Practical Pd/C-mediated allylic substitution in water

Article abstract of DOI:10.1021/jo050952t

Pd/C-mediated allylic substitution in water is described as an interesting alternative to classical homogeneous conditions. The reaction applied to allylic acetates showed a wide range of compatibility with various nitrogen, sulfur, oxygen, and carbon nucleophiles. Notably, the method features inexpensive reagents and a nontoxic solvent. Moreover, measurement of the palladium content in water by ICP-MS shows low palladium contamination (4 ppm) of the solvent, rendering this method safer for the environment compared to homogeneous conditions. The first asymmetric example of Pd/C-mediated allylic substitution is also disclosed.

Full text of DOI:10.1021/jo050952t

Practical Pd/C-Mediated Allylic Substitution in Water
Franc¸ois-Xavier Felpin* and Yannick Landais*
Universite´ Bordeaux-I, Laboratoire de Chimie Organique et Organome´tallique,
351 Cours de la Libe´ration, 33405 Talence Cedex, France
fx.felpin@lcoo.u-bordeaux1.fr; y.landais@lcoo.u-bordeaux1.fr
Received May 12, 2005
Pd/C-mediated allylic substitution in water is described as an interesting alternative to classical
homogeneous conditions. The reaction applied to allylic acetates showed a wide range of
compatibility with various nitrogen, sulfur, oxygen, and carbon nucleophiles. Notably, the method
features inexpensive reagents and a nontoxic solvent. Moreover, measurement of the palladium
content in water by ICP-MS shows low palladium contamination (4 ppm) of the solvent, rendering
this method safer for the environment compared to homogeneous conditions. The first asymmetric
example of Pd/C-mediated allylic substitution is also disclosed.
SCHEME 1. General Mechanism in Homogeneous
Conditions
Introduction
Palladium-catalyzed allylic substitution constitutes one
of the most important tools for carbon-carbon and
carbon-heteroatom bond formation (Scheme 1).1 Very
high catalytic activities and stereo- and regioselectivities
under mild conditions can be achieved using these
transformations. The usual conditions, however, have
several drawbacks and suffer from some limitations from
an industrial point of view. Most of the studies have been
carried out using expensive and air-sensitive Pd catalysts
(Pd(PPh3)4, Pd2(dba)3, ...) where Pd contamination of the
solvent and the product constitutes a limitation for large-
scale applications. Moreover, Pd-catalyzed reactions are
generally carried out in organic and often toxic solvents.
The problem of contamination from the metal has been
addressed by using polymer-supported catalysts2 or
heterogeneous Pd catalysts.3 In this context, palladium
on activated charcoal (Pd/C) has recently emerged as a
powerful catalyst for various carbon-carbon bond forma-
tion reactions.4 Another important feature is the compat-
ibility of Pd/C with water as solvent or cosolvent. Water
possesses many advantages over usual organic solvents.5
It is the least expensive and safest solvent available that
is nonflammable, inexplosive, and nontoxic. From a
practical point of view, organic transformations in water
represent the “ideal” conditions for a chemist, as dry
catalysts, reagents, and glassware are not required. The
reaction can even sometimes be performed under air
atmosphere. In an effort to develop “green” transforma-
tions during the course of a project requiring the prepa-
ration of various allyl sulfones through Pd-catalyzed
allylation,6 it was found that Pd/C could advantageously
replace Pd(Ph3)4 as a catalyst and that the reaction could
be carried out in water.7,8 This interesting observation
led us to explore more in depth the potential of this
(4) For recent reviews, see: (a) Blaser, H.-U.; Indolese, A.; Schnyder,
A.; Steiner, H.; Studer, M. J. Mol. Catal. A: Chem. 2001, 173, 3-18.
(b) Biffis, A.; Zecca, M.; Basato, M. J. Mol. Catal. A: Chem. 2001, 173,
249-274.
(1) For comprehensive reviews, see: (a) Trost, B. M.; Van Vranken,
V. L. Chem. Rev. 1996, 96, 395-422. (b) Trost, B. M.; Crawley, M. L.
Chem. Rev. 2003, 103, 2921-2943. (c) Comprehensive Asymmetric
Catalysis; Jacobsen, E. N., Pfaltz, A., Yamamoto, H., Eds.; Springer:
Berlin, 1999; Vols. I-III.
(2) (a) Danjo, H.; Tanaka, D.; Hayashi, T.; Uozumi, Y. Tetrahedron
1999, 55, 14341-14352. (b) Uozumi, Y.; Shibatomi, K. J. Am. Chem.
Soc. 2001, 123, 2919-2920, and references cited herein.
(3) Dos Santos, S.; Tong, Y.; Quignard, F.; Choplin, A.; Sinou, D.;
Dutasta, J. P. Organometallics 1998, 17, 78-89.
(5) Breslow, R. Acc. Chem. Res. 1991, 24, 159-164.
(6) (a) James, P.; Landais, Y. Org. Lett. 2004, 6, 325-328. (b) James,
P.; Felpin, F.-X.; Landais, Y.; Schenk, K. Unpublished results.
(7) For reviews on palladium reactions in water, see: (a) Genet, J.-
P.; Savignac, M. J. Organomet. Chem. 1999, 576, 305-317. (b)
Lindstro¨m, U. M. Chem. Rev. 2002, 102, 2751-2772. (c) Manabe, K.;
Kobayashi, S. Chem. Eur. J. 2002, 8, 4094-4101. (d) Sinou, D. Adv.
Synth. Catal. 2002, 344, 221-237.
10.1021/jo050952t CCC: $30.25 © 2005 American Chemical Society
Published on Web 07/07/2005
J. Org. Chem. 2005, 70, 6441-6446
6441

Felpin and Landais
TABLE 1. Optimization of Reaction Conditions
result indicates a genuine Pd/C-catalyzed reaction. From
these preliminary results, it should be highlighted that
neither water-soluble phosphines nor phase-transfer
catalysts or surfactants were required in order to obtain
high yield.
Scope of the Reaction. To explore further the scope
of this new process, we examined the reaction of three
different allylic acetates with a variety of nucleophiles.
The reaction showed a wide range of compatibility with
various nitrogen, sulfur, oxygen, and carbon nucleophiles.
Linear allylic acetate 1 gave good to excellent yields
(up to 96%) irrespective of the nature of the nucleophile.
When morpholine was used as nucleophile, better con-
version was found when DME was used as cosolvent
(entry 5). It should be noted, however, that no improve-
ment was observed using the same cosolvent and p-TsNa
(entry 2). While no base was required with p-TsNa and
morpholine, K2CO3 emerged as a base of choice with
oxygen and carbon nucleophiles. With Meldrum’s acid,
only the product resulting from the double alkylation
could be isolated in high yield (94%, entry 6). Another
important point that deserves comment is the regiose-
lectivity of the reaction. Similar to most homogeneous
Pd-catalyzed reactions, only linear compounds were
formed, except in the case of morpholine, where 4% of
the branched regioisomer was also isolated (entry 5).
As expected, branched allylic acetates were found to
be less reactive, and 5 mol % Pd/C associated with 20
mol % Ph3P was required to complete the reaction in
practicable yields. Reducing the amount of Pd/C-Ph3P
led to a dramatic increase of reaction time, and competi-
tive hydrolysis side reaction of acetate into its corre-
sponding alcohol occurred. This phenomenon was not
observed with cinnamyl acetate 1, even with prolonged
reaction times. However with 5 mol % Pd/C, hydrolysis
was present in less than 5% with acetates 3 and 4.
Whereas Meldrum’s acid afforded a single product result-
ing from a dialkylation process (entries 11, 15), the use
of diethylmalonate yielded exclusively the monoalkyla-
tion product (entry 14). These results were unanticipated,
as monoalkylation is the major result of similar homo-
geneous Pd-catalyzed reaction. Although reaction of
Meldrum’s acid with acetate 4 is known in the litera-
ture,12 to the best of our knowledge, compounds resulting
from a double alkylation have not been described. Other
nucleophiles also reacted well with branched acetates and
broaden the scope of this catalytic system (entries 8, 10,
12).
a Determined on the crude reaction mixture by 1H NMR.
b Yields are for isolated products. n.d.: not determined.
catalytic system, which to our knowledge remains un-
known for such a reaction.9 We report here the scope and
limitations of this methodology along with some mecha-
nistic considerations.
Results and Discussion
Optimization of Reaction Conditions. To evaluate
the potential of the Pd/C-mediated allylic alkylation in
water, we first selected cinnamyl acetate 1 as a model
substrate with the sodium salt of p-toluenesulfinic acid
(p-TsNa) as the nucleophile (Table 1). A number of
parameters were evaluated. Under optimized conditions
cinnamyl acetate 1 in water reacted with p-TsNa in the
presence of 10% Pd/C10 corresponding to 1 mol % and 4
mol % PPh3 under air to give the corresponding allylic
sulfone 2 in 96% yield (entry 3). A decrease of the
temperature from 70 °C to 40 °C resulted in a lower
conversion (40%) after 36 h of stirring (entry 1). Increas-
ing the catalyst loading led somewhat to an enhanced
reaction rate but with a significant diminished yield
(entry 2). Alternatively, a mixture of water and DME as
a solvent system could be used albeit with lower yield in
this case (vide infra) (entry 4). When triphenylphosphine
was omitted, allylic alkylation occurred at a slower rate
but with total conversion after 24 h of stirring. However,
subsequent studies showed that lower conversions were
observed with branched allylic acetates under PPh3-free
Pd/C conditions. The phosphine probably acts as a
stabilizing agent for Pd, generating in situ a more
reactive Pd(0)-PPh3 complex. Palladium-free allylic alky-
lation has recently been reported.11 However in our case
no reaction occurred in the absence of Pd/C. Starting
material was recovered quantitatively (entries 6, 7). This
Dry 10% Pd/C, although inexpensive and commercially
available, is pyrophoric under air atmosphere, requiring
specific attention during manipulations on a large scale.
To make the reaction safer on a large scale, we envisioned
the use of wet Pd/C. While Pd(OH)2 did not work at all,
5% Pd/C (E 105 CA/W from Degussa AG) gave yields and
reaction times similar to those of dry 10% Pd/C (entries
3, 9, 13).
(8) For recent examples of palladium-catalyzed allylic substitution
in water, see: (b) Blart, E.; Genet, J.-P.; Safi, M.; Savignac, M.; Sinou,
D. Tetrahedron 1994, 50, 505-514. (b) Lemaire-Audoire, S.; Blart, E.;
Savignac, M.; Pourcelot, G.; Genet, J.-P.; Bernard, J.-M. Tetrahedron
Lett. 1994, 35, 8783-8786. (c) Rabeyrin, C.; Nguefack, C.; Sinou, D.
Tetrahedron Lett. 2000, 41, 7461-7464. (d) Kobayashi, S.; Lam, W.;
Manabe, K. Tetrahedron Lett. 2000, 41, 6115-6117. (e) Hashizume,
T.; Yonehara, K.; Ohe, K.; Uemura, S. J. Org. Chem. 2000, 65, 5197-
5201. (f) Feuerstein, M.; Laurenti, D.; Doucet, H.; Santelli, M.
Tetrahedron Lett. 2001, 42, 2313-2315.
(9) An isolated report described the allylation of diethylamine with
allyl acetate catalyzed by Pd/C in toluene. But to have acceptable yields
in their conditions authors used 2650 equiv of Ph3P. They concluded
that “...hetereogeneous palladium catalysts such as Pd/C are generally
not useful for this reaction...” See: Bergbreiter, D. E.; Chen, B. J.
Chem. Soc., Chem. Commun. 1983, 1238-1239.
(10) 10% Pd/C was purchased from Aldrich.
(11) Chevrin, C.; Le Bras, J.; He´nin, F.; Muzart, J. Tetrahedron Lett.
2003, 44, 8099-8102.
On a substrate (i.e., acetate 14) required for our radical
cyclization project6 we compared the results obtained by
13
using Pd(PPh3)4 and Pd/C for the preparation of the
(12) Chen, W.; Xu, L.; Chatterton, C.; Xiao, J. Chem. Commun. 1999,
1247-1248.
(13) Inomata, K.; Yamamoto, T.; Kotake, H. Chem. Lett. 1981, 1357-
1360.
6442 J. Org. Chem., Vol. 70, No. 16, 2005

Practical Pd/C-Mediated Allylic Substitution
TABLE 2. Scope of the Reaction
a Determined on the crude reaction mixture by 1H NMR. b Yields of isolated products. c 4% of the branched isomer was also isolated.
d 5% Pd/C (E 105 CA/W) from Degussa AG was used.
TABLE 3. Comparison Pd(PPh3)4-Pd/C
yield (95%) and with greater regiodiscrimination favoring
the desired linear isomer 15 compared to Pd(PPh3)4.
These results highlight the efficiency of the heteroge-
neous Pd/C catalyst compared to the “classical” homoge-
neous Pd(PPh3)4 catalyst.
Mechanistic Studies. The mechanism of homoge-
neous Pd-mediated allylic alkylation has been extensively
studied1 and is summarized in Scheme 1. Oxidative
addition of an allylic leaving group I to Pd(0) gives an
(η3-allyl)palladium(II) complex II, which reacts with
various nucleophiles to furnish allylic compounds III.
To gain further insight into the Pd/C-mediated allylic
alkylation mechanism, we examined the reaction of
p-TsNa with two different acetates, 17 and 18, which
should give the same product (i.e., sulfone 2) according
to the above mechanism (Table 4). As expected, allylic
sulfone 2 was the only product observed with very similar
a Ratio determined on the crude reaction mixture by 1H NMR.
b Yields of isolated products. Combined yield of 15 and 16.
corresponding allyl sulfone 15. The optimized procedures
for each catalytic system are reported in Table 3.
Although a higher temperature was required, the use of
Pd/C led to the corresponding allyl sulfone 15 in higher
J. Org. Chem, Vol. 70, No. 16, 2005 6443

Felpin and Landais
TABLE 4. Mechanistic Studies
Conclusion
In conclusion, we reported the first Pd/C-mediated
allylic substitution in water. This catalytic process is
attractive, environment friendly, and requires an inex-
pensive source of Pd catalyst. This process should be
appealing for industrial scale purposes. We have dem-
onstrated, for the first time, the feasibility of an asym-
metric version, although the yield remains modest. The
developed methodology may find numerous applications
because of its practicability. Total synthesis of natural
products using this methodology will be reported shortly.
a Determined on the crude reaction mixture by 1H NMR.
b Yields of isolated products.
Experimental Section
trans-Cinnamyl-p-tolyl Sulfone (2). A solution of cin-
namyl acetate 1 (264 mg, 1.5 mmol) in H2O (4 mL) was treated
with p-TsNa (534 mg, 3 mmol), Ph3P (15.7 mg, 4 mol %), and
10% Pd/C (15.9 mg, 1 mol %). The resulting mixture was
stirred at 70 °C for 18 h. The mixture was filtered over a pad
of Celite. The filtrate was washed with CH2Cl2. The aqueous
phase was extracted with CH2Cl2 (2×). The collected organic
extracts were dried over anhydrous MgSO4, filtered, and
concentrated under reduced pressure. Purification by flash
chromatography (20% EtOAc-pentane) gave 2 as a colorless
solid (392 mg, 96%). Mp: 120 °C [lit.16 120-121 °C]. IR
TABLE 5. Asymmetric Attempts
1
(KBr): ν 1577, 1593, 2972, 3022 cm-1. H NMR (CDCl3, 300
MHz): δ 2.44 (s, 3H), 3.95 (dd, 2H, J ) 0.8, 7.5 Hz), 6.11 (dt,
1H, J ) 7.5, 15.5 Hz), 6.41 (dd, 1H, J ) 15.5 Hz), 7.29-7.34
(m, 7H), 7.77 (d, 2H, J ) 8.3 Hz). 13C NMR (CDCl3, 75 MHz):
δ 21.5, 60.5, 115.3, 126.5, 128.4, 128.4, 128.6, 129.6, 135.5,
135.8, 138.9, 144.7. HRMS (ESI): calcd for C16H16O2NaS (M
+ Na+) 295.0769, found 295.0757.
4-Cinnamylmorpholine (5) and 4-(1-Phenylallyl)mor-
pholine. A solution of cinnamyl acetate 1 (264 mg, 1.5 mmol)
in H2O (2 mL) and DME (2 mL) was treated with morpholine
(0.26 mL, 3 mmol), Ph3P (15.7 mg, 4 mol %), and 10% Pd/C
(15.9 mg, 1 mol %). The resulting mixture was stirred at 70
°C for 4 h. The mixture was filtered over a pad of Celite. The
filtrate was washed with CH2Cl2. The aqueous phase was
extracted with CH2Cl2 (2×). The collected organic extracts were
dried over anhydrous MgSO4, filtered, and concentrated under
reduced pressure. Purification by flash chromatography (20%
EtOAc-pentane to 100% EtOAc) gave 5 as a colorless oil (283
mg, 93%) and its branched isomer as a colorless oil (12 mg,
4%).
4-Cinnamylmorpholine 5. IR (neat): ν 1578, 1598, 2957,
3058 cm-1. 1H NMR (CDCl3, 300 MHz): δ 2.51-2.54 (m, 4H),
3.17 (dd, 2H, J ) 1.1, 6.8 Hz), 3.76 (t, 4H, J ) 4.5 Hz), 6.29
(dt, 1H, J ) 6.8, 13.6 Hz), 6.56 (d, 1H, J ) 15.8 Hz), 7.22-
7.41 (m, 5H). 13C NMR (CDCl3, 75 MHz): δ 61.4, 67.0, 126.1,
126.3, 127.5, 128.5, 133.3, 136.8. HRMS (ESI): calcd for C13H18-
NO (M+) 204.1388, found 204.1404.
4-(1-Phenylallyl)morpholine. IR (neat): ν 1602, 1640,
2956, 3027 cm-1. 1H NMR (CDCl3, 300 MHz): δ 2.30-2.37 (m,
2H), 2.48-2.53 (m, 2H), 3.63 (d, 1H, J ) 5.8 Hz), 5.11 (dd,
1H, J ) 1.5, 9.8 Hz), 5.24 (dd, 1H, J ) 1.1, 17.3 Hz), 5.85-
5.97 (m, 1H), 7.22-7.36 (m, 5H). 13C NMR (CDCl3, 75 MHz):
δ 52.0, 67.1, 75.5, 116.6, 127.2, 127.9, 128.6, 139.7, 141.6.
HRMS (ESI): calcd for C13H18NO (M+) 204.1388, found
204.1402.
a Determined by chiral HPLC. b Yields of isolated products.
yields irrespective of the nature of the acetate. Branched
acetate 17 rearranges to the linear allylic sulfone 2 (entry
1), and (Z)-allyl acetate 18 isomerizes into (E)-allyl
product (entry 2). From these observations we concluded
that Pd/C-mediated allylic substitution in water proceeds
through a mechanism close to that of homogeneous Pd
catalysis.
Several recent studies have shown that Pd/C-mediated
Heck14 and Suzuki15 reactions proceeded through homo-
geneous catalytic pathways via Pd species dissolved in
solution. For our reaction, ICP-MS was used to evaluate
the amount of Pd leaching into the solvent that did not
redeposit on the charcoal. After 18 h of stirring during
the transformation of 1 to 2, the concentration of solu-
bilized Pd was only 4 ppm (based on 0.029 mmol Pd
introduced), indicating 1.3% of the metal used for the
reaction had leached into the solvent.
Asymmetric Attempts. Finally, we studied an asym-
metric version of this new catalytic system by using chiral
diphosphine ligands (Table 5). Whereas (-)-DIOP in-
duced negligible enantioselectivity, (R)-BINAP afforded
12 in 80% ee, albeit in low yield. Although these results
are far from satisfactory, they show that enantioselective
Pd/C-mediated allylation is possible, in principle. More-
over, to our knowledge, this result is the first example
of a Pd/C-catalyzed asymmetric C-C bond formation
reaction. Further optimization of these preliminary re-
sults is thus currently under investigation.
5,5-Dicinnamyl-2,2-dimethyl-1,3-dioxane-4,6-dione (6).
A solution of cinnamyl acetate 2 (264 mg, 1.5 mmol) in H2O
(4 mL) was treated with K2CO3 (414 mg, 3 mmol), Medrum’s
acid (432 mg, 3 mmol), Ph3P (15.7 mg, 4 mol %), and 10% Pd/C
(15.9 mg, 1 mol %). The resulting mixture was stirred at 70
°C for 5 h. The mixture was filtered over a pad of Celite. The
filtrate was washed with CH2Cl2. The aqueous phase was
(14) (a) Zhao, F.; Bhanage, B. M.; Shirai, M.; Arai, M. Chem. Eur.
J. 2000, 6, 843-848. (b) Ko¨hler, K.; Heidenreich, R. G.; Krauter, J. G.
E.; Pietsch, J. Chem. Eur. J. 2002, 8, 622-631.
(15) (a) LeBlond, C. R.; Andrews, A.; Sun, Y.; Sowa, J. R., Jr. Org.
Lett. 2001, 3, 1555-1557. (b) Conlon, D. A.; Pipik, B.; Ferdinand, S.;
LeBlond, C. R.; Sowa Jr, J. R.; Izzo, B.; Collins, P.; Ho, G.-J.; Williams,
J. M.; Shi, Y.-J.; Sun, Y. Adv. Synth. Catal. 2003, 345, 931-935.
(16) Bellesia, F.; Grandi, R.; Pagnoni, U. M.; Trave, R. J. Chem. Res.
Synop. 1981, 4, 112-113.
6444 J. Org. Chem., Vol. 70, No. 16, 2005

Practical Pd/C-Mediated Allylic Substitution
extracted with CH2Cl2 (2×). The collected organic extracts were
dried over anhydrous MgSO4, filtered, and concentrated under
reduced pressure. Purification by flash chromatography (20%
EtOAc-pentane) gave 6 as a colorless solid (263 mg, 94%).
Mp: 131-132 °C [lit.17 131 °C]. IR (KBr): ν 1576, 1596, 1741,
1773, 2996, 3056 cm-1. 1H NMR (CDCl3, 300 MHz): δ 1.55 (s,
6H), 2.97 (d, 4H, J ) 7.9 Hz), 6.10 (dt, 2H, J ) 7.9, 15.8 Hz),
6.56 (d, 2H, J ) 15.8 Hz), 7.22-7.36 (m, 10H). 13C NMR
(CDCl3, 75 MHz): δ 29.7, 42.1, 56.3, 106.0, 121.7, 126.3, 127.9,
128.6, 136.0, 136.2, 168.7. HRMS (ESI): calcd for C24H24O4-
Na (M + Na+) 399.1572, found 399.1572.
1.41-1.85 (m, 8H), 1.74 (s, 6H), 1.97 (m, 4H), 3.20 (m, 2H),
5.57-5.60 (m, 1H), 5.74-5.86 (m, 3H). 13C NMR (CDCl3, 75
MHz): δ 22.2, 22.2, 24.8, 25.3, 26.4, 30.1, 30.1, 40.4, 40.8, 60.7,
61.2, 105.7, 105.7, 124.8, 125.1, 130.1, 130.6, 167.2, 167.4,
167.6 (rotamers). HRMS (ESI): calcd for C18H24O4Na (M +
Na+) 327.1572, found 327.1570.
(E)-1,3-Diphenyl-2-propenyl-p-tolyl Sulfone (11). Pre-
pared as described for 2, with acetate 4 (378 mg, 1.5 mmol),
p-TsNa (534 mg, 3 mmol), Ph3P (78.6 mg, 20 mol %), and 10%
Pd/C (79.5 mg, 5 mol %) in H2O (4 mL) at 70 °C for 31 h.
Purification by flash chromatography (20% EtOAc-pentane)
gave 11 as a colorless solid (354 mg, 68%). Mp: 157-158 °C
1-((E)-3-(4-Methoxyphenoxy)prop-1-enyl)benzene (7).
A solution of cinnamyl acetate 2 (264 mg, 1.5 mmol) in H2O
(4 mL) was treated with K2CO3 (414 mg, 3 mmol), p-methox-
yphenol (372 mg, 3 mmol), Ph3P (15.7 mg, 4 mol %), and 10%
Pd/C (15.9 mg, 1 mol %). The resulting mixture was stirred at
70 °C for 5 h. The mixture was filtered over a pad of Celite.
The filtrate was washed with CH2Cl2. The aqueous phase was
extracted with CH2Cl2 (2×). The collected organic extracts were
dried over anhydrous MgSO4, filtered, and concentrated under
reduced pressure. Purification by flash chromatography (10%
EtOAc-pentane) gave 7 as a colorless solid (327 mg, 91%).
Mp: 106-107 °C [lit.18 107-109 °C]. IR (KBr): ν 1577, 1638,
[lit.19 157-158 °C]. IR (KBr): ν 1596, 1639, 2920, 3060 cm-1
.
1H NMR (CDCl3, 300 MHz): δ 2.40 (s, 3H), 4.83 (d, 1H, J )
7.2 Hz), 6.50-6.64 (m, 2H), 7.20-7.39 (m, 12H), 7.55 (d, 2H,
J ) 8.3 Hz). 13C NMR (CDCl3, 75 MHz): δ 21.6, 75.3, 120.2,
126.7, 128.4, 128.6, 128.6, 128.8, 129.3, 129.3 129.7, 132.5,
134.4, 135.9, 137.9, 144.5. HRMS (ESI): calcd for C22H20NaSO2
(M + Na+) 371.1082, found 371.1067.
Diethyl 2-[(E)-1,3-Diphenyl-2-propenyl]malonate (12).
A solution of acetate 4 (378 mg, 1.5 mmol) in H2O (4 mL) was
treated with K2CO3 (414 mg, 3 mmol), diethyl malonate (455
µL, 3 mmol), Ph3P (78.6 mg, 20 mol %), and 10% Pd/C (79.5
mg, 5 mol %). The resulting mixture was stirred at 70 °C for
5 h. The mixture was filtered over a pad of Celite. The filtrate
was washed with CH2Cl2. The aqueous phase was extracted
with CH2Cl2 (2×). The collected organic extracts were dried
over anhydrous MgSO4, filtered, and concentrated under
reduced pressure. Purification by flash chromatography (5%
EtOAc-pentane) gave 12 as a colorless oil (369 mg, 70%). IR
1
2954, 3046 cm-1. H NMR (CDCl3, 300 MHz): δ 3.78 (s, 3H),
4.66 (dd, 2H, J ) 1.5, 5.6 Hz), 6.42 (dt, 1H, J ) 5.6, 15.8 Hz),
6.73 (d, 1H, J ) 16.2 Hz), 6.84-6.93 (m, 4H), 7.24-7.44 (m,
5H). 13C NMR (CDCl3, 75 MHz): δ 55.7, 69.4, 114.7, 115.8,
124.8, 126.5, 127.8, 128.6, 132.8, 136.5, 152.8, 154.0. HRMS
(ESI): calcd for C16H16O2Na (M + Na+) 263.1048, found
263.1047.
Cyclohex-2-enyl-p-tolyl Sulfone (8). Prepared as de-
scribed for 2, with acetate 3 (210 mg, 1.5 mmol), p-TsNa (534
mg, 3 mmol), Ph3P (78.6 mg, 20 mol %), and 10% Pd/C (79.5
mg, 5 mol %) in H2O (4 mL) at 70 °C for 6 h. Purification by
flash chromatography (20% EtOAc-pentane) gave 8 as a
colorless oil (230 mg, 65%). IR (neat): ν 1597, 1649, 2936, 3034
cm-1. 1H NMR (CDCl3, 300 MHz): δ 1.42-1.55 (m, 1H), 1.73-
1.97 (m, 5H), 2.44 (s, 3H), 3.69-3.76 (m, 1H), 5.74-5.80 (m,
1H), 6.03-6.10 (m, 1H), 7.33 (d, 1H, J ) 7.9 Hz), 7.74 (d, 1H,
J ) 8.3 Hz). 13C NMR (CDCl3, 75 MHz): δ 19.5, 21.6, 22.7,
24.3, 61.8, 118.7, 129.1, 129.6, 134.4, 135.1, 144.5. HRMS
(ESI): calcd for C13H16O2NaS (M + Na+) 259.0769, found
259.0776.
1
(KBr): ν 1600, 1731, 2982, 3060 cm-1. H NMR (CDCl3, 250
MHz): δ 1.02 (t, 3H, J ) 7.1 Hz), 1.21 (t, 3H, J ) 7.1 Hz),
3.93 (d, 1H, J ) 11.3 Hz), 3.98 (q, 2H, J ) 7.1 Hz), 4.18 (q,
2H, J ) 7.1 Hz), 4.27 (dd, 1H, J ) 8.7, 11.3 Hz), 6.34 (dd, 1H,
J ) 8.3, 15.4 Hz), 6.49 (d, 1H, J ) 15.8 Hz), 7.20-7.34 (m,
10H). 13C NMR (CDCl3, 75 MHz): δ 13.8, 14.1, 49.2, 57.8, 61.3,
61.5, 126.3, 127.1, 127.5, 128.0, 128.4, 128.6, 129.3, 131.7,
136.8, 140.3, 167.4, 167.8. HRMS (ESI): calcd for C22H24NaO4
(M + Na+) 375.1572, found 375.1563.
Diethyl 2-[(1R)-2E)-1,3-Diphenyl-2-propenyl]malonate
(12). A solution of acetate 4 (378 mg, 1.5 mmol) in H2O (4 mL)
was treated with K2CO3 (414 mg, 3 mmol), diethyl malonate
(455 µL, 3 mmol), (R)-BINAP (93 mg, 10 mol %), and 10% Pd/C
(79.5 mg, 5 mol %). The resulting mixture was stirred at 70
°C for 5 h. The mixture was filtered over a pad of Celite. The
filtrate was washed with CH2Cl2. The aqueous phase was
extracted with CH2Cl2 (2×). The collected organic extracts were
dried over anhydrous MgSO4, filtered, and concentrated under
reduced pressure. Purification by flash chromatography (5%
EtOAc-pentane) gave 12 as a colorless oil (111 mg, 21%), 80%
ee, determined by chiral HPLC, Chiralpak AD-H (hexane/
i-PrOH ) 90/10, 11.4 min for (S)-12 and 15.3 min for (R)-12).
N,N-Dibenzylcyclohex-2-enamine (9). A solution of ac-
etate 3 (210 mg, 1.5 mmol) in H2O (4 mL) was treated with
dibenzylamine (0.58 mL, 3 mmol), Ph3P (78.6 mg, 20 mol %),
and 10% Pd/C (79.5 mg, 5 mol %). The resulting mixture was
stirred at 70 °C for 12 h. The mixture was filtered over a pad
of Celite. The filtrate was washed with CH2Cl2. The aqueous
phase was extracted with CH2Cl2 (2×). The collected organic
extracts were dried over anhydrous MgSO4, filtered, and
concentrated under reduced pressure. Purification by flash
chromatography (10% EtOAc-pentane) gave 9 as a colorless
oil (287 mg, 69%). IR (neat): ν 1603, 1650, 2931, 3061 cm-1
.
2,2-Dimethyl-5,5-bis((E)-1,3-diphenylallyl)-1,3-dioxane-
4,6-dione (13). Prepared as described for 6, with acetate 4
(378 mg, 1.5 mmol), Meldrum’s acid (432 mg, 3 mmol), Ph3P
(78.6 mg, 20 mol %), and 10% Pd/C (79.5 mg, 5 mol %) in H2O
(4 mL) at 70 °C for 5 h. Purification by flash chromatography
(10% EtOAc-pentane) gave 11 as a mixture of two inseparable
diastereoisomers (86:14) (261 mg, 66%). Mp: 106 °C. IR (KBr):
1H NMR (CDCl3, 300 MHz): δ 1.46-1.64 (m, 2H), 1.81-1.85
(m, 1H), 1.91-2.06 (m, 3H), 3.37-3.40 (m, 1H), 3.58 (d, 2H, J
) 14.0 Hz), 3.78 (d, 2H, J ) 14.0 Hz). 13C NMR (CDCl3, 75
MHz): δ 21.8, 23.2, 25.3, 53.8, 54.5, 126.6, 128.1, 128.5, 130.0,
130.8, 140.9. HRMS (ESI): calcd for C20H24N (M+) 278.1909,
found 278.1917.
ν 1599, 1650, 1728, 1760, 3060 cm-1 1H NMR (CDCl3, 300
.
5,5-Di(cyclohex-2-enyl)-2,2-dimethyl-1,3-dioxane-4,6-
dione (10). Prepared as described for 6, with acetate 3 (210
mg, 1.5 mmol), Meldrum’s acid (432 mg, 3 mmol), Ph3P (78.6
mg, 20 mol %), and 10% Pd/C (79.5 mg, 5 mol %) in H2O (4
mL) at 70 °C for 6 h. Purification by flash chromatography
(10% EtOAc-pentane) gave 10 as a mixture of two inseparable
diastereoisomers (1:1) (162 mg, 71%). Mp: 201 °C. IR (KBr):
MHz): δ 0.55 (s, 6H × 0.86), 0.87 (s, 6H × 0.14), 4.36 (d, 2H
× 1, J ) 10.2 Hz), 6.27 (d, 2H × 0.14, J ) 15.8 Hz), 6.46 (d,
2H × 0.86, J ) 15.8 Hz), 6.92 (dd, 2H × 0.14, J ) 10.1, 15.8
Hz), 7.17-7.45 (m, 20H × 1 + 2H × 0.86). 13C NMR (CDCl3,
75 MHz): δ 28.3 (0.86), 28.7 (0.14), 54.7 (0.86), 55.4 (0.14),
63.7 (0.86), 64.0 (0.14), 106.1 (0.86), 106.2 (0.14), 124.9 (0.86),
126.5 (0.14), 126.7 (0.86), 127.2 (0.14), 127.6 (0.14), 127.7 (0.86),
127.8 (0.86), 128.4 (0.14), 128.6 (0.14), 128.6 (0.86), 129.0 (0.86),
129.2 (0.86), 130.1 (0.14), 134.3 (0.14), 135.4 (0.86), 136.7 (0.14),
1
1648, 1731, 1764, 2930 cm-1. H NMR (CDCl3, 300 MHz): δ
(17) Prat, M.; Moreno-Man˜as, M.; Ribas, J. Tetrahedron 1988, 44,
7205-7212.
(18) Zhang, W.; Haight, A. R.; Hsu, M. C. Tetrahedron Lett. 2002,
37, 6575-6578.
(19) Sato, T.; Homma, I. Bull. Chem. Soc. Jpn. 1971, 44, 1885-1891.
J. Org. Chem, Vol. 70, No. 16, 2005 6445

Felpin and Landais
137.0 (0.86), 139.0 (0.14), 139.3 (0.86), 167.1 (0.86), 167.2 (0.14).
HRMS (ESI): calcd for C36H32NaO4 (M + Na+) 551.2198, found
551.2206.
1-(6-tert-Butylocta-1,7-dien-3-ylsulfonyl)-4-methylben-
zene (16). Mixture of diastereoisomers. IR (neat): ν 1597,
1
1638, 1738, 2963, 3071 cm-1. H NMR (CDCl3, 250 MHz): δ
1-((E)-6-tert-Butylocta-2,7-dienylsulfonyl)-4-methyl-
benzene (15) and 1-(6-tert-Butylocta-1,7-dien-3-ylsul-
fonyl)-4-methylbenzene (16). With Pd/C. Prepared as
described for 2, with acetate 14 (336 mg, 1.5 mmol), p-TsNa
(294 mg, 1.65 mmol), Ph3P (15.7 mg, 4 mol %), and 10% Pd/C
(15.9 mg, 1 mol %) in H2O (4 mL) at 70 °C for 16 h. Purification
by flash chromatography (20% EtOAc-pentane) gave 15 and
16 (15/16: 95/5) (456 mg, 95% combined yield).
0.80 (s, 9H), 0.8-1.24 (m, 1H), 1.32-1.76 (m, 3H), 1.83-1.97
(m, 0.5H), 2.09-2.22 (m, 0.5H), 2.43 (s, 3H), 3.38-3.51 (m,
1H), 4.82-5.08 (m, 3H), 5.25-5.31 (m, 1H), 5.36-5.69 (m, 2H),
7.30 (d, 2H, J ) 6.9 Hz), 7.69 (dd, 2H, J ) 1.6, 6.9 Hz). 13C
NMR (CDCl3, 75 MHz): δ 21.6, 25.3, 25.3, 26.0, 26.3, 27.6,
27.6, 32.5, 32.6, 54.3, 55.5, 69.6, 70.3, 116.8, 116.9, 123.2, 123.5,
129.2, 129.2, 129.3, 130.4, 130.8, 134.6, 139.0, 139.4, 144.4,
144.4. HRMS (LSIMS): calcd for C19H28O2S2 (M+) 320.1805,
found 320.1810.
With Pd(PPh3)4. A solution of acetate 14 (336 mg, 1.5
mmol) in THF (8 mL) and MeOH (2 mL) was treated with
p-TsNa (294 mg, 1.65 mmol) and Pd(PPh3)4 (86.7 mg, 5 mol
%). The resulting mixture was stirred for 12 h and then diluted
with Et2O and water. The organic phase was extracted three
times with Et2O. The collected organic extracts were dried
(MgSO4) and concentrated under reduced pressure. Purifica-
tion by flash chromatography (15% EtOAc-pentane) gave 15
and 16 (15/16: 8/2) (413 mg, 86% combined yield). Some
fractions from flash chromatography have been obtained pure
for analysis.
Acknowledgment. The authors acknowledge the
Institut Universitaire de France for financial support.
Degussa AG is gratefully acknowledged for a generous
gift of 5% Pd/C (E 105 CA/W). We also thank Mr. Olivier
Brugier (ISTEEM, Montpellier 2) for ICP-MS analysis
and Mr. Pierre Guenot (CRMPO, Universite´ de Rennes
1) for HRMS analysis. Thank are also due to Dr. F.
Robert (University Bordeaux 1), Mr. Edouard Godineau
(University Bordeaux 1), and Mr. Soumya Mitra (The
Ohio State University) for helpful discussions.
1-((E)-6-tert-Butylocta-2,7-dienylsulfonyl)-4-methyl-
benzene (15). IR (neat): ν 1598, 1637, 1665, 2963, 3070 cm-1
.
1H NMR (CDCl3, 250 MHz): δ 0.81 (s, 9H), 0.95-1.10 (m, 1H),
1.35-1.57 (m, 2H), 1.67-1.85 (m, 1H), 1.95-2.09 (m, 1H), 2.43
(s, 3H), 3.72 (d, 2H, J ) 6.4 Hz), 4.86 (dd, 1H, J ) 2.5, 17.0
Hz), 5.01 (dd, 1H, J ) 2.2, 10.1 Hz), 5.33-5.54 (m, 3H), 7.32
(d, 2H, J ) 7.9 Hz), 7.72 (d, 2H, J ) 8.2 Hz). 13C NMR (CDCl3,
75 MHz): δ 21.6, 27.6, 27.8, 31.0, 32.5, 54.5, 60.2, 116.0, 116.4,
128.5, 129.5, 135.5, 139.7, 141.7, 144.4. HRMS (LSIMS): calcd
for C19H28O2S2Na (M + Na+) 343.1708, found 343.1710.
Supporting Information Available: Preparation of ac-
etate 14 and copies of 1H and 13C NMR of all compounds. This
material is available free of charge via the Internet at
http://pubs.acs.org.
JO050952T
6446 J. Org. Chem., Vol. 70, No. 16, 2005