Convenient synthesis of α,β-unsaturated sulfones via a Mizoroki-Heck reaction of arylboronic acids with phenyl vinyl sulfones

Article abstract of DOI:10.1016/j.tetlet.2004.03.179

Palladium acetate catalyzed Mizoroki-Heck reaction of arylboronic acids with phenyl vinyl sulfones afford α,β-unsaturated sulfones in good yields.

Full text of DOI:10.1016/j.tetlet.2004.03.179

Tetrahedron
Letters
Tetrahedron Letters 45 (2004) 4021–4022
Convenient synthesis of a,b-unsaturated sulfones via a Mizoroki–
Heck reaction of arylboronic acids with phenyl vinyl sulfones
George W. Kabalka* and Sankar K. Guchhait
The University of Tennessee, Departments of Chemistry and Radiology, Rm 612 Buehler Dabney Hall, Knoxville,
TN 37996-1600, USA
Received 5 February 2004; revised 25 March 2004; accepted 29 March 2004
Abstract—Palladium acetate catalyzed Mizoroki–Heck reaction of arylboronic acids with phenyl vinyl sulfones afford a,b-unsat-
urated sulfones in good yields.
Ó 2004 Elsevier Ltd. All rights reserved.
Vinyl sulfones are extensively used as intermediates in
organic synthesis1–6 due to the chemical versatility of the
sulfone moiety. Vinyl sulfones are also excellent accep-
stable and readily handled without special precautions.
As a part of an ongoing research program focused on
the use of boronic acids in organic synthesis,24–29 we
investigated their use in the synthesis of alkenyl sulfones.
We wish to report the results of this study.
7
tors in Michael additions and 2p partners in cycload-
dition reactions.8 Several biologically active sulfone
molecules, prepared from alkenyl sulfones,9–12 and a,b-
unsaturated sulfones, have been found to have anti-
cancer13;14 and carcinogenesis-suppressing activity.15;16
Heating phenyl vinyl sulfone with p-tolylboronic acid in
the presence of palladium acetate and sodium carbonate
in N,N-dimethylformamide at 60°C under a nitrogen
atmosphere afforded b-p-tolylvinyl phenyl sulfone in poor
yield. However, carrying out the reaction in the presence
of oxygen markedly improved the yield. Optimal reaction
yields were obtained when sulfone (1.0 mmol), organ-
oboronic acid (1.2 mmol), sodium carbonate (2.0mmol),
and palladium acetate (10 mol %) were allowed to react in
an oxygen atmosphere at 60°C. N,N-Dimethylformamide
was found to be a more effective solvent than DMSO,
MeCN, EtOH, PEG-400, or toluene. Palladium powder
and nickel chloride were completely ineffective catalysts in
the reaction (Scheme 1).
Numerous methods have been developed for the syn-
thesis of alkenyl sulfones. Recent examples include hy-
drozirconation of 1-alkenyl sulfones,17 hydrozirconation
of terminal alkynes followed by reaction with sulfonyl
chlorides,18 hydrotelluration of 1-alkenyl sulfones,19
cerium(IV) ammonium nitrate mediated oxidative
addition of sulfinate and iodine to alkenes,20 boron tri-
fluoride, or AIBN catalyzed addition of polystyrene-
supported selenosulfonates to alkenes,21 Heck reactions
of polystyrene–resin supported aryl iodides with vinyl
sulfones,22 and the reaction of alkenyltriphenylbismu-
thonium tetrafluoroborates with arylsulfinate salt.23
These methods are sometimes complex, do not tolerate
sensitive functional groups, and the reagents and start-
ing materials are not always readily available.
A variety of arylboronic acids readily underwent reac-
tion with phenyl vinyl sulfone to produce the corre-
sponding b-arylvinyl phenyl sulfones in good to high
yields (Table 1). Aliphatic vinylboronic acids produced
modest yields (<20%) but alkylboronic acids were
unreactive. Functional groups such as methoxy, nitro,
acetyl, chloro, bromo were unaffected by the reaction. It
Organoboronic acids comprise a family of organome-
tallic reagents that tolerate a wide range of functional
groups. They are widely available, generally eco-
friendly, relatively inert to air and water, and thermally
Keywords: Vinyl sulfones; Arylboronic acids; Palladium catalysis.
* Corresponding author. Tel.: +1-865-974-3260; fax: +1-865-974-2997;
e-mail: kabalka@utk.edu
Scheme 1.
0040-4039/$ - see front matter Ó 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2004.03.179

4022
G. W. Kabalka, S. K. Guchhait / Tetrahedron Letters 45 (2004) 4021–4022
Table 1. Reactions of arylboronic acids with phenyl vinyl sulfones
(Scheme 1)30
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Entry
R
Time (h)
15
Yield (%)a;b
8417
Me
1
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M.; Kolb, H. J. Org. Chem. 2000, 65, 8819.
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14. Reddy, P. E.; Reddy, R. M. V. Chem. Abstr. 1999, 130,
281870.
2
3
15
15
8117
7631
MeO
O N
2
O
C
4
15
7032
H C
3
15. Konopa, J. K.; Konieczny, M. T.; Horowska, B. J.;
Kunikowski, A. J.; Asao, T.; Nishino, H.; Yamada, Y.
Jpn. Patent JP 9003037, 1997.
16. Konopa, J. K.; Konieczny, M. T.; Horowska, B. J.;
Kunikowski, A. J.; Asao, T.; Nishino, H.; Yamada, Y.
Chem. Abstr. 1997, 126, 185889.
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1958.
18. Duan, D.-H.; Huang, X. Synlett 1999, 317.
19. Huang, X.; Liang, C.-G.; Xu, Q.; He, Q.-W. J. Org. Chem.
2001, 66, 74.
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Tetrahedron Lett. 2001, 42, 6763.
21. Qian, H.; Huang, X. Synlett 2001, 1913.
22. Berteina, S.; Wendeborn, S.; Brill, W. K.-D.; Mesmaeker,
A. D. Synlett 1998, 676.
5
6
18
18
7917;31
7417
Cl
Br
Me
Me
7
8
18
18
7433
7034
CH CH
a Isolated yields based on vinyl sulfone.
b All compounds characterized by elemental analysis and NMR spec-
troscopy.
23. Matano, Y.; Yoshimune, M.; Azuma, N.; Suzuki, H. J.
Chem. Soc., Perkin Trans. 1 1996, 1971.
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is noteworthy that the reaction is insensitive to the
electronic nature of the functional groups present in the
arylboronic acids. In addition, sterically hindered, 2,6-
dimethylphenylboronic acid (entry 7) readily partici-
pates in the reaction.
27. Kabalka, G. W.; Venkataiah, B. Tetrahedron Lett. 2002,
43, 3703.
In conclusion, we have developed a novel synthesis of b-
arylvinyl phenyl sulfones via a Mizoroki–Heck type
reaction of boronic acids with phenyl vinyl sulfones. The
method tolerates a wide variety of functional groups, is
straightforward, and provides good yields of products
from readily accessible starting materials.
28. Kabalka, G. W.; Namboodiri, V.; Wang, L. Chem.
Commun. 2001, 775.
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30. Phenyl vinyl sulfone (1 mmol) was placed in an oven-dried,
round bottomed flask under a nitrogen atmosphere. Dry
dimethylformamide (2.5 mL) was added and the resultant
solution stirred. Arylboronic acid (1.2 mmol), Na2CO3
(2.0 mmol) and Pd(OAc)2 (10.0 mmol %) were then added.
A balloon filled with oxygen was attached to the flask and
the mixture was stirred at 60°C for the indicated time. The
resultant mixture was diluted with ethyl acetate (50 mL) and
washed with water (3 ꢀ 10 mL). The organic layer was
separated, dried over anhydrous MgSO4, and filtered. The
solvent was removed under reduced pressure and the product
purified by silica gel chromatography (ethyl acetate–hexane).
1H and 13H NMR spectra were carried out in CDCl3.
31. Nair, V.; Augustine, A.; Suja, T. D. Synthesis 2002, 2259.
Acknowledgement
We thank the National Institutes of Health and the
Robert H. Cole Foundation for financial support of this
research.
1
References and notes
32. White solid, mp 150 °C, H NMR (250 MHz, CDCl3): d
2.60 (3H), 7.02 (d, J ¼ 15:5 Hz, 1H), 7.53–7.64 (m, 5H),
7.71 (d, J ¼ 15:5 Hz, 1H), 7.97 (d, J ¼ 7:8 Hz, 4H); 13C
NMR (62.5 MHz, CDCl3): d 26.6, 127.6, 128.6, 128.8,
129.3, 129.7, 133.5, 136.4, 138.5, 140.0, 140.6, 197.0. Anal.
Calcd for C16H14O3S: C, 67.11; H, 4.93. Found: C, 67.05;
H, 5.01.
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