Palladium/benzoquinone-catalyzed electrochemical oxidation of alcohols under anaerobic conditions

Article abstract of DOI:10.1055/s-2007-985568

Primary and secondary alcohols are oxidized to aldehydes and ketones, respectively, under anaerobic conditions in DMF at 80°C, in the presence of a base and catalytic amounts of Pd(OAc)₂ and p-benzoquinone. The latter oxidizes the transient Pd(0) formed in the catalytic cycle to Pd(II) and p-hydroquinone is re-oxidized electrochemically. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-2007-985568

LETTER
2173
Palladium/Benzoquinone-Catalyzed Electrochemical Oxidation of Alcohols
Under Anaerobic Conditions
Electrochemical
h
xidationof
r
A
lcohol
i
s
stian Amatore,* Chama Cammoun, Anny Jutand*
Ecole Normale Supérieure – CNRS, Département de Chimie, 24 Rue Lhomond, 75231 Paris Cedex 5, France
Fax +33(1)44323325; E-mail: Anny.Jutand@ens.fr
Received 4 June 2007
line ligand (Sheldon et al. in 2000).6 Kinetic resolution of
chiral secondary alcohols in the presence of a chiral ligand
for the palladium(II) moieties have been reported by
Sigman et al.,7 Stoltz et al.,8 and Moberg et al.9 in 2001.
Abstract: Primary and secondary alcohols are oxidized to alde-
hydes and ketones, respectively, under anaerobic conditions in
DMF at 80 °C, in the presence of a base and catalytic amounts of
Pd(OAc)2 and p-benzoquinone. The latter oxidizes the transient
Pd(0) formed in the catalytic cycle to Pd(II) and p-hydroquinone is
re-oxidized electrochemically.
In the absence of an extra base, the acetate ligand was pro-
posed to act as a base which deprotonates the Pd(II)-ligat-
ed alcohol in an intramolecular reaction. A Pd(0) moiety
is formed together with the aldehyde or ketone from an in-
termediate Pd(II)-alkoxide after a b-hydride elimina-
tion.5b The key step is the oxidation of the Pd(0) moiety
back to Pd(II). Dioxygen plays the role of the oxidant.
However, such oxidation proceeds via the formation of a
peroxo complex O2PdLn,10,11 whose decomposition by
acetic acid affords Pd(OAc)2Ln.5b,10 The latter reaction
gives H2O2 which decomposed to H2O and 1/2 O2 by 3 Å
MS.4b
Key words: palladium, benzoquinone, catalysis, electrochemical
oxidation, alcohols
Aerobic Pd-catalyzed oxidation of alcohols has been a
challenge for a long time.1 Palladium(II) acetate proved
to be an efficient catalyst for the oxidation for primary/
secondary allylic or benzylic alcohols to the correspond-
ing aldehydes/ketones, in the presence of a base in
DMSO and dioxygen, as reported by Larock et al. in 1998
(Scheme 1).2
These previous reports evidence that the use of dioxygen
as an oxidant may exhibit some inconvenience, such as: i)
limitation of the rate of the catalytic cycle by the slow dis-
solution of dioxygen (a consequence is the instability of
the transient Pd(0) complex before being oxidized by
dioxygen), ii) formation of peroxo palladium complex-
es,10,11 and iii) formation of H2O2 at the origin of side re-
actions, unless it is decomposed in situ.
Pd(OAc)2 (5 mol%)
R1CH(OH)R2
R1COR2
O2, base, DMSO, 80 °C
R1 = aryl, alkenyl R2 = H, alkyl
Scheme 1
The mechanism of this aerobic Pd-catalyzed oxidation of
alcohols was recently reported by Stahl et al. who con-
firmed that DMSO behaved as a ligand for palladium(0)
and palladium(II) moieties and not as a redox mediator.3a
The turnover of the catalytic reaction is limited by the dis-
solution of O2 into the solvent at high catalyst loading.3b
Other catalytic systems such as Pd(OAc)2/pyridine (1:4)
were developed in the absence of purposely added base in
toluene, as reported by Uemura et al. in 1998.4 The
presence of 3 Å molecular sieves was, however, required
to decompose H2O2 formed in the catalytic process.4b The
catalytic system Pd(OAc)2/Et3N (1:2) allowed the
oxidation of benzylic and aliphatic alcohols at 25 °C
(Sigman et al., 2002),5a whereas a well-defined complex
Pd(OAc)(NHC)2(H2O) (NHC = N-heterocyclic carbene)
afforded high turnover numbers.5b However, all reactions
were still conducted in the presence of 3 Å MS.5 The oxi-
dation of alcohols was performed in water with Pd(OAc)2
catalyst ligated to a water-soluble disulfonate phenanthro-
As an alternative to dioxygen, Pd(0) can be oxidized back
to Pd(II) by an oxidative addition of 1,2-dichloroethane
used in stoichiometric amount, as developed by Muzart et
al. in 1995 under biphasic conditions.12 Whereas p-benzo-
quinone is well known to oxidize Pd(0) to Pd(II) in Pd(II)-
catalyzed reactions, as pioneered by Bäckvall et al.,13 it
has never been used in the Pd(II)-catalyzed oxidation of
alcohols. It is worthwhile to note that a stoichiometric
amount of benzoquinone would be required with forma-
tion of a stoichiometric amount of the carcinogenic co-
product, p-hydroquinone. In a recent work, we established
that p-benzoquinone used in catalytic amount could act as
a redox mediator for the Pd(OAc)2-catalyzed vinylation of
arenes (Scheme 2, eq. 1).14 The Pd(0) complex formed in
the catalytic cycle is oxidized to Pd(II) by p-benzoquinone
(BQ) giving p-hydroquinone (HQ, Scheme 2, eq. 2)
which is recycled back to p-benzoquinone by oxidation at
an anode (Scheme 2, eq. 3).14
We now report preliminary results using the same proce-
dure for the Pd-catalyzed oxidation of alcohols under
anaerobic conditions in DMF (Scheme 3).15
SYNLETT 2007, No. 14, pp 2173–2178
0
3
.0
9
.2
0
0
7
Advanced online publication: 13.08.2007
DOI: 10.1055/s-2007-985568; Art ID: G15807ST
© Georg Thieme Verlag Stuttgart · New York

2174
C. Amatore et al.
LETTER
Pd(OAc)2 (10 mol%)
Pd(OAc)2 (10 mol%)
p-benzoquinone (10 mol%)
p-benzoquinone (10 mol%)
Ar
+ 2 H+ + 2 e–
(1)
(2)
R1CH(OH)R2
R1COR2 + 2 H+ + 2 e–
ArH +
R
R
HOAc
argon, base, DMF, ∆
R1 = aryl, alkenyl, alkyl; R2 = H, aryl, alkyl
Pd(II) +
HO
OH
via Pd(0) +
O
O
C anode: oxidation of p-hydroquinone to p-benzoquinone
Ni cathode: reduction of H+ to H2
HQ
BQ
HQ
BQ + 2 e– + 2 H+
(3)
Scheme 3
Scheme 2
carried out in DMF in a divided cell at constant potential
The oxidation of primary benzylic alcohols (1a–d) to (oxidation peak potential of the p-hydroquinone) at a car-
aldehydes was catalyzed by Pd(OAc)2 associated with
bon woven anode. Protons from acetic acid were reduced
p-benzoquinone used in catalytic amount and recycled by at a nickel grid cathode. Electrolyses were interrupted
electrochemical oxidation (Table 1).16 Electrolyses were when the current dropped to the background level. After
Table 1 Pd-Catalyzed Oxidation of Benzylic Alcohols 1 to Aldehydes 2a
H
Pd(OAc)2 (10 mol%)
OH
p-benzoquinone (10 mol%)
O
+ 2 H+ + 2 e–
K2CO3, DMF, 80 °C, 2 h
R
R
1a: R = H
2a–d
1b: R = 4-Cl
1c: R = 4-Me
1d: R = 4-MeO
77–98%
2 mmol
Entry
1
Pd-Cat.
(10%)
Co-cat.
(10%)
A (E, V)b
Base
(equiv/1)
Temp.
Time
(min)
Yield of
Recycl. 1
(°C)
80
r.t.
50
80
110
80
80
r.t.
70
70
80
80
80
80
80
80
80
ArCHO 2 (%)c (%)d
1
2
1a
1a
1a
1a
1a
1a
1a
1b
1b
1b
1b
1c
1c
1d
1a
1a
1a
No
BQ
BQ
BQ
BQ
BQ
BQ
BQ
BQ
BQ
BQ
BQ
BQ
BQ
BQ
No
C (+0.75)
C (+0.75)
C (+0.75)
C (+0.75)
C (+0.75)
C (+0.75)
C (+0.75)
C (+0.75)
C (+0.75)
Ce
K2CO3 (1)
K2CO3 (1)
K2CO3 (1)
K2CO3 (1)
K2CO3 (1)
NaOAc (1)
NaOAc (2)
K2CO3 (2)
K2CO3 (2)
K2CO3 (2)
K2CO3 (1)
K2CO3 (1)
K2CO3 (1)
K2CO3 (1)
K2CO3 (1)
K2CO3 (1)
K2CO3 (1)
–
340
–
0
27
29
77
65
45
46
48
72
64
65
65.5
71.5
98
56
65
40
100
56
56
27
37
37
39
21
11
17
20
13
10
0
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(PPh3)4
3
4
60
5
85
6
240
60
7
8
120
120
150
190
135
330
80
9
10
11
12
13
14
15
16
17
C (+0.75)
C (+0.75)
Pt (+0.75)
C (+0.75)
C (+0.5)
Pt (+0.5)
C (+0.5)
195
130
195
45
28
56
No
No
a The electrolyses were performed on 2 mmol of 1 in DMF (10 mL).
b Anode: C (carbon woven, apparent area: 4 cm2), Pt (platinum grid, apparent area: 4 cm2). E: electrolysis potential in V vs. SCE.
c Yields were determined by 1H NMR spectroscopy on the crude after workup; CHCl2CHCl2 was used as internal standard. The aldehydes were
then isolated by flash chromatography.
d Yields were determined by 1H NMR spectroscopy on the crude after workup; CHCl2CHCl2 was used as internal standard.
e Electrolysis conducted at constant current: I = 300 mA.
Synlett 2007, No. 14, 2173–2178 © Thieme Stuttgart · New York

LETTER
Electrochemical Oxidation of Alcohols
2175
workup, some starting alcohol was sometimes recovered,
which means that the electrolyses were stopped before
completion. An electrolysis was carried out at constant
current but with slightly less efficiency (entries 9 and 10
in Table 1). The best base was K2CO3 (K2CO3 > NaOAc)
used in stoichiometric amount at 80 °C (entries 4–7).
Electrolyses performed at a platinum grid electrode were
slower because of lower electrode specific area (entry 13
and 14). In all cases, the reactions proceeded with a high
selectivity in favor of the aryl aldehyde without formation
of aryl carboxylic acid thanks to the absence of O2.
ArCH2OH
hydroquinone
oxidation
– 2 e–
– 2 H+
base
ArCH2O–
AcO–
2 H+
Pd(OAc)2
benzoquinone
10 mol%
AcO–
[Pd0]
AcO Pd
H
H
The reaction did not work in the absence of Pd(OAc)2 (en-
try 1), establishing that the mechanism of the oxidation of
the benzylic alcohol is not a direct redox process. The pro-
posed mechanism is displayed in Scheme 4. Benzyl alco-
hol (PhCH2OH) did not exhibit any oxidation peak in
DMF over the investigated potential range (up to +2 V vs.
SCE in DMF at a glassy carbon electrode). No oxidation
peak was observed after addition of K2CO3 as a base,
which is indicative of a slow deprotonation process at
25 °C. A Pd(II)-alkoxide is formed by substitution of one
acetate ligand of Pd(OAc)2 by the alkoxide at sufficiently
high temperature (80 °C). It undergoes a b-hydride elimi-
nation which generates the aldehyde and a hydrido-Pd(II),
HPdOAc.17 A fast reductive elimination affords a Pd(0)
moiety. This reversible reductive elimination is drawn by
the oxidation of Pd(0) by the p-benzoquinone which also
serves as a ligand for the Pd(0).13 Therefore, the rate of the
catalytic reaction results from a fine-tuning between the
rate of deprotonation of the alcohol by the base and the
oxidation of the Pd(0) moiety by p-benzoquinone.
O
Ar
HOAc
reductive
elimination
AcOPdH
C–H activation
β-hydride
elimination
ArCHO
Scheme 4 Mechanism of the oxidation of benzylic alcohols to alde-
hydes catalyzed by Pd(OAc)2/p-benzoquinone
Pd(OAc)2 (10 mol%)
PhCHO + 2 H+ + 2 e–
PhCH2OH
K2CO3, DMF, 80 °C
1a
2a
C anode: oxidation of "Pd0n" stabilized by X– = OAc–, CO3
2–
Scheme 5
AcO Pd
H
PhCOMe + AcOPdH
Ph
O
Me
The Pd-catalyzed oxidation was also performed in the
absence of p-benzoquinone at lower potentials. The
reactions were, however, slower and led to catalyst de-
composition (Scheme 5, entries 15 and 16 in Table 1).
The very structure of the Pd(0) complex which is oxidized
at the anode is still speculative. Palladium(0) aggregates
or nanoparticles stabilized by acetate or carbonate ions
were certainly formed, as proposed in Pd(OAc)2-cata-
lyzed Heck reactions.18 The palladium complex Pd(PPh3)4
may also be used as catalyst (entry 17 in Table 1) but re-
sulted less efficient than Pd(OAc)2 when used alone.
Complex PdCl2(PPh3)2 was not efficient at all, even in the
presence of added chloride ions which ought to stabilize
Pd(0) complexes.19
C–H activation
β-hydride elimination
Scheme 6
The oxidation of the sec-phenethyl alcohol 3a was, how-
ever, slower than that of the benzyl alcohol 1a. The mech-
anism is certainly similar to that proposed in Scheme 4.
However, the b-hydride elimination reported in Scheme 6
ought to be more difficult than that from a primary palla-
dium(II)-alkoxide (one available H instead of two H).
The reaction is not restricted to secondary benzylic alco-
hols. Oxidation of cyclic or acyclic secondary alcohols
(3e and 3f) worked as well.
The oxidation of secondary benzylic alcohols to ketones
proceeded under similar conditions at 80 °C in the pres-
ence of a stoichiometric amount of K2CO3 (Table 2).
Miscellaneous reactions were also observed. The oxida-
tion of the allylic alcohol 3h in the presence of K2CO3 (1
equiv) yielded the a,b-unsaturated aldehyde 4h in 64%
Pd(OAc)2 (10 mol%)
p-benzoquinone (10 mol%)
O
Ph
Ph
OH
OH
K2CO3 (1 equiv), DMF, 80 °C
70 min, 64%
90 min, 30%
3h
3i
Ph
H
idem
4h
Scheme 7
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2176
C. Amatore et al.
LETTER
Table 2 Pd(OAc)2/p-Benzoquinone-Catalyzed Oxidation of Secondary Alcohols 3 to Ketones 4a
O
OH
Pd(OAc)2 (10 mol%)
p-benzoquinone (10 mol%)
R1
R2
R1
R2 + 2 H+ + 2 e–
K2CO3, DMF, 80 °C
4
3
C anode: oxidation of p-hydroquinone to p-benzoquinone
Ni cathode: reduction of H+ to H2
3
Base (equiv/3)
Time (min)
300
Yield of R1COR2 4 (%)b
Recycl. 3 (%)b
OH
O
K2CO3 (1)
35
3a
4a (60)
O
OH
K2CO3 (1)
90
0
O
O
4b (97)
3b
3c
3d
O
OH
K2CO3 (1)
K2CO3 (1)
K2CO3 (1)
75
90
90
23
4c (41)
OH
O
0
4d (98)
OH
O
41
3e
3f
4e (29)
OH
O
K2CO3 (1)
K2CO3 (2)
90
27
15
4f (58)c
OH
O
OH
O
110
H
3g
4g (80)
a All reactions were performed with 2 mmol of alcohol 3 in DMF (10 mL) at 80 °C with Pd(OAc)2 = p-benzoquinone = 10 mol% at the con-
trolled potential of E = +0.75 V vs. SCE (anode: carbon woven).
b Yields were determined by 1H NMR spectroscopy on the crude after workup; CHCl2CHCl2 was used as internal standard. The ketones 4 were
then isolated by flash chromatography.
c The a,b-unsaturated ketone (E)-Me(CH2)4CH=CHCOMe (6f) was formed in 6% yield.
yield (recovered 3h: 9%; Scheme 7). The oxidation of the A plausible mechanism for the formation of the unexpect-
nonallylic alcohol 3i performed under the same ex- ed a,b-unsaturated aldehyde 4h from the saturated alcohol
perimental conditions unexpectedly afforded the same 3i is proposed in Scheme 8. The oxidation of 3i gives the
a,b-unsaturated aldehyde 4h in 30% yield (recovered 3i: expected saturated aldehyde 4i and transient HPdOAc (as
69%; Scheme 7).
in Scheme 4). The reverse syn-addition of HPdOAc on the
C=C bond20 of the enolic form 4¢i of 4i leads to the inter-
Synlett 2007, No. 14, 2173–2178 © Thieme Stuttgart · New York

LETTER
Electrochemical Oxidation of Alcohols
2177
OH
O
Pd(OAc)2 (10 mol%)
p-benzoquinone (10 mol%)
Ph
H
Ph
H
Ph
OH
K2CO3, DMF, 80 °C
3i
4i
+ HPdOAc
4'i
+ HPdOAc
– HPdOAc
OAc
Pd(OAc)2 (10 mol%)
p-benzoquinone (10 mol%)
H
H
O
– HPdOAc
+ HPdOAc
Pd
Ph
OH
Ph
H
OH
Ph
H
K2CO3, DMF, 80 °C
H
3h
4h
H
5
Scheme 8
(4) (a) Nishimura, T.; Onoue, T.; Ohe, K.; Uemura, S.
mediate complex 5. The allylic alcohol 3h is formed after
a reversible syn-b-hydride elimination. Its further oxida-
tion affords the a,b-unsaturated aldehyde 4h, as observed
independently (Scheme 7, top reaction). The fact that nei-
ther the saturated aldehyde 4i nor the allylic alcohol 3h
were observed during the oxidation of 3i (only 4i at traces
level) suggests that they were present at stationary con-
centration in the successive equilibria which are shifted by
the oxidation of 3h to 4h.21 Interestingly, the oxidation of
3i led to the a,b-unsaturated aldehyde 4h after activation
of two C–H bonds by a Pd(II) moiety.
Tetrahedron Lett. 1998, 39, 6011. (b) Nishimura, T.;
Onoue, T.; Ohe, K.; Uemura, S. J. Org. Chem. 1999, 64,
6750.
(5) (a) Schultz, M. J.; Park, C. C.; Sigman, M. S. Chem.
Commun. 2002, 3034. (b) Jensen, D. R.; Schultz, M. J.;
Mueller, J. A.; Sigman, M. S. Angew. Chem. Int. Ed. 2003,
42, 3810.
(6) ten Brink, G.-J.; Arends, I. W. C. E.; Sheldon, R. A. Science
2000, 287, 1636.
(7) Jensen, D. R.; Pugsley, M. S.; Sigman, M. S. J. Am. Chem.
Soc. 2001, 123, 7475.
(8) Ferreira, E. M.; Stoltz, B. M. J. Am. Chem. Soc. 2001, 123,
7725.
The Pd/BQ-catalyzed oxidation of 2-nonanol (3f) gave
ketone 4f as the major product (Table 2). The a,b-unsatur-
ated ketone (E)-n-pentyl-CH=CHCOMe (6f) was also
formed in 6% yield by a mechanism similar to that pro-
posed in Scheme 8.22
(9) Hallman, K.; Moberg, C. Adv. Synth. Catal. 2001, 343, 260.
(10) Popp, B. V.; Stahl, S. S. J. Am. Chem. Soc. 2006, 128, 2804.
(11) Adamo, C.; Amatore, C.; Ciofini, I.; Jutand, A.; Lakmini, H.
J. Am. Chem. Soc. 2006, 128, 6829.
(12) Aît-Mohand, S.; Hénin, F.; Muzart, J. Tetrahedon Lett.
1995, 36, 2473.
(13) Grennberg, H.; Gogoll, A.; Bäckvall, J.-E. Organometallics
1993, 12, 1790.
(14) Amatore, C.; Cammoun, C.; Jutand, A. Adv. Synth. Catal.
2007, 349, 292.
In conclusion, the oxidation of alcohols to aldehydes or
ketones is catalyzed by Pd(OAc)2 associated to catalytic
p-benzoquinone. The reaction is made catalytic because
the Pd(0) generated in the reaction is oxidized back to
Pd(II) by p-benzoquinone. p-Benzoquinone may be also
used in catalytic amount because the p-hydroquinone
formed in the oxidation process is recycled back to p-ben-
zoquinone by oxidation at an anode. This anaerobic pro-
cess appears to be quite general and selective and avoids
the formation of H2O2, as formed in aerobic reactions.
Work is in progress to optimize the reactions.
(15) For anaerobic electrochemical oxidation of alcohols
catalyzed by [(trpy)(bpy)Ru(IV)=O]2+ in H2O, see:
(a) Moyer, B. A.; Thompson, M. S.; Meyer, T. J. J. Am.
Chem. Soc. 1980, 102, 2310. (b) Thompson, M. S.; De
Giovani, W. F.; Moyer, B. A.; Meyer, T. J. J. Org. Chem.
1984, 49, 4972. (c) De Giovani, W. F.; Deronzier, A.
J. Electroanal. Chem. 1992, 337, 285. (d) Geneste, F.;
Moinet, C. New J. Chem. 2004, 28, 722. (e) Geneste, F.;
Moinet, C. J. Electroanal. Chem. 2006, 594, 105.
(16) General Procedure for Preparative Electrolyses
The electrosynthesis of 2d (entry 14 in Table 1) was carried
out in a two-compartment air-tight three-electrode cell under
argon at 80 °C. The two compartments were separated by a
sintered glass disk. The anode was a carbon cloth (ca. 4 cm2
surface area). The cathode was a nickel foam (ca. 1 cm2
surface area). The reference was a sat. calomel electrode
separated from the solution by a bridge filled with a solution
of n-Bu4NBF4 (0.3 M) in DMF (2 mL). The anodic and
cathodic compartments were, respectively, filled with 10 mL
of DMF and 2 mL of DMF containing n-Bu4NBF4 (0.3 M).
Then 250 mL (2 mmol) of alcohol 1d was added to the anodic
compartment followed by 276 mg (2 mmol) of K2CO3, 21.6
mg (0.2 mmol) of sublimated p-benzoquinone, and 45 mg
(0.2 mmol) of Pd(OAc)2. Afterwards, 343 mL (6 mmol) of
AcOH was introduced into the cathodic compartment. The
electrolysis was conducted at a controlled potential of +0.75
V, using a Tacussel PJT 35-2 potentiostat. The electrolysis
Acknowledgment
This work has been supported in part by the Centre National de la
Recherche Scientifique (UMR CNRS-ENS-UPMC 8640) and the
Ministère de la Recherche (Ecole Normale Supérieure). We thank
Johnson Matthey for a loan of palladium salt.
References and Notes
(1) For recent reviews, see: (a) Sheldon, R. A.; Arends, I. W. C.
E.; ten Brink, G.-J.; Dijksman, A. Acc. Chem. Res. 2002, 35,
774. (b) Stahl, S. S. Angew. Chem. Int. Ed. 2004, 43, 3400.
(2) Peterson, K. P.; Larock, R. C. J. Org. Chem. 1998, 63, 3185.
(3) (a) Steinhoff, B. A.; Fix, S. R.; Stahl, S. S. J. Am. Chem. Soc.
2002, 124, 766. (b) Steinhoff, B. A.; Stahl, S. S. J. Am.
Chem. Soc. 2006, 128, 4348.
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2178
C. Amatore et al.
LETTER
(19) Amatore, C.; Jutand, A. Acc. Chem. Res. 2000, 33, 314.
was stopped after 80 min (passage of 1015 cb). After cooling
to r.t., the anodic compartment was hydrolyzed with 50 mL
of H2O. After extraction with Et2O, the organic phase was
dried on MgSO4 and evaporated. The yield of 2d (98% yield)
was determined on the crude mixture by 1H NMR (250
MHz) spectroscopy using CHCl2CHCl2 (0.5 mmol) as
internal standard added to the crude mixture after workup.
The alcohol 1d was not detected on the NMR spectra of the
crude mixture. Product 2d was isolated as pure compound by
flash chromatography (eluent: PE–EtOAc, 80:20). 1H NMR
(250 MHz, CDCl3): d = 3.71 (s, 3 H, OCH3), 6.84 (d, 2 H,
J = 8.7 Hz, o-H relative to OMe), 7.67 (d, 2 H, J = 8.7 Hz,
o-H relative to CHO), 9.71 (s, 1 H, CHO). 13C NMR (62.89
MHz, CDCl3): d = 55.25 (OCH3), 113.56 (COMe), 114.64
(o-C relative to OMe), 129.95 (CCHO), 131.83 (o-C relative
to CHO), 190.69 (C=O). MS (CI, NH3): m/z = 154 [M +
(20) Heck, R. F. J. Am. Chem. Soc. 1971, 93, 6896.
(21) (a) Interestingly, one reviewer has made the observation that
compounds 4i and 3h may also be formed in a palladium-
catalyzed Heck reaction between a phenyl halide and the
allyl alcohol via HPdX elimination and reverse re-addition
(see ref. 21b). In that case, the aldehyde 4i is the major
product. In our case, the b-H elimination from 5 should also
give the major product 4i but the minor 3h (in equilibrium
with 4i via 5) is quenched by its Pd/BQ-catalyzed oxidation
to 4h. As a result, 4i is fully consumed via the oxidation of
3h. (b) de Meijere, A.; Meyer, F. E. Angew. Chem., Int. Ed.
Engl. 1994, 33, 2379.
(22) In the latter case, 6f is the minor product because the
formation of the intermediate allylic alcohol (E)-n-pentyl-
CH=CHCH(OH)Me (7f) is less favored than the formation
of 3h in which the C=C bond is conjugated with the phenyl
group (Scheme 8). Moreover, the oxidation of the secondary
alcohol 7f became more difficult than the oxidation of the
primary alcohol 3h (Scheme 8).
+
NH4 ], 137 [M + H+].
(17) For b-hydride elimination of HPdOAc and subsequent
reductive elimination, see: Heck, R. F. J. Am. Chem. Soc.
1969, 91, 6707.
(18) Reetz, M. T.; Westermann, E. Angew. Chem. Int. Ed. 2000,
39, 165.
Synlett 2007, No. 14, 2173–2178 © Thieme Stuttgart · New York

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