Mechanism of N-fluorobenzenesulfonimide promoted diamination and carboamination reactions: Divergent reactivity of a Pd(IV) species

Article abstract of DOI:10.1021/ja906915w

The mechanism of the Pd-catalyzed diamination and carboamination of alkenes promoted by N-fluorobenzenesulfonimide (NFBS) was investigated. Stereochemical labeling experiments established that the diamination reaction proceeds via overall syn addition of

Full text of DOI:10.1021/ja906915w

Published on Web 10/13/2009
Mechanism of N-Fluorobenzenesulfonimide Promoted
Diamination and Carboamination Reactions: Divergent
Reactivity of a Pd(IV) Species
Paul A. Sibbald, Carolyn F. Rosewall, Rodney D. Swartz, and Forrest E. Michael*
Department of Chemistry, Box 351700, UniVersity of Washington,
Seattle, Washington 98195-1700
Received August 21, 2009; E-mail: michael@chem.washington.edu
Abstract: The mechanism of the Pd-catalyzed diamination and carboamination of alkenes promoted by
N-fluorobenzenesulfonimide (NFBS) was investigated. Stereochemical labeling experiments established
that the diamination reaction proceeds via overall syn addition of the two nitrogen groups, whereas
carboamination is the result of an anti addition of arene and nitrogen to the alkene. The intermediate Pd-
alkyl complex arising from aminopalladation was observed, and an X-ray crystal structure of its 2,2′-bipyridine
(bipy) complex was obtained, revealing strong chelation of the amide protecting group to palladium.
Aminopalladation was shown to be an anti-selective process in both the presence and the absence of
added ligands, proceeding via external attack of the nitrogen on a Pd-coordinated alkene. The intermediate
Pd-alkyl complex was converted to diamination product upon exposure to NFBS with inversion of
configuration via oxidative addition followed by dissociation of the benzenesulfonimide anion and SN2
displacement of the Pd-C bond. Conversely, arylation of the Pd-alkyl complex proceeds via retention of
stereochemistry, consistent with C-H activation of the arene at the Pd(IV) center. A small intermolecular
isotope effect (kH/kD ) 1.1) and a large intramolecular isotope effect (kH/kD ) 4) were measured for this
process, indicating that C-H activation occurs via a poorly selective product-determining coordination of
the arene followed by a highly selective C-H activation. Competition between arenes reveals an unusual
reactivity order of toluene > benzene > bromobenzene > anisole.
Introduction
and Lloyd-Jones have each reported palladium-catalyzed di-
aminations of alkenes using ureas and sulfamides in conjunction
Oxidative aminations of alkenes such as oxyaminations,
diaminations, and carboaminations are of special importance
in synthetic chemistry. These reactions allow for the transforma-
tion of the ubiquitous carbon-carbon double bond into motifs
with a range of important applications. Over the past several
decades, numerous oxidative aminations of alkenes have been
developed using a range of metal catalysts and stoichiometric
reagents.1
Vicinal diaminations of alkenes have been accomplished using
stoichiometric quantities of palladium,2 mercury,3 selenium,4
osmium,5 cobalt,6 and copper.7 Recently, a number of catalytic
diaminations have been reported. Mun˜iz and Booker-Milburn
with an external oxidant.8,9 Shi has developed several metal-
catalyzed diamination reactions that use strained three-membered
ring hydrazines as nitrogen sources.10
Development of an efficient method for addition of a nitrogen
and carbon across an alkene is another important reaction, in
part because of its rarity. Wolfe has shown that aryl bromides
can be used to form C-C bonds via a Pd-catalyzed carboami-
nation of aminoalkenes.11 Chemler has reported a doubly
intramolecular Cu-catalyzed bicyclization of arylsulfonami-
doalkenes and arylamidoalkenes to give products resulting from
carboamination and aminooxygenation of the olefin.12 Booker-
(1) Reviews: (a) Cardillo, G.; Orena, M. Tetrahedron 1990, 46, 3321–
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127, 11250–11251.
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130, 763–773. (b) Mun˜iz, K.; Ho¨velmann, C. H.; Streuff, J.; Campos-
Gomez, E. Pure Appl. Chem. 2008, 80, 1089–1096.
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A R T I C L E S
Sibbald et al.
Figure 1. Palladium-catalyzed diamination and carboamination with NFBS.
Milburn and Lloyd-Jones have reported a closely related Pd-
catalyzed carboamination of dienes using arylureas.13
We recently disclosed a series of remarkable palladium-
catalyzed oxidative aminations using N-fluorobenzenesulfon-
imide (NFBS) as an oxidant and/or an electrophilic source of
nitrogen (Figure 1). This set of reactions displayed a drastic
solvent effect. In non-nucleophilic solvents, such as CH2Cl2 and
EtOAc, diamination of the alkene took place by incorporation
of benzenesulfonimide from the NFBS reagent.14 In the presence
of aromatic solvents, the reaction course was diverted to the
formation of carboamination products via incorporation of 1
equiv of the arene (eq 2).15 The change in reactivity observed
with the same key reagents is remarkable. We sought to
understand the mechanisms of diamination and carboamination
in order to expand the already impressive scope of this Pd/NFBS
system. The results of our mechanistic investigation are
presented herein.
Figure 2. Assignment of diamination stereoselectivity via thiourea 3.
Results and Discussion
Overall Stereochemistry of the Diamination and Carboami-
nation Reactions. To obtain information about the mechanisms
of the diamination and carboamination reactions, the overall
stereoselectivity of both processes was investigated by taking
advantage of stereospecifically deuterium-labeled substrate (E)-
1-d (Figure 2). When substrate (E)-1-d was subjected to
diamination conditions (10 mol % Pd(OCOCF3)2, NFBS), only
one 1H NMR resonance was absent in diamination product 2-d,
indicating that a highly stereoselective reaction had taken place.
To establish the stereochemistry, diamination product 2 was
deprotected to give the free diamine and cyclized to give bicyclic
thiourea product 3. The cis/trans relationship between the
Figure 3. Assignment of carboamination stereoselectivity via cyclic
amide 6.
1
methylene and methine protons was determined by H NMR
and NOESY spectroscopy. The reaction sequence was repeated
with deuterated substrate 2-d, and the resonance with the cis
coupling constant of 9.5 Hz disappeared, indicating that
diamination proceeded with overall syn selectivity.
The overall syn selectivity for this catalyst system is distinct
from that observed in other catalytic diamination reactions.
Mun˜iz has reported an intramolecular diamination of sulfony-
lureas that proceeds via overall anti selectivity.8a Chemler
observed a nonstereospecific diamination in a Cu-catalyzed
system, giving a 1:1 diastereomeric mixture of syn and anti
products, presumably due to the intermediacy of radical species.7
Submitting substrate (E)-4-d to the carboamination reaction
conditions also afforded a single stereoisomer of product 5-d
(Figure 3). To determine the overall stereoselectivity, carboami-
nation product 5 was cyclized under Friedel-Crafts conditions
to give tricyclic amide 6. The reaction sequence was repeated
with deuterated substrate 5-d, and the 1H NMR resonance with
(11) (a) Wolfe, J. P. Eur. J. Org. Chem. 2007, 57, 1–582. (b) Ney, J. E.;
Wolfe, J. P. Angew. Chem., Int. Ed. 2004, 43, 3605–3608. (c) Ney,
J. E.; Wolfe, J. P. J. Am. Chem. Soc. 2005, 127, 8644–8651. (d)
Nakhla, J. S.; Kampf, J. W.; Wolfe, J. P. J. Am. Chem. Soc. 2006,
128, 2893–2901. (e) Fritz, J. A.; Nakhla, J. S.; Wolfe, J. P. Org. Lett.
2006, 8, 2531–2534. (f) Bertrand, M. B.; Leathen, M. L.; Wolfe, J. P.
Org. Lett. 2007, 9, 457. (g) Nakhla, J. S.; Wolfe, J. P. Org. Lett. 2007,
9, 3279–3289. (h) Fritz, J. A.; Wolfe, J. P. Tetrahedron 2008, 64,
6838–6852. (i) Giampietro, N. C.; Wolfe, J. C. J. Am. Chem. Soc.
2008, 130, 12907–12911. (j) Bertrand, M. B.; Neukom, J. D.; Wolfe,
J. P. J. Org. Chem. 2008, 73, 8851–8860. (k) Lemen, G. S.;
Giampietro, N. C.; Hay, M. B.; Wolfe, J. P. J. Org. Chem. 2009, 74,
2533–2540. (l) Leathen, M. L.; Rosen, B. R.; Wolfe, J. P. J. Org.
Chem. 2009, 74, 5107–5110. (m) Nakhla, J. S.; Schultz, D. M.; Wolfe,
J. P. Tetrahedron 2009, 65, 6549–6570.
1
J ) 14.1 Hz was absent (trans diaxial), while the H NMR
resonance with J ) 3.9 Hz was still present (cis), establishing
that carboamination proceeds with overall anti selectivity. The
overall anti selectivity for this catalyst system is also distinct
from previous carboamination examples reported by Yorimitsu,
Oshima,16 and Wolfe,11 in which overall syn selectivity is
observed, and Chemler,12b which again proceeds with stereo-
chemical scrambling. Furthermore, it is important to note that
(12) (a) Fuller, P. H.; Chemler, S. R. Org. Lett. 2007, 9, 5477–5480. (b)
Sherman, E. S.; Fuller, P. H.; Kasi, D.; Chemler, S. R. J. Org. Chem.
2007, 72, 3896–3905. (c) Zeng, W.; Chemler, S. R. J. Am. Chem.
Soc. 2007, 129, 12948–12949. (d) Fuller, P. H.; Kim, J. W.; Chemler,
S. R. J. Am. Chem. Soc. 2008, 130, 17638–17639. (e) Sherman, E. S.;
Chemler, S. R. AdV. Synth. Catal. 2009, 351, 467–471.
(13) Houlden, C. E.; Bailey, C. D.; Ford, J. G.; Gagne´, M. R.; Lloyd-
Jones, G. C.; Booker-Milburn, K. I. J. Am. Chem. Soc. 2008, 130,
10066–10067.
(14) Sibbald, P. A.; Michael, F. E. Org. Lett. 2009, 11, 1147–1149.
(15) Rosewall, C. F.; Sibbald, P. A.; Liskin, D. V.; Michael, F. E. J. Am.
Chem. Soc. 2009, 131, 9488–9489.
(16) Hayashi, S.; Yorimitsu, H.; Oshima, K. Angew. Chem., Int. Ed. 2009,
48, 7224–7226.
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Promoted Diamination and Carboamination Reactions
A R T I C L E S
Figure 4. Observation and isolation of intermediate Pd-alkyl complexes.
the carboamination and diamination reactions promoted by
NFBS proceed with opposite stereoselectivities.
Figure 5. Crystal structure of bipy-Pd-alkyl [(CF3CO2)2H] complex 10.
Bond distances (Å): Pd-O ) 2.024, Pd-C ) 2.010, Pd-N2 ) 2.102,
Pd-N3 ) 2.026.
Alkene Aminopalladation. Since the diamination and car-
boamination products observed in the presence of NFBS and
catalytic Pd(II) differ only in the identity of the exocyclic group,
our initial hypothesis was that these products arose from
divergent reactions of a common intermediate. The most likely
candidate for such an intermediate is the Pd-alkyl complex
arising from aminopalladation of the alkene. Similar Pd
complexes have often been invoked as intermediates in alkene
amination reactions, and a few have been reported to be
observable, albeit without full characterization.8a,17 To confirm
the intermediacy of a Pd-alkyl complex and to determine the
stereochemical outcomes of both the aminopalladation and
Pd-C bond functionalization steps, the reaction between the
aminoalkene and the Pd complex in the absence of NFBS was
investigated.
Figure 6. Syn versus anti aminopalladation.
Aminoalkene substrate 7 was treated with Pd(OCOCF3)2 in
CD3CN and monitored by 1H NMR spectroscopy. After 15 min,
complete consumption of the starting alkene was observed,
Pd salt were found in the crystal structure as a complex
counterion between trifluoroacetate and trifluoroacetic acid.
With stable Pd-alkyl complexes in hand, it was possible to
determine the stereochemistry of the initial aminopalladation
step. Initial palladation can proceed either through insertion of
a coordinated alkene into a Pd-N bond to form the product of
syn aminopalladation or via external nucleophilic attack of the
nitrogen on a Pd-coordinated alkene, giving the anti aminopal-
ladation product (Figure 6). Examples of both syn and anti
heteropalladation have been established as viable possibilities
in alkene functionalization reactions. In a number of early studies
by Stille, Ba¨ckvall, and Kurosawa, anti oxypalladation was
reported.19 It was later observed by Henry and Thompson that
oxypalladation selectivity could be controlled through the
concentration of Cl- present (syn oxypalladation at low con-
centrations and anti oxypalladation at higher concentrations).20,21
A number of recent reports including those by Mun˜iz,8a,22
Stahl,23 Sanford,24 and Wolfe11b-d report initial syn aminopal-
1
replaced by new H NMR resonances corresponding to a Pd-
alkyl complex tentatively identified as 8 (Figure 4). As expected,
this putative Pd-alkyl complex was unstable, decaying over the
course of several hours at room temperature. However, treatment
of the putative Pd-alkyl complex with various ligands (pyridine,
2,2′-bipyridine (bipy), bis(diphenylphosphinomethyl)pyridine
(PNP)) prevented this decay and gave Pd-alkyl complexes (9,
10) that were bench-stable for a minimum of several weeks at
room temperature. A closely related Pd-alkyl complex bearing
a tridentate PNP ligand but with a tetrafluoroborate counterion
(9-BF4) has been previously isolated and characterized as an
intermediate in a catalytic hydroamination reaction.18 The H
1
NMR spectrum of the species formed by trapping Pd-alkyl
complex 8 with free PNP ligand was identical to that previously
formed from the dicationic (PNP)Pd complex 11 and the
aminoalkene substrate in the presence of base.
To further confirm its structure, crystals of the Pd-alkyl
complex with 2,2′-bipyridine (10) were obtained from Et2O/
MeCN, and an X-ray crystal structure was solved (Figure 5).
The structure reveals tight chelation of the oxygen of the
acetamide protecting group, which is possibly responsible for
the abnormal stability of this complex with respect to ꢀ-hydride
elimination. Interestingly, both trifluoroacetates of the original
(19) James, D. E.; Hines, L. F.; Stille, J. K. J. Am. Chem. Soc. 1976, 98,
1806–1809. Stille, J. K.; Divakaruni, R. J. Am. Chem. Soc. 1978, 100,
1303–1304. Ba¨ckvall, J.-E.; Åkermark, B.; Ljunggren, S. O. J. Chem.
Soc., Chem. Commun. 1977, 264–265. Ba¨ckvall, J.-E.; Åkermark, B.;
Ljunggren, S. O. J. Am. Chem. Soc. 1979, 101, 2411–2416. Ba¨ckvall,
J. E.; Bjo¨rkman, E. E. J. Org. Chem. 1980, 45, 2893–2898. Majima,
T.; Kurosawa, H. J. Chem. Soc., Chem. Commun. 1977, 610–611.
(20) Hamed, O.; Henry, P. M.; Thompson, C. J. Org. Chem. 1999, 64,
7745–7750.
(17) Hegedus, L. S.; McKearin, J. M. J. Am. Chem. Soc. 1982, 104, 2444–
(21) This result was later supported by Hayashi and co-workers, who
observed anti-palladation in the presence of chloride and syn-
palladation in the absence of chloride. Hayashi, T.; Yamasaki, K.;
Mimura, M.; Uozumi, Y. J. Am. Chem. Soc. 2004, 126, 3036–3037.
2451.
(18) Cochran, B. M.; Michael, F. E. J. Am. Chem. Soc. 2008, 130, 2786–
2792.
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A R T I C L E S
Sibbald et al.
Figure 7. Formation of deuterated palladium-PNP-alkyl complex 9-d in
the presence and absence of tridentate ligand.
Figure 9. Reaction of Pd-alkyl complex 10 with NFBS.
The preference for anti aminopalladation in this system, in
contrast to the general preference for syn aminopallada-
tion observed by others, is likely due to two factors. First, the
reaction conditions here are relatively acidic, which has already
been shown to promote anti aminopalladation reactions.20,21
Second, many of the reports of syn aminopalladation involve
addition of relatively acidic N-H bonds to alkenes (phthalimides
and sulfonamides), which can be more easily deprotonated to
form the Pd-amide necessary for syn addition. The amides and
carbamates in this study are more difficult to deprotonate and
more nucleophilic as neutral species, so the external attack
mechanism (anti addition) is favored.
Figure 8. Stereochemistry of aminopalladation as determined from bipy-
Pd-alkyl complex 10.
ladation in oxidative aminations of alkenes. Stahl has also
conducted a systematic study of syn versus anti aminopalladation
and has concluded that syn addition is usually preferred.25
Pd-Alkyl Complex Functionalization. Having established that
the overall stereochemical outcome is syn for the diamination
reaction and anti for the carboamination reaction, and since the
stereochemistry of the aminopalladation step is anti, the
stereochemistry of the Pd-alkyl functionalization steps in each
reaction can be deduced. Specifically, diamination must occur
with inversion of stereochemistry at the Pd-C bond, whereas
carboamination must occur with retention of stereochemistry.
To confirm the intermediacy of Pd-alkyl complex 10 in the
diamination reaction, the isolated bipy-Pd-alkyl complex 10 was
dissolved in CH2Cl2, and [Et3NH][N(SO2Ph)2] and NFBS were
added. Conversion to diamination product 12 was observed in
52% yield (Figure 9). In situ generation of 10-d followed by
treatment with [Et3NH][N(SO2Ph)2] and NFBS afforded deu-
terated diamination product 12-d with the same relative stere-
ochemistry as was observed in the catalytic reaction (Figure
2).26
To determine the stereoselectivity of the initial palladation
step, the (PNP)Pd-alkyl complex was formed from deuterated
alkene (E)-7-d under two distinct sets of conditions (Figure 7).
First, 9-d can be formed by treatment of the dicationic (PNP)Pd
complex 11 with alkene (E)-7-d in the presence of mild base.
It is unlikely that syn aminopalladation can occur in the presence
of the tridentate ligand due to the lack of an additional
coordination site, so this experiment is expected to yield only
the anti aminopalladation product. Alternately, the same Pd-
alkyl complex can be formed by aminopalladation with Pd(O-
COCF3)2 without added ligand, followed by trapping with the
tridentate ligand. Both reactions afforded the same stereoisomer
of the deuterium labeled Pd-alkyl complex. Therefore, it appears
that anti aminopalladation is predominant with this substrate
1
in both the presence and absence of added ligand. H NMR
coupling constants are also consistent with anti aminopallada-
tion.
The inversion of stereochemistry in the amination of the Pd-
alkyl complex can be explained by the mechanism depicted in
Figure 10. Oxidative addition of the N-F bond to the Pd(II)-
alkyl complex generates Pd(IV) species B. Dissociation of a
benzenesulfonimide anion and SN2 displacement of the Pd(IV)-
alkyl would regenerate Pd(II) and explain the overall inversion
of stereochemistry in this step. A similar dissociative mechanism
has been shown to predominate in the functionalization of
Pt(IV)-alkyl complexes.27
Further confirmation of the stereochemistry of aminopalla-
dation comes from the X-ray crystal structure of bipy-Pd-alkyl
complex 10. When the deuterated Pd-alkyl complex 8-d was
1
trapped with bipy to form 10-d, the H NMR resonance with
the large vicinal coupling constant of 12.5 Hz was absent (Figure
8). On the basis of the half-chair conformation adopted by 10
in the crystal structure, this result is consistent with anti
aminopalladation.
Treatment of bipy-Pd-alkyl complex 10 with NFBS in toluene
results in conversion to the carboamination product 13, albeit
in low yield (Figure 9). Poor solubility of complex 10 in toluene
may be responsible for the reduced efficiency of the stoichio-
metric carboamination. Since our proposed mechanism of
carboamination requires an open coordination site (see below),
(22) Mun˜iz’ mechanistic study8a has recently been called into question.
On the basis of calculations, Lin and co-workers suggest that the
reaction actually goes through an anti aminopalladation followed by
reductive elimination rather than the syn aminopalladation/nucleophilic
attack reported by Mun˜iz Yu, H.; Fu, Y.; Guo, Q.; Lin, Z.
Organometallics 2009, 28, 4507–4512.
(23) Liu, G.; Stahl, S. S. J. Am. Chem. Soc. 2006, 128, 7179–7181. Liu,
G; Stahl, S. S. J. Am. Chem. Soc. 2007, 129, 6328–6335.
(24) Desai, L. V.; Sanford, M. S. Angew. Chem., Int. Ed. 2007, 46, 5737–
5740.
(26) See Supporting Information for details.
(27) Williams, B. S.; Goldberg, K. I. J. Am. Chem. Soc. 2001, 123, 2576–
(25) Liu, G.; Stahl, S. S. J. Am. Chem. Soc. 2007, 129, 6328–6335.
2587.
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Promoted Diamination and Carboamination Reactions
A R T I C L E S
Figure 10. Proposed mechanism for Pd-C bond amination.
Table 1. Arene Competition Experimentsa
R/R′
H
Me
Br
OMe
H
Me
Br
1
1.1
1
2.1
2.1
0.6
0.5
1
0.4
0.5
0.7
1
Figure 11. Inter- and intramolecular isotope effects.
0.9
1.8
2.4
OMe
1.4
A mechanism that explains the experimental data is illustrated
in Figure 12. The Pd(II) alkyl complex is inert toward arenes
in the absence of NFBS, so initial oxidative addition to form a
Pd(IV) complex (B) must be the first step in functionalization
of the Pd-C bond. Arene incorporation from the Pd-alkyl
complex occurs with retention of stereochemistry, which is
consistent with C-H bond activation at Pd(IV) followed by
reductive elimination. Direct nucleophilic displacement of the
Pd(IV)-C bond by the arene would result in inversion of
configuration, so it can be ruled out.
A mechanism for C-H activation must explain the following
key observations: (1) the high para selectivity, (2) the low
intermolecular selectivity between arenes, (3) the low reactivity
of anisole, (4) the high intramolecular isotope effect, and (5)
the low intermolecular isotope effect. At first glance, many of
these observations are unusual for aromatic activation. C-H
activations of toluene at Pt(II), Pd(II), and Ir(III) are generally
poorly regioselective, often giving statistical mixtures of meta
and para isomers.29 In this system, however, very high para
selectivity is observed. This could be a result of the higher
electrophilicity of the Pd(IV) center; C-H activations at Pt(IV)30
and Rh(III)31 give high para selectivity under kinetic condi-
tions.32
a Number represents ratio of top row to left column incorporation,
i.e., anisole product is 0.4 times as prevalent as benzene product.
Determined by H NMR spectroscopy.
1
the blocking of these sites by the bipy ligand may also be
responsible for the low yield of this stoichiometric reaction.
To indirectly probe the arene activation step, carboamination
reactions were run with various mixtures of arenes, and the
relative extent of incorporation of the two arenes was determined
(Table 1). Interestingly, while a methyl substituent offered a
slight enhancement in reactivity, both halide and methoxy
groups made the arene less likely to be incorporated. Further-
more, these substituent effects are approximately multiplicative
and rather small, never approaching an order of magnitude. To
ensure that the polarity of the solvent mixture did not affect
selectivity, carboamination of substrate 1 was run in varying
ratios of anisole/toluene. Little variation in the relative rate of
anisole incorporation relative to toluene incorporation was
observed (see Supporting Information). It should also be noted
that all monosubstituted arenes that participate in this reaction
give exclusively para substitution on the aromatic ring.15
Substrate 1 was subjected to carboamination conditions in a
1:1 mixture of toluene and toluene-d8 to determine the inter-
molecular isotope effect. A small normal isotope effect was
observed (kH/kD ) 1.1, Figure 11). No scrambling of deuterium
between toluene and toluene-d8 was observed in either the
product. In contrast, when substrate 1 was treated with 1,3,5-
trideuterobenzene, a large primary isotope effect (kH/kD ) 4)
was observed. A similar large difference between inter- and
intramolecular isotope effects has been observed by Mayer in
an arene C-H activation by a RedO complex.28
(29) Shilov, A. E.; Shul’pin, G. B. Chem. ReV. 1997, 97, 2897–2932.
Fujiwara, Y.; Asano, R.; Moritani, I.; Teranishi, S. J. Org. Chem. 1976,
41, 1681–1683. Ackerman, L. J.; Sadighi, J. P.; Kurtz, D. M.; Labinger,
J. A.; Bercaw, J. E. Organometallics. 2003, 22, 3884–3890. Ishiyama,
T.; Takagi, J.; Ishida, K.; Miyaura, N.; Anastasi, N. R.; Hartwig, J. F.
J. Am. Chem. Soc. 2002, 124, 390–391.
(30) Shul’pin, G. B. Zh. Obshch. Khim. 1981, 51, 2100. Shul’pin, G. B.;
Nizova, G. V.; Nikitaev, A. T. J. Organomet. Chem. 1984, 276, 115–
153.
(31) Aoyama, Y.; Yoshida, T.; Sakurai, K.; Ogoshi, H. Organometallics
1986, 5, 168–173.
(32) However, indirect evidence for a directed C-H activation at Pd(IV)
indicates that it is poorly regioselective: Hull, K. L.; Lanni, E. L.;
Sanford, M. S. J. Am. Chem. Soc. 2006, 128, 14047–14049.
(28) Brown, S. N.; Myers, A. W.; Fulton, J. R.; Mayer, J. M. Organome-
tallics 1998, 17, 3364–3374.
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A R T I C L E S
Sibbald et al.
Figure 12. Mechanism for arene incorporation from Pd-alkyl complex.
Figure 13. Proposed mechanistic cycle.
In electrophilic aromatic substitution mechanisms with either
conventional electrophiles or electrophilic metal centers, the rate
of reaction with anisole is usually much faster than that of
toluene, which is faster than that of benzene.29-31,33 However,
in this system anisole was substantially less reactive than
benzene, indicating that the methoxy group is operating
exclusively as an inductively electron-withdrawing group in the
product-determining step.
product (Figure 10).28,34 In this mechanism, the observed
intermolecular arene incorporation selectivities do not reflect
the actual C-H bond activation step and therefore tell us nothing
about the nature of that C-H bond cleavage. They must instead
reflect the relative propensity to bind to the Pd(IV) intermediate.
Electron-rich arenes should bind more strongly to an electro-
philic Pd(IV) species than electron-poor arenes, which would
explain the observed reactivity order toluene > benzene >
bromobenzene. The fact that anisole is the least reactive arene
in competition experiments seems to imply that it binds
especially poorly to Pd(IV), perhaps indicating that the induc-
tively electron-withdrawing character of the methoxy group is
the primary determinant of binding selectivity.
The only observations that allow any insight into the actual
C-H bond breaking step are the intramolecular isotope effect
and the high para regioselectivity. Both of these are consistent
with either a σ-bond metathesis process or an electrophilic
aromatic substitution mechanism with rate-limiting deprotona-
tion. We favor the σ-bond metathesis mechanism based on the
similarity of the isotope effects and regioselectivities to the C-H
activation at a Re(IV)dO.28
The differences between the intramolecular and intermolecular
selectivities are striking. High levels of intramolecular selectivity
are observed in both the deuterium isotope effect (kH/kD ) 4)
and the regioselectivity (exclusively para substitution). On the
other hand, relatively low levels of intermolecular selectivity
are observed in the isotope effect (kH/kD ) 1.1) and arene
competition (kanis/kbenz ) 2.4) experiments.
The observation of different inter- and intramolecular kinetic
isotope effects requires that the C-H activation cannot be a
one-step process, i.e,. it must take place in two separate steps
with different selectivities. The intramolecular KIE is in the
normal range for a C-H bond breaking step, but the intermo-
lecular KIE is very small, implying that the step that determines
the intermolecular selectivity occurs before the C-H bond
breaking step. A plausible explanation is that binding of the
arene to the highly electrophilic Pd(IV) center is the intermo-
lecular selectivity-determining step, followed by subsequent
rapid C-H activation and reductive elimination to form the
Conclusion
In conclusion, we have described the mechanism of a PdII/
PdIV reaction cycle in which NFBS is used as a versatile oxidant
and/or electrophile in catalytic diamination and carboamination
reactions. The unified catalytic cycle for both reactions is
depicted in Figure 13. Initial activation of the substrate by the
Pd catalyst occurs by an anti aminopalladation of the alkene to
form a Pd-alkyl complex. Oxidative addition of NFBS to this
species generates a reactive Pd(IV) species that is the branch
(33) (a) DeYonker, N. J.; Foley, N. A.; Cundari, T. R.; Gunnoe, T. B.;
Peterson, J. L. Organometallics 2007, 26, 6604–6611. (b) Thompson,
M. E.; Baxter, S. M.; Bulls, A. R.; Burger, B. J.; Nolan, M. C.;
Santarsiero, B. D.; Schaefer, W. P.; Bercaw, J. E. J. Am. Chem. Soc.
1987, 109, 203–219. (c) Olah, G. A.; Flood, S. H.; Kuhn, S. J.; Moffatt,
M. E.; Overchuck, N. A. J. Am. Chem. Soc. 1964, 86, 1046–1054. (d)
Olah, G. A.; Flood, S. H.; Moffatt, M. E. J. Am. Chem. Soc. 1964,
86, 1065–1066.
(34) (a) Zhong, H. A.; Labinger, J. A.; Bercaw, J. E. J. Am. Chem. Soc.
2002, 124, 1378–1399. (b) Jones, W. D.; Feher, F. D. Acc. Chem.
Res. 1989, 22, 91–100.
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Promoted Diamination and Carboamination Reactions
A R T I C L E S
Acknowledgment. The University of Washington and the
National Science Foundation are acknowledged for financial
support.
point between diamination and carboamination processes. In the
diamination reaction, dissociation of the benzenesulfonimide
anion occurs, followed by SN2 displacement of the Pd-C bond
to form the second C-N bond and regenerate Pd(II). In the
presence of arenes, C-H activation at Pd(IV) takes place to
generate a Pd(IV)-aryl species that undergoes reductive elimina-
tion to form the carboamination product. This C-H activation
occurs via product determining complexation to Pd(IV) followed
by a highly regioselective C-H activation. The results of this
study show a significant deviation from the mechanisms
observed in similar oxidative difunctionalizations and will play
a significant role in further development of Pd-catalyzed
reactions using NFBS.
Supporting Information Available: Reaction conditions and
experimental data for the synthesis of all new compounds. This
material is available free of charge via the Internet at http://
pubs.acs.org.
JA906915W
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