Cyclopropanation of cyclohexenone by diazomethane catalyzed by palladium diacetate: Evidence for the formation of palladium(0) nanoparticles

Article abstract of DOI:10.1021/om070141a

The diazomethane-mediated cyclopropanation of cyclohexenone using Pd(OAc)₂ and different sources of Pd(0) species as precatalysts has been studied. In the presence of an excess of diazomethane, Pd-(OAc)₂ rapidly evolves to the formation of palladium nanoparticles (less than 1 min), which are active as catalysts in the cyclopropanation process. The nature of these particles has been analyzed through transmission electron microscopy showing a size distribution between 6 and 40 nm. These nanoparticles generated in situ are more active man Pd(0) complexes, preformed nanoparticles, and commercial palladium powder. Cyclic voltammetry measurements of the reaction solution after completion show the presence of Pd(0) species. This is the first time that Pd(0) nanoparticles are evidenced in a cyclopropanation reaction. Moreover, the reduction of Pd(OAc)₂ to Pd(0) in the presence of diazomethane has been theoretically studied through density functional calculations. The formation of methyl and allyl acetates as organic byproducts has been predicted by the theoretical calculations, and these species, as well as oligomers derived from them, have been detected by spectrometric and spectroscopic techniques (MS, NMR, and IR).

Full text of DOI:10.1021/om070141a

3306
Organometallics 2007, 26, 3306-3314
Cyclopropanation of Cyclohexenone by Diazomethane Catalyzed by
Palladium Diacetate: Evidence for the Formation of Palladium(0)
Nanoparticles
Ona Illa,† Cristo´bal Rodr´ıguez-Garc´ıa,† Carles Acosta-Silva,† Isabelle Favier,‡
David Picurelli,‡ Antonio Oliva,† Montserrat Go´mez,*,‡,§ Vicenc¸ Branchadell,*,† and
Rosa M. Ortun˜o*,†
Departament de Qu´ımica, UniVersitat Auto`noma de Barcelona, 08193 Bellaterra, Barcelona, Spain,
Departament de Qu´ımica Inorga`nica, UniVersitat de Barcelona, Mart´ı i Franque`s, 1-11,
08028 Barcelona, Spain, and Laboratoire He´te´rochimie Fondamentale et Applique´e, UMR CNRS 5069,
118 Route de Narbonne, 31062 Toulouse Cedex 9, France
ReceiVed February 13, 2007
The diazomethane-mediated cyclopropanation of cyclohexenone using Pd(OAc)2 and different sources
of Pd(0) species as precatalysts has been studied. In the presence of an excess of diazomethane, Pd-
(OAc)2 rapidly evolves to the formation of palladium nanoparticles (less than 1 min), which are active
as catalysts in the cyclopropanation process. The nature of these particles has been analyzed through
transmission electron microscopy showing a size distribution between 6 and 40 nm. These nanoparticles
generated in situ are more active than Pd(0) complexes, preformed nanoparticles, and commercial palladium
powder. Cyclic voltammetry measurements of the reaction solution after completion show the presence
of Pd(0) species. This is the first time that Pd(0) nanoparticles are evidenced in a cyclopropanation reaction.
Moreover, the reduction of Pd(OAc)2 to Pd(0) in the presence of diazomethane has been theoretically
studied through density functional calculations. The formation of methyl and allyl acetates as organic
byproducts has been predicted by the theoretical calculations, and these species, as well as oligomers
derived from them, have been detected by spectrometric and spectroscopic techniques (MS, NMR,
and IR).
molecular palladium species, as proposed by Dupont10 and in
agreement with the results obtained by de Vries using ligand-
free palladium catalysts.11
Introduction
For metal-catalyzed processes, many studies have been
reported to establish the true nature of the catalyst. From the
point of view of the reactivity, it is more appropriate to classify
catalysts as homogeneous or heterogeneous depending on
whether the substrate interacts with one or many types of active
sites.1 Recently, tests commonly used to evaluate the nature of
the catalyst have been reviewed.2,3 However, when metal
nanoparticles are involved, it is even more difficult to conclude
about the catalyst nature, because they are placed at the frontier
between classical homogeneous and heterogeneous catalysts.4
This dilemma has been found in many palladium-catalyzed
reactions.5,6 In the last years, the possible formation of palladium
nanoparticles has been postulated for several catalytic pro-
cesses.7,8 In particular, for Pd-catalyzed C-C coupling reac-
tions,9 palladium nanoparticles seem to act as a reservoir of
Cyclopropanation of olefins with diazoalkanes catalyzed by
metal complexes is a widely used synthetic method.12-29
(9) For a general review concerning the Pd catalyst nature in Heck and
Suzuki couplings, see: Phan, N. T. S.; van der Sluys, M.; Jones, C. W.
AdV. Synth. Catal. 2006, 348, 609.
(10) Cassol, C. C.; Umpierre, A. P.; Machado, G.; Wolke, S. I.; Dupont,
J. J. Am. Chem. Soc. 2005, 127, 3298.
(11) (a) Reetz, M. T.; de Vries, J. G. Chem. Commun. 2003, 1787. (b)
de Vries, A. H. M.; Mulders, J. M. C. A.; Mommers, J. H. M.; Henderickx,
H. J. W.; de Vries, J. G. Org. Lett. 2003, 5, 3285.
(12) Doyle, M. P. Chem. ReV. 1986, 86, 919.
(13) Tomilov, Y. V.; Dokichev, V. A.; Dzhemilev, U. M.; Nefedov, O.
M. Russ. Chem. ReV. 1993, 62, 799.
(14) Doyle, M. P. In ComprehensiVe Organometallic Chemistry 2, Vol
12; Hegedus, L. S., Ed.; Pergamon: New York, 1995; p 387.
(15) Lautens, M.; Klute, W.; Tam, W. Chem. ReV. 1996, 96, 49.
(16) Davies, H. M. L. Aldrichim. Acta 1997, 30, 107.
(17) Doyle, M. P.; Protopopova, M. N. Tetrahedron 1998, 54, 7919.
(18) Doyle, M. P.; Forbes, D. C. Chem. ReV. 1998, 98, 911.
(19) Herndon, J. W. Coord. Chem. ReV. 2000, 206, 237.
(20) Lebel, H.; Marcoux, J.-F.; Molinaro, C.; Charette, A. B. Chem. ReV.
2003, 103, 977.
(21) Paulissen, R.; Hubert, A. J.; Teyssie´, P. Tetrahedron Lett. 1972,
1465.
(22) Mende, U.; Radu¨chel, B.; Skuballa, B.; Vorbru¨ggen, H. Tetrahedron
Lett. 1975, 629.
* Corresponding authors. E-mail: (M.G.) gomez@chimie.ups-tlse.fr;
(V.B.) vicenc@klingon.uab.cat; (R.M.O.) rosa.ortuno@uab.es.
† Universitat Auto`noma de Barcelona.
‡ Universitat de Barcelona.
§ Laboratoire He´te´rochimie Fondamentale et Applique´e.
(1) Schwartz, J. Acc. Chem. Res. 1985, 18, 302.
(2) Widegren, A.; Finke, R. G. J. Mol. Catal. A: Chem. 2003, 198, 317.
(3) Dyson, P. J. Dalton Trans. 2003, 2964.
(4) Astruc, D.; Lu, F.; Ruiz Aranzaes, J. Angew. Chem., Int. Ed. 2005,
44, 7852.
(5) Amatore, C.; Jutand, A. Acc. Chem. Res. 2000, 33, 314.
(6) Phan, N. T. S.; Van Der Sluys, M.; Jones, C. W. AdV. Synth. Catal.
2006, 348, 609.
(23) Kottwitz, J.; Vorbru¨ggen, H. Synthesis 1975, 636.
(24) Suda, M. Synthesis 1981, 714.
(25) Anciaux, A. J.; Hubert, A. J.; Noels, A. F.; Petinot, N.; Teyssie´, P.
J. Org. Chem. 1980, 45, 695.
(26) Ortun˜o, R. M.; Ibarzo, J.; AÄ lvarez-Larena, AÄ .; Piniella, J. F.
Tetrahedron Lett. 1996, 37, 4059.
(7) de Vries, J. G. Dalton Trans. 2006, 421.
(8) Thathagar, M. B.; ten Elshof, J. E.; Rothenberg, G. Angew. Chem.,
Int. Ed. 2006, 45, 2886.
(27) Denmark, S. E.; Stavenger, R. A.; Faucher, A. M.; Edwards, J. P.
J. Org. Chem. 1997, 62, 3375.
10.1021/om070141a CCC: $37.00 © 2007 American Chemical Society
Publication on Web 05/27/2007

Cyclopropanation of Cyclohexenone by Diazomethane
Organometallics, Vol. 26, No. 14, 2007 3307
Scheme 1
Palladium diacetate has been shown to be an efficient catalyst
in the diazomethane-mediated cyclopropanation of different
kinds of olefins.21-29 Nevertheless, the mechanism of the
reaction is still controversial and not completely understood. It
is currently assumed that the first step involves the formation
of a palladium-carbene complex, resulting from the reaction
between the palladium(II) complex and diazomethane.12,27 The
interaction of the olefin with this complex could lead to the
formation of a palladacyclobutane intermediate.
Scheme 2
The ability of palladium to coordinate olefins has led to the
postulation of an alternative mechanism in which diazomethane
attacks a previously coordinated olefin.25 Tomilov et al.13 have
suggested that the catalytically active species is a Pd(0) complex,
which would be produced from the reduction of palladium(II)
compounds in the presence of diazomethane. Actually, the
precipitation of palladium black has been observed from the
reaction between Pd(II) compounds and diazomethane.13,30,31
The transition-metal-catalyzed cyclopropanation of olefins has
been the subject of theoretical studies.32-41 We have studied
the cyclopropanation of ethylene by diazomethane using pal-
ladium diformate as a model of palladium diacetate.34 Accord-
ingly, the cyclopropanation is possible only after the reaction
of palladium diformate with two diazomethane molecules to
form a bis(formyloxymethyl)palladium complex in which two
methylene groups have been inserted into Pd-O bonds. The
coordination of the third diazomethane molecule initiates the
catalytic cycle, in which the highest transition state is the one
corresponding to nitrogen elimination (Gibbs energy: 23.7 kcal
mol-1 at 298.15 K with respect to [Pd(formyloxymethyl)2] +
diazomethane).
be more efficient catalysts for the cyclopropanation of olefins
than Pd(II) complexes. However, the mechanism for the Pd(II)
to Pd(0) reduction remains unclear.
In the present paper, we report the results of our investigation
on the cyclopropanation of cyclohexenone by diazomethane
using Pd(OAc)2 or Pd(0) compounds as catalytic precursors.
The palladium species formed have been analyzed, during and/
or after the reaction, both in the solid state (by transmission
electron microscopy (TEM) and far-IR spectroscopy) and
solution (by cyclic voltammetry). Furthermore, the mechanism
of Pd(II) to Pd(0) reduction has been studied through density
functional theoretical (DFT) calculations, which have allowed
the prediction of the byproducts resultant from such a process;
their formation has been experimentally confirmed by mass
spectrometry and spectroscopic techniques.
Bernardi et al.35 have theoretically studied the cyclopropa-
nation of ethylene in the presence of [PdCl2(PH3)2] and have
shown that the catalytically active species is a carbenoid
complex in which methylene has inserted into one of the Pd-
Cl or Pd-P bonds. The most favorable cyclopropanation
pathway involves activation barriers of 28-29 kcal mol-1
.
On the other hand, Straub37 has reported a theoretical study
on the mechanism of cyclopropanation of ethylene by diaz-
omethane catalyzed by [Pd(ethylene)n] (n ) 1, 2, 3) complexes.
The highest point along the reaction coordinate is the transition
state corresponding to nitrogen elimination (Gibbs energy: 20.1
kcal mol-1 at 273.15 K with respect to [Pd(ethylene)2] +
diazomethane). These results show that Pd(0) complexes may
Results and Discussion
1. Pd-Catalyzed Cyclohexenone Cyclopropanation. The
reaction between cyclohexenone 1 and diazomethane catalyzed
by Pd(OAc)2 to afford bicylo[4.1.0]heptan-2-one, 2, was studied
as a model reaction (Scheme 1).
In our earlier studies,26,28 we demonstrated that a large excess
(ca 20 equiv) of diazomethane is necessary to achieve an
efficient cyclopropanation in a few minutes. Upon addition of
diazomethane to the solution of 1 and Pd(OAc)2, an immediate
production of nitrogen and formation of Pd(0) were observed.
After completion, the palladium formed was exhaustively
washed to remove organic materials and reused in a further
reaction obtaining a 1:1 mixture of cyclohexenone 1 and
cyclopropane 2.
The reactant addition sequence is crucial: only a very low
conversion was observed when cyclohexenone was poured into
a mixture containing the catalyst and diazomethane, in contrast
to the high conversion obtained when the diazomethane is
poured into the cyclohexenone solution containing palladium
diacetate.
After these preliminary observations and with the aim of
obtaining more experimental data about the nature of the
palladium catalytic species involved in the cyclohexenone
(28) Rodr´ıguez-Garc´ıa, C.; Ibarzo, J.; AÄ lvarez-Larena, A.; Branchadell,
V.; Oliva, A.; Ortun˜o, R. M. Tetrahedron 2001, 57, 1025.
(29) Marko, I. E.; Giard, T.; Sumida, S.; Gies, A.-E. Tetrahedron Lett.
2002, 43, 2317.
(30) McCrindle, R.; Arsenault, G. J.; Farwaha, R.; McAlees, A. J.;
Sneddon, D. W. J. Chem. Soc., Dalton Trans. 1989, 761.
(31) Vallgårda, J.; Appleberg, U.; Cso¨regh, I.; Hacksell, U. J. Chem.
Soc., Perkin Trans. 1 1994, 461.
(32) Rodr´ıguez-Garc´ıa, C.; Gonza´lez-Blanco, O.; Oliva, A.; Ortun˜no, R.
M.; Branchadell, V. Eur. J. Inorg. Chem. 2000, 1073.
(33) Bernardi, F.; Bottoni, A.; Miscioni, G. P. Organometallics 2000,
19, 5529.
(34) Rodr´ıguez-Garc´ıa, C.; Oliva, A.; Ortun˜no, R. M.; Branchadell, V.
J. Am. Chem. Soc. 2001, 123, 6157.
(35) Bernardi, F.; Bottoni, A.; Miscioni, G. P. Organometallics 2001,
20, 2751.
(36) Fraile, J. M.; Garc´ıa, J. I.; Mart´ınez-Merino, V.; Mayoral. J. A.;
Salvatella, L. J. Am. Chem. Soc. 2001, 123, 7616.
(37) Straub, B. F. J. Am. Chem. Soc. 2002, 124, 14195.
(38) Straub, B. F.; Gruber, I.; Rominger, F. Hofmann, P. J. Organomet.
Chem. 2003, 684, 124.
(39) Iwakura, I.; Ikeno, T.; Yamada, T. Org. Lett. 2004, 6, 949.
(40) Fraile, J. M.; Garc´ıa, J. I.; Gil, M. J.; Mart´ınez-Merino, V.; Mayoral,
J. A.; Salvatella, L. Chem.-Eur. J. 2004, 10, 758.
(41) Cornejo, A.; Fraile, J. M.; Garc´ıa, J. I.; Gil, M. J.; Mart´ınez-Merino,
V.; Mayoral, J. A.; Salvatella, L. Organometallics 2005, 24, 3448.

3308 Organometallics, Vol. 26, No. 14, 2007
Illa et al.
Table 1. Cyclopropanation of Cyclohexenone 1 by
Diazomethane to Afford 2, Using Different Palladium
Precatalysts
[Pd4]coll, remained unaltered (Figure 2). In this case, it seems
that the stabilizing ligand also prevents the approach of
cyclohexenone and/or diazomethane to the metal surface.
a
entry
Pd precatalyst
Pd/1/CH2N2
timeb
1/2c
For the best precatalyst used, cyclopropanation of 1 was also
carried out using a lower Pd/substrate ratio (0.1/1, entry 9) and
75% of cyclopropane 2 was obtained, showing the palladium
catalytic role.
1
2
3
4
5
6
7
Pd(OAc)2
Pd2(dba)3
1/1/20
1/1/20
1/1/20
1/1/20
1/1/20
1/1/20
1/1/20
5
5
10
5
240
180
5
10/90
50/50
100/0
60/40
100/0
100/0
60/40
Pd(PPh3)4
Pd(s)d
[Pd3]coll
[Pd4]coll
In view of these results, we decided to study more exhaus-
tively Pd(OAc)2 as a catalytic precursor of cyclohexenone
cyclopropanation.
Pd(OAc)2 + dba
(Pd/dba ) 1/3)
Pd(OAc)2 + PPh3
(Pd/PPh3 ) 1/4)
Pd(OAc)2
8
1/1/20
5
5
100/0
25/75
With the purpose of monitoring the diazomethane decomposi-
tion, 1 equiv of Pd(OAc)2 and 20 equiv of diazomethane were
stirred in dichloromethane at -80 °C. After 5 min, when all
initial diazomethane had already disappeared and presumably
all Pd(OAc)2 had been reduced, 20 more equivalents of
diazomethane were added to the reaction mixture and the stirring
was continued for an additional 4 min. Figure 3 shows the
variation of diazomethane concentration after the two additions
of diazomethane. After the first addition, the diazomethane
concentration decreased to 50% in only 30 s, whereas after the
second addition, the time necessary to reach the same diminution
was more than 1 min. Therefore, the diazomethane disappear-
ance is faster for the first addition than for the second one.
9
0.1/1/20
b
c
a Initial relative concentrations. Reaction time in minutes. Determined
by GC. d Commercial palladium black.
cyclopropanation (Scheme 1), we decided to study this process
using other palladium sources. In particular, we have used Pd2-
(dba)3 and Pd(PPh3)4, as typical molecular precursors, Pd(0)
sponge, as a typical heterogeneous catalyst, and preformed
palladium nanoparticles, [Pd3]coll and [Pd4]coll using a func-
tionalized polymer (3), which is a classical method to isolate
nanoparticles,42 and a ligand (4), respectively (Scheme 2).43 This
choice was done to observe the influence of both kinds of
stabilizers in the reactivity herein considered. In all cases,
diazomethane was poured into a dichloromethane solution
containing cyclohexenone and the palladium compound at room
temperature, and the results are summarized in Table 1.
The comparison of the results obtained under the same reac-
tion conditions (entries 1-6, Table 1) shows that palladium dia-
cetate presents the highest activity, giving 90% conversion in
5 min (entry 1). The activity of Pd2(dba)3 is worse than Pd-
(OAc)2, giving only 50% conversion (entry 2). This result is
similar to that obtained when dba is added to palladium diacetate
(entry 7). In this case, mono- and bis-cyclopropanation of the
two double bonds of dba were also observed, so that dba cyclo-
propanation competes with cyclohexenone cyclopropanation.
It is noteworthy the lack of activity of Pd(PPh3)4 (entry 3)
and of the preformed nanoparticles (entries 5 and 6). The strong
Pd-phosphine interaction in Pd(PPh3)4 probably prevents the
creation of vacant coordination sites for diazomethane or
cyclohexenone. In fact, when 4 equiv of PPh3 was added to
Pd(OAc)2, no cyclopropanation at all was observed (entry 8)
and the 31P NMR spectrum of the reaction mixture revealed
the formation of Ph3PO (25 ppm) and Pd(PPh3)4 (22 ppm).
These results are in accordance with those previously described
by Jutand et al.44 on the reduction of Pd(II) to Pd(0) by
triphenylphosphine as reducing agent.
This fast decomposition of diazomethane by Pd(OAc)2
explains why very low or no conversion was observed when
cyclohexenone was added to a mixture containing diazomethane
and Pd(OAc)2 in dichloromethane or ether.
The organic species resulting from decomposition of Pd-
(OAc)2 by diazomethane were analyzed by electrospray ioniza-
tion (ESI) mass spectrometry, revealing the presence of
significant signals. For instance, a peak attributable to CH3C-
(O)OCH3 was observed at m/z 74, and signals at m/z 100 +
14n corresponding to CH3C(O)O(CH2)nCHdCH2 were also
detected. Furthermore, other peaks with masses fitting well to
a CH3C(O)O(CH2)nOC(O)CH3 structure (132 + 14n) were
1
identified. In addition, H NMR and IR spectra of a sample
corresponding to 0.5 min reaction time corroborated these
structures. Thus the 1H NMR spectrum in CDCl3 showed signals
at δ 1.5 and 1.8 (CH2), 2.0 (CH3CdO), 3.7 (CH3OCdO), 4.1
(CH2OCdO), 4.7 (CdC-CH2OCdO and vinyl protons), 4.9,
5.3, and 5.4 (several cis/trans vinyl protons), and 7.3 (CH2d
CHOCdO) ppm, compatible with the proposed structures.
Concerning the IR spectrum, absorptions at 1578 and 1635 (Cd
C) and 1720 (CdO) cm-1 were observed.
Under cyclopropanation conditions, a black precipitate is
always observed using palladium acetate as precursor. In order
to know the nature of the insoluble palladium species formed,
TEM analyses were carried out (Figure 4). For the cyclopro-
panation using a 1/1 Pd/1 ratio (entry 1, Table 1), small
palladium particles (mean diameter ca. 5 nm) forming ag-
glomerates were observed (Figure 4a). On the other hand, bigger
nanoparticles were detected when the Pd/1 ratio was 0.1/1 (entry
9, Table 1), showing two populations at ca. 26 and 40 nm
(Figure 4b).
The behavior of the preformed nanoparticles has been
investigated by TEM analysis. In the case of nanoparticles
stabilized by polymer, [Pd3]coll, agglomeration was observed
after 5 min of reaction time (Figure 1), leading to a diminution
of the active surface. The lack of activity in the cyclopropanation
may be due to the coordination of Lewis base centers to the
active sites in the surface. On the contrary, the size of the
nanoparticles sterically stabilized by the oxazolinyl-phosphinite,
With the aim of proving the catalytic role of the Pd
nanoparticles, the reaction was carried out at -80 °C and
monitored by TEM and GC. A 1/20 mixture of Pd(OAc)2 and
diazomethane in dichloromethane at -80 °C was stirred for 5
min, and then 1 equiv of cyclohexenone and an additional 15
equiv of diazomethane were added. After 6 min (overall time),
95% cyclopropane 2 was determined by GC. The black solid
formed during the catalytic reaction was analyzed by TEM
(Figure 5), showing the presence of nanoparticles that increased
(42) Schmid, G., Ed. Nanoparticles. From theory to application; Wiley-
VCH: Weinheim, 2004.
(43) Palladium nanoparticles were prepared from Pd2(dba)3, in the
presence of an stabilizer, polymer 1 or ligand 2, under hydrogen atmosphere
in THF solution (Scheme 2) The reaction was stirred for 1 h at room
temperature. The dibenzylidenacetone (dba) decoordination is therefore
favored and partially reduced (dbaH). To eliminate the organic byproducts,
the black residue was washed with hexane (monitored by TLC and 1H
NMR).
(44) Amatore, C.; Jutand, A.; Amine, M. Organometallics 1992, 11, 3009.

Cyclopropanation of Cyclohexenone by Diazomethane
Organometallics, Vol. 26, No. 14, 2007 3309
Figure 1. TEM micrographs of [Pd3] nanoparticles stabilized by polymer: (a) at the initial time (mean diameter, ca. 22 nm); (b) after 5
min (mean diameter, ca. 50 nm).
Figure 2. TEM micrographs of [Pd4] nanoparticles stabilized by ligand: (a) at the initial time (mean diameter, ca. 4 nm); (b) after 5 min
(mean diameter, ca. 5 nm).
could act as catalysts themselves or as a reservoir of Pd(0)
molecular species that would be the active catalysts of the
reaction.
In order to analyze the oxidation state of palladium species
in solution, we carried out cyclic voltammetry studies of the
reaction mixture after cyclopropanation of 1. The measurements
were carried out in dichloromethane from -2 to +2 V
(electrochemically stable solvent region) in the presence of
tetrabutylammonium hexafluorophosphate as supporting elec-
trolyte. No redox reactions of cyclohexanone 1 are expected in
the studied region.45 Free acetate (sodium acetate was measured)
and 2-cyclohexen-1-one were not detected after cyclopropana-
tion. To study the electrochemical behavior of Pd(0) and Pd-
(II) species under our conditions, Pd2(dba)3 and Pd(OAc)2 were
considered (Figure 6). For Pd2(dba)3, Pd(0) to Pd(II) oxidation
appeared at +1.1 V (two peaks at -1.5 and -1.2 V were also
observed due to dba reduction), according to published data.46
The palladium acetate cyclovoltammogram showed two peaks
corresponding to reduction processes, at +0.8 V (acetate
reduction) and at -0.6 V (Pd(II) reduction).47
Figure 3. Variation of the diazomethane concentration with time
in the presence of Pd(OAc)2 at -80 °C.
their size with time from 6 to 13 nm. The formation of bulk
metal was not observed in any case.
The solution mixture after cyclopropanation showed two
peaks corresponding to irreversible reduction processes, at -1.0
and -1.6 V, and one oxidation peak at +0.8 V, for both
When a similar experiment was carried out at room temper-
ature, 83% of cyclopropane 2 was obtained 1 min after the
addition of cyclohexenone. The formed nanoparticles were
bigger (estimated mean diameter ca. 40 nm) and considerably
less active.
(45) House, H. O.; Prabhu, A. V.; Wilkins, G. M.; Lee, L. F. J. Org.
Chem. 1976, 41, 3067.
(46) Amatore, C.; Broeker, G.; Jutand, A.; Khalil, F. J. Am. Chem. Soc.
1997, 119, 5176.
(47) (a) Amatore, C.; Blart, E.; Geˆnet, J. P.; Jutand, A.; Lemaire-Audoire,
S.; Savignac, M. J. Org. Chem. 1995, 60, 6829. (b) Amatore, C.; Jutand,
A.; M’Barki, M. A. Organometallics 1992, 11, 3009.
All these results point out the role of Pd nanoparticles in the
cyclopropanation of cyclohexenone. These nanoparticles are
formed from the reduction of Pd(OAc)2 by diazomethane and
remain stable and active during the reaction. These nanoparticles

3310 Organometallics, Vol. 26, No. 14, 2007
Illa et al.
Figure 4. TEM micrographs after cyclohexenone cyclopropanation at room temperature: (a) using Pd/1 ) 1/1; (b) using Pd/1 ) 0.1/1.
Figure 5. TEM micrographs: (a) after 1 min reaction time between CH2N2 and Pd(OAc)2 (before addition of cyclohexenone), mean
diameter, ca. 6 nm; (b) at 5 min reaction time between CH2N2 and Pd(OAc)2 (before addition of cyclohexenone), mean diameter, ca. 10
nm; (c) after 8 min reaction time between CH2N2 and Pd(OAc)2 (3 min after addition of cyclohexenone), mean diameter, ca. 13 nm.
Reaction temperature ) -80 °C.
in the region 550-200 cm-1, excluding the presence of
palladium oxide (see the Supporting Information).48
From the results described up to now it is evident that, in the
presence of diazomethane, palladium diacetate reduces to form
Pd(0) species, probably small nanoparticles, which play a role
in the cyclopropanation of cyclohexenone. However, the mech-
anism of Pd(II) to Pd(0) reduction remains unclear. With the
purpose of its elucidation, we carried out a theoretical study
concerning this process.
2. Theoretical Study of the Pd(II) to Pd(0) Reduction. In
our previous work, we have shown that the formation of a bis-
(formyloxymethyl)palladium complex from the reaction of
palladium dicarboxylate with two diazomethane molecules is
very favorable.34 Therefore, we have now started our investiga-
tion with a bis(acetyloxymethyl)palladium complex, which
henceforth will be named A(1) (see below).
The Pd(II) to Pd(0) reduction mechanism involves many
steps, which are summarized in Scheme 3. A, B, C, ..., refer to
the kind of intermediate, whereas n refers to the number of
Figure 6. Cyclic voltammograms of Pd(OAc)2, Pd2(dba)3, and
solution mixture after cyclopropanation.
methylene groups in the acetyloxyalkyl ligand on the right-hand
side. In complexes E and F one of the methylene groups has
recorded voltammograms from -2 to +2 V and from +2 to
become part of the CdC double bond of the alkene ligand.
-2V (Figure 6). The reduction peak at -1.0 V could be
The mechanism begins with an A(n) complex. The first two
associated with a Pd(II) to Pd(0) process, in agreement with
voltammograms of Pd(II) species. The oxidation observed at
steps involve coordination of diazomethane and elimination of
nitrogen to form a palladium-carbene complex C(n). This
+0.8 V could be related to a Pd(0) to Pd(II) process, according
intermediate may evolve following two different pathways. One
to Pd(0) species voltammograms (see Figure 6 for Pd2(dba)3).
of them leads to A(n+1), which differs from A(n) in one
The peak at -1.6 V could be due to the reduction of other
methylene group and which can initiate another cycle. The
metallic species.
alternative path leads to the formation of F(n-1), which is a
It is noteworthy that Pd(0) species were still present in the
Pd(0) complex. We have studied these processes starting from
reaction mixture after cyclopropanation was completed. In
addition, the far-IR spectrum (400-200 cm-1) of the residue
obtained from the cyclopropanation solution after organic phase
separation was measured and no absorption band was observed
(48) Nakamoto, K. Infrared and Raman Spectra of Inorganic and
Coordination Compounds, PartB; 5th ed.; Jonh Wiley & Sons: New York,
1997.

Cyclopropanation of Cyclohexenone by Diazomethane
Organometallics, Vol. 26, No. 14, 2007 3311
Scheme 3
Figure 7. Structures of A(1) and intermediates involved in the
reaction with diazomethane. Selected interatomic distances
are in Å.
Scheme 4
Table 2. Gibbs Activation and Reaction Energies (in kcal
mol-1)a for Reactions Shown in Scheme 3
∆Gq
∆G°
A(1) + CH2N2 f B(1)
B(1) f C(1) + N2
C(1) f D(1)
D(1) f A(2)
C(1) f E(0)
19.3
17.6
2.9
5.4
3.9
10.5
2.3
-11.3
-47.3
-35.1
-5.2
A(1) and from A(2). The formation of a Pd(0) complex is
favored only for the second cycle, which leads to F(1).
Table 2 presents the computed Gibbs activation and reaction
energies of the processes that originate in A(1), and the
structures of selected stationary points are shown in Figures 7
and 8.
Figure 7 shows the structures of the intermediates involved
in the reaction between A(1) and diazomethane. The coordina-
tion of diazomethane to A(1) leads to the formation of B(1),
which loses nitrogen, leading to the palladium-carbene complex
C(1). Two different transformations are possible for C(1), as
summarized in Scheme 3. The structures of the corresponding
stationary points are shown in Figure 8.
E(0) f F(0)
8.0
a In dichloromethane at 298 K and 1 mol L-1
.
activation energy for the conformational rearrangement is 4.6
kcal mol-1. The global process starting from C(1) can be viewed
as the methylene insertion into the CH2-O bond of the cis
acetyloxymethyl ligand.
The electronic structure of complexes shown in Figures 7
and 8 has been studied using the NBO method. Table 3 presents
the Pd net charges and the number of 4d lone pairs on Pd
identified by the NBO procedure. Three different situations
emerge. In most of the complexes, the net charge on Pd is in
the 0.35-0.46 range and there are four 4d lone pairs on Pd.
These complexes correspond to Pd(II). In C(1) the net charge
on Pd is notably larger and there are only three 4d lone pairs
on Pd, which fits to a Pd(IV) complex. Moreover, the NBO
procedure identifies only a σ bond between Pd and methylene
and a p lone pair on the methylene carbon atom. This result
points to a resonant structure b for C(1) (see Scheme 4). As a
matter of fact, the methylene group in C(1) is slightly pyramidal,
with a sum of bond angles around the carbon atom of 351.4°.
Finally, the results obtained for F(0) show that it is a Pd(0)
complex.
C(1) may evolve to D(1) through the formation of a C-O
bond between the coordinated methylene and the terminal
oxygen of the acetyloxymethyl ligand.
Alternatively, C(1) may undergo a C-C coupling between
the methylene ligand and the methylene group of the cis
acetyloxymethyl ligand along with a R-hydride elimination
leading to the formation of the olefin-hydride complex E(0).
This complex easily evolves to the F(0) through a C-H
reductive elimination involving the acetyloxymethyl ligand. This
is a Pd(0) complex with vinyl acetate and methyl acetate ligands.
The most favorable process for C(1) is its evolution to D(1)
(∆Gq ) 2.9 kcal mol-1 in dichloromethane). However, D(1) is
unstable and rapidly evolves to A(2), through the cleavage of
one of the CH2-O bonds and a C-C coupling. Figure 8 shows
the most stable conformer of A(2), but the evolution from D(1)
leads first to the A(2)′ conformer (see Figure 9), which is 7.6
kcal mol-1 higher in Gibbs energy than A(2). The Gibbs
A(2) may be the origin of the same kind of transformations
as A(1). Table 4 presents the computed Gibbs activation and
reaction energies. A(2) may coordinate a new diazomethane
molecule, and two different isomers of the corresponding
complex diazomethane-A(2) can be formed (see Figure 10).
The coordination on the side of the acetyloxyethyl ligand is

3312 Organometallics, Vol. 26, No. 14, 2007
Illa et al.
Table 4. Gibbs Activation and Reaction Energies (in kcal
mol-1)a for Reactions Shown in Scheme 3
∆Gq
∆G°
A(2) + CH2N2 f B(2)
A(2) + CH2N2 f B(2)′
B(2) f C(2) + N2
C(2) f D(2)
16.5
19.8
17.2
8.2
5.4
12.0
2.2
1.5
D(2) f A(3)
C(2) f E(1)
E(1) f F(1)
2.9
5.1
7.6
-53.0
-43.5
-6.1
a In dichloromethane at 298 K and 1 mol L-1
.
Figure 10. Structure of complexes containing A(2) and diaz-
omethane.
Figure 8. Structures of stationary points corresponding to rear-
rangements from C(1). Selected interatomic distances are in Å.
Figure 11. Structures of stationary points corresponding to the
D(2) to A(3) rearrangement. Selected interatomic distances
are in Å.
place with no energy barrier. We have optimized the geometry
for different values of the Pd-diazomethane distance in the
range between 3.6 and 3.0 Å. These structures present an
imaginary frequency corresponding to the approach of both
fragments. The frequencies have been projected for vibrations
perpendicular to the path, and the Gibbs energies have been
calculated. The Gibbs energy presents a maximum for R ) 3.5
Å, from which we have computed the Gibbs activation energy
Figure 9. Structures of conformers A(2), A(2)′, and A(2)′′.
Table 3. Net Charge (Q, in au) on Pd and Number of Pd 4d
Lone Pairs (LP) from the NBO Analysis of Complexes
Shown in Figures 7 and 8
Q
LP
A(1)
B(1)
C(1)
D(1)
A(2)
E(0)
F(0)
0.458
0.398
0.674
0.415
0.449
0.348
0.160
4
4
3
4
4
4
5
relative to the most stable structure of A(2) of 16.5 kcal mol-1
.
An alternative reaction pathway for A(2) would be a
â-hydride elimination to form an isomer of E(0) with the hydride
trans relative to the methylene group of the acetyloxymethyl
ligand. The corresponding Gibbs activation and reaction energies
are 22.2 and 21.1 kcal mol-1, respectively. Therefore, this
process is less favorable than the coordination of diazomethane
to A(2) (see Table 4). E(0) could be reached from the trans
isomer of A(2), which is 20.1 kcal mol-1 higher in Gibbs energy;
consequently the process is not expected to be favorable.
C(2) may undergo the same kind of rearrangements as C(1).
The D(2) to A(3) rearrangement takes place in two steps through
an intermediate I, as shown in Figure 11. The first step consists
in the cleavage of the C-O bond involving the â methylene
group and leads to the formation of an (ethylene)(acetyloxym-
thermodynamically more favorable (B(2), ∆G ) 5.4 kcal mol-1
)
than the coordination on the side of the acetyloxymethyl ligand
(B(2)′, ∆G ) 12.0 kcal mol-1).
The coordination on the side of the acetyloxyethyl ligand may
take place after a conformational rearrangement in which this
ligand adopts an extended disposition, leaving a free coordina-
tion site in Pd (A(2)′′ in Figure 9). This process involves a Gibbs
activation energy of 13.2 kcal mol-1 and a Gibbs reaction energy
of 4.9 kcal mol-1. Then the coordination of diazomethane takes

Cyclopropanation of Cyclohexenone by Diazomethane
Organometallics, Vol. 26, No. 14, 2007 3313
Scheme 5
rearrangement paths are always unimolecular processes. These
results allow us to discard the catalysis by Pd(II) complexes in
the cyclopropanation process.
The results of calculations show that the most favorable Pd-
(II) to Pd(0) reduction path would lead to the formation of
methyl acetate and allyl acetate. On the contrary, vinyl acetate
is not expected to be formed. All these predictions are confirmed
by the experimental results. Other products detected by mass
spectrometry come from oligomerization of such monomers
under the reaction conditions used.
Table 5. Gibbs Activation and Reaction Energies (in kcal
mol-1)a for Alkyl Diacetate Reductive Elimination from A(n)
Complexes
Concluding Remarks
Pd(OAc)2 rapidly decomposes in the presence of diaz-
omethane, leading to the formation of Pd(0) nanoparticles, which
are active for the catalytic diazomethane-mediated cyclopropa-
nation of cyclohexenone. To our knowledge, this is the first
time that evidence and a description are provided for Pd(0)
nanoparticles formed under the catalytic conditions of the
Pd(OAc2)-promoted cyclopropanation reactions. These nano-
particles may act as catalysts themselves or as a reservoir of
Pd(0) molecular species, which would be the active catalysts.
The reactivity of the palladium nanoparticles depends on their
size (in general, the smallest particles are the most active due
to their high specific surface) and the nature of stabilizers (the
presence of strong Lewis donor centers can poison the catalyst).
These nanoparticles generated in situ are more active than Pd-
(0) complexes, preformed nanoparticles, and commercial pal-
ladium powder.
∆Gq
∆G°
A(1)
A(2)
A(3)
51.9
45.9
39.0
38.4
30.2
22.9
a In dichloromethane at 298 K and 1 mol L-1
.
ethyl)Pd complex with a Gibbs activation energy of 2.9 kcal
mol-1 and a Gibbs reaction energy of -34.3 kcal mol-1. The
second step is the insertion of ethylene into the Pd-CH2 bond,
and the Gibbs activation and reaction energies are 13.9 and
-18.3 kcal mol-1, respectively.
The rearrangement from C(2) to E(1) is now kinetically more
favorable than the rearrangement to D(2), in contrast with the
results obtained for C(1). So, the final product would be F(1),
which is a Pd(0) complex.
Moreover, we have shown that the Pd(II) to Pd(0) reduction
mechanism involves the formation of methyl and allyl acetates,
and oligomers coming from them, which have been identified
by mass spectrometry.
The Gibbs reaction energies for the dissociation of methyl
acetate and allyl acetate ligands from F(1) are -5.3 and 27.6
kcal mol-1, respectively, so that the dissociation of the methyl
acetate ligand is favorable. The subsequent dissociation of the
allyl acetate ligand to form a bare Pd atom involves a Gibbs
reaction energy of 40.4 kcal mol-1. However, the process could
be facilitated by the formation of Pd aggregates.
Experimental Section
Computational Details. All calculations are based on the density
functional theory using the BPW91 functional,51,52 which is the
functional used in previous studies.32,34 Geometries have been fully
optimized using the LANL2DZ basis set supplemented with d
polarization functions for C, N, and O. This basis set uses effective
core potentials for Pd51 and the D95 basis set for the remaining
atoms.52 Harmonic vibrational frequencies have been computed for
all structures to characterize them as energy minima or transition
states. The electronic structure of several complexes has been
analyzed using the NBO method.53 Solvent effects have been taken
into account for geometries optimized in the gas phase using the
PCM method54 and using dichloromethane (ꢀ ) 8.93) as solvent.
All these calculations have been done using the Gaussian-03
program.55 The energies of all structures have been recomputed
through single-point calculations with the ADF program56 using
In addition to F(n) complexes Pd(0) could also be obtained
from reductive elimination of alkyl diacetates from A(n)
complexes (see Scheme 5). We have studied this process for
A(1), A(2), and A(3). The computed Gibbs activation and
reaction energies are shown in Table 5.
Reductive elimination is unfavorable, but becomes more
feasible as the number of methylene units increases. However,
the Gibbs activation energies are much larger than those
corresponding to the coordination of an additional diazomethane
molecule, so that it does not seem to be the mechanism of
reduction.
Up to now we have shown how palladium diacetate may
evolve to Pd(0) in the presence of diazomethane. The proposed
mechanism involves as intermediates palladium-carbene com-
plexes, which would participate in a Pd(II)-catalyzed cyclopro-
panation. To elucidate the feasibility of this mechanistic
pathway, we have studied the reaction between one of them,
C(1), and cyclohexenone. We have located the transition state
for the cyclopropanation, and the computed Gibbs activation
energy in dichloromethane is 13.0 kcal mol-1. This value is
notably higher than the Gibbs activation energies associated with
the two intramolecular rearrangements considered for C(1) (see
Table 2), so that in the presence of cyclohexenone the Pd(II)/
Pd(0) reduction is more favorable than Pd(II)-catalyzed cyclo-
propanation. Similar values of Gibbs activation energies are
expected for the reactions of cyclohexenone with other pal-
ladium-carbene complexes, such as C(2), since the major
contribution comes from the entropy variation associated with
the molecularity change. On the other hand, the alternative
(49) Becke, A. D. Phys. ReV. A 1988, 38, 3098.
(50) (a) Wang, Y.; Perdew, J. P. Phys. ReV. B 1991, 44, 13298. (b)
Perdew, J. P.; Chevary, J. A.; Vosko, S. H.; Jackson, K. A.; Pederson, M.
R.; Singh, D. J.; Fiolhais, C. Phys. ReV. B 1992, 46, 6671.
(51) Hay, P. J.; Wadt, W. R. J. Chem. Phys. 1985, 82, 299.
(52) Dunning, T. H.; Hay, P. J. Modern Theoretical Chemistry, Vol. 3;
Schaeffer, H. F., III, Ed.; Plenum: New York, 1976; p 1.
(53) Reed, A. E.; Curtiss, L. A.; Weinhold, F. Chem. ReV. 1988, 88,
899.
(54) (a) Miertus, S.; Scrocco, E.; Tomasi, J. J. Chem. Phys. 1981, 55,
117. (b) Cance`s, E.; Menucci, B.; Tomasi, J. J. Chem. Phys. 1997, 107,
3032.
(55) Frisch, M. J.; et al. Gaussian 03, Revision C.02; Gaussian, Inc.:
Wallingford, CT, 2004.
(56) (a) te Velde, G.; Bickelhaupt, F. M.; Baerends, E. J.; Fonseca Guerra,
C.; van Gisbergen, S. J. A.; Snijders, J. G.; Ziegler, T. J. Comput. Chem.
2001, 22, 931. (b) ADF2005.01, SCM; Theoretical Chemistry, Vrije
Universiteit, Amsterdam: The Netherlands, http://www.scm.com.

3314 Organometallics, Vol. 26, No. 14, 2007
Illa et al.
an uncontracted Slater orbital TZ2P basis set. The inner electrons
of Pd (up to the 3d shell), C, N, and O have been treated with the
frozen core approximation.57 Relativistic effects have been included
using the ZORA method.58 The reference state for the reported
Anal. Found: C, 49.71; H, 9.15; N, 7.42; S, 1.47; Pd, 10.55. Mean
diameter (TEM, nm): 22. Analysis for [Pd4]coll: Anal. Found: C,
39.25; H, 6.13; N, 0.41; Pd, 42.14. Mean diameter (TEM, nm): 4.
General Cyclopropanation Procedure. Cyclohexenone (25 mg,
0.26 mmol) and Pd(OAc)2 (5.84 mg, 0.026 mmol) were introduced
in an Erlenmeyer vessel, and then a 0.2 M solution of diazomethane
in dichloromethane (26 mL, 5.2 mmol) was added. The mixture
was stirred for 5 min at room temperature. Immediately a N2 leak
and a color change of the solution, brown to gray, were observed.
The reaction progress was monitored by GC using authentic samples
of cyclohexenone 1 and cyclopropane 2 as external standards.
Kinetic Studies. A solution of 0.12 M diazomethane in dichlo-
romethane (21 mL, 2.52 mmol) was added to a flask containing
Pd(OAc)2 (29 mg, 0.13 mmol) and cooled at -80 °C by an external
bath. The mixture was stirred for 5 min at -80 °C. The concentra-
tion of diazomethane at different reaction times was determined
by addition of a known amount of benzoic acid to reaction aliquots,
and the excess of benzoic acid was then titrated with 0.2 M aqueous
NaOH.
Gibbs energies in solution is 298.15 K and 1 mol L-1
.
Cyclic Voltammetry Studies. Experiments were carried out in
a three-electrode cell. The auxiliary electrode was a stirring platinum
disk electrode (2 mm diameter); the reference electrode was a Ag/
AgCl electrode, and the working electrode, a platinum wire. The
cyclic voltammetry was performed at a scan rate of 0.1 V/s, and
-
0.1 M NBu4+PF6 was used as supporting electrolyte. Dichlo-
romethane solutions from a catalytic mixture, Pd(OAc)2 (80 mg,
mmol), Pd2(dba)3 (80 mg, mmol), and cyclohexenone (25 mg,
mmol) in 10 mL of solvent were measured. Redox-potential values
were confirmed by measuring solutions at different concentrations.
Pd Nanoparticle Synthesis. To a solution of Pd2(dba)3 (10 mg,
0.011 mmol) in 50 cm3 of distilled and degassed THF in a Fischer-
Porter bottle was added a solution of polymer 3 (139 mg, 0.44
mmol; monomer/palladium ) 20) or ligand 4 (1.65 mg, 4.4 × 10-2
mmol). The mixture was then pressurize at 3 bar of hydrogen at
room temperature and stirred for 1 h. During this time the solution
color changed from violet to black, with formation of a colloidal
suspension. The mixture was then depressurized under nitrogen
atmosphere and the solvent removed under reduced pressure. The
residue was then washed with hexane (6 × 15 mL) to eliminate
dba and its reduced products (monitored by TLC). The black solid
Acknowledgment. The authors wish to thank the Ministerio
de Educacio´ y Ciencia (CTQ 2004-1067/BQU and CTQ2004-
1546/BQU), the Generalitat de Catalunya, and the CNRS
(France) for financial support. Access to computational facilities
of Centre de Supercomputacio´ de Catalunya (CESCA) is
gratefully acknowledged.
obtained was dried under reduced pressure. Analysis for [Pd3]coll
:
Supporting Information Available: Cyclic voltammograms of
Pd2(dba)3 and Pd(OAc)2. Far-IR spectrum of the residue obtained
from the cyclopropanation solution. Cartesian coordinates and total
energies for all structures obtained from theoretical calculations.
This material is available free of charge via the Internet at
http://pubs.acs.org.
(57) Baerends, E. J.; Ellis, D. E.; Ros, P. Chem. Phys. 1973, 2, 41.
(58) (a) van Lenthe, E.; Baerends, E. J.; Snijders, J. G. J. Chem. Phys.
1993, 99, 4597. (b) van Lenthe, E.; Baerends, E. J.; Snijders, J. G. J. Chem.
Phys. 1994, 101, 9783. (c) van Lenthe, E.; Snijders, J. G.; Baerends, E. J.
J. Chem. Phys. 1996, 105, 6505. (d) van Lenthe, E.; van Leeuwen, R.;
Baerends, E. J.; Snijders, J. G. Int. J. Quantum Chem. 1996, 57, 281. (e)
van Lenthe, E.; Ehlers, A. E.; Baerends, E. J. J. Chem. Phys. 1999, 110,
8943.
OM070141A