 mmol) in dry benzene-d6 (1.2 mL) at 40 °C in
an NMR tube.
during the reaction when 6i was subjected to the catalytic
diamination conditions, which provides an opportunity to get
some insight into the C-N bond formation. Using pre-
equilibrium and steady-state approximations, the concentration
of intermediate A for the diamination is expressed in eq 3 (see
Supporting Information). The corresponding reciprocal of eq 3
is shown as eq 4, which indicates that the plot of 1/[A] against
[6]/[5] should be a straight line and PPh3 would have little
impact on the slope. Diamination of 6i was carried out with 20
mol % Pd(PPh3)4 and varying amounts of PPh3 added in an
NMR tube at 40 °C. The data of [A], [5], and [6i] were collected
for the plot after the reaction reached steady state (∼20%
conversion of 5). As shown in Figure 11, the plot of 1/[A]
against [6i]/[5] gives three almost overlapped straight lines with
different amounts of PPh3 present in the reaction, illustrating
that PPh3 has little impact on [A] as expected based on eq 4.
These results support that the reaction between intermediate A
and the olefin proceeds via the pathway proposed in Scheme 8.
One PPh3 ligand in intermediate A is substituted by olefin 6
via ligand exchange to form olefin complex B before the C-N
formation. This proposed pathway is consistent with the
observation that no diamination was observed with bidentate
phosphorus ligands (Table 2, entries 15 and 16). According to
the proposed pathway, one ligand is still attached to the Pd
during the C-N bonds formation, providing opportunities for
asymmetric induction with a chiral ligand. High enantioselec-
tivity has indeed been achieved for this diamination with a
BINOL-tetramethylpiperidine based phosphorus amidite ligand.23a
Conclusions
Various conjugated dienes and a triene can be efficiently
diaminated with high yields and high regio- and diastereo-
selectivity using Pd(PPh3)4 as catalyst and di-tert-butyldiaz-
iridinone (5) as nitrogen source. The catalyst loading was
reduced to 1-2 mol % by slowly adding di-tert-butyldiaz-
iridinone (5) under solvent-free conditions. A detailed
catalytic pathway has been proposed based on the NMR
spectroscopy and kinetic studies (Scheme 8). The Pd(0)
[likely Pd(PPh3)2] first inserts into the N-N bond of di-tert-
butyldiaziridinone (5) to form a symmetric four-membered
1
Pd(II) intermediate (A), which can be detected by H, 13C,
and 31P NMR spectroscopy. This four-membered Pd(II)
intermediate forms an olefin complex (B) via ligand exchange
between the olefin substrate and the PPh3. The resulting Pd-
diene complex (B) undergoes migratory insertion into the
internal double bond to form a π-allyl Pd intermediate (C),
which gives the diamination product and regenerates the
Pd(0) catalyst after reductive elimination. For reactive
substrates such as 1-methoxybutadiene (6g) and alkyl dienes,
kinetic studies show that the diamination is first-order in di-
tert-butyldiaziridinone (5) and the Pd(0) catalyst, zero-order
in the olefin substrate, and inverse first-order in PPh3, which
is consistent with the fact that the Pd(0) insertion into the
N-N bond of di-tert-butyldiaziridinone (5) is the rate-
determining step. Further studies show that the four-
membered Pd(II) complex generated from Pd(OAc)2 and
dilithium salts of di-tert-butylurea can also regioselectively
diaminate the internal double bond of a diene although the
reaction efficiency needs to be improved. This result further
validates the four-membered Pd(II) intermediate in the
K2k1k-2[5]
[A] )
[Pd(PPh3)4]0
(3)
(4)
K2k1k-2[5] + k2k3[6]
k2k3
1
[A]
[6]
1
)
·
+
K2k1k-2[Pd(PPh3)4]0 [5]
[Pd(PPh3)4]0
7. Diamination with Urea. The above studies show that the
four-membered Pd(II) species A resulting from the Pd(0)
insertion into the N-N bond of di-tert-butyldiaziridinone 5 is
an active intermediate for the diamination of dienes. It has been
reported that some four-membered Pd(II) species can be
generated by reacting PdX2 with dilithium salts of ureas,37 which
prompted us to investigate if such a process could be used for
9
J. AM. CHEM. SOC. VOL. 132, NO. 10, 2010 3531

A R T I C L E S
Zhao et al.
proposed catalytic pathway and opens up new opportunities
for diamination using urea salts. The studies presented in
this work provide a better understanding of the Pd(0)-
catalyzed diamination process and will facilitate further
development of more effective diamination systems.
Supporting Information Available: The procedures for di-
amination, NMR spectroscopy studies, and kinetic studies along
with the kinetic analysis. This material is available free of charge
via the Internet at http://pubs.acs.org.
JA909459H
Acknowledgment. We are grateful to the generous financial
support from the General Medical Sciences of the National Institutes
of Health (GM083944-02).
(37) For a leading reference, see: Paul, F.; Fischer, J.; Ochsenbein, P.;
Osborn, J. A. C. R. Chimie 2002, 5, 267.
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3532 J. AM. CHEM. SOC. VOL. 132, NO. 10, 2010