Rh-catalyzed sequential hydroarylation/hydrovinylation-heterocyclization of β-(2-aminophenyl)-α,β-ynones with organoboron derivatives: A new approach to functionalized quinolines

Article abstract of DOI:10.1055/s-2006-956462

4-Aryl and 4-vinyl quinolines were prepared via a sequential procedure involving regioselective Rh(acac)(C₂H₂)/dppf-catalyzed hydroarylation/hydrovinylation of β-(2-aminophenyl)-α,β-ynones with arylboronic acids or potassium aryl and

Full text of DOI:10.1055/s-2006-956462

3218
LETTER
Rh-Catalyzed Sequential Hydroarylation/Hydrovinylation–Heterocyclization
of b-(2-Aminophenyl)-a,b-ynones with Organoboron Derivatives:
A New Approach to Functionalized Quinolines
New
A
pproac
h
to
i
Functio
o
nalized Quin
r
olines gio Abbiati,a Antonio Arcadi,b Fabio Marinelli,*b Elisabetta Rossi,a Mirella Verdecchiab
a
Ist. di Chimica Organica ‘Alessandro Marchesini’, Università di Milano, via Venezian 21, 20133 Milano, Italy
b
Dipartimento di Chimica, Ingegneria Chimica e Materiali, Università degli Studi dell’Aquila, via Vetoio – Coppito due, 67010 L’Aquila,
Italy
Fax +39(0862)433753; E-mail: fmarinel@univaq.it
Received 27 July 2006
catalyzed Suzuki–Miyaura cross-coupling reaction15
could represent a general entry into 4-aryl and 4-vi-
nylquinolines. Indeed, the reaction of 1a with NaI in ace-
tic acid gave the 4-iodoquinoline 3a (Scheme 1, a);
Abstract: 4-Aryl and 4-vinyl quinolines were prepared via a se-
quential procedure involving regioselective Rh(acac)(C2H2)/dppf-
catalyzed hydroarylation/hydrovinylation of b-(2-aminophenyl)-
a,b-ynones with arylboronic acids or potassium aryl and vinyl trif-
luoroborates, followed by nucleophilic attack of the amino group subsequent cross-coupling with phenylboronic acid at
room temperature16 resulted in the formation of 4aa in
onto the carbonyl.
good yield (Scheme 1, b).
Key words: quinolines, hydroarylation, rhodium, alkynones, aryl-
boronic acids
I
O
Ar
NaI
The quinoline scaffold is found in a variety of biologically
active compounds, and quinoline-containing drugs are
widely used in treatment of Plasmodium falciparum ma-
laria.1 Pharmacological studies on new quinoline deriva-
tives appears frequently in current literature dealing with
HIV-1 replication inhibition,2 antimicrobial activity,3 an-
tihelmintic properties,4 antimalarial activity5 and inhibi-
tion of VEGF receptors;6 in particular, 4-arylquinolines
have been evaluated for their activity against West Nile
Virus,7 and have found application as ligands of peripher-
al benzodiazepine receptor.8 Moreover, conjugated poly-
mers incorporating a 2,4-diarylquinoline subunit are
useful chemosensors for fluoride ion,9 and 1,8-di(4-
quinolyl)naphtalene derivatives are selective fluorescent
sensors for metal ions in aqueous solution.10 Consequent-
ly, there is a great current synthetic interest in assembling
quinoline ring system from acyclic precursors.11
a)
AcOH, 60 °C
70%
N
Ar
NH2
1a
3a
Ph
N
K3PO4
Pd(OAc)2, TBAB
b)
3a
PhB(OH)2
+
EtOH, r.t.
65%
Ar
4a
PhB(OH)2
K3PO4
Pd(OAc)2,
TBAB
NaI, TsOH
c)
1a
3a
EtOH, 80 °C
EtOH, 80 °C
47% overall
Ar = 2,4-dimethylphenyl
As a part of our ongoing efforts12 to discover new routes
to heterocycles starting from functionalized alkynes bear-
ing proximate nucleophilic centers, we focused on b-(2-
aminophenyl)-a,b-ynones 1 as useful building blocks for
the synthesis of quinolines through sequential processes
involving conjugate-addition-type13 or cycloaddition14
reactions followed by cyclization through nucleophilic
attack of the amino group onto the carbonyl (cycloamina-
tion). In this context, we showed that the reaction of 1 with
NaI in acetic acid affords 4-iodoquinolines 3. The poten-
tial of 3 as precursors for increasing molecular complexity
via palladium-catalyzed reactions has been considered;13
therefore, the combined addition of NaI to 1/palladium-
Scheme 1
Nevertheless, the one-pot synthesis of 4-aryl and 4-vi-
nylquinolines 4 starting from 1 represents a more interest-
ing challenge.17 In order to achieve this goal, we
investigated the development of a one-pot/two-step syn-
thetic protocol. NaI (2 equiv) was added to 1a in ethanol
at 80 °C in the presence of 1 equivalent of TsOH; after the
complete conversion of 1a to 3a (3 h), PhB(OH)2 (1.3
equiv), K3PO4 (3 equiv), Pd(OAc)2 (0.03 equiv) and
TBAB (0.08 equiv) were added to the reaction mixture
allowing the formation of 4a in 47% overall yield after
6 hours at 80 °C (Scheme 1, c). Probably there is room for
optimization; however, the main drawback of this proce-
dure is constituted by the acidic conditions required in the
first step,18 while the Suzuki–Miyaura cross-coupling
SYNLETT 2006, No. 19, pp 3218–3224
0
1
.1
2
.2
0
0
6
Advanced online publication: 23.11.2006
DOI: 10.1055/s-2006-956462; Art ID: G21106ST
© Georg Thieme Verlag Stuttgart · New York

LETTER
New Approach to Functionalized Quinolines
3219
requires the presence of a base.15 This hampers the possi- tained under different reaction conditions are reported in
bility of a multicomponent process. Considering that se- Table 1. By using Rh(acac)(C2H2)/dppf as catalyst, 4a
quential processes that allows the direct conversion of was isolated in good to high yield with almost complete
starting materials into products are more environmentally regioselectivity (NMR and GC-MS analysis showed that
benign than traditional multistep procedures,17 we turned its regioisomeric purity is higher than 96%).
to a completely different methodology.
O
PhB(OH)3
Rh(acac)(C2H4),
phosphine
The Pd-catalyzed hydroarylayion/hydrovinylation reac-
tion of disubstituted alkynes with aryl halides or vinyl tri-
flates represents a useful tool in heterocyclic synthesis,
since the syn-stereochemistry of the addition allows cy-
clization reactions to occur when the two substituents on
the triple bond posses suitable nucleophilic/electrophilic
centers.19 The palladium-catalyzed sequential hydroaryla-
tion of a,b-ynones 1 with aryl iodides/cycloamination has
been previously investigated.20 Disappointingly, the reac-
tion proceeded with low regioselectivity, affording a mix-
ture of 4-aryl- and 3-arylquinolines.
4a
solvent, 80–100 °C
NH2
1a
Scheme 3
According to a reported procedure,21a an excess of 2a is
necessary to obtain the best result (entry 1); however, the
quantity of boronic acid could be reduced with still-ac-
ceptable results (entry 3–5). The use of a 2:1 Rh/dppf ratio
seems preferable to a 1:1 ratio (entries 1, 2). The replace-
ment of dioxane with a greener solvent such as aqueous
ethanol is also possible, although in our hands the former
gave better yields (entries 7–9). The dppp was slightly less
effective than dppf in dioxane–water (compare entries 1
and 6), and in ethanol the two ligands gave similar yields.
On the other hand, the rhodium-catalyzed hydroarylation
of alkynes with arylboronic acids has recently received
much attention.21 The reaction shows the same stere-
ochemical outcome of the above-mentioned palladium-
catalyzed process, but electronic factors seems to play a
more important role in determining the regioselectivity.21e
In particular, methyl trimethylsilylpropynoate was selec-
tively arylated at the b-position with respect to the carbo-
nyl, despite the presence of a bulky SiMe3 group on that
position.21a
We next extended the methodology to different a,b-
ynones/boron derivatives.23,24 Our results are summarized
in Table 2. Quinolines 4 were isolated in moderate to high
yields; reaction conditions are not fully optimized, and
five equivalents of arylboronic acid 2 were generally
used, although the use of a lower excess is also possible
(entries 3, 4). The process tolerates electron-withdrawing
as well as electron-donating substituents on the a,b-ynone
and arylboronic acid moieties. Substituents on the benzen-
ic ring of quinoline can also be introduced (entry 12), and
heteroarylboronic acids can be used as well (entries 8–
11). Moreover, the use of aryl- and vinyltrifluoroborate
salts 5 is allowed (entries 5, 6, 14); the reactions of 1 with
5 were not optimized, and were carried out in the same
manner as arylboronic acids.23 Organotrifluoroborate salts
have emerged as promising new compounds that can
overcome some limitations of other organoboron deriva-
tives;25 however, to the best of our knowledge, these salts
have not been used in the rhodium-catalyzed hydroaryla-
tion of alkynes. Finally, starting from the vinyl-substitut-
ed a,b-ynone 1g, 2-vinyl-4-arylquinolines or 2,4-
divinylquinolines can be obtained (entries 13, 14). It is
also worth nothing that addition of the organorhodium in-
termediates onto the ketone moiety of 1 was never ob-
served under the present reaction conditions. This process
(that is a useful tool for the conversion of aldehydes to
alcohols26a and ketones26b) has been reported starting from
cyclobutanones and ArB(OH)2 in the presence of
Rh(acac)(C2H4)2/t-Bu3P and Cs2CO3 in dioxane at
100 °C27a or, intramolecularly, starting from 5-yn-1-ones
at room temperature.27b
Then, we envisaged that a,b-ynones 1 could be regiose-
lectively converted into 4 in a sequential manner employ-
ing this methodology (Scheme 2).
O
R
R1
R2
O
R2
Rh(I)
+ RB(OH)2
R1
NH2
NH2
R3
R3
1
2
– H2O
R
N
R2
R1
R3
4
Scheme 2
Although several examples of rhodium-catalyzed tandem
addition–cyclization reactions have been described,22 to
the best of our knowledge, the sequential rhodium-cata-
lyzed addition of an organoboron species to alkynones/cy-
cloamination reaction has not been yet studied. Herein, we
report the results of our investigation.
The reaction of phenylboronic acid with 1a was chosen as
a model system (Scheme 3), and some of the results ob-
Synlett 2006, No. 19, 3218–3224 © Thieme Stuttgart · New York

3220
G. Abbiati et al.
LETTER
Table 1 Rhodium-Catalyzed Sequential Hydroarylation–Cyclization of 1a with Phenylboronic Acid 2aa
Entry
Solvent
Temp (°C)
100
Time (h)
Equiv of 2a
Yield of 4a (%)b
1
2
3
4
5
6
7
8
9
10:1 dioxane–H2O
10:1 dioxane–H2O
10:1 dioxane–H2O
10:1 dioxane–H2O
10:1 dioxane–H2O
10:1 dioxane–H2O
95:% EtOH–H2O
95:% EtOH–H2O
95:% EtOH–H2O
4
5
5
2
3
4
5
5
5
5
80
100
6
65c
55
100
5.5
5.5
5.5
4
100
67
100
70
100
75d
67
80
4
100
4
66
100
4
67d
a Reactions were carried out on a 0.4 mmol scale in 1 mL of solvent under nitrogen atmosphere using the following molar ratios:
1a:Rh(acac)(C2H2):dppf = 1:0.033:0.066.
b Yields are based on 1a, refer to single runs and are given for isolated product.
c Using 0.033 equiv of dppf.
d Using dppp as ligand.
Table 2 Synthesis of 4-Aryl/Vinylquinolines 4a,b
Entry
1
a,b-Ynone 1
Organoboron
compound 2
Reaction time Quinoline 4
(h)
Yield (%)
55
F
F
5
O
B(OH)2
NH2
2b
1a
N
4b
2
1a
5
70
B(OH)2
2c
N
4c
3
4
2a
2a
5
82
O
Ph
N
OMe
NH2
OMe
1b
4d
4d
1b
6.5
75c
Synlett 2006, No. 19, 3218–3224 © Thieme Stuttgart · New York

LETTER
New Approach to Functionalized Quinolines
3221
Table 2 Synthesis of 4-Aryl/Vinylquinolines 4a,b (continued)
Entry
4
a,b-Ynone 1
Organoboron
compound 2
Reaction time Quinoline 4
(h)
Yield (%)
1b
2c
8
60
N
OMe
4e
5
6
1b
1b
8
6
4e
50
61
BF3–K+
5c
Ph
Ph
BF3–K+
5d
N
OMe
4f
7
8
2a
4.5
82
68
O
Ph
N
COMe
NH2
COMe
1c
1c
4g
16
B(OH)2
S
S
2e
N
COMe
4h
9
2a
2a
7
5
50
59
Ph
N
O
NH2
4i
1d
10
O
Ph
N
CF3
NH2
CF3
1e
4j
Synlett 2006, No. 19, 3218–3224 © Thieme Stuttgart · New York

3222
G. Abbiati et al.
LETTER
Table 2 Synthesis of 4-Aryl/Vinylquinolines 4a,b (continued)
Entry
11
a,b-Ynone 1
Organoboron
compound 2
Reaction time Quinoline 4
(h)
Yield (%)
80
1e
5
B(OH)2
O
O
2f
CF3
N
4k
12
13
2a
20
60d
Ph
N
O
OMe
F
OMe
F
F
NH2
F
4l
1f
7
75
COMe
O
COMe
tBu
B(OH)2
NH2
2g
5d
N
1g
1g
tBu
4m
14
7
60
Ph
N
tBu
4n
a Reactions were carried out at 100 °C on a 0.4 mmol scale in 1 mL of dioxane and 0.1 mL of H2O, under N2 atmosphere, using the following
molar ratio: 1:2:Rh(acac)(C2H4)2:dppf = 1:5:0.033:0.066 or 1:5:Rh(acac)(C2H4)2:dppf = 1:5:0.033:0.066.
b Yields refer to single runs and are given for pure isolated product.
c Using 3 equiv of 2a.
d Using 0.06 equiv of Rh(acac)(C2H4)2 and 0.12 equiv of dppf.
In conclusion, we have developed an efficient and exper-
imentally simple procedure for the conversion of b-(2-
aminophenyl)-a,b-ynones 1 into 4-aryl and 4-vinylquino-
lines 4 through an unprecedented sequential process in-
References and Notes
(1) Bray, P. G.; Ward, S. A.; O’Neill, P. M. Curr. Top.
Microbiol. 2005, 295, 3.
(2) (a) Zouhiri, F.; Danet, M.; Bérnard, C.; Normand-Bayle, M.;
Mouscadet, J. F.; Leh, H.; Thomas, C. M.; Mbemba, G.;
d’Angelo, J.; Desmaële, D. Tetrahedron Lett. 2005, 46,
2201. (b) Normand-Bayle, M.; Bérnard, C.; Zouhiri, F.;
Mouscadet, J. F.; Leh, H.; Thomas, C. M.; Mbemba, G.;
Desmaële, D.; d’Angelo, J. Bioorg. Med. Chem. Lett. 2005,
15, 4019.
(3) Narender, P.; Srinivas, U.; Ravinder, M.; Anada Rao, B.;
Ramesh, C.; Harakishore, K.; Gangadasu, B.; Murthy, U. S.
N.; Jayathirtha Rao, V. Bioorg. Med. Chem. 2006, 14, 4600.
(4) Rossiter, S.; Péron, J. M.; Whitfield, P. J.; Jones, K. Bioorg.
Med. Chem. Lett. 2005, 15, 4806.
volving
a regioselective rhodium-catalyzed hydro-
arylation–cycloamination reaction.
Acknowledgment
Work supported by the Ministero dell’Università e della Ricerca
Scientifica e Tecnologica, Rome, and by the University of L’Aquila
(Italy).
(5) Joshi, A. A.; Viswanathan, C. L. Bioorg. Med. Chem. Lett.
2006, 16, 2613.
(6) Kiselyov, A. S.; Piatnitsky, E.; Semenova, M.; Semenov, V.
V. Bioorg. Med. Chem. Lett. 2006, 16, 602.
Synlett 2006, No. 19, 3218–3224 © Thieme Stuttgart · New York

LETTER
New Approach to Functionalized Quinolines
3223
(7) Goodell, J. R.; Puig-Basagoiti, F.; Forshey, B. M.; Shi, P. Y.;
Ferguson, D. M. J. Med. Chem. 2006, 49, 2127.
(8) Cappelli, A.; Pericot Mohr, G.; Gallelli, A.; Giuliani, G.;
Anzini, M.; Vomero, S.; Fresta, M.; Porcu, P.; Maciocco, E.;
Concas, A.; Biggio, G.; Donati, A. J. Med. Chem. 2003, 46,
3568.
(9) Tong, H.; Wang, L.; Jing, X.; Wang, F. Macromolecules
2003, 36, 2584.
(10) Tumambac, G. E.; Rosencrance, C. M.; Wolf, C.
Tetrahedron 2004, 60, 11293.
(11) Selected references: (a) Anguille, S.; Brunet, J. J.; Chu, N.
C.; Diallo, O.; Pages, C.; Vincendeau, S. Organometallics
2006, 25, 2943. (b) Ichikawa, J.; Sakoda, K.; Moriyama, H.;
Wada, Y. Synthesis 2006, 1590. (c) Savitha, G.; Perumal, P.
T. Tetrahedron Lett. 2006, 47, 3589. (d) Kouznestov, V. V.;
Bohorquez, A. R. R.; Saavedra, L. A.; Medina, R. F. Mol.
Diversity 2006, 10, 29. (e) Janza, B.; Studer, A. Org. Lett.
2006, 8, 1875. (f) Jia, C. S.; Wang, G. W. Lett. Org. Chem.
2006, 3, 289. (g) Lin, X. F.; Cui, S. L.; Wang, Y. G.
Tetrahedron Lett. 2006, 47, 3127. (h) Sivaprasad, G.;
Rajesh, R.; Perumal, P. T. Tetrahedron Lett. 2006, 47, 1783.
(i) Duggineni, S.; Sawant, D.; Saha, B.; Kundu, B.
Tetrahedron 2006, 62, 3228. (j) Chaudhuri, M. K.; Hussain,
S. J. Chem. Sci. 2006, 118, 199.
N2, closed and the mixture was stirred at 100 °C for 4.5 h.
After cooling, the mixture was purified by column
chromatography (silica gel; hexane–EtOAc, 97:3) to give 4g
(0.106 g, 82% yield); mp 116–117 °C. IR (KBr): 1690,
1610, 1600 cm–1. 1H NMR (CDCl3): d = 8.29 (d, J = 8.5 Hz,
2 H), 8.26–8.22 (m, 1 H), 8.09 (d, J = 8.5 Hz, 2 H), 7.91 (d,
J = 8.4 Hz, 2 H), 7.83 (s, 1 H, C3–H), 7.78–7.70 (m, 1 H),
7.54–7.45 (m, 6 H), 2.65 (s, 3 H). 13C NMR (CDCl3):
d = 197.8, 155.4, 149.5, 148.8, 143.8, 138.2, 137.4, 130.2,
129.8, 129.5, 128.8, 128.6, 128.5, 127.7, 126.9, 126.0,
125.7, 119.2, 26.8. MS (EI): m/z (%) = 323 (100) [M+], 309
(8), 281 (20).
(24) Characterization of other quinoline derivatives.
Compound 4a: oil. IR (neat): 1610, 1590, 1550 cm–1. 1H
NMR (CDCl3): d = 8.22 (d, J = 8.3 Hz, 1 H), 7.95 (d, J = 7.9
Hz, 1 H), 7.76–7.68 (m, 1 H), 7.55–7.44 (m, 8 H), 7.14 (s, 1
H), 7.17–7.10 (m, 1 H), 2.45 (s, 3 H), 2.38 (s, 3 H). 13C NMR
(CDCl3): d = 159.8, 148.4, 148.3, 138.3, 138.2, 137.8, 135.9,
131.7, 130.0, 129.8, 129.6, 129.4, 128.6, 128.3, 126.7,
126.3, 125.6, 125.1, 122.6, 21.2, 20.4. MS (EI): m/z
(%) = 309 (100) [M+].
Compound 4b: oil. IR (neat): 1610, 1590, 1550 cm–1. 1H
NMR (CDCl3): d = 8.22 (d, J = 8.4 Hz, 1 H), 7.89 (d, J = 8.3
Hz, 1 H), 7.76–7.68 (m, 1 H), 7.54–7.42 (m, 5 H), 7.24–7.09
(m, 3 H), 7.13 (s, 1 H), 2.44 (s, 3 H), 2.37 (s, 3 H). 13C NMR
(CDCl3): d = 162.9 (d, J = 248.0 Hz, C–F), 159.9, 148.5,
147.2, 138.4, 137.7, 135.9, 134.2 (d, J = 3.2 Hz), 131.7,
131.4, 131.2, 130.1, 129.8, 129.5, 126.8, 126.5, 125.3,
122.7, 115.7 (d, J = 21.5 Hz), 21.2, 20.4. MS (EI): m/z
(%) = 327 (100) [M+].
(12) Arcadi, A.; Marinelli, F.; Rossi, L.; Verdecchia, M.
Synthesis 2006, 2019.
(13) Arcadi, A.; Marinelli, F.; Rossi, E. Tetrahedron 1999, 55,
13233.
(14) Abbiati, G.; Arcadi, A.; Marinelli, F.; Rossi, E. Eur. J. Org.
Chem. 2003, 1423.
(15) Suzuki, A. In Handbook of Organopalladium Chemistry for
Organic Synthesis, Vol. 1; Negishi, E., Ed.; Wiley: New
York, 2002, 249–262.
(16) Deng, Y.; Gong, L.; Mi, A.; Liu, H.; Jiang, Y. Synthesis
2003, 337.
(17) Clark, J.; Macquarrie, D. In Handbook of Green Chemistry
and Technology; Blackwell Science Ltd.: Oxford, 2002.
(18) Taniguchi, M.; Kobayashi, S.; Nakagawa, M.; Hino, T.;
Kishi, Y. Tetrahedron Lett. 1986, 27, 4763.
(19) (a) Arcadi, A.; Cacchi, S.; Fabrizi, G.; Marinelli, F.;
Verdecchia, M. Synlett 2006, 909. (b) Cacchi, S.; Fabrizi,
G. In Handbook of Organopalladium Chemistry for Organic
Synthesis, Vol. 1; Negishi, E., Ed.; Wiley: New York, 2002,
1335–1359.
(20) Cacchi, S.; Fabrizi, G.; Marinelli, F. Synlett 1999, 401.
(21) (a) Hayashi, T.; Inoue, K.; Taniguchi, N.; Ogasawara, M. J.
Am. Chem. Soc. 2001, 123, 9918. (b) Lautens, M.; Yoshida,
M. Org. Chem. 2002, 4, 123. (c) Lautens, M.; Yoshida, M.
J. Org. Chem. 2003, 68, 762. (d) Genin, E.; Michelet, V.;
Genêt, J. P. Tetrahedron Lett. 2004, 45, 4157. (e)Genin,E.;
Michelet, V.; Genêt, J. P. J. Organomet. Chem. 2004, 689,
3820.
(22) (a) Miura, T.; Sasaky, T.; Nakazawa, H.; Murakami, M. J.
Am. Chem. Soc. 2005, 127, 1390. (b) Miura, T.; Shimada,
M.; Murakami, M. Synlett 2005, 667. (c) Miura, T.;
Murakami, M. Org. Lett. 2005, 7, 3340. (d) Shitani, R.;
Okamoto, K.; Hayashi, T. Chem. Lett. 2005, 34, 1294.
(e) Matsuda, T.; Makino, M.; Murakami, M. Chem. Lett.
2005, 34, 1416. (f) Miura, T.; Shimada, M.; Murakami, M.
J. Am. Chem. Soc. 2005, 127, 1094. (g) Shintani, R.;
Okamoto, K.; Otomaru, Y.; Ueyama, K.; Hayashi, T. J. Am.
Chem. Soc. 2005, 127, 54.
Compound 4c: oil. IR (neat): 1600, 1590, 1550 cm–1.1H
NMR (CDCl3): d = 8.24 (d, J = 8.3 Hz, 1 H), 7.98 (d, J = 8.4
Hz, 1 H), 7.74–7.66 (m, 1 H), 7.48–7.42 (m, 5 H), 7.30 (d,
J = 7.9 Hz, 2 H), 7.13 (s, 1 H), 7.17–7.09 (s, 1 H), 2.45 (s, 3
H), 2.43 (s, 3 H), 2.37 (s, 3 H). 13C NMR (CDCl3): d = 159.8,
148.4, 148.3, 138.2, 137.8, 135.8, 135.2, 131.6, 129.9,
129.8, 129.5, 129.3, 128.7, 126.7, 126.2, 125.6, 125.3,
122.6, 21.3, 21.2, 20.4. MS (EI): m/z (%) = 323 (100) [M+].
Compound 4d: oil. IR (neat): 1610, 1600, 1550 cm–1. 1H
NMR (CDCl3): d = 8.20 (d, J = 8.5 Hz, 1 H), 8.14 (d, J = 8.8
Hz, 2 H), 7.85 (d, J = 8.3 Hz, 1 H), 7.74 (s, 1 H), 7.71–7.63
(m, 1 H), 7.53–7.50 (m, 5 H), 7.43–7.35 (m, 1 H), 7.01 (d,
J = 8.8 Hz, 2 H), 3.83 (s, 3 H). 13C NMR (CDCl3): d = 160.8,
156.4, 148.9, 148.8, 138.5, 132.1, 129.9, 129.5, 129.4,
128.9, 128.5, 128.3, 125.9, 125.6, 125.5, 118.8, 114.2, 55.3.
MS (EI): m/z (%) = 311 (100) [M+].
Compound 4e: mp 118–120 °C. IR (KBr): 1600, 1550 cm–1.
1H NMR (CDCl3): d = 8.21–8.10 (m, 1 H), 8.15 (d, J = 8.8
Hz, 2 H), 7.84 (d, J = 8.4 Hz, 1 H), 7.74 (s, 1 H), 7.72–7.65
(m, 1 H), 7.43 (d, J = 8.0 Hz, 2 H), 7.44–7.35 (m, 1 H), 7.32
(d, J = 8.0 Hz, 2 H), 7.01 (d, J = 8.8 Hz, 2 H), 3.84 (s, 1 H),
2.45 (s, 1 H). 13C NMR (CDCl3): d = 160.9, 156.5, 149.1,
148.9, 138.2, 135.7, 132.4, 129.9, 129.5, 129.34, 129.27,
128.9, 127.4, 125.8, 125.7, 118.8, 114.2, 55.4, 21.3. MS
(EI): m/z (%) = 325 (100) [M+].
Compound 4f: mp 120–121 °C. IR (KBr): 1620, 1600, 1550
cm–1. 1H NMR (CDCl3): d = 8.17–8.10 (m, 4 H), 7.97 (s, 1
H), 7.79 (d, J = 16.1 Hz, 1 H), 7.72–7.59 (m, 3 H), 7.52–7.30
(m, 5 H), 7.04 (d, J = 8.8 Hz, 2 H), 3.86 (s, 3 H). 13C NMR
(CDCl3): d = 160.7, 156.8, 148.8, 143.5, 136.8, 134.8, 132.5,
130.2, 129.4, 128.9, 128.7, 127.1, 125.9, 123.7, 123.3,
114.7, 114.2, 55.4. MS (EI): m/z (%) = 337 (100) [M+].
Compound 4h: mp 89–90 °C. IR (KBr): 1680, 1610, 1590
cm–1. 1H NMR (CDCl3): d = 8.25–8.23 (m, 1 H), 8.27 (d,
J = 8.5 Hz, 2 H), 8.08 (d, J = 8.5 Hz, 2 H), 8.10–8.05 (m, 1
H), 7.87 (s, 1 H), 7.94–7.17 (m, 1 H), 7.60–7.50 (m, 3 H),
7.40–7.35 (m, 1 H), 2.65 (s, 3 H). 13C NMR (CDCl3):
(23) Typical Procedure: To a mixture of 1c (0.106 g, 0.40
mmol), phenylboronic acid (0.244 g, 2 mmol),
Rh(acac)(C2H4)2 (0.0035 g, 0.014 mmol) and dppf (0.015 g,
0.027 mmol) in a screw-capped Pyrex tube were added
dioxane (1 mL) and H2O (0.1 mL). The tube was purged with
Synlett 2006, No. 19, 3218–3224 © Thieme Stuttgart · New York

3224
G. Abbiati et al.
LETTER
d = 197.8, 155.5, 148.5, 144.5, 143.4, 138.5, 137.4, 130.2,
129.9, 128.9, 127.7, 127.0, 126.5, 125.6, 125.1, 119.1, 26.7.
MS (EI): m/z (%) = 329 (71) [M+], 314 (100), 286 (41).
Compound 4i: mp 112–113 °C. IR (KBr): 1600, 1560 cm–1.
1H NMR (CDCl3): d = 8.30 (d, J = 8.6 Hz, 1 H), 8.26–8.20
(m, 1 H), 8.01 (d, J = 8.4 Hz, 1 H), 7.96–7.90 (m, 2 H), 7.81–
7.72 (m, 2 H), 7.67 (s, 1 H), 7.61–7.47 (m, 9 H). 13C NMR
(CDCl3): d = 159.0, 148.7, 138.7, 138.1, 134.0, 131.3, 130.1,
129.6, 129.1, 128.6, 128.5, 128.4, 127.8, 126.6, 125.9,
125.7, 125.5, 125.4, 123.4. MS (EI): m/z (%) = 331 (100)
[M+], 255 (40).
J2 = 13.4 Hz), 157.3, 156.1, 146.8 (dd, J1 = 3.2 Hz, J2 = 5.4
Hz), 137.8, 131.8, 130.7, 129.4, 129.0, 128.8, 128.6, 125.4,
121.4, 111.3, 105.2–104.2 (two overlapping multiplets),
55.7. MS (EI): m/z (%) = 347 (100) [M+], 316 (51).
Compound 4m: mp 88–90 °C. IR (KBr): 1790, 1590, 1550
cm–1. 1H NMR (CDCl3): d = 8.15–8.06 (m, 3 H), 7.74–7.60
(m, 4 H), 7.52 (s, 1 H), 7.46–7.42 (m, 1 H), 6.81 (t, J = 2.6
Hz, 1 H), 3.05–2.95 (m, 1 H), 2.66 (s, 3 H), 2.60–2.25 (m, 2
H), 2.10–1.90 (m, 2 H), 1.45–1.35 (m, 2 H), 0.94 (s, 9 H). 13
C
NMR (CDCl3): d = 197.5, 158.4, 148.4, 147.0, 139.2, 137.6,
134.0, 133.0, 130.9, 130.1, 129.3, 128.8, 128.5, 128.3,
128.1, 126.0, 125.0, 118.3, 43.9, 32.2, 27.9, 27.5, 27.2, 26.7,
24.3. MS (EI): m/z (%) = 384 (100) [M+], 327 (40).
Compound 4n: mp 117–119 °C. IR (KBr): 1590, 1550, 1510
cm–1. 1H NMR (CDCl3): d = 8.13–8.06 (m, 2 H), 7.78 (d,
J = 15.9 Hz, 1 H), 7.74 (s, 1 H), 7.70–7.56 (m, 3 H), 7.51–
7.26 (m, 4 H), 7.30 (d, J = 15.9 Hz, 1 H), 6.81 (t, J = 2.6 Hz,
1 H), 3.05–2.92 (m, 1 H), 2.65–2.30 (m, 2 H), 2.20–2.00 (m,
2 H), 1.50–1.35 (m, 2 H), 0.94 (s, 9 H). 13C NMR (CDCl3):
d = 158.9, 148.4, 142.7, 137.8, 136.9, 134.5, 130.4, 130.2,
129.1, 128.9, 128.6, 127.1, 125.7, 125.4, 123.9, 123.2,
114.2, 44.0, 32.3, 27.9, 27.7, 27.3, 23.3. MS (EI): m/z
(%) = 368 (50) [M+], 353 (15), 311 (100).
Compound 4j: mp 82–83 °C. IR (KBr): 1600, 1560 cm–1. 1H
NMR (CDCl3): d = 8.49 (s, 1 H), 8.37 (d, J = 7.5 Hz, 1 H),
8.25 (d, J = 8.6 Hz, 1 H), 7.91 (d, J = 8.5 Hz, 1 H), 7.80 (s,
1 H), 7.80–7.60 (m, 3 H), 7.55–7.44 (m, 6 H). 13C NMR
(CDCl3): d = 155.1, 149.7, 148.9, 140.4, 138.2, 130.8, 130.3,
129.8, 129.6, 129.3, 128.7, 128.6, 126.8, 125.9 (q, J = 3.6
Hz), 125.7, 124.4 (q, J = 3.7 Hz), 118.9, 29.7. MS (EI): m/z
(%) = 349 (100) [M+].
Compound 4k: mp 75–77 °C. IR (KBr): 1600, 1570, 1550
cm–1. 1H NMR (CDCl3): d = 8.48–8.33 (m, 3 H), 8.19 (d,
J = 8.4 Hz, 1 H), 8.06 (s, 1 H), 7.76–7.55 (m, 5 H), 7.01 (d,
J = 3.3 Hz, 1 H), 6.63 (m, 1 H). 13C NMR (CDCl3):
d = 155.2, 151.0, 149.2, 144.1, 140.2, 136.9, 130.7, 130.5,
129.8, 129.3, 127.2, 125.9 (q, J = 3.6 Hz), 125.2, 124.4 (q,
J = 3.7 Hz), 123.7, 116.1, 112.4, 112.1. MS (EI): m/z
(%) = 339 (100) [M+].
(25) (a) Darses, S.; Genêt, J. P. Eur. J. Org. Chem. 2003, 4313.
(b) Molander, G. A.; Figueroa, R. Aldrichimica Acta 2005,
38, 49.
(26) (a) Ueda, M.; Miyaura, N. J. Org. Chem. 2000, 65, 4450.
(b) Pucheault, M.; Darses, S.; Genêt, J. P. J. Am. Chem. Soc.
2004, 126, 15356.
(27) (a) Matsuda, T.; Makino, M.; Murakami, M. Org. Lett. 2004,
6, 1257. (b) Takezawa, A.; Yamaguchi, K.; Toshimichi, O.;
Yamamoto, Y. Synlett 2002, 1733.
Compound 4l: mp 125–127 °C. IR (KBr): 1610, 1590, 1570
cm–1. 1H NMR (CDCl3): d = 7.96 (s, 1 H), 7.97–7.91 (m, 1
H), 7.56–7.49 (m, 5 H), 7.46–7.10 (m, 4 H), 7.01 (d, J = 8.2
Hz, 1 H), 3.85 (s, 3 H). 13C NMR (CDCl3): d = 159.6 (dd,
J1 = 247.1 Hz, J2 = 12.0 Hz), 158.8 (dd, J1 = 259.9 Hz,
Synlett 2006, No. 19, 3218–3224 © Thieme Stuttgart · New York