Palladium-catalyzed allylic C-H amination of alkenes with N-fluorodibenzenesulfonimide: Water plays an important role

Article abstract of DOI:10.1039/c2cc16720d

A new palladium-catalyzed highly regioselective allylic C-H amination of alkenes with NFSI in the presence of a catalytic amount of water was developed and successfully expanded to Selectfluor-mediated palladium-catalyzed aminations of alkenes with N-tosy

Full text of DOI:10.1039/c2cc16720d

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COMMUNICATION
Palladium-catalyzed allylic C–H amination of alkenes with
N-fluorodibenzenesulfonimide: water plays an important rolew
Tao Xiong, Yan Li,* Lujia Mao, Qian Zhangz and Qian Zhang*
Received 30th October 2011, Accepted 22nd December 2011
DOI: 10.1039/c2cc16720d
A new palladium-catalyzed highly regioselective allylic C–H
amination of alkenes with NFSI in the presence of a catalytic
amount of water was developed and successfully expanded to
Selectfluor-mediated palladium-catalyzed aminations of alkenes
with N-tosylcarbamates in water at room temperature.
Recently, palladium-catalyzed highly efficient allylic C–H
aminations of terminal alkenes were realized by employing
the strong oxidant PhI(OPiv)2, during which the high
oxidation state Pd(IV) center might facilitate the reductive
elimination to construct the C–N bond.7d In addition,
activated by platinum or palladium hydroxy dimers, the
formation of p-benzylic and p-allylic platinum or palladium
species directly from benzylic and allylic C–H bonds was
realized.8 Therefore, by choosing F+ as oxidant, we attempt
to realize allylic C–H bond activation/amination utilizing
the in situ generated palladium hydroxy complex5a and
Pd(II)/Pd(IV) catalytic cycle. In this communication, a new
palladium-catalyzed intermolecular allylic C–H amination of
alkenes with NFSI in the presence of a catalytic amount of
water is described (Scheme 1). In addition, with this protocol,
palladium-catalyzed Selectfluor-mediated aminations of
alkenes with N-tosylcarbamates were successfully realized at
room temperature in water.
Amines are ubiquitous in both naturally occurring and
man-made compounds which demonstrate high levels of bio-
logical activity.1 Direct construction of a C–N bond via C–H
amination is one of the most exciting and challenging fields
in the synthesis of amines. Accordingly, the research area of
metal catalyzed C–H amination especially utilizing palladium2
has led to significant results. Recently, C–H functionalization
via a Pd(II)/Pd(IV) catalytic cycle received much attention by
employing various oxidants.3 However, mixtures of products
were usually obtained because many of the commonly used
oxidants contain oxygen, nitrogen, or halogen moieties
that are subsequently capable of participating in reductive
elimination. As a result, the use of bystanding F+ oxidants
for addressing this widespread problem in organometallic
chemistry was proposed4a and some excellent results were
obtained.4 Very recently, we realized the copper-catalyzed
benzylic C–H and aromatic C–H dehydrogenative-cross-
coupling (DCC) reactions by employing Selectfluor as oxidant,5a
and palladium-catalyzed benzylic5b or aromatic5c C–H amina-
tion reactions with N-fluorodibenzenesulfonimide (NFSI).
The high selectivities for benzylic C–H bonds prompted us
to investigate allylic C–H direct amination reactions with
NFSI.
Our study began by examining the amination reaction of
2-allylisoindoline-1,3-dione (1a) with NFSI. With Pd(OAc)2
(0.1 equiv.) as the catalyst, the reaction of 1a (1.2 mmol) and
NFSI (1.0 equiv.) was conducted at 60 1C in perchloro-
methane for 5.5 h; an allylic amination product 2a, an
isomerized9 internal alkene 3a and an aminooxygenation10
product 4a were generated in 66%, 11% and 14% yields,
respectively (eqn (1)). However, when NBS was employed
instead of NFSI, no reaction occurred. The observation of
aminooxygenation product 4a led us to perform the reaction
of 1a under anhydrous conditions. Surprisingly, when the
above reaction was performed under anhydrous conditions,
after 5.5 h, only isomerization product 3a was obtained in
44% yield, along with 51% 1a recovered. However, by adding
0.1, 0.3 and 0.5 equiv. of water to the above anhydrous
reaction of 1a and NFSI, within 5.5 h, 2a was obtained in
57%, 75%, and 75% yields, respectively. Thus, the reaction
was further optimized by adding 0.3 equiv. of water. After
optimizations (including the solvent, temperature, additives
Oxidative amination reactions of alkenes are synthetically
attractive because they lead to a net increase in substrate
functionality and significant developments on the aza-Wacker
process have been achieved.6 Comparatively, the competitive
oxidative allylic amination, which needs an additional C–H
activation step for the formation of a p-allylPd(II) intermediate,
is less common especially for intermolecular reactions.7
Department of Chemistry, Northeast Normal University, Changchun,
130024, China. E-mail: liy078@nenu.edu.cn, zhangq651@nenu.edu.cn;
Fax: +86-431-85099759
w Electronic supplementary information (ESI) available: Experimental
procedures and analytical data for all compounds. See DOI: 10.1039/
c2cc16720d
Scheme 1 Pd(OAc)2 catalyzed allylic C–H amination in the presence
z Please note that Qian Zhang and Prof. Qian Zhang are two different
persons.
of catalytic amount of water.
c
2246 Chem. Commun., 2012, 48, 2246–2248
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Table 1 Allylic C–H amination of 1b–1o with NFSIa,b
Scheme 2 The proposed mechanism for the allylic C–H amination of
alkenes.
a reductive elimination to give the oxidative amination
product 2 and regenerates Pd(0) catalyst, since the reaction
also works catalytically with Pd(0) catalysts (as evidenced by
data in ESIw). An alternative mechanism via a Pd(II)/Pd(IV)
catalytic cycle cannot be excluded for the formation of 2 from
intermediate D.14 4a might also be formed via the aminooxy-
genation10 of 1a with intermediate B.
a
Reactions were carried out with 1 (1.2 mmol), NFSI (1.0 equiv.),
Pd(OAc)2 (0.1 equiv.) and H2O (0.3 equiv.) in CCl4 (5 mL) at 60 1C
with KF (2.0 equiv.) as additive. Isolated yield. Yield of 2 and
To gain further evidence, 19F NMR and ESI/MS experiments
were performed. We hypothesized that a diagnostic Pd–F signal
would be visible in the 19F NMR spectrum if we were to react
NFSI with Pd(dba)2. To our delight, in anhydrous CDCl3, a
single peak at ꢀ386 ppm was observed characteristic of a Pd–F
bond15 and no signal appeared in CDCl3 without pre-treatment
with 4 A molecular sieves. This result showed that the Pd–F
bond in PdFN(SO2Ph)2 was easily broken in the presence of
water. The ESI mass spectrum of a mixture of Pd(dba)2 and
NFSI showed the signals corresponding to the cationic
p-allylPd(II) species I (m/z 222.9), the cationic Pd(II) acetonitrile
complex II (m/z 442.9), HPdF + Na+ species III (m/z 148.9) and
Pd(H2O)(CH3CN) + Na+ species IV (m/z 187.9). In addition,
the Pd(II)(H2O) complex V (m/z 743.1), Pd(II) acetonitrile
complex VI (m/z 723.1) and cationic FPd(II)(PPh3)(H2O) VII
(m/z 404.9) (all the signals containing the characteristic isotope
distribution for palladium) also were observed by the reaction of
Pd(PPh3)4 and NFSI. The ESI mass spectra suggested the
presence of the key palladium hydroxo complex B.15,16
b
c
d
nonallylic isomers. NaHCO3 (1.0 equiv.) as additive.
and palladium catalysts, see ESIw), 2a could be obtained in
88% yield.
ð1Þ
We next explored the scope of this allylic amination reaction
with other alkenes (Table 1). Alkenes 1b–g led to linear
(E)-allylamine derivatives 2b–g in 63–85% yields and with
high regioselectivity. Both homoallylic internal alkene 1h and
terminal alkene 1i substrates gave the same amination product
2h along with some nonallylic isomerization products,
although a relatively longer reaction time was needed for 1h.
Starting from cyclic alkenes 1j and 1k, the allylic amination
reactions were also achieved forming allylic phthalimides
2j and 2k in good yields. Based on our recent interest in the
reactions of acetoacetanilide derivatives,11 we attempted
amination reaction of NFSI with substrate 1l. Amination
product 2l was obtained in 66% yield with the amide group
preserved. In addition, by employing NaHCO3 as an additive,
simple aliphatic alkenes 1m, 1n and 1o could also react with
NFSI to afford the corresponding amination products 2m, 2n
and 2o in moderate yields. As shown in Table 1, these
reactions are tolerant to a wide range of functionalities, such
as ketal, amide, methyl aryl ether, silyl, cyano and ester
functional groups.
Most C–H bond activation/functionalization reactions are
usually carried out in organic solvents and the extrusion of
moisture has been essential. Therefore, it is highly important to
develop metal-catalyzed direct C–H functionalization reactions
under ambient conditions of air and water. The mechanism
described in Scheme 2 suggests the important role of water in the
transformation from 1 to 2. Therefore, with water as solvent, F+
mediated allylic C–H aminations with N-tosylcarbamates
were tested. To our delight, Selectfluor mediated reaction of
allylbenzene derivatives with N-tosylcarbamates afforded
amination product 6 in 65–82% yields at room temperature
(Scheme 3). It should be noted that the transformations from
1 to 2/6 represent one of the most operationally convenient
palladium-catalyzed allylic C–H aminations reported to date.6
In summary, we have presented a new palladium/water
catalyzed highly regioselective allylic C–H amination of
alkenes with NFSI, in which the allylic C–H bond might be
activated by the in situ generated Pd(OH)N(SO2Ph)2 catalyst
via the reaction of PdFN(SO2Ph)2 with water. In addition, this
methodology is successfully expanded to Selectfluor-mediated
Although the mechanistic details of this transformation are
not very clear at the moment, we propose the possible catalytic
cycle for the formation of 2 in Scheme 2. The suggested initial step
is the oxidation of Pd(0) by NFSI to form Pd(II) species A,12 which
reacts with water to provide a key Pd(II) hydroxo complex B.12,13
Intermediate B performs the C–H activation to provide a
p-allylPd(II) intermediate D via C. Intermediate D undergoes
c
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Scheme 3 Allylic C–H amination of allylbenzene derivatives with
N-tosylcarbamates in water.
palladium-catalyzed aminations of allylbenzene derivatives
with N-tosylcarbamates in water at room temperature. Other
attractive advantages of this method include compatibility
with alkenes bearing a wide range of functional groups and
the use of mild reaction conditions. This new C–H amination
strategy might open a new way to direct C–H functionalization
in water, and the related studies are underway.
We gratefully acknowledge the NCET (08-0756), the NSFC
(21172033), the Fundamental Research Funds for the Central
Universities (09ZDQD07) and the Science Foundation for
Young Teachers of Northeast Normal University for financial
support of this research.
9 Alkene isomerization is a common process catalyzed by palladium
hydrides, see: J. Tsuji, Palladium Reagents and Catalysts. Innovations
in Organic Synthesis, Wiley, Chichester, 1995.
Notes and references
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14 We also prepared p-allylPd(OAc)/2 complex 5 and investigated its
reactivity with NFSI [eqn (2)]. When the mixture of equal amounts
of 5 and NFSI reacted in perchloromethane at 60 1C for 0.5 h, 2b
was formed in 79% yield, for the preparation of p-allylPd(OAc)/2
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15 For 19F NMR and the proposed possible conversion procedure in
ESI/MS, see the ESIw.
16 The mixture of allylbenzene (1.5 equiv.), Pd(dba)2 (0.025 mmol),
water (4.0 equiv.) and NFSI (4.0 equiv.) in perchloromethane
(1 mL) was reacted at room temperature for 30 min and 50 mL
was used to perform the ESI in acetonitrile, the palladium isotope
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c
2248 Chem. Commun., 2012, 48, 2246–2248
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