Palladium-Catalyzed N-Vinylation of
Sulfoximines
Juan R. Dehli and Carsten Bolm*
Institut fu¨r Organische Chemie der RWTH Aachen,
Professor-Pirlet-Str. 1, D-52056 Aachen, Germany
FIGURE 1. Successfully applied N-arylated sulfoximines in
copper-catalyzed C-C bond-forming reactions.
Received August 18, 2004
SCHEME 1. Palladium-Catalyzed Coupling of
S-Methyl-S-phenylsulfoximine (4a) and
r-Bromostyrene (5a) To Give 6
Abstract: New previously unavailable N-vinyl sulfoximines
have been synthesized by intermolecular palladium-cata-
lyzed coupling between sulfoximines and vinyl bromides in
excellent yield. Hydrogenation of the vinyl moiety opens a
novel way to R-branched N-alkyl sulfoximines.
During the past decade, various sulfoximines have
been shown to be applicable as chiral ligands in metal-
catalyzed asymmetric reactions.1,2 However, although the
results of these pioneering studies were very promising
in terms of catalytic activity and stereoselectivity, they
still fell short when compared to other well-established
ligand structures.3 It was not until a general methodology
for the N-arylation of sulfoximines (via palladium-
catalyzed cross-coupling with aryl halides4 and sul-
fonates5) had been developed that a new generation of
these compounds (exemplified by 1, 2, or 3, Figure 1)
reached the required level to compete with the above-
mentioned ligands in metal-catalyzed asymmetric Diels-
Alder,6 hetero-Diels-Alder,7 allylic alkylation,8 and Mu-
kaiyama-type aldol reactions.9
On the other hand, during the last years, several
groups reported on palladium-catalyzed coupling reac-
tions of vinyl bromides with amines,10 amides,11 azoles,12
and trialkylsilylimines,13 based on the methodology
introduced by Buchwald and Hartwig for the arylation
of amines.14 In the frame of our ongoing studies concern-
ing the synthesis of new sulfoximines with novel struc-
tural motives and taking into account the excellent
results obtained with sulfoximine ligands in which the
nitrogen was directly bound to an sp2 carbon, we regarded
the development of a method for the introduction of a
vinyl moiety at the sulfoximine nitrogen of utmost
importance. S-Methyl-S-phenylsulfoximine (4a) and R-bro-
mostyrene (5a) were chosen as model substrates for the
synthesis of 5, and this educt combination was tested for
coupling under various reaction conditions (Scheme 1).
We were pleased to find that under the optimized
conditions for the N-arylation of sulfoximines [using Pd2-
dba3 (5 mol % in Pd), rac-BINAP (7.5 mol %), NaO-t-Bu
(1.5 equiv) in refluxing toluene],4 the coupling proceeded
with complete conversion within 24 h. Furthermore, no
byproducts were detected by NMR and GC if dry and
nonacidic conditions were maintained throughout the
workup.
* To whom correspondence should be addressed. Fax: +49 241 809
2391. Phone: +49 241 809 4675.
(1) (a) Okamura, H.; Bolm, C. Chem. Lett. 2004, 33, 482-487. (b)
Harmata, M. Chemtracts-Org. Chem. 2003, 16, 660-666.
(2) For a recent review on sulfoximines, see: Reggelin, M.; Zur, C.
Synthesis 2000, 1-64.
(3) (a) Catalytic Asymmetric Synthesis, 2nd ed.; Ojima, I., Ed.; Wiley-
VCH: Weinheim, Germany, 2000. (b) Comprehensive Asymmetric
Catalysis, Jacobsen, E. N., Pfaltz, A., Yamamoto, H., Eds.; Springer-
Verlag: Berlin, Germany, 1999. (c) Transitions Metals for Organic
Synthesis; Beller, M., Bolm, C., Eds.; Wiley-VCH: Weinheim, Germany,
1998. (d) Bolm, C., Gladysz, J., Eds. Chem. Rev. 2003, 103, 2761-
3400.
(4) (a) Bolm, C.; Hildebrand, J. P. J. Org. Chem. 2000, 65, 169-
175. (b) Bolm, C.; Hildebrand, J. P. Tetrahedron Lett. 1998, 39, 5731-
5734. (c) Bolm, C.; Martin, M.; Gibson, L. Synlett 2002, 832-834. (d)
Harmata, M.; Hong, X.; Ghosh, S. K. Tetrahedron Lett. 2004, 45, 5233-
5236. (e) For a related intramolecular R-arylation of sulfoximines,
see: Bolm, C.; Okamura, H.; Verrucci, M. J. Organomet. Chem. 2003,
687, 444-450. (f) For a recently reported Cu-promoted N-arylation,
see: Cho, G.-Y.; Re´my, P.; Jansson, J.; Moessner, C.; Bolm, C. Org.
Lett. 2004, 6, 3293-3296. Due to its aqueous and acidic workup, this
methodology was expected to be incompatible with the water and acid
sensitivity of the vinyl sulfoximines prepared here.
A series of experiments was then performed in order
to investigate the reagent flexibility of the coupling
process (Table 1). A control reaction under the same
conditions in the absence of palladium confirmed that the
(10) (a) Barluenga, J.; Ferna´ndez, M. A.; Aznar, F.; Valde´s, C. Chem.
Eur. J. 2004, 10, 494-507. (b) Barluenga, J.; Ferna´ndez, M. A.; Aznar,
F.; Valde´s, C. Chem. Commun. 2002, 2362-2363. (c) For a recent report
on the use of vinyl chlorides as coupling partners, see: Barluenga, J.;
Ferna´ndez, M. A.; Aznar, F.; Valde´s, C. Chem. Commun. 2004, 1400-
1401.
(5) Bolm, C.; Hildebrand, J. P.; Rudolph, J. Synthesis 2000, 911-
913.
(6) (a) Bolm, C.; Martin, M.; Simic, O.; Verrucci, M. Org. Lett. 2003,
5, 427-429. (b) Bolm, C.; Martin, M.; Gescheidt, G.; Palivan, C.;
Neshchadin, D.; Bertagnolli, H.; Feth, M.; Schweiger, A.; Mitrikas, G.;
Harmer, J. J. Am. Chem. Soc. 2003, 125, 6222-6227.
(11) (a) Kozawa, Y.; Mori, M. Tetrahedron Lett. 2002, 43, 111-114.
(b) For the amidation of meso-brominated porphyrines, see: Gao, G.-
Y.; Chen, Y.; Zhang, X. P. Org. Lett. 2004, 6, 1837-1840.
(12) Lebedev, A. Y.; Izmer, V. V.; Kazyul’kin, D. N.; Beletskaya, I.
P.; Voskoboynikov, A. Z. Org. Lett. 2002, 4, 623-626.
(13) Barluenga, J.; Aznar, F.; Valde´s, C. Angew. Chem., Int. Ed.
2004, 43, 343-345.
(14) (a) Muci, A. R.; Buchwald, S. L. Top. Curr. Chem. 2002, 219,
131-209. (b) Hartwig, J. F. In Modern Amination Methods; Ricci, A.,
Ed.; Wiley-VCH: Weinheim, Germany, 2000; pp 195-262.
(7) (a) Bolm, C.; Verrucci, M.; Simic, O.; Cozzi, P. G.; Raabe, G.;
Okamura, H. Chem. Commun. 2003, 2826-2827. (b) Bolm, C.; Simic,
O. J. Am. Chem. Soc. 2001, 123, 3830-3831.
(8) (a) Bolm, C.; Simic, O.; Martin, M. Synlett 2001, 1878-1880. (b)
Harmata, M.; Ghosh, S. K. Org. Lett. 2001, 3, 3321-3323.
(9) Langner, M.; Bolm, C. Angew. Chem., in press.
10.1021/jo0485583 CCC: $27.50 © 2004 American Chemical Society
Published on Web 11/04/2004
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J. Org. Chem. 2004, 69, 8518-8520