Microwave-assisted palladium-catalyzed allylation of β-enaminones

Article abstract of DOI:10.1055/s-0034-1378540

A new palladium-catalyzed approach for the C-allylation of β-enaminones under microwave irradiation is reported. This methodology provides an easy access to a variety of α-allylated enaminones. The reaction takes place with the preservation of the enamine function, which is poised for further transformations towards nitrogen-containing heterocycles. Georg Thieme Verlag Stuttgart New York.

Full text of DOI:10.1055/s-0034-1378540

2196▌
LETTER
lMetteircrowave-Assisted Palladium-Catalyzed Allylation of β-Enaminones
Allylation of β-Enaminones
Imen Erray,a,b,c Farhat Rezgui,a Julie Oble,*b,c Giovanni Poli*b,c
a
Laboratoire de Chimie Organique Structurale et Macromoléculaire, Faculté des Sciences Campus Universitaire, Université de Tunis El Manar,
2092 Tunis, Tunisia
b
Sorbonne Universités, UPMC Univ Paris 06, UMR 8232, Institut Parisien de Chimie Moléculaire, FR2769 Institut de Chimie Moléculaire,
75005, Paris, France
Fax +33(1)44274287; E-mail: giovanni.poli@upmc.fr, julie.oble@upmc.fr
c
CNRS, UMR 8232, Institut Parisien de Chimie Moléculaire, 75005, Paris, France
Received: 12.06.2014; Accepted after revision: 26.06.2014
Due to their particular reactivity, combining the nucleo-
philicity of enamines with the electrophilicity of enones,
β-enamino carbonyl scaffolds are versatile nitrogen-con-
taining building blocks,9 which have been employed for
Abstract: A new palladium-catalyzed approach for the C-allylation
of β-enaminones under microwave irradiation is reported. This
methodology provides an easy access to a variety of α-allylated
enaminones. The reaction takes place with the preservation of the
enamine function, which is poised for further transformations to- transition-metal-catalyzed syntheses of various hetero-
cyclic derivatives.10 We thought that such structures could
wards nitrogen-containing heterocycles.
keep the conventional carbonucleophilic reactivity toward
transiently generated η3-allylpalladium complexes, yet,
derailing from the classical reactivity in the subsequent
evolution of the iminium ion generated. Indeed, due to the
increased acidity of the newly allylated carbon atom,
elimination to regenerate the enamine function can be pre-
dicted (Scheme 2, right) instead of the classical iminium
ion hydrolysis (Scheme 2, left).
Key words: enaminone, palladium, allylation, allyl acetate, micro-
wave irradiation
Palladium-catalyzed transformations have gained an im-
portant place in the toolbox of synthetic chemists.1 During
the last 30 years, the Tsuji–Trost allylation arose as a ver-
satile method for the functionalization of a wide array of
scaffolds.2,3 In particular, enamines have been amongst
the first nucleophiles shown to smoothly react with a
η3-allylpalladium complex, as reported by Tsuji et al. in
their seminal paper.4 Indeed, such structures can be effi-
ciently allylated at carbon, leading to the corresponding
γ,δ-unsaturated carbonyls after hydrolysis of the iminium
ion intermediate (Scheme 1, eq. 1).5 On the other hand,
C-allylation of enamines with conservation of the nitro-
gen atom is a hitherto unsolved and challenging transfor-
mation,6 of high potential interest for the synthesis of
nitrogen-containing frameworks. To reach this goal, and
in keeping with our ongoing interest in η3-allylpalladium
chemistry,7 we herein report a new protocol of allylation
of β-enaminones,8 wherein the enamine function is pre-
served (Scheme 1, eq. 2).
With this idea in mind, we undertook an investigation of
the palladium-catalyzed allylation using β-enaminone 1a,
[readily prepared from 4-(trimethylsilyl)-3-butyn-2-one
and benzylamine and isolated in E/Z ratio of 1:1.3]11 as the
model substrate. As recent studies showed that the combi-
nation of Pd(OAc)2 with a phosphinoferrocene ligand in a
molecular ratio of 1:1.1 allows efficient allylations of
enamines,5c,g,h we decided to carry out our first reaction
with 10 mol% of Pd(OAc)2, 11 mol% of dppf [1,1′-bis(di-
phenylphosphino)ferrocene] and one equivalent of allyl
phosphate in toluene at 60 °C or 40 °C. Pleasantly, the de-
sired allylated enaminone 2a could be obtained in 31% or
30% NMR yields12 after 18 hours at 60 °C or 65 hours at
40 °C, respectively (Table 1, entries 1 and 2).13
R2
R1
H
X
R2
O
[Pd(0)] cat
N
hydrolysis
– NH2R2
NH
(1)
R1
R3
previous reports
R1
X
R3
R3
R1
R1
R1
[Pd(0)] cat
R3
O
O
O
R3
(2)
this work
H
HN
R2
N
HN
R2
X
R3
X
R2
Scheme 1 Pd-mediated allylation of enamine derivatives
SYNLETT 2014, 25, 2196–2200
Advanced online publication: 31.07.2014
0
9
3
6
-
5
2
1
4
1
4
3
7
-
2
0
9
6
DOI: 10.1055/s-0034-1378540; Art ID: st-2014-b0509-l
© Georg Thieme Verlag Stuttgart · New York

LETTER
Allylation of β-Enaminones
2197
base
H
H
H
R1
EWG
R1
O
EWG
H
H
X
O
H
H
H
R2
R2
R2
R2
N
N
N
X
R3
R3
R3
allylated (N-free) carbonyl
from classical enamine
allylated enamine
from activated enamine
Scheme 2 Concept: expected different evolution in the allylation of classical vs. EWG-activated enamines
Table 1 Allylation of Enaminone 1a under Thermal Conditionsa
traces of water do not play a role in the degradation pro-
cess (Table 1, entry 3).
Pd(OAc)2 (10 mol%)
dppf (11 mol%)
Despite the yield improvement, the prolonged reaction
time remained a drawback. Hence, in order to speed up the
reaction, we decided to test microwave irradiation (Table
2).14
O
O
base (1 equiv)
toluene, temp, time
conv. 85–95%
LG
+
HN
Bn
1a
E/Z = 1:1.3
HN
Bn
1 equiv
2a
E/Z ~ 1:1
Table 2 Allylation of Enaminone 1a under Microwave Irradiationa
Pd(OAc)2 (10 mol%)
dppf (11 mol%)
Entry LG
Base
Temp Time (h)Yield
(°C)
(%)b
O
O
base (1 equiv)
LG
toluene, MW, temp, time
+
HN
Bn
1a
E/Z ~ 1:1,3
HN
Bn
2a
E/Z ~ 1:1
1
2
3
4
5
6
OP(O)(OEt)2
OP(O)(OEt)2
–
60
40
60
60
40
40
18
65
18
18
65
65
31
30
52c
50
33
63
–
OP(O)(OEt)2
OP(O)(OEt)2
OAc
proton sponge
lutidine
Entry LG (equiv)
Base
Temp Time Yield
(°C)
(min) (%)b
–
c
1
2
3
4
5
6
OP(O)(OEt)2 (1) proton sponge
100
100
100
100
130
100
60
60
60
90
60
60
–
OAc
proton sponge
OAc (1)
OAc (2)
OAc (2)
OAc (2)
OAc (2)
proton sponge
proton sponge
proton sponge
proton sponge
68
a Unless otherwise noted, all reactions were conducted in sealed tube
under argon atmosphere at 0.5 M concentration with 1a (1 equiv), al-
lylic partner (1 equiv), Pd(OAc)2 (10 mol%), dppf (11 mol%), and
base (1 equiv) in toluene.
72 (60)d
71
41
31
b Spectroscopic (1H NMR) yields using an internal standard (1,3,5-tri-
methoxybenzene).
c The same yield was obtained in the presence of the following addi-
tives: i) 4 Å MS; ii) H2O (10 equiv).
lutidine
Et
N
N
N
Et
P
N
7
8
OAc (2)
OAc (2)
100
100
60
60
47
42
However, we noticed some degradation, likely due to the
hydrolysis of the iminium intermediate. Therefore, we hy-
pothesized that the use of additives such as non-nucleop-
hilic amine bases could favor the regeneration of the
enamine moiety by deprotonation at the α-position of the
t-Bu
DBU
a Unless otherwise noted, all reactions were conducted in sealed tube
carbonyl (Scheme 2, right), and thus improve the efficien- under argon atmosphere and microwave irradiation at 0.5 M concen-
tration with 1a (1 equiv), allylic partner (1 or 2 equiv), Pd(OAc)2 (10
cy of this transformation. Indeed, adding proton sponge
[1,8-bis(dimethylamino)naphthalene] or lutidine (2,6-di-
methylpyridine) demonstrated a beneficial effect, and al-
mol%), dppf (11 mol%), and base (1 equiv) in toluene.
b Spectroscopic (1H NMR) yields using an internal standard (1,3,5-tri-
methoxybenzene).
c Degradation.
lylated enaminone 2a was formed in 52% and 50% NMR
yields, respectively, after 18 hours at 60 °C (Table 1, en-
tries 3 and 4). The same effect was observed in the pres-
ence of 1 equivalent of proton sponge with allyl acetate as
the allylic partner, in which case an improved 63% NMR
yield was obtained after 65 hours at 40 °C (Table 1, com-
pare entries 5 vs. 6). Finally, experiment of entry 6 (Table
1), when run in the presence of 4 Å molecular sieves, led
to the same yield as when run without, demonstrating that
d Isolated yield in parentheses.
While allyl phosphate only gave degradation after one
hour at 100 °C under microwave irradiation (Table 2, en-
try 1), allyl acetate afforded the desired allylated enami-
none 2a in 68% NMR yield (Table 2, entry 2). An
1
improved (72% H NMR) yield was obtained when two
equivalents of allylic partner were used (Table 2, entry 3).
© Georg Thieme Verlag Stuttgart · New York
Synlett 2014, 25, 2196–2200

2198
I. Erray et al.
LETTER
The time (Table 2, entry 4), the temperature (Table 2, en-
try 5), and the nature of the base (Table 2, entries 5–8)
were also screened, and the best result was obtained with
one equivalent of proton sponge after one hour of micro-
wave irradiation at 100 °C. An investigation of the influ-
ence of the solvent (toluene, dioxane, DMF, EtOH,
DMSO, THF) and the nature of both the palladium cata-
lyst and the ligand was also undertaken.15 We found the
optimal yield for allylation of enaminone 1a (1H NMR
yield 72%, isolated yield 60%) was obtained in the pres-
ence of two equivalents of allyl acetate with 10 mol% of
Pd(OAc)2, 11 mol% of dppf, and one equivalent of proton
sponge in toluene after one hour, under microwave heat-
ing at 100 °C (Table 2, entry 3).16,17
Table 3 Scope of the Allylation with Different Allylic Partners
R2
Pd(OAc)2 (10 mol%)
dppf (11 mol%)
proton sponge (1 equiv)
R1
LG
O
R1
O
+
R2
2 equiv
HN
Bn
toluene, MW, 100 °C, 1 h
NH
Bn
1a
2l–n
Entry
LG
OAc
R1
R2
Yield (%)a
1
2
3
4
5
6
H
Me
Me
H
2l 13 (14)b
c
OP(O)(OEt)2
OAc
H
–
Me
Me
Ph
Ph
2m 0
With these optimized conditions in hand, we began to ex-
plore the scope of the allylation with allyl acetate on a se-
ries of β-enaminones (Scheme 3). Benzyl (2a–c), allyl
(2d), and alkyl groups (2e–g) on the secondary amine
moiety were well tolerated and provided the target allylat-
ed enaminones in good to moderate yields. A less nucleo-
philic enaminone, such as N-tosyl-enaminone 1h only
gave 13% of N-allylated product 3h, which proved that
the electron-richness of the nitrogen atom is crucial for the
reaction at the carbon atom. Moreover, the tertiary enam-
c
OP(O)(OEt)2
OAc
H
–
H
2n 29
OP(O)(OEt)2
H
2n 68 (42)b
a Spectroscopic (1H NMR) yields using an internal standard (1,3,5-tri-
methoxybenzene).
b Isolated yield in parentheses.
c Degradation.
inone 1i was unreactive. The presence of a methyl substit- Next, we studied the reaction between β-enaminone 1a
uent at the C3-position was also investigated, in which and various allylic partners (Table 3). While but-3-en-2-yl
case a 23% yield (53% 1H NMR yield) was obtained for acetate (Table 3, entry 1) only afforded the corresponding
the allylated enaminone 2j. Finally, a β-enamino ester branched allylated enaminone 2l with low yield, crotyl ac-
could be used, leading to 2k in a low yield (20%). We etate gave no reaction (Table 3, entry 3). The correspond-
speculate that in this case the weakly acidic character of ing phosphates led only to degradation (Table 3, entries 2
the α-proton favors degradation of the iminium intermedi- and 4). On the other hand, the use of cinnamyl acetate
ate over enamine regeneration.
gave exclusively the linear product 2n with 29% 1H NMR
yield without trace of the branched isomer (Table 3, entry
Pd(OAc)2 (10 mol%)
dppf (11 mol%)
R1
R1
proton sponge (1.0 equiv)
O
O
OAc
2.0 equiv
+
toluene, MW, 100 °C, 1 h
R3
HN
R2
R3
HN
R2
1a–k
2a–k
Ph
O
O
O
O
O
O
HN
Bn
HN
HN
HN
n-Bu
HN
t-Bu
HN
Bn
PMB
2a 72 (60)
2b 44 (43)
2c 50 (57)
2d 33 (32)
2e 48 (47)
2f 47 (34)
MeO2C
O
O
O
O
HN
HN
Cy
N
N
HN
Bn
2j 53 (23)
Bn
2k 37 (20)
Ts
3h (13)
Bn
2g 69 (40)
2i (not observed)
Scheme 3 Scope of the allylation with allyl acetate. NMR yields (%) given; isolated yields (%) given in parentheses.
Synlett 2014, 25, 2196–2200
© Georg Thieme Verlag Stuttgart · New York

LETTER
Allylation of β-Enaminones
2199
5). Nevertheless, an improved (68% 1H MR, 42% isolat-
ed) yield was obtained when two equivalents of cinnamyl
phosphate were used (Table 3, entry 6).
Supporting Information for this article is available online
at http://www.thieme-connect.com/products/ejournals/journal/
10.1055/s-00000083.SunogIpimrfiantoSuIpg
n
fonirtat
ori
Finally, we wished to verify that this transformation takes
place via a direct C-allylation as opposed to N-allylation
and [3,3]-sigmatropic rearrangement (Scheme 4).
References and Notes
(1) (a) Beller, M.; Bolm, C. Transition Metals for Organic
Synthesis: Building Blocks and Fine Chemicals, 2nd ed.;
Vol. 1 and 2; Weinheim, Wiley-VCH 2004. (b) Negishi, E.
Handbook of Organopalladium Chemistry for Organic
Synthesis; Wiley-Interscience: New York, 2002. (c) Tsuji, J.
Palladium Reagents and Catalysts: Innovations in Organic
Synthesis; Wiley: New York, 2004. (d) Diederich, F.; de
Meijere, A. Metal-Catalyzed Cross-Coupling Reactions;
Wiley-VCH: Weinheim, 2004, 2nd ed.
(2) For reviews, see: (a) Trost, B. M.; Vranken, D. L. V. Chem.
Rev. 1996, 96, 395. (b) Trost, B. M. Chem. Pharm. Bull.
2002, 50, 1. (c) Trost, B. M.; Crawley, M. L. Chem. Rev.
2003, 103, 2921. (d) Lu, Z.; Ma, S. Angew. Chem. Int. Ed.
2008, 47, 258.
R1
[3,3]
N-allylation
O
N
R2
R1
R1
OAc
O
H
O
+
[Pd(0)] cat
base
N
HN
R2
R1
R2
H
O
H
elimination
C-allylation
N
(3) Poli, G.; Prestat, G.; Liron, F.; Kammerer-Pentier, C. In
Transition Metal Catalyzed Enantioselective Allylic
Substitution in Organic Synthesis; Kazmaier, U., Ed.; Top.
Organomet. Chem. 2012, 38; 1.
X
R2
Scheme 4 Possible mechanistic paths toward the allylated product
(4) Tsuji, J.; Takahashi, H.; Morikawa, M. Tetrahedron Lett.
1965, 6, 4387.
To this purpose, tertiary enaminone 1i was synthesized
and submitted to the reaction conditions (in the absence of
the allyl partner). After one hour under microwave heat-
ing at 100 °C, only unreacted starting material (SM) was
recovered (Scheme 3 and Scheme 5). Consequently, we
assume that a direct C-allylation mechanism is operating,
leading to an iminium intermediate, which would then un-
dergo elimination to regenerate the enamine function
(Scheme 1, eq. 2; Scheme 2, right).18
(5) For examples of Pd-catalyzed enamine allylations, see:
(a) Ibrahem, I.; Córdova, A. Angew. Chem. Int. Ed. 2006, 45,
1952. (b) Bihelovic, F.; Matovic, R.; Vulovic, B.; Saicic, R.
N. Org. Lett. 2007, 9, 5063. (c) Liu, D.; Xie, F.; Zhang, W.
Tetrahedron Lett. 2007, 48, 7591. (d) Mukherjee, S.; List, B.
J. Am. Chem. Soc. 2007, 129, 11336. (e) Zhao, X.; Liu, D.;
Xie, F.; Zhang, W. Tetrahedron 2009, 65, 512. (f) Usui, I.;
Schmidt, S.; Breit, B. Org. Lett. 2009, 11, 1453. (g) Vulovic,
B.; Bihelovic, F.; Matovic, R.; Saicic, R. N. Tetrahedron
2009, 65, 10485. (h) Zhao, X.; Liu, D.; Xie, F.; Liu, Y.;
Zhang, W. Org. Biomol. Chem. 2011, 9, 1871. (i) Afewerki,
S.; Ibrahem, I.; Rydfjord, J.; Breistein, P.; Córdova, A.
Chem. Eur. J. 2012, 18, 2972. (j) Li, M.; Datta, S.; Barber,
D. M.; Dixon, D. J. Org. Lett. 2012, 14, 6350. (k) Jiang, G.;
List, B. Angew. Chem. Int. Ed. 2011, 50, 9471.
Pd(OAc)2 (10 mol%)
dppf (11 mol%)
proton sponge (1 equiv)
O
SM
N
toluene, MW, 100 °C, 1 h
(6) For examples of Pd-catalyzed C-alkenylation of enamides
with conservation of the nitrogen atom, see: (a) Gigant, N.;
Gillaizeau, I. Org. Lett. 2012, 14, 3304. (b) Gigant, N.;
Chausset-Boissarie, L.; Rey-Rodriguez, R.; Gillaizeau, I. C.
R. Chim. 2013, 16, 358.
Bn
1i
Scheme 5 Control experiment
(7) For recent examples, see: (a) Kammerer, C.; Prestat, G.;
Madec, D.; Poli, G. Chem. Eur. J. 2009, 15, 4224. (b) Vogel,
S.; Bantreil, X.; Maitro, G.; Prestat, G.; Madec, D.; Poli, G.
Tetrahedron Lett. 2010, 51, 1459. (c) Bantreil, X.; Prestat,
G.; Moreno, A.; Madec, D.; Fristrup, P.; Norrby, P. O.;
Pregosin, P. S.; Poli, G. Chem. Eur. J. 2011, 17, 2885.
(d) Boutier, A.; Kammerer-Pentier, C.; Krause, N.; Prestat,
G.; Poli, G. Chem. Eur. J. 2012, 18, 3840. (e) Giboulot, S.;
Liron, F.; Prestat, G.; Wahl, B.; Sauthier, M.; Castanet, Y.;
Mortreux, A.; Poli, G. Chem. Commun. 2012, 48, 5889.
(f) Lorion, M. M.; Gasperini, D.; Oble, J.; Poli, L. Org. Lett.
2013, 15, 3050. (g) Rajabi, J.; Lorion, M. M.; Linh, Ly. V.;
Liron, F.; Oble, J.; Prestat, G.; Poli, G. Chem. Eur. J. 2014,
20, 1539. (h) Mistico, L.; Ay, E.; Huynh, V.; Bourderioux,
A.; Chaumeil, H.; Chemla, F.; Ferreira, F.; Oble, J.; Pérez-
Luna, A.; Poli, G.; Prestat, G. J. Organomet. Chem. 2014,
760, 124. (i) Rigamonti, M.; Prestat, G.; Broggini, G.; Poli,
G. J. Organomet. Chem. 2014, 760, 149. (j) Liron, F.; Oble,
J.; Lorion, M. M.; Poli, G. Eur. J. Org. Chem. 2014, in press;
DOI: 10.1002/ejoc.201402049.
In summary, we have developed a palladium-catalyzed in-
termolecular C-allylation of β-enaminones under micro-
wave irradiation, leading to the corresponding α-allylated
substrate. The preservation of the nitrogen atom in this
transformation is a new feature of high potential interest
in relation to the synthesis of heterocyclic and biologically
relevant targets. Extension of this methodology for the
synthesis of nitrogen-containing frameworks is currently
under way in our laboratory.
Acknowledgment
We thank Ahlem Abidi for her contribution in preliminary experi-
ments and Omar Khaled for HRMS analyses. CNRS, UPMC, and
Labex Michem are acknowledged for financial support. Support th-
rough CMST COST Action, CM1205 (CARISMA) is also grateful-
ly acknowledged. I.E. thanks the University de Tunis El Manar for
financial support.
© Georg Thieme Verlag Stuttgart · New York
Synlett 2014, 25, 2196–2200

2200
I. Erray et al.
LETTER
(12) In order to avoid the hydrolysis of the unreacted starting
(8) During the redaction of this manuscript, a related study
dealing with the Pd-catalyzed cyclization of N-tosyl-
substituted β-enaminocarbonyl compounds with allylic
bisacetates was reported, see: Yoshida, M.; Kinoshita, K.;
Namba, K. Org. Biomol. Chem. 2014, 12, 2394; according to
the authors, the corresponding N-benzylated substrates did
not react under their reaction conditions.
(9) For reviews, see: (a) Elassar, A.-Z. A.; El-Khair, A. A.
Tetrahedron 2003, 59, 8463. (b) Negri, G.; Kascheres, A. J.
J. Heterocycl. Chem. 2004, 41, 461. (c) Stanovnik, B.;
Steve, J. Chem. Rev. 2004, 2433. (d) Ferraz, H. M. C.;
Goncalo, E. R. S. Quim. Nova 2007, 30, 957. (e) Govindh,
B.; Diwakar, B. S. Murthy Y. L. N. Org. Commun. 2012, 5,
105.
material and/or the product, the yields were determined by
1H NMR spectroscopy of the crude mixture (obtained after
rapid filtration on silica gel and evaporation) using 1,3,5-
trimethoxybenzene as internal standard.
(13) In general, the allylated product 2a was obtained with an
average 1:1 E/Z ratio (determined by 1H NMR spectroscopy
of the crude mixture). This ratio is variable and can change
during silica gel purification.
(14) For a recent review, see: Caddick, S.; Fitzmaurice, R.
Tetrahedron 2009, 65, 3325.
(15) See Supporting Information.
(16) When the reaction was carried out without either the
precatalyst/ligand system or the precatalyst, only unreacted
enaminone 1a was recovered with traces of the
corresponding imino–enol tautomer 1a′ (see Supporting
Information).
(17) General Procedure
(10) For some selected Pd-catalyzed reactions, see: (a) Iida, H.;
Yuasa, Y.; Kibayashi, C. J. Org. Chem. 1980, 45, 2938.
(b) Kasahara, A.; Izumi, T.; Murakami, S.; Yanai, H.;
Takatori, M. Bull. Chem. Soc. Jpn. 1986, 59, 927.
(c) Sakamoto, T.; Nagano, T.; Kondo, Y.; Yamanaka, H.
Synthesis 1990, 215. (d) Michael, J. P.; Chang, S.-F.;
Wilson, C. Tetrahedron Lett. 1993, 34, 8365. (e) Koerber-
Plé, K.; Massiot, G. Synlett 1994, 759. (f) Chen, L.-C.;
Yang, S.-C.; Wang, H.-M. Synthesis 1995, 385. (g) Latham,
E. J.; Stanfoth, S. P. Chem. Commun. 1996, 2253.
(h) Latham, E. J.; Stanfoth, S. P. J. Chem. Soc., Perkin
Trans. 1 1997, 2059. (i) Blache, Y.; Sinibaldi-Troin, M.-E.;
Voldoire, A.; Chavignon, O.; Gramain, J.-C.; Teulade, J.-C.;
Chapat, J.-P. J. Org. Chem. 1997, 62, 8553. (j) Kirschbaum,
S.; Waldmann, H. J. Org. Chem. 1998, 63, 4936.
(k) Edmonson, S. D.; Mastracchio, A.; Parmee, E. R. Org.
Lett. 2000, 2, 1109. (l) Yamazaki, K.; Kondo, Y. J. Comb.
Chem. 2002, 4, 191. (m) Yamazaki, K.; Nakamura, Y.;
Kondo, Y. J. Org. Chem. 2003, 68, 6011. (n) Sorensen, U.
S.; Pombo-Villar, E. Helv. Chim. Acta 2004, 87, 82.
(o) Dajka-Halász, B.; Monsieurs, K.; Eliás, O.; Károlyházy,
L.; Tapolcsányi, P.; Maes, B. U. W.; Riedl, Z.; Hajós, G.;
Dommisse, R. A.; Lemière, G. L. F.; Košmrlj, J.; Mátyus, P.
Tetrahedron 2004, 60, 2283. (p) Gu, Z.-Y.; Zhu, T.-H.; Cao,
J.-J.; Xu, X.-P.; Wang, S.-Y.; Ji, S.-J. ACS Catal. 2014, 4,
49. For some selected Cu-catalyzed reactions, see: (q) Yan,
S.; Wu, H.; Wu, N.; Jiang, Y. Synlett 2007, 2699. (r) Cacchi,
S.; Fabrizi, G.; Filisti, E. Org. Lett. 2008, 10, 2629.
(s) Bernini, R.; Fabrizi, G.; Cacchi, S. Angew. Chem. Int. Ed.
2009, 48, 8078. For Fe-catalyzed reactions, see: (t) Guan,
Z.-H.; Ren, Z.-Y.; Liu, X.-Y.; Liang, Y.-M. Chem. Commun.
2010, 46, 2823. For Au-catalyzed reactions, see: (u) Arcadi,
A.; Di Giuseppe, S.; Marinelli, F.; Rossi, E. Tetrahedron:
Asymmetry 2001, 12, 2715. (v) Saito, A.; Konishi, T.;
Hanzawa, Y. Org. Lett. 2010, 12, 372.
To a suspension of Pd(OAc)2 (13 mg, 0.057 mmol, 10
mol%), dppf (35 mg, 0.063 mmol, 11 mol%), and proton
sponge (0.12 g, 0.57 mmol, 1 equiv) in THF (0.5 mL) in a
Schlenk flask equipped with a septum, under argon
atmosphere, was added allyl acetate (0.12 mL, 1.14 mmol,
2.0 equiv). After 5 min stirring, a solution of enaminone 1a
(100 mg, 0.57 mmol, 1 equiv) in THF (0.5 mL) was added,
the flask was sealed, and the mixture was stirred during 1 h
under microwave irradiation at 100 °C. The resulting crude
was filtered on a plug of silica gel. The solvent was removed,
and the mixture was purified by flash chromatography on
silica gel (EtOAc–cyclohexane, 20:80) to afford 86 mg of
the allylated enaminone 2a as a mixture of Z and E isomers.
Analytical Data for Compound 2a
Yield 60%; yellow oil; Z/E ratio = 1.7:1 (analysis of the
crude 1H NMR spectrum showed a Z/E ratio of 1:1). IR
(film): 3272, 3030, 2920, 1638 cm–1. 1H NMR (300 MHz,
CDCl3): δ = 10.24 [br s, 1 H, NH(Z)], 7.42–7.25 [m, 11 H,
=CHNH(E) + CHAr(Z+E)], 6.66 [d, J = 12.4 Hz, 1 H,
=CHNH(Z)], 5.94–5.71 [m, 2 H, HC=CH2(Z+E)], 5.10–4.99
(m, 4 H, HC=CH2(Z+E)], 4.43 (d, J = 5.9 Hz, 2 H, CH2Ph(E)],
4.39 (d, J = 6.1 Hz, 2 H, CH2Ph(Z)], 3.12 [dt, J = 6.0, 1.6 Hz,
2 H, CH2CH=CH2(E)], 2.94 [dt, J = 5.8, 1.6 Hz, 2 H,
CH2CH=CH2(Z)], 2.22 (s, 3 H, CH3CO(E)], 2.13 (s, 3 H,
CH3CO(Z)]. 13C NMR (75 MHz, CDCl3): δ = 198.2, 194.2,
153.0, 149.5, 138.6, 138.5, 138.4, 136.0, 128.9, 128.8,
127.8, 127.6, 127.0, 126.9, 114.8, 114.6, 102.8, 52.5, 52.2,
35.6, 28.0, 27.6, 24.4. HRMS: m/z calcd for C14H17NONa
[M + Na]+: 238.1208; found: 238.1204.
(18) Formation of the linear product, when using cinnamyl
acetate, is a further proof of the direct C-allylation
mechanism.
(11) Bromidge, S. M.; Entwistle, D. A.; Goldstein, J.; Orlek, B.
S. Synth. Commun. 1993, 23, 487.
Synlett 2014, 25, 2196–2200
© Georg Thieme Verlag Stuttgart · New York

Copyright of Synlett is the property of Georg Thieme Verlag Stuttgart and its content may not
be copied or emailed to multiple sites or posted to a listserv without the copyright holder's
express written permission. However, users may print, download, or email articles for
individual use.