Iron-catalyzed C-N cross-coupling of sulfoximines with aryl iodides

Article abstract of DOI:10.1002/adsc.200700508

An inexpensive and experimentally simple, iron-catalyzed N-arylation reaction of NH-sulfoximines with aryl iodides is reported. This complementary method to the known palladium- and copper-catalyzed ones features the use of a combination of environmentall

Full text of DOI:10.1002/adsc.200700508

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DOI: 10.1002/adsc.200700508
À
Iron-Catalyzed C N Cross-Coupling ofSulfoximines with Aryl
Iodides
Arkaitz Correaa and Carsten Bolma,*
a
Institut für Organische Chemie der RWTH Aachen, Landoltweg 1, 52056 Aachen, Germany
Phone: (+49)-241-809-4675; fax: (+49)-241-809-2391; e-mail: carsten.bolm@oc.rwth-aachen.de
Received: October 22, 2007; Revised: December 12, 2007; Published online: February 5, 2008
Supporting information for this article is available on the WWW under http://asc.wiley-vch.de/home/.
Abstract: An inexpensive and experimentally
simple, iron-catalyzed N-arylation reaction of NH-
sulfoximines with aryl iodides is reported. This com-
plementary method to the known palladium- and
copper-catalyzed ones features the use of a combi-
nation of environmentally friendly FeCl3 and N,N’-
dimethylethylenediamine (DMEDA) as catalytic
system and allows the efficient preparation of vari-
ous N-arylsulfoximines in high yields.
and N,N’-dimethylethylenediamine (DMEDA) as che-
lating ligand.
Despite their applications as chiral auxiliaries and
precursors for biologically relevant molecules,[9,10] sul-
foximines have attracted a great deal of attention due
to their effectiveness as versatile chiral ligands for
asymmetric catalysis.[11] The construction of the NH-
sulfoximine core is well-established,[9,12] and among
the modifications on its four substituents, the aryla-
tion at the sulfoximine nitrogen atom is of particular
interest, given the importance of the resulting N-aryl
sulfoximine derivatives. Hence, we have extensively
studied this transformation and several protocols uti-
lizing either palladium or copper catalysts were de-
scribed.[13] Pleasingly, we have now found that such a
cross-coupling reaction can be catalyzed by inexpen-
À
Keywords: N-arylation; C N cross-coupling; homo-
geneous catalysis; iron; sulfoximines
The development of cost-efficient and environmental- sive and easy-to-handle iron salts, and the experimen-
À
ly friendly, metal-catalyzed C N cross-coupling proto- tal results are disclosed in this communication.
cols for the preparation of valuable nitrogen com-
We initiated our study by selecting the coupling of
pounds is one of the most pressing goals for modern phenyl iodide (1a) and (rac)-S-methyl-S-phenylsulfox-
chemistry and chemical industry.[1] So far, this field imine (2) as a model reaction. The results of this pre-
has been largely dominated by palladium-[2] and liminary screening are summarized in Table 1. When
copper-based[3] methods and, despite their efficiency, applying the previously reported conditions for the
the search for alternative and less expensive catalysts iron-catalyzed N-arylation of nitrogen heterocycles
to accomplish such processes is a major focus of syn- and amides (Table 1, entry 1),[6] the target N-phenyl-
thetic organic chemists. In this context, iron salts offer sulfoximine 3a was obtained in low yield along with
attractive advantages and, due to their sustainability, unreactive NH-sulfoximine 2. The use of other bases
they are recognized as ideal catalysts mainly in the (Cs2CO3, NaO-t-Bu and K2CO3) led to the desired
[4,5]
À
field of C C cross-coupling reactions.
Along these arylated product in slightly better yields, but, unfortu-
lines, we have recently reported novel and highly nately, full conversion was not achieved in those cases
À
À
practical ligand-assisted, iron-catalyzed C N and C
(Table 1, entries 2, 3 and 4, respectively). Notably,
O cross-couplings applying either nitrogen[6] and when performing the target coupling utilizing a weak
oxygen nucleophiles,[7] respectively, together with dif- base such as K2CO3 for prolonged reaction times, full
ferently substituted aryl halides. In connection with conversion was observed and the N-phenylsulfox-
our expertise in the field of sulfoximine chemistry
A
and following with our ongoing research on the devel- entry 5). Interestingly, increasing the catalyst loading
opment of iron-based catalytic processes,[8] we report had a perceptibly beneficial effect on the reaction
herein the development of an advantageous N-aryla- outcome and the desired product 3a was obtained in
tion reaction of NH-sulfoximines with aryl iodides. yields ranging from 65 to 99% after 24 h (Table 1, en-
The success of latter protocol relies on the employ- tries 6, 7 and 8). We concluded thus that the optimal
ment of a combination of catalytic amount of FeCl3 conditions for the N-arylation of sulfoximine 2 in-
Adv. Synth. Catal. 2008, 350, 391 – 394
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391

Arkaitz Correa and Carsten Bolm
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Table 1. Fe-catalyzed N-arylation of sulfoximine
phenyl iodide (1a).[a]
2
with
Table 2. Fe-catalyzed N-arylation of sulfoximine 2 with aryl
halides 1.[a]
Entry FeCl3 (equivs.) DMEDA Base
Yield of
Entry Aryl halide
X
R
Product Yield [%][b]
A
3a [%][b]
1
2
3
4
5
6
7
8
1a
1b
1c
1d
1e
1f
1g
1h
1i
I
I
I
I
I
I
I
I
I
I
I
I
H
2-OMe
2-Cl
3a
3b
3c
3d
3e
3f
3g
3h
3i
96
73
74
76
78
95
84
78
86
78
88
83
9
1
2
3
4
5
6
7
8
9
10
0.10
0.10
0.10
0.10
0.10
0.15
0.20
0.30
0.20
0
0.20
0.20
0.20
0.20
0.20
0.30
0.40
0.40
0
K3PO4
Cs2CO3
NaO-t-Bu 43
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
24
16
2-I
40
2-Me
3-Me
3,5-Me2
4-OMe
4-F
4-NO2
4-Me
4-CO2Et 3l
82[c]
65
96
99
trace
trace
9
10
11
12
13
14
15
16
1j
1k
1l
1m
1n
1o
1p
3j
3k
0.40
[a]
Reaction conditions: 1a (1.5 equivs.), 2 (1.0 equiv.), FeCl3,
DMEDA, base (2.0 equivs.), toluene (1 mLmmolÀ1 of 2),
1358C, 24 h, argon atmosphere.
Yield of isolated product after flash chromatography.
Reaction time: 72 h.
Br
H
3a
3n
3h
3p
Br 4-CF3
Br 4-OMe
Br 3-NO2
12
trace
10
[b]
[c]
[a]
Reaction conditions: 1 (1.5 equivs.), 2 (1.0 equiv.), FeCl3
(0.20 equivs.), DMEDA (0.40 equivs.), K2CO3 (2.0
equivs.), toluene (1 mLmmolÀ1 of 2), 1358C, 24 h, argon
atmosphere.
volved the use of a combination of 20 mol% of FeCl3
and 40 mol% of DMEDA in the presence of K2CO3
as base in toluene at 1358C.[14] Note that variable
yields were observed according to the purity and com-
[b]
Yield of isolated product after flash chromatography.
This valuable protocol was not restricted to the em-
mercial origin of the required FeCl3.[15] Test reactions ployment of S-methyl-S-phenylsulfoximine (2) as nu-
in the absence of either ligand (Table 1, entry 9) or cleophile and proved also applicable for the efficient
iron source (Table 1, entry 10) verified the crucial role N-arylation of other NH-sulfoximines with phenyl
that both species played in the described coupling iodide as reacting partner. Particularly noteworthy is
process.[16] When the latter reaction was performed in that even sulfoximines bearing bulky substituents at
the presence of air and moisture the target product the a-carbon were reactive and that their coupling
was obtained in a remarkable 82% yield. Additional- proceeded well too (Scheme 1).
ly, the coupling of enantiopure sulfoximine (S)-2 and
In summary, we have developed an efficient and ex-
phenyl iodide (1a) provided the sulfoximine 3a as a perimentally simple ligand-assisted iron-catalyzed N-
single enantiomer.[17] Therefore, the present iron cata- arylation of various NH-sulfoximines with differently
lyst can indeed be a practical alternative to effect the substituted aryl iodides. The key finding for this pro-
À
target C N cross-coupling and appears suitable for in- tocol is the catalytic effect of a combination of readily
dustrial-scale synthesis, when financial, operational available and inexpensive FeCl3 and DMEDA. Our
and environmental issues are of concern.
results expand the application of iron salts as promis-
The scope of the iron-catalyzed arylation of NH- ing cost-efficient catalysts in organic synthesis, and
sulfoximines was subsequently explored, and the in- hence further investigation to improve the catalyst
fluence of differently substituted aryl halides was performance as well as mechanistic studies are in
evaluated. Both electron-rich (R=Me, OMe) and progress in our laboratories.
electron-poor (R=Cl, I, F, NO2, CO2Et) aryl iodides
coupled with sulfoximine 2 in excellent yields (73–
96%, Table 2, entries 1–12). Furthermore, it is re-
markable that ortho substituents did not hamper the
Experimental Section
N-arylation process. Unfortunately, aryl bromides
were less reactive and furnished the corresponding N-
General Procedure for N-Arylation ofSulfoximines
arylsulfoximines 3 in much lower yields (Table 2, en-
tries 13–16).
A sealable tube equipped with a magnetic stir bar was
charged with NH-sulfoximine (1.0 equiv.), anhydrous FeCl3
392
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Adv. Synth. Catal. 2008, 350, 391 – 394

À
Iron-Catalyzed C N Cross-Coupling of Sulfoximines with Aryl Iodides
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Scheme 1. Fe-catalyzed N-arylation of sulfoximines 2 with
phenyl iodide (1a). Reaction conditions: 1a (1.5 equivs.), 2
(1.0 equiv.), FeCl3 (20 mol%), DMEDA (40 mol%), K2CO3
(2.0 equivs.), toluene (1 mLmmolÀ1 of 2), 1358C, 24 h (for
3r and 3s: 30 h), argon atmosphere.
[4] For general reviews, see: a) C. Bolm, J. Legros, J.
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Cossy, Angew. Chem. 2007, 119, 6641; Angew. Chem.
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115, 5645; Angew. Chem. Int. Ed. 2003, 42, 5487; b) J.
Legros, C. Bolm, Angew. Chem. 2004, 116, 4321;
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Bolm, Chem. Eur. J. 2005, 11, 1086; d) V. Lecomte, C.
Bolm, Adv. Synth. Catal. 2005, 347, 1666; e) O. G. Man-
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nishi, C. Bolm, Adv. Synth. Catal. 2007, 349, 861.
(0.20 equivs.) and K2CO3 (2.0 equivs.). The aperture of the
tube was then covered with a rubber septum, and an argon
atmosphere was established. The aryl halide (1.5 equivs.),
DMEDA (0.40 equivs.) and toluene (1 mL/mmol of sulfox-
A
placed by a teflon-coated screwcap, and the reaction vessel
was placed in a 1358C oil bath. After stirring at this temper-
ature for 24 h, the heterogeneous mixture was cooled to
room temperature and diluted with dichloromethane. The
resulting solution was directly filtered through a pad of
silica and concentrated to deliver the product, which was pu-
rified by silica gel chromatography to yield the N-arylated
product. The identity and purity of the known products was
confirmed by 1H and 13C NMR spectroscopic analysis and
the newproducts were fully characterized. See Supporting
Information for full details.
Acknowledgements
The authors are grateful to the Fonds der Chemischen Indus-
trie for financial support. A. C. thanks the Basque Govern-
ment for being supported by ꢀPrograma de Perfeccionamien-
to de Doctores en el extranjero del Departamento de Educa-
ción, Universidades e Investigaciónꢁ. We also thank Dr. M. J.
McGrath and J. Sedelmeier for providing samples of sulfox-
A
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Arkaitz Correa and Carsten Bolm
COMMUNICATIONS
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[14] Attempts to perform the target process at lower tem-
peratures failed, and 1358C proved to be a crucial tem-
perature for the coupling to occur.
[15] All experiments were carried out with anhydrous FeCl3
(purity>98%) provided by Merck. When utilizing an-
hydrous FeCl3 (purity>97%) obtained from Fluka the
coupling product was obtained in 85% yield. Using an-
hydrous FeCl3 (purity>99.99%) provided by Aldrich
led to 3a in 41% yield. Similar observations have been
recently described by Cahiez and co-workers in the
iron-catalyzed alkylation of aromatic Grignard re-
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Moyeux, Angew. Chem. 2007, 119, 4442; Angew. Chem.
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[16] Among the ligands tested, DMEDA clearly proved to
be superior to other ligands such as N,N’-dimethylgly-
cine, 2,2,6,6-tetramethyl-3,5-heptanedione or pinacolin-
ic acid in the target FeCl3-catalyzed coupling.
[17] HPLC analysis of N-phenylsulfoximine 3a: Chiralcel
OD-H. 9:1 heptane/2-propanol, 0.5 mLminÀ1
; tR =
41 min (S), tR =62 min (R).
394
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ꢀ 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2008, 350, 391 – 394