Iron thiolate complexes: Efficient catalysts for coupling alkenyl halides with alkyl grignard reagents

Article abstract of DOI:10.1002/chem.201200184

Ironing out the kinks: Efficient new catalytic systems based on iron thiolates are described for the iron-catalyzed cross-coupling of alkyl Grignard reagents with alkenyl halides (see scheme). The reaction is highly chemo- and stereoselective. With this new procedure, the use of N-methylpyrrolidone as a co-solvent is no longer required. Copyright

Full text of DOI:10.1002/chem.201200184

DOI: 10.1002/chem.201200184
Iron Thiolate Complexes: Efficient Catalysts for Coupling Alkenyl Halides
with Alkyl Grignard Reagents
Gꢀrard Cahiez,* Olivier Gager, Julien Buendia, and Cindy Patinote[a]
À
Recently, iron-catalyzed C C coupling reactions have
been extensively studied because they are an interesting
way to avoid using palladium or nickel complexes, which are
toxic and/or expensive. Valuable advances have been made
in this field over the last few years by our group[1] and
others,[2] however, there is currently a reduction in the rate
Scheme 1. The influence of NMP on the iron-catalyzed coupling between
alkenyl halides and alkyl Grignard reagents.[1c]
of discovery and improvement of iron-catalyzed coupling re-
actions. In fact, most reactions reported until now use FeCl3
or most frequently [FeACHTNUGTRNEUNG(acac)3] (acac=acetylacetonate) as
catalysts and only a few original ligands have been pro-
posed.[3] Moreover, the majority of the ligands tested were
chosen by analogy with palladium or nickel chemistry and li-
gands specially designed for use with iron are rare. On the
basis of this observation it seemed to us that the discovery
of specific new ligands is the next challenge to improve the
couplings previously described and to widen the scope of
the application of iron catalysis in organic synthesis.
and we report herein our results concerning an efficient new
catalytic system based on iron(II) thiolates.
In the first set of experiments, iron(II) thiolates were pre-
pared by mixing FeCl3 or FeCl2 with 3 or 2 equivalents, re-
spectively, of RSMgCl[6] in THF at 08C (see the Supporting
Information). These compounds were then directly used[7] as
precatalysts to perform the coupling of 1-bromo-2-methyl-
propene with OctMgCl at between À5 and 08C (Table 1).
It is well known that iron–sulfur protein complexes are in-
volved in numerous biological processes occurring through
redox reactions and exhibit remarkable properties.[4] Even if
the catalytic intermediates involved in cross-coupling reac-
tions are quite different, we thought that it could be inter-
esting to use thiolates as ligands to modify the redox poten-
tial of the catalytic species formed during the iron-catalyzed
Grignard reactions and, consequently, their reactivity. Previ-
ously, we have shown that alkyl Grignard reagents react
with alkenyl halides chemo- and stereoselectively in the
Table 1. Cross-coupling of 1-bromo-2-methylpropene with nOctMgCl in
the presence of various iron-based catalytic systems.
Catalytic system
Yield
[%][a]
1
2
3
4
5
6
[Fe
[Fe
[Fe
[Fe
N
39
82 (76)[c]
51
88
presence of [FeACHTUNGTRENNUNG(acac)3] to give excellent yields of the cross-
[Fe(S-2-naphthyl)2] (5%)
87,[d] 90[e]
86
coupling product when N-methylpyrrolidone (NMP) is used
[Fe(S-2-naphthyl)2][e] (1%)
as a cosolvent (Scheme 1).[1c]
[a] Determined by GC analysis. Pentadecane (C15H32) was used as the in-
ternal standard. [b] Based on (CH3)2C=CHBr. [c] Yield of the isolated
product, see ref. [1c]. [d] Precatalyst prepared from FeCl3. [e] Precatalyst
prepared from FeCl2.
This procedure is very efficient, however, NMP was re-
cently identified to be a reprotoxin[5] and, in the future, it
would be preferable to limit its use for industrial applica-
tions as a part of sustainable development. Therefore, we
decided to select this reaction to perform our investigations
Iron(II) octylthiolate led to a 51% yield of 2-methylundec-
2-ene (Table 1, entry 3). This yield is not as good as with
[Fe
ACHTUNGTRENNUNG
better than with [FeAHCTUNGTRENNUNG
[a] Dr. G. Cahiez, Dr. O. Gager, Dr. J. Buendia, C. Patinote
Laboratoire de Synthꢀse Organique Sꢁlective et
de Chimie Organomꢁtallique
of various iron alkylthiolates as ligands, however, did not
allow us to obtain better results, and we, therefore, turned
our attention to iron arylthiolates. These attempts were
more successful since good yields (87–90%) were obtained
by using a precatalyst prepared from thiophenol (Table 1,
entry 4) or 2-naphthalenethiol (Table 1, entry 5). The iron
arylthiolate can be successfully prepared from either FeCl3
Department of Chemistry (UFR SMBH)
CNRS-Universitꢁ de Paris 13 (UMR 7244)
74 Rue Marcel Cachin, 93017 Bobigny (France)
E-mail: gerard.cahiez@univ-paris13.fr
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/chem.201200184.
5860
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Chem. Eur. J. 2012, 18, 5860 – 5863

COMMUNICATION
Table 3. Cross-coupling of 1-chlorodecene with nBuMgCl and iPrMgCl
in the presence of various iron-based catalytic systems.
or FeCl2 (Table 1, entry 5). It is interesting to note that the
yields obtained with iron arylthiolates are better than that
previously obtained by using [FeACTHNUTRGNENUG(acac)3] and NMP as a co-
solvant (Table 1, entry 2). Interestingly, only 1% iron 2-
naphthylthiolate is enough to efficiently catalyze the reac-
tion (Table 1, entry 6).
To study the scope and limitations of the reaction, we
chose to use iron 2-naphthylthiolate as the precatalyst
(Table 1, entries 5 and 6). Indeed, this iron thiolate always
RMgCl
Catalytic System
Yield
[%][a]
1
2
3
4
5
6
7
8
BuMgCl
BuMgCl
BuMgCl
BuMgCl
BuMgCl
iPrMgCl
iPrMgCl
iPrMgCl
[Fe
(acac)3] (5%), NMP (9 equiv)[b]
87
87
85
93
93
50
85
86
[Fe(S-2-naphthyl)2][c] (5%)
[Fe(S-2-naphthyl)2][d] (5%)
gave similar or slightly higher yields than [FeACTHNUGTRENUNG(SPh)2]. For in-
[Fe(S-2-naphthyl)2][d] (5%), NMP (7.5%)
[Fe(S-2-naphthyl)2][d] (5%), LiCl[e] (10%)
[Fe(S-2-naphthyl)2][d] (5%)
stance, the coupling of (E)-1-bromooct-1-ene with BuMgCl
led to a 90% yield of (E)-5-dodecene 3 with the 2-naphthyl-
derived catalyst instead of 85% with the phenyl-derived one
(Scheme 2).
[Fe(S-2-naphthyl)2][d] (5%), NMP (7.5%)
[Fe(S-2-naphthyl)2] (5%), LiCl[e] (10%)
[a] Determined by GC analysis. Hexadecane (C16H34) was used as the in-
ternal standard. [b] Based on OctCH=CHCl. [c] Prepared from FeCl3.
[d] Prepared from FeCl2. [e] Prepared from FeCl2·2LiCl, see ref. [9].
Alkenyl chlorides also react with alkyl Grignard reagents
in the presence of iron 2-naphthylthiolate (Table 3, entries 2
and 3). However, they are less reactive than the correspond-
ing bromides and generally gave slightly lower yields (about
5–7% less). However, we have determined that it is possible
to improve these results by working with a precatalyst ob-
tained by mixing iron 2-naphthylthiolate and NMP (1:1.5)[8]
(Table 3, entry 4). It is important to note that only 7.5%
NMP is then necessary instead of the 900% (9 equiv) re-
quired when the reaction is performed with FeCl3 or [Fe-
Scheme 2. Stereoselectivity of the reaction.
Furthermore, we have found that the reaction is highly
stereoselective (Scheme 2). Thus, (Z)- and (E)-1-bromooct-
1-enes afforded the corresponding (Z)- and (E)-olefins 3
and 4, respectively, with complete retention of configura-
tion.
Moreover, the scope of the reaction is very wide and vari-
ous mono- or disubstituted alkenyl bromides were success-
fully used (Table 2). Indeed, alkenyl bromides and iodides
led to similar yields (Table 2, entries 6 and 7).
AHCTUNGTERG(NNUN acac)3] as the catalyst. Finally, we found that NMP can be
completely eliminated because similar results were obtained
by adding 2 equivalents of LiCl to the iron 2-naphthylthio-
late[9] (Table 3, entry 5).
The beneficial influence of NMP or LiCl is more impor-
tant when the coupling is performed with a secondary alkyl
Grignard reagent. Thus, the reaction of iPrMgCl with 1-
chlorodecene led to only a 50% yield of 2-methyldodec-3-
ene in the presence of iron 2-naphthylthiolate (Table 3,
entry 6), whereas 85 and 86% yields were obtained in the
presence of iron 2-naphthylthiolate complexed with NMP
(Table 3, entry 7) or LiCl (Table 3, entry 8), respectively. It
should be noted that the same coupling performed accord-
Table 2. Iron-catalyzed coupling of alkenyl bromides or iodides with pri-
mary alkyl Grignard reagents.
Alkenyl halide
Product
Yield
[%][a]
1
2
3
93
92
85
ing to the previous procedure ([FeACHTUNGTRNEUNG
(acac)3] (5%)/NMP)[1c]
leads to only a 62% yield. Various alkenyl chlorides
(Table 4, entries 1–3), as well as secondary alkyl Grignard
reagents (Table 4, entries 3–5 and 7–9), were coupled suc-
cessfully under these reaction conditions. It is also possible
to introduce a tertiary alkyl group, although the yield is
lower because a competitive b-hydrogen elimination reac-
tion probably occurs (Table 4, entry 6). It should be noted
that these results compare advantageously to those obtained
4
87
5
6
90
93
with the previous procedure ([Fe
ACHTUNGTERN(NGNU acac)3] (1%), NMP
(9 equiv)).[1c]
The reaction is highly chemoselective, and thus, various
functionalized Grignard reagents were used successfully
(Table 5). It is interesting to note that the use of a magnesi-
7
93
[a] Yield of the pure isolated product. Precatalyst: [Fe(S-2-naphthyl)2].
Chem. Eur. J. 2012, 18, 5860 – 5863
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www.chemeurj.org
5861

G. Cahiez et al.
Table 4. Iron-catalyzed coupling of alkenyl chlorides or bromides with
alkyl Grignard reagents.
Table 6. Selective iron-catalyzed coupling of functionalized alkenyl hal-
ides.
R from
RMgCl
Alkenyl
halide
Product
Yield
[%][a]
R from Functionalized
RMgCl alkenyl halide
Product
Yield
[%][a]
1
2
3
Bu
75[b]
77[c]
84[b]
1
2
Bu
89
Bu
sBu
71[b]
c-Hex
4
5
iPr
78[c]
76[c]
3
c-Hex
80[b]
c-Hex
4
5
Bu
Bu
82
85
6
7
tBu
sBu
59[b]
[a] Yield of the isolated product. [b] The precatalyst was prepared by
mixing FeCl3 (5%), 2-naphthylSMgCl (15%), and NMP (7.5%).
90,[b] 87[c]
8
9
sBu
89[b]
c-Hex
82[b,c]
[a] Yield of the isolated product. [b] Precatalyst: [Fe(S-2-naphthyl)2]
(5%), NMP (7.5%). [c] Precatalyst: [Fe(S-2-naphthyl)2] (5%), LiCl
(10%).
Scheme 3. Iron thiolate-catalyzed aryl–alkyl coupling reactions.
lective than the previous [FeACHTNUGRTNEUNG
(acac)3]/NMP procedure.[2a] For
instance, coupling product 31, prepared from 4-chlorobenzo-
nitrile, was obtained in only 55% yield under these new re-
action conditions.
Table 5. Iron-catalyzed alkenylation of functionalized alkyl Grignard re-
agents.
Grignard
reagent
Product
Yield
[%][a]
In summary, we have shown that iron(II) arylthiolate
complexes are effective precatalysts for the iron-catalyzed
coupling reaction of alkenyl or aryl halides with alkyl
Grignard reagents. The reaction proceeds highly chemo- and
stereoselectively and, moreover, the yields are often slightly
better than those obtained through the previously described
1
2
94
88
3
4
93
90
procedure that uses [FeACTHNUTRGNE(NUG acac)3] in the presence of NMP as
a cosolvent. This is the first iron-catalyzed coupling proce-
dure by using thiolates as ligands. It is important to note
that, in contrast to the related previous procedures, NMP is
not required as a cosolvent, which is especially interesting
for industrial applications because NMP was recently identi-
fied as a reprotoxin.[5]
5
79[e]
[a] Yield of the isolated product. [b] From PhCH=CHBr, E/Z=85:15.
[c] From MeCH=CHBr, E/Z=71:29. [d] From HexCH=CHBr, E/Z=
97:3. [e] Overall yield after hydrolysis of the acetal.
um alcoholate did not perturb the reaction (Table 5, en-
tries 2–4).
Keywords: alkenes · alkenylation · cross-coupling · Grignard
reaction · iron · iron-catalyzed reactions · thiolates
Functionalized alkenyl halides were also coupled in good
yields (Table 6). For instance, ester (Table 6, entry 4), enone
(Table 6, entries 1–3) and even ketone (Table 6, entry 5)
groups are well tolerated by these reaction conditions.
Iron(II) 2-naphthylthiolate can also be used as the preca-
talyst to couple aryl halides with alkyl Grignard reagents
(Scheme 3). As with alkenyl halides, the use of NMP is not
necessary. However, the reaction is sometimes less chemose-
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Chem. Eur. J. 2012, 18, 5860 – 5863

Iron Thiolate Complexes
COMMUNICATION
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a mixture of FeCl3 and RSH, but the yields of coupling products are
generally slightly lower if this procedure is utilized. Thus, under the
same reaction conditions (Table 1, entry 5), 1-bromo-2-methylpro-
pene then reacts with OctMgCl to afford 2-methyl-2-decene in 86 in-
stead of 90% yield.
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[7] A precatalyst stored for 24 h at room temperature led to the same re-
sults.
[8] The complex [(FeCl3)2ACTHNUTRGNE(NUG dmf)3] has been described. See: K. Ogura, T.
Koyama, S. Seto, J. Am. Chem. Soc. 1972, 94, 307. We discovered that
it is possible to prepare a similar complex with NMP: [(FeCl3)2-
AHCTUNGRTEG(NNNU nmp)3]. The ratio FeCl3/NMP is 1:1.5.
[9] [Fe(S-2-naphthyl)2] can be prepared from either of the ate complexes
FeCl2·2LiCl or FeCl3·2LiCl. It should be noted that the addition of
LiCl does not significantly improve the yield when the reaction is per-
formed with 5% FeCl3. Thus, the coupling of OctCH=CHCl with
BuMgCl led to a 56% yield of OctCH=CHBu in the presence of 5%
FeCl3 and a 57% yield in the presence of 5% FeCl3·2LiCl.
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Received: January 17, 2012
Published online: March 29, 2012
Chem. Eur. J. 2012, 18, 5860 – 5863
ꢂ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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5863