Palladium-Catalyzed Cross-Coupling of Acetates of Baylis-Hillman Adducts and Potassium Organotrifluoroborates

Article abstract of DOI:10.1021/ol0351798

(Matrix presented) The cross-coupling of potassium organotrifluoroborates and acetates of Baylis-Hillman adducts proceeds readily in moderate to excellent yield in the presence of Pd(OAc)₂. The reaction tolerates hindered trifluoroborate salts,

Full text of DOI:10.1021/ol0351798

ORGANIC
LETTERS
2003
Vol. 5, No. 21
3803-3805
Palladium-Catalyzed Cross-Coupling of
Acetates of Baylis−Hillman Adducts and
Potassium Organotrifluoroborates
George W. Kabalka,* Bollu Venkataiah, and Gang Dong
Departments of Chemistry and Radiology, The UniVersity of Tennessee,
KnoxVille, Tennessee 37996-1600
kabalka@utk.edu
Received June 25, 2003
ABSTRACT
The cross-coupling of potassium organotrifluoroborates and acetates of Baylis−Hillman adducts proceeds readily in moderate to excellent
yield in the presence of Pd(OAc)2. The reaction tolerates hindered trifluoroborate salts, and the process is stereoselective.
The palladium catalyzed cross-coupling of organoboron
compounds and organic electrophiles to form carbon-carbon
bonds is an important synthetic reaction.1 The availability
of the prerequisite reagents and the mild reaction conditions
all contribute to the versatility of the reaction. Significantly,
the reaction is unaffected by water, and a broad range of
functional groups are tolerated. The cross-coupling is both
regio- and stereoselective.
Palladium catalysts have been used in a wide variety of
synthetically useful reactions involving stabilized carbon
nucleophiles.2 However, few studies have been reported in
which boron reagents are used as nucleophiles in allylic
coupling reactions.3 Hayashi and co-workers described the
reaction of phenylboronic acid with allyl acetates in water
using a resin-supported palladium catalyst;4 later, Balme
extended the reaction utilizing various Pd catalytic systems
and solvents.5 These results encouraged us to study the
reaction of organoborates with Baylis-Hillman acetates.
The Baylis-Hillman reaction provides molecules pos-
sessing hydroxyl, alkene, and electron-withdrawing groups
in close proximity, which makes it valuable in a number of
stereoselective processes.6 In a continuation of our study of
reactions involving organoboron reagents in nonconventional
solvents,7 we studied the cross-coupling reaction of potassium
organotrifluoroborates with acetates of Baylis-Hillman
adducts in the presence of Pd catalysts using methanol as
the solvent.
We first examined the reaction of p-tolylboronic acid with
a Baylis-Hillman acetate adduct; however, no reaction
occurred. Potassium acetate was then added as a base, but
the acetate behaved as a nucleophile and the SN2′ substitution
product formed instead of desired product.8 We then carried
out a reaction using cesium fluoride as the base since it has
* To whom correspondence should be addressed.
(1) (a) Miyaura, N.; Suzuki, A. Chem. ReV. 1995, 95, 2457. (b) Suzuki,
A. J. Organomet. Chem. 1999, 576, 147. (c) Sambasivarao, K.; Lahiri, K.;
Kashinath, D. Tetrahedron 2002, 58, 9633.
(2) (a) Trost, B. M.; Van Vranken, D. L. Chem. ReV. 1996, 96, 395. (b)
Tsuji, J. Transition Metal Reagents and Catalysts; Wiley: New York, 2000.
(3) (a) Miyaura, N.; Yamada, K.; Suginome, H.; Suzuki, A. J. Am. Chem.
Soc. 1985, 107, 972. (b) Legros, J.-Y.; Fiaud, J.-C. Tetrahedron Lett. 1990,
31, 7453. (c) Moreno-Mana, M.; Pajuelo, F.; Pleixats, R. J. Org. Chem.
1995, 60, 2396. (d) Miyaura, N.; Tanabe, Y.; Suginome, H.; Suzuki, A. J.
Organomet. Chem. 1982, 233, C13. (e) Miyaura, N.; Suginome, H.; Suzuki,
A. Tetrahedron Lett. 1984, 25, 761. (f) Ortar, G. Tetrahedron Lett. 2003,
44, 4311.
(4) Uozumi, Y.; Danjo, H.; Hayashi, T. J. Org. Chem. 1999, 64, 3384.
(5) Bouyssi, D.; Gerusz, V.; Balme, G. Eur. J. Org. Chem. 2002, 2445.
(6) (a) Drewes, S. E.; Ross, G. H. P. Tetrahedron 1988, 44, 4653. (b)
Basavaiah, D.; Dharmarao, P.; Suguna H. R. Tetrahedron 1996, 52, 8001.
(7) (a) Kabalka, G. W.; Malladi, R. R. Chem. Commun. 2000, 2191. (b)
Kabalka, G. W.; Namboodiri, V.; Wang, L. Chem. Commun. 2001, 775.
(c) Kabalka, G. W.; Wang, L. Tetrahedron Lett. 2002, 43, 3067. (d) Kabalka,
G. W.; Venkataiah, B. Tetrahedron Lett. 2002, 43, 3703.
10.1021/ol0351798 CCC: $25.00 © 2003 American Chemical Society
Published on Web 09/18/2003

Scheme 1
Table 1. Reaction of Potassium p-Tolyltrifluoroborate with
Baylis-Hillman Adduct Acetatesa
Table 2. Reaction of Different Potassium
Organotrifluoroborates with Baylis-Hillman Adduct Methyl
3-Phenyl-3-acetoxy-2-methylene
entry
R′
time (h)
isolated yield (%)
1
2
3
4
5
6
phenyl
p-methoxyphenyl
3-thiofuryl
2-methylphenyl
2,6-dimethylphenyl
2,6-difluorophenyl
3
8
3
5
12
48
86
76
61
76
53
68
We then utilized potassium organotrifluoroborate salts,
which are more nucleophilic than the corresponding boronic
acids. They are also air and moisture stable and can be
synthesized readily from corresponding boronic acids by the
addition of KHF2.10 Recent studies indicate that trifluorobo-
rate salts have many advantages when compared to boronic
acids.10c,11 Reactions of Baylis-Hillman acetate adducts (1)
with potassium organotrifluoroborates (2) take place in the
presence of 3 mol % Pd(OAc)2 in methanol at room
temperature in good yields. 3-Acetoxy-2-methyleneal-
kanoates react with a variety of potassium organotrifluo-
roborates to provide (E)-2-substituted 2-alkenoates (3) as the
major products. Regioisomer 4 was also observed (Scheme
1).12 However, 3 and 4 are readily separated by column
chromatography.
(8) Kabalka, G. W.; Venkataiah, B.; Dong G. Tetrahedron Lett. 2003,
44, 4673.
(9) (a) Wright, S. W.; Hageman, D. L.; McClure, L. D. J. Org. Chem.
1994, 59, 6095.
(10) (a) Vedejs, E.; Chapman, R. W.; Fields, S. C.; Lin, S.; Schrimpf,
M. R. J. Org. Chem. 1995, 60, 3020. (b) Petasis, N. A.; Yudin, A. K.;
Zavialov, I. A.; Prakash, G. K. S.; Olah, G. A. Synlett 1997, 606. (c) Darses,
S.; Genet, J.-P.; Brayer, J.-L.; Demoute, J.-P. Tetrahedron Lett. 1997, 38,
4393.
a All reactions were carried out in the presence of 3 mol % Pd(OAc)2 at
room temperature for 3 h. b All products exhibited satisfactory spectral (1H,
13C NMR) and analytical properties. c Isolated yields.
(11) (a) Darses, S.; Michaud, G.; Genet, J.-P. Tetrahedron Lett. 1998,
39, 5045. (b) Batey, R. A.; Quach, T. D. Tetrahedron Lett. 2001, 42, 9099.
(c) Molander, G. A.; Ito, T. Org. Lett. 2001, 3, 393. (d) Molander, G. A.;
Biolatto, B. Org. Lett. 2002, 4, 1867. (e) Pucheault, M.; Darses, S.; Genet,
J.-P. Eur. J. Org. Chem. 2002, 3552.
been shown to be effective in Suzuki coupling reactions.3f,9
The desired reaction occurred, but a significant quantity of
the homo-coupling product formed.
3804
Org. Lett., Vol. 5, No. 21, 2003

Scheme 2
The reaction of 3-acetoxy-2-methylenealkanenitriles pro-
acetate adducts. The protocol is applicable to aryl, heteroaryl,
and alkenyltrifluoroborate salts. The reaction of vinylborates
is stereospecific. No additional base or ligand is required,
and the reaction takes place at room temperature in a
straightforward fashion.17
vides (Z)-2-substituted alk-2-enenitriles (5). In this case, the
formation of regioisomers was not observed (Scheme 1,
Table 1). The formation of esters and nitriles is consistent
with earlier studies.6,13
The stereochemistry of the products was established by
comparing NMR values of olefinic and methylene protons
with literature values.14 In all cases, the stereoselectivity was
Acknowledgment. We thank the Department of Energy
and The Robert H. Cole Foundation for their support.
1
found to be >98:2, as determined by H NMR analysis.
1
Supporting Information Available: H and 13C spectral
Several types of potassium trifluoroborates participate in
this reaction (Table 2). These include aryl, heteroaryl, and
even sterically hindered trifluoroborate salts. Alkenyltri-
fluoroborates can also be utilized (Scheme 2). It is notewor-
thy that (E)- and (Z)-alkenyl trifluoroborates couple with
Baylis-Hillman acetates stereospecifically.15,16
and analytical data. This material is available free of charge
via the Internet at http://pubs.acs.org.
OL0351798
(15) Similar selectivity was observed in the Suzuki cross-coupling of
potassium alkenyltrifluoroborates: Molander, G. A.; Bernardi, C. R. J. Org.
Chem. 2002, 67, 8424.
In conclusion, we have developed a Pd-catalyzed coupling
(16) It is interesting to note that trifluoroborate reagents have been shown
to be ineffective in Suzuki coupling reactions with certain catalyst systems.
See: Littke, A. F.; Dai, C.; Fu, G. C. J. Am. Chem. Soc. 2000, 122, 4020.
(17) General Procedure. The acetate of Baylis-Hillman adduct 1 (1
mmol) and 3 mol % Pd(OAc)2 is added to a solution of potassium
organotrifluoroborate salt 2 (1 mmol) in methanol (5 mL) at 0 °C under a
nitrogen atmosphere. The reaction mixture is allowed to stir at room
temperature until completion (TLC monitoring). The mixture is then diluted
with diethyl ether (10 mL) and filtered to remove solids. The solvent is
removed under reduced pressure and the product purified by chromatography
(silica gel) to afford analytically pure product.
of potassium organotrifluoroborates with Baylis-Hillman
(12) Isomer 4 was isolated in 18% yield for the aliphatic Baylis-Hillman
reagent (Table 1, entry 4).
(13) Wang, S.-Z.; Yamamoto, K.; Yamada, H.; Takahashi, T. Tetrahe-
dron 1992, 48, 2333.
(14) (a) Basavaiah, D.; Sarma, P. K. S.; Bhavani, A. K. D. Chem.
Commun. 1994, 1091. (b) Basavaiah, D.; Pandiaraju, S.; Padmaja, K. Synlett
1996, 393. (c) Basavaiah, D.; Krishnamacharyulu, M.; Suguna H. R.;
Pandiaraju, S. Tetrahedron Lett. 1997, 38, 2141.
Org. Lett., Vol. 5, No. 21, 2003
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