Carbon-nitrogen bond-forming reactions of palladacycles with hypervalent iodine reagents

Article abstract of DOI:10.1021/om061052l

Palladium(II) complexes containing bidentate cyclometalated C-N chelating ligands are shown to react with PhI=NTs at room temperature to insert "NTs" into the Pd-C bond. This "NTs" insertion reaction has been applied to palladacyclic complexes of azobenze

Full text of DOI:10.1021/om061052l

Organometallics 2007, 26, 1365-1370
1365
Carbon-Nitrogen Bond-Forming Reactions of Palladacycles with
Hypervalent Iodine Reagents
Allison R. Dick, Matthew S. Remy, Jeff W. Kampf, and Melanie S. Sanford*
Department of Chemistry, UniVersity of Michigan,
930 North UniVersity AVenue, Ann Arbor, Michigan 48109
ReceiVed NoVember 15, 2006
Palladium(II) complexes containing bidentate cyclometalated C∼N chelating ligands are shown to
react with PhIdNTs at room temperature to insert “NTs” into the Pd-C bond. This “NTs” insertion
reaction has been applied to palladacyclic complexes of azobenzene, benzo[h]quinoline, and 8-eth-
ylquinoline. The newly aminated organic ligands can be liberated from the metal center by protonolysis
with trifluoroacetic acid or HCl.
of activated and/or weak C-H bonds (e.g., tertiary, secondary,
benzylic, or C-H bonds R to heteroatoms).2
Introduction
Compounds containing carbon-nitrogen bonds are of great
importance in many areas of chemistry, and as a result,
transition metal catalyzed approaches to C-N bond formation
have been the subject of intense recent research. In particular,
Pd- and Cu-catalyzed aminations of aryl halides have proven
to be powerful and widely used synthetic methods for the
construction of arylamines.1 However, despite their great utility,
these transformations remain fundamentally limited by the fact
that the aryl coupling partner must be prefunctionalized with a
halide at the desired position, which increases the number of
steps required in a synthetic sequence.
An alternative approach to the synthesis of amines would be
the direct conversion of C-H bonds into C-N bondssan
attractive transformation from the standpoints of atom economy
and synthetic simplicity.2 Several effective methods for the intra-
and intermolecular amination of sp3 C-H bonds have been
developed, and these typically utilize rhodium carboxylate,
copper homoscorpionate, or metalloporphyrin based catalysts
in conjunction with either PhIdNR or PhI(OAc)2/MgO/RNH2
as the aminating reagent.3 The mechanism of these transforma-
tions generally involves direct insertion of a metallonitrene into
the C-H bond. As a result, the observed selectivities typically
parallel those of radical reactions, with preferential amination
Our group and others have developed a number of Pd-
catalyzed processes for converting C-H bonds into C-O,4
C-halogen,4a,5 and C-C bonds6 using iodine(III) reagents as
terminal oxidants. In contrast to the aminations described above,
these transformations proceed via C-H activation to form
discrete organometallic palladacyclic intermediates.7 As such,
selectivity is dictated by proximity to a directing group and by
steric effects, rather than by the strength/degree of activation
of the C-H bonds. We have had a longstanding interest in
extending these reactions to C-N bond formation, because such
a transformation could serve as a valuable complement to both
the amination of aryl halides and the metallonitrene insertion
reactions described above. This report describes the development
of a method for PdII-mediated oxidative C-H bond amination.8,9
We demonstrate that diverse palladacyclic complexes (which
were all initially formed by directed C-H activation) undergo
stoichiometric amination reactions with PhIdNTs and related
(4) (a) Kalberer, E. W.; Whitfield, S. R.; Sanford, M. S. J. Mol. Catal.
A 2006, 251, 108-113. (b) Kalyani, D.; Sanford, M. S. Org. Lett. 2005, 7,
4149-4152. (c) Desai, L. V.; Hull, K. L.; Sanford, M. S. J. Am. Chem.
Soc. 2004, 126, 9542-9543. (d) Dick, A. R.; Hull, K. L.; Sanford, M. S.
J. Am. Chem. Soc. 2004, 126, 2300-2301. (e) Yoneyama, T.; Crabtree, R.
H. J. Mol. Catal. A 1996, 108, 35-40.
(5) (a) Kalyani, D.; Dick, A. R.; Anani, W. Q.; Sanford, M. S.
Tetrahedron 2006, 62, 11483-11498. (b) Kalyani, D.; Dick, A. R.; Anani,
W. Q.; Sanford, M. S. Org. Lett. 2006, 8, 2523-2526. (c) Hull, K. L.;
Anani, W. Q.; Sanford, M. S. J. Am. Chem. Soc. 2006, 128, 7134-7135.
(d) Giri, R.; Chen, X.; Yu, J.-Q. Angew. Chem., Int. Ed. 2005, 44, 2112-
2115.
(6) (a) Deprez, N. R.; Kalyani, D.; Krause, A.; Sanford, M. S. J. Am.
Chem. Soc. 2006, 128, 4972-4973. (b) Kalyani, D.; Deprez, N. R.; Desai,
L.V.; Sanford, M. S. J. Am. Chem. Soc. 2005, 127, 7330-7331. (c)
Daugulis, O.; Zaitsev, V. G. Angew. Chem., Int. Ed. 2005, 44, 4046-4048.
(7) For mechanistic investigations into these transformations, see: (a)
Dick, A. R.; Kampf, J. W.; Sanford, M. S. J. Am. Chem. Soc. 2005, 127,
12790-12791. (b) Dick, A. R.; Kampf, J. W.; Sanford, M. S. Organome-
tallics 2005, 24, 482-485.
(8) For recent examples of the catalytic conversion of C-H bonds to
C-N bonds, see the following. (a) Cu catalysis: Chen, X.; Hao, X.-S.;
Goodhue, C. E.; Yu, J.-Q. J. Am. Chem. Soc. 2006, 128, 6790-6791. (b)
Cu catalysis: Uemura, T.; Imoto, S.; Chatani, N. Chem. Lett. 2006, 35,
842-843. (c) PdII/0 catalysis: Tsang, W. C. P.; Zheng, N.; Buchwald, S.
L. J. Am. Chem. Soc. 2005, 127, 14560-14561.
(9) While our work was in progress, a related Pd-catalyzed, directed C-H
bond amination reaction using K2S2O8/NRH2 was reported: Thu, H.-Y.;
Yu, W.-Y.; Che, C.-M. J. Am. Chem. Soc. 2006, 128, 9048-9049.
* To whom correspondence should be addressed. E-mail:
mssanfor@umich.edu.
(1) For a review on Pd-catalyzed amination of aryl halides, see: Muci,
A. R.; Buchwald, S. L. Top. Curr. Chem. 2002, 219, 131-209. For recent
examples of Cu-catalyzed amination reactions, see: (a) Zhu, D.; Wang,
R.; Mao, J.; Xu, L.; Wu, F.; Wan, B. J. Mol. Catal. A 2006, 256, 256-
260. (b) Yeh, V. S. C.; Wiedeman, P. E. Tetrahedron Lett. 2006, 47, 6011-
6016. (c) Shafir, A.; Buchwald, S. L. J. Am. Chem. Soc. 2006, 128, 8742-
8743.
(2) For a relevant review, see: Dick, A. R.; Sanford, M. S. Tetrahedron
2006, 62, 2439-2463 and references therein.
(3) For a recent review, see: Espino, C. G.; Du Bois, J. Modern Rhodium-
Catalyzed Organic Reactions; Wiley: New York, 2005; pp 379-416. For
selected examples, see: (a) Fructos, M. R.; Trofimenko, S.; Diaz-Requejo,
M. M.; Perez, P. J. J. Am. Chem. Soc. 2006, 128, 11784-11791. (b) Liang,
C.; Robert-Peillard, F.; Fruit, C.; Muller, P.; Dodd, R. H.; Dauban, P. Angew.
Chem., Int. Ed. 2006, 45, 4641-4644. (c) Espino, C. G.; Fiori, K. W.;
Kim, M.; Du Bois, J. J. Am. Chem. Soc. 2004, 126, 15378-15379. (d) He,
L.; Chan, P. W. H.; Tsui, W.-M.; Yu, W.-Y.; Che, C.-M. Org. Lett. 2004,
6, 2405-2408. (e) Espino, C. G.; Wehn, P. W.; Chow, J.; Du Bois, J. J.
Am. Chem. Soc. 2001, 123, 6935-6936. (f) Espino, C. G.; Du Bois, J.
Angew. Chem., Int. Ed. 2001, 40, 598-600. (g) Yu, X.-Q.; Huang, J.-S.;
Zhou, X.-G.; Che, C.-M. Org. Lett. 2000, 2, 2233-2236. (h) Breslow, R.;
Gellman, S. H. J. Am. Chem. Soc. 1983, 105, 6728-6729.
10.1021/om061052l CCC: $37.00 © 2007 American Chemical Society
Publication on Web 02/16/2007

1366 Organometallics, Vol. 26, No. 6, 2007
Dick et al.
Scheme 1. Double Amination of Palladacycle 1
oxidants.10 Investigations of the scope of these reactions as well
as mechanistic insights into the key “NTs” insertion step are
described below.
Results and Discussion
Our initial studies focused on demonstrating the feasibility
of the stoichiometric oxidative amination of palladacycles
(complexes that are typically formed via directed C-H activa-
tion reactions). We selected PhIdNTs11 as the amination reagent
on the basis of (i) our previous success using hypervalent iodine
compounds in Pd-catalyzed C-H functionalization reactions and
(ii) literature precedent for the insertion of “O” into Pd-C
Figure 1. ORTEP diagram for complex 3. H atoms are not shown.
Selected bond distances (Å): Pd-N1 ) 2.020, Pd-N2 ) 1.931,
Pd-N4 ) 1.968, Pd-O3 ) 2.279. Selected bond angles (deg):
N2-Pd-N1 ) 82.7, N2-Pd-N4 ) 93.1, N4-Pd-N1 ) 175.3,
N1-Pd-O3 ) 118.5, N4-Pd-O3 ) 65.8, N2-Pd-O3 ) 158.5.
bonds
using
the
analogous
iodine(III)
oxidant
ArIdO.12 The chloride-bridged azobenzene dimer 1 was chosen
as the initial substrate, because its reactivity with ArIdO had
been explored previously.12
Scheme 2. Proposed Mechanism of Formation of Product 3
When 1 was treated with 2 equiv of PhIdNTs (1 equiv per
Pd) in MeCN at room temperature, the initially bright orange
heterogeneous mixture gradually became deep purple over the
course of 12 h. 1H NMR analysis of the crude reaction showed
significant quantities of unreacted starting material along with
a complex mixture of products, and the major product (3) was
isolated from this mixture via preparative TLC. Interestingly,
this dark purple solid was not the expected monoaminated
1
palladacycle 2. Instead, H NMR spectroscopy revealed the
presence of resonances associated with two inequivalent NTs
groups. As shown in Scheme 1, these data suggested that 2 equiv
of the iodine(III) reagent was required to form the observed
product (3). Indeed, when the stoichiometry of the reaction was
adjusted (such that 2 equiv of PhIdNTs were added per 1 equiv
planar complex is occupied by a sulfonyl oxygen atom.14 As
summarized in Scheme 2, we believe that 3 is formed by (i)
initial “NTs” insertion into the Pd-C bond, (ii) decoordination,
σ-bond rotation, and recoordination to the other nitrogen atom
of the azo linkage to form a more favorable five-membered
palladacycle, (iii) ortho C-H activation of the adjacent ring,
and (iv) a second “NTs” insertion event to afford the final
product.
We next turned our attention to palladacycles of benzo[h]-
quinoline, which do not offer the possibility for a second ortho
C-H activation event. A series of cyclometalated benzo[h]-
quinoline complexes, including the acetate-bridged dimer 4, the
chloride-bridged dimer 5, and the in situ generated monomeric
pyridine complexes 6 and 7 (Figure 2), were treated with 1.3
equiv of PhIdNTs in MeCN. The crude reactions were then
evaporated to dryness, treated with CDCl3 containing 25%
C5D5N (in order to convert any halide- and/or acetate-bridged
PdII products to more readily detectable monomers), and assayed
1
of Pd), the H NMR yield of 3 nearly doubled (from 19% to
32%). When the amount of PhIdNTs was further increased to
4-5 equiv per [Pd], the starting material was almost completely
consumed, and product 3 was obtained in 50% yield by 1H NMR
spectroscopy (4 equiv) and 18% isolated yield (5 equiv).13
Crystals of 3 suitable for X-ray crystallographic analysis were
obtained by slow diffusion of pentane into a chlorobenzene
solution of 3 at room temperature, and a labeled view of the
structure is shown in Figure 1. As anticipated on the basis of
1
the H NMR spectral data, 3 contains a PdII center ligated by
two different NTs ligands and one nitrogen of the azobenzene.
In the solid state, the fourth coordination site of this square-
(10) Mahy, J. P.; Battioni, P.; Bedi, G.; Mansuy, D.; Fisher, J.; Weiss,
R.; Morgenstern-Badarau, I. Inorg. Chem. 1988, 27, 353-359.
(11) These iminoiodinane reagents are commonly used in the metal-
catalyzed aziridination of olefins. In addition, analogous reagents are
believed to form in situ in the amination reactions discussed in ref 3. For
a relevant review, see: Halfen, J. A. Curr. Org. Chem. 2005, 9, 657-669.
(12) Bhawmick, R.; Biswas, H.; Bandyopadhyay, P. J. Organomet. Chem.
1995, 498, 81-83.
(14) In solution, coordinated water is observed by 1H NMR spectroscopy
as a broad singlet, whose chemical shift varies significantly with concentra-
tion. Addition of ∼2 equiv of pyridine to an NMR sample displaying one
such singlet resulted in new peaks for both free and metal-bound pyridine.
A new signal also appeared at ∼1.6 ppm, consistent with free H2O liberated
from the metal center. See the Supporting Information for full details.
(13) Purification of this compound required both a basic extractive
workup and multiple chromatographic separations. Complex 3 appears to
be unstable under both of these conditions, resulting in low isolated yields.

C-N Bond-Forming Reactions of Palladacycles
Organometallics, Vol. 26, No. 6, 2007 1367
Scheme 3. Amination of the Benzo[h]quinoline Palladacycle
7a
Figure 2. Benzo[h]quinoline complexes examined in amination
reactions.
a Legend: (a) 8.0 equiv of pyridine (Py), THF, room temperature;
(b) 1.3 equiv of PhIdNTs, THF, room temperature, 78% yield.
Table 1. Major Products Observed in Reactions of 4-7 with
PhIdNTs
Figure 3. ORTEP diagram for complex 8b. H atoms are not shown.
Selected bond distances (Å): Pd-N1 ) 2.050, Pd-N2 ) 1.997,
Pd-N3 ) 2.026, Pd-Cl ) 2.3277. Selected bond angles (deg):
N2-Pd-N1 ) 86.84, N2-Pd-N3 ) 89.14, N3-Pd-N1 )
175.97, N1-Pd-Cl ) 93.67, N3-Pd-Cl ) 90.30, N2-Pd-Cl
) 175.04.
entry
complex
product (yield, %)
product (yield, %)
1
2
3
4
4a
5a
6a
7
8a (31)
8b (9)
8a (16)
8b (51)
9a (<2)
9b (18)
9a (5)
9b (<2)
Scheme 4. Amination of Palladacycle 7 with Electronically
Diverse Oxidants
a Significant quantities of additional unidentified inorganic and organic
side products were observed.
by 1H NMR spectroscopy. With the PdII starting materials 4-6,
this sequence afforded a complex and largely inseparable
mixture of inorganic and organic compounds. However, in all
three cases, significant quantities (9-31%) of the desired “NTs”
insertion product 8a or 8b were formed. These PdII complexes
1
were identified in the crude H NMR spectra, by comparison
to independently synthesized samples of 8a/8b. Interestingly,
the organic products 9a/9b, which result from C-X coupling
(X ) Cl, OAc, depending on the counterion associated with
the starting Pd complex), could also be identified in some of
these reactions.4d As summarized in Table 1, these chlorinated
and/or acetoxylated organic products were formed in yields of
up to 18%, and the formation of substantial quantities of these
organic side products was inversely correlated to the yield of
the desired “NTs” insertion product.
In contrast to the reactions of 4-6, the monomeric chloride
complex 7 reacted with PhIdNTs to produce a single major
inorganic product (8b) in 51% yield (based on 1H NMR
spectroscopy of the crude reaction mixture), and complex 8b
was isolated as a yellow solid in 42% yield. The isolated yield
could be improved to 78% when the reaction was conducted in
THF (Scheme 3). Notably, the C-Cl bond-forming reductive
elimination product 9b was not observed in this transformation.
The structure of 8b was confirmed by 1H NMR spectroscopy,
which clearly showed the incorporation of a single NTs moiety
into the starting complex. In addition, crystals suitable for X-ray
analysis were obtained by slow diffusion of ether into a
chlorobenzene solution of 8b, and the solid-state structure of
8b is shown in Figure 3. In this square-planar palladium(II)
complex, the chloride ligand resides trans to the new NTs moiety
and the pyridine trans to the nitrogen atom of the benzoquinoline
ligand. The Pd-N and Pd-Cl bond lengths are comparable to
those found in related complexes,15 and, as expected, the bond
to the anionic nitrogen is the shorter of the two Pd-N bonds
(1.997 versus 2.050 Å). The most remarkable feature of this
structure is a face-to-face interaction between the aryl ring of
the Ts group and the benzoquinoline ligand. Interestingly, this
interaction twists the rigid benzoquinoline significantly out of
planarity (τN1-C13-C12-C11 ) 14.9(7)°).
The reactions of the in situ generated palladacycle 7 with
hypervalent iodide oxidants derived from electronically diverse
benzenesulfonamides were also explored. As summarized in
Scheme 4, these transformations proceeded in modest to good
yields with oxidants containing both electron-donating and
electron-withdrawing substituents on the aryl group of the
sulfonamide. When the rates of sulfonamide insertion into
isolated monomer 716 were measured under identical reaction
conditions, the formation of 8b was found to proceed to
completion within 30 min, while the reactions to form 10a and
10b required 2 and 2.5 h, respectively, to reach complete
(15) (a) Bugarcˇic´, Z., D.; Liehr, G.; van Eldik, R. Dalton Trans. 2002,
951-956. (b) Peters, J. C.; Harkins, S. B.; Brown, S. D.; Day, M. W. Inorg.
Chem. 2001, 40, 5083-5091.
(16) Cockburn, B. N.; Howe, D. V.; Keating, B. F.; Johnson, B. F. G.;
Lewis, J. J. Chem. Soc., Dalton Trans. 1973, 404-410.

1368 Organometallics, Vol. 26, No. 6, 2007
Dick et al.
Scheme 5. Amination of 8-Ethylquinoline Palladacycle 11
Scheme 6. Possible Mechanisms for Insertion of “NTs” into
the Pd-C Bond
ates in the reactions of Pd-C bonds with both inorganic and
organic peroxides.19 Finally, the observation of organic side
products 9a, 9b, and 13 resulting from C-X coupling (X )
OAc, Cl) is also consistent with a mechanism involving PdIV
intermediates. Both C-OAc7a and C-Cl5a,b,20 bond-forming
reductive elimination have been shown to be facile from PdIV
centers; in contrast, analogous reactions at PdII complexes are
generally kinetically slow and/or thermodynamically unfavor-
able.21,22 As such, we hypothesize that 9b and 13 are generated
by a C-Cl coupling reaction from intermediate I that is
competitive with “NTs” insertion into the Pd-C bond.
conversion. However, it is difficult to draw definitive mecha-
nistic conclusions from these kinetic data, due to the dramatically
varied solubilities of these iodine(III) aminating reagents as well
as their susceptibility toward hydrolysis under the reaction
conditions.
With optimal conditions for the NTs insertion reaction in
hand, we next sought to liberate the newly aminated organic
ligands from the Pd center via protonoloysis of the Pd-N bond.
A series of acidic reaction conditions were examined to achieve
this goal, and the results are reported in Table 2. Interestingly,
no C-N bond cleavage was observed in neat AcOH at room
temperature or at 100 °C (Table 2, entries 1 and 2). In contrast,
neat trifluoroacetic acid afforded appreciable (∼15%) conversion
to product 8b′ at room temperature (entry 3). The addition of 5
equiv of HCl resulted in quantitative cleavage of the Pd-N bond
to afford 8b′ (entry 5), and analogous conditions were also
effective for the release of 3′ from complex 3 (entry 6) and of
12′ from complex 12 (entry 7). Notably, with the success of
these protonolysis reactions, we have established the feasibility
of the three elementary stepss(i) cyclopalladation, (ii) oxidative
amination, and finally (iii) protonolysissrequired for Pd-
catalyzed directed oxidative C-H amination reactions.
In conclusion, this report has described a new mild reaction
for the stoichiometric conversion of C-H bonds into amines
via palladacyclic intermediates. This transformation is proposed
to proceed via a stepwise mechanism involving a PdIV-imido
intermediate. Efforts to achieve catalytic C-N bond formation
via this pathway are ongoing in our laboratories. Notably, while
this work was in progress, Che and co-workers reported a related
Analogous NTs insertion reactions were also examined with
palladacycles containing sp3 Pd-C bonds. For example, the
8-ethylquinoline complex 11 reacted with 1.3 equiv of
PhIdNTs to afford 12 in 9% yield (as determined by 1H NMR
spectroscopy) along with a number of unidentified Pd-containing
species (Scheme 5). Interestingly, the C-Cl bond-forming
reductive elimination product 13 was identified as the major
organic byproduct of this reaction. Removal of the chloride
ligand from 11 with AgOTf prior to addition of the oxidant
eliminated this competing transformation and increased the 1H
NMR yield of aminated palladacycle 12 to 19%.17
There are at least two possible mechanisms for the “NSO2-
Ar” insertion reactions: a stepwise process (Scheme 6, mech-
anism A) and a concerted pathway (Scheme 6, mechanism B).
The stepwise mechanism would involve (i) initial nucleophilic
attack of the Pd(II) center on PhIdNTs, (ii) loss of PhI to form
a discrete Pd(IV) imido intermediate (I), and (iii) collapse of
this intermediate to afford the insertion product. Alternatively,
the concerted process would proceed by a transition state
involving a three-centered interaction between the Pd(II) center,
the bound carbon, and the “NTs” group (III in Scheme 6).
While these two mechanisms are difficult to definitively
distinguish from one another, we currently favor mechanism A
for several reasons. First, the closely related reaction of
ArIdO with palladacycles has been proposed to proceed via a
stepwise mechanism similar to A.18 In addition, PdIV-oxo
intermediates analogous to I have been proposed as intermedi-
(19) (a) Valk, J.-M.; Boersma, J.; van Koten, G. Organometallics 1996,
15, 4366-4372. (b) Alsters, P. L.; Teunissen, H. T.; Boersma, J.; Spek, A.
L.; van Koten, G. Organometallics 1993, 12, 4691-4696.
(20) (a) Alsters, P. L.; Engel, P. F.; Hogerheide, M. P.; Copijn, M.; Spek,
A. L.; van Koten, G. Organometallics 1993, 12, 1831-1844. (b) Lagunas,
M.; Gossage, R. A.; Spek, A. L.; van Koten, G. Organometallics 1998, 17,
731-741. (c) Fahey, D. R. J. Organomet. Chem. 1971, 27, 283-292.
(21) For C-Cl bond-forming reductive elimination from PdII, see: (a)
Roy, A. H.; Hartwig, J. F. J. Am. Chem. Soc. 2001, 123, 1232-1233. (b)
Roy, A. H.; Hartwig, J. F. J. Am. Chem. Soc. 2003, 125, 13944-13945.
(22) For studies of the electronic requirements of C-O bond-forming
reductive elimination from PdII, see: (a) Widenhoefer, R. A.; Buchwald,
S. L. J. Am. Chem. Soc. 1998, 120, 6504-6511. (b) Widenhoefer, R. A.;
Zhong, H. A.
(17) Significant quantities of (py)2PdCl2 were also identified by 1H NMR
in both the crude reaction mixture and partially purified samples (Rajput,
J.; Moss, J. R.; Hutton, A. T.; Hendricks, D. T.; Arendse, C. E.; Imrie, C.
J. Organomet. Chem. 2004, 689, 1553-1568). The origin of its formation
is unclear at this time, but we believe it contributes significantly to the low
yield.
(18) (a) Kamaraj, K.; Bandyopadhyay, D. Organometallics 1999, 18,
438-446. (b) Kamaraj, K.; Bandyopadhyay, D. J. Am. Chem. Soc. 1997,
119, 8099-8100.

C-N Bond-Forming Reactions of Palladacycles
Organometallics, Vol. 26, No. 6, 2007 1369
Table 2. Acid Cleavage To Release the Aminated Ligands
was performed on EMD TLC plates pre-coated with 250 µm
thickness silica gel 60 F254. Preparative TLC was performed on
Whatman PK6F silica gel plates (60 Å, 500 µm layer thickness).
Product 3. Complex 1 (150.0 mg, 0.23 mmol, 1 equiv) was
suspended in MeCN (15 mL), and PhIdNTs (700.0 mg, 1.9 mmol,
4 equiv relative to [Pd]) was added. The resulting mixture was
stirred at 25 °C for 12 h, during which time the color changed
from bright orange to dark purple. Additional oxidant (173.0 mg,
0.46 mmol, 1 equiv) was added, and the mixture was stirred for an
additional 24 h. The reaction mixture was diluted with CH2Cl2 and
washed with 0.5 M aqueous NaOH (to remove free H2NTs) until
the aqueous layer remained colorless. The organic layer was dried
with MgSO4, and the solvent was removed under vacuum to afford
a dark purple solid. The crude product was purified by chroma-
tography on silica gel (gradient column from 100% toluene to 10%
MeCN in toluene; Rf ) 0.13 in 10% MeCN in toluene). The product
was further purified by preparative TLC (with 10% MeCN in
toluene as eluent), which provided complex 3 (51.2 mg, 18% yield)
1
as a purple solid that was ∼90% pure by H NMR spectroscopy.
a Percent conversion determined by 1H NMR spectroscopy. b Isolated
yield.
Pure material was obtained from a second purification by prepara-
tive TLC (with 10% MeCN in toluene as eluent), in which only
the bottom of the purple band with Rf ) 0.13 was isolated. The
low isolated yields of complex 3 appear to be due to decomposition
of this product during the basic extraction and during chromato-
Pd-catalyzed directed oxidative C-H amination reaction that
uses K2S2O8 as a stoichiometric oxidant.9 The further develop-
ment of this methodology will provide an attractive complement
to existing transformations such as the catalytic amination of
aryl halides and nitrene insertion into activated C-H bonds.
1
graphic purification on silica gel. H NMR (CDCl3): δ 7.94 (1H,
dd, J ) 8.5, 1.0 Hz), 7.88-7.85 (3H, multiple peaks), 7.75 (1H,
dd, J ) 8.0, 1.5 Hz), 7.68 (2H, d, J ) 8.5 Hz), 7.64 (1H, dd, J )
8.5, 1.5 Hz), 7.48 (1H, ddd, J ) 8.5, 7.5 Hz, 2.0 Hz), 7.27 (1H, td,
J ) 7.5, 1.5 Hz), 7.23 (2H, d, J ) 8.0 Hz), 7.21 (1H, ddd, J ) 8.0,
7.0, 1.0 Hz), 7.06 (2H, d, J ) 8.0 Hz), 6.77 (1H, ddd, J ) 8.0, 7.0,
1.5 Hz), 2.35 (3H, s), 2.27 (3H, s). 13C NMR (DMSO-d6): δ 150.05,
148.10, 147.78, 141.77, 140.05, 139.85, 134.59, 134.18, 132.96,
129.15, 128.84, 128.50, 128.21, 127.36, 126.18, 126.00, 124.87,
123.01, 122.39, 118.12, 20.84, 20.82. HRMS-electrospray (m/z):
[M + Na]+ calcd for C26H22N4O4S2PdNa, 647.0015; found,
647.0026.
Note: the 1H NMR signals associated with the Ts groups shifted
significantly, depending on concentration. In addition, the 1H NMR
spectra of 3 often contained broad singlets, with chemical shifts
that varied dramatically with concentration, which are due to
coordinated/associated water molecules. See the Supporting Infor-
mation for further discussion.
Experimental Section
Instrumentation. NMR spectra were obtained on a Varian Inova
1
500 (499.90 MHz for H; 125.70 MHz for 13C) or a Varian Inova
1
1
400 (399.96 MHz for H; 100.57 MHz for 13C) spectrometer. H
NMR chemical shifts are reported in parts per million (ppm) relative
to TMS, with the residual solvent peak used as an internal reference.
Multiplicities are reported as follows: singlet (s), doublet (d),
doublet of doublets (dd), doublet of doublet of doublets (ddd),
doublet of triplets (dt), triplet of doublets (td), triplet of triplets
(tt), triplet (t), doublet of quartets (dq), quartet (q), multiplet (m),
and broad resonance (br). High-resolution mass spectral data were
obtained on a Micromass AutoSpec Ultima magnetic sector mass
spectrometer.
Product 8a. Complex 8b (33.1 mg, 0.06 mmol, 1 equiv) was
dissolved in 5 mL of CH2Cl2 in a 20 mL scintillation vial equipped
with a Teflon stirbar. Silver acetate was added, and the mixture
was stirred for 30 min. AgCl was removed by filtration through
Celite, and the Celite pad was washed with CH2Cl2 (3 × 5 mL).
The yellow solution was concentrated, and a solid was precipitated
with Et2O. The yellow solid was collected on a fritted filter (21.1
Materials and Methods. Benzo[h]quinoline was purchased from
TCI America or Aldrich and used as received. Azobenzene was
purchased from Acros and recrystallized from ethanol prior to use.
PhIdNTs23 and the OMe- and NO2-substituted variants24 were
prepared according to literature procedures from commercially
available sulfonamides. Cyclopalladated complexes of azobenzene,25
benzo[h]quinoline,26,27 and 8-ethylquinoline28 were prepared by
directed C-H activation reactions using literature procedures. PdCl2
and Na2PdCl4 were purchased from Pressure Chemical and used
as received. Solvents were purchased from Fisher Scientific and
used without further purification. All reactions were carried out
under an ambient atmosphere. Flash chromatography was performed
on Silicycle Silica P flash silica gel (40-63 µm particle size, 60 Å
pore diameter, 50 m2/g surface area), and thin layer chromatography
1
mg, 61% yield). H NMR (CDCl3): δ 8.96 (2H, dt, J ) 5.1, 1.6
Hz), 8.68 (1H, dd, J ) 5.5, 1.6 Hz), 8.04 (1H, dd, J ) 8.0 , 1.5
Hz), 7.88-7.72 (5H, multiple peaks), 7.47-7.41 (3H, multiple
peaks), 7.31 (1H, dd, J ) 7.9, 5.5 Hz), 7.14 (2H, d, J ) 8.1 Hz),
6.48 (2H, d, J ) 7.9 Hz), 1.99 (3H, s), 1.79 (3H, s). 13C NMR
(CDCl3): δ 177.54, 151.78, 151.30, 141.92, 140.44, 139.57, 139.13,
138.49, 137.96, 135.97, 130.28, 130.06, 129.11, 127.79, 127.39,
126.71, 126.36, 125.61, 124.91, 124.02, 121.69, 23.86, 21.06.
HRMS-electrospray (m/z): calcd for [C27H23N3O4PdS - C5H5N
+ Na+], 534.9920; found, 534.9928.
(23) Yamada, Y.; Yamamoto, T.; Okawara, M. Chem. Lett. 1975, 361-
362.
(24) So¨dergren, M. J.; Alonso, D. A.; Bedekar, A. V.; Andersson, P. G.
Products 8b, 10a, and 10b (General Procedure). Complex 5
(51.2 mg, 0.08 mmol, 1 equiv) was suspended in MeCN or THF
(8 mL) in a 20 mL scintillation vial equipped with a Teflon stirbar.
Pyridine (50 µL, 0.66 mmol, 8 equiv) was added to convert 5 to
the corresponding monomer 7, and the reaction mixture was stirred
until all of the solids dissolved. The iminoiodinane reagent (0.21
mmol, 2.6 equiv, 1.3 equiv per [Pd]) was added, and the reaction
mixture was stirred at 25 °C for between 4 and 18 h. The solvent
Tetrahedron Lett. 1997, 38, 6897-6900.
(25) Cope, A. C.; Siekman, R. W. J. Am. Chem. Soc. 1965, 87, 3272-
3273.
(26) Nonoyama, M.; Suzuki, K.; Yamasaki, K. Proc. Jpn. Acad. 1969,
45, 605-608.
(27) Selbin, J.; Gutierrez, M. A. J. Organomet. Chem. 1983, 246, 95-
104.
(28) Holcomb, H. L.; Nakanishi, S.; Flood, T. C. Organometallics 1996,
15, 4228-4234.

1370 Organometallics, Vol. 26, No. 6, 2007
Dick et al.
was removed under vacuum, and the product was purified by
recrystallization. The reaction times and purification conditions
varied between substrates and are reported in detail below.
Product 8b. Procedure 1 (in MeCN). Reaction time: 4 h. The
product was recrystallized twice from CH2Cl2/Et2O. Each crop of
crystals was collected on a fritted filter and washed with ether (3
× 25 mL). Product 8b was obtained as a pale yellow solid (48.2
mg, 42% yield).
and the Celite pad was washed with MeCN (80 mL). PhIdNTs
(515 mg, 1.4 mmol, 1.3 equiv) was added, and the resulting
suspension was stirred for 8 h at 25 °C. The reaction mixture was
filtered through Celite, and LiCl (90 mg, 2.1 mmol, 1.7 equiv) was
added to the resulting orange solution. The reaction mixture was
stirred for 30 min, and then the solvent was removed under vacuum.
The crude oil was dissolved in CH2Cl2 (50 mL), and the organic
layer was washed with H2O (3 × 100 mL) and brine (1 × 100
mL). The organic layer was dried with MgSO4, filtered, and
concentrated under vacuum. The product was recrystallized twice
from CH2Cl2/Et2O, and each crop was collected on a fritted filter
and washed with Et2O (3 × 50 mL). The resulting mixture contained
complex 12 and a second PdII species [(py)2PdCl2] in a 1:1.5 ratio
by 1H NMR spectroscopy (calculated yield: 93 mg (16%)).
Removal of py2PdCl2 was accomplished by two additional recrys-
tallizations from THF/Et2O. The isolated yield of pure 12 was very
low (∼4%) as a result of these multiple recrystallizations; however,
the crude yield of this reaction was determined by 1H NMR
Procedure 2 (in THF). Reaction time: overnight. The product
was recrystallized from CH2Cl2/hexanes, collected on a fritted filter,
and washed with a 60/40 mixture of hexanes and isopropyl alcohol
(3 × 20 mL). Product 8b was obtained as a pale yellow solid (70.9
1
mg, 78% yield). H NMR (CDCl3): δ 9.16 (1H, dd, J ) 5.5, 1.6
Hz), 9.00 (2H, dt, J ) 5.1, 1.6 Hz), 8.05 (1H, dd, J ) 8.0, 1.6 Hz),
7.88-7.73 (5H, multiple peaks), 7.47-7.42 (3H, multiple peaks),
7.33 (1H, dd, J ) 7.9, 5.5 Hz), 7.05 (2H, dt, J ) 8.5, 2.0 Hz), 6.48
(2H, dd, J ) 8.4, 0.4 Hz), 1.99 (3H, s). 13C NMR (CDCl3): δ
154.24, 152.59, 141.96, 140.61, 139.33, 138.93, 138.58, 138.16,
136.01, 130.39, 129.86, 128.39, 127.86, 127.64, 126.68, 126.22,
125.60, 125.04, 124.15, 121.96, 21.08. Anal. Calcd for C25H20-
ClN3O2PdS: C, 52.83; H, 3.55; N, 7.39. Found: C, 52.56; H, 3.26;
N, 7.10.
1
spectroscopy to be 19%. H NMR (CDCl3): δ 9.61 (1H, dd, J )
5.4, 1.6 Hz), 9.16 (2H, dt, J ) 4.9, 1.5 Hz), 8.02 (1H, dd, J ) 8.2,
1.6 Hz), 7.82 (1H, tt, J ) 7.8, 1.6 Hz), 7.63 (1H, dd, J ) 7.2, 1.4
Hz), 7.54 (1H, dd, J ) 8.1, 1.5 Hz), 7.46 (1H, dd, J ) 7.2, 0.8
Hz), 7.42 (2H, ddd, 7.7, 5.1, 1.4 Hz), 7.28 (2H, dt, J ) 8.7, 2.2
Hz), 7.23 (1H, dd, J ) 8.1, 5.4 Hz), 6.36 (2H, d, J ) 8.1 Hz), 4.39
(1H, q, J ) 7.2 Hz), 2.42 (3H, d, J ) 7.1 Hz), 1.96 (3H, s). 13C
NMR (CDCl3): δ 157.2, 153.2 140.6, 140.2, 140.0, 139.9, 139.3,
138.4, 132.1, 129.7, 128.2, 127.2, 127.0, 126.3, 125.0, 120.6, 56.0,
28.8, 21.0. HRMS-electrospray (m/z): calcd for [C23H22ClN3O2-
PdS - C5H5N + Na+], 488.9632; found, 488.9636.
Product 10a. Reaction time: overnight. Note: 4 equiv of oxidant
per [Pd] was used. The product was recrystallized three times from
CH2Cl2/Et2O. Notably, the first addition of Et2O to a CH2Cl2
solution of 10a resulted in the precipitation of an unidentified black
solid. The yellow solution was decanted away from this solid, and
further addition of ether led to crystallization of the desired product
10a. None of this black solid was observed in subsequent
recrystallizations. Each crop of crystals was collected on a fritted
filter and washed with ether (3 × 25 mL). Product 10a was obtained
as a light yellow solid (51.4 mg, 55% yield). 1H NMR (CDCl3): δ
9.21 (1H, dd, J ) 5.5, 1.6 Hz), 9.00 (2H, dt, J ) 5.2, 1.6 Hz), 8.08
(1H, dd, J ) 7.9, 1.5 Hz), 7.88-7.72 (5H, multiple peaks), 7.47-
7.43 (3H, multiple peaks), 7.35 (1H, dd, J ) 7.9, 5.5 Hz), 7.09
(2H, dt, J ) 8.9, 2.9 Hz), 6.17 (2H, dt, J ) 8.9, 2.9 Hz), 3.56 (3H,
s). 13C NMR (CDCl3): δ 160.89, 154.25, 152.57, 141.97, 138.97,
138.58, 138.41, 136.00, 134.30, 130.41, 129.88, 128.41, 128.07,
127.67, 126.77, 125.60, 125.03, 124.25, 122.09, 112.44, 55.37.
Anal. Calcd for C25H20ClN3O3PdS: C, 51.38; H, 3.45; N, 7.19.
Found: C, 51.54; H, 3.46; N, 7.08.
Determination of 1H NMR Yields for the Reactions of “NTs”
Insertion Products with Acid. A 20 mL scintillation vial equipped
with a Teflon stirbar was charged with the Pd complex (0.04 mmol).
A mixture of MeCN (8 mL) and an appropriate amount of HCl
(added as 1 M HCl in ether) was added, and the reaction mixture
was stirred for 24 h. The resulting mixture was diluted with H2O
(3 mL), and the organic products were extracted into EtOAc (3 ×
5 mL). The organic layers were combined, dried with MgSO4,
filtered, and evaporated to dryness. The resulting oils were analyzed
by 1H NMR spectroscopy in order to determine the percent
conversion. Notably, the reactions with AcOH and TFA were
carried out using the acid as the solvent.
Product 10b. Reaction time: 8 h. The product was recrystallized
twice from CH2Cl2/Et2O. Each crop of crystals was collected on a
fritted filter and washed with ether (3 × 25 mL). Product 10b was
Acknowledgment. We thank Jim Windak and Paul Lennon
for mass spectral analysis. We thank the NIH NIGMS (No.
RO1-GM073836), the Camille and Henry Dreyfus Foundation,
the Arnold and Mabel Beckman Foundation, Amgen, Boehringer
Ingelheim, Bristol Myers Squibb, Eli Lilly, and Merck Research
Labs for support of this work. We are also grateful to Eli Lilly
for a graduate fellowship to A.R.D. We also thank the SCrALS
program at the Small-Crystal Crystallography Beamline 11.3.1
at the Advanced Light Source (ALS) for acquiring crystal-
lographic data for complex 3.
1
obtained as a bright yellow solid (72.6 mg, 76% yield). H NMR
(CDCl3): δ 9.20 (1H, dd, J ) 5.4, 1.6 Hz), 8.96 (2H, dt, J ) 4.9,
1.4 Hz), 8.07 (1H, dd, J ) 8.0, 1.5 Hz), 7.93-7.79 (5H, multiple
peaks), 7.53-7.44 (5H, multiple peaks), 7.39 (1H, dd, J ) 8.0, 5.7
Hz), 7.32 (2H, dt, J ) 8.7, 2.3 Hz). 13C NMR (CDCl3): δ 154.15,
152.52, 148.30, 147.29, 141.63, 138.89, 137.85, 136.15, 130.69,
130.09, 128.33, 127.14, 126.95, 126.86, 126.25, 125.27, 124.47,
122.50, 122.35. Note: only 19 (rather than the expected 20) carbon
resonances were observed for 10b, presumably due to overlapping
peaks. Anal. Calcd for C24H17ClN4O4PdS: C, 48.09; H, 2.86; N,
9.35. Found: C, 48.27; H, 2.91; N, 9.38.
Product 12. Complex 11 (400 mg, 1.1 mmol, 1 equiv) was
dissolved in MeCN (80 mL) in a 100 mL round-bottom flask
equipped with a Teflon stirbar. AgOTf (545 mg, 2.1 mmol, 2 equiv)
was added, and the reaction mixture was stirred for 30 min. The
resulting suspension was filtered through Celite to remove AgCl,
Supporting Information Available: Text, tables, figures and
CIF files giving additional experimental details regarding the
synthesis and characterization of inorganic and organic products
as well as X-ray crystallographic data. This material is available
free of charge via the Internet at http://pubs.acs.org.
OM061052L