Iron-catalyzed cross-coupling between alkenyl and dienyl sulfonates and functionalized arylcopper reagents

Article abstract of DOI:10.1055/s-2006-932451

Functionalized arylcopper reagents react readily with alkenyl sulfonates in the presence of catalytic amounts of Fe(acac)₃, (10 mol%) providing the expected cross-coupling products in good yields. Ester or cyano group are tolerated. This cross-coupling can be performed with dienyl sulfonates leading to the corresponding substituted dienes. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-2006-932451

LETTER
407
Iron-Catalyzed Cross-Coupling between Alkenyl and Dienyl Sulfonates and
Functionalized Arylcopper Reagents
I
ron-Catalyzed Cro
u
ss-Coupling
i
betw
e
l
en Alke
l
nyl and
a
D
ienyl Su
u
lfonates me Dunet, Paul Knochel*
Department Chemie und Biochemie, Ludwig-Maximilians-Universität München, Butenandtstrasse 5-13, 81377 München, Germany
Fax +49(89)218077680; E-mail: Paul.Knochel@cup.uni-muenchen.de
Received 19 December 2005
methylbenzene (4d) in 74% yield (entry 4). The alkenyl
Abstract: Functionalized arylcopper reagents react readily with
triflate 1a and the alkenyl nonaflate 1b react similarly
when treated with phenylcopper 2a, providing both 2,2-
diphenylvinylbenzene (4a) in 86% and 81%, respectively
alkenyl sulfonates in the presence of catalytic amounts of Fe(acac)3
(10 mol%) providing the expected cross-coupling products in good
yields. Ester or cyano group are tolerated. This cross-coupling can
be performed with dienyl sulfonates leading to the corresponding (entries 1 and 6). A cyano functionality is also tolerated
substituted dienes.
and the copper derivative 2e reacts with the alkenyl non-
aflate 1b to give the expected cross-coupling product 4e in
56% yield (entry 7). The cross-coupling of vinyl nonaflate
1c with functionalized arylcopper reagents provides the
corresponding functionalized styrene derivatives in ac-
ceptable yields (entries 8–10). Thus, p-carbethoxyphenyl-
copper 2b reacts within 30 minutes with 1c leading to the
desired ethyl 4-vinylbenzoate 4f in 64% yield. In contrast,
22 hours are required for the reaction of 1-naphthylcopper
2f with 1c to go to completion, providing 1-vinylnaphtha-
lene (4g) in 71% yield. Sterically hindered organocopper
reagents, such as 2e, react as well, leading to the desired
cross-coupling product in 59% yield (entry 5). It is inter-
esting to notice that although aryl sulfonates showed little
reactivity towards arylcopper reagents,4a here alkenyl sul-
fonates prove to be much more reactive under our condi-
tions, following the general tendency (alkenyl halides are
more reactive than aryl halides in cross-couplings).
Key words: catalysis, cross-coupling, organomagnesium reagents,
triflates, nonaflates
Palladium- and nickel-catalyzed cross-coupling reactions
have been extensively used for forming new carbon–car-
bon bonds between C-sp2 centers.1 Recently, iron- and co-
balt-catalyzed reactions have also been reported.2,3
Whereas arylmagnesium derivatives react with aryl
halides to give homocoupling products, we have found
that the corresponding arylcopper derivatives give mainly
the desired cross-coupling products.4
Herein, we wish to report an improved iron(III)-catalyzed
cross-coupling between alkenyl triflates and nonaflates of
type 15 and functionalized arylcopper derivatives of type
2 prepared from the corresponding arylmagnesium deriv-
atives 3.6 The cross-coupling reactions occur readily in
DME and are complete within one hour at 25 °C leading
to products of type 4 in 41–90% yield (Scheme 1 and
Table 1). Remarkably, electron-poor arylcopper deriva-
tives react well with the corresponding alkenyl sulfonates
to provide the expected products in good yields. Thus, p-
carbethoxyphenylcopper 2b undergoes a smooth cross-
coupling reaction with the triflate 1a producing ethyl 4-
(2,2-diphenylvinyl)benzoate (4b) in 77% yield (entry 2).7
Under these conditions, 3-trifluoromethylphenylcopper
(2d) reacts with 1a to give 3-(2,2-diphenylvinyl)trifluoro-
These cross-coupling reactions can also be performed
with dienyl sulfonates8 (compounds 1d–f) yielding the
corresponding dienes in moderate to good yield. Thus,
nonaflate 1d reacts with 3-trifluoromethylphenylcopper
2d providing the expected cross-coupling product 4k in
90% yield (entry 12). Ethyl 4-cyclohexa-1,5-dienyl-
benzoate (4j) is obtained under the same conditions in
86% yield (entry 11). Interestingly, acyclic systems lead
to different results. Thus, the dienyl nonaflate 1f reacts
poorly with phenylcopper 2a (entry 15), leading to the
R
Fe(acac)3
R3
R2
OSO2R1
R2
MgCl
(10 mol%)
R3
R2
Cu(CN)MgCl
CuCN·2LiCl
+
DME, r.t.
THF, –20 °C
R2
R
R
1a: R1 = CF3; R2 = Ph ; R3 = H
1b: R1 = C4F9; R2 = Ph; R3 = H
1c: R1 = C4F9; R2 = H; R3 = H
3
2
4: 41–90%
Scheme 1
SYNLETT 2006, No. 3, pp 0407–0410
1
5.
0
2.
2
0
0
6
Advanced online publication: 06.02.2006
DOI: 10.1055/s-2006-932451; Art ID: G40605ST
© Georg Thieme Verlag Stuttgart · New York

408
G. Dunet, P. Knochel
LETTER
Table 1 Products of Type 4 Obtained by the Cross-Coupling Reaction of Enol Sulfonates of Type 1 and Organocopper Reagents of Type 2a
Entry
1
Enol sulfonate of type 1
Organocopper reagent of type 2
Product of type 4
Yield (%)b
86c
OTf
Ph
Cu(CN)MgCl
Ph Ph
Ph Ph
4a
2a
1a
CO2Et
EtO2C
Cu(CN)MgCl
Cu(CN)MgCl
2
3
4
1a
1a
1a
77
Ph Ph
4b
2b
OMe
MeO
78
Ph Ph
2c
4c
F3C
74 (41,d 59e)
CF3
Ph Ph
Cu(CN)MgCl
2d
4d
5
6
1a
59
Cu(CN)MgCl
Ph Ph
2e
2a
4e
ONf
Ph
81c
Ph Ph
Ph Ph
1b
4a
NC
CN
Ph Ph
4f
7
8
9
1b
56
64
71
Cu(CN)MgCl
2f
EtO2C
2b
ONf
1c
4g
1c
1c
Cu(CN)MgCl
Cu(CN)MgCl
2g
Br
4h
Br
10
11
12
13
62
2h
2b
4i
86f
90f
72f
ONf
CO2Et
1d
4j
CF3
1d
2d
2g
4k
Naphthyl
4l
1d
ONf
14
15
2c
2a
Complex mixture
–
1e
41
ONf
Ph
1f
4m
a Unless stated otherwise, all reactions were carried out on a 1 mmol scale using 2.8 equiv of arylcopper derivative and 10 mol% of Fe(acac)3.
b Isolated yield of analytically pure product.
c Reaction carried out with 2 equiv of arylcopper reagent.
d Isolated yield when 2.8 equiv of arylmagnesium chloride was used instead of arylcopper derivative.
e GC conversion after 4 h in the case where no Fe(acac)3 is used.
f Reaction carried out with 1.4 equiv of arylcopper reagent.
Synlett 2006, No. 3, 407–410 © Thieme Stuttgart · New York

LETTER
Iron-Catalyzed Cross-Coupling between Alkenyl and Dienyl Sulfonates
409
A. J. Org. Chem. 2004, 69, 3950. (z) Scheiper, B.;
Bonnekessel, M.; Krause, H.; Fürstner, A. J. Org. Chem.
2004, 69, 3943.
cross-coupling product 4m in 41% yield, whereas dienyl
nonaflate 1e leads to a complex mixture under the same
conditions (entry 14).
(3) (a) Fürstner, A.; De Souza, D.; Parra-Rapado, L.; Jensen, J.
T. Angew. Chem. Int Ed. 2003, 42, 5388. (b) Nakamura,
M.; Matsuo, K.; Ito, S.; Nakamura, E. J. Am. Chem. Soc.
2004, 126, 3686. (c) Nagano, T.; Hayashi, T. Org. Lett.
2004, 6, 1297. (d) Martin, R.; Fürstner, A. Angew. Chem.
Int. Ed. 2004, 43, 3955. (e) Martin, R.; Fürstner, A. Chem.
Lett. 2005, 34, 624.
(4) (a) Sapountzis, I.; Lin, W.; Kofink, C. C.; Despotopoulou,
C.; Knochel, P. Angew. Chem. Int. Ed. 2005, 44, 1654.
(b) Korn, T.; Knochel, P. Angew. Chem. Int. Ed. 2005, 44,
2947.
(5) (a) Alkenyl sulfonates 1a and 1b were prepared by treating
the corresponding aldehyde with 1.4 equiv of t-BuOK in
refluxing THF for 4 h and quenching of the resulting enolate
with N-phenyl-bis(trifluoromethanesulfonimide) and
nonafluorobutanesulfonyl fluoride (NfF), respectively.
Compounds 1c and 1f were prepared following a literature
procedure, see ref. 5b. Nonaflate 1d was obtained from the
corresponding ketone via treatment with LDA and NfF.
Dienyl nonaflate 1g was prepared from the corresponding
commercially available trimethylsilyl enol ether upon
treatment with MeLi, followed by NfF. (b) Lyapkalo, I. M.;
Webel, M.; Reißig, H.-U. Eur. J. Org. Chem. 2001, 4189.
(6) (a) Krasovskiy, A.; Knochel, P. Angew. Chem. Int. Ed. 2004,
43, 3333. (b) Liu, C.-Y.; Knochel, P. Org. Lett. 2005, 7,
2543. (c) Ren, H.; Krasovskiy, A.; Knochel, P. Chem.
Commun. 2005, 543. (d) Ren, H.; Krasovskiy, A.; Knochel,
P. Org. Lett. 2004, 6, 4215.
In summary, we have shown that alkenyl sulfonates react
with functionalized arylcopper reagents in the presence of
Fe(acac)3 under mild conditions (r.t.). This cross-coupling
can also be applied to various dienyl sulfonates leading to
the corresponding functionalized dienes. The use of an
iron salt as catalyst offers a good alternative to palladium-
and nickel-catalyzed cross-coupling reactions, in terms of
cost and toxicity, which makes this cross-coupling attrac-
tive. Extensions of this method are currently underway in
our laboratory.
Acknowledgment
We thank Merck Research laboratories (MSD), the Ludwig-
Maximilians-University (Munich) and the Fonds der Chemischen
Industrie for financial support. We thank also Chemetall GmbH
(Frankfurt) and BASF AG (Ludwigshafen) for the generous gift of
chemicals.
References
(1) (a) Metal-Catalyzed Cross-Coupling Reactions, 2nd ed.;
de Meijere, A.; Diederich, F., Eds.; Wiley-VCH: Weinheim,
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(c) Cross-Coupling Reactions. A Practical Guide; Miyaura,
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Marquais, S. Pure Appl. Chem. 1996, 68, 669. (k) Cahiez,
G.; Marquais, S. Tetrahedron Lett. 1996, 37, 1773.
(7) Typical Procedure – Preparation of Ethyl 4-(2,2-Di-
phenylvinyl)benzoate (4b).
A 25 mL flame-dried Schlenk tube flushed with argon was
charged with ethyl 4-iodobenzoate (2.9 mmol, 773 mg),
DME (5 mL) and cooled to –20 °C. Isopropylmagnesium
chloride (2.9 mmol, 1.33 mL of a 2.1 M solution in THF)
was then slowly added and the reaction mixture was stirred
at –20 °C until GC analysis of reaction aliquots indicated
complete exchange. Subsequently, a solution of
CuCN·2LiCl (2.8 mmol, 2.8 mL of a 1 M solution in THF)
was added and the reaction mixture was stirred for 20 min.
A solution of (2,2-diphenylvinyl)trifluoromethanesulfonate
(330 mg, 1 mmol) and Fe(acac)3 (38 mg, 0.1 mmol) in DME
(3 mL) was added at once at –20 °C and the reaction mixture
was stirred at r.t. for 1 h. The reaction was quenched with sat.
NH4Cl (aq), and extracted several times with Et2O. The
combined organic phases were washed with a 2:1 mixture of
NH3 (aq) and NH4Cl (aq), sat. brine, dried over MgSO4 and
concentrated under reduced pressure. Purification via
column chromatography (elution with a 99:1 pentane–Et2O
mixture) afforded the stilbene (4b) as a yellow oil (254 mg,
77%). 1H NMR (300 MHz, CDCl3): d = 7.72 (unresolved d,
J = 8.4 Hz, 2 H), 7.21–7.28 (m, 8 H), 7.08–7.13 (m, 2 H),
6.99 (unresolved d, J = 8.6 Hz, 2 H), 6.91 (s, 1 H), 4.25 (q,
J = 7.1 Hz, 2 H), 1.27 (t, J = 7.1 Hz, 3 H). 13C NMR (75
MHz, CDCl3): d = 166.8, 145.3, 143.3, 142.4, 140.2, 130.7,
129.7, 129.6, 129.1, 128.7, 128.7, 128.3, 128.1, 128.1,
127.5, 61.2, 14.7. HRMS: m/z calcd: 328.1463; found:
328.1455. MS (EI, 70 eV): m/z (%) = 328 (100), 283 (18),
255 (48), 239 (14).
(l) Cahiez, G.; Avedissian, H. Synthesis 1998, 1199.
(m) Shinokubo, K.; Oshima, K. Eur. J. Org. Chem. 2004,
2081. (n) Fakhfakh, M. A.; Franck, X.; Hocquemiller, R.;
Figadère, B. J. Organomet. Chem. 2001, 624, 131.
(o) Hocek, M.; Dvoráková, H. J. Org. Chem. 2003, 68,
5773. (p) Hölzer, B.; Hoffmann, R. W. Chem. Commun.
2003, 732. (q) Dohle, W.; Kopp, F.; Cahiez, G.; Knochel, P.
Synlett 2001, 1901. (r) Hojo, M.; Murakami, Y.; Aihara, H.;
Sakuragi, R.; Baba, Y.; Hosomi, A. Angew. Chem. Int. Ed.
2001, 40, 621. (s) Nakamura, N.; Hirai, A.; Nakamura, E. J.
Am. Chem. Soc. 2001, 122, 978. (t) Alvarez, E.; Cuvigny,
T.; du Penhoat, C. H.; Julia, M. Tetrahedron 1998, 44, 119.
(u) Finandanese, V.; Marchese, G.; Martina, V.; Ronzini, L.
Tetrahedron Lett. 1984, 25, 4805. (v) Fürstner, A.; Leitner,
A.; Méndez, M.; Krause, H. J. Am. Chem. Soc. 2002, 124,
13856. (w) Fürstner, A.; Leitner, A. Angew. Chem. Int. Ed.
2002, 41, 609. (x) Fürstner, A.; Leitner, A. Angew. Chem.
Int. Ed. 2003, 42, 308. (y) Seidel, G.; Laurich, D.; Fürstner,
1-[2-(4-Methoxyphenyl)-1-phenylvinyl]benzene (4c): 1H
NMR (300 MHz, CDCl3): d = 7.21–7.29 (m, 7 H), 7.18–7.20
(m, 1 H), 7.12–7.16 (m, 2 H), 6.88 (unresolved d, J = 8.6 Hz,
2 H), 6.84 (s, 1 H), 6.59 (unresolved d, J = 8.8 Hz, 2 H), 3.67
(s, 3 H). 13C NMR (75 MHz, CDCl3): d = 158.8, 144.0,
141.0, 141.0, 131.2, 130.8, 130.5, 129.1, 128.5, 128.0,
Synlett 2006, No. 3, 407–410 © Thieme Stuttgart · New York

410
G. Dunet, P. Knochel
LETTER
125.4, 125.3, 61.2, 23.3, 22.2; 14.7. HRMS: m/z calcd:
127.8, 127.7, 127.6, 113.8, 55.5. HRMS: m/z calcd:
286.1358; found: 286.1341. MS (EI, 70 eV): m/z (%) = 286
(100), 165 (15).
228.1150; found: 228.1135. MS (EI, 70 eV): m/z (%) = 228
(100), 200 (10), 183 (32), 155 (87), 153 (19), 128 (10).
1-(Cyclohexa-1,5-dienyl)-3-(trifluoromethyl)benzene
(4k): 1H NMR (300 MHz, CDCl3): d = 7.54 (s, 1 H), 7.30–
7.52 (m, 3 H), 6.22 (dq, J = 9.7 Hz, J = 1.8 Hz, 1 H), 6.06 (tt,
J = 4.6 Hz, J = 1.3 Hz, 1 H), 5.98 (dtd, J = 9.7 Hz, J = 4.3
Hz, J = 0.9 Hz, 1 H), 2.23–2.33 (m, 2 H), 2.09–2.19 (m, 2
H). 13C NMR (75 MHz, CDCl3): d = 141.8, 135.3, 129.2,
129.0, 128.8, 125.4, 124.8, 123.8, 122.6, 23.2, 22.2. HRMS:
m/z calcd: 224.0813; found: 224.0839. MS (EI, 70 eV): m/z
(%) = 224 (82), 223 (32), 209 (58), 183 (87), 155 (100).
1-(Cyclohexa-1,5-dienyl)naphthalene (4l): 1H NMR (300
MHz, CDCl3): d = 7.90–7.98 (m, 1 H), 7.73–7.79 (m, 1 H),
7.68 (d, J = 8.0 Hz, 1 H), 7.32–7.43 (m, 3 H), 7.24 (dd,
J = 7.1 Hz, J = 1.3 Hz, 1 H), 6.1 (dq, J = 9.7 Hz, J = 1.8 Hz,
1 H), 5.82–5.93 (m, 2 H), 2.29–2.39 (m, 2 H), 2.18–2.29 (m,
2 H). 13C NMR (75 MHz, CDCl3): d = 140.8, 136.7, 134.1,
131.8, 128.8, 128.7, 127.7, 126.4, 126.4, 126.0, 126.05,
125.98, 125.9, 125.8, 23.2, 22.4. HRMS: m/z calcd:
206.1096; found: 206.1078. MS (EI, 70 eV): m/z (%) = 207
(15), 206 (100), 205(90), 178 (53), 165 (49).
1-{(2-[3-(Trifluoromethyl)phenyl]-1-phenyl-
vinyl}benzene (4d): 1H NMR (300 MHz, CDCl3): d = 7.21–
730 (m, 9 H), 7.16–7.19 (m, 2 H), 7.08–7.13 (m, 3 H), 6.90
(s, 1 H). 13C NMR (75 MHz, CDCl3): d = 145.0, 143.1,
140.0, 138.5, 132.9, 130.5, 129.2, 128.7, 128.3, 128.2,
128.0, 126.8, 126.7, 126.6, 123.6, 123.3. HRMS: m/z calcd:
324.1126; found: 324.1118. MS (EI, 70 eV): m/z (%) = 324
(100), 283 (10), 255 (13), 178 (11).
3-(2,2-Diphenylvinyl)benzonitrile (4f): 1H NMR (300
MHz, CDCl3): d = 7.22–7.32 (m, 9 H), 7.19–7.21 (m, 1 H),
7.11–7.16 (m, 2 H), 7.05–7.11 (m, 2 H), 6.83 (s, 1 H). 13C (75
MHz, CDCl3): d = 145.8, 142.9, 139.7, 139.1, 134.0, 133.3,
132.6, 130.5, 130.4, 129.5, 129.3, 129.1, 128.7, 128.6,
128.5, 128.1, 125.9, 112.6. HRMS: m/z calcd: 281.1204;
found: 281.1186. IR (KBr): 3435 (w), 3056, 2228, 1616,
1491, 1444, 796, 765, 701 cm–1.
Ethyl 4-(Cyclohexa-1,5-dienyl)benzoate (4j): 1H NMR
(300 MHz, CDCl3): d = 7.92 (unresolved d, J = 8.4 Hz, 2 H),
7.36 (unresolved d, J = 8.4 Hz, 2 H), 6.26 (dq, J = 9.7 Hz,
J = 1.8 Hz, 1 H), 6.11 (unresolved t, J = 4.4 Hz, 1 H), 5.93–
6.01 (m, 1 H), 4.30 (q, J = 7.1 Hz, 2 H), 2.23–2.33 (m, 2 H),
2.09–2.19 (m, 2 H), 1.32 (t, J = 7.1 Hz, 3 H). 13C (75 MHz,
CDCl3): d = 166.9, 145.3, 135.6, 130.1, 129.2, 128.6, 125.5,
(8) For the reaction of dienyl sulfonates with cuprates, see:
Karlström, A. S. E.; Rönn, M.; Thorarensen, A.; Bäckvall,
J.-E. J. Org. Chem. 1998, 63, 2517.
Synlett 2006, No. 3, 407–410 © Thieme Stuttgart · New York