Palladium-catalyzed domino carbopalladation/C-H activation for the synthesis of tetrasubstituted alkenes bearing five- and seven-membered rings

Article abstract of DOI:10.1055/s-0032-1317325

A Pd-catalyzed domino carbopalladation/C-H-activation reaction of phenoxyphenyl-substituted propargylic alcohols was used for the synthesis of tetrasubstituted alkenes bearing either a dihydroindene or benzo[7]annulene motif. These compounds are of intere

Full text of DOI:10.1055/s-0032-1317325

2516▌
LETTER
letter
Palladium-Catalyzed Domino Carbopalladation/C–H Activation for the Syn-
thesis of Tetrasubstituted Alkenes Bearing Five- and Seven-Membered Rings
Tetrasubstituted Alkenes Bearing 5- and 7-Membered Rings
Lutz F. Tietze,*a Tim Hungerland,a Christian Depken,a Christian Maaß,b Dietmar Stalkeb
a
Institute of Organic and Biomolecular Chemistry of the Georg-August-University Göttingen, Tammannstr. 2, 37077 Göttingen, Germany
Fax +49(551)399476; E-mail: ltietze@gwdg.de
b
Institute of Inorganic Chemistry of the Georg-August-University Göttingen, Tammannstr. 4, 37077 Göttingen, Germany
Received: 30.07.2012; Accepted after revision: 05.09.2012
O
Abstract: A Pd-catalyzed domino carbopalladation/C–H-activa-
tion reaction of phenoxyphenyl-substituted propargylic alcohols
was used for the synthesis of tetrasubstituted alkenes bearing either
a dihydroindene or benzo[7]annulene motif. These compounds are
of interest for the construction of molecular switches and motors.
O
OH
A
C
B
Pd(OAc)2, Ph3P, K2CO3
DMF, 100 °C, 2 h, MW
Br
OH
87%
O
D
E
Key words: palladium, domino reaction, C–H activation, tetra-
substituted alkenes, catalysis
O
1
2
Scheme 1 Pd-catalyzed domino carbopalladation–C–H-activation re-
action of alkyne 1 to give the tetrasubstituted alkene 2
Chemistry has reached a high level of performance and al-
lows the preparation of complex molecular structures.
Herein, transition-metal-mediated transformations and es-
pecially palladium-catalyzed cross-coupling reactions
have emerged as powerful synthetic tools.1 However, one
major drawback is the prerequisite for prefunctionaliza-
tion of one or both coupling partners. A more appropriate
procedure in terms of economy and ecology is the direct
C–H functionalization using readily available substrates.2
Furthermore, combining the C–H activation with other
Pd-catalyzed reactions in a domino mode would be even
more appropriate and would allow the construction of
complex structures with multiple bond formations in an
economically and ecologically benign fashion.3,4 Thus,
the design of novel domino reactions employing palladium-
catalyzed transformations of unfunctionalized aromatic
scaffolds is a very promising approach especially for the
preparation of new materials and natural products.5
of the five-membered system the amount of palladium can
be drastically reduced, and finally we have shown that in-
stead of Pd(OAc)2 also Pd on carbon can be used as cata-
lyst. In this case, the use of acetate either as base or as
ligand turned out to be essential.
Reaction of the propargylic alcohols 3 with a tether of
n = 1 using Pd(OAc)2 in the presence of triphenylphos-
phane and potassium carbonate led to the desired alkenes
7, whereas reaction of the propargylic alcohols 4 with a
5
OH
R
n
4
R
n
OH
Br
O
O
Recently, we have developed domino carbopalladation–
Stille and domino carbopalladation–Heck-type reactions
for the synthesis of overcrowded tetrasubstituted helical
alkenes.6a,b These compounds are of great interest as mo-
lecular switches and motors.7 Though the approaches give
good yields and are highly efficient, the use of stannanes
is not very appropriate. To our delight, we were able to re-
place the ecologically less suitable Stille reaction by a di-
rect C–H activation. Thus, the ecologically more friendly
domino carbopalladation/C–H-activation reaction of al-
kyne 1 using 20 mol% of Pd(OAc)2 gave the alkene 2 in
87% yield (Scheme 1).6c
3a–d: n = 1
4a–d: n = 3
7a–d: n = 1
8a–d: n = 3
‡
‡
R
n
OH
n
OH
R
O
Pd
LPd
Br
O
Here we show that several other tetrasubstituted alkenes
containing a five- and a seven-membered ring system B
can be prepared using this method. Moreover, in the case
H
O
O
L = OAc
5
6
SYNLETT 2012, 23, 2516–2520
Advanced online publication: 28.09.2012
DOI: 10.1055/s-0032-1317325; Art ID: ST-2012-B0644-L
© Georg Thieme Verlag Stuttgart · New York
0
9
3
6
-
5
2
1
4
1
4
3
7
-
2
0
9
6
Scheme 2 Proposed mechanism for the domino transformation of
propargylic alcohols 3 and 4 to give alkenes 7 and 8

LETTER
Tetrasubstituted Alkenes Bearing 5- and 7-Membered Rings
2517
Table 1 Domino Reaction of 3a–d and 4a–d to Give the Dihydroin-
denes 7a–d and the Benzo[7]annulenes 8a–d
5
OH
R
4
n
n
R
Pd(OAc)2, PPh3, K2CO3
(5.00 equiv)
OH
Br
DMF, 100 °C, 2 h, MW
O
O
3a–d: n = 1
4a–d: n = 3
7a–d: n = 1
8a–d: n = 3
Entry Substrate R (n)
Pd(OAc)2 Product Yield
(mol%)
(%)a
1
2
3a
3a
3a
3b
3b
3b
3b
3b
3c
3c
3c
3d
3d
3d
3d
4a
4b
4c
4d
4d
H (1)
20
10
5
7a
7a
7a
7b
7b
7b
7b
7b
7c
7c
7c
7d
7d
7d
7d
8a
8b
8c
8d
8d
76
H (1)
65
3
H (1)
60
4
5-MeO (1)
5-MeO (1)
5-MeO (1)
5-MeO (1)
5-MeO (1)
5-F (1)
20
10
5
71
5
76
6
97
7
2
88
8
10
20
10
5
75b
74c
73
9
10
11
12
13
14
15
16
17
18
19
20
5-F (1)
5-F (1)
70
4,5-OCH2O (1)
4,5-OCH2O (1)
4,5-OCH2O (1)
4,5-OCH2O (1)
H (3)
20
10
5
99
99
83
1.5
20
20
20
20
10
63
48d
65c
20c,e
72c
46c
4-Me (3)
4-F (3)
4-F3C (3)
4-F3C (3)
OH
O
R
Figure 1 Crystal structure of dihydroindene 7d (top), benzo[7]annu-
lene derivative 8b (middle), and ketone 10 (bottom); depicted are the
corresponding anisotropic displacement parameters at the 50% prob-
ability level
H
PhO
O
9a: R = H
9c: R = F
10
a Yield of isolated products.
tether of n = 3 gave the alkenes 8 (Scheme 2, Table 1).
The reaction tolerates electron-donating as well as elec-
tron-withdrawing substituents in the substrates. We have
also investigated the influence of the catalyst loading on
the yields. For the substrates 3 usually the best results
were obtained with 5–10 mol% of Pd(OAc)2 with up to
b Reaction conditions: Pd/C (10 mol%), LiOAc (4.0 equiv), n-
Bu4NOAc (3.0 equiv), MeCN–DMF–H2O (5:5:1), 140 °C, 4 h, MW.
c dppp = 1,3-bis(diphenylphosphino)propane as ligand.
d Combined yield; inseparable mixture of 8a and 9a (30%); formation
of 10 as byproduct (traces).
e Formation of 9c (6%) as byproduct.
© Georg Thieme Verlag Stuttgart · New York
Synlett 2012, 23, 2516–2520

2518
L. F Tietze et al.
LETTER
99% yield, but as shown for 3b and 3d even 2 and 1.5
mol%, respectively, gave reasonable yields.
alkyne 14 (2.00 equiv)
n-BuLi (2.00 equiv)
THF, –78 °C, addition of
aldehyde 11, overnight
OH
5
4
R
O
As already mentioned, the transformations of 3 as shown
for 3b can also be carried out using Pd/C (Table 1, entry
8).8 The best yields were obtained in the presence of
LiOAc (Table 2), but the use of n-Bu4NOAc or KOAc
also led to the product 7b though in lower yields. Howev-
er, using Li2CO3 or Cs2CO3 as a base a conversion did not
take place. We therefore assume that after the oxidative
addition and carbopalladation of 3 to give 5 an acetate-
bridged complex 6 is formed as transition state within the
C–H activation.9
Br
O
R
H
(yields over two steps)
Br
11a–d
5 M HCl, THF,
70 °C, 2–3 h
3a: R = H
3b: R = 5-MeO
3c: R = 5-F
23%
51%
34%
OMe
R
3d: R = 4,5-OCH2O 51%
Br
12a–d
Furthermore, the use of either Pd(PPh3)4 or PdCl2/Ph3P in
the presence of K2CO3 also led to alkene 7b but only with
moderate yields.
OH
O
As expected, the formation of the seven-membered-ring
compounds 8 from alkynes 4 occurred in lower yields as
compared to the domino carbopalladation/C–H-activation
reaction of 3 (Table 1); however, 8d could still be ob-
tained from 4d in a good yield of 72% (Table 1, entry 19).
R
Br
H
R
Br
O
alkyne 14 (2.00 equiv)
n-BuLi (2.00 equiv)
THF, –78 °C, 13,
overnight
13a–d
Here, however, 20 mol% of Pd(OAc)2 had to be used to
obtain reasonable results. The general lower yields in the
formation of 8 can be explained by the unfavorable inter-
mediate formation of an eight-membered palladacycle in
5. This might also be the reason for the formation of sig-
4a: R = H
4b: R = Me
4c: R = F
91%
96%
52%
O
4d: R = F3C 67%
14
nificant amounts of the carbopalladation product 9a, Scheme 3 Synthesis of propargylic alcohols 3a–d and 4a–d by
alkynylation of the aldehydes 11a–d and 13a–d with 14
which was difficult to separate from the alkene 8a and the
ketone 10. In the reaction of 4c the alkene 9c was also de-
tected as byproduct but could be separated chromato-
graphically.
The synthesis of the precursors 3a–d and 4a–d for the
domino reactions was achieved by an alkynylation of the
corresponding aldehydes 11a–d and 13a–d,11 respective-
ly, with the metalated alkyne 14 (Scheme 3). Due to their
instability, the aldehydes 11 were not isolated but formed
in situ by an acid-catalyzed hydrolysis of the correspond-
ing enol ethers 12a–d.12
The structure elucidation of the products was performed
using NMR spectroscopy and mass spectrometry. More-
over, for 7d, 8b, and 10, crystal structures were obtained
(Figure 1).10
Table 2 Domino Reaction of 3b to Give 7b Using Pd/C, PdCl2, and Pd(PPh3)4
Entry
Catalyst
Base
Solvent
Yield (%)a,b
1
2
3
4
5
6
7
8
9
Pd/C
LiOAc, n-Bu4NOAc
LiOAc
MeCN–DMF–H2Oc
75
Pd/C
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
62
Pd/C
n-Bu4NOAc
KOAc
62
Pd/C
55
Pd/C
K2CO3
n.c.d
n.c.d
decomp.
45
Pd/C
Li2CO3
Pd/C
Cs2CO3
Pd(PPh3)4
K2CO3
e
PdCl2
K2CO3
34
a Yield of isolated products.
b Reaction conditions: catalyst (10 mol%), base (4.0 equiv), solvent, 140 °C, 4 h, MW.
c In a 5:5:1 mixture.
d n.c. = no conversion.
e Ph3P (0.5 equiv) was added as ligand.
Synlett 2012, 23, 2516–2520
© Georg Thieme Verlag Stuttgart · New York

LETTER
Tetrasubstituted Alkenes Bearing 5- and 7-Membered Rings
2519
123.4 (C-5′′), 129.5 (C-3′′′, C-5′′′), 129.9 (C-4′′), 133.1 (C-3′), 133.7
(C-6′′), 137.1 (C-1′), 157.2 (C-2′′), 157.3 (C-1′′′), 158.6 (C-5′) ppm.
ESI-MS (MeOH): m/z (%) = 447.1 (20) [M + Na]+, 869.1 (100) [2M
+ Na]+. HRMS: m/z calcd for C23H19BrO3: 445.0393 [M + Na]+,
447.0378 [M + Na]+; found: 447.0379.
In summary, we have demonstrated that the domino
carbopalladation/C–H-activation reaction is a suitable and
highly efficient method for the synthesis of otherwise dif-
ficult to obtain tetrasubstituted alkenes 7a–d and 8a–d
bearing a dihydroindene- and a benzo[7]annulene motif,
respectively, in excellent to reasonable yields. The sub-
strates 3a–d and 4a–d for the domino reaction could eas-
ily be obtained in a few steps starting from readily
available building blocks.
General Procedure for the Palladium-Catalyzed Domino Reac-
tions: Synthesis of 7a
A solution of propargylic alcohol 3a (30.0 mg, 76.3 μmol, 1.00
equiv), Ph3P (20.0 mg, 76.3 μmol, 1.00 equiv), and K2CO3 (117 mg,
854 μmol, 11.2 equiv) in DMF (2.8 mL) was thoroughly degassed
before Pd(OAc)2 (3.80 mg, 15.0 μmol, 20 mol%) was added. The
reaction mixture was heated to 100 °C for 2 h under microwave ir-
radiation. After cooling to r.t. and quenching by addition of a sat. aq
NH4Cl solution (10 mL) the aqueous layer was extracted with
MTBE (100 mL). The combined organic extracts were dried over
MgSO4 and concentrated in vacuo. The crude product was purified
by flash column chromatography (SiO2, PE–MTBE = 5:1) to yield
7a as a yellow solid (18.1 mg, 76%).
General Procedure for the Palladium-Catalyzed Heck Reaction
with Homoallylic Alcohols: Synthesis of 13c
A stirred solution of 2-bromo-4-fluoro-iodobenzene (1.23 g, 4.07
mmol, 1.00 equiv), 3-butenol (700 μL, 8.15 mmol, 2.00 equiv),
NaHCO3 (860 mg, 10.2 mmol, 2.50 equiv), and Et3BnNCl (870 mg,
4.07 mmol, 1.00 equiv) in DMF (15 mL) was thoroughly degassed
with argon for 15 min followed by addition of Pd(OAc)2 (44.9 mg,
200 μmol, 5 mol%). The reaction mixture was heated to 40 °C for
26 h, and after cooling to r.t. and washing with a sat. aq NH4Cl so-
lution (100 mL) the aqueous layer was extracted with MTBE (3 ×
50 mL). The combined organic extracts were dried over Na2SO4 and
concentrated in vacuo. Flash column chromatography (SiO2, PE–
MTBE = 5:1) yielded 13c as a brown oil (520 mg, 52%).
1H NMR (600 MHz, CDCl3): δ = 2.01 (s, 1 H, OH), 2.99 (d,
J = 17.1 Hz, 1 H, 3-Ha), 3.30 (dd, J = 17.1, 6.2 Hz, 1 H, 3-Hb), 5.41
(d, J = 6.0 Hz, 1 H, 2-H), 6.99 (t, J = 7.7 Hz, 1 H, 6-H), 7.15 (ddd,
J = 7.6, 5.9, 1.2 Hz, 1 H, 2′-H), 7.19 (td, J = 7.4, 0.9 Hz, 1 H, 5-H),
7.27–7.20 (m, 3 H, 7′-H, 5′-H, 4-H), 7.31–7.27 (m, 2 H, 4′-H, 6′-H),
7.36 (ddd, J = 8.2, 7.3, 1.6 Hz, 1 H, 3′-H), 7.68 (d, J = 8.1 Hz, 1 H,
7-H), 7.80 (dd, J = 7.7, 1.4 Hz, 1 H, 1′-H), 8.10 (dd, J = 7.8, 1.5 Hz,
1 H, 8′-H) ppm. 13C NMR (125 MHz, CDCl3): δ = 40.7 (C-3), 72.6
(C-2), 116.4 (C-5′), 117.0 (C-4′), 122.4 (C-2′), 123.6 (C-7′), 124.1
(C-7), 124.6 (C-1a′), 125.6 (C-4), 126.1 (C-8′), 126.3 (C-6), 126.4
(C-8a′), 126.5 (C-9′), 128.1 (C-6′), 128.6 (C-5), 129.1 (C-1′), 129.3
(C-3′), 137.9 (C-7a), 140.3 (C-1), 144.5 (C-3a), 153.3 (C-5a′), 154.2
(C-4a′) ppm. MS (EI, 70 eV): m/z (%) = 312.1 (18) [M]+, 295.1 (18)
[M – OH]+, 181.1 (100) [M – C9H8O]+. HRMS (EI): m/z calcd for
C22H16O2: 312.1150 [M]+; found: 312.1158.
1H NMR (300 MHz, CDCl3): δ = 1.94 (quin, J = 7.8 Hz, 2 H, 3-H2),
2.49 (td, J = 7.2, 1.5 Hz, 2 H, 2-H2), 2.74 (t, J = 7.4 Hz, 2 H, 4-H2),
6.96 (td, J = 8.3, 2.8 Hz, 1 H, 5′-H), 7.17 (dd, J = 8.5, 6.0 Hz, 1 H,
6′-H), 7.28 (dd, J = 8.3, 2.8 Hz, 1 H, 3′-H), 9.78 (t, J = 1.5 Hz, 1 H,
CHO) ppm. 13C NMR (125 MHz, CDCl3): δ = 22.4 (C-3), 34.4 (C-
4), 43.0 (C-2), 114.6 (C-5′), 120.0 (C-3′), 124.1 (C-2′), 130.9 (C-6′),
136.4 (C-1′), 161.8 (C-4′), 201.7 (C-1) ppm. ESI-MS (MeOH): m/z
(%) = 243.0 (78) [M – H]–. HRMS: m/z calcd for C10H10BrFO:
242.9826 [M – H]–; found: 242.9826.
Acknowledgment
General Procedure for the Hydrolysis of Enol Ethers and Cou-
pling with Alkynes: Synthesis of 3b
We thank the Deutsche Forschungsgemeinschaft, the Center for
Material Crystallography, and the Fonds der Chemischen Industrie
for generous support.
A solution of enol ether 12b (500 mg, 2.06 mmol, 1.00 equiv) in
THF (1.8 mL) was heated to 70 °C and treated with 5 M HCl (0.43
mL) for 3 h. The reaction was finished by addition of ice and a sat.
aq NaHCO3 solution (10 mL) immediately upon appearance of by-
product indicated by TLC. The aqueous layer was extracted with
EtOAc (100 mL). The combined organic extracts were then dried
over Na2SO4 and concentrated in vacuo. The crude aldehyde was
subsequently used for the next step.
Supporting Information for this article is available online at
http://www.thieme-connect.com/ejournals/toc/synlett.SupInpfioomgrattr
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nSupprigI
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tnnofrmat
A solution of alkyne 14 (783 mg, 4.11 mmol, 2.00 equiv) in THF
(4.0 mL) was lithiated by dropwise addition of n-BuLi (1.62 mL,
2.5 M in n-hexane, 2.00 equiv) at –78 °C. The reaction mixture was
stirred 15 min at –78 °C, warmed to r.t. over 30 min and was then
slowly added to a solution of the crude aldehyde in THF (8.0 mL)
at –78 °C. The reaction solution was stirred over night at –78 °C,
warmed to r.t. over 1 h and finished by addition of a sat. aq NH4Cl
solution (40 mL). The aqueous layer was extracted with MTBE (3
× 100 mL), the combined organic extracts were dried over Na2SO4
and concentrated in vacuo. Flash column chromatography (SiO2,
PE–MTBE = 5:1) yielded 3b [445 mg, 51% (over 2 steps)] as a yel-
low oil.
1H NMR (600 MHz, CDCl3): δ = 1.83 (s, 1 H, OH), 3.05 (qd,
J = 13.6, 6.8 Hz, 2 H, 1-H2), 3.71 (s, 3 H, OCH3), 4.75 (t, J = 6.8 Hz,
1 H, 2-H), 6.65 (dd, J = 8.8, 3.1 Hz, 1 H, 4′-H), 6.88 (d, J = 3.0 Hz,
1 H, 6′-H), 6.93 (d, J = 7.9 Hz, 1 H, 3′′-H), 6.96–6.94 (m, 2 H, 2′′′-
H, 6′′′-H), 7.07 (q, J = 7.4 Hz, 2 H, 5′′-H, 4′′′-H), 7.27 (td, J = 8.3,
1.7 Hz, 1 H, 4′′-H), 7.33–7.29 (m, 2 H, 3′′′-H, 5′′′-H), 7.38 (d,
J = 8.8 Hz, 1 H, 3′-H), 7.43 (dd, J = 7.7, 1.5 Hz, 1 H, 6′′-H) ppm.
13C NMR (125 MHz, CDCl3): δ = 44.1 (C-1), 55.4 (CH3), 62.3 (C-
2), 81.5 (C-4), 94.4 (C-3), 114.3 (C-4′), 114.9 (C-2′), 115.3 (C-1′′),
117.6 (C-6′), 118.2 (C-2′′′, C-6′′′), 119.4 (C-3′′), 122.9 (C-4′′′),
References and Notes
(1) (a) Tietze, L. F.; Ila, H.; Bell, H. P. Chem Rev. 2004, 104,
3453. (b) De Meijere, A.; Diederich, F. Metal-Catalyzed
Cross-Coupling Reactions; Wiley-VCH: Weinheim, 2004.
(c) Torborg, C.; Beller, M. Adv. Synth. Catal. 2009, 351,
3027. (d) Wu, X.-F.; Anbarasan, P.; Neumann, H.; Beller,
M. Angew. Chem. Int. Ed. 2010, 49, 9047. (e) Kamba, N.;
Iwasata, T.; Terao, N. Chem. Soc. Rev. 2011, 40, 4937.
(f) Jana, R.; Pathak, T. P.; Sigman, M. S. Chem. Rev. 2011,
111, 1417.
(2) For recent reviews on C–H activation, see: (a) Bellina, F.;
Rossi, R. Chem. Rev. 2010, 110, 1082. (b) Lyons, T. W.;
Sanford, M. S. Chem. Rev. 2010, 110, 1147. (c) Yeung, C.
S.; Dong, V. M. Chem. Rev. 2011, 111, 1215.
(d) Ackermann, L. Chem. Rev. 2011, 111, 1315.
(e) Neufeldt, S. R.; Sanford, M. S. Acc. Chem. Res. 2012, 45,
936.
(3) For recent reviews on palladium-catalyzed domino
reactions, see: (a) Tietze, L. F. Chem. Rev. 1996, 96, 115.
(b) Tietze, L. F.; Brasche, G.; Gericke, K. M. Domino
Reactions in Organic Synthesis; Wiley-VCH: Weinheim,
2006. (c) Tietze, L. F.; Levy, L. The Mizoroki–Heck
© Georg Thieme Verlag Stuttgart · New York
Synlett 2012, 23, 2516–2520

2520
L. F Tietze et al.
LETTER
Reaction in Domino Processes, In The Mizoroki–Heck
Reaction; Oestreich, M., Ed.; Wiley-VCH: Weinheim, 2008,
281–344. (d) Tietze, L. F.; Düfert, A. Pure Appl. Chem.
2010, 82, 1375. (e) Tietze, L. F.; Düfert, A. Domino
Reactions Involving Catalytic Enantioselective Conjugate
Additions, In Catalytic Asymmetric Conjugate Reactions;
Cordova, A., Ed.; Wiley-VCH: Weinheim, 2010, 321–350.
(f) Vlaar, T.; Ruijter, E.; Orru, R. V. A. Adv. Synth. Catal.
2011, 353, 809.
M.; Kratzert, D.; Stalke, D.; Werz, D. B. Org. Lett. 2012, 14,
346.
(6) (a) Tietze, L. F.; Düfert, A.; Lotz, F.; Sölter, L.; Oum, K.;
Lenzer, T.; Beck, T.; Herbst-Irmer, R. J. Am. Chem. Soc.
2009, 131, 17879. (b) Tietze, L. F.; Düfert, M. A.;
Hungerland, T.; Oum, K.; Lenzer, T. Chem.–Eur. J. 2011,
17, 8452. (c) Tietze, L. F.; Hungerland, T.; Düfert, A.;
Objartel, I.; Stalke, D. Chem.–Eur. J. 2012, 18, 3286.
(7) (a) Feringa, B. L.; Qu, D.-H. Angew. Chem. Int. Ed. 2010,
49, 1107. (b) Feringa, B. L.; Browne, W. R. Molecular
Switches 2011. (c) Ruangsupapichat, N.; Pollard, M. M.;
Harutyunyan, S. R.; Feringa, B. L. Nat. Chem. 2011, 3, 53.
(8) For a review on C–C coupling reactions employing
heterogeneous palladium catalysts, see: Yin, L.; Liebscher,
J. Chem. Rev. 2007, 107, 133.
(4) (a) Saget, T.; Cramer, N. Angew. Chem. Int. Ed. 2010, 49,
8962. (b) Kim, B.-S.; Lee, S.-Y.; Youn, S.-W. Chem.–Asian
J. 2011, 6, 1952. (c) Luo, Y.; Pan, X.-L.; Wu, J. Org. Lett.
2011, 13, 1150. (d) Seashore-Ludlow, B.; Danielsson, J.;
Somfai, P. Adv. Synth. Catal. 2012, 354, 205. (e) Mahendar,
L.; Krishna, J.; Reddy, A. G. K.; Ramulu, B. V.;
Satyanarayana, G. Org. Lett. 2012, 14, 628. (f) Lasikova, A.;
Dohanosova, J.; Hlavinova, L.; Toffano, M.; Vo-Thann, G.;
Lozisek, J.; Gracza, T. Tetrahedron: Asymmetry 2012, 23,
818. (g) Giboulot, S.; Liron, F.; Prestat, G.; Wahl, B.;
Sauthier, M.; Castanet, Y.; Montreux, A.; Poli, G. Chem.
Commun. 2012, 48, 5889.
(9) For recent examples about the concerted metalation–
deprotonation pathway, see: (a) Rousseaux, S.; Gorelsky, S.
I.; Chung, B. K. W.; Fagnou, K. J. Am. Chem. Soc. 2010,
132, 10692. (b) Lapointe, D.; Fagnou, K. Chem. Lett. 2010,
39, 1119. (c) Gorelsky, S. I.; Lapointe, D.; Fagnou, K.
J. Org. Chem. 2012, 77, 658.
(5) For recent examples of palladium-catalyzed domino
reactions including C–H activation, see: (a) Tietze, L. F.;
Lotz, F. Eur. J. Org. Chem. 2006, 4676. (b) Candito, D. A.;
Lautens, M. Angew. Chem. Int. Ed. 2009, 48, 6713.
(c) Wang, G.-W.; Yuan, T.-T.; Li, D.-D. Angew. Chem. Int.
Ed. 2011, 50, 1380. (d) Chai, D. I.; Thansandote, P.;
Lautens, M. Chem.–Eur. J. 2011, 17, 8175. (e) Lu, Z.; Cui,
Y.; Jia, Y. Synthesis 2011, 2595. (f) Liu, R.; Zhang, J. Adv.
Synth. Catal. 2011, 353, 36. (g) Leibeling, M.; Pawliczek,
(10) CCDC-881349 (7d), CCDC-881350 (8b), and CCDC-
881351 (10) contain the supplementary crystallographic data
for this paper. These data can be obtained free of charge via
the internet from The Cambridge Crystallographic Data
Centre (www.ccdc.cam.ac.uk/data_request/cif).
(11) For preparation of aldehydes 13, see: Satyanarayana, G.;
Maier, M. E. Org. Lett. 2008, 10, 2361.
(12) For preparation of enol ethers 12, see: Wünsch, B. Arch.
Pharm. (Weinheim, Ger.) 1990, 323, 493.
Synlett 2012, 23, 2516–2520
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