Allylic substitution mediated by water and palladium: Unusual role of a palladium(II) catalyst and ESI-MS analysis

Article abstract of DOI:10.1021/om0495877

Allylic substitution of PhCH(OAc)CH=CHPh by CH₂(COMe) ₂ in a basic MeOH/H₂O mixture could be achieved in the absence of a palladium catalyst and lead to a mixture of PhCH(CH(COMe) ₂)CH=CHPh and PhCH(OMe)CH=CHPh in 40% and 55% yields, respectively. The process is induced by water, and nucleophilic attack addition occurred on a stabilized carbocation as the intermediate. Addition of a catalytic amount of PdCl₂(CH₃CN)₂ did not accelerate the reaction but improved the selectivity, and PhCH(CH(COMe)₂)CH=CHPh was then obtained in 92% yield while PhCH(OMe)-CH=CHPh was observed in trace amounts. An ESI-MS analysis of the reaction mixture led us to assume that a palladium acetylacetonate complex is involved in the formation of PhCH(CH(COMe) ₂)CH=CHPh.

Full text of DOI:10.1021/om0495877

4796
Organometallics 2004, 23, 4796-4799
Allylic Su bstitu tion Med ia ted by Wa ter a n d P a lla d iu m :
Un u su a l Role of a P a lla d iu m (II) Ca ta lyst a n d ESI-MS
An a lysis
Carole Chevrin, J ean Le Bras, Franc¸oise He´nin, and J acques Muzart*
Unite´ Mixte de Recherche “Re´actions Se´lectives et Applications”, CNRS-Universite´ de Reims
Champagne-Ardenne, BP 1039, 51687 Reims Cedex 2, France
Anna Pla-Quintana and Anna Roglans*
Department of Chemistry, Universitat de Girona, Campus de Montilivi, 17071 Girona, Spain
Roser Pleixats
Department of Chemistry, Universitat Auto`noma de Barcelona, Cerdanyola del Valle`s,
08193 Barcelona, Spain
Received J une 7, 2004
Summary: Allylic substitution of PhCH(OAc)CHdCHPh
by CH2(COMe)2 in a basic MeOH/ H2O mixture could
be achieved in the absence of a palladium catalyst and
lead to a mixture of PhCH(CH(COMe)2)CHdCHPh and
PhCH(OMe)CHdCHPh in 40% and 55% yields, respec-
tively. The process is induced by water, and nucleophilic
attack addition occurred on a stabilized carbocation as
the intermediate. Addition of a catalytic amount of
PdCl2(CH3CN)2 did not accelerate the reaction but im-
proved the selectivity, and PhCH(CH(COMe)2)CHdCHPh
was then obtained in 92% yield while PhCH(OMe)-
CHdCHPh was observed in trace amounts. An ESI-MS
analysis of the reaction mixture led us to assume that a
palladium acetylacetonate complex is involved in the
formation of PhCH(CH(COMe)2)CHdCHPh.
catalytic reactions, the data being directly acquired from
the reaction mixture.5 ESI-MS has been recently used
for the screening of palladium catalysts6 and for the
determination of the mechanism of the Heck reaction
with arene diazonium salts.7 Therefore, we have used
this method to investigate the role of 2 and LH in the
reaction of 1 with a ca cH under aqueous conditions. The
identification of the species detected by ESI-MS was
aided by comparison between the observed and calcu-
lated isotope distribution patterns. Because 46Pd and
17Cl display six and two isotopes, respectively, the ions
containing these atoms should be mass-detected as
clusters of isotopomeric ions whose center depends on
the most abundant isotope (106 for Pd and 35 for Cl).8
All ESI-MS analyses were performed with samples
dissolved in 1/1 MeOH/H2O, since this mixture is the
most appropriate in the allylic alkylation of 1 in the
presence of 2 and LH.2 The mobile phase used in all ESI
experiments was a 70:30 mixture of MeOH and H2O.
The use of water as solvent for organic synthesis is
very attractive for environmental, economic, and safety
reasons,1 and we have recently shown that water may
promote the allylic substitution of 1-acetoxy-1,3-diphe-
nylpropene (1) with high yields in the absence of any
palladium complex.2 However, with acetylacetone
(a ca cH) as nucleophilic species in a MeOH/H2O mix-
ture, the selectivity toward the C-C bond formation was
low; this was improved by addition of catalytic amounts
of a PdII salt, namely PdCl2(CH3CN)2 (2) and the hydro-
philic ligand [(HOCH2CH2NHCOCH2)2NCH2]2 (LH).3
The reaction times needed to achieve the complete
consumption of 1 were similar under both conditions
(eq 1).2
(1) (a) Li, C.-J .; Chan, T.-H. Organic Reactions in Aqueous Media;
Wiley: New York, 1997. (b) Organic Synthesis in Water; Grieco, P. A.,
Ed.; Blackie Academic: London, 1998. (c) Cornils, B.; Herrmann, W.
A. Aqueous-Phase Organometallic Catalysis; Wiley: New York, 1998.
(2) Chevrin, C.; Le Bras, J .; He´nin, F.; Muzart, J . Tetrahedron Lett.
2003, 44, 8099.
(3) Le Bras, J .; Muzart, J . Tetrahedron Lett. 2002, 43, 431.
(4) (a) For
a monograph on ESI-MS: Cole, R. B. Electrospray
Ionization Mass Spectrometry, Fundamentals, Instrumentation and
Applications; Wiley: New York, 1997. For the application of ESI-MS
to inorganic and organometallic chemistry, see the following reviews
and references therein: (b) Colton, R.; D’Agostino, A.; Traeger, J . C.
Mass Spectrom. Rev. 1995, 14, 79. (c) Henderson, W.; Nicholson, B.
K.; McCaffrey, L. J . Polyhedron 1998, 17, 4291. (d) Traeger, J . C. Int.
J . Mass Spectrom. 2000, 200, 387. (e) Plattner, D. A. Int. J . Mass
Spectrom. 2001, 207, 125.
(5) (a) Wilson, S. R.; Pe´rez, J .; Pasternak, A. J . Am. Chem. Soc. 1993,
115, 1994. (b) Aliprantis, A. O.; Canary, J . W. J . Am. Chem. Soc. 1994,
116, 6985. (c) Ripa, L.; Hallberg, A. J . Org. Chem. 1996, 61, 7147. (d)
Brown, J . M.; Hii, K. K. Angew. Chem., Int. Ed. Engl. 1996, 35, 657.
(e) Hii, K. K.; Claridge, T. D. W.; Brown, J . M. Angew. Chem., Int. Ed.
Engl. 1997, 36, 984. (f) Aramend´ıa, M. A.; Lafont, F.; Moreno-Man˜as,
M.; Pleixats, R.; Roglans, A. J . Org. Chem. 1999, 64, 3592. (g) Griep-
Raming, J .; Meyer, S.; Bruhn, T.; Metzger, J . O. Angew. Chem., Int.
Ed. 2002, 41, 2738. (h) Moreno-Man˜as, M.; Pleixats, R.; Spengler, J .;
Chevrin, C.; Estrine, B.; Bouquillon, S.; He´nin, F.; Muzart, J .; Pla-
Quintana, A.; Roglans, A. Eur. J . Org. Chem. 2003, 274. (i) Chen, P.
Angew. Chem., Int. Ed. 2003, 42, 2832.
Electrospray ionization mass spectrometry (ESI-MS)4
allows the observation of intermediates involved in
(6) (a) Markert, C.; Pfaltz, A. Angew. Chem., Int. Ed. 2004, 43, 2498.
(b) Tomazela, D. M.; Gozzo, F. C.; Ebeling, G.; Livotto, P. R.; Eberlin,
M. N.; Dupont, J . Inorg. Chim. Acta 2004, 357, 2349.
* To whom correspondence should be addressed. E-mail:
jacques.muzart@univ-reims.fr (J .M.); anna.roglans@udg.es (A.R.).
(7) Sabino, A. A.; Machado, A. H. L.; Correia, C. R. D.; Eberlin, M.
N. Angew. Chem., Int. Ed. 2004, 43, 2514.
10.1021/om0495877 CCC: $27.50 © 2004 American Chemical Society
Publication on Web 08/28/2004

Notes
Organometallics, Vol. 23, No. 20, 2004 4797
Ta ble 1. Electr osp r a y Ma ss Sp ectr a l Da ta for Va r iou s Mixtu r es
mixture
identified speciesa
entry
1
2
3
1, room temp
H, room temp
LH + PdCl2(CH3CN)2, room temp
ESI(+): 193, [1 - OCOCH3]+
L
ESI(+): 465, [LH + H]+; 487, [LH + Na]+
ESI(+): 465, [LH + H]+; 567-574 (569), [LHkP d Cl2 - 2Cl - H]+;
603-611 (607): [LHkP d Cl2 - Cl]+
ESI(-): 601-609 (605), [LHkP d Cl2 - Cl - 2H]-;
637-645 (641), [LHkP d Cl2 - H]-
4
5
1 + LH + PdCl2(CH3CN)2, room temp
ESI(+): 193, [1 - OCOCH3]+; 465, [LH + H]+;
567-574 (569), [LHkP d Cl2 - 2Cl - H]+;
603-611 (607), [LHkP d Cl2 - Cl]+
1 + LH + PdCl2(CH3CN)2 + 2 a ca cH +
2 K2CO3, 50 °C for 1 or 24 h
ESI(+): 331, [3 + K]+; 503, [LH + K]+;
605-612 (607), [LHkP d Cl2 - 2Cl - 2H + K]+;
641-649 (645), [LHkP d Cl2 - Cl - H + K]+;
705-712 (707), [LHkP d Xka ca c - H - X + K]+ (X ) Cl, OAc)
ESI(-): 565-572 (567), [LHkP d Cl2 - 2Cl - 3H]-;
601-609 (605), [LHkP d Cl2 - Cl - 2H]-;
6
1 + LH + PdCl2(CH3CN)2 + 2 a ca cH
2 K2CO3, 50 °C for 24 h
701-709 (705), [LHkP d Clka ca c - H]-
7b
LH + PdCl2(CH3CN)2 + a ca cH
2 K2CO3, room temp
ESI(+): 567-574 (569), [LHkP d Cl2 - 2Cl - H]+;
605-612 (607), [LHkP d Cl2 - 2Cl - 2H + K]+;
641-649 (645), [LHkP d Cl2 - Cl - H + K]+;
667-674 (669), [LHkP d Clka ca c - Cl]+;
705-712 (707), [LHkP d Clka ca c - H - Cl +K]+
ESI(+): 567-574 (569), [LHkP d Cl2 - 2Cl - H]+;
603-611 (607), [LHkP d Cl2 - Cl]+; 667-674 (669), [LHkP d Clka ca c - Cl]+
ESI(+): 293, [3 + H]+; 331, [3 + K]+;
8
LH + PdCl2(CH3CN)2 + a ca cH, room temp
9b
1 (excess) + LH + PdCl2(CH3CN)2 +
a ca cH + 2 K2CO3, 50 °C for 1.5 h
567-574 (569), [LHkP d Cl2 - 2Cl - H]+;
605-612 (607), [LHkP d Cl2 - 2Cl - 2H + K]+;
641-649 (645), [LHkP d Cl2 - Cl - H + K]+;
667-674 (669), [LHkP d Xka ca c - X]+ (X ) Cl, OAc);
705-712 (707), [LHkP d Xka ca c - H - X + K]+ (X ) Cl, OAc)
ESI(+): 315, [3 + Na]+; 487, [LH + Na]+;
10
1 + 0.2 LH + 0.2 PdCl2(CH3CN)2 +
2 a ca cH + 2 Na2CO3, 50 °C for 1.5 h
589-596 (591), [LHkP d Cl2 - 2Cl - 2H + Na]+;
689-696 (691), [LHkP d Xka ca c - H - X + Na]+ (X ) Cl, OAc)
ESI(+): 559-566 (561), [Pd(Ph(CH)3Ph)(PPh3)]+;
821-828 (823), [Pd(Ph(CH)3Ph)(PPh3)2]+
11
1 + Pd(PPh3)4
a
Reported m/z values are from the lowest to the highest mass in the isotope envelope of the clusters; the value in parentheses is the
b
most abundant peak. An analogous experiment was performed using Na2CO3 instead of K2CO3, observing the same species as sodium
adducts. The observation of the same species as sodium and potassium adducts confirms the identity of the species detected.
The ESI(+)-MS of 1 showed one peak at m/z 193
corresponding to the cationic allylic structure [1 -
OCOCH3]+ (Table 1, entry 1) while the spectrum of LH
afforded two peaks at m/z 465 and 487, consistent with
the protonated ligand [LH + H]+ and the sodium adduct
[LH + Na]+ (entry 2).9 The analysis of the ESI(+) mass
spectrum of a 1/1 mixture of 2 and LH led us to assume
the formation of the complex LHkP d Cl2 (eq 2),
mixture at 50 °C for 1.5 h. No new species were observed
on working in negative-ion mode ESI(-).
The reaction of an equimolecular mixture of 1, 2, and
LH with 2 equiv of both a ca cH and K2CO3 in MeOH/
H2O at 50 °C was then monitored (entry 5). After 1 h,
the ESI(+) mass spectrum showed a variety of signals:
(i) two peaks at m/z 331 and 503, corresponding to the
potassium adducts of the substitution product [3 + K]+
and the ligand [LH + K]+ respectively;10 (ii) two clusters
at m/z 607 and 645, attributed to the cationic species
[LHkP d Cl2 - 2Cl - 2H + K]+ and [LHkP d Cl2 - Cl -
H
+ K]+; one cluster at m/z 707, attributed to
[LHkP d Xka ca c - H - X + K]+ (X ) Cl, OAc),
consistent with the formation of the palladium enolate
complex LHkP d Xka ca c.
(8) Electrospray mass spectrometry analyses were recorded on a
Navigator quadrupole mass spectrometer (Finnigan AQA Thermo-
Quest) equipped with an electrospray ion source. The instrument was
operated either in the positive ESI(+) or in the negative ESI(-) ion
mode at a probe tip voltage of 3 kV. The samples were taken directly
from the reaction mixture and dissolved in MeOH to get an ap-
proximate concentration of 4 mM. The samples were introduced into
the mass spectrometer ion source directly through a Rheodyne injector
with a 20 µL sample loop. The mobile phase flow (100 µL/min of 70/30
v/v MeOH/H2O) was delivered by a P2000 HPLC pump (ThermoQuest)
to the vaporization nozzle of the electrospray ion source (165 °C for
ESI(+) and 140 °C for ESI(-)), and nitrogen was employed as both a
drying and a nebulizing gas. Skimmer cone voltages were varied
between 10 and 100 eV. Spectra were typically an average of 15-20
scans. Theoretical isotope patterns were calculated by use of the
Isoform program and used to aid assignment.
since two clusters attributable to the cationic species
[LHkP d Cl2 - 2Cl - H]+ and [LHkP d Cl2 - Cl]+ were
observed at m/z 569 and 607, respectively (entry 3).
Injecting the same mixture in negative-ion mode ESI-
(-) showed a cluster centered at m/z 605, corresponding
to the same species as above, but as the anionic form
[LHkP d Cl2 - Cl - 2H]-. In addition, a new cluster was
observed centered at m/z 641 and was consistent with
the species [LHkP d Cl2 - H]- (entry 3).
The ESI(+)-MS spectrum of a stoichiometric mixture
of 1, 2, and LH (entry 4) afforded the signals of the
clusters already observed in entries 1-3, and further-
more, a similar spectrum was obtained after heating the
(9) Association of the substrate with ions is common. [M + H]+ and
[M + Na]+ are often observed; the latter appears from the reaction
with traces of cations present even in HPLC-grade solvent.4c
(10) No adduct was observed between product 3 and Pd(II) in the
reaction medium or in a mixture of 3, LH, and 2.

4798 Organometallics, Vol. 23, No. 20, 2004
Notes
F igu r e 1. ESI(+)-MS spectrum of the reaction mixture: 1 (excess) + LH + PdCl2(CH3CN)2 + a ca cH + 2 K2CO3 at 50 °C
after 1.5 h of reaction (entry 9 in Table 1).
Prolonging the reaction time to 24 h or working with
catalytic amounts of 2 and LH (0.2 equiv of each)
afforded similar data. However, in negative-ion mode
ESI(-) a new cluster was observed centered at m/z 705
corresponding to [LHkP d Clka ca c - H]- (entry 6).
Although the anion [LHkP d OAcka ca c - H]- has not
been detected by ESI(-), such a species where Cl has
been substituted by OAc cannot be excluded. Thus, an
intermediate of general formula LHkP d kXa ca c is con-
sidered (X ) Cl, OAc).
and even in the absence of a base (entry 8). Its formation
may therefore be explained by direct reaction of 2 with
a ca cH or by a transmetalation reaction with the
potassium enolate a ca cK (eq 3).11,12
It should be noted that the enolate complex
LHkP d Clka ca c was detected at room temperature from
LH + 2 + a ca cH in the presence of K2CO3 (entry 7)
The addition of an excess of 1 to the sample examined
in entry 7 followed by heating at 50 °C for 1.5 h led to
an ESI(+) mass spectrum showing the above signals (as
K+ adducts) and also those of 3 (entry 9 and Figure 1).
Under catalytic conditions, the use of Na2CO3 as base
instead of K2CO3 afforded two peaks at m/z 315 and 487
corresponding to [3 + Na]+ and [LH + Na]+ and two
clusters at m/z 591 and 691 consistent with the cations
(11) Several kinds of coordination modes are known between
Pd(II) and acetylacetone; see: (a) Kanda, Z.; Nakamura, Y.; Kawaguchi,
S. Inorg. Chem. 1978, 17, 910. (b) Otani, Y.; Nakamura, Y.; Kawaguchi,
S.; Okeya, S. Hinomoto, T. Bull. Chem. Soc. J pn. 1982, 55, 1467. The
O,C,O′ chelation was chosen in our case according to the reactivity of
the palladium enolate complex with 1.

Notes
Organometallics, Vol. 23, No. 20, 2004 4799
Sch em e 1
effective nucleophile than a ca cK and MeOK. We have
also observed that the selectivity decreased strongly
when the Pd-catalyzed reaction was carried out in
MeOH instead of MeOH/H2O (eq 5):
[LHkP d Cl2 - 2Cl - 2H + Na]+ and [LHkP d Xka ca c -
H - X + Na]+ (X ) Cl, OAc) (entry 10).
Under all above experimental conditions, we have not
been able to detect a cluster containing a Ph(CH)3Ph
fragment, although (η3-allyl)palladium intermedi-
ates are observable by ESI(+)-MS under Pd0 condi-
tions. Indeed, two clusters centered at m/z 561 and
823 corresponding to [Pd(Ph(CH)3Ph)(PPh3)]+ and
[Pd(Ph(CH)3Ph)(PPh3)2]+, respectively, were revealed
from the ESI(+)-MS analysis of a stoichiometric mixture
of 1 and Pd(PPh3)4 in MeOH/H2O (entry 11), these clus-
ters probing the in situ formation of η3-allyl complexes
(eq 4).
the ether 4 and alcohol 5 were isolated in addition to 3.
As observed in the metal-free process,2 water favors the
formation of 3 and the corresponding process may be
described as shown in Scheme 1, which involves the
nucleophilic attack of LHkP d Xka ca c on the water-
activated substrate. We should point out that, in this
scheme, LH may be exchanged for the corresponding
mono (or multi)-deprotonated ligand.
To test the potential of LH as a hydrophilic ligand for
the immobilization of palladium, catalytic amounts of
LH and 2 (0.05 equiv of each) were first reacted with 1
and 2 equiv of both a ca cH and K2CO3 in MeOH/H2O
at 50 °C for 24 h. Extraction of the mixture by CH2Cl2
and separation of the organic phase yielded 90% of 3.
Successive recycling experiments performed using the
recovered aqueous phases afforded 3 in 85, 84, 85, and
85% yield. All of these runs provided slight traces of the
ether 4. These results led us to assume that a PdII
complex is truly immobilized in water by means of LH.
In conclusion, the present study has revealed the
surprising role of a PdII salt in the allylic substitution
reaction of 1-acetoxy-1,3-diphenylpropene with acetyl-
acetone carried out in an aqueous medium. ESI-MS
studies have not allowed the observation of an (η3-allyl)-
palladium intermediate but have demonstrated the
formation of a palladium acetylacetonate complex. This
enolate would react with the substrate to afford
3-(1,3-diphenyl-2-propenyl)-2,4-pentanedione through
a highly selective reaction which involves a dramatic
role of water. Ligand LH is also adapted for the immobi-
lization of PdII in water, since recycling experiments
have been carried out without noticeable loss of activity.
From the above ESI-MS analysis, it appears that the
classical (η3-allyl)palladium intermediate is absent from
both 1/2/LH and 1/a ca cH/M2CO3/2/LH (M ) K, Na)
aqueous mixtures. In addition, a mixture of 2, LH, and
K2CO3 in MeOH/H2O heated to 50 °C led to black
particles, due to the reduction of PdII species,13 while
such particles were not observed in the course of the
palladium-mediated reaction depicted in eq 1. Since the
reaction time to obtain the full consumption of 1 under
the reaction conditions depicted in eq 1 was independent
of the presence of palladium, this latter species is not a
catalyst of the acetate anion displacement. In contrast,
the 3 selectivity was increased from 40 to 92% under
the PdII conditions. Ether 4 is not an intermediate in
the formation of 3, since its conversion was lower than
5% when subjected to the Pd-catalyzed conditions for
24 h. Without palladium, the selectivity depends on the
relative nucleophilicity and stability of the potassium
enolate, a ca cK, and potassium methanolate, MeOK, in
the aqueous medium. The high selectivity of the reaction
carried out in MeOH/H2O in the presence of 2 and LH
is probably connected to the formation of the palladium
enolate complex LHkP d Xka ca c, which could be a more
Ack n ow led gm en t. We are indebted to Prof. M.
Moreno-Man˜as (Universitat Auto`noma de Barcelona) for
fruitful advice, to “Re´gion Champagne-Ardenne” for a
Ph.D. studentship to C.C., and to the Engelhard Co. for
generous gifts of palladium salts. Financial support from
the European Community (COST D12/0028/99), PAI
(Picasso), the MEC of Spain (Project BQU2002-04002-
C02), and the CIRIT-Generalitat de Catalunya (Projects
2000SGR0062 and 2001SGR-00291) is gratefully ac-
knowledged.
(12) For the preparation of palladium enolate complexes of 1,3-
diketones, see: (a) Shaw, B. L.; Perera, S. D.; Staley, E. A. Chem.
Commun. 1998, 1361. (b) Nowotny, M.; Henefeld, U.; Van Koningsveld,
H.; Maschmeyer, T. Chem. Commun. 2000, 1877. (c) Hamashima, Y.;
Hotta, D.; Sodeoka, M. J . Am. Chem. Soc. 2002, 124, 11240 and
references cited therein. (d) Gavrielatos, E.; Athanasellis, G.; Heaton,
B. T.; Steiner, A.; Bickley, J . F.; Igglessi-Markopoulou, O.; Markopou-
los, J . Inorg. Chim. Acta 2003, 351, 21.
Su p p or tin g In for m a tion Ava ila ble: Figures giving ob-
served electrospray mass spectra and calculated isotopic
distribution of all detected species tabulated in Table 1. This
material is available free of charge via the Internet at
http://pubs.acs.org.
(13) Muzart, J . Tetrahedron 2003, 31, 5789.
OM0495877