Efficient reoxidation of palladium by a hybrid catalyst in aerobic palladium-catalyzed carbocyclization of enallenes

Article abstract of DOI:10.1002/chem.200900980

A hybrid catalyst was used to obtain efficient Pd-catalyzed aerobic carbocylization of enallenes to bicyclic trienes. The Hybrid catalysts were obtained by the oxidation of enallenes with molecular oxygen at room temperature in the presence of catalytic a

Full text of DOI:10.1002/chem.200900980

COMMUNICATION
DOI: 10.1002/chem.200900980
Efficient Reoxidation of Palladium by a Hybrid Catalyst in Aerobic
Palladium-Catalyzed Carbocyclization of Enallenes
Eric V. Johnston, Erik A. Karlsson, Staffan A. Lindberg, Bjçrn ꢀkermark, and
Jan-E. Bꢁckvall*[a]
Oxidation reactions play an important role in synthetic
transformations, and there is a current need for the develop-
ment of more selective and more efficient catalytic oxida-
tion methods. There is an increasing demand from society to
develop bioinspired, environmentally benign oxidation pro-
cesses.[1] In such processes, it is desirable to use oxidants
Scheme 1. Electron transfer facilitated by an ETM.
such as molecular oxygen and hydrogen peroxide, which do
not give rise to any waste products and, therefore, fulfill the
requirement of “green chemistry”.[1a,2] In a catalytic oxida-
tion reaction, the substrate-selective catalyst, which may be
a transition metal, oxidizes the substrate to the desired
product. The reduced form of the catalyst is subsequently
reoxidized by the oxidant, which in a green process should
be O2 or H2O2. Direct reoxidation of the transition-metal
catalyst by O2 or H2O2 have been reported.[3,4,5,6] This ap-
proach fails in many cases owing to a high activation barrier
that leads to slow electron transfer between the reduced
form of the metal and O2 or H2O2, and this may result in
catalyst deactivation through competing pathways. One way
to overcome this large jump in oxidation potential is to
mimic the biological respiratory chain, which uses several
coupled redox catalysts as electron-transfer mediators
(ETMs). For example, in a metal-catalyzed oxidation, an
ETM may be employed to facilitate electron transfer be-
tween the reduced substrate-selective catalyst (Mred) and the
stoichiometric oxidant (O2 or H2O2, Scheme 1).
our research group reported an aerobic Pd-catalyzed oxida-
tive carbocyclization of allene-substituted olefins with the
aid of two ETMs (Scheme 2).[8] One way to increase the effi-
ciency of this aerobic carbocyclization would be to covalent-
ly link the two ETMs into one catalyst, thus enhancing the
rate of the reoxidation of palladium. We have recently de-
signed and prepared hybrid catalysts 1 and 2, which consist
of a Schiff base unit with pendant hydroquinone groups
(Scheme 2).[9] Herein, we describe the use of the hybrid cat-
alyst 1 to obtain efficient Pd-catalyzed aerobic carbocyliza-
tion of enallenes 3 to bicyclic trienes 4.
The starting materials 3a–e were prepared as previously
described (see the Supporting Information).[10,11] The hybrid
catalysts 1 and 2 were prepared according to a new method
developed in our laboratory.[12] Oxidation of 3a with molec-
ular oxygen at room temperature in the presence of catalytic
amounts of PdACTHNUTRGNE(UNG OAc)2 (5 mol%) and hybrid catalyst 1
(5 mol%) in THF under an O2 atmosphere resulted in mod-
erate conversion to 4a and long reaction times (Table 1,
entry 1). The use of other solvents such as dichloromethane,
acetonitrile, or toluene gave no significant increase in the
rate. However, the rate of the aerobic oxidation of 3a was
improved in the presence of a protic solvent. Thus, oxidation
of 3a with molecular oxygen at room temperature in THF/
There are only a handful of examples of palladium-cata-
À
lyzed aerobic oxidations involving C C bond formation
À
compared with the number of examples involving C O and
À
C N bond formation, and in most of them high catalytic
loading or high oxygen pressure is required.[7] Previously,
MeOH in the presence of catalytic amounts of PdACHTUNGTRENNUNG(OAc)2
[a] E. V. Johnston, E. A. Karlsson, S. A. Lindberg, B. ꢀkermark,
J.-E. Bꢁckvall
(5 mol%) and hybrid catalyst 1 (5 mol%) resulted in an in-
creased conversion, yet still with long reaction times
(Table 1, entry 2).
Department of Organic Chemistry, Arrhenius Laboratory
Stockholm University, 106 91 Stockholm (Sweden)
Fax : (+46)8-154-908
Interestingly, carrying out the reaction in pure methanol
led to a significant increase in the rate of the aerobic oxida-
tion at room temperature, with full conversion to 4a after
E-mail: jeb@organ.su.se
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/chem.200900980.
Chem. Eur. J. 2009, 15, 6799 – 6801
ꢂ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
6799

idation with catalyst 2 in place
of 1. Oxidation of 3a by using
2.5 mol% of 2 and 2.5 mol% of
PdACTHNURTGENNUG(OAc)2 reached full conver-
sion to 4a after 4 h (Table 1,
entry 9). This is significantly
slower than the corresponding
reaction with hybrid 1, which
reached full conversion after
only 0.3 h. The slower reaction
is most likely due to the fact
that catalyst 2 is quite insoluble
in ethanol.
To estimate the efficiency of
hybrid catalyst 1, we ran the
corresponding reaction to that
of Table 1, entry 6, but with
separate
CoACTHNGUTERN(UNG salmdpt)
(2.5 mol%, salmdptH2 =bis[3-
(salicylideneimino)propyl]me-
thylamine) and benzoquinone
(5 mol%). The separate-com-
ponent reaction reached com-
pletion after 1.5 h, whereas in
Scheme 2. In biomimetic aerobic oxidation, the use of ETMs enables low-energy electron transfer from the
substrate to molecular oxygen. The merging of two ETMs would facilitate the electron transfer (E=CO2Me,
R=R’=Me or R,R’=(CH2)5).
Table 1. PdII-catalyzed aerobic allylic oxidation of substrate 3a.[a]
Table 1, entry 6 in which hybrid catalyst 1 was used, the cor-
responding reaction took only 0.3 h. This illustrates that
hybrid catalyst 1 accelerated the reaction of substrate 3a by
a factor of five, and also gave a more selective reaction.
To study the scope of the reaction, a variety of substrates
were tested under the reaction conditions described above
for the aerobic oxidation of 3a with 1 mol% each of Pd-
Catalyst
[mol%]
Solvent
THF
THF/MeOH 4:1 23
MeOH
T
Time Conversion
G
[8C] [h]
[%][b]
AHCTUNGRTEGNUN(N OAc)2 and 1. All of the substrates 3a–e afforded 4a–e in
high yields (Table 2, entries 1–5). The effect of ring size was
studied (Table 2, entries 1 and 5), and as previously report-
ed, six- and eight-membered-ring derivatives led to cis-fused
ring systems.[9] The reaction proceeded readily with sub-
strates that contained either terminal or internal alkenes.
To investigate whether there was any direct reoxidation of
palladium by O2 in ethanol, we carried out the reaction of
3a without the hybrid catalyst 1 at 758C. The reaction was
very unselective and gave <5% of the desired oxidation
product, and substantial amounts of byproducts were
formed. Two nonoxidative side reactions predominate: the
Pd0-catalyzed cycloisomerization[13] and the thermal Alder-
ene reaction of 3a.[14] Clearly, the catalytic reoxidation
system is necessary for this reaction to proceed in a selective
manner.
Although palladium-catalyzed oxidation reactions with
direct reoxidation of Pd0 by molecular oxygen are efficient
in some cases, this approach fails in many other cases as a
result of unfavored electron transfer between Pd0 and O2.
Thus, to obtain high selectivity and high efficiency in Pd-cat-
alyzed aerobic oxidations, the use of cocatalysts (ETMs) are
often required. The use of the hybrid catalyst 1 gives ap-
proximately a five-fold decrease in reaction time compared
1
2
3
4
5
6
7
Pd
Pd
Pd
Pd
Pd
Pd
Pd
N
23
24
24
5
47
95
100
23
40
40
75
75
75
75
3
100
3
100
0.3
2
0.8
4
100
EtOH
EtOH
100 (97)[c]
100 (97)[c]
100
8[d] Pd
PdACHTUNGTRENNUNG(OAc)2 (2.5)/2 (2.5) EtOH
N
9
[a] All reactions were carried out on a 1 mmol scale in 5 mL of solvent
under O2 (1 atm) with palladium acetate and hybrid catalyst 1 or 2.
[b] Conversions were determined by using 1H NMR spectroscopy after
filtration through a silica plug. [c] Isolated yield. [d] 2 mL of solvent was
used.
5 h. An increase of the temperature to 408C allowed the cat-
alytic loading to be lowered to 2.5 mol%, which gave full
conversion within 3 h (Table 1, entry 4). The use of ethanol
gave the same result (Table 1, entry 5). By increasing the
temperature of the reaction in ethanol to 758C, full conver-
sion of 3a to 4a was obtained after 0.3 h. A decrease in the
catalytic loading to 1 mol% of PdACTHNUTRGNEUNG(OAc)2, and 1 mol% of
hybrid 1 gave 4a with full conversion and in 97% isolated
yield after 2 h. When the amount of solvent was reduced
from 5 mL to 3 mL, the reaction was completed in 0.8 h
(Table 1, entry 8). We also carried out the corresponding ox-
with the use of separate benzoquinone and Co
ACHTUNGTREN(NUNG salmdpt) cat-
alysts in ethanol. In the absence of hybrid catalyst 1 or any
6800
www.chemeurj.org
ꢂ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2009, 15, 6799 – 6801

Palladium-Catalyzed Carbocyclization Reactions
COMMUNICATION
Table 2. Palladium(II)-catalyzed aerobic allylic oxidation of 1.[a]
Keywords: carbocyclization
catalysts · oxidation · palladium
· electron transfer · hybrid
Substrate
Product
T [h]
Yield[b] [%]
1
2
0.8
97
[1] a) J. Piera, J. E. Bꢁckvall, Angew. Chem. 2008, 120, 3558–3576;
Angew. Chem. Int. Ed. 2008, 47, 3506–3523; b) F. G. Gelalcha, G.
Anilkumar, M. K. Tse, A. Brꢃckner, M. Beller, Chem. Eur. J. 2008,
14, 7687; c) P. C. A. Bruijnincx, I. L. C. Buurmans, S. Gosiewska,
M. A. H. Moelands, M. Lutz, A. L. Spek, G. van Koten, R. J. M.
Klein Gebbink, Chem. Eur. J. 2008, 14, 1228.
[2] R. A. Sheldon, I. W. C. E. Arends, G. J. ten Brink, A. Dijksman,
Acc. Chem. Res. 2002, 35, 774.
[3] For a review on direct reoxidation of Pd by molecular oxygen, see:
S. S. Stahl, Angew. Chem. 2004, 116, 3480; Angew. Chem. Int. Ed.
2004, 43, 3400.
[4] For examples of direct reoxidation of Pd by O2, see: a) R. M. Trend,
Y. K. Ramtohul, B. M. Stoltz, J. Am. Chem. Soc. 2005, 127, 17778;
b) B. A. Steinhoff, S. R. Fix, S. S. Stahl, J. Am. Chem. Soc. 2002, 124,
766; c) M. Dams, D. E. De Vos, S. Selen, P. A. Jacobs, Angew. Chem.
2003, 115, 3636; Angew. Chem. Int. Ed. 2003, 42, 3512; d) D. R.
Jensen, M. J. Schultz, J. A. Mueller, M. S. Sigman, Angew. Chem.
2003, 115, 3940; Angew. Chem. Int. Ed. 2003, 42, 3810.
[5] a) K. Sato, M. Aoki, M. Ogawa, T. Hashimoto, R. Noyori, J. Org.
Chem. 1996, 61, 8310; b) K. Sato, M. Aoki, J. Takagi, R. Noyori, J.
Am. Chem. Soc. 1997, 119, 12386.
11
94
96
3
2–3
4
5
2–3
2–3
94
96
[6] G. J. ten Brink, I. W. C. E. Arends, R. A. Sheldon, Science 2000, 287,
1636.
[7] See, for example: a) M. Rçnn, P. G. Andersson, J. E. Bꢁckvall, Tetra-
hedron Lett. 1997, 38, 3603; b) E. M. Ferreira, B. M. Stoltz, J. Am.
Chem. Soc. 2003, 125, 9578; c) K. T. Yip, J.-H. Li, O.-Y. Lee, D.
Yang, Org. Lett. 2005, 7, 5717; d) E. M. Beck, N. P. Grimster, R.
Hatley, M. J. Gaunt, J. Am. Chem. Soc. 2006, 128, 2528; e) C.
Adamo, C. Amatore, I. Ciofini, A. Jutand, H. Lakmini, J. Am.
Chem. Soc. 2006, 128, 6829.
[a] The reactions were carried out on a 1 mmol scale with PdACTHNUTRGNEUNG(OAc)2
(1 mol%), hybrid catalyst 1 (1 mol%) in EtOH (2 mL) at 758C under O2
(1 atm). [b] Isolated yield of pure product.
[8] J. Piera, K. Nꢁrhi, J. E. Bꢁckvall, Angew. Chem. 2006, 118, 7068;
Angew. Chem. Int. Ed. 2006, 45, 6914.
[9] B. W. Purse, L. H. Tran, J. Piera, B. ꢀkermark, J. E. Bꢁckvall, Chem.
Eur. J. 2008, 14, 7500.
[10] J. Franzꢄn, J.-E. Bꢁckvall, J. Am. Chem. Soc. 2003, 125, 6056.
[11] The acyclic starting materials 3b and 3d were obtained in the same
way as the cyclic starting materials 3a, 3c, and 3e from the corre-
sponding acyclic allylic bromide.
[12] E. V. Johnston, E. A. Karlsson, L.-H. Tran, B. ꢀkermark, J. E. Bꢁck-
vall, Eur. J. Org. Chem., DOI: 10.1002/ejoc.200900312; for a previ-
ously published procedure for the synthesis of 1 and 2 see Ref. [9].
[13] K. Nꢁrhi, J. Franzꢄn, J. E. Bꢁckvall, Chem. Eur. J. 2005, 11, 6937–
6943.
other ETMs, the aerobic carbocyclization is several orders
of magnitude slower and other competitive side reactions
take over. The use of hybrid catalyst 1 is an important com-
plement to the systems that are already used for reoxidation
of Pd0 by O2. The efficiency of intramolecular electron
transfer allows for low catalytic loading and mild reaction
conditions. This will significantly extend the use of aerobic
metal-catalyzed oxidations.
[14] K. Nꢁrhi, J. Franzꢄn, J. E. Bꢁckvall, J. Org. Chem. 2006, 71, 2914–
2917.
Received: April 14, 2009
Published online: June 19, 2009
Acknowledgements
We thank the Swedish Research Council and the K & A Wallenberg
Foundation for financial support. We also thank Dr. Katrin Roland for
initial studies of the carbocyclization of 3a in methanol.
Chem. Eur. J. 2009, 15, 6799 – 6801
ꢂ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
6801