Palladium(II)-catalyzed conjugate addition of arylsiloxanes in water

Article abstract of DOI:10.1021/ol071067v

Equation Presented Palladium-phosphinous acids catalyze the conjugate addition of arylsiloxanes to a wide range of α.β-unsaturated substrates in water microwave-assisted procedure is described that uses 5 mol % of POPd1 to afford /-substituted ketones, aldehydes, esters, nitriles, an nitroalkanes in 83% to 96% yield within 4 h. This method eliminates the need for stoichiometric additives and an excess of arylsiloxane, an does not require an inert atmosphere.

Full text of DOI:10.1021/ol071067v

ORGANIC
LETTERS
2007
Vol. 9, No. 14
2737-2740
Palladium(II)-Catalyzed Conjugate
Addition of Arylsiloxanes in Water
Rachel Lerebours and Christian Wolf*
Department of Chemistry, Georgetown UniVersity, Washington, DC 20057
cw27@georgetown.edu
Received May 7, 2007
ABSTRACT
Palladium−phosphinous acids catalyze the conjugate addition of arylsiloxanes to a wide range of
r
,
â
-unsaturated substrates in water. A
microwave-assisted procedure is described that uses 5 mol % of POPd1 to afford
â
-substituted ketones, aldehydes, esters, nitriles, and
nitroalkanes in 83% to 96% yield within 4 h. This method eliminates the need for stoichiometric additives and an excess of arylsiloxane, and
does not require an inert atmosphere.
In recent years, increasing efforts have been devoted to
transition metal-catalyzed conjugate additions of organome-
tallic reagents to R,â-unsaturated ketones and other Michael
acceptors.1 This important carbon-carbon bond-forming
reaction is usually accomplished with organoboronic acids
in the presence of rhodium catalysts.2 The use of palladium
catalysts is less common because they can form carbon-
bound enolates that undergo â-hydride elimination toward
Heck reaction products.3 Miyaura and others demonstrated
that this can be controlled with dicationic palladium(II)
complexes which effectively catalyze 1,4-additions with
minimal formation of Heck-type byproducts.4 Copper cata-
lysts have proved very useful in combination with Grignard5
or organozinc6 reagents, and rhodium-catalyzed conjugate
additions of arylstannanes7 and aryltitanium8 compounds
have also been described.
The use of silicon compounds provides an attractive
alternative to these methods due to the general availability,
low toxicity, and insensitivity of arylsiloxanes to various
functional groups.9 Several protocols suitable for rhodium-
catalyzed 1,4-addition of arylsiloxanes or arylchlorosilanes
to R,â-unsaturated ketones, esters, and amides have been
developed.10 By contrast, few palladium(II)-catalyzed con-
(4) (a) Nishikata, T.; Yamamoto, Y.; Miyaura, N. Angew. Chem., Int.
Ed. 2003, 42, 2768-2770. (b) Lu, X.; Lin, S. J. Org. Chem. 2005, 70,
9651-9653. (c) Lin, S.; Lu, X. Tetrahedron Lett. 2006, 47, 7167-7170.
(5) (a) Villacorta, G. M.; Rao, C. P.; Lippard, S. J. J. Am. Chem. Soc.
1988, 110, 3175-3182. (b) Ahn, K.-H.; Klassen, R. B.; Lippard, S. J.
Organometallics 1990, 9, 3178-3181.
(6) (a) Shintani, R.; Fu, G. C. Org. Lett. 2002, 4, 3699-3702. (b)
Duursma, A.; Minnaard, A. J.; Feringa, B. L. J. Am. Chem. Soc. 2003,
125, 3700-3701. (c) Sebesta, R.; Pizzuti, M. G.; Boersma, A. J.; Minnaard,
A. J.; Feringa, B. L. Chem. Commun. 2005, 1711-1713.
(7) (a) Huang, T.-S.; Li, C.-J. Org. Lett. 2001, 3, 2037-2039. (b) Huang,
T.; Meng, Y.; Vemkatraman, S.; Wang, d.; Li, C.-J. J. Am. Chem. Soc.
2001, 123, 7451-7452. (c) Oi, S.; Moro, M.; Ito, H.; Honma, Y.; Miyano,
S.; Inoue, Y. Tetrahedron 2002, 58, 91-97.
(1) (a) Rossiter, B.; Swingle, N. M. Chem. ReV. 1992, 92, 771-806. (b)
Miyaura, N.; Suzuki, A. Chem. ReV. 1995, 95, 2457-2483. (c) Krause, N.;
Hoffmann-Ro¨der, A. Synthesis 2001, 171-196.
(2) (a) Sakai, M.; Hayashi, H.; Miyaura, N. Organometallics 1997, 16,
4229-4231. (b) Ramnauth, J.; Poulin, O.; Bratovanov, S. S.; Rakhit, S.;
Maddaford, S. P. Org. Lett. 2001, 3, 2571-2573. (c) Hayashi, T.; Takahashi,
M.; Takaya, Y.; Ogasawara, M. J. Am. Chem. Soc. 2002, 124, 5052-5058.
(d) Cauble, D. F.; Gipson, J. D.; Krische, M. J. J. Am. Chem. Soc. 2003,
125, 1110-1111. (e) Fagou, K.; Lautens, M. Chem. ReV. 2003, 103, 169-
196. (f) Hayashi, T.; Yamasaki, K. Chem. ReV. 2003, 103, 2829-2844. (g)
Itooka, R.; Iguchi, Y.; Miyaura, N. J. Org. Chem. 2003, 68, 6000-6004.
(h) Chen, G.; Tokunaga, N.; Hayashi, T. Org. Lett. 2005, 7, 2285-2288.
(i) Navarre, L.; Pucheault, M.; Dsarses, S.; Genet, J.-P. Tetrahedron Lett.
2005, 46, 4247-4250. (j) Yamamoto, T.; Iizuka, M.; Ohta, T.; Ito, Y. Chem.
Lett. 2006, 35, 198-199.
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metallics 2005, 24, 5025-5032.
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10.1021/ol071067v CCC: $37.00
© 2007 American Chemical Society
Published on Web 06/13/2007

jugate additions with arylsiloxanes are known.11 Among
Michael acceptors, R,â-conjugated aldehydes and ketones
have been identified as the most reactive substrates and have
been studied more extensively than unsaturated esters and
nitroalkenes.12 To date, a broadly applicable method that
allows 1,4-additions of arylsiloxanes to a wide range of
Michael acceptors providing the corresponding â-substituted
products in high yields has not been reported.
We have recently introduced palladium-phosphinous acid
catalysts to Hiyama cross-coupling and oxidative esterifica-
tion of aldehydes with tetramethyl orthosilicate.13 This class
of catalysts shows remarkable stability to air and water,
which facilitates operation and catalyst recycling, and has
been successfully applied in Suzuki, Stille, Sonogashira, and
other cross-coupling reactions (Figure 1).14 Since palladium-
investigate the usefulness of palladium-phosphinous acids
for conjugate addition of arylsiloxanes to R,â-unsaturated
compounds.
Initial screening of the palladium-phosphinous acids
shown above in acetonitrile or aqueous solvents revealed that
the reaction between 2-cyclohexen-1-one, 1, and phenyltri-
methoxysilane, 2, proceeds in the presence of 5 mol % of
POPd1 and tetrabutylammonium fluoride in refluxing water,
generating 3-phenylcyclohexanone, 3, in 52% yield after 24
h. Further screening of KF, CsF, and several tetraalkyl-
ammonium fluoride sources showed that 3 can be obtained
in 85% yield when tetraethylammonium fluoride, TEAF, is
employed. We were pleased to find that the POPd1-catalyzed
conjugate addition of 2 to 1 can be conveniently conducted
in a microwave, providing 3 in 89% yield within 4 h.
We then decided to study the scope of the palladium-
phosphinous acid-catalyzed conjugate addition using the
conditions summarized in Scheme 1. To our disappointment,
Scheme 1. POPd1-catalyzed Conjugate Addition
yields decreased significantly when we applied our procedure
to other arylsiloxanes or Michael acceptors such as unsatur-
ated nitriles.
Following Miyaura’s reports on copper-promoted 1,4-
additions of arylsiloxanes to enones we realized that the
addition of catalytic amounts of Cu(BF4)2 or Cu(ACN)4PF6
to the reaction mixture overcomes these problems.11a In
particular, the use of 5 mol % of POPd1 and 10 mol % of
Cu(ACN)4PF6 as cocatalyst resulted in a broadly applicable
conjugate addition procedure that tolerates a range of
arylsiloxanes and R,â-unsaturated substrates (Table 1). Under
these conditions, conjugate addition of arylsiloxanes, includ-
ing 4-aminophenyltrimethoxysilane, 8, 3-furyltrimethoxysi-
lane, 10, and 2-thienyltrimethoxysilane, 12, to 2-cyclohexen-
1-one, 1, or 2-cyclopenten-1-one, 14, furnishes the corre-
sponding â-substituted cycloalkanones 3, 5, 7, 9, 11, 13, and
15 in 83-96% yield (entries 1-7). Excellent results were
also obtained with R,â-unsaturated aldehyde 16 and ester
18 (entries 8 and 9). Importantly, our procedure is applicable
to unsaturated nitriles and nitroalkenes. Addition of 2 to
cinnamonitrile, 20, and methacrylonitrile, 22, gave 3,3-
diphenylpropionitrile, 21, and 2-methyl-3-phenylpropionitrile,
23, in 83% and 93% yield, respectively (entries 10 and 11).
(E)-â-Nitrostyrene, 24, and 1-nitrocyclohexene, 26, undergo
POPd1-catalyzed 1,4-addition to form 2,2-diphenylnitro-
ethane, 25, and 2-phenylnitrocyclohexane, 27, in 88% and
87% yield (entries 12 and 13).
Figure 1. Structures of palladium-phosphinous acids.
(II) complexes have been found to undergo relatively fast
transmetalation with organosilicon species, we decided to
(10) (a) Huang, T.-S.; Li, C.-J. Chem. Commun. 2001, 2348-2349. (b)
Mori, A.; Danda, Y.; Fujii, T.; Hirabayashi, K.; Osakada, K. J. Am. Chem.
Soc. 2001, 123, 10774-10775. (c) Koike, T.; Du, X.; Mori, A.; Osakada,
K. Synlett 2002, 301-303. (d) Murata, M.; Shimazaki, R.; Ishikura, M.;
Watanabe, S.; Masuda, Y. Synthesis 2002, 717-719. (e) Oi, S.; Honma,
Y.; Inoue, Y. Org. Lett. 2002, 4, 667-669. (f) Oi, S.; Taira, A.; Honma,
Y.; Inoue, Y. Org. Lett. 2003, 5, 97-99. (g) Oi, S.; Taira, A.; Honma, Y.;
Sato, T.; Inoue, Y. Tetrahedron: Asymmetry 2006, 17, 598-602.
(11) (a) Nishikata, T.; Yamamoto, Y.; Miyaura, N. Chem. Lett. 2003,
32, 752-753. (b) Nishikata, T.; Yamamoto, Y.; Miyaura, N. Organome-
tallics 2004, 23, 4317-4324. (c) Gini, F.; Hessen, B.; Feringa, B. L.;
Minnaard, A. J. Chem. Commun. 2007, 710-712.
(12) Denmark, S. E.; Amishiro, N. J. Org. Chem. 2003, 68, 6997-7003.
(13) (a) Wolf, C.; Lerebours, R.; Tanzini, E. H. Synthesis 2003, 2069-
2073. (b) Wolf, C.; Lerebours, R. Org. Lett. 2004, 6, 1147-1150. (c)
Lerebours, R.; Wolf, C. Synthesis 2005, 2287-2292. (d) Lerebours, R.;
Wolf, C. J. Am. Chem. Soc. 2006, 128, 13052-13053.
(14) (a) Li, G. Y. Angew. Chem., Int. Ed. 2001, 40, 1513-1516. (b) Li,
G. Y. J. Org. Chem. 2002, 67, 3643-3650. (c) Wolf, C.; Lerebours, R. J.
Org. Chem. 2003, 68, 7077-7084. (d) Wolf, C.; Lerebours, R. J. Org. Chem.
2003, 68, 7551-7554. (e) Wolf, C.; Lerebours, R. Org. Biomol. Chem.
2004, 2, 2161-2164. (f) Bigeault, J.; Giordano, L.; Buono, G. Angew.
Chem., Int. Ed. 2005, 44, 4753-4757. (g) Lerebours, R.; Camacho-Soto,
A.; Wolf, C. J. Org. Chem. 2005, 70, 8601-8604. (h) Wolf, C.; Ekoue-
Kovi, K. Eur. J. Org. Chem. 2006, 1917-1925.
Important features of microwave-assisted palladium-
phosphinous acid-catalyzed conjugate additions with aryl-
siloxanes include high yields and short reaction times while
2738
Org. Lett., Vol. 9, No. 14, 2007

an inert atmosphere and the use of organic cosolvents are
unnecessary. The results summarized in Table 1 compare
favorably with yields obtained by previously developed
methods.11,12 For example, palladium-catalyzed formation of
cycloalkanones 3 and 15 in 73-78% and 60% yield,
respectively, has been reported. However, these procedures
generally require the use of 2.5 equiv of phenylsiloxane 2,
significantly longer reaction times (at least 23 h), and organic
solvents or water/dioxane mixtures under inert atmosphere.
2,2-Diphenylnitroethane 25 has been prepared in 70% yield
from 2 and 24 with palladium acetate as catalyst in the
presence of 4 equiv of TBAF and SbCl3, but no product was
obtained when 1-nitrocyclohexene 26 was employed in the
same reaction. To the best of our knowledge, the palladium-
catalyzed addition of arylsiloxanes to unsaturated esters and
nitriles is unprecedented.
Table 1. POPd1-Catalyzed Conjugate Addition of
Arylsiloxanes to R,â-Unsaturated Substratesa
A proposed catalytic cycle is shown in Scheme 2.
Dissociation of POPd1 generates a cationic palladium(II)
Scheme 2. Proposed Mechanism of the POPd1-Catalyzed
Conjugate Addition
catalyst that undergoes transmetalation with a hypervalent
arylsiloxane. Coordination of an R,â-unsaturated substrate
such as 2-cyclohexen-1-one to the arylpalladium(II) species
then affords a C-bound enolate that dissociates, presumably
via formation of the corresponding palladium O-enolate, to
form the Michael addition product while the catalytically
active palladium complex is regenerated. Since palladium-
(II) enolates are known to undergo fast hydrolytic cleavage,15
the last step is likely to be faster than â-hydride elimination
when the reaction is carried out in aqueous solvents.16 The
usefulness of POPd1 in conjugate additions of arylsiloxanes
a General procedure: The Michael acceptor (1.00 mmol), arylsiloxane
(1.30 mmol), Cu(ACN)4PF6 (0.1 mmol), and POPd1 (0.05 mmol) in 0.25
mL of water, 120 °C, 4 h.
(15) Albeniz, A. C.; Catalina, N. M.; Espinet, P.; Redon, R. Organo-
metallics 1999, 18, 5571-5576.
Org. Lett., Vol. 9, No. 14, 2007
2739

to a wide range of Michael acceptors with pure water as
solvent can therefore be attributed to the general stability of
palladium-phosphinous acids under aqueous conditions
which prevents precipitation of palladium black, and fast
dissociation of intermediate palladium(II) enolates toward
â-substituted conjugate addition products.
In summary, we have successfully employed a palladium-
phosphinous acid catalyst in microwave-assisted conjugate
additions of arylsiloxanes to a wide range of R,â-unsaturated
substrates in water. This reaction provides access to â-sub-
stituted ketones, aldehydes, esters, nitriles, and nitroalkanes
which are obtained in high yields. Attractive features of the
POPd1-catalyzed procedure are the broad application spec-
trum, tolerance of functional groups, short reaction times,
and operational simplicity due to the stability of palladium-
phosphinous acids to water and air.
Acknowledgment. We thank Combiphos Catalysts, Inc.
(www.combiphos.com) for providing POPd1.
Supporting Information Available: Synthetic procedures
and NMR spectra. This material is available free of charge
via the Internet at http://pubs.acs.org.
(16) Formation of Heck reaction products was not observed.
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