Palladium-catalyzed N-arylation of sulfoximines with aryl bromides and aryl iodides

Article abstract of DOI:10.1021/jo991342u

Various N-arylated sulfoximines have been synthesized in high yield by a direct approach which is based on a palladium-catalyzed cross-coupling strategy. Aryl bromides of variable substitution pattern were found to be the most effective coupling partners,

Full text of DOI:10.1021/jo991342u

J . Org. Chem. 2000, 65, 169-175
169
P a lla d iu m -Ca ta lyzed N-Ar yla tion of Su lfoxim in es w ith Ar yl
Br om id es a n d Ar yl Iod id es
Carsten Bolm* and J ens P. Hildebrand
Institut fu¨r Organische Chemie der RWTH Aachen, Prof.-Pirlet-Strasse 1, D-52056 Aachen, Germany
Received August 24, 1999
Various N-arylated sulfoximines have been synthesized in high yield by a direct approach which
is based on a palladium-catalyzed cross-coupling strategy. Aryl bromides of variable substitution
pattern were found to be the most effective coupling partners, whereas aryl iodides showed a
nonpredictable behavior requiring lithium or silver salts as additives to ensure product formation
in acceptable yields. Coupling of (S)-2-(2′-bromophenyl)-4-tert-butyloxazoline with enantiomerically
pure (-)-(RS)-S-methyl-S-phenylsulfoximine afforded the corresponding product in good yield as a
single diastereomer, showing that the palladium-catalyzed arylation proceeds in a stereospecific
manner. The reaction with dibromobenzenes yielded the monosulfonimidoyl arenes in all cases,
suggesting that the introduction of the sulfonimidoyl moiety deactivates the arene, thus preventing
a second coupling step.
In tr od u ction
Since the discovery of the sulfonimidoyl moietys
contained in (2S,5S)-methionine sulfoximine (1, Figure
1)sin the 1940s,1 sulfoximines have been widely used as
versatile building blocks in organic synthesis.2 Applica-
F igu r e 1.
tions of the sulfonimidoyl group range from the use as
chiral auxiliary3 or chiral ligand4 to its incorporation into
nitrogen and the R-carbon. Functionalization is usually
accomplished by deprotonation followed by addition of
an appropriate electrophile. The sulfoximine-nitrogen can
easily be acylated, alkylated, or benzylated by this route.2
In contrast, the synthesis of N-aryl sulfoximines is
difficult: it is accomplished either by oxidation of N-aryl
sulfimines with permanganate or peracid6a,b or by a
multistep reaction sequence starting from N-aryl sulfon-
imidoyl chlorides, which are converted into the corre-
sponding sulfoximines by treatment with an organome-
tallic reagent such as alkyl- or aryllithium.6c-f The
obvious disadvantages of these syntheses are insufficient
functional group tolerance and the fastidious preparation
of the sulfonimidoyl halide precursors from the corre-
sponding sulfinamides, which includes the use of tert-
butyl hypochlorite.
peptidic structures.5
Representing nitrogen analogues of sulfones, sulfox-
imines show several characteristic features such as (i)
the stereogenic sulfur atom, (ii) the acidified hydrogens
at the R-carbon to sulfur, (iii) the decreased nucleophi-
licity of the sulfoximine-nitrogen compared to imines, and
(iv) its structural and configurational stability toward
thermal, reductive, basic, and acidic strain. These prop-
erties allow the use of this functional group even under
drastic reaction conditions as well as the simple and
efficient derivatization of sulfoximines at the imine-
* E-mail: Carsten.Bolm@oc.rwth-aachen.de. Fax: (Int.) +49 241
8888 391. Tel: (Int.) +49 241 80 4675.
(1) Whitehead, J . K.; Bentley, H. R. J . Chem. Soc. 1952, 1572.
(2) (a) J ohnson, C. R. Aldrichim. Acta 1985, 18, 3. (b) J ohnson, C.
R. Acc. Chem. Res. 1973, 6, 341. (c) J ohnson, C. R. In Comprehensive
Organic Chemistry; Barton, D., Ollis, W. D., Eds.; Pergamon Press:
Oxford, 1979; Vol. 3, p 223. (d) Pyne, S. G. Sulfur Rep. 1992, 12, 57.
(3) For some recent examples see: (a) Pyne, S. G.; Dong, Z.; Skelton,
B. W.; White, A. H. J . Org. Chem. 1997, 62, 2337. (b) Reggelin, M.;
Heinrich, T. Angew. Chem. 1998, 110, 3005; Angew. Chem., Int. Ed.
1998, 37, 2883. (c) Bosshammer, S.; Gais, H.-J . Synthesis 1998, 919.
(d) For a recent application of sulfoximines in natural product synthesis
see: Paquette, L. A.; Gao, Z.; Ni, Z.; Smith, G. F. J . Am. Chem. Soc.
1998, 120, 2543. (e) For the synthesis of benzothiazines containing the
sulfonimidoyl fragment see: Harmata, M.; Kahraman, M.; J ones, D.
E.; Pavri, N.; Weatherwax, S. E. Tetrahedron 1998, 54, 9995.
(4) (a) Bolm, C.; Felder, M.; Mu¨ller, J . Synlett 1992, 439. (b) Bolm,
C.; Felder, M. Tetrahedron Lett. 1993, 34, 6041. (c) Bolm, C.; Mu¨ller,
J .; Schlingloff, G.; Zehnder, M.; Neuburger, M. J . Chem. Soc., Chem.
Commun. 1993, 182. (d) Bolm, C.; Seger, A.; Felder, M. Tetrahedron
Lett. 1993, 34, 8079. (e) Bolm, C.; Felder, M. Synlett 1994, 655. (f) Bolm,
C.; Mu¨ller, P. Tetrahedron Lett. 1995, 36, 1625. (g) Bolm, C.; Mu¨ller,
P. Acta Chem. Scand. 1996, 50, 305. (h) Bolm, C.; Kaufmann, D.;
Zehnder, M.; Neuburger, M. A. Tetrahedron Lett. 1996, 37, 3985.
(5) (a) Bolm, C.; Kahmann, J . D.; Moll, G. Tetrahedron Lett. 1997,
38, 1169. For the use of substituted â-carboxy sulfoximines as transi-
tion-state analogue inhibitors of carboxypeptidase A, see: (b) Mock,
W. L.; Zhang, J . Z. J . Biol. Chem. 1991, 266, 6393. (c) Mock, W. L.;
Tsay, J .-T. J . Am. Chem. Soc. 1989, 111, 4467. (d) Mock, W. L.; Zhang,
J . Z.; Ni, C.-Z.; Clardy, J . J . Org. Chem. 1990, 55, 5791.
In recent years, the palladium-catalyzed amination of
aryl halides and aryl triflates established independently
by Buchwald and Hartwig has become a general method
for the synthesis of arylamines.7 It has also been suc-
cessfully applied to the synthesis of arylated imines and
azoles.8,9 Despite their decreased nucleophilicity at the
(6) For the oxidation of N-aryl sulfimines to sulfoximines see: (a)
Claus, P. K.; Rieder, W.; Hofbauer, P.; Vilsmaier, E. Tetrahedron 1975,
31, 505. (b) Huang, S.-L.; Swern, D. J . Org. Chem. 1979, 44, 2510. For
the synthesis of N-aryl sulfoximines with tert-butyl hypochlorite see:
(c) Heintzelman, R. W.; Bailey, R. B.; Swern, D. J . Org. Chem. 1976,
41, 2207. (d) J ohnson, C. R.; Bis, K. G.; Cantillo, J . H.; Meanwell, N.
A.; Reinhard, M. F. D.; Zeller, J . R.; Vonk, G. P. J . Org. Chem. 1983,
48, 1. (e) Harmata, M. Tetrahedron Lett. 1989, 30, 437. (f) Harmata,
M.; Claassen, R. J ., II. Tetrahedron Lett. 1991, 32, 6497.
(7) For recent reviews see: (a) Hartwig, J . F. Synlett 1997, 329. (b)
Hartwig, J . F. Angew. Chem. 1998, 110, 2154; Angew. Chem., Int. Ed.
1998, 37, 2046. (c) Frost, C. G.; Mendonc¸a, P. J . Chem. Soc., Perkin
Trans. 1 1998, 2615. (d) Baran˜ano, D.; Mann, G.; Hartwig, J . F. Curr.
Org. Chem. 1997, 1, 287. (e) Wolfe, J . P.; Wagaw, S.; Marcoux, J .-F.;
Buchwald, S. L. Acc. Chem. Res. 1998, 31, 805. (f) Hartwig, J . F. Acc.
Chem. Res. 1998, 31, 852.
10.1021/jo991342u CCC: $19.00 © 2000 American Chemical Society
Published on Web 12/17/1999

170 J . Org. Chem., Vol. 65, No. 1, 2000
Bolm and Hildebrand
Sch em e 1
Sch em e 2
sulfonimidoyl-nitrogen, we expected sulfoximines to re-
semble other nitrogen-based substrates in amination and
imination reactions and hoped to develop a novel method
for the direct introduction of an aryl group at the
sulfoximine nitrogen by a palladium-catalyzed coupling
strategy.10 Using aryl bromides as coupling partners,
N-arylated sulfoximines were obtained from simple and
easily accessible precursors in high yield (Scheme 1).
In this article we disclose our results of a detailed study
demonstrating the scope and the limitations of this
arylation method. The coupling reaction is applicable to
a large variety of substituted aryl bromides with different
electronic and steric properties. However, aryl iodides
proved problematic: substrates with electron-withdraw-
ing substituents underwent imination only in the pres-
ence of lithium or silver salts, and 2-iodo anisole was even
found to be unreactive.
Ta ble 1. Ca ta lytic Cou p lin g of Meth yl 2-Br om oben zoa te
(2) a n d S-Meth yl S-P h en yl Su lfoxim in e (3) Usin g
Differ en t P a lla d iu m Com p lexes a n d Mon o- a n d
Bid en ta te P h osp h in e Liga n d sa
temp time
yield
entry
precatalyst
basef
[°C]
[h] solvent [%]
1b Pd(OAc)2/P(o-tolyl)3
2b Pd(OAc)2/P(o-tolyl)3
3b Pd2(dba)3/P(o-tolyl)3
Cs2CO3
NaOtBu
Cs2CO3
Cs2CO3
Cs2CO3
110
70
110
100
110
36 toluene <4
36 toluene <4
36 toluene <4
4c
Pd(PPh3)4
36 toluene
36 toluene
36 toluene
36 THF
18
82
76
53
89
96
72
92
87
90
94
90
5b Pd(OAc)2/BINAP
6b Pd(OAc)2/BINAP
7b Pd(OAc)2/BINAP
8d Pd2(dba)3/BINAP
NaOtBu 110
Cs2CO3
Cs2CO3
110
110
110
48 toluene
48 toluene
48 toluene
48 toluene
48 toluene
48 toluene
48 toluene
48 toluene
9d Pd(OAc)2/Tol-BINAP Cs2CO3
10d Pd(OAc)2/Tol-BINAP NaOtBu 110
12d Pd(OAc)2/BINAP
11e
PdCl2(DPPF)/DPPF
Cs2CO3
Cs2CO3
110
110
110
110
110
13d Pd2(dba)3/Tol-BINAP Cs2CO3
14d Pd(OAc)2/DPPP
Cs2CO3
Cs2CO3
15d Pd(OAc)2/DPEphos
Resu lts a n d Discu ssion
a
Conditions: 1 equiv of methyl 2-bromobenzoate, 1.2 equiv of
b
Syn th esis of N-Ar yl Su lfoxim in es fr om Ar yl Br o-
m id es. Methyl 2-bromobenzoate (2) was considered as
an appropriate substrate for the reaction with S-methyl-
S-phenylsulfoximine (3) (Scheme 2),10 and this combina-
tion was tested with various mono- and bidentate phos-
phines and different palladium sources in order to
determine the optimal conditions for the catalytic N-
arylation (Table 1).
Palladium catalysts bearing monodentate phosphine
ligands were not effective in catalyzing the arylation of
3 (entries 1-4): while tetrakis(triphenylphosphine)-
palladium(0) is known to be a poor catalyst in related
intermolecular amination reactions,7 the unsatisfying
performance of more hindered tri-ortho-tolylphosphine in
combination with both palladium(II) and palladium(0)
precursors was suprising taking into account that this
catalyst system represents the successful first-generation
catalyst for palladium-catalyzed aminations.
However, the yields of coupling product could be
greatly improved by changing to bidentate phosphine
ligands (entries 5-15). Here, BINAP11 and Tol-BINAP12
gave the best results, affording N-[2-(methyl oxycarbo-
nyl)phenyl]-S-methyl-S-phenylsulfoximine (4) in good to
high yield, with Tol-BINAP being slightly more effective.
Employing PdCl2(DPPF)/DPPF13 and Pd(OAc)2/DPEp-
hos14 resulted in slightly lower yields. Pd(OAc)2/DPPP
(1,3-diphenylphosphinopropane) afforded the N-arylated
product in excellent, 94% yield (entry 14), but the
efficiency of this catalyst was substrate dependent, giving
S-methyl-S-phenylsulfoximine as a 0.1 M solution. 4 mol %
Pd(OAc)2 or Pd2(dba)3, 6 mol % phosphine ligand. c 10 mol %
d
catalyst. 5 mol % Pd(OAc)2 or Pd2(dba)3, 7.5 mol % phosphine
ligand. e 5 mol % PdCl2(DPPF), 20 mol % DPPF. f 1.4 equiv of base
was used.
low yields with other aryl halides (vide infra). The use
of cesium carbonate15 as base gave the best results, and
toluene was found to be superior to THF (entries 5-7, 9,
10).
The catalytic cycle of the N-arylation, which is most
probably similar to related palladium-catalyzed amina-
tion reactions, is depicted in Scheme 3.
After initial reduction of the Pd(II) precursor to phos-
phine-ligated Pd(0), oxidative addition into the aryl-
bromide bond takes place to generate an aryl-palladium-
(II)-bromide complex [L2Pd(aryl)(Br)]. The sulfoximine
then coordinates to palladium, and in the presence of
base an aryl-palladium-sulfoximide intermediate is
formed, which can undergo reductive elimination to the
N-arylated product, regenerating the catalytically active
Pd(0) species.
Sulfoximines exhibit lower nucleophilic character at
the nitrogen than amines and imines, and they are more
comparable in reactivity to azoles or imidazoles. This is
also consistent with the higher catalyst loading and
prolonged reaction times compared to similar reactions
with amines or imines. Although oxidative addition of
palladium into the aryl-bromide bond is assumed to be
rate-determining in amination reactions with DPPF and
(8) Wolfe, J . P.; Åhman, J .; Sadighi, J . P.; Singer, R. A.; Buchwald,
S. L. Tetrahedron Lett. 1997, 38, 6367.
(9) (a) Mann, G.; Hartwig, J . F.; Driver, M. S.; Ferna´ndez-Rivas, C.
J . Am. Chem. Soc. 1998, 120, 827. (b) Hartwig, J . F.; Kawatsura, M.;
Hauck, S. I.; Shaughnessy, K. H.; Alcazar-Roman, L. M. J . Org. Chem.
1999, 64, 5575.
(10) Bolm, C.; Hildebrand, J . P. Tetrahedron Lett. 1998, 39, 5731.
(11) Racemic BINAP [2,2′-bis(diphenylphosphino)-1,1′-binaphthyl]
was used in all runs.
(12) Tol-BINAP [2,2′-bis(di-p-tolylphosphino)-1,1′-binaphthyl] was
used either as the (S)- or the (R)-enantiomer; both gave identical results
in the arylation reactions.
(14) DPEphos: 2,2′-bis(diphenylphosphino)-1,1′-diphenyl ether. (a)
For the synthesis of DPEphos see: Kranenburg, M.; van der Burgt, Y.
E. M.; Kamer, P. C. J .; van Leeuwen, P. W. N. M.; Goubitz, K., Fraanje,
J . Organometallics 1995, 14, 3081. For its use in related amination
reactions see: (b) Sadighi, J . P.; Harris, M. C.; Buchwald, S. L.
Tetrahedron Lett. 1998, 39, 5327. (c) Hamann, B. C.; Hartwig, J . F. J .
Am. Chem. Soc. 1998, 120, 3694.
(15) The lower yields that were obtained with NaO-t-Bu could be
due to partial ester hydrolysis. Cesium carbonate was suggested to be
the base of choice owing to its greater functional group tolerance. For
a short overview of the application of Cs2CO3 in organic synthesis see:
Flessner, T.; Doye, S. J . Prakt. Chem. 1999, 341, 186.
(13) DPPF: 1,1′-(diphenylphosphino)ferrocene.

Pd-Catalyzed N-Arylation of Sulfoximines
J . Org. Chem., Vol. 65, No. 1, 2000 171
drogen elimination to form an imine,17 it was supposed
that the reaction of an enantiopure sulfoximine would
proceed with retention of configuration. We have been
engaged in exploring optically active sulfoximines as
ligands for asymmetric catalysis4 in recent years, and
thus we chose (S)-2-(2′-bromophenyl)-4-tert-butyl oxazo-
line18 [(S)-19] and (RS)-3 as suitable substrates which
would directly produce compound (RS,S)-20, a potential
ligand for asymmetric catalysis (Scheme 4).
Sch em e 3
The results for the palladium-catalyzed arylation of
(RS)-S-methyl-S-phenylsulfoximine [(RS)-3] with (S)-19
in the presence of various bisphosphines are depicted in
Table 3.
Indeed, 20 was obtained in moderate yield when
slightly modified conditions were used with an excess of
(RS)-3 or (S)-19 (entries 1 and 2). We then discovered
that couplings are best performed when equal amounts
of both coupling partners are employed. Here, the yield
of 20 was raised to 86% with Pd(OAc)2/DPEphos as
catalyst. Only one diastereomer was obtained, indicating
that the coupling proceeded without racemization at the
chiral sulfur atom. Although not rigorously proven, we
assume that the coupling occurred with retention of
configuration at sulfur, giving the (RS,S)-configured
product.19
N-Ar yla t ion R ea ct ion s w it h Dib r om ob en zen es.
Since we have been involved in the development of C2-
symmetric bissulfoximines20 in recent years, we decided
to probe the arylation protocol for the synthesis of
bissulfonimidoyl aryls. 1,2-Dibromobenzene (21) was
considered as a suitable precursor and was reacted with
2.5 equiv of 3 in the presence of Pd(OAc)2/BINAP (5 mol
% and 7.5 mol %) under standard reaction conditions.
Surprisingly, only monosulfonimidoyl arene 22 was
formed with the second bromide still attached to the
aromatic moiety (Scheme 5). However, the isolated yield
of monobrominated 22 was remarkable at 74%. Again,
use of phosphines other than BINAP were not successful.
For example, using DPPP afforded 22 in only 17% yield.
The identical result was obtained when 1,3-dibromoben-
zene (24) was used as starting material, yielding 25 in
51% yield (Scheme 6). Apparently, a possible steric
hindrance of the adjacent bulky sulfonimidoyl moiety,
which is introduced in the first step, cannot be respon-
sible for the failure of the second coupling.
BINAP ligands, we think that in the present case the
rate of arylation depends on the reductive elimination
of the N-aryl sulfoximine from a palladium-sulfoximide
aryl complex. In related couplings with azoles it was
found that the reductive elimination of N-aryl azoles is
less favorable than that of the corresponding arylamines
and that the rates for reductive elimination of different
types of sp2-hybridized nitrogens from palladium differ
markedly.9 Alternatively, the low nucleophilicity of the
sulfoximine could retard coordination to palladium and
formation of the intermediary (BINAP)Pd[(sulfoximide)-
(aryl)] complex.
Since BINAP and Tol-BINAP afforded the highest
yields with methyl 2-bromobenzoate (2), these two ligands
were chosen for all couplings with other sulfoximines and
aryl bromides (Table 2).
Reactions with aryl bromides bearing electron-with-
drawing substituents proceeded smoothly, and the yields
of the corresponding N-aryl sulfoximine were uniformly
high regardless of the substitution pattern of either
substrate (entries 1, 5, 6, 11-15, and 18-20). A com-
parison of the yields obtained with BINAP and Tol-
BINAP shows that these ligands differ only slightly in
their effectiveness. However, carrying out the arylation
under standard conditions with (4-tert-butyl)bromoben-
zene (7b ) afforded (4-tert-butylphenyl)-S-methyl-S-
phenylsulfoximine (9) in only poor yield with either
BINAP or Tol-BINAP (entries 2, 3). Interestingly, em-
ploying an excess of aryl bromide led to smooth reaction,
and the desired product 9 was obtained in 67% yield
(entry 4).16 Similarly, 3-bromoanisole (7d ), which gave
only low yields under standard conditions with BINAP
(entry 7), was formed in good yield by this modified
protocol (entry 8).
Neither employing a higher catalyst loading of 10 mol
% Pd(OAc)2/15 mol % BINAP nor a larger excess of
S-methyl-S-phenylsulfoximine (3) of up to 4 equiv re-
sulted in the formation of the desired bissulfoximine. We
also did not observe the corresponding hydrodehaloge-
nated monocoupled product, so that we conclude that
palladium probably does not insert into the second aryl-
bromide bond after substitution with the first sulfonimi-
doyl group. Since several groups reported related bisam-
ination reactions with the corresponding phenyl21 and
N-Ar ylation of (RS)-S-Meth yl-S-ph en ylsu lfoxim in e
Usin g a Ch ir a l Ar yl Br om id e. Since differently sub-
stitued sulfoximines are chiral at the central sulfur atom,
we wondered if the palladium-catalyzed arylation of
enantiomerically pure sulfoximines would occur in a
stereospecific manner. Since partial racemization in
palladium-catalyzed aminations is mainly due to â-hy-
(17) Partial racemization of optically active amines was observed
by Buchwald and co-workers with P(o-tolyl)3 as ligand in the synthesis
of chiral arylamines. Racemization was avoided utilizing chelating
ligands such as BINAP and DPPF: Wagaw, S.; Rennels, R. A.;
Buchwald, S. L. J . Am. Chem. Soc. 1997, 119, 8451.
(18) Zhou, Q.-L.; Pfaltz, A. Tetrahedron 1994, 50, 4467.
(19) 1H NMR shift experiments with 18 obtained from racemic and
enantiomerically pure 3 provide further evidence that the coupling
proceeds without racemization (see Supporting Information).
(20) Bolm, C.; Bienewald, F.; Harms, K. Synlett 1996, 775.
(21) (a) Louie, J .; Hartwig, J . F.; Fry, A. J . J . Am. Chem. Soc. 1997,
119, 11695. (b) Yamamoto, T.; Nishiyama, M.; Koie, Y. Tetrahedron
Lett. 1998, 39, 2367.
(16) On the other hand, DPEphos, which was among the best ligands
for methyl 2-bromobenzoate (2), afforded (4-tert-butylphenyl)-S-methyl-
S-phenylsulfoximine (9) in a disappointing yield of 23% under these
modified conditions.

172 J . Org. Chem., Vol. 65, No. 1, 2000
Ta ble 2. P a lla d iu m -Ca ta lyzed Cou p lin g of Ar yl Br om id es w ith Su lfoxim in esa
Bolm and Hildebrand
a
All reactions were carried out under an atmosphere of argon in toluene at 110 °C with 1.4 equiv of Cs2CO3, 5 mol % Pd(OAc)2, and
b
7.5 mol % of bisphosphine ligand. Method A1: 1.2 equiv of sulfoximine and 1 equiv of aryl bromide were used with BINAP as ligand.
Method A2: 1.2 equiv of sulfoximine and 1 equiv of aryl bromide were employed with Tol-BINAP as ligand. Method B: 1 equiv of sulfox-
imine and 1.2 equiv of aryl bromide were used with BINAP as ligand. c S,S-Dimethylsulfoximine (5) was added as a 2.0 M solution in
d
THF. Yields refer to isolated and pure material and are an average of at least two runs. Yields are relative to the limiting starting
material.
pyridine22 derivatives as well as bisiminations with
benzophenone imine,8 we assume that the sulfonimidoyl
moiety deactivates the second bromide on the aryl group
toward oxidative addition.23 This is further supported by
the observation that other palladium-catalyzed processes
with 22 as substrate such as Suzuki couplings with
phenylboronic acid or aminations with (-)-R-methyl
benzylamine also failed.24
N-Ar yla tion w ith Ar yl Iod id es. To determine the
scope of the sulfoximine arylation, we turned our atten-
tion to aryl iodides as potential coupling partners. Aryl
iodides are more susceptible toward oxidative addition
of palladium than the corresponding bromides; therefore,
we expected our protocol to be applicable to them, too.
(22) Wagaw, S.; Buchwald, S. L. J . Org. Chem. 1996, 61, 7240.

Pd-Catalyzed N-Arylation of Sulfoximines
J . Org. Chem., Vol. 65, No. 1, 2000 173
Sch em e 4
Sch em e 5
Ta ble 3. Cou p lin g of (RS)-3 w ith (S)-19 To Give (RS,S)-20
Usin g Va r iou s P a lla d iu m Ca ta lysts
Sch em e 6
ratio of
yield of
entry
Pd-source/ligand
(RS)-3:(S)-19
(RS,S)-20 (%)
1
2
3
4
5
Pd(OAc)2/BINAP
Pd(OAc)2/BINAP
Pd(OAc)2/BINAP
PdCl2(DPPF)/DPPF
Pd(OAc)2/DPEphos
1:2
2:1
1:1
1:1
1:1
54
61
82
75
86
Hartwig and Driver reported that anilines can be coupled
with aryl iodides in high yields by using (DPPF)PdCl2/
DPPF in THF,25 whereas Buchwald and Wolfe found that
aryl iodides are competent substrates in amination
reactions with BINAP when dioxane was used as solvent
and that the amination could be carried out at room
temperature in the presence of crown ethers. They
reported that aryl iodides display a significantly different
reactivity than aryl bromides in related aminations,26 and
examples of palladium-catalyzed arylation reactions of
sp2-hybridized nitrogen nucleophiles with aryl iodides are
still very rare.27 Indeed, attempts to apply our general
reaction conditions for aryl bromides to aryl iodides with
both electron-withdrawing and electron-releasing sub-
stituents were uniformly unsuccessful. Carrying out the
reaction of 3 with 2-methyl iodobenzoate (26a ) in 1,4-
dioxane or using NaO-t-Bu as base together with 18-
crown-6 in THF met with failure. Changing to (DPPF)-
PdCl2/DPPF afforded N-[2-(methyloxycarbonyl)phenyl]-
S-methyl-S-phenylsulfoximine (4), albeit in poor yield
(17%). Finally, N-arylated sulfoximines could be obtained
from aryl iodides in acceptable yield when more “con-
ventional” additives were added to the reaction mixture
(Table 4). Thus, employing lithium bromide as additive
in the reaction of 3 with 2-methyl iodobenzoate (26a )
catalyzed by Pd(OAc)2/BINAP, 4 was formed in 56% yield
(entry 1).28 Probing another electron-deficient aryl iodide,
4-(nitrophenyl) iodide (26c) in the reaction with S-
methyl-S-(p-tolyl)sulfoximine (6), gave the corresponding
N-arylated product 28 in moderate yield (31%) (entry 7).
When lithium chloride was used in these couplings,
inferior yields resulted in all cases (entries 2, 8), and
employing the corresponding sodium salts (i.e., NaCl,
NaBr) gave even lower yields.
In contrast, N-(4-nitrophenyl)-S-methyl-S-(p-tolyl)sul-
foximine (28) was obtained in 79% yield in the presence
of 2 equiv of silver triflate (entry 9). In independent
studies we found that 4-(nitrophenyl) triflate reacts with
S-methyl S-(p-tolyl)sulfoximine (6) under otherwise iden-
tical reaction conditions to give 28 in 86% isolated yield.
These results could indicate that after oxidative addition
of Pd into the aryl-iodide bond and efficient exchange
of iodide for triflate both reactions proceed via the same
intermediates. Methyl 2-iodobenzoate (26a ) yielded 4 in
a surprising yield (7%) under these conditions (entry 3).29
Electron-rich and ortho-substituted 2-iodoanisole (26b)
did not react in the presence of any of the employed
additives (entries 4-6).30
Con clu sion . We have developed a novel protocol for
the direct arylation of sulfoximines which is based on
palladium-catalyzed cross-coupling methodology. This
approach is general and high yielding for aryl bromides;
however, dibromo aryls react exclusively at one bromide
to produce the corresponding (bromophenyl) sulfoximines,
which are inert toward a second palladium-catalyzed
substitution. Furthermore, it was demonstrated that
enantiomerically pure sulfoximines can be arylated in a
stereospecific manner to directly produce potential ligands
for asymmetric catalysis. Aryl iodides require lithium or
silver salts to undergo the coupling. However, the ef-
fectiveness of the additives is not uniform and they have
to be optimized for individual substrates.
(23) The separate reaction of isolated 22 with 3 did not result in
the formation of bissulfoximine 23. While this article was under review,
Harmata published a paper on the synthesis of chiral benzothiazines
derived from 1,3- and 1,4-dibromobenzenes bearing additional formyl
groups (see: Harmata, M.; Pavri, N. Angew. Chem. 1999, 111, 2577;
Angew. Chem., Int. Ed. 1999, 38, 2419). Applying our protocol, they
succeeded in substituting both bromines. However, the corresponding
bissulfoximines were formed in only moderate yield.
(24) Bolm, C.; Hildebrand, J . P. Unpublished results.
(25) Driver, M. S.; Hartwig, J . F. J . Am. Chem. Soc. 1996, 118, 7217.
(26) (a) Wolfe, J . P.; Buchwald, S. L. J . Org. Chem. 1996, 61, 1133.
(b) Room-temperature arylation of amines with aryl iodides using
crown ethers as additives: Wolfe, J . P.; Buchwald, S. L. J . Org. Chem.
1997, 62, 6066. (c) For room-temperature arylations of amines with
aryl iodides using a highly reactive Pd catalyst see: Hamann, B. C.;
Hartwig, J . F. J . Am. Chem. Soc. 1998, 120, 7369. (d) Intramolecular
amination with aryl iodides: Wolfe, J . P.; Rennels, R. A.; Buchwald,
S. L. Tetrahedron 1996, 52, 7525.(e) For a high-yielding palladium-
catalyzed reaction of an aryl iodide with diphenylhydrazone see:
Hartwig, J . F. Angew. Chem. 1998, 110, 2249; Angew. Chem., Int. Ed.
1998, 37, 2090.
(27) For an example of a copper(I)-catalyzed high-yielding arylation
protocol of imidazoles see: Kiyomori, A.; Marcoux, J .-F.; Buchwald,
S. L. Tetrahedron Lett. 1999, 40, 2657.
(28) The analogous reaction with PdCl2(DPPF)/DPPF and 2 equiv
of LiBr in THF afforded only 34% of coupled product.
Exp er im en ta l Section
Gen er a l P r oced u r es. Unless otherwise specified, all re-
agents were purchased from commercial suppliers and used
without further purification. Bromobenzene was distilled
before use. 1,4-Dioxane, toluene, and THF were distilled from
sodium benzophenone ketyl radical under argon. All other
(29) No product derived from hydrodehalogenation (methyl ben-
zoate) was observed as side product as determined by GC/MS.
(30) This result is in contrast to Buchwald’s protocol, which gives
good to high yields with both electron-poor and electron-rich aryl
iodides (ref 26b), and Hartwig reported that aniline can be coupled
with 2-iodoanisole in 96% yield (ref 25).

174 J . Org. Chem., Vol. 65, No. 1, 2000
Bolm and Hildebrand
Ta ble 4. P d -Ca ta lyzed N-Ar yla tion of 3 a n d 6 w ith Ar yl Iod id es in th e P r esen ce of Va r iou s Ad d itives
solvents were reagent grade and used as received. S,S-
Dimethyl sulfoximine (5), S-methyl S-phenyl sulfoximine (3),
and S-methyl-S-(p-tolyl)sulfoximine (6) were prepared accord-
ing to reported methods.1,2 Racemic 3 was resolved into its
enantiomers using the method of Brandt and Gais.31 Unless
otherwise noted all reactions were carried out under argon
using standard Schlenk and vacuum line techniques. Yields
refer to average yields of pure material of at least two runs of
coupling reactions. 1H NMR and 13C NMR spectra were
recorded relative to TMS as internal standard. All microanaly-
ses were conducted at the Institut fu¨r Organische Chemie der
RWTH Aachen. The synthesis of N-phenyl-S-methyl-S-phen-
ylsulfoximine (16),6 N-phenyl-S,S-dimethyl sulfoximine (12),32
and N-[4-(methyloxycarbonyl)phenyl]-S,S-dimethylsulfoximine
(10)6b has been reported previously.
Rep r esen ta tive P r oced u r es (A1/A2) for th e Cou p lin g
of Su lfoxim in es w ith Ar yl Br om id es. A dry 25 mL two-
neck flask equipped with a magnetic stirbar, a septum inlet,
and a reflux condenser was charged with Pd(OAc)2 (5 mol %)
and diphosphine (7.5 mol %; A1, BINAP; A2, Tol-BINAP)
under an argon atmosphere. Then, toluene was added (10 mL),
followed by the aryl bromide (1 mmol), the sulfoximine (1.25
mmol), and cesium carbonate (1.4 mmol). After heating the
mixture to reflux for 48 h, it was allowed to cool to room
temperature, diluted with methyl tert-butyl ether, and filtered
through a plug of Celite, and the Celite was rinsed with methyl
tert-butyl ether. The solvents were removed in vacuo, and the
resulting oily residue was purified by flash column chroma-
tography.
N-[2-(Meth yloxyca r bon yl)p h en yl]-S-m eth yl-S-p h en yl-
su lfoxim in e (4) was obtained from methyl 2-bromobenzoate
(2) in 96% yield as a yellow oil using Tol-BINAP (method A2).
1H NMR (300 MHz, CDCl3): δ 3.23 (s, 3H), 3.94 (s, 3H), 6.88-
6.96 (m, 1H), 7.20-7.24 (m, 2H), 7.50-7.62 (m, 4H), 8.15 (m,
2H). 13C NMR (75 MHz, CDCl3): δ 45.18, 51.8, 120.48, 123.25,
124.98, 127.74, 128.39, 129.53, 131.15, 132.30, 138.33, 143.97,
166.96. MS (EI, 70 eV): 289 (M, 100), 194 (64). IR (cap. film):
3022, 2929, 1723, 1482, 1301, 1204. Anal. Calcd for C15H15
-
NO3S: C, 62.26; H, 5.22; N, 4.84. Found: C, 62.09; H, 5.21;
N, 4.74.
N-[3-(Cyan o)ph en yl]-S-m eth yl-S-ph en ylsu lfoxim in e (8)
was obtained from 3-bromobenzonitrile (7a ) following the
general method A1 in 78% yield as a yellow oil using BINAP.
1H NMR (400 MHz, CDCl3): δ 3.27 (s, 3H), 7.09-7.25 (m, 4H),
7.53-7.64 (m, 3H), 7.93-7.96 (m, 2H). 13C NMR (100 MHz,
CDCl3): δ 46.46, 112.91, 119.24, 125.15, 126.34, 127.89, 128.67,
130.02, 133.96, 138.68, 146.47. MS (EI, 70 eV): 256 (86), 193
(100). IR (cap. film): 3022, 2925, 2228, 1588, 1472, 1279. Anal.
Calcd for C14H12N2O3S: C, 65.60; H, 4.71; N, 10.92. Found:
C, 65.58; H, 4.91; N, 10.98.
N -(4-(t er t -Bu t yl)p h e n yl)-S -m e t h yl-S -p h e n ylsu lfox-
im in e (9) was obtained from 4 tert-butylbromobenzene (7b)
following the general procedure B in 67% yield as a yellow oil
using BINAP. 1H NMR (300 MHz, CDCl3): δ 1.23 (s, 9H), 3.22
(s, 3H), 6.90-6.96 (m, 2H), 7.11-7.17 (m, 2H), 7.50-7.62 (m,
3H), 7.98-8.01 (m, 2H). 13C NMR (75 MHz, CDCl3): δ 31.39,
45.91, 122.699, 125.84, 128.60, 129.51, 133.14, 139.77, 141.85,
144.35. MS (EI, 70 eV): 287 (M), 272 (100%). IR (cap. film):
Rep r esen ta tive P r oced u r e (B) for th e Rea ction of
Su lfoxim in es w ith 4-ter t-Bu tylbr om oben zen e (7b) a n d
3-Br om oa n isole (7d ) w ith Cesiu m Ca r bon a te As Ba se.
A dry Schlenk tube, equipped with a magnetic stirbar, was
charged with Pd(OAc)2 (5 mol %), BINAP (7.5 mol %), and
toluene (10 mL). Then, the aryl bromide (1.2 mmol) was added,
followed by the sulfoximine (1 mmol) and base (1.4 mmol). The
tube was then sealed, and the mixture was heated at 110 °C
for 48 h. Workup and purification were carried out in ac-
cordance with the general procedure A.
Rep r esen ta tive P r oced u r e (C) for th e Rea ction of
Su lfoxim in es w ith Ar yl Iod id es in th e P r esen ce of
Ad d itives. A dry Schlenk tube, equipped with a magnetic
stirbar, was charged with Pd(OAc)2 (5 mol %), BINAP (7.5 mol
%), and toluene (10 mL). Then, the aryl bromide (1.2 mmol)
was added, followed by the sulfoximine (1 mmol), the additive
(2 mmol), and cesium carbonate (1.4 mmol). The tube was then
sealed, and the mixture was heated at 110 °C for 48 h. Workup
and purification were then performed as noted in general
procedure A.
3029, 2961, 1605, 1505, 1446, 1291. Anal. Calcd for C17H21-
NOS: C, 71.04; H, 7.36; N, 4.87. Found: C, 71.01; H, 7.61; N,
5.18.
N-[3-(Meth oxy)ph en yl]-S-m eth yl S-(p-tolyl)su lfoxim in e
(11) was obtained from 3-bromoanisole (7d ) following the
general procedure B in 74% yield as a pale yellow oil using
BINAP. 1H NMR (300 MHz, CDCl3): δ 2.40 (s, 3H), 3.22 (s,
3H), 3.70 (s, 3H), 6.41-6.45 (m, 1H), 6.58-6.62 (m, 2H), 6.97-
7.02 (m, 1H), 7.29-7.32 (m, 2H), 7.82-7.86 (m, 2H). 13C NMR
(75 MHz, CDCl3): δ 21.52, 46.17, 55.08, 107.66, 108.93, 115.64,
128.62, 129.46, 130.20, 136.29, 144.16, 146.36, 160.21. MS (EI,
70 eV): 275 (M, 100). IR (cap. film): 3004, 2928, 1597, 1481,
1297. Anal. Calcd for C15H17NO2S: C, 65.60; H, 6.22; N, 5.08.
Found: C, 65.24; H, 6.46; N, 5.36.
N-[4-(Tr iflu or om eth yl)p h en yl]-S-m eth yl S-p h en ylsu l-
foxim in e (13) was obtained from 4-(trifluoromethyl)bro-
mobenzene (7f) following the general procedure A1 in 82%
yield as a yellow oil using BINAP. 1H NMR (300 MHz,
CDCl3): δ 3.26 (s, 3H), 7.06 (d, 2H, J ) 8.3 Hz), 7.33 (d, 2H,
(32) Furukawa, N.; Takahashi, F.; Yoshimura, T.; Oae, S. Tetrahe-
dron 1979, 35, 317.
(31) Brandt, J .; Gais, H.-J . Tetrahedron: Asymmetry 1997, 8, 909.

Pd-Catalyzed N-Arylation of Sulfoximines
J . Org. Chem., Vol. 65, No. 1, 2000 175
J ) 7.8 Hz), 7.50-7.63 (m, 3H), 7.94 (m, 2H). 13C NMR (75
MHz, CDCl3): δ 46.38, 122.88, 126.15, 126.48, 128.56, 129.82,
133.69, 138.85, 148.81. MS (EI, 70 eV): 299 (M, 100). IR
(KBr): 3029, 2928, 1613, 1514, 1326, 1269. Anal. Calcd for
C14H12F3NOS: C, 56.17; H, 4.04; N, 4.67. Found: C, 56.44; H,
4.02; N, 4.68.
N-[4-(Meth yloxyca r bon yl)p h en yl]-S-m eth yl-S-p h en yl-
su lfoxim in e (14) was obtained from 4-bromo methylbenzoate
(7c) following the general procedure A1/A2 as a yellow oil in
89% (BINAP) and 90% (Tol-BINAP) yield, respectively. 1H
NMR (300 MHz, CDCl3): δ 3.30 (s, 3H); 3.82 (s, 3H); 7.00 (d,
J ) 8.8 Hz, 2H), 7.54-7.60 (m, 3H), 7.78 (d, J ) 6.8 Hz, 2H),
7.95 (d, J ) 7.1 Hz, 2H). 13C NMR (75 MHz, CDCl3): δ 46.28,
51.73, 122.47, 123.18, 128.54, 129.77, 130.87, 133.71, 138.57,
149.82, 167.08. MS (EI, 70 eV): 289 (M, 100), 166 (51). IR (cap.
N-[3-(Br om o)p h en yl]-S-m et h yl-S-p h en ylsu lfoxim in e
(25). To a dry Schlenk tube equipped with a magnetic stirbar
was added Pd(OAc)2 (11 mg, 5 mol %) and BINAP (46 mg, 7.5
mol %) followed by toluene (10 mL). Then, 1,3-dibromobenzene
(24) (234 mg, 1 mmol) and S-methyl S-phenyl sulfoximine (3)
(465 mg, 2.5 equiv) were added and finally cesium carbonate
(918 mg, 2.8 equiv). The tube was sealed, and the mixture was
heated at 110 °C for 48 h. It was then allowed to cool to room
temperature, and then methyl tert butyl ether was added. The
mixture was filtered through a pad of Celite, and the Celite
was washed with methyl tert-butyl ether followed by evapora-
tion of the solvent. The resulting residue was subjected to
column chromatography (hexanes/methyl tert-butyl ether,
1:1.5) to afford 158 mg of N-[3-(bromo)phenyl]-S-methyl-S-
1
phenylsulfoximine (25) in 51% yield as a yellow oil. H NMR
(300 MHz, CDCl3): δ 3.24 (s, 3H), 6.92-7.03 (m, 3H), 7.12-
7.15 (m, 1H), 7.52-7.64 (m, 3H), 7.94-7.96 (m, 2H). 13C NMR
(75 MHz, CDCl3): δ 46.14, 121.81, 122.60, 124.67, 126.30,
128.59, 129.74, 130.22, 133.58, 139.07, 146.81. MS (EI, 70
eV): 310 (M, 50), 167 (100). IR (KBr): 3022, 2925, 1588, 1473,
1312, 1189. Anal. Calcd for C13H12NOSBr: C, 50.33; H, 3.89;
N, 4.51. Found: C, 50.66; H, 3.84; N, 4.41.
film): 3001, 1716, 1505, 1263, 1178. Anal. Calcd for C15H15
NO3S: C, 62.26; H, 5.22; N, 4.84. Found: C, 62.09; H, 5.28;
N, 4.75.
-
N-[2-(Cyan o)ph en yl]-S-m eth yl-S-ph en ylsu lfoxim in e (15)
was obtained from 2-bromobenzonitrile (7g) following the
general procedure A2 in 94% yield using Tol-BINAP as a
1
yellow oil. H NMR (300 MHz, CDCl3): δ 3.31 (s, 3H), 6.87-
(RS,S)-2-[S-Met h yl-S-p h en ylsu lfon im id oyl]p h en yl-4-
ter t-bu tyloxa zolin e (20). A dry Schlenk flask equipped with
a magnetic stirbar was charged with Pd(OAc)2 (11 mg, 5 mol
%) and DPEphos (40 mg, 7.5 mol %) against a positive argon
flow, followed by toluene (10 mL). Then, (RS)-S-methyl-S-
phenylsulfoximine (1 equiv, 155 mg, 1 mmol), (S)-2-(2′-bro-
mophenyl)-4-tert-butyloxazoline [(S)-19] (1 equiv, 282 mg, 1
mmol), and cesium carbonate (1.4 equiv, 459 mg, 1.4 mmol)
were added, and the Schlenk flask was sealed. The mixture
was heated to 110 °C for 48 h, allowed to cool to room
temperature, and diluted with methyl tert-butyl ether. The
crude reaction mixture was filtered through a pad of Celite,
the Celite was rinsed with methyl tert butyl ether, and the
combined ethereal solutions were removed in vacuo. The
resulting oily residue was purified by column chromatography
(hexanes/methyl tert butyl ether, 1:1) to yield the title com-
pound in 86% (306 mg). [R]D ) -92.2 (c ) 1.0, CHCl3). 1H NMR
(300 MHz, CDCl3): δ 1.01 (s, 9H), 3.20 (s, 3H), 4.14-4.24 (m,
2H), 4.33-4.40 (m, 1H), 6.89-6.95 (m, 1H), 7.13-7.23 (m, 2H),
7.49-7.62 (m, 4H), 8.22-8.26 (m, 2H). 13C NMR (75 MHz,
CDCl3): δ 25.93, 34.07, 46.23, 68.73, 76.21, 127.72, 127.97,
128.05, 128.16, 128.27, 128.30, 129.29, 131.52, 133.07, 143.64,
163.25. MS (EI, 70 eV): 356 (M, 15), 159 (100). IR (CHCl3):
3062, 2958, 1651, 1487, 1298. HRMS calcd for C20H24N2O2S:
356.155851. Found: 356.155617.
6.91 (d, J ) 7.7 Hz, 1H), 7.12-7.15 (d, J ) 7.7 Hz, 1H), 7.21-
7.27 (m, 1H), 7.48-7.50 (d, J ) 7.7 Hz, 1H), 7.54-7.66 (m,
3H), 8.03-8.07 (m, 2H). 13C NMR (75 MHz, CDCl3): δ 46.03,
118.53, 121.50, 122.04, 128.24, 129.78, 133.27, 133.36, 133.78,
138.62, 148.96. MS (EI, 70 eV): 256 (M, 100). IR (cap. film):
3069, 2220, 1591, 1479, 1284. Anal. Calcd for C14H12N2O3S:
C, 65.60; H, 4.71; N, 10.92. Found: C, 65.34; H, 4.68; N, 10.85.
N-[4-(Met h yloxyca r b on yl)p h en yl]-S-m et h yl-S-(p -t ol-
yl)su lfoxim in e (17) was obtained from 4-bromo methylben-
zoate (7c) following the general method A1/A2 as an off-white
solid in 88% (BINAP) and 93% (Tol-BINAP) yield, respectively.
1H NMR (300 MHz, CDCl3): δ 2.39 (s, 3H), 3.26 (s, 3H), 3.81
(s, 3H), 6.98-7.02 (d, J ) 8.4 Hz, 2H), 7.29-2.32 (d, J ) 7.9
Hz, 2H), 7.77-7.83 (m, 4H). 13C NMR (75 MHz, CDCl3): δ
22.11, 47.08, 52.26, 122.99, 123.33, 129.10, 130.94, 131.36,
136.14, 145.20, 151.04, 167.69. Mp: 102 °C. MS (EI, 70 eV):
303 (m, 100). IR (cap. film): 3021, 2950, 1711, 1601, 1269.
Anal. Calcd for C16H17NO3S: C, 63.34; H, 5.64; N, 4.61.
Found: C, 63.23; H, 5.62; N, 4.54.
N-[4-(Cyan o)ph en yl]-S-m eth yl-S-ph en ylsu lfoxim in e (18)
was obtained from 4-bromobenzonitrile (7h ) following the
general method A1 in 93% yield as a yellow oil using BINAP.
1H NMR (300 MHz, CDCl3): δ 3.29 (s, 3H), 6.99-7.03 (d,
J ) 7.8 Hz, 2H), 7.36-7.39 (d, J ) 8.8 Hz, 2H), 7.54-7.66 (m,
3H), 7.92-7.95 (d, J ) 7.7 Hz, 2H). 13C NMR (75 MHz,
CDCl3): δ 46.48, 104.07, 119.63, 123.16, 128.38, 129.85, 133.17,
133.84, 138.41, 150.15. MS (EI, 70 eV): 256 (M, 100). IR (cap.
film): 3022, 2928, 2220, 1601, 1499, 1298. Anal. Calcd for
N-[4-(Nitr o)ph en yl]-S-m eth yl-S-(p-tolyl)su lfoxim in e (28)
was obtained from 4-(nitrophenyl) iodide (26c) following the
general procedure C with 2 equiv of AgOTf as additive in 79%
yield as a yellow solid. Mp: 122 °C. 1H NMR (300 MHz,
CDCl3): δ 2.42 (s, 3H), 3.30 (s, 3H), 6.98-7.01 (d, J ) 8.8 Hz,
2H), 7.33-7.36 (d, J ) 8.0 Hz, 2H), 7.80-7.82 (d, J ) 8.3 Hz,
2H), 7.96-7.98 (d, J ) 8.8 Hz, 2H). 13C NMR (75 MHz,
CDCl3): δ 21.58, 46.70, 122.35, 125.11, 128.38, 130.55, 135.01,
141.52, 145.12, 152.90. MS (EI, 70 eV): 290 (M, 52), 59 (100).
IR (cap. film): 3017, 2932, 1585, 1490, 1275. Anal. Calcd for
C
14H12N2O3S: C, 65.60; H, 4.71; N, 10.92. Found: C, 65.59; H,
4.57; N, 10.90.
N-[2-(Br om o)p h en yl]-S-m et h yl-S-p h en ylsu lfoxim in e
(22). To a dry Schlenk tube equipped with a magnetic stirbar
was added Pd(OAc)2 (11 mg, 5 mol %) and BINAP (47 mg, 7.5
mol %) followed by toluene (10 mL). Then, 1,2-dibromobenzene
(21) (234 mg, 1 mmol) and S-methyl S-phenyl sulfoximine (3)
(465 mg, 2.5 equiv) were added and finally cesium carbonate
(918 mg, 2.8 equiv). The tube was sealed, and the mixture was
heated at 110 °C for 48 h. It was then allowed to cool to room
temperature, and finally, methyl tert-butyl ether was added.
The mixture was filtered through a pad of Celite, and the
Celite washed with methyl tert-butyl ether followed by evapo-
ration of the solvent. The resulting residue was subjected to
column chromatography (hexanes/methyl tert-butyl ether,
1:1.5) to afford 224 mg of N-[2-(bromo)phenyl]-S-methyl-S-
C
14H14N2O2S: C, 57.92; H, 4.86; N, 9.65. Found: C, 57.91; H,
4.80; N, 9.58.
Ack n ow led gm en t. We thank the Fonds der Che-
mischen Industrie and the Deutsche Forschungsge-
meinschaft (DFG) within the Collaborative Research
Center (SFB) 380 “Asymmeric Synthesis by Chemical
and Biological Methods” for financial support of this
work. We are also grateful to Degussa-Hu¨ls AG for the
generous donation of palladium salts.
1
phenylsulfoximine (22) (74%). H NMR (300 MHz, CDCl3): δ
3.22 (s, 3H); 6.72-6.80 (m, 1H); 6.96-7.08 (m, 1H); 7.18-7.24
(d, 7.8 Hz, 1H); 7.48-7.65 (m, 4H); 8.05-8.12 (d, 7.0 Hz, 2H).
13C NMR (75 MHz, CDCl3): δ 45.35, 119.77, 123.57, 123.89,
127.46, 128.14, 129.37, 133.31, 133.90, 138.44, 143.27. MS (EI,
70 eV): 310 (M, 50), 167 (100). IR (cap. film): 3060, 1581, 1470,
1321, 1206. Anal. Calcd for C13H12NOSBr: C, 50.33; H, 3.89;
N, 4.51. Found: C, 50.70; H, 4.00; N, 4.83.
Su p p or tin g In for m a tion Ava ila ble: Spectral character-
ization (1H NMR, 13C NMR) of all new compounds. This
material is available free of charge via the Internet at
http://pubs.acs.org.
J O991342U