Palladium catalyzed oxidation of monoterpenes: NMR study of palladium(II)-monoterpene interactions

Article abstract of DOI:10.1016/j.jorganchem.2005.03.026

Reactions of the monoterpenes β-pinene, limonene and myrcene with Pd(II) complexes in acetic acid solutions were studied by ¹H NMR spectroscopy. Various π-allyl palladium complexes were detected in situ and their interaction with CuCl₂ has been investigated. The results clarify the mechanism of allylic oxidation of these substrates mediated by Pd(II)/Cu(II)-based catalytic systems. Originally introduced to regenerate reduced palladium species, CuCl₂ has been shown to play an important role in the formation and/or decomposition of key reaction intermediates - π-allyl palladium complexes. β-Pinene and myrcene readily react with Pd(OAc)₂ giving corresponding π-allyls, with two complexes acyclic and cyclic being formed from myrcene. On the other hand, the formation of π-allyl complexes from limonene occurs at a significant rate only in the presence of CuCl₂. NMR observations, including selective paramagnetic enhancement of spin-lattice relaxation, indicate that π-allyl palladium intermediates specifically interact with Cu(II) ions in the reaction solutions. Such interaction probably involves Cu(II) bonding to Pd(II) via bridging ligands, and seems to be responsible for the accelerative effect of CuCl ₂ in the palladium catalyzed oxidation of the monoterpenes. Indeed, most of these reactions do not occur at all in the absence of CuCl₂.

Full text of DOI:10.1016/j.jorganchem.2005.03.026

Journal of Organometallic Chemistry 690 (2005) 2996–3003
www.elsevier.com/locate/jorganchem
Palladium catalyzed oxidation of monoterpenes: NMR study
of palladium(II)–monoterpene interactions
a
Jos e´ Ailton Gon c¸ alves , M a´ rcio Jos e´ da Silva , Dorila Pil o´ -Veloso ,
a
a
b
Oliver W. Howarth , Elena V. Gusevskaya
a,
*
a
Departamento de Qu ı´ mica, Universidade Federal de Minas Gerais, Belo Horizonte 31270-901, MG, Brazil
b
Centre for NMR, Department of Chemistry, University of Warwick, Coventry CV4 7AL, UK
Received 5 January 2005; revised 11 March 2005; accepted 16 March 2005
Available online 26 April 2005
Abstract
Reactions of the monoterpenes b-pinene, limonene and myrcene with Pd(II) complexes in acetic acid solutions were studied by
H NMR spectroscopy. Various p-allyl palladium complexes were detected in situ and their interaction with CuCl has been inves-
tigated. The results clarify the mechanism of allylic oxidation of these substrates mediated by Pd(II)/Cu(II)-based catalytic systems.
1
2
Originally introduced to regenerate reduced palladium species, CuCl has been shown to play an important role in the formation
2
and/or decomposition of key reaction intermediates – p-allyl palladium complexes. b-Pinene and myrcene readily react with
Pd(OAc) giving corresponding p-allyls, with two complexes acyclic and cyclic being formed from myrcene. On the other hand,
2
the formation of p-allyl complexes from limonene occurs at a significant rate only in the presence of CuCl . NMR observations,
2
including selective paramagnetic enhancement of spin-lattice relaxation, indicate that p-allyl palladium intermediates specifically
interact with Cu(II) ions in the reaction solutions. Such interaction probably involves Cu(II) bonding to Pd(II) via bridging ligands,
2
and seems to be responsible for the accelerative effect of CuCl in the palladium catalyzed oxidation of the monoterpenes. Indeed,
most of these reactions do not occur at all in the absence of CuCl2.
Ó 2005 Elsevier B.V. All rights reserved.
Keywords: Palladium; Oxidation; Limonene; b-Pinene; Myrcene
1
. Introduction
interested in palladium mediated oxidative transforma-
tions of monoterpenes, such as limonene, b-pinene,
camphene and myrcene [10–16]. We have reported effi-
cient and selective oxidations of limonene and b-pinene
into allylic acetates in PdCl (cat)/CuCl (cat)/O and
Palladium catalyzed oxidations represent a commer-
cially valuable pathway to oxygenated products from
olefins and dioxygen, the most abundant and cheapest
oxidant [1–5]. However, their applications to natural
product synthesis are rather scare. Sufficiently abundant
monoterpenes are particularly important precursors of
oxygenated materials of interest to the flavor and fra-
grance industry, which is essentially based on the chem-
istry of terpenes [6–9]. For several years, we have been
2
2
2
Pd(OAc) (cat)/H O systems, respectively [10,11]. A
2
2
2
conventional Wacker catalyst (PdCl /CuCl ) has been
2
2
used to promote a novel oxidative cyclization of myrcene
giving new acetates with a cyclopentane skeleton [13].
Recently, we have developed a chloride-free multi-com-
ponent catalytic combination Pd(OAc) /benzoquinone/
2
Cu or Mn acetates for the aerobic oxidation of limonene
[15]. A good control of chemo- and regioselectivities in
the allylic oxidation of limonene has been achieved
through the addition of p-toluenesulfonic acid.
*
Corresponding author. Tel.: +55 31 3 499 57 55; fax: +55 31 3 499
7 00.
E-mail address: elena@ufmg.br (E.V. Gusevskaya).
5
0
022-328X/$ - see front matter Ó 2005 Elsevier B.V. All rights reserved.
doi:10.1016/j.jorganchem.2005.03.026

J.A. Gon c¸ alves et al. / Journal of Organometallic Chemistry 690 (2005) 2996–3003
2997
The products of the oxidation of limonene, b-pinene
Monoterpene
b a
-Allyl palladium complex
b a
and myrcene reported in the works cited above seem to
arise via the intermediate formation of p-allyl palladium
complexes, with CuCl2 (if any) having behavior far
exceeding that of a simple reoxidation agent. We have
PdX/
2
c
supposed that one of the specific functions of CuCl is
2
1
1a (X=Cl, OAc)
to assist at the decomposition of the p-allyl intermedi-
ates due to the formation of bridging Pd–Cl–Cu com-
plexes, but no spectroscopic studies to support this
hypothesis have been carried out so far.
In the case of camphene, the only allylic hydrogen is
at a bridgehead position and not easily abstracted, so
allylic oxidation products are not expected. Indeed,
the oxidation of camphene with hydrogen peroxide
c
c
b
d
a
b
a
PdX/
2
e
2
2a (X=Cl, OAc)
catalyzed by Pd(OAc)2 resulted in glycol derivatives
ꢀ
b10
b10
a
7
b
a
a
[
11], whereas a PdðIIÞ=NO ðn ¼ 2; 3Þ catalytic system
PdX/2
6
c
n
PdX/2
promoted its oxidative coupling [12,14]. We have
recently studied by in situ NMR the interaction of
camphene with palladium(II) complexes and obtained
evidence for the formation of r-vinyl palladium
hydride intermediates [16].
This paper reports NMR studies of the reactions be-
tween other monoterpenes, i.e., b-pinene, limonene and
myrcene, and Pd(II) complexes in acetic acid solutions.
We have detected the formation of various p-allyl palla-
dium complexes and investigated their interaction with
3
3
4
2
1
d e
c
4
5
2
1
c
1
5
2
5
4
3
de OAc
6
6
OAc
8
7
7
9
10
8
9
8
9
3
3a (X=Cl, OAc)
3b (X=Cl, OAc)
Scheme 1.
are shown in Scheme 2. With a PdCl /CuCl catalytic sys-
2
2
CuCl . The results clarify the mechanism of allylic oxi-
2
tem, limonene gives mainly carveyl acetate 4 with up to
90% selectivity [10], whereas myrcene selectively forms
the products of oxidative cyclization 5 and 6 [13]. It has
been suggested that all these compounds originate from
corresponding p-allyl palladium complexes. On the other
hand, a palladium catalyzed oxidation of b-pinene in ace-
dation of these substrates mediated by Pd(II)/Cu(II)-
based catalytic systems.
2
. Experimental
tic acid solutions containing CuCl is strongly compli-
2
All reagents were purchased from commercial sources
cated by its skeletal rearrangement accompanied by the
addition of nucleophiles present in the solutions [10]. A
combined selectivity of only 15% for allylic oxidation
products 7–10 has been detected after 22 h of the reaction
([b-pinene] = 0.25 M, [Pd(OAc) ] = 0.01 M, [CuCl ] =
and used as received, unless otherwise indicated. Myr-
cene was purchased from Aldrich and distilled before
use. The reactions were carried out in a stirred glass
reactor and followed by measuring the dioxygen uptake
2
2
(
1
2
if any) and/or by gas chromatography (GC) (Shimadzu
7A, Carbowax 20 M). NMR spectra were recorded at
5 °C using a Bruker DRX-400 AVANCE spectrometer
0.02 M, [LiCl] = 0.05 M, 25 °C). Main products are a-ter-
penyl acetate 11 and bornyl derivatives 12, arising from
the nucleophilic attack by acetate or chloride ions on
the carbonium ions formed by the protonation of original
b-pinene. A selective allylic oxidation of b-pinene was
achieved in a CuCl -free system, using Pd(OAc) as cata-
lyst and hydrogen peroxide as both a final oxidant and
reoxidant for reduced palladium species [11]. Pinocarveol
8 and myrtenol 10, along with their acetates 7 and 9, were
obtained with 75% combined selectivity.
operating at 400 MHz. Chemical shifts are referenced to
tetramethylsilane as internal standard. In NMR stan-
dard experiments, concentrations of monoterpenes and
Pd(OAc) were 20 and 10 mM, respectively. CD COOD
(99.5 atom% D) was used as a solvent in NMR experi-
ments. T1 measurements used a standard inversion-
recovery method with 20 s relaxation delays.
2
2
2
3
CuCl , originally introduced to regenerate palladium,
2
plays a key role in the oxidation of limonene and myr-
cene. Both reactions are accelerated by increased Cu(II)
concentration, with an approximately first order rate
dependence being observed. Moreover, substitution of
3
. Results and discussion
In acetic acid solutions, all three monoterpenes stud-
ied, i.e., b-pinene (1), limonene (2) and myrcene (3)
Scheme 1) undergo a palladium catalyzed oxidation by
dioxygen. The main products formed in these reactions
CuCl by other conventional reoxidants dramatically af-
2
(
fects the oxidation reactions. Although nitrate ions
readily oxidize reduced palladium species in acetic acid

2998
J.A. Gon c¸ alves et al. / Journal of Organometallic Chemistry 690 (2005) 2996–3003
AcO
OAc
X = Cl, OAc
X
X
4
8
5
6
7
OAc
OH
X
OH
OAc
9
10
11
12
Scheme 2.
solutions and are reoxidized back by dioxygen, neither
significant oxygen consumption nor the formation of
oxidation products from myrcene have been observed
in the presence of Pd(OAc) /LiNO , Pd(OAc2)/
sities of these signals slowly increase with reaction time.
After 1.5 h and then 5 h, 10% and 35% of b-pinene,
respectively, was converted into p-allyl complex 1a.
After ca. 7 h, equimolar amounts of 1a, based on
2
3
Cu(NO ) or Pd(OAc )/benzoquinone catalytic combi-
3
Pd(OAc) added, were detected in the reaction solution
2
2
2
ꢀ
nations [13]. The PdðIIÞ=NO system also showed a very
(1/1a ꢁ 1/1). The spectral characteristics of complex 1a
are in agreement with those previously reported for re-
lated complexes [17–19]. Measurements of spin-lattice
3
low activity in the oxidation of limonene and b-pinene
[
12]. In the case of b-pinene, a reasonable selectivity of
ca. 50% for oxidation products 8 and 10 was obtained
only in chloroform solutions, whereas in acetic acid
the concomitant acid-catalyzed isomerization/nucleo-
philic addition reactions predominated.
We studied the interaction of b-pinene, limonene and
myrcene with palladium complexes in the absence and in
the presence of Cu(II) ions in deuteriated acetic acid.
relaxation times (T ) of the hydrogens of 1 and 1a pro-
1
vide additional evidence for the signal attribution. The
values of T obtained for the hydrogens of 1a were much
1
shorter (by ca. 10 times) than those of the hydrogens of
b-pinene, which is fully consistent with much higher
molecular weight of 1a and its consequent, much faster
relaxation (Table 2).
Solutions of monoterpene (1 equiv.) and Pd(OAc)
(
Then, CuCl (0.125 equiv.) was introduced into the sys-
tem and the spin-lattice relaxation times of the hydrogen
nuclei of the substrates and of the reaction intermediates
were measured. It has been observed that the addition of
The addition of CuCl (0.125 equiv.) and LiCl (1
2
2
1
0.5 equiv.) were monitored by H NMR for 3–7 h.
equiv.) had no detectable effect on the signals of
b-pinene, however the signals of 1a became much broad-
er, especially those of allylic hydrogens H , H and H .
2
a
b
c
In addition, significant shielding (12–36 Hz) of the sig-
nals of 1a was observed in the presence of paramagnetic
Cu(II), with the changes in chemical shifts of the allylic
hydrogens being greater than those of the methyl groups
(Table 1). Moreover, a specific paramagnetic relaxation
enhancement of the hydrogens of p-allyl palladium com-
plex 1a occurs in the presence of Cu(II), i.e., the allylic
hydrogens relax much faster (by 4–8 times) than other
hydrogens of the molecule. For example, the value of
T or H is ca. 8 times shorter than those of the methyl
Pd(OAc) to the solution of monoterpenes leads to the
2
appearance of various new signals in the NMR spectra.
The analysis of the changes in their intensities, chemical
shifts and relaxation times induced by Cu(II) permitted
us to clarify the mechanism of the Pd(II)/Cu(II) cata-
lyzed allylic oxidation of these monoterpenes and to
understand their different reactivities.
The addition of Pd(OAc) to the acetic acid solution
2
1
a
of b-pinene resulted in no detectable changes in chemical
shifts, widths and relative intensities of its H NMR sig-
nals, even after 7 h (Table 1). Thus, no p-olefin palla-
dium complex is formed in significant concentrations
from b-pinene during the reaction. On the other hand,
some signals attributed to p-allyl palladium complex
groups. As can be seen from Table 2, the introduction of
Cu(II) results as expected in somewhat faster relaxation
of all nuclei in the solution: T of the hydrogens of
1
1
b-pinene and of the methyl hydrogens of 1a becomes
3–4 times shorter than in the absence of CuCl . How-
2
ever, the allylic hydrogens of 1a relax up to 14 times fas-
ter in the presence of CuCl , a much greater increase.
1
a (Scheme 1, Table 1) appear in the spectrum: two sing-
2
lets at 1.00 and 1.38 ppm from methyl groups and three
broadened signals from allylic hydrogens (singlets at
In presence of a small concentration of paramagnetic
ions, the spin-lattice relaxation is known to be often
dominated by pairwise electron–nuclear dipole–dipole
2
.95 and 3.72 ppm and doublet at 4.11 ppm). The inten-

J.A. Gon c¸ alves et al. / Journal of Organometallic Chemistry 690 (2005) 2996–3003
2999
Table 1
NMR data for b-pinene (1) and p-allyl palladium complex 1a
1
b
1
b
b-Pinene (1) d( H)
p-Allyl palladium complex 1a d( H)
H
a
H
b
CH
4.61 (br.s) 4.55 (br.s) 0.72 (s) 1.23 (s)
4.61 (br.s) 4.55 (br.s) 0.72 (s) 1.23 (s) 2.95 (br.s) 3.72 (br.s) 4.11 (br.d) 1.00 (s) 1.38 (s)
+ 0.125 equiv. 4.61 (br.s) 4.55 (br.s) 0.72 (s) 1.23 (s) 2.86 (br.s) 3.63 (br.s) 4.05 (br.d) 0.95 (s) 1.35 (s)
3
CH
3
H
a
H
b
H
c
CH
3
CH
3
a
1
1
1
a
+ 0.5 equiv. Pd(OAc)
+ 0.5 equiv. Pd(OAc)
2
2
a
2
CuCl + 1 equiv. LiCl
c
Dd (Hz)
0
0
0
0
36
36
24
20
12
a
[
b-pinene] = 20 mM, 25 °C, solvent: CD
3
COOD.
Resonance multiplicities in parentheses: (s) singlet, (d) doublet, (br) broadened.
Chemical shift changes induced by the addition of Pd(OAc) and/or CuCl /LiCl.
b
c
2
2
Table 2
2
+
Relaxation times (T
1
) for the protons of b-pinene (1) and p-allyl palladium complex 1a in the absence and in the presence of Cu
b-Pinene (1) T (s) of proton(s) p-Allyl palladium complex 1a T (s) of proton(s)
CH CH
1
1
H
a
H
b
3
CH
3
H
a
H
b
H
c
3
CH
3
2
+a
In the absence of Cu
In the presence of Cu
Increase factor T
3.87
0.86
4.5
3.62
0.90
4.0
2.48
0.70
3.5
2.34
0.68
3.4
0.22
0.02
0.41
0.03
0.27
0.04
6.8
0.55
0.15
3.7
0.54
0.16
3.4
2
+b
c
1
/T1(Cu)
11.0
14.0
a
[
[
b-pinene] = 20 mM, [Pd(OAc)
b-pinene] = 20 mM, [Pd(OAc)
2
] = 10 mM, 25 °C, solvent: CD
3
COOD.
b
c
2
] = 10 mM, [CuCl COOD.
2+
2
] = 2.5 mM, [LiCl] = 20 mM, 25 °C, solvent: CD
3
Ratio between the relaxation times in the absence and in the presence of Cu
.
interactions between an unpaired spin of the paramag-
netic center and the magnetic moment of a resonant nu-
cleus. Therefore, the relaxation time may be used with
care as a measure of its distance from the paramagnetic
center. The larger the distance, the weaker the paramag-
netic contribution to the relaxation. Thus, a specific
paramagnetic relaxation (Table 2) as well as paramag-
netic shifts (Table 1) of the signals of 1a indicate a spe-
cific interaction between p-allyl complex 1a and Cu(II)
ions, with the latter being spatially more proximate to
the allylic hydrogens of the molecule. It is reasonable
to suggest that such interaction is realized via the forma-
tion of bimetallic p-allyl palladium–copper complexes
with bridging acetate or, more probably, chloride li-
gands X as shown in Scheme 3.
plex 1a first broadened but then became thinner before
rapidly returning to their original widths. Simulta-
neously, the yellow-brown solution (a color of Pd(OAc)2
and anhydrous CuCl ) changed to green (a color of
2
Cu(OAc) ), which indicated a substitution of chloride li-
2
gands on Cu(II) by acetate groups due to a ligand ex-
change with Pd(II). The addition of LiCl to this
solution turned it back to brown, with the signals of
p-allyl complex 1a becoming broadened again because
of the specific interaction with paramagnetic Cu(II) ions.
The allylic oxidation of b-pinene, as well as its isom-
erization, is slow at room temperature, with only trace
amounts of oxidation products 7 and 9 being formed
during the NMR experiments. At higher temperatures,
a conversion of b-pinene begins; however, as mentioned
above, the acid-catalyzed isomerization of b-pinene
accompanied by the nucleophilic addition of chloride
and acetate groups occurs faster than its palladium cat-
alyzed oxidation.
It is worthwhile to emphasize the importance of chlo-
ride ions in the formation of such bimetallic complexes.
When only CuCl , without LiCl, was added to the mix-
2
ture of 1 and 1a in acetic acid, the signals of p-allyl com-
R1
R (R )
3
1
X
X
X
L
CuCl
2
R2
Pd
Cu
R2
+
PdX2
+
2CuCl
-
L
OAc
R3
X=Cl, OAc)
R (R )
1
3
O2
(
Scheme 3.

3000
J.A. Gon c¸ alves et al. / Journal of Organometallic Chemistry 690 (2005) 2996–3003
Differently from b-pinene, limonene (2) reacts very
slowly with Pd(OAc) in acetic acid solutions at room
ence of CuCl , the T values of the hydrogens of limo-
2 1
nene generally become 4–8 times shorter, but those of
2a decrease ca. 20 times. This is most probably induced
by the binding of Cu(II) to Pd(II) via bridging ligands
(Table 3). The decomposition of these complexes occurs
even at room temperature, giving carveyl acetate 4 in the
presence of CuCl2.
2
temperature. Only trace amounts of p-allyl complex
1
a (Scheme 1) were detected by H NMR after a 5-h
2
reaction (two singlets at 1.65 and 1.73 ppm from methyl
groups and triplet at 4.75 ppm from two allylic hydro-
gens). It should be mentioned that NMR study of the
interaction between limonene and Pd(II) complexes is
complicated by a partial signal overlap in the region
of 4.7–4.8 ppm between the signals from allylic hydro-
gens H and H of complex 2a and the signals from ter-
Thus, the formation of the p-allyl palladium com-
plex from limonene in acetic acid solutions proceeds
at a significant rate only in the presence of CuCl2.
On the other hand, b-pinene readily forms the corre-
sponding p-allyl complex without the assistance of
CuCl ; though even in this case CuCl also accelerates
a
b
minal vinylic hydrogens H of limonene and those from
e
its oxidation product 4 as well as from vinylic hydro-
gens of 2a itself (Table 3). The spectral characteristics
of complex 2a agree with those previously reported
for related complexes [18,20]. As in the case of
b-pinene, the addition of Pd(OAc)2 resulted in no
detectable changes in chemical shifts, widths and rela-
2
2
the process. This effect can be explained by the partic-
ipation in these processes of bimetallic Pd–Cu com-
plexes formed in the reaction solutions. We have
previously reported the spectroscopic data obtained
during the study of a related Wacker oxidation of pro-
pylene, which indicate the formation of heterometallic
Pd–Cu species in acetic acid solutions [21]. It is known
that p-allyl palladium complexes are formed from ole-
fins via the intermediate formation of p-olefin com-
plexes. Then a formal oxidative addition of the olefin
molecule to palladium(II) occurs giving palladium(IV)
hydride intermediates. The presence of electrophilic
Cu(II) ions bound to palladium via bridging ligands
should favor the olefin coordination to the palladium
atom bearing now a more positive partial charge.
1
tive intensities of H NMR signals of limonene, even
in the presence of CuCl . Thus, in acetic acid solutions,
2
the p-olefin palladium complex, which should be a
short-lived intermediate, is not formed from limonene
in measurable concentrations.
The addition of CuCl (0.125 equiv.) and LiCl (1
2
equiv.) dramatically accelerates the formation of both
p-allyl complex 2a and oxidation product 4 from limo-
nene. Within a few minutes at room temperature, the
concentrations of 2a and 4 in the solution reach 35%
and 7% of the initial concentration of limonene, respec-
tively. Thus, a significant fraction of the Pd(II) ions
present in the solution is rapidly converted to allylic
complex 2a (initial molar ratio limonene/Pd(II) = 2).
Due to the partial signal overlapping mentioned above,
the times of the spin-lattice relaxation of the hydrogens
of 2a were determined in this case from the null points
through which their relatively sharp resonances pass as
Moreover, CuCl can be also involved in the oxidative
2
decomposition of the palladium(IV) hydrides resulting
in p-allyl complexes [18].
The paramagnetic relaxation enhancements show
that both the p-allyl complexes, 1a and 2a, specifically
interact with Cu(II) ions, most probably, via the forma-
tion of bimetallic p-allyl Pd–Cu complexes with bridging
chloride (or acetate) ligands. The decomposition of these
complexes results in the products of the allylic oxidation
of limonene and b-pinene as shown in Scheme 3. There
is in fact a large difference in the reactivity of complexes
they recover from their inversion. The values of T ob-
1
tained for the hydrogens of 2a are, as expected, much
shorter than those of limonene (Table 3). A specific
interaction of Cu(II) ions with p-allyl complex 2a was
confirmed as previously by the substantial and specific
added relaxation enhancement they induce. In the pres-
1a and 2a in the presence of CuCl , with the latter com-
2
plex, formed from limonene, being much more reactive
towards a nucleophilic attack by acetate group leading
Table 3
NMR data for limonene (2) and p-allyl palladium complex 2a: chemical shifts (d) and relaxation times (T
1
)
Limonene (2)
p-Allyl palladium complex 2a
H
a
H
e
CH3(c)
CH3(d)
H
a
and H
b
CH3(c)
1
a
3
4.75 (t, J = 6.4)
d( H)
T
5.40 (br.s)
3.14
0.39
4.70 (s)
1.44
0.32
1.65 (s)
1.81
0.32
1.73 (s)
1.95
0.29
1.68 (s)
e
1.18
b
(s) in the absence of Cu
2+
e
1
1.00
c
2+
e
e
T1(Cu) (s) in the presence of Cu
Increase factor T
0.05
0. 05
d
1
/T1(Cu)
8.0
4.5
5.6
6.7
20.0
23.6
a
Resonance multiplicities and coupling constants (Hz) in parentheses: (s) singlet, (t) triplet, (br) broadened.
b
c
[
[
Limonene] = 20 mM, [Pd(OAc)
Limonene] = 20 mM, [Pd(OAc)
2
] = 10 mM, 25 °C, solvent: CD
3
COOD.
2
] = 10 mM, [CuCl COOD.
2
] = 2.5 mM, [LiCl] = 20 mM, 25 °C, solvent: CD
3
d
e
2+
Ratio between the relaxation times in the absence and in the presence of Cu
Determined from the null points through which the resonances pass as they recover from their inversion.
.

J.A. Gon c¸ alves et al. / Journal of Organometallic Chemistry 690 (2005) 2996–3003
3001
to carveyl acetate 4, i.e., a net allylic oxidation. The
presence of electrophilic Cu(II) ions bound to palladium
in p-allylic intermediates should render them more sus-
ceptible to such attack.
A high stability of the p-allyl complexes formed from
b-pinene, even in the presence of Cu(II) ions, seems to be
responsible for the low selectivity obtained in the oxida-
tion of b-pinene. In acetic acid solutions, especially in
those containing chloride ions, this substrate undergoes
a double-bond protonation followed by isomerization or
nucleophilic addition that is much faster than the allylic
oxidation. A selective allylic oxidation of b-pinene has
been realized only in a chloride-free system, using
Pd(OAc) as a catalyst [11]. This result is completely
2
consistent with the expected relative reactivities of p-al-
lyl palladium chlorides and p-allyl palladium acetates,
with the latter being much more prone to collapse to
allylically substituted systems [18]. Thus, under such
conditions, the allylic oxidation of b-pinene successfully
competes with its protonation. On the other hand, we
have failed to develop a selective oxidation of limonene
in the CuCl free systems, i.e., Pd(OAc) (cat)/LiNO -
2
2
3
(
cat)/O and Pd(OAc) (cat)/H O , which can now be ex-
2 2 2 2
plained by a key role of CuCl in the formation of p-allyl
2
palladium complexes from limonene and also in their
decomposition.
The other monoterpene studied, myrcene (3), readily
reacts with Pd(II) complexes in acetic acid solution even
at room temperature, giving the acyclic and cyclic p-al-
lyl–palladium complexes 3aand 3b (Scheme 1). Spectral
characteristics of these compounds, consistent with
those of related complexes [22–24], are presented in
Tables 4 and 5. The intensities of the signals of 3a and
3
b slowly increase with reaction time and, at 4 h, corre-
spond to ca. 40% conversion of myrcene, which is
slightly less then an equimolar proportion based on pal-
ladium added (initial ratio 3/Pdꢁ2/1). The values of T
1
obtained for the hydrogens of 3a and 3b are, as ex-
pected, much shorter (by 5–10 times) than T for the
1
hydrogens of myrcene itself. The cyclic complex 3b,
which seems to be a precursor of substituted cyclopent-
enes 5 and 6, predominates in the reaction of myrcene
with Pd(OAc) (3a/3b = 1/2).
2
It is interesting that the addition of LiCl (1 equiv.)
leads to a further increase in the relative amounts of
the cyclic complex 3b (3a/3b ꢁ 1/5). We also note that
in the absence of chloride ions, the signals of all allylic
hydrogens in both allylic complexes 3a and 3b, as well
as hydrogens H and H in 3a are slightly broadened
e
d
and become well resolved only after the addition of
LiCl. No products of the oxidation of myrcene appear
in detectable concentrations in the absence of CuCl2.
Next, we studied the interaction of these intermediates
with CuCl . The addition of CuCl (0.125 equiv.) imme-
2
2
diately results in significant broadening the signals of p-
allyl complexes 3a and 3b but not the signals of myrcene

3002
J.A. Gon c¸ alves et al. / Journal of Organometallic Chemistry 690 (2005) 2996–3003
Table 5
NMR data for p-allyl palladium complex 3b: chemical shifts (d) and relaxation times (T
1
)
1
a
b
(s)
c
d
Carbon atom
Hydrogen atom
d( H)
T
1
T
1(Cu) (s)
T1(Cu) (s)
2
3
4
5
6
7
H-2
H-3
H-4
H-5
2.30–2.40 (m)
2.50–2.60 (m)
2.30–2.40 (m)
2.30–2.40 (m)
5.33–5.38 (m)
0.63
0.56
0.63
0.63
1.20
0.45
0.59
0.78
0.59
0.59
1.33
0.48
0.69
0.61
0.69
0.69
0.96
0.41
H
H
H
H
H
c
3
a
a
b
b
(1st isomer)
(2nd isomer)
(1st isomer)
(2nd isomer)
3.07 (d, Ja–c = 12.4)
3
3.05 (d, Ja–c = 11.7)
3
3.85 (d, Jb–c = 7.4)
0.49
0.51
0.44
3
3.89 (d, Jb–c = 7.1)
9
H-9
H-10
1.49 (br.s)
1.49 (br.s)
0.50
0.50
0.56
0.56
0.59
0.59
1
0
a
b
c
Resonance multiplicities and coupling constants (Hz) in parentheses: (s) singlet, (d) doublet, (m) multiplet, (br) broadened.
[
[
Myrcene] = 20 mM, [Pd(OAc)
Myrcene] = 20 mM, [Pd(OAc)
2
] = 10 mM, [LiCl] = 20 mM, 25 °C, solvent: CD
] = 10 mM, [CuCl ] = 2.5 mM, [LiCl] = 20 mM, 25 °C, solvent: CD COOD.
3
COOD.
2
2
3
d
2
More 2.5 mM of CuCl were added to the solution.
itself. This clearly indicates a specific interaction of
Cu(II) ions with the allylic intermediates. Measuring
spin-lattice relaxation times showed, to our surprise, no
significant increase in the relaxation times of any nucleus
present in the solutions, which the paramagnetic Cu(II)
ions should induce. Indeed, as can be seen in Tables 4
and 5, the relaxation times of the hydrogens of 3a and
These results show that CuCl interacts with p-allyl–
2
palladium complexes of myrcene and promotes their fast
decomposition to oxidation products. However, no
paramagnetic enhancement of spin-lattice relaxation is
observed here because, as a result of this reaction, all
Cu(II) ions added are rapidly reduced to diamagnetic
Cu(I) (the reaction mechanism is discussed below).
3
the absence and in the presence of CuCl . Moreover,
b as well as of the myrcene itself are very similar in
The addition of extra amounts of CuCl (more 0.125
2
equiv.) to the solution promoted a further conversion
of myrcene with the formation of 5 and 6 in stoichiom-
etric amounts relative to Cu(II). After initial broaden-
ing, the signals of the p-allylic intermediates rapidly
returned to their original widths. All Cu(II) ions added
were converted into Cu(I) because no significant de-
crease in spin-lattice relaxation times of the nuclei of
either myrcene or p-allyl–palladium complexes was ob-
served in this case (Tables 4 and 5).
2
1
when the H NMR spectrum of the solution was re-mea-
sured after the T experiment, all the previously broad-
1
ened signals of 3a and 3b became well resolved and
returned to their original widths. Simultaneously, a fast
conversion of myrcene into 5 and 6 (as well as into some
unidentified products) was observed even at room tem-
perature, with the total amounts of these products
approximately corresponding to the amounts of CuCl2
added. The formation of the products 5 and 6 was mon-
itored by the integrals of the signals from the vinylic
hydrogens at 6.50–6.57 ppm (doublet of doublets) and
So, once again, the accelerative effect of CuCl on the
2
decomposition of p-allyl–palladium complexes has been
confirmed spectroscopically. The proposed pathway of
myrcene oxidative cyclization is shown in Scheme 4.
5
.62–5.68 ppm (broadened signal) [13].
X
X
X
[
Pd]
Pd
Cu
L
CuCl
2
1
2
-
-
-
PdX
2
OAc
OAc
2CuCl
HX
OAc
-
L
5
X
L
X
X
Cu
Pd
[
Pd]
1
5
4
CuCl
2
2
3
-
-
-
PdX
2
OAc
OAc
2CuCl
OAc
HX
L
-
3
3b (X=Cl, OAc)
Scheme 4.
6

J.A. Gon c¸ alves et al. / Journal of Organometallic Chemistry 690 (2005) 2996–3003
3003
First, two isomers of p-allyl complex 3b are formed
from s-cis and s-trans conformations of myrcene. It
Acknowledgments
should be mentioned that, as in the case of b-pinene
and limonene, the addition of Pd(II) ions, even together
We acknowledge the financial support from the
CNPq and FAPEMIG (Brazil) and scholarships from
CNPq (MJS and JAG). The authors thank Ivana Silva
Lula for technical assistance in the NMR studies.
1
with CuCl , results in no detectable changes in H NMR
2
signals of myrcene. Thus, intermediate p-olefin palla-
dium complexes formed from myrcene should be present
during the reaction, albeit in non-detectable low concen-
trations. The p-allyl palladium intermediates decompose
probably via anti-elimination [25] giving two isomers of
substituted vinyl cyclopentene 5 and 6 and a palla-
dium(II) hydride, with hydrogen being abstracted from
carbons 2 or 5. As confirmed by the NMR study, a coor-
dination of Pd(II) with Cu(II) in 3b is crucial for the
reactivity of this intermediate towards the decomposi-
References
[1] J.-L. Malleron, J.-C. Fiaud, J.-Y. Legros, Handbook of Palla-
dium-catalyzed Organic Reactions, Academic Press, London,
1
997.
2] R.F. Heck, Palladium Reagents in Organic Synthesis, Academic
[
[
Press, London, 1985.
3] G. Poli, G. Giambastiani, A. Heumann, Tetrahedron 56 (2000)
5959.
tion. In the absence of CuCl , no appreciable reaction
2
occurs under the conditions studied. Palladium hydride
undergoes an intramolecular redox reaction resulting in
a proton and Pd(0) complex, which is recycled by CuCl2.
The reduced Cu(I) species can be oxidized back to
Cu(II) by dioxygen, thus keeping the catalytic system ac-
tive. This occurs readily in a catalytic reactor under in-
tense stirring, whereas it is strongly limited by an
oxygen transfer process in the NMR tube. Thus, the pal-
ladium metal and Cu(I) ions are formed at the end of
NMR experiments.
[4] J. Tsuji, Palladium Reagents and Catalysts: Innovations in
Organic Synthesis, Wiley, New York, 1997.
[5] J.-E. Backvall, in: M. Guisnet (Ed.), Heterogeneous Catalysis and
Fine Chemicals, Elsevier Science Publishers, Amsterdam, 1988, p.
1
05.
[6] D.H. Pybus, C.S. Sell (Eds.), The Chemistry of Fragrances, RSC
Paperbacks, Cambridge, 1999.
[
[
[
7] H. Mimoun, Chimia 50 (1996) 620.
8] C. Chapuis, D. Jacoby, Appl. Catal. A 221 (2001) 93.
9] W.E. Erman, Chemistry of the Monoterpenes. An Encyclopedic
Handbook, Marcel Dekker, New York, 1985.
[
[
[
[
[
10] E.V. Gusevskaya, J.A. Gon c¸ alves, J. Mol. Catal. A 121 (1997)
31.
1
11] E.V. Gusevskaya, V.S. Ferreira, P.A. Robles-Dutenhefner, Appl.
Catal. A 174 (1998) 177.
12] M.J. da Silva, E.V. Gusevskaya, J. Mol. Catal. A. 176 (2001)
4
. Conclusions
2
13] J.A. Gon c¸ alves, O.W. Howarth, E.V. Gusevskaya, J. Mol. Catal.
3.
In summary, a specific function of CuCl in the palla-
2
dium catalyzed allylic oxidation of some monoterpenes
has been clarified by in situ NMR. Originally, intro-
duced to regenerate reduced palladium species, CuCl2
was shown to play an important role in the formation
and/or decomposition of key reaction intermediates –
p-allyl palladium complexes. While b-pinene and myr-
A 185 (2002) 17.
14] M.J. da Silva, E.V. Gusevskaya, J. Brazil Chem. Soc. 14 (2003)
83.
[15] J.A. Gon c¸ alves, E.V. Gusevskaya, Appl. Catal. A 258 (2004) 93.
[
16] J.A. Gon c¸ alves, M.J. da Silva, R.B. Alves, O.W. Howarth, E.V.
Gusevskaya, J. Organomet. Chem. 689 (2004) 302.
[
[
17] B.M. Trost, P.E. Strege, Tetrahedron Lett. 30 (1974) 2603.
18] B.M. Trost, P.E. Strege, L. Weber, T.J. Fullerton, T.J. Dietsche,
J. Am. Chem. Soc. 100 (1978) 3407.
cene readily react with Pd(OAc) in acetic acid solutions
2
giving stable p-allyls, the formation of corresponding
complexes from limonene occurs at a significant rate
at room temperature only in the presence of CuCl2.
The results of the NMR experiments, in particular selec-
tive paramagnetic relaxation enhancement, indicate that
the p-allyl palladium intermediates specifically interact
with paramagnetic Cu(II) ions in the reaction solutions.
Such interaction probably involves Cu(II) bonding to
Pd(II) via bridging ligands and seems to be responsible
[19] P.S. Pregosin, H.R. Ruegger, R. Salzmann, A. Albinati, F.
Lianza, R.W. Kunz, Organometallics 13 (1994) 83.
[
20] A.C. Albeniz, P. Espinet, Y.-S. Lin, Organometallics 14 (1996)
977.
2
[
21] A.V. Karandin, E.V. Gusevskaya, V.A. Likholobov, A.G. Stepa-
nov, E.P. Talzi, Kinet. Catal. 31 (1990) 506.
[22] K. Dunne, F.J. McQuillin, J. Chem. Soc. C (1970) 2196.
[
[
[
23] M. Takahashi, H. Suzuki, Y. Moro-oka, T. Ikawa, Chem. Lett.
1979) 53.
(
24] M. Takahashi, H. Urata, H. Suzuki, Y. Moro-oka, T. Ikawa, J.
Organomet. Chem. 266 (1984) 327.
for the accelerative effect of CuCl in the palladium cat-
2
alyzed oxidation of the monoterpenes. Most of these
reactions do not occur at all in the absence of CuCl2.
25] J.M. Takacs, E.C. Lawson, F. Clement, J. Am. Chem. Soc. 119
(1997) 5956.