Scope and mechanism of allylic C-H amination of terminal alkenes by the palladium/PhI(OPiv)2 catalyst system: Insights into the effect of naphthoquinone

Article abstract of DOI:10.1021/ja1030936

Palladium-catalyzed oxidative amination of unactivated alkyl olefins has been developed to produce linear (E)-allylimides with high regioselectivity. This highly efficient transformation of alkenes has been achieved by enhancing the reoxidation of palladi

Full text of DOI:10.1021/ja1030936

Published on Web 08/06/2010
Scope and Mechanism of Allylic C-H Amination of Terminal
Alkenes by the Palladium/PhI(OPiv)2 Catalyst System: Insights
into the Effect of Naphthoquinone
Guoyin Yin, Yichen Wu, and Guosheng Liu*
State Key Laboratory of Organometallics Chemistry, Shanghai Institute of Organic Chemistry,
Chinese Academy of Sciences, 354 Fenglin Road, Shanghai, China 200032
Received April 13, 2010; E-mail: gliu@mail.sioc.ac.cn
Abstract: Palladium-catalyzed oxidative amination of unactivated alkyl olefins has been developed to
produce linear (E)-allylimides with high regioselectivity. This highly efficient transformation of alkenes
has been achieved by enhancing the reoxidation of palladium with the strong oxidant PhI(OPiv)2. The
present work also provides the first systematic analysis of the mechanism of the allylic C-H oxidative
amination. It has been found that naphthoquinone (NQ) plays a vital role in promoting olefin coordination
to the palladium catalyst: in the absence of NQ, the turnover-limiting step is olefin coordination to
palladium catalyst; in the presence of NQ, the reaction involves a rapid equilibration to give a nitrogen-
coordinated olefin-Pd(NQ) complex that undergoes turnover-limiting allylic C-H bond activation to
generate a π-allyl-Pd intermediate. This work provides valuable insights for further studies on the
functionalization of unactivated olefins.
Scheme 1. Palladium-Catalyzed Oxidative Amination
Introduction
The ubiquity of nitrogen atoms in natural and synthetic
products sparks interest in developing new methods for the
preparation of nitrogen-containing molecules.1 Among the
strategies of C-N bond formation, the metal-catalyzed cross-
coupling reaction represents one of the most powerful methods.2,3
For instance, the palladium-catalyzed coupling of aryl halides
with various amines, pioneered by both the Buchwald and
Hartwig laboratories, have been extensively studied and broadly
used to synthesize pharmaceutical compounds.4 In contrast,
oxidative-coupling reactions, particularly methods that enable
direct amination of C-H bonds, have been the focus of recent
interest.5-8 For example, Rh-catalyzed C-H amination through
highly reactive metallo-nitreneoids,5 Pd- or Cu-mediated C-H
oxidative amination assisted by directing groups,6 and Pd-
catalyzed allylic C-H oxidative amination7,8 have been reported.
Examples for the latter case are particularly scarce (Scheme 1b).
More commonly, palladium-catalyzed amination of alkenes
proceeds through an aminopalladation pathway, rather than
allylic C-H bond activation.3,9,10 For instance, Stahl and co-
workers have reported a few examples of palladium-catalyzed
aerobic intermolecular oxidative amination of olefins to afford
imine or enamine products (Scheme 1a).9
Because of the value of allylic amines in organic synthesis,
methods to affect allylic amination of olefins have attracted
(4) For selective reviews and recent examples, see: (a) Surry, D. S.;
Buchwald, S. L. Angew. Chem., Int. Ed. 2008, 47, 6338–6361. (b)
Hartwig, J. F. Acc. Chem. Res. 2008, 41, 1534–1544. (c) Hicks, J. D.;
Hyde, A. M.; Martinez Cuezva, A.; Buchwald, S. L. J. Am. Chem.
Soc. 2009, 131, 16720–16734. (d) Fors, B. P.; Watson, D. A.; Biscoe,
M. R.; Buchwald, S. L. J. Am. Chem. Soc. 2008, 130, 13552–13554.
(e) Biscoe, M. R.; Fors, B. P.; Buchwald, S. L. J. Am. Chem. Soc.
2008, 130, 6686–6687. (f) Ogata, T.; Hartwig, J. F. J. Am. Chem.
Soc. 2008, 130, 13848–13849. (g) Shen, Q.; Ogata, T.; Hartwig, J. F.
J. Am. Chem. Soc. 2008, 130, 6586–6596. (h) Shen, Q.; Hartwig, J. F.
J. Am. Chem. Soc. 2006, 128, 10028–10029.
(1) Brown, E. G. Ring Nitrogen and Key Biomolecules; Springer: Boston,
MA, 1998.
(2) For recent reviews on the metal catalyzed C-N bond formation, see:
(a) Andersson, P. G.; Backvall, J.-E. In Handbook of Organopalladium
Chemistry for Organic Synthesis; Negishi, E., Ed.; Wiley-Interscience:
New York, 2002; p 1859. (b) Davies, H. M. L.; Long, M. S. Angew.
Chem., Int. Ed. 2005, 44, 3518–3520. (c) Jiang, L.; Buchwald, S. L.
In Metal-Catalyzed Cross-Coupling Reactions, 2nd ed.; Wiley-VCH:
Weinheim, 2004; Vol. 2, p 699. (d) Hartwig, J. F. In Handbook of
Organopalladium Chemistry for Organic Synthesis; Negishi, E., Ed.;
Wiley-Interscience: NewYork, 2002; p 1051.
(3) For recent reviews on the metal catalyzed amination of alkenes, see:
(a) Mueller, T. E.; Hultzsch, K. C.; Yus, M.; Foubelo, F.; Tada, M.
Chem. ReV. 2008, 108, 3795–3892. (b) Chianese, A. R.; Lee, S. J.;
Gagne, M. R. Angew. Chem., Int. Ed. 2007, 46, 4042–4059. (c) Zeni,
G.; Larock, R. C. Chem. ReV. 2006, 106, 4644–4680. (d) Beccalli,
E. M.; Broggini, G.; Martinelli, M.; Sottocornola, S. Chem. ReV. 2007,
107, 5318–5365. (e) Stahl, S. S. Angew. Chem., Int. Ed. 2004, 43,
3400–3420.
(5) C-H amination via nitrenes: (a) Espino, C. G.; Fiori, K. W.; Kim, M.;
Du Bois, J. J. Am. Chem. Soc. 2004, 126, 15378–15379. (b) Lebel,
H.; Huard, K.; Lectard, S. J. Am. Chem. Soc. 2005, 127, 14198–14199.
(c) Liang, C.; Robert-Peillard, F.; Fruit, C.; Mu¨ller, P.; Dodd, R. H.;
Dauban, P. Angew. Chem., Int. Ed. 2006, 45, 4641–4644. (d) Stokes,
B. J.; Dong, H.; Leslie, B. E.; Pumphrey, A. L.; Driver, T. G. J. Am.
Chem. Soc. 2007, 129, 7500–7501. (e) Thu, H.-Y.; Yu, W.-Y.; Che,
C.-M. J. Am. Chem. Soc. 2006, 128, 9048–9049. (f) Smitrovitch, J. H.;
Davies, I. W. Org. Lett. 2004, 6, 533–535.
9
11978 J. AM. CHEM. SOC. 2010, 132, 11978–11987
10.1021/ja1030936  2010 American Chemical Society

Effect of Naphthoquinone on Pd-Catalyzed Amination of Alkenes
A R T I C L E S
substantial interest.11 Very recently, several successful pal-
ladium-catalyzed intra- and intermolecular oxidative allylic
C-H aminations of unactivated alkenes have been reported.8
White and co-workers reported that the allylic C-H amina-
tion of terminal alkenes can be achieved using a Pd(II)-
sulfoxide catalytic system: a catalytic amount of a Lewis acid
[e.g., (salen)CrIII], or a Brønsted base was required to carry
out the reaction, and a stoichiometric amount of benzoquinone
(BQ) was used as the oxidant.8a,b Although the reactions
produce oxidative amination products with high regioselec-
tivity, the prolonged reaction time (72 h) and high catalyst
loading (10 mol %) limit the utility of this transformation in
organic synthesis. Meanwhile, palladium-catalyzed aerobic
oxidative allylic amination of olefins was reported by our
laboratory, and these reactions also afford linear allylamine
derivatives with highly regioselectivity.8c However, for their
broader applications in organic transformations, we need to
address the following limitations: (1) an excess of the alkene
(3 equiv relative to the nitrogen nucleophile) and high catalyst
loading (10-20 mol %) are required in order to have good
yields; (2) dioxygen pressure (6 atm) is needed to achieve
higher catalytic turnover; (3) a significant degree of double
bond isomerization exists in the products (up to 40%). Herein,
we describe a novel and highly efficient synthetic route to
allylamine derivatives via highly selective palladium-
catalyzed intermolecular oxidative allylic C-H amination.
This new procedure, using PhI(OPiv)2 as the oxidant along
with a substoichiometric amount of naphthoquinone (NQ),
provides major improvements: the olefin can be used as the
limiting reagent, low catalyst loading (1-5 mol %) can be
employed, and reaction times (5-8 h) are shortened.
Furthermore, the detailed mechanistic studies reported here
show that NQ plays a very important role in promoting olefin
coordination to palladium catalyst resulting in turnover-
limiting allylic C-H bond activation to give a π-allyl-Pd
intermediate.
(6) (a) Tsang, W. C. P.; Zheng, N.; Buchwald, S. L. J. Am. Chem. Soc. 2005,
127, 14560–14561. (b) Inamoto, K.; Saito, T.; Katsuno, M.; Sakamoto,
T.; Hiroya, K. Org. Lett. 2007, 9, 2931–2934. (c) Tsang, W. C. P.;
Munday, R. H.; Brasche, G.; Zheng, N.; Buchwald, S. L. J. Org. Chem.
2008, 73, 7603–7610. (d) Mei, T.-S.; Wang, X.; Yu, J.-Q. J. Am. Chem.
Soc. 2009, 131, 10806–10807. (e) Wasa, M.; Yu, J.-Q. J. Am. Chem.
Soc. 2008, 130, 14058–14059. (f) Jordan-Hore, J. A.; Johansson,
C. C. C.; Gulias, M.; Beck, E. M.; Gaunt, M. J. J. Am. Chem. Soc. 2008,
130, 16184–16186. (g) Chen, X.; Hao, X.-S.; Goodhue, C. E.; Yu, J.-
Q. J. Am. Chem. Soc. 2006, 128, 6790–6791. (h) Brasche, G.; Buchwald,
S. L. Angew. Chem., Int. Ed. 2008, 47, 1932–1934. (i) Hamada, T.; Ye,
X.; Stahl, S. S. J. Am. Chem. Soc. 2008, 130, 833–835. (j) Shi, Z.; Zhang,
C.; Li, S.; Pan, D.; Ding, S.; Cui, Y.; Jiao, N. Angew. Chem., Int. Ed.
2009, 48, 4572–4576.
Results and Discussion
One observation from our previous studies suggests that
the limitation of using excess alkene substrates is due to the
isomerization of terminal alkenes to internal alkenes, which
are ineffective substrates for amination (eq 1).8c,12 To achieve
(7) For the early studies on the intramolecular allylic amination of alkenes
with substrate limitation, see: (a) Hedegus, L. S.; Allen, G. F.; Bozell,
J. J.; Waterman, E. L. J. Am. Chem. Soc. 1978, 100, 5800–5807. (b)
Weider, P. R.; Hegedus, L. S.; Asada, H.; D’Andreq, S. V. J. Org.
Chem. 1985, 50, 4276–4281. (c) Heathcock, C. H.; Stafford, J. A.;
Clark, D. L. J. Org. Chem. 1992, 57, 2575–2585. (d) Larock, R. C.;
Hightower, T. R.; Hasvold, L. A.; Peterson, K. P. J. Org. Chem. 1996,
61, 3584–3585.
(8) For the recent intermolecular allylic amination, see: (a) Reed, S. A.;
Mazzotti, A. R.; White, M. C. J. Am. Chem. Soc. 2009, 131, 11701–
11706. (b) Reed, S. A.; White, M. C. J. Am. Chem. Soc. 2008, 130,
3316–3318. (c) Liu, G.; Yin, G.; Wu, L. Angew. Chem., Int. Ed. 2008,
47, 4733–4736. For the intramolecular reactions, see: (d) Fraunhoffer,
K. J.; White, M. C. J. Am. Chem. Soc. 2007, 129, 7274–7276. (e)
Wu, L.; Qiu, S.; Liu, G. Org. Lett. 2009, 11, 2707–2710. (f) Nahra,
F.; Liron, F.; Prestat, G.; Mealli, C.; Messaoudi, A.; Poli, G.
Chem.sEur. J. 2009, 15, 11078–11082. (g) Beccalli, E. M.; Broggini,
G.; Paladino, G.; Penoni, A.; Zoni, C. J. Org. Chem. 2004, 69, 5627–
5630. For the diamination of alkenes involving allylic C-H activation,
see: (h) Wang, B.; Du, H.; Shi, Y. Angew. Chem., Int. Ed. 2008, 47,
8224–8227.
more efficient transformations of alkenes, alkene isomeriza-
tion must be minimized. Mechanistically, the isomerization
of terminal alkenes is possibly catalyzed by palladium black
or Pd nanoparticles, generated from the catalyst decomposi-
tion due to the rate-limiting mass-transfer of oxygen gas into
solution.13,14 We hypothesized that, if soluble strong oxidants
were used instead of oxygen, the reoxidation of Pd(0) might
be more efficient (Scheme 2). In addition, the strong oxidants
might oxidize the π-allyl-Pd(II) species directly to an allyl-
Pd(IV) intermediate which could undergo reductive elimina-
tion to regenerate Pd(II) (Scheme 3).15 Thus, the minimiza-
tion or elimination of palladium catalyst decomposition might
be expected, which could reduce or inhibit the alkene
isomerization and result a more efficient allylic C-H oxidative
amination.
(9) For selected examples on Pd-catalyzed aerobic oxidative amination
of alkenes, see: (a) Timokhin, V. I.; Anastasi, N. R.; Stahl, S. S. J. Am.
Chem. Soc. 2003, 125, 12996–12997. (b) Brice, J. L.; Harang, J. E.;
Timokhin, V. I.; Anastasi, N. R.; Stahl, S. S. J. Am. Chem. Soc. 2005,
127, 2868–2869. (c) Timokhin, V. I.; Stahl, S. S. J. Am. Chem. Soc.
2005, 127, 17888–17893. (d) Rogers, M. M.; Wendlandt, J. E.; Guzei,
I. A.; Stahl, S. S. Org. Lett. 2006, 8, 2257–2260. (e) Rogers, M. M.;
Kotov, V.; Chatwichien, J.; Stahl, S. S. Org. Lett. 2007, 9, 4331–
4334.
Guided by this strategy, we initiated our studies by testing
the reactions of 1-undecene 1a with methyl N-tosylcarbamate
2a catalyzed by Pd(OAc)2 (5 mol %), in the presence of a
(10) For recent examples for Pd-catalyzed oxidative amination of alkenes,
see: (a) Alexanian, E. J.; Lee, C.; Sorensen, E. J. J. Am. Chem. Soc.
2005, 127, 7690–7691. (b) Liu, G.; Stahl, S. S. J. Am. Chem. Soc.
2006, 128, 7179–7181. (c) Desai, L. V.; Sanford, M. S. Angew. Chem.,
Int. Ed. 2007, 46, 5737–5740. (d) Streuff, J.; Ho¨velmann, C. H.;
Nieger, M.; Mun˜iz, K. J. Am. Chem. Soc. 2005, 127, 14586–14587.
(e) Mun˜iz, K. J. Am. Chem. Soc. 2007, 129, 14542–14543. (f) Michael,
F. E.; Sibbald, P. A.; Cochran, B. M. Org. Lett. 2008, 10, 793–796.
(g) Sibbald, P. A.; Michael, F. E. Org. Lett. 2009, 11, 1147–1149. (h)
Rosewall, C. F.; Sibbald, P. A.; Liskin, D. V.; Michael, F. E. J. Am.
Chem. Soc. 2009, 131, 9488–9489.
(12) There are a lot of palladium black observed in the reaction eq 1.
(13) The catalyst decomposition is possibly resulted by rate-limiting mass-
transfer of oxygen gas into solution, for detail see: Steinhoff, B. A.;
Stahl, S. S. J. Am. Chem. Soc. 2006, 128, 4348–4355, and references
therein.
(14) The alternate pathway for alkene isomerization involving Pd-hydride
species cannot exclude, in which Pd-hydride is generated from the
oxidative addition of HX to Pd(0); for detail see: Amatore, C.; Jutand,
A.; Meyer, G.; Carelli, I.; Chiarotto, I. Eur. J. Inorg. Chem. 2000,
1855–1859.
(11) For the reviews on the allylic amination of alkenes, see: (a) Johannsen,
M.; Jørgensen, K. A. Chem. ReV. 1998, 98, 1689–1708. (b) Mu¨ller,
T. E.; Beller, M. Chem. ReV. 1998, 98, 675–703.
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A R T I C L E S
Yin et al.
Scheme 2. Possible Mechanism for the Oxidative Amination of
Alkenes and Alkene Isomerization
Table 1. Screen Result of Oxidative Allylic Amination with Various
Oxidantsa
entry
oxidant
additive
yieldb
1
2
3
4
5
6
7
8
(tBuO)2
H2O2 ·urea
tBuOOAc
K2S2O8
(PhCOO)2
PhlO
Phl(OAc)2
Phl(OPiv)2
Phl(OPiv)2
Phl(OPiv)2
Phl(OPiv)2
Phl(OPiv)2
Phl(OPiv)2
Phl(OPiv)2
BQ
39% (57:43)
20% (66:34)
43% (64:36)
58% (65:35)
70% (87:13)
47% (84:16)
60% (90:10)
68% (91:9)
41% (90:10)
83% (93:7)
72% (91:9)
63% (95:5)
36% (99:1)
76% (90:10)
31% (71:29)
5% (nd)
9
MA (20 mol %)
NQ (20 mol %)
BQ (20 mol %)
NQ (20 mol %)
NQ (20 mol %)
NQ (20 mol %)
10
11
12c
13d
14e
15f
16f
Scheme 3. Proposed Mechanistic Hypothesis for Allylic Oxidative
Amination
NQ
a Reaction condition: 1a (0.2 mmol), 2a (0.4 mmol), oxidant (0.3
mmol), and Bu4NOAc (0.2 mmol) in NMP (0.25 mL) at 40 °C for 8 h.
b Isolated yield, the data in parentheses is the ratio of allylimide and
stoichiometric amount of base16 and various oxidants (Table
1). Although most of the oxidants examined (including t-butyl
peroxide, hydrogen peroxide, t-butyl peracetate, K2S2O8, and
PhIO) produced significant quantities of linear (E)-allylic
amination product 3a with high regioselectivity (Table 1, entries
1-8), PhI(OPiv)2 performed the best to afford 3a in about 70%
yield, including around 10% nonallylic isomers (entry 8).
Furthermore, in the case of PhI(OPiv)2, we were delighted to
discover that isomerization of 1a was not detected. This
observation prompted us to optimize the reaction conditions.
We tested some electron-deficient alkenes, such as maleic
anhydride (MA), BQ, and NQ as additives in this reaction: NQ
(20 mol %) was found to give the best result (83% yield, entries
9-11). In addition, the amount of isomers of product 3a was
reduced to 7%. The isomers of product 3a were further reduced
by increasing the amount of Bu4NOAc; however, the reaction
yield also decreased (entries 10 and 12-13). Control experi-
ments indicated that both BQ and NQ17 alone are not good
oxidants for this transformation. In addition, no catalytic
turnover was observed when NQ was used as the oxidant (entries
15-16).
nonallylic isomers, which determined by HNMR. c Bu4NOAc (2 equiv).
1
d Bu4NOAc (3 equiv). e [PdOAc(Allyl)]2 (2.5 mol %). f Oxidant (2
equiv). MA ) maleic anhydride, NQ ) 1,4-naphthoquinone, BQ )
benzoquinone.
1-4). Next, we examined a range of terminal alkenes bearing
different functional groups, with various electronic and steric
properties. In the case of alkene 1b with a longer alkyl chain,
the reaction afforded product 4 with results similar to 1a (entry
5). When the alkene substrates 1c-1j, bearing an imide, ester,
ether, or carbonate group, were employed under similar reaction
conditions, linear allylic amination products were formed with
high selectivity and excellent yields (entries 6-15). Importantly,
no isomers were detected in those reactions run in the presence
of 20 mol % of base. The substrate 1k bearing a bulky group,
which was not a viable substrate with our previous catalytic
system, afforded the corresponding products 13 in a moderate
yield (entry 16). A number of allylarenes 1l-1p, bearing
electron-withdrawing and electron-donating groups, were dem-
onstrated to be the most effective substrates under the standard
reaction conditions (entries 17-24). In comparison, the sub-
strates 1o and 1p with electron-withdrawing groups afforded a
slightly lower yield than substrates 1m and 1n with electron-
donating groups (entries 18, 21-23). It is very important that
the reaction of 1m underwent smooth oxidative amination in
good yields with only 1-2 mol % catalyst loading (entries
19-20). For the enyne substrate 1q, the reaction generated the
conjugated enyne imide product 20 in 63% yield with a Z:E
ratio of 30:70 (entry 25). Furthermore, this catalytic system is
compatible with the substrates having Br and I: the reactions
of 1h, 1j, and 1p generated allylimides in good yields without
halogen loss (entries 11, 15, and 23). Overall, compared to the
aerobic oxidative conditions (olefin 3 equiv, Pd catalyst 10 mol
%, see last column of Table 2),8c the newly discovered
Pd(OAc)2/PhI(OPiv)2 catalytic system provides a significant
improvement in product yield and chemoselectivity (quite low-
level of isomerization) and allows use of the olefin as the
limiting reagent and is compatible with low catalyst loading
(1-5 mol %).
With optimized reaction conditions, attention was turned to
the scope of this Pd-catalyzed allylic C-H oxidative amination
process. We first examined the reactivity of different nitrogen
nucleophiles. Some O-alkyl N-sulfonylcarbamates, such as
2a-2d, underwent effective oxidative amination with 1a to
afford corresponding products 3a-3d with excellent yields and
with only a small amount of nonallylic isomers (Table 2, entries
(15) For the reviews on the C-N bond formation through Pd(IV) intermedi-
ate using strong oxidants, see: (a) Mun˜iz, K. Angew. Chem., Int. Ed.
2009, 48, 9412–9423. (b) Lyons, T. W.; Sanford, M. S. Chem. ReV.
2010, 110, 1147–1169. For selected examples see refs 6d-6f,10e,10f
and the references therein. In addition, the alternative mechanism
involving Pd(III) complex is also possible, see: (c) Powers, D. C.;
Geibel, M. A. L.; Klein, J. E. M. N.; Ritter, T. J. Am. Chem. Soc.
2009, 131, 17050–17051. (d) Powers, D. C.; Ritter, T. Nat. Chem.
2009, 1, 302.
(16) In our previous studies,8c although the reaction afforded the allylic
C-H amination product with very low yield (< 10%), the alkenes
isomerization was inhibited when a stoichometric amount of base
(NaOAc) was used.
(17) 1,4-Naphthoquinone has been used as oxidant in palladium-catalyzed
alcohol oxidation, see: Lloyd, W. G. J. Org. Chem. 1967, 32, 2816–
2819.
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Effect of Naphthoquinone on Pd-Catalyzed Amination of Alkenes
A R T I C L E S
Table 2. Pd-Mediated Oxidative Allylic C-H Aminationa
a The reaction was conducted on a 0.2 mmol scale in 0.25 mL of NMP: NQ ) 1,4-naphthoquinone. b Isolated yield, the data in parentheses is the
ratio of allylimide and the nonallylimide isomers which was determined by 1HNMR. c Bu4NOAc (1 equiv). d Pd(OAc)2 (2 mol %). e Pd(OAc)2 (1 mol
%). f Pd (OAc)2 (10 mol %). g Z:E ratio of 20. h The reaction condition of ref 8c: alkene 1 (3 equiv), imide 2 (1 equiv), and Pd catalyst (10 mol %).
General Mechanistic Considerations. Although the palladium-
catalyzed allylic C-H oxidative functionalization of alkenes,
such as acetoxylation, amination, and alkylation, have been
studied, systematic mechanistic investigations are quite rare. We
would like to understand the mechanism of the efficient
palladium-catalyzed allylic C-H oxidative amination of alkenes
described above to provide a rational basis for the further
development of alkene functionalizations.
argued against the possibility of aminopalladation/ꢀ-hydride
elimination pathway and in favor of a mechanism involving a
π-allyl-Pd intermediate (eq 2).
The products of these reactions are consistent with a mech-
anism involving a π-allylpalladium complex generated from
allylic C-H activation. However, an alternative pathway
involving anti-Markovnikov aminopalladation/ꢀ-hydride elimi-
nation cannot be excluded.18 In order to differentiate between
these two mechanistic scenarios, a deuterium labeled substrate
1r-d2 was treated under the standard reaction conditions. The
aminopalladation/ꢀ-hydride elimination mechanism predicts
formation of 22a-d2 but not 22b-d2. The observed formation of
nearly equal amounts of products 22a-d2 and 22b-d2, however,
When a mixture of equal amounts of 1a and cinnamyl acetate
23 was treated under the standard conditions, 3a was formed
in 88% yield, and substrate 23 was quantitatively recovered (eq
3). In a separate experiment, no reaction of 23 occurred (eq 4).
Thus, the failure to observe the formation of cross amination
(18) For some examples on the palladium-catalyzed amination of alkenes
with N-tosylcarbamate as nitrogen nucleophile, which were proposed
to go through trans-aminopalladation pathway, see ref 9a and (a) Lei,
A.; Lu, X. Org. Lett. 2000, 2, 2699–2702. (b) Lei, A.; Lu, X. Org.
Lett. 2000, 2, 2357–2360. (c) Lei, A.; Liu, G.; Lu, X. J. Org. Chem.
2002, 67, 974–980, and the references therein.
(19) For the transformation via Pd(0/II) mechanism, White and coworker
have reported that the reaction of allylic acetate with 2a afforded the
allylic amination product and isomer of allylic acetate, which involved
an oxidative addition of Pd(0), see the Supporting Information of ref
8b.
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A R T I C L E S
Yin et al.
Table 3. Amination of π-Allylpalladium Complexa
product 14 ruled out allylic acetate 23 as an intermediate.19
These results are consistent with a mechanism involving allyl
C-H bond activation to afford a π-allylpalladium intermediate
which is then attacked by the nitrogen nucleophile (Scheme 2).
entry
[O]
time
product
yieldb
1
2
3
4
5
none
9 h
9 h
9 h
40 min
9 h
(PhCOO)2
Phl(OAc)2
Phl(OAc)2
NQ
3a
25
25
3a
11% (only E)
40% (67:33)
34% (83:17)
45% (only E)
a The reaction was conducted on a 0.05 mmol scale in 0.25 mL of
NMP. b Isolated yield, the data in parentheses were the ratio of E and Z.
shorter reaction time (entries 3 and 4). In addition, the reaction
afforded 3a in 45% yield in the presence of NQ (entry 5).
These preliminary results demonstrate that this transformation
proceeds by an irreversible allylic C-H activation to generate
a π-allyl-Pd complex, followed by an irreversible nucleophilic
attack to afford amination products.
Several control experiments were performed: (1) the reaction
of 1 m-d2 with 2a afforded 15-d1 in 39% yield within 30 min,
and 46% 1 m-d2 was recovered without any isomerization or
loss of deuterium label from the starting material (eq 5); (2)
the reaction of π-allylpalladium complex 24 with 2a, in the
presence of excess olefin 1m, afforded amination product 3a
in 49% yield; no formation of olefin 1a or cross amination
product 15 was observed (eq 6). These results suggest that the
allylic C-H bond activation is an irreversible step to generate
a π-allyl-Pd intermediate.
The Effect of Quinones. In nearly every reaction studied thus
far, the benzoquinone or its analogue was used as an oxidant
to carry out the palladium reoxidation. Furthermore, benzo-
quinone has been demonstrated as a ligand to promote nucleo-
philic attack on the π-allyl-Pd complex.21,22 However, the effect
of benzoquinone on the allylic C-H bond activation has not
been investigated.23 As mentioned above, the palladium cata-
lyzed allylic C-H amination reaction proceeds very well with
quinones (20 mol %) in the presence of a stoichiometric amount
of PhI(OPiv)2. In addition, the reaction can also be conducted
in the absence of quinones. Thus, comparison of these two
catalytic systems should provide an excellent opportunity to
investigate the effect of quinones on the catalytic reaction.
First, a series of substituted quinones was investigated in the
reactions of p-methoxy-allylbenzene 1m with 2a. Although all
of these reactions afforded the oxidative amination product with
good to excellent yields (Table 4), faster rates were observed
in the presence of quinones bearing electron-withdrawing
substituents. Furthermore, the independent studies found that
the fastest initial rate was seen with NQ as the electron-
withdrawing ligand, and the slowest rate was obtained in the
absence of any quinone (Figure 1A). On the other hand,
variation of the NQ concentration resulted in a systematic change
in the reaction rate: a first-order dependence on [NQ] was seen
at low concentration (below 0.08 M), and a zero-order depen-
dence was seen at high concentration (above 0.15 M, Figure
1B). On the basis of these results, further kinetic studies focused
on two catalytic systems: Pd(OAc)2/PhI(OPiv)2 (without NQ)
and Pd(OAc)2/NQ/PhI(OPiv)2 (with NQ).
Furthermore, no cross coupling amination products were
observed in the reaction of 1m and 2a in the presence of 3b.
This establishes that the amination of the π-allyl-Pd complex
is also an irreversible step (eq 7).
Table 4. Effect of Various Quinonesa
Finally, the stoichiometric reactions of π-allylPd complex 24
with nitrogen nucleophile 2a were studied. As shown in Table
3, the reaction did not afford any amination products in the
absence of NQ (entry 1). However, when benzoyl peroxide was
added as the oxidant, the reaction afforded the amination product
3a at 11% yield (entry 2). In the case of PhI(OAc)2, the reaction
afforded amination products 25 in 40% yield,20 even within a
a Reaction conditions: 1m (0.2 mmol), 2a (0.4 mmol), Pd(OAc)2
(0.01 mmol), additive (0.04 mmol), Bu4NOAc (0.04 mmol), Phl(OPiv)2
(0.3 mmol) in NMP (0.25 mL) at 40 °C. b Isolated yield.
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Effect of Naphthoquinone on Pd-Catalyzed Amination of Alkenes
A R T I C L E S
Figure 1. Effect of the initial rate on the substituted quinines (A) and the dependence of initial rate on NQ concentration (B): (A) [olefin] ) 0.377 M;
[TsNHCOOMe] ) 0.753 M; [PhI(OOCtBu)2] ) 0.565 M; [Bu4NOAc] ) 0.075 M; [quinone] ) 0.075 M; [Pd(OAc)2] ) 0.019 M in NMP. (B) [olefin] )
0.377 M, [TsNHCOOMe] ) 0.753 M, [PhI(OPiv)2] ) 0.565 M; [Bu4NOAc] ) 0.075 M; [Pd(OAc)2] ) 0.019 M; [NQ] ) 0-0.377 M in NMP.
Figure 2. Dependence of the initial rate on olefin (A), nucleophile (B), catalyst (C), and oxidant (D) concentrations under the catalytic system with 1,4-
naphthoquinone (NQ). Reaction condition: (A) [TsNHCOOMe] ) 0.753 M, [PhI(OPiv)2] ) 0.565 M, [Bu4NOAc] ) 0.075 M, [NQ] ) 0.075 M, [Pd(OAc)2]
) 0.019 M, [olefin] ) 0.283-1.883 M; (B) [olefin] ) 0.377 M, [Pd(OAc)2] ) 0.019 M, [PhI(OPiv)2] ) 0. 565 M, [NQ] ) 0.075 M, [Bu4NOAc] ) 0.075
M, [TsNHCOOMe] ) 0.118-1.507 M; (C) [olefin] ) 0.377 M, [TsNHCOOMe] ) 0.753 M, [PhI(OPiv)2] ) 0.565 M, [Bu4NOAc] ) 0.075 M, [NQ] )
0.075 M, [Pd(OAc)2] ) 0.002-0.075 M; (D) [olefin] ) 0.377 M, [TsNHCOOMe] ) 0.753 M, [Pd(OAc)2] ) 0.018 M, [Bu4NOAc] ) 0.075 M, [NQ] )
0.075 M, [PhI(OPiv)2] ) 0.118-0.753 M.
Kinetic Studies. Kinetic studies revealed distinct differences
between the two catalytic systems: one with NQ and one without
NQ. The dependence of the initial rate on olefin, imides,
palladium catalyst, and PhI(OPiv)2 concentration was evaluated
in each case by monitoring the formation of product by gas
chromatography. In the catalytic system with NQ (standard
reaction condition), the rate exhibited a saturation rate depen-
dence on the olefin 1m and on nucleophile 2a concentration,
and first-order dependence of catalyst concentration (Figure 2).
In contrast, without NQ in the catalytic system, the rate exhibited
first-order dependence on olefin concentration, zero-order
dependence on nitrogen nucleophile concentration, and first-
order dependence on catalyst concentration (Figure 3). The rate
exhibited zero-order dependence on the [PhI(OPiv)2] in both
catalytic systems, indicating that palladium reoxidation is not
the rate limiting step in either system.
Deuterium kinetic isotope effects (KIEs) in the two catalytic
systems were also evaluated under the standard conditions:
intramolecular isotope effects were determined from the reaction
of deuterium labeled olefin 1 m-d1 (eq 8); intermolecular
deuterium kinetic isotope effects (KIEs) were determined by
comparing the initial rates with substrates 1m versus 1 m-d2
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A R T I C L E S
Yin et al.
Figure 3. Dependence of the initial rate on olefin (A), nucleophile (B), catalyst (C), and oxidant (D) concentrations in the absence of 1,4-naphthoquinone
(NQ). Reaction condition: (A) [TsNHCOOMe] ) 0.753 M, [PhI(OPiv)2] ) 0.565 M, [Bu4NOAc] ) 0.075 M, [Pd(OAc)2] ) 0.019 M, [olefin] ) 0.118-1.507
M; (B) [olefin] ) 0.377 M, [Pd(OAc)2] ) 0.019 M, [PhI(OPiv)2] ) 0.565 M, [Bu4NOAc] ) 0.075 M, [TsNHCOOMe] ) 0.118-1.883 M; (C) [olefin] )
0.377 M, [TsNHCOOMe] ) 0.753 M, [PhI(OPiv)2] ) 0.565 M, [Bu4NOAc] ) 0.075 M, [Pd(OAc)2] ) 0.0077-0.046 M; (D) [olefin] ) 0.377 M;
[TsNHCOOMe] ) 0.753 M; [Bu4NOAc] ) 0.075 M; [Pd(OAc)2] ) 0.019 M; [PhI(OPiv)2] ) 0.188-0.753 M.
Table 5. Kinetic Isopotic Effect at Different Concentrations of 2a in
(Table 5). Similar intramolecular KIE values [kH/kD ) 1.78 (with
NQ) and 1.50 (without NQ)] were obtained in the two catalytic
the Presence of NQa
systems. In contrast, while the NQ system showed an intermo-
lecular KIE value (kH/kD ) 1.83 ( 0.1) similar to the
intramolecular isotope effect (entry 2),24 almost no intermo-
lecular kinetic isotope effect (KIE value: kH/kD ) 0.93 ( 0.1)
was observed in the catalytic system without NQ (entry 1).
Furthermore, kinetic isotope effects at different concentrations
of nucleophile were studied in the presence of NQ. The observed
kinetic isotope effects have no significant dependence on the
concentration of nucleophile (Table 5, entries 2-5). In addition,
when these reactions of 1 m-d2 were stopped by addition of
excess pyridine at around 20% conversion, the starting material
1 m-d2 was recovered without any H/D scrambling (Table 5,
entries 2-4), which indicated that the allylic C-H bond
activation is an irreversible step.
a Reaction condition: olefin (0.2 mmol, 0.4 M), Pd(OAc)2 (5 mol %),
NQ (20 mol %), Bu4NOAc (20 mol %), PhI(OPiv)2 (1.5 equiv), NMP.
Therefore, it is very difficult to access the precise mechanism
of these catalytic systems. However, the kinetic data outlined
above, together with isotopic labeling studies and kinetic
isotope effects, provide valuable insight into the reaction
mechanism.
Proposed Mechanism and Analysis of Kinetic Data. The
palladium-catalyzed allylic C-H oxidative amination system
containing many components and additives is very complex.
(21) (a) Popp, B. V.; Stahl, S. S. Top. Organomet. Chem. 2007, 22, 149–
189. (b) Ba¨ckvall, J.-E.; Nordberg, R. E.; Wilhelm, D. J. Am. Chem.
Soc. 1985, 107, 6892–6898. (c) Grennberg, H.; Simon, V.; Ba¨ckvall,
J.-E. J. Chem. Soc., Chem. Commun. 1994, 265–266. (d) Ba¨ckvall,
J.-E.; Gogoll, A. Tetrahedron Lett. 1988, 29, 2243–2246. (e) Chen,
M. S.; Prabagaran, N.; Labenz, N. A.; White, M. C. J. Am. Chem.
Soc. 2005, 127, 6970.
(20) The formation of 25 is raised from PhI and 3a catalyzed by Pd catalyst,
see the Supporting Information for details.
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Effect of Naphthoquinone on Pd-Catalyzed Amination of Alkenes
A R T I C L E S
Scheme 4. Possible Mechanism for the Pd-Catalyzed Allylic C-H Oxidative Amination Reaction in the Absence of NQ [NQ )
1,4-Naphthoquinone, X ) OAc or OPiv]
The Effect of NQ. In the absence of NQ, the first-order
dependence on both olefin and palladium catalyst suggests that
the turnover-limiting step is likely the coordination of the olefin
to palladium (Scheme 4A). This outcome is noteworthy because
it contradicts the widespread assumption that the allylic C-H
bond activation proceeds via fast π-complexation of the alkene
to Pd, followed by subsequent slow hydrogen abstraction.25,26
Increasing support for rate-limiting π-complexation of the alkene
to Pd has been found in recent studies by Bercaw and
co-workers.27 The C-H activation step can also be ruled out
as turnover-limiting based on the absence of an intermolecular
kinetic isotope effect (KIE ) 0.93 ( 0.1, Table 5, entry 1).
The observed zero-order dependence on the nitrogen nucleophile
rules out its involvement before the turnover limiting step. Thus,
nucleophilic attack on the π-allyl-Pd complex cannot be
involved in the turnover limiting step. Moreover, the imide
cannot be coordinated to Pd in the rate limiting step.
As mentioned above, a kinetic isotope effect was not observed
in the intermolecular reaction. However, an intramolecular
kinetic isotope effect was still observed (KIE ) 1.50, eq 8). In
order to explain this observation, the possible mechanism was
drawn in Scheme 4B: although the turnover-limiting coordina-
tion of olefin to the palladium catalyst results in an equal amount
of intermediate II-1 and II-2, different rates of C-H versus
C-D bond cleavage and the formation of syn- as well as anti-
allyl-Pd complexes (syn- and anti-III) might result in the
formation of different amounts of amination products 3-d1 and
3 (for details, see the Supporting Information).
In the presence of NQ, the observed saturation dependences
of olefin and nitrogen nucleophile rule out the coordination of
olefin to palladium as the turnover-limiting step. The significant
kinetic isotope effects observed in both intermolecular (KIE )
1.83 ( 0.1, Table 5, entry 2) and intramolecular reactions (eq
8, KIE ) 1.78) indicate that the allylic C-H bond activation is
involved in the turnover-limiting step under the standard
conditions. The saturation rate dependence on the nitrogen
nucleophile concentration in principle can be explained in two
ways. First, there might be a kinetic competition between
reversal of π-allyl-Pd complex formation and nucleophilic attack
by the imide on the π-allyl-Pd complex: at high imide
concentration, the rate would plateau and π-allyl-Pd complex
formation would become rate limiting; but at low imide
concentration, some reversal of the π-allyl-Pd complex back to
alkene would compete with nucleophilic trapping by imide
(Scheme 5A). Second, the reaction may involve rapid equilibra-
tion to give nitrogen coordinated Pd complex VI that undergoes
turnover limiting allylic C-H activation (Scheme 5B).
(22) For the non-allylic substitution reaction systems, benzoquinone-
promoted reductive elimination at PdII is also well-precedented, see
ref 31 and (a) Pe´rez-Rodriguez, M.; Braga, A. A. C.; Garcia-Melchor,
M.; Pe´rez-Temprano, M. H.; Casares, J. A.; Ujaque, G.; de Lera, A. R.;
Alvarez, R.; Maseras, F.; Eapinet, P. J. Am. Chem. Soc. 2009, 131,
3650–3657. (b) Albe´niz, A. C.; Espinet, P.; Martin-Ruiz, B.
Chem.sEur. J. 2001, 7, 2481–2489. (c) Hull, K. L.; Sanford, M. S.
J. Am. Chem. Soc. 2009, 131, 9651–9653.
(23) Benzoquinone plays a important role in Csp2-H activation, see: Chen,
X.; Li, J.-J.; Hao, X.-S.; Goodhue, C. E.; Yu, J.-Q. J. Am. Chem. Soc.
2006, 128, 78–79.
(24) The similar kinetic isotope effect (KIE ) 2.2) was obtained in the
allylic alkylation with BQ as oxidant, see: (a) Lin, S.; Song, C.-X.;
Cai, G.-X.; Wang, W.-H.; Shi, Z.-J. J. Am. Chem. Soc. 2008, 130,
12901–12903. Furthermore, the large KIE values (3.44-5.45) were
observed in the allylic C-H activation of 1-methylenehexane with the
stoichiometric amount of PdCl2 in the various catalytic systems, for
details see the following. (b) Chrisope, D. R.; Beak, P. J. Am. Chem.
Soc. 1986, 108, 334–335. (c) Chrisope, D. R.; Beak, P.; Saunders,
W. H. J. Am. Chem. Soc. 1988, 110, 230–238.
(25) Maitlis, P. M.; Espinet, P.; Russel, M. J. H. In ComprehensiVe
Organometallic Chemsitry; Wilkinson, G.; Stone, F. G. A.; Abel,
E. W., Eds.; Vol 6.; Pergamon: Oxford, 1982.
(26) The rate determining pre-equilibrium step is quite rare in the literature,
see: (a) Trost, B. M.; Metzner, P. J. J. Am. Chem. Soc. 1980, 102,
3572–3577. (b) Trost, B. M.; Strege, P. E.; Weber, L.; Fullerton, T. J.;
Dietsche, T. J. J. Am. Chem. Soc. 1978, 100, 3407–3415.
These two possible mechanisms make different predictions
about the loss of label from olefin 1 m-d2 and about variation
of the kinetic isotope effect as a function of imide concentration.
The kinetic competition mechanism (path a, Scheme 5A)
predicts extensive H/D exchange and a diminished isotope effect
(27) (a) Lin, B.-L.; Labinger, J. A.; Bercaw, J. E. Can. J. Chem. 2009, 87,
264–271. (b) Bercaw, J. E.; Hazari, N.; Labinger, J. A.; Oblad, P. F.
Angew. Chem., Int. Ed. 2008, 47, 9941–9943.
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A R T I C L E S
Yin et al.
Scheme 5. Possible Mechanism To Explain the Saturation Rate Dependence on the Nitrogen Nucleophile Concentration in the Presence of
NQ [NQ ) 1,4-naphthoquinone, X ) OAc or OPiv]
at low imide concentration, where the C-H activation step is
partially reversible. In contrast, rate limiting C-H activation
of a reversibly formed Pd complex VI predicts no H/D exchange
and a isotope effect that does not change with imide concentra-
tion (path b, Scheme 5B). Experimentally, over a concentration
range of imide, the intermolecular kinetic isotope effect was
constant within experimental error (Table 5, entries 2-5). In
addition, no H/D exchange was observed in the reactions of 1
m-d2. These results are consistent with the mechanism involving
rate limiting C-H activation of Pd complex VI (path b) and
rule out the mechanism involving partially reversible C-H
activation (path a).
C-N Bond Formation and Catalyst Regeneration. As shown
in Scheme 6, there are two possible pathways for the C-N bond
formation: (1) the π-allylPd(II) complex might react with
nucleophilic reagent 2 to afford product and release Pd(0), which
is then oxidized by PhI(OPiv)2 to regenerate Pd(II) (Scheme 6,
top); (2) the π-allylPd(IV) intermediate, which is formed via
oxidation of π-allylPd(II) by PhI(OPiv)2, might react with 2 to
give amination product and Pd(II) (Scheme 6, bottom).
Scheme 6. Possible Mechanism for the C-N Bond Formation and
Palladium Catalyst Regeneration
A rate law was derived based on the proposed mechanism in
Scheme 5B (eq 9).28
K1K2k3[1][2][NQ][Pd]T
[HX] + K1[HX][1][NQ]+K1K2[1][2][NQ]
rate )
(9)
The kinetic behaviors observed in the presence of NQ, such as
the first order dependence on palladium catalyst, saturation
dependences on olefin, NQ and nitrogen nucleophile are all
readily accommodated with this rate law.
On the basis of the above analysis, the addition of NQ changes
the reaction mechanism by enabling the fast and reversible
coordination between olefin and palladium. The possible reason
is that coordination of the π-acid ligand NQ increases the
electron-deficiency of the palladium center,29 which makes the
olefin coordination step faster (Scheme 4A or 5B, step 1).30
However, the precise nature of the interaction between NQ and
palladium catalyst is not clear at this moment.31
In the absence of NQ, the palladium-catalyzed oxidative
amination reactions afford allylamine derivatives in good yield.
However, no amination product was formed in the stoichiometric
reaction of π-allyl-Pd complex 24 with imide 2a (Table 3, entry
1). In contrast, this stoichiometric reaction afforded the ami-
nation product in the presence of oxidants (entries 2-4). These
results indicate that the C-N bond formation in the absence of
NQ probably involves a allyl-Pd(IV) intermediate, which comes
from the oxidation of π-ally-Pd(II) by oxidant (e.g., benzoyl
peroxide and PhI(OPiv)2).15,32,33 The high oxidation state Pd(IV)
center would facilitate the reductive elimination to construct
the C-N bond (Scheme 6, bottom).
(28) For deducing the rate expression, see the Supporting Information for
details. In addition, it is hard to explain the relationship between the
initiate rate and base concentration because this catalytic system is
quite complex. But, if the base and PhI(OPiv)2 was keep in the same
concentration, the HX concentration should be a constant.
(29) For the review and selected examples on the related coordination
between electron-deficient olefins and palladium, see: (a) Johnson,
J. B.; Rovis, T. Angew. Chem., Int. Ed. 2007, 46, 840–871. (b) Luo,
X.; Zhang, H.; Duan, H.; Liu, Q.; Zhu, L.; Zhang, T.; Lei, A. Org.
Lett. 2007, 9, 4571–4574. (c) Shi, W.; Luo, Y.; Luo, X.; Chao, L.;
Zhang, H.; Wang, J.; Lei, A. J. Am. Chem. Soc. 2008, 130, 14713–
14720. (d) Zhang, H.; Luo, X.; Wongkhan, K.; Duan, H.; Li, Q.; Zhu,
L.; Wang, J.; Batsanov, A. S.; Howard, J. A. K.; Marder, T. B.; Lei,
A. Chem.sEur. J. 2009, 15, 3823–3829.
(31) Because the observation of the PdII(BQ) complex is extremely rare in
the literature, and its isolation has remained unsuccessful, the relative
study cannot currently be conducted by experiments. For the theoretical
studies on allylPd(II)-BQ complexes by computational calculation, see:
(a) Szabo´, K. J. Organometallic 1998, 17, 1677–1686. (b) Karlsson,
E. A.; Ba¨ckvall, J.-E. Chem.sEur. J. 2008, 14, 9175–9180.
(32) The allyl-Pd(IV) complexes have been reported from the reaction of
stable Pd(II) cycle with allyl bromide, see: (a) Guo, R.; Portscheller,
J. L.; Day, V. W.; Malinakova, H. C. Organometallic 2007, 26, 3874–
3883. (b) Canty, A. J.; Jin, H.; Roberts, A. S.; Skelton, B. W.; Trail,
P. R.; White, A. H. Organometallic 1995, 14, 199–206. (c) Brown,
D. G.; Byers, P. K.; Canty, A. J. Organometallic 1990, 9, 1231–1235.
(d) Byers, P. K.; Canty, A. J. J. Chem. Soc. Chem. Commun. 1988,
639–641.
(30) The olefin-Pd(II) complexes are very reactive, which can be prepared
from the reaction of olefin with highly nucleophilic palladium salt,
such as PdCl2(PhCN)2 or Na2PdCl4. However, there are no any records
on the palladate of olefin with weak nucleophilic Pd(OAc)2. For details,
see: Maitlis, P. M. In The Organic Chemistry of Palladium; Academic
Press: New York and London, 1971; Vol 1.
(33) During our preparation of our manuscript, Szabo´ and coworkers
recently reported a Pd-catalyzed allylic C-H acetoxylation of olefins
with PhI(OAc)2 as oxidant, in which they proposed a mechanism
involving η3-allyl-Pd(IV) intermediates, see: Pilarski, L. T.; Selander,
N.; Bo¨se, D.; Szabo´, K. J. Org. Lett. 2009, 11, 5518–5521.
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Effect of Naphthoquinone on Pd-Catalyzed Amination of Alkenes
A R T I C L E S
In the presence of NQ, the stoichiometric reaction of 24 with
2a in the presence of NQ produced allylic imide 3a (Table 3,
entry 5). Thus, an oxidation to Pd(IV) is not required for product
formation (but might be involved). In the catalytic reaction in
the presence of NQ, C-N bond formation occurs after the
turnover-limiting allylic C-H bond activation. Thus, these two
mechanisms are possible in this case, and it is difficult to
differentiate at this moment.
the reaction involves a rapid equilibration to give a nitrogen-
coordinated olefin-Pd(NQ) complex that undergoes turnover-
limiting allylic C-H bond activation to generate a π-allyl-Pd
intermediate. This work provides valuable insights for further
studies on the functionalization of unactivated olefins.
Acknowledgment. We are grateful for financial support from
the Chinese Academy of Sciences, the National Nature Science
Foundation of China (Nos. 20821002, 20872155, 20972175, and
20923005), the National Basic Research Program of China (973-
2009CB825300), and the Science and Technology Commission of
the Shanghai Municipality (08PJ1411600 and 08dj1400100). G.L.
thanks Prof. Hairong Guan at University of Cincinnati and Prof.
Charles P. Casey at University of Wisconsin at Madison for helpful
discussions.
Summary
We have developed a highly efficient palladium-catalyzed
oxidative amination of unactivated alkyl olefins to produce linear
(E)-allylimide with high regioselectivity. The highly efficient
transformation was achieved by facilitating the reoxidation of
palladium catalyst with the strong oxidant PhI(OPiv)2. The
present work also provides the first systematic analysis of the
mechanism of the allylic C-H oxidative amination. It was found
that the reaction proceeds by turnover-limiting olefin coordina-
tion to palladium catalyst in the absence of any quinone.
However, a substoichiometric amount of NQ plays a vital role
in promoting olefin coordination to the palladium catalyst, and
Supporting Information Available: Experimental procedures
and spectroscopic data. This material is available free of charge
via the Internet at http://pubs.acs.org.
JA1030936
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