Iron-catalyzed, directed oxidative arylation of olefins with organozinc and grignard reagents

Article abstract of DOI:10.1021/ol1009448

(Figure presented) Chelation-controlled arylation of olefins with organozinc or Grignard reagents proceeds in the presence of an iron catalyst, under mild conditions and typically without the need of external ligands, to afford substituted olefins in high

Full text of DOI:10.1021/ol1009448

ORGANIC
LETTERS
2010
Vol. 12, No. 12
2838-2840
Iron-Catalyzed, Directed Oxidative
Arylation of Olefins with Organozinc
and Grignard Reagents
Laurean Ilies, Jun Okabe, Naohiko Yoshikai,† and Eiichi Nakamura*
Department of Chemistry, School of Science, The UniVersity of Tokyo, Hongo,
Bunkyo-ku, Tokyo 113-0033, Japan
nakamura@chem.s.u-tokyo.ac.jp
Received April 26, 2010
ABSTRACT
Chelation-controlled arylation of olefins with organozinc or Grignard reagents proceeds in the presence of an iron catalyst, under mild conditions
and typically without the need of external ligands, to afford substituted olefins in high yield and with complete regio- and stereocontrol.
The cross-coupling of olefins with organometallic reagents
has recently emerged1 as an attractive alternative to the
Mizoroki-Heck reaction2 to selectively construct polysub-
stituted olefins, compounds of interest for bioactive molecules
and materials science. The catalyst of choice utilized so far
for this “oxidative Heck” reaction was a late transition metal
such as palladium or rhodium.1 Iron is attracting much
attention recently,3 but its application for the Heck-type
coupling of olefins has been largely neglected.4 We report
herein the iron-catalyzed arylation of olefins with organozinc
and Grignard reagents, where we achieved complete regio- and
stereoselectivity by designing the reaction to proceed through
a putative ferracycle intermediate (such as A in eq 1).
On the basis of our previous work on pyridine- and imine-
directed C-H bond activation,5 we assumed that formation
of a ferracycle such as A would facilitate addition of a phenyl
† Present address: Division of Chemistry and Biological Chemistry,
School of Physical and Mathematical Sciences, Nanyang Technological
University, Singapore 637371.
(1) Selected examples: (a) Ruan, J.; Li, X.; Saidi, O.; Xiao, J. J. Am.
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M. C. J. Am. Chem. Soc. 2008, 130, 11270. (c) Su, Y.; Jiao, N. Org. Lett.
2009, 11, 2980. (d) Jung, Y. C.; Mishra, R. K.; Yoon, C. H.; Jung, K. W.
Org. Lett. 2003, 5, 2231. (e) Martinez, R.; Voica, F.; Genet, J.-P.; Darses,
S. Org. Lett. 2007, 9, 3213. (f) Hirabayashi, K.; Ando, J.; Nishihara, Y.;
Mori, A.; Hiyama, T. Synlett 1999, 99. (g) Hirabayashi, K.; Nishihara, Y.;
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Y.; Fujii, T.; Hirabayashi, K.; Osakada, K. J. Am. Chem. Soc. 2001, 123,
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Zani, L. Chem. ReV. 2004, 104, 6217. (c) Enthaler, S.; Junge, K.; Beller,
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Acc. Chem. Res. 2008, 41, 1500. (e) Czaplik, W. M.; Mayer, M.; Cvengros,
J.; Jacobi von Wangelin, A. ChemSusChem 2009, 2, 396. (f) Sarhan,
A. A. O.; Bolm, C. Chem. Soc. ReV. 2009, 38, 2730. (g) Correa, A.;
Manchen˜o, O. G.; Bolm, C. Chem. Soc. ReV. 2008, 37, 1108.
(4) Loska, R.; Volla, C. M. R.; Vogel, P. AdV. Synth. Catal. 2008, 350,
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(2) (a) Bra¨se, S.; de Meijere, A. Metal-Catalyzed Cross-Coupling
Reactions; de Meijere, A., Diederich, F., Eds.; Wiley-VCH: New York,
2004; Chapter 5. (b) Heck, R. F. ComprehensiVe Organic Synthesis; Trost,
B. M., Ed.; Pergamon: New York, 1991; Vol. 4, Chapter 4.3. (c) Beletskaya,
I. P.; Cheprakov, A. V. Chem. ReV. 2000, 100, 3009. (d) Cabri, W.;
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(5) (a) Norinder, J.; Matsumoto, A.; Yoshikai, N.; Nakamura, E. J. Am.
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10.1021/ol1009448  2010 American Chemical Society
Published on Web 05/25/2010

iron species6,7 to 2-pyridyldimethylvinylsilane (1),8,9 and
following ꢀ-hydride elimination would afford a phenylated
olefin 2 (eq 1). The reaction of 1 with diphenylzinc generated
in situ from phenylmagnesium bromide and ZnCl2·TMEDA
(TMEDA ) N,N,N′,N′-tetramethylethylenediamine)10 in the
presence of a catalytic amount of Fe(III) salt11 afforded 2
as a single regio- and stereoisomer in moderate yield, together
with reduced starting material 3, and a trace amount of the
reduction product of 2 (eq 1 and Table 1, entry 1). By
generated via ꢀ-hydride elimination of A, and hence we
investigated several oxidants to suppress the formation of 3
(Table 1). 1,2-Dichloroisobutane, a compound we previously
used to oxidize iron intermediate species,5a,b was not effective
in this case (entry 2), nor was its linear congener, 1,2-
dichloroethane (entry 3). The use of 1,2-dibromoethane
significantly suppressed the reduction of 1 (entry 4), and
1-bromo-2-chloroethane was found to be an optimal oxidant
(entry 5), allowing the formation of 2 in 92% NMR yield,
when the reaction was performed at room temperature for
20 h (entry 6). Molecular oxygen could also be utilized, but
it was less efficient (entry 7). Acetophenone also largely
suppressed the reduction (entry 8).
Table 1. Screening of Oxidants To Suppress the Formation of
the Reduced Byproduct 3a
With the optimized conditions in hand, we investigated
the scope and limitations of the present reaction (Table 2).
Table 2. Iron-Catalyzed Directed Oxidative Arylation of Olefins
with Organozinc and Grignard Reagentsa
a Reaction of 1 (0.5 mmol) with Ph2Zn generated from ZnCl2·TMEDA
(3.0 equiv) and PhMgBr (6.0 equiv), in the presence of Fe(acac)3 (10 mol
b
%), oxidant (1.5-2.0 equiv) in THF at 0 °C for 3 h. 1H NMR yield.
Isolated yield in parentheses. c Reaction performed at room temperature
for 20 h.
comparison, substrates without a directing group (e.g., 1-octene,
styrene, dimethylphenylvinylsilane), substrates possessing an
oxygen-directing group (e.g., vinyl acetate), or substrates
possessing a pyridine group unsuitable for forming a ferracycle
(e.g., 2-vinylpyridine) did not react at all.
We assumed that the reduced byproduct 3 was formed
from the reduction of 1 with an iron hydride species
(6) (a) Zhang, D.; Ready, J. M. J. Am. Chem. Soc. 2006, 128, 15050.
(b) Hojo, M.; Murakami, Y.; Aihara, H.; Sakuragi, R.; Baba, Y.; Hosomi,
A. Angew. Chem., Int. Ed. 2001, 40, 621
.
(7) (a) Yamagami, T.; Shintani, R.; Shirakawa, E.; Hayashi, T. Org.
Lett. 2007, 9, 1045. (b) Shirakawa, E.; Yamagami, T.; Kimura, T.;
Yamaguchi, S.; Hayashi, T. J. Am. Chem. Soc. 2005, 127, 17164. (c)
a Reaction conditions: starting material, Ar2Zn or PhMgBr (4.0 equiv),
Fe(acac)3 (10 mol %), 1-bromo-2-chloroethane (2.0 equiv) in THF at rt.
b The product was obtained as a single regio- and stereoisomer. c Isolated
yield. d 1,2-Dichloroisobutane was used as an oxidant. e PPh3 (20 mol %)
was used as a ligand.
Nakamura, M.; Hirai, A.; Nakamura, E. J. Am. Chem. Soc. 2000, 122, 978
.
(8) Itami, K.; Mitsudo, K.; Yoshida, J. Angew. Chem., Int. Ed. 2001,
40, 2337
.
(9) (a) Itami, K.; Mitsudo, K.; Kamei, T.; Koike, T.; Nokami, T.;
Yoshida, J. J. Am. Chem. Soc. 2000, 122, 12013. (b) Itami, K.; Nokami,
T.; Ishimura, Y.; Mitsudo, K.; Kamei, T.; Yoshida, J. J. Am. Chem. Soc.
2001, 123, 11577
.
Grignard reagents could also be utilized, albeit the yield was
lower (entry 2). Both electron-rich (entries 3, 4, and 7) and
electron-deficient (entries 8 and 9) organozinc reagents
reacted with good yields, whereas sterically demanding
(10) The reaction did not proceed with pristine Ph2Zn, and TMEDA
played a beneficial role (Supporting Information).
(11) Fe(acac)3 of various purities and anhydrous FeCl3 gave similar
results. Fe(II) salts could also be used. The reaction did not proceed in the
absence of an iron salt (Supporting Information).
Org. Lett., Vol. 12, No. 12, 2010
2839

reagents gave lower yields (entry 6). It should be noted that
the reaction proceeded with complete regio- and stereose-
lectivity, and in all cases, the product was obtained as a single
trans isomer. Diarylated compounds were not observed in
any cases, even when excess organometallic reagent was
used.12 The obtained compounds can be utilized as a versatile
platform for further functionalization.13
8-Vinylquinoline also reacted smoothly to give the cor-
responding phenylated product in excellent yield and with
complete selectivity, and in this case the Grignard reagent
was higher yielding than the corresponding zinc reagent
(entries 10 and 11). It should be noted that a product resulting
from the addition of the Grignard reagent to quinoline in a
1,2-fashion14 was not observed. Quinolines are a ubiquitous
motif for natural products and bioactive compounds, such
as antimalarial drugs.15
In conclusion, we have developed an iron-catalyzed,
chelation-controlled reaction of olefins with organozinc and
Grignard reagents. This reaction proceeds with catalytic
amounts of iron salt, typically without the need for expensive
ligands, and affords a variety of olefin derivatives with
perfect control of regio- and stereoselectivity. To the best
of our knowledge, this is the first application of iron catalysis
for an oxidative Heck-type reaction, which allows the use
of organozinc reagents and Grignard reagents as a nucleo-
philic partner.
Acknowledgment. We thank MEXT (KAKENHI Spe-
cially Promoted Research for E.N., No. 22000008) and the
Global COE Program for Chemistry Innovation.
Supporting Information Available: Experimental details
and characterization of the new compounds. This material
is available free of charge via the Internet at http://pubs.acs.org.
(12) Under these conditions, substituted olefins such as (E)-2-py-
ridyldimethyl-1-hexenylsilane did not react.
(13) (a) Itami, K.; Yoshida, J. Synlett 2006, 157. (b) Itami, K.; Ohashi,
Y.; Yoshida, J. J. Org. Chem. 2005, 70, 2778.
(14) For example: Goldstein, S. W.; Dambek, P. J. Synthesis 1989, 221.
(15) Weissbuch, I.; Leiserowitz, I. Chem. ReV. 2008, 108, 4899.
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