Iron-catalyzed desulfinylative C-C cross-coupling reactions of sulfonyl chlorides with grignard reagents

Article abstract of DOI:10.1002/anie.200704858

(Chemical Equation Presented) A friendly couple: Conditions have been uncovered that allow the desulfinylative C-C cross-coupling reaction of inexpensive sulfonyl chlorides and Grignard reagents (see scheme, acac = acetylacetonate, NMP = N-methylpyrrolidone). The reactions rely on environmentally friendly iron catalysts and do not require expensive and/or toxic ligands.

Full text of DOI:10.1002/anie.200704858

Angewandte
Chemie
DOI: 10.1002/anie.200704858
Homogeneous Catalysis
À
Iron-Catalyzed Desulfinylative C C Cross-Coupling Reactions of
Sulfonyl Chlorides with Grignard Reagents**
Chandra M. Rao Volla and Pierre Vogel*
Dedicated to Professor Horst Prinzbach on the occasion of his birthday
Carbon–carbon cross-coupling reactions are very important
in the areas of material science and medicinal chemistry. Most
current methods require expensive transition-metal catalysts
ence of Pd- or Ni-based catalysts, only products of aryl–aryl
homocoupling were formed. Alkanesulfonyl chlorides are
[
16]
not suitable reagents in Pd-catalyzed desulfinylative CÀC
(
for example, based on Cu, Pd, Co, Ni, Pt, Ru, and Rh) and
cross-coupling reactions as they undergo concurrent b elimi-
nation with the formation of the corresponding alkenes.
Herein we report for the first time that alkane- and
alkenesulfonyl chlorides undergo smooth desulfinylative
CÀC cross-coupling reactions with Grignard reagents in the
ligands (for example, phosphines). Early reports by Kharasch
[1]
[2]
and Reinmuth in 1954 and then by Tamura and Kochi in
971 suggested that inexpensive Grignard reagents and alkyl
halides can be coupled in the presence of iron catalysts
Scheme 1, Equation (1)].
1
[
presence of catalytic amounts of [Fe(acac) ] (acetylacetonate)
3
without the need for any extra ligands.
Treatment of n-octanesulfonyl chloride with PhMgBr in
THF at 808C in the presence of [Fe(acac) ] (5 mol%)
3
afforded the coupling product n-octylbenzene in 28% yield,
together with 5% of the corresponding sulfone (n-octylphe-
nylsulfone; Table 1, entry 2). In the absence of any catalyst
Scheme 1. Fe-catalyzed cross-coupling reaction ofGrignard reagents
with alkyl halides and the Fe-catalyzed acylation ofGrignard reagents.
Table 1: Optimization ofthe reaction conditions of r the Fe-catalyzed
Apart from a few exceptions, this discovery remained
dormant until 1992, when studies by Cahiez et al. and more
desulfinylative CÀC cross-coupling reaction of nOctSO Cl with PhMgBr.
2
[
3]
[
4]
[5]
recently by the research groups of Fürstner, Knochel,
[
a]
[a]
[
6]
[7]
[8,9]
Entry Conditions
iron catalyst (equiv)
nOctPh [%] nOctSO Ph [%]
2
Nakamura, Bedford, and Cossy.
However, in 1982
[
10]
Julia and co-workers reported the Fe-catalyzed CÀC cross-
coupling reaction of Grignard reagents with vinylic sulfones,
while in 1983 Molander et al. reported the Fe-catalyzed cross-
1
2
3
no catalyst, 08C to RT
–
28
76
5
–
[
b]
[Fe(acac) ] (5%), THF, 808C
3
[
11]
FeCl (10%), TMEDA (2 equiv), decomp
3
coupling of aryl Grignard reagents with alkenyl halides, and
[
c]
[
12]
THF, 808C
in 1984 Marchese and co-workers
developed the
[
d]
4
5
[Fe(acac) ] (5%), THF, 808C
16
58
48
–
3
Fe-catalyzed acylation of Grignard reagents [Scheme 1,
Equation (2)].
[Fe(acac) ] (5%), TMEDA
3
[e]
(
10%), THF, 808C
Our research group has demonstrated that sulfonyl
chlorides can be used as electrophilic partners in desulfiny-
lative CÀC cross-coupling reactions catalyzed by palladium
6
7
[Fe(acac) ] (5%), HMTA(10%), 65
–
–
3
[
e]
THF, 808C
[Fe(acac) ] (5%), THF/NMP,
72
3
[
e]
[
13]
[14]
808C
complexes or palladium nanoparticles in ionic liquids.
However, when we attempted to carry out desulfinylative
[a] Yield determined after flash chromatography. [b] Grignard reagent
was added immediately. [c] Starting materials were decomposed and no
cross-coupled product or sulfone was observed. [d] Reaction was done in
a microwave reactor, Grignard reagent was added to the reaction at
À788C, and was heated for 1.5 h at 808C. [e] Grignard reagent in THF
[
15]
Corriu–Kumada CÀC cross-coupling reactions
between
Grignard reagents and arenesulfonyl chlorides in the pres-
À1
[
*] C. M. Rao Volla, Prof. Dr. P. Vogel
Laboratoire de Glycochimie et Synth›se AsymØtrique (LGSA)
Swiss Federal Institute ofTechnology (EPFL)
Batochime
was added slowly (2 mLh ). TMEDA=N,N,N’,N’-tetramethylethylene-
diamine, HMTA=hexamethylenetetramine.
1
015 Lausanne (Switzerland)
(
08C to 258C), the sulfone was the sole product, and was
Fax: (+41)21-693-9375
E-mail: pierre.vogel@epfl.ch
obtained in 76% yield (Table 1, entry 1). Importantly, when
the Grignard reagent was added slowly through a syringe
pump, the formation of the sulfone was completely sup-
pressed. Only decomposition products were observed under
the conditions developed by Nakamura et al. for the cross-
coupling reaction between aromatic Grignard reagents and
alkyl halides (Table 1, entry 3).
[
**] We are grateful to the Swiss National Science Foundation (Bern)
and the Roche Research Foundation (Basel). We also thank F.
Sepulveda, M. Rey, and A. Razaname for their technical help, as well
as A. Yella and Dr. S. R. Dubbaka for helpful discussions.
[
6]
Supporting information for this article is available on the WWW
under http://www.angewandte.org or from the author.
Angew. Chem. Int. Ed. 2008, 47, 1305 –1307
ꢀ 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
1305

Communications
When the reaction was carried out in refluxing diethyl
Table 2: Scope ofthe Fe-catalyzed desul fi nylative C ÀC cross-coupling reaction
ofsul of nyl chlorides with Grignard reagents.
ether or 1,2-dimethoxyethane (DME), the yields were
low because of the competitive homocoupling of the
Grignard reagents. If carried out at 258C, the reaction
gives a larger proportion of the sulfone, as expected for
all our desulfinylative CÀC cross-coupling reac-
[
a]
Entry
R
R’
Product
Yield [%]
1
2
3
4
5
6
7
8
9
Ph
Ph
Ph
Ph
nBu
BuPh
nOctPh
61
72
[
13,14,16]
[3]
tions.
Additives such as TMEDA and HMTA
[b]
n-C H
8
17
were beneficial to the reaction (Table 1, entries 5 and
). The best yield of n-octylbenzene was obtained in the
n-C H
C H Ph
54
47
23
46
35
1
0
21
33
10 21
6
n-C16
H
C H33Ph
16
dec-1-ene
2-methyldec-1-ene
2-methylundec-2-ene
1-methyl-4-octylbenzene 68
CH =CH
CH =C(Me)
Me
4-MeC H
n-C H
absence of any ligand and using a mixture of THF and N-
methylpyrrolidone (NMP) as the solvent at 808C
2
8
17
n-C H
2
8
17
17
17
17
C
=
CH
n-C H
[3]
2
8
(
Table 1, entry 7). We found that the yield of the CÀC
n-C H
6
4
8
cross-coupling reaction depends on the quality of the
[c]
4-MeOC H
n-C H
1-methoxy-4-octylben-
zene
82
6
4
8
Grignard reagent. Interestingly, no CÀC cross-coupling
[
d]
product was observed in the reaction of PhMgBr or
10
11
allyl
Ph
n-C H
–
–
8
17
PhMgCl with n-octyl chloride in the presence of [Fe-
Bn
Bn
diphenylmethane
4-methylC H Bn
55
58
6
12
13
14
15
4-MeC H
PhCH CH MgCl n-C H
Ph
Ph
(
acac) ]. This result shows that sulfonyl chlorides are
6
4
6
4
3
C H Ph
2
2
8
17
10 21
better electrophilic partners than the corresponding
chlorides in these reactions. Our optimized conditions
were then applied to a wide range of sulfonyl chlorides
and Grignard reagents (Table 2).
[
d]
EtOCOCH2
1-ethyl-
–
a-
–
78
naphthyl
n-C H
iPr
iPr
(PhCH CH )naphthalene
2 2
a-(n-octyl)naphthalene
cumene
16
17
a-naphthyl
Ph
traces
24
29
8
17
Unlike alkyl halides, which were found to react
sluggishly with alkenyl Grignard reagents under the
18
4-MeC H
p-cymene
6
4
[
6]
19
4-MeC H
sBu
2-(4-methylphenyl)bu-
tane
64
6
4
conditions developed by Nakamura et al., alkanesul-
fonyl chlorides undergo the desulfinylative CÀC cross-
2
2
2
23
24
0
1
2
Ph
Ph
sBu
2-phenylbutane
phenylcyclopentane
4-cyclopentylanisole
phenylcyclohexane
2-cyclohexylpropene
57
63
71
68
48
coupling reaction with alkenyl Grignard reagents. Unex-
pectedly, allyl- and benzylmagnesium bromides failed to
give CÀC cross-coupling products; only decomposition of
cyclopentyl
cyclopentyl
cyclohexyl
cyclohexyl
4-MeOC H
Ph
CH C(Me)
2=
6
4
n-octanesulfonyl chloride into
[
[
[
e]
e]
e]
1
-chlorooctane was observed. No 1-chlorooctane was
25
n-C H
68
61
55
6
13
observed when n-octanesulfonyl chloride was heated
either alone in deuterated THF or in the presence of
26
n-C H
8
17
[
[
Fe(acac) ] in THF. This experiment demonstrates that
Fe(acac) ] alone is not capable of catalyzing the
27
Ph
Ph
4-MeC
(E)-stilbene
R=Ph
3
3
28
29
34
32
42
desulfinylation of sulfonyl chlorides. The required cata-
lyst must be a reduced form of Fe resulting from the
reaction of [Fe(acac) ] with the Grignard reagents.
H
6
4
R=4-MeC
R=4-
H
6 4
30
4-MeOC H
6
4
[
4,9]
MeOC H
6 4
3
Interestingly, (E)-styrenesulfonyl chloride reacted
with phenyl-, n-hexyl-, and n-octylmagnesium bromide
to give exclusively E alkenes ( H NMRanalysis of the
crude reaction mixture). Unknown camphor derivatives
were obtained by applying the methodology to camphor-
sulfonyl chloride and various Grignard reagents. These
compounds might be useful as chiral auxiliaries and ligands.
[
a] Yields of isolated products after flash chromatography. [b] 56% yield using
PhMgCl instead ofPhMgBr. [c] 61% yield fo r the reaction at 25 8C, concurrent
formation of the corresponding sulfone. [d] No C C cross-coupling product
observed. [e] E alkene is formed exclusively. Bn=benzyl.
1
À
A possible mechanism for our desulfinylative CÀC cross-
coupling reaction of sulfonyl chlorides with Grignard reagents
is shown in Scheme 2. As proposed by Fürstner and co-
[
4]
workers, low-valent iron species probably react in a similar
0
fashion as Pd catalysts. At this stage we cannot exclude a
multiple-step process that involves radical intermedi-
[7,17,18]
ates
during the formal oxidative additions and reductive
eliminations of the metallic catalytical species.
For the first time, conditions have been uncovered that
allow the desulfinylative CÀC cross-coupling of inexpensive
sulfonyl chlorides and Grignard reagents. These conditions
rely on environmentally friendly iron catalysts and do not
require expensive and/or toxic ligands.
Scheme 2. Hypothetical mechanism for the desulfinylative CÀC cross-
coupling reaction ofsul of nyl chlorides and Grignard reagents catalyzed
Received: October 19, 2007
by [Fe(acac) ]. L=THF or NMP.
Published online: January 3, 2008
3
1
306
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Angewandte
Chemie
Keywords: cross-coupling · Grignard reagents ·
homogeneous catalysis · iron · sulfonyl chlorides
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