Fe(III)-catalyzed cross-coupling between functionalized arylmagnesium compounds and alkenyl halides

Article abstract of DOI:10.1055/s-2001-18748

Functionalized arylmagnesium reagents bearing an ester, cyano, nonaflate or trialkylsilyloxy group undergo fast cross-coupling reactions with alkenyl iodides or bromides in the presence of catalytic amounts of Fe(acac)₃ (5 mol%) at-20 °C within

Full text of DOI:10.1055/s-2001-18748

LETTER
1901
Fe(III)-Catalyzed Cross-Coupling Between Functionalized Arylmagnesium
Compounds and Alkenyl Halides
F
e(III)-Catalyzed Cross
o
-
Coupling lfgang Dohle,a Felix Kopp,a Gerard Cahiez,*b Paul Knochel*a
a
Department Chemie, Ludwig-Maximilians-Universität München, Butenandtstrasse 5-13, 81377 München, Germany
Fax +49(89)21807680; E-mail: Paul.Knochel@cup.uni-muenchen.de
b
Département de Chimie (associé au CNRS), Ecole Supérieure de Chimie Organique et Minérale, 13, Boulevard de l'Hautil,
95092 Cergy-Pontoise, France
Received 17 July 2001
corresponding arylmagnesium reagents of type 2 by the
reaction with i-PrMgBr (1.1 equiv) in THF at –20 °C for
1–4 hours. The resulting functionalized organomagne-
sium reagent 2 is treated with an alkenyl iodide or bro-
Abstract: Functionalized arylmagnesium reagents bearing an ester,
cyano, nonaflate or trialkylsilyloxy group undergo fast cross-cou-
pling reactions with alkenyl iodides or bromides in the presence of
catalytic amounts of Fe(acac)3 (5 mol%) at –20 °C within 1 hour re-
sulting in the formation of the desired cross-coupling products in mide 3 (0.7 equiv) at –20 °C in the presence of Fe(acac)3
satisfactory yields. Excellent yields can be achieved by performing
(5 mol%) for 15–30 min. A fast cross-coupling reaction
the cross-coupling reaction on solid phase by generating the Grig-
nard reagent on the resin.
occurs affording the desired polyfunctionalized products
of type 4 in 50–73% yield (Scheme 1 and Table). The re-
action proceeds with retention of the configuration of the
double bond, affording only E-products.
Key words: magnesium, iodine-magnesium exchange, iron(III)-
catalysis, cross-coupling reaction
Thus, p-carbethoxyphenylmagnesium bromide 2a reacts
with (E)-1-iodohexene 3a providing the cross-coupling
Transition metal catalyzed cross-coupling reactions are
product 4a11a in 60% yield (entry 1 of the Table). Similar-
amongst the most useful methods for forming new car-
ly, sulfonylamido-alkenyl iodide 3b9 reacts with 2a pro-
bon-carbon bonds between two Csp2-centres.1 Although
ducing the (E)-styrene derivative 4b in 69% yield (entry
in most of these reactions Pd(0)-catalysis2 is used, other
2). Both reactions give as side products the cross-coupling
transition metals such as Cu(I)3 or Ni(0)4 have been used.
product (10–15%) of the alkenyl halide 3 and the excess
Following the pioneering work of Kochi,5 one of us has
of i-PrMgBr and reductive coupling of the functionalized
recently shown the synthetic utility of Fe(acac)3 as a cata-
arylmagnesium species 2 affording the corresponding
lyst in cross-coupling reactions between alkylmagnesium
homo-coupling biaryl derivatives (10–15%) as shown by
reagents and various alkenyl halides.6 Herein, we wish to
GC and GC/MS analysis. Interestingly, cross-coupling re-
report that iron(III) catalysis also allows cross-coupling
actions between functionalized aryl iodides 1 and phenyl-
reactions between functionalized arylmagnesium reagents
magnesium bromide 2b to the corresponding biaryls do
and alkenyl iodides or bromides to take place under very
not occur under various reaction conditions. In order to es-
mild reaction conditions. This is especially important if
tablish, if the carbethoxy group influences the yield of the
arylmagnesium derivatives bearing sensitive functional
reaction, we carried out a calibration experiment with
groups like an ester or cyano are used, since these organo-
phenylmagnesium bromide and 3b, but the desired cross-
metallics are only stable up to 0 °C for a few hours.7 Thus,
coupling product 4c was obtained in a similar yield (65%;
various aryl iodides of type 1 bearing functional groups
entry 3). The cyano- or nonaflate-substituted arylmagne-
such as an ester, cyano, trialkylsilyloxy group or nonaflate
sium species 2c and 2d undergo a cross-coupling reaction
(OSO2(CF2)3CF3 = ONf)8 are smoothly converted into the
R
X
I
MgBr
R
i-PrMgBr
3: X = Br, I
THF, -20 °C
1-4 h
Fe(acac)3 (5 mol%)
THF, -20 °C, 15-30 min
FG
FG
FG
1
2
4: 50-73%
FG = CO2Et, CN, OTIPS, ONf
Scheme 1
Synlett 2001, No. 12, 30 11 2001. Article Identifier:
1437-2096,E;2001,0,12,1901,1904,ftx,en;G14701ST.pdf.
© Georg Thieme Verlag Stuttgart · New York
ISSN 0936-5214

1902
W. Dohle et al.
LETTER
Table Cross-Coupling Products 4 Obtained by the Reaction of Functionalized Arylmagnesium Bromides 2 with Alkenyl Bromides or Iodides
3 in the Presence of Catalytic Amounts of Fe(acac)3 in THF
Entry
1
Grignard reagent 2
Alkenyl halide 3
Product of type 4
Yield (%)a
EtO2C
EtO2C
Bu
I
60
3a
MgBr
Bu
4a
2a
EtO2C
2
2a
69
N
Ph
SO2CF3
I
3b
Ph
N
SO2CF3
4b
MgBr
Ph
3
3b
65
Ph
4c
N
2b
SO2CF3
NC
NC
4
5
3a
3a
60
73
Bu
MgBr
4d
2c
CO2Et
CO2Et
NfO
NfO
Bu
MgBr
4e
2d
NfO
MgBr
NfO
Bu
Ph
6
7
8
3a
50
62
62
2e
2e
4f
Ph
NfO
Br
3c
4g
TIPSO
MgBr
TIPSO
Ph
3c
2f
4h
a Yield of analytically pure product.
with (E)-1-iodohexene in 60% and 73% yield respectively arylmagnesium compound 2f reacts with 3c providing the
(entries 4–5). A reactive alkenyl bromide, such as [(E)-2- desired product 4h in 62% yield (entry 8).
bromoethenyl]benzene (3c), reacts smoothly with the
Grignard reagent 2e leading to the E-stilbene derivative
4g in 62% yield (entry 7). Similarly, the electron-rich
on the resin.10 Thus, the resin-attached m- and p-iodoben-
These cross-coupling reactions can be easily performed
on solid phase by generating the arylmagnesium species
Synlett 2001, No. 12, 1901–1904 ISSN 0936-5214 © Thieme Stuttgart · New York

LETTER
Fe(III)-Catalyzed Cross-Coupling Reactions
1903
1) i-PrMgBr (5 equiv)
THF, -20 °C, 1h
O
R
HO2C
2)
R
3a, 3c (15 equiv)
O
X
I
Fe(acac)3 (5 mol%)
-20 °C, 30 min
3) TFA/CH2Cl2/H2O 9:1:1
15 min, rt
5a: meta-iodo
5b: para-iodo
HO2C
HO2C
R
R
6a: R = Bu; 90%a
6b: R = Ph; 84%a
6c: R = Bu; 94%a
6d: R = Ph; 86%a
Scheme 2 aHPLC puritity measured at 254 nm. Isolated yields are >85%.
zoate 5a and 5b were treated with an excess of i-PrMgBr
(5 equiv) in THF (–20 °C; 1 h), producing the correspond-
ing arylmagnesium species. Its reaction with an excess of
alkenyl halide (3a or 3c; 15 equiv) in the presence of
Fe(acac)3 (5 mol%) at –20 °C for 30 min produces, after
cleavage from the resin (TFA/CH2Cl2/H2O 9:1:1; 15 min
at r.t.), the corresponding benzoic acid derivatives 6a–d11b
with excellent HPLC purities and usually in more than
85% isolated yield (Scheme 2).
(4) (a) Kumada, M. Pure Appl. Chem. 1980, 52, 669. (b) Luh,
T.-Y. Acc. Chem. Res. 1991, 24, 257. (c) Sengupta, S.;
Leite, M.; Raslan, D. S.; Quesnelle, C.; Snieckus, V. J. Org.
Chem. 1992, 57, 4066. (d) Indolese, A. F. Tetrahedron Lett.
1997, 38, 3513. (e) Shirakawa, E.; Yamasaki, K.; Hiyama,
T. Synthesis 1998, 1544. (f) Sophia, A.; Karlström, E.;
Itami, K.; Bäckvall, J.-E. J. Org. Chem. 1999, 64, 1745.
(g) Tang, X. Q.; Montgomery, J. J. Am. Chem. Soc. 2000,
122, 6950. (h) Montgomery, J. Acc. Chem. Res. 2000, 33,
467. (i) Giovannini, R.; Knochel, P. J. Am. Chem. Soc. 1998,
120, 11186. (j) Lipshutz, B. H. Adv. Synth. Catal. 2001, 343,
313. (k) Lipshutz, B. H.; Bulow, G.; Fernandez-Lazaro, F.;
Kim, S.-K.; Lowe, R.; Mollard, P.; Stevens, K. L. J. Am.
Chem. Soc. 1999, 121, 11664.
In summary, we have shown that alkenyl iodides or bro-
mides react under mild conditions (–20 °C, less than 1 h)
with functionalized arylmagnesium bromides in the pres-
ence of Fe(acac)3 (5 mol%). This method is of special in-
terest when functionalized arylmagnesium reagents are
used since with a Ni(0) or Pd(0) catalysis the cross-cou-
pling reaction occurs only at temperatures above 20 °C re-
sulting in a destruction of the sensitive functions (ester,
cyano) present in the magnesium reagent or in the cross-
coupling product.
(5) (a) Tamura, M.; Kochi, J. K. J. Am. Chem. Soc. 1971, 93,
1487. (b) Tamura, M.; Kochi, J. K. Synthesis 1971, 93, 303.
(c) Tamura, M.; Kochi, J. K. J. Organomet. Chem. 1971, 31,
289. (d) Tamura, M.; Kochi, J. K. Bull. Chem. Soc. Jpn.
1971, 44, 3063. (e) Tamura, M.; Kochi, J. K. Synthesis
1971, 303. (f) Kochi, J. K. Acc. Chem. Res. 1974, 7, 351.
(g) Neumann, S.; Kochi, J. K. J. Org. Chem. 1975, 40, 599.
(h) Smith, R. S.; Kochi, J. K. J. Org. Chem. 1976, 41, 502.
(i) See also: Molander, G.; Rahn, B.; Shubert, D. C.; Bonde,
S. E. Tetrahedron Lett. 1983, 24, 5449.
Acknowledgement
(6) (a) Cahiez, G.; Marquais, S. Pure Appl. Chem. 1996, 68,
669. (b) Cahiez, G.; Marquais, S. Tetrahedron Lett. 1996,
37, 1773. (c) Cahiez, G.; Avedissian, H. Synthesis 1998,
1199.
We thank the DFG (Leibniz program) for financial support. W. D.
thanks BASF AG (Ludwigsafen) for a fellowship. We thank BASF
AG and Degussa (Hanau) for generous gifts of chemicals.
(7) Varchi, G.; Jensen, A. E.; Dohle, W.; Ricci, A.; Cahiez, G.;
Knochel, P. Synlett 2001, 477; and references cited therein.
(8) Rottländer, M.; Knochel, P. J. Org. Chem. 1998, 63, 203.
(9) Preparation of the iodosulfonamide 3b: N-Benzyl-1,1,1-
trifluoromethanesulfonamide12 (3.70 g; 15.5 mmol) was
dissolved in acetone (8 mL) and potassium carbonate (4.28
g; 31.0 mmol) was added. The suspension was stirred
overnight at r.t. Then (E)-1,5-diiodopent-1-ene13 (5.00 g;
15.5 mmol) was added and the reaction mixture was stirred
overnight at r.t. until completion (GC analysis). The reaction
mixture was then quenched with saturated NH4Cl solution
and extracted with ether. The combined organic phases were
dried over MgSO4 and concentrated in vacuo. The residue
was purified by flash column chromatography using pentane
as eluent to give 3b (4.50 g; 10.4 mmol; 67%) as a colourless
oil.
References
(1) (a) Metal-catalyzed Cross-Coupling Reactions; Diederich,
F.; Stang, P. J., Eds.; Wiley-VCH: Weinheim, 1998.
(b) Nicolaou, K. C.; Sorensen, E. J. Classics in Total
Synthesis; VCH: Weinheim, 1996, 565. (c) Tsuji, J.
Transition Metal Reagents and Catalysts: Innovations in
Organic Synthesis; Wiley: New York, 1995. (d) Erdik, E.
Tetrahedron 1992, 48, 9577.
(2) Tsuji, J. Palladium Reagents and Catalysts: Innovations in
Organic Synthesis; Wiley: Chichester, 1995, .
(3) For an excellent review, see: Lipshutz, B. H.; Sengupta, S.
Org. React. 1992, 41, 135.
Synlett 2001, No. 12, 1901–1904 ISSN 0936-5214 © Thieme Stuttgart · New York

1904
W. Dohle et al.
LETTER
(10) Boymond, L.; Rottländer, M.; Cahiez, G.; Knochel, P.
Angew. Chem. Int. Ed. 1998, 37, 1701.
Acid 6c: Wang resin loaded with 4-iodobenzoic acid (150
mg; 0.63 mmol/g; 0.095 mmol) was placed in a dry argon
flushed 10 mL Schlenk tube equipped with a rubber septum
and a magnetic stirring bar and allowed to swell in dry THF
(0.5 mL) for 5 min at –20 °C. Then iso-propylmagnesium
bromide (0.87 mL; 0.55 M in THF; 0.48 mmol) was added
slowly and the resin was stirred for 1 h. Then a solution of
iron (III) acetylacetonate (1.7 mg; 4.8 mmol) and 1-
iodohex-1-ene (303 mg; 1.44 mmol) in THF was added at –
20 °C and the reaction mixture was stirred for 30 min at this
temperature. After completion of the reaction (checked by
analytical HPLC) the resin was filtered and sequentially
washed three times with THF (2 mL), DMF (2 mL) and
methanol (2 mL). Finally it was washed three times with
CH2Cl2 (2 mL). The product resin (100 mg) was placed in a
2 mL-syringe equipped with a polyethylene filter plate and
treated with TFA/CH2Cl2/H2O 9:1:1 (1 mL) for 15 min at r.t.
After removing the volatiles in vacuo 6c (11.2 mg; 54.9
mol; 87% yield; 94% HPLC purity) was obtained as a white
solid (mp: 238–245 °C dec.).
(11) Typical Procedures: (a) Reaction in solution. Preparation
of Ethyl 4-[(1E)-hex-1-enyl]benzoate 4a (entry 1 of the
table): Ethyl 4-iodobenzoate (384 mg; 1.4 mmol)was placed
in a dry argon flushed 50 mL Schlenk-flask equipped with a
rubber septum and magnetic stirring bar. Dry THF (3.0 mL)
was added and the solution was cooled to –20 °C. Then iso-
propylmagnesium bromide (6.0 mL; 0.55 M in THF; 3.3
mmol) was added slowly and the reaction mixture was
stirred at this temperature until the exchange reaction was
complete (checked by TLC). The resulting suspension was
then transferred dropwise via cannula into another dry argon
flushed Schlenk-flask containing a solution of iron (III)
acetylacetonate (18 mg; 5.1 mol)and 1-iodohex-1-ene (212
mg; 1.0 mmol) in dry THF (2.0 mL) stirring at –20 °C. After
the reaction was complete (checked by TLC and GC)
methanol (3 mL) and water (30 mL) were added and the
reaction mixture was extracted with ethyl acetate (3 30
mL). The combined organic phases were washed with brine
(30 mL), dried over MgSO4 and concentrated in vacuo. The
residue was purified by flash column chromatography using
98:2 pentane/ethyl acetate as eluent giving the product 4a
(140 mg; 0.60 mmol; 60%) as a colourless oil. (b) Reaction
on solid phase. Preparation of 4[(1E)-Hex-1-enyl]benzoic
(12) Hendrickson, J. B.; Bergeron, R.; Sternbach, D. D.
Tetrahedron 1975, 31, 2517.
(13) Jabri, N.; Alexakis, A.; Normant, J. F. Bull. Soc. Chim. Fr.
1983, 2, 321.
Synlett 2001, No. 12, 1901–1904 ISSN 0936-5214 © Thieme Stuttgart · New York