Iron-catalyzed cross-coupling of alkyl halides with alkenyl Grignard reagents

Article abstract of DOI:10.1002/anie.200702206

(Chemical Equation Presented) Cheap and safe: An iron-catalyzed cross-coupling reaction between alkyl halides and alkenyl Grignard reagents is described. This C-C bond coupling reaction is promoted by the cheap and nontoxic FeCl₃ and displays good tolerance against various functional groups.

Full text of DOI:10.1002/anie.200702206

Angewandte
Chemie
DOI: 10.1002/anie.200702206
Homogeneous Catalysis
Iron-Catalyzed Cross-Coupling of Alkyl Halides with Alkenyl
Grignard Reagents
Amandine GuØrinot, SØbastien Reymond, and Janine Cossy*
À
Transition-metal-catalyzed C C bond coupling between vinyl
metal reagents and unactivated alkyl halides is a useful
reaction[1–3] that can be realized using copper,[4] palladium,
[1–3,5]
nickel,or cobalt complexes as catalysts.
For example,
primary alkyl bromides can be coupled with alkenyl tin
reagents using
a
palladium-catalyzed Stille coupling.[6]
Negishi cross-coupling reactions of alkyl halides with alkenyl
zinc reagents[7] or with alkenyl zirconium species[8] also
proceeded in the presence of palladium complexes. Recently,
[Co(acac)3] (acac = acetylacetonate) was used as a catalyst for
the cross-coupling reaction of primary and secondary alkyl
halides with 1-(trimethylsilyl)ethenylmagnesium.[9] This reac-
tion was shown to proceed through a radical pathway,and the
cross-coupling products were obtained in good to excellent
yields. Nevertheless,20 to 40 mol% of the cobalt complex
were required,and no reaction occurred with other alkenyl
Grignard reagents.[9]
Scheme 1. Cross-coupling between alkenyl Grignardreagents andalkyl
halides catalyzed by FeCl3.
As synthetic organic methods are increasingly concerned
with the growing importance of sustainable chemistry,iron-
catalyzed cross-coupling reactions are one of the promising
Scheme 2. Influence of the FeIII source on catalysis of the cross-
coupling between alkenyl Grignard I and alkyl iodide 1.
À
research areas for the construction of C C bonds,since iron is
inexpensive and more environmentally friendly than palla-
[10,11]
dium,cobalt,or nickel.
After the pioneering works of
When the reaction was performed in the presence of FeCl3
(10 mol%) and N,N,N’,N’-tetramethylethylenediamine
(TMEDA,1.9 equiv) in THF at 0 8C for 10 min and then at
room temperature for 30 min,compound 2 was obtained in
70% yield as a mixture of (E)- and (Z)-isomers (Scheme 2).[19]
To ensure full conversion of the starting material,dropwise
addition of the alkenyl Grignard reagent at 08C over 1 h was
essential.
In order to simplify the analysis of the cross-coupled
products,three other alkenylmagnesium bromides II, III
(commercially available),and IV (prepared from the corre-
sponding bromide;[9] Scheme 3) of a single configuration were
examined in the FeCl3-catalyzed alkenylation of halides 1–15.
Kochi and co-workers in the 1970s,[12,13] only recently have the
groups of Cahiez,[14] Fürstner,[15] and Nakamura,[16] extended
the scope of iron-catalyzed processes,notably by developing
efficient cross-coupling reactions between aromatic Grignard
reagents and alkyl halides.[17] Although coupling reactions
between vinyl bromide derivatives and alkyl Grignard
reagents have been reported using the iron catalyst [Fe-
(acac)3],[14c] to our knowledge,the iron-catalyzed cross-
coupling reaction between alkyl halides and alkenyl Grignard
reagents has never been reported. Herein,we report that
FeCl3 efficiently catalyzes cross-coupling reactions between
various alkyl halides and alkenyl Grignard reagents in good to
excellent yields (Scheme 1).
When
a solution of alkenylmagnesium bromide II
We first turned our attention to [Fe(acac)3] as the catalyst
(40 mol%).[18] When alkyl iodide 1 was treated with 1-methyl-
1-propenylmagnesium bromide I (7:3 mixture of (E)- and (Z)-
isomers,2 equiv) in THF/NMP (NMP = N-methyl-2-pyrroli-
done) from 08C to room temperature for 2 h,no conversion
was observed (Scheme 2). We next examined the conditions
developed by Nakamura for the cross-coupling reaction
between aromatic Grignard reagents and alkyl halides.[16]
(2 equiv) and TMEDA (1.9 equiv) in THF was slowly added
over 1 h at 08C (at a rate of around 5 mLhÀ1) to a solution of
alkyl iodide 1 and FeCl3 (10 mol%) in THF,olefin 16 was
formed in 87% yield. This coupling reaction appeared to be
general,as alkyl halides 2–6 and 9–12 were transformed to the
corresponding olefinic compounds 17–21 and 22–25 using the
above-mentioned conditions (Table 1). Olefin 17 was isolated
[*] A. GuØrinot, Dr. S. Reymond, Prof. Dr. J. Cossy
Laboratoire de Chimie Organique, ESPCI, CNRS
10 Rue Vauquelin, 75231 Paris Cedex 05 (France)
Fax : (+33)1-4079-4660
Scheme 3. Alkenyl Grignardreagents examinedin the FeCl 3-catalyzed
cross-coupling reaction with halides 1–15.
E-mail: janine.cossy@espci.fr
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Table 1: FeCl3-catalyzedcross-coupling reaction of alkenyl Grignard II
with halides 1–15.[a]
compatible with polar functionalities,as bromoacetal
6
could be transformed to the olefinic acetal 21 in 50% yield.
Concerning bromoesters 7–9,the position of the ester group
relative to the halide showed an important influence on the
outcome of the cross-coupling reaction. When a-bromoester 7
or b-bromoester 8 was examined,complex reaction mixtures
were observed with no trace of the cross-coupling product.
Nevertheless,when the ester functionality was present at the
d-position,ethyl 5-bromovalerate ( 9) was converted to the
olefinic ester 22 in good yield (62%).
Entry
Halide
Product (yield of isolated product)
1
2[b]
3
The cross-coupling reaction with secondary alkyl bro-
mides was also effective. Cycloheptyl bromide (10) was
transformed into the corresponding alkene 23 in 94% yield
4
[20]
(Table 1,entry 10).
Benzyl 4-bromopiperidine-1-carboxyl-
ate (11) was transformed to 24,which was isolated along with
the elimination product 24’ and the reduction product 24’’ in
70% yield and a ratio of 7:2:1 (for the origin of these
byproducts,see the proposed mechanism below). However,
when the linear secondary alkyl bromide 12 was treated with
Grignard II,the cross-coupling product 25 was isolated as a
mixture with the elimination products 25’ and 25’’. Alkyl
chlorides and aryl halides are unreactive under the reaction
conditions (Table 1,entries 13–15).
5
6[b]
7
8
To evaluate the scope of this cross-coupling,alkenyl
Grignard reagents III and IV were reacted with alkyl halides
1–3, 5, 9 and 26 under the same reaction conditions but with
5 mol% FeCl3.[21] These results are summarized in Table 2.
The olefinic compounds 27–32 resulting from the cross-
9
10[c]
Table 2: FeCl3-catalyzedcross-coupling reaction of alkenyl Grignard III and IV
with alkyl halides.[a]
11[b][d]
Alkenyl Grignard III
Entry Halide Product (yield)
IV
Product (yield)
12[c][d]
1
2
13[e]
14
15
3
4
[a] See the Experimental Section for general procedure; TBDPS=
tBuPh2Si, TIPS=iPr3Si, Cbz=benzyloxycarbonyl. [b] Reaction carried
out using 5 mol% of FeCl3. [c] Yielddeterminedby NMR spectroscopy.
[d] Ratio determined by GC–MS analysis. [e] Reactions with alkyl
chlorides are sluggish and lead to complex reaction mixtures.
5[b]
in an excellent yield (98%) from phenethyl iodide 2. When
alkyl bromides were used,the cross-coupling reaction was still
efficient; olefins 18–20 were obtained in yields around 80%
from bromides 3–5. In the case of (3-bromo-butoxy)benzene
(5),olefin 20 was isolated as a 13:1 mixture with the
6[c]
[a] Reactions carried out according to the general procedure using 5 mol% of
FeCl3. [b] Reaction carriedout using 10 mol% of FeCl 3. [c] Yielddeterminedby
elimination product 20’. The coupling reaction is also NMR spectroscopy.
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Angewandte
Chemie
coupling reaction between 1–3, 5, 9,and 26 with reagent III
were isolated in yields similar to those obtained with alkenyl
Grignard II,except for compound 31,which was obtained in
higher yield (98%) from ethyl 5-bromovalerate (9).
Concerning the alkenyl Grignard reagent IV,which was
prepared from the commercially available (1-bromovinyl)tri-
methylsilane,[9] the yields obtained for the cross-coupling
products were in general lower than those previously
obtained with reagents II or III. Moreover,cross-coupling
products 34 and 36 were isolated along with the elimination
and reduction products,and the analyses of the crude reaction
mixtures for compounds 33, 34, 36,and 37 showed the
formation of the homocoupled product 2,3-bis(trimethyl-
silyl)-buta-1,3-diene (35). The formation of these byproducts
is probably the result of a competitive pathway (dispropor-
tionation,pathway A in Scheme 4),which can be rationalized
by the mechanism for the coupling of aryl Grignards and alkyl
Scheme 5. Cross-coupling between alkenyl Grignardreagents andalkyl
halides 38 and 41.
radical clock than iodo olefin 38. When 41 and Grignard III
were allowed to react,the major compound observed by GC–
1
MS and H NMR spectroscopy of the crude product was the
linear cross-coupling product 42 derived from the radical
opening of the cyclopropyl ring prior to the cross-coupling
with Grignard III (Scheme 5).
This result suggests that the iron-catalyzed cross-coupling
of alkenyl Grignard reagents with alkyl halides probably
proceeds by a radical pathway (single electron transfer
mechanism) for the oxidative addition step (Scheme 4).
However,the mechanism of this reaction remains obscure
and both organometallic and radical pathways could be
operational.[22]
In summary,we have reported the first iron-catalyzed
cross-coupling reaction between alkyl halides and alkenyl
Grignard reagents. This FeCl3-mediated reaction is selective,
as no coupling products were observed with aryl halides. The
reaction also tolerates various functionalities such as ethers,
À
Scheme 4. Plausible mechanism for the alkenyl–alkyl coupling.
halides proposed by Hayashi (Scheme 4).[17a] In the original
Hayashi mechanism,[17a] the oxidative addition step proceeds
through a concerted pathway,contrary to the mechanism
recently proposed by Cahiez in which the iron-catalyzed
coupling of aryl Grignard and alkyl halides would occur
through a two-step single-electron transfer.[14e]
acetals,esters,amides,and silyl ethers. This C
C bond
coupling reaction catalyzed by the inexpensive and environ-
mentally friendly FeCl3 seems to proceed by a radical
mechanism.
To determine if a radical pathway was operational under
our cross-coupling conditions,we first turned our attention to
iodo olefin 38 (Scheme 5). Indeed,it has been shown that d-
unsatured alkyl halides could afford 5-exo-trig cyclization
prior to the cross-coupling with aryl Grignard reagents.[15b,23]
The treatment of iodo olefin 38 under our reaction conditions
with reagents II or IV produced direct cross-coupling
products 39 and 40,respectively,and no trace of the cyclized
product was observed (Scheme 5). However,this result is
inconclusive,since Martin and Fürstner reported that 5- exo-
trig cyclization prior to the cross-coupling reaction was highly
substrate-dependant.[15b] Consequently,we studied the reac-
tion with cyclopropylmethyl bromide (41),which is a faster
Experimental Section
General procedure: A solution of the alkenyl Grignard reagent (0.5m
in THF,2 equiv) and TMEDA (1.9 equiv) was added dropwise (at a
rate of around 5 mLhÀ1) using a syringe pump to a solution of alkyl
halide (1 equiv) and FeCl3 (10 mol%) in THF at 08C. After further
30 min at 08C,the reaction mixture was quenched by adding an
aqueous saturated NH4Cl solution. After extractive workup,the
crude product was purified by silica-gel chromatography.
Received: May 18,2007
Revised: June 28,2007
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Communications
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Keywords: alkyl halides · Grignard reagents ·
homogeneous catalysis · iron · sustainable chemistry
.
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[20] Yield determined by NMR spectroscopy.
[21] Other alkenyl Grignard reagents were also examined. When
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styrylmagnesium bromide was used,incomplete conversion was
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