Palladium(0)-catalyzed Suzuki-Miyaura cross-coupling reactions of potassium aryl- and heteroaryltrifluoroborates with alkenyl bromides

Article abstract of DOI:10.1021/jo0608366

Efficient palladium(0)-catalyzed Suzuki-Miyaura cross-couplings are described. The reactions involving potassium aryl- and heteroaryltrifluoroborates with alkenyl bromides can generally be carried out using ≤2 mol % of palladium catalyst and 3 equiv of ba

Full text of DOI:10.1021/jo0608366

Palladium(0)-Catalyzed Suzuki-Miyaura Cross-Coupling Reactions
of Potassium Aryl- and Heteroaryltrifluoroborates with Alkenyl
Bromides
Gary A. Molander* and Tiziano Fumagalli
Roy and Diana Vagelos Laboratories, Department of Chemistry, UniVersity of PennsylVania,
Philadelphia, PennsylVania 19104-6323
gmolandr@sas.upenn.edu
ReceiVed April 20, 2006
Efficient palladium(0)-catalyzed Suzuki-Miyaura cross-couplings are described. The reactions involving
potassium aryl- and heteroaryltrifluoroborates with alkenyl bromides can generally be carried out using
e2 mol % of palladium catalyst and 3 equiv of base in toluene/H2O. When stereodefined alkenyl bromides
are employed, the resulting styrene derivatives are accessed stereospecifically. A variety of functional
groups are tolerated in both coupling partners.
Introduction
and increase its scope,3 surprisingly little research has been
performed on the nature of the organoboron moiety itself.
Boronic acids and boronate esters are the most commonly used
derivatives in the Suzuki-Miyaura cross-coupling reactions.
However, these are not without their limitations. Boronic acids
are subject to cyclic trimerization with loss of water, giving
anhydrides (boroxines). This creates difficulties in their direct
purification and in the determination of the proper stoichiometry
for coupling. Moreover, many boronic acids are prone to
protodeborination4 or homocoupling in the Suzuki process.5
The Suzuki-Miyaura reaction is one of the mildest methods
known for metal-mediated carbon-carbon bond formation.1 This
reaction, involving organoboron compounds, presents many
significant advantages over other protocols for similar cross-
couplings. For example, most organoborons can be prepared
easily via transmetalation or hydroboration, and they have a
tolerance for a broad range of functional groups. Additionally,
the inorganic boron-containing byproducts are less toxic than
those of organostannanes used in Stille coupling,2 and they can
be readily removed by a simple workup procedure. By contrast,
the complete removal of tin-containing byproducts is a well-
recognized problem, and the presence of even traces of these
compounds in organic products must be avoided if possible.
(3) (a) Old, D. W.; Wolfe, J. P.; Buchwald, S. L. J. Am. Chem. Soc.
1998, 120, 9722-9723. (b) Wolfe, J. P.; Singer, R. A.; Yang, B. H.;
Buchwald, S. L. J. Am. Chem. Soc. 1999, 121, 9550-9561. (c) Littke, A.
F.; Dai, C.; Fu, G. C. J. Am. Chem. Soc. 2000, 122, 4020-4028. (d) Bedford,
R. B.; Cazin, C. S. J. Chem. Commun. 2001, 1540-1541. (e) Littke, A. F.;
Fu, G. C. Angew. Chem., Int. Ed. 1999, 37, 3387-3388. (f) Zhang, C.;
Huang, J.; Trudell, M. L.; Nolan, S. P. J. Org. Chem. 1999, 64, 3804-
3805. (g) Netherton, M. R.; Dai, C.; Neuschutz, K.; Fu, G. C. J. Am. Chem.
Soc. 2001, 123, 10099-10100. (h) Kirchoff, J. H.; Dai, C.; Fu, G. C. Angew.
Chem., Int. Ed. 2002, 41, 1945-1947. (i) Gstottmayr, C. W. K.; Bohm, V.
P. W.; Herdtweck, F.; Grosche, M.; Herrmann, W. A. Angew. Chem., Int.
Ed. 2002, 41, 1363-1365. (j) Botella, L.; Na´jera, C. Angew. Chem., Int.
Ed. 2002, 41, 179-181. (k) Kirchhoff, J. H.; Netherton, M. R.; Hills, I. D.;
Fu, G. C. J. Am. Chem. Soc. 2002, 124, 13662-13663. (l) Kabalka, G. W.;
Pagni, R. M.; Hair, C. M. Org. Lett. 1999, 1, 1423-1425. (m) Kabalka, G.
W.; Namboodiri, V.; Wang, L. Chem. Commun. 2001, 775. (n) LeBlond,
C. R.; Andrews, A. T.; Sowa, J. R., Jr.; Sun, Y. Org. Lett. 2001, 3, 1555-
1557. (o) Sakurai, H.; Tsukuda, T.; Hirao, T. J. Org. Chem. 2002, 67, 2721-
2722. (p) Grasa, G. A.; Viciu, M. S.; Huang, J.; Zhang, C.; Trudell, M. L.;
Nolan, S. P. Organometallics 2002, 21, 2866-2873 and references therein.
(q) Bei, X.; Turner, H. W.; Weinberg, W. H.; Guram, A. S.; Petersen, J. L.
J. Org. Chem. 1999, 64, 6797-6803. (r) Yin, J.; Rainka, M. P.; Zhang,
X.-X.; Buchwald, S. L. J. Am. Chem. Soc. 2002, 124, 1162-1163. (s)
Parrish, C. A.; Buchwald, S. L. J. Org. Chem. 2001, 66, 3820-3827. (t)
Feuerstein, M.; Berthiol, F.; Doucet, H.; Santinelli, M. Synlett 2002, 1807-
1810 and references therein.
Although considerable efforts have been made to develop
metal-ligand catalyst systems that facilitate the Suzuki coupling
(1) For reviews, see: (a) Miyaura, N.; Suzuki, A. Chem. ReV. 1995, 95,
2457-2483. (b) Tsuji, J. Palladium Reagents and Catalysis; Wiley and
Sons: Chichester, U.K., 1995. (c) Suzuki, A. In Metal-Catalyzed Cross-
Coupling Reactions; Diederich, F., Stang, P. J., Eds.; VCH: Weinheim,
Germany, 1998; pp 49-97. (d) Suzuki, A. J. Organomet. Chem. 1999, 567,
147-168. (e) Suzuki, A. J. Organomet. Chem. 2002, 653, 83-90. (f) Kotha,
S.; Lahiri, K.; Dhurke, K. Tetrahedron 2002, 58, 9633-9695. (g) Hassan,
J.; Sevignon, M.; Gozzi, C.; Schulz, E.; Lemaire, M. Chem. ReV. 2002,
102, 1359-1469. (h) Suzuki, A.; Brown, H. C. Organic Syntheses Via
Boranes; Aldrich Chemical Co., Inc.: Milwaukee, WI, 2003; Vol. 3. (i)
Miyaura, N., Ed. Cross-Coupling Reactions; Springer-Verlag: Berlin, 2002.
(2) (a) Stille, J. K. Angew. Chem., Int. Ed. Engl. 1986, 25, 508-524.
(b) Farina, V.; Krishnamurthy, V.; Scott, W. J. Org. React. 1997, 50, 1-652.
For discussions concerning the toxicity of organotin compounds, see: (c)
De Mora, S. J. Tributyltin: Case Study of an EnVironmental Contaminant;
Cambridge University Press: New York, 1996. (d) Boyer, I. J. Toxicology
1989, 55, 253-298.
10.1021/jo0608366 CCC: $33.50 © 2006 American Chemical Society
Published on Web 06/24/2006
J. Org. Chem. 2006, 71, 5743-5747
5743

Molander and Fumagalli
TABLE 1. Optimizing the Cross-Coupling Reaction of Phenyltrifluoroborate with an Alkenyl Bromide
entry
catalyst/ligand
solvent
time
19 h
6 h
5 h
7 h
35 min
temp
base
% yielda
1
2
3
4
5
5 mol % of Pd(OAc)2/10 mol % of PPh3
1.2 mol % of Pd(PPh3)4
1.2 mol % of Pd(PPh3)4
1.2 mol % of Pd(PPh3)4
2 mol % of Pd(PPh3)4
THF/H2O (10:1)
THF/H2O (10:1)
Tol/H2O (10:1)
Tol/H2O (10:1)
Tol/H2O (2.6:1)
70 °C
70 °C
90 °C
90 °C
90 °C
Cs2CO3
Cs2CO3
Cs2CO3
43b
51b
92c
Cs2CO3
97c
a The reaction was carried out under inert atmosphere (N2), with degassed solvents. The reactions were performed at concentrations of approximately 0.3
M in organic halide. b 1H NMR yield. c Isolated yield.
Boronate esters, even though they perform better from this
point of view, lack atom economy. In fact, the diols utilized to
create them (e.g., catechol or pinacol) add considerable expense
to the overall process and, additionally, must be separated from
the coupled products.
Organotrifluoroborates are unique compounds that have been
shown to overcome many of the limitations inherent in other
organoboron coupling partners. Indeed, it has previously been
revealed that potassium organotrifluoroborates provide solutions
to many of these problems and restrictions, and a variety of
cross-coupling protocols have been revealed.6 Potassium orga-
notrifluoroborates are easily prepared on large scale (>100 g)
from boronic acids or boronate esters by treatment with an
aqueous solution of KHF2 (eq 1),7 which, on a molar basis, is
half the price of catechol and 25 times less expensive than
pinacol.
coupling reactions,6 we sought to extend their utility to systems
not previously reported. Herein we report Suzuki-Miyaura
cross-coupling reactions carried out between potassium aryl-
and heteroaryltrifluoroborates and alkenyl bromides, which
complements our previous efforts in the synthesis of unsaturated
arenes using alkenyltrifluoroborates and aryl halides.9
Results and Discussion
Attention was initially focused on the determination of
optimal conditions for the Suzuki-Miyaura cross-coupling
reaction between potassium phenyltrifluoroborates (1a) and (Z)-
(6-bromohex-5-enyloxy)-tert-butyldimethylsilane (2a), survey-
ing the conditions in terms of catalysts, ligands, base, and
solvents to obtain tert-butyldimethyl[(Z)-6-(phenyl)hex-5-enyl-
oxy]silane (3aa, Table 1).
Initially, Pd(OAc)2, PPh3, and Cs2CO3 were employed in
THF/H2O at 70 °C overnight (19 h),6c obtaining 43% of the
cross-coupled product 3aa (Table 1, entry 1). Next, the catalyst
was changed to a Pd(0) source, Pd(PPh3)4, resulting in a 51%
yield of 3aa in just 6 h (Table 1, entry 2). After settling on
Pd(PPh3)4 as the catalyst, the solvent mixture was changed from
THF/H2O to toluene/H2O (10:1) at 90 °C, thereby achieving a
92% yield of 3aa (Table 1, entry 3). Even though fluoride is
often used as a base in boronic acid mediated cross-coupling
reactions, we and others have found that exogenous aqueous
base is required for organotrifluoroborate cross-couplings.6c,10
To re-establish this point, the reaction was performed under
identical experimental conditions but in the absence of added
base; only starting material was recovered after 7 h at 90 °C
(Table 1, entry 4). Finally, efforts were made to increase the
rate of the reaction while maintaining a high yield. By keeping
the total toluene/H2O solvent volume constant but decreasing
the relative amount of toluene, the rate of the reaction was
increased, and the reaction time could be decreased. Thus,
employing 2 mol % of Pd(PPh3)4 in toluene/H2O (2.6:1) at 90
°C provided a 97% yield of 3aa in 35 min (Table 1, entry 5 or
Table 2, entry 1). This procedure was utilized as the basis for
all further studies. Under these conditions, the halide and catalyst
were soluble in the organic phase, while the base dissolved in
the water. Initially, the trifluoroborate was suspended in the
reaction mixture. Over time, two homogeneous phases were
created.
3 equiv of KHF2
ArB(OH)2
8ArBF3K
(1)
solvent, H2O
rt
The organotrifluoroborates thus generated are monomeric,
crystalline solids that can be stored on the shelf indefinitely.
Many (>50) are currently sold commercially. The byproducts
of the cross-coupling of organotrifluoroborates with organic
halides are inorganic salts that are readily separable from the
desired products. Finally, organotrifluoroborates can be em-
ployed in complex molecule synthesis in which a Suzuki-
Miyaura cross-coupling to a valuable partner comprises a key
transformation.8
Having previously established the efficiency and the advan-
tages of the organotrifluoroborate partners in a variety of cross-
(4) (a) Roques, B. P.; Florentin, D.; Callanquin, M. J. Heterocycl. Chem.
1975, 12, 195-196. (b) Roques, B. P.; Florentin, D.; Callanquin, M. J.
Heterocycl. Chem. 1976, 13, 1265-1272. (c) Kuivila, H. G.; Nahabedian
K. V. J. Am. Chem. Soc. 1961, 83, 2159-2163.
(5) Wong, M. S.; Zhang, X. L. Tetrahedron Lett. 2001, 42, 4087-4089.
(6) (a) Molander, G. A.; Biolatto, B. Org. Lett. 2001, 3, 393-396. (b)
Molander, G. A.; Biolatto, B. Org. Lett. 2002, 4, 1867-1870. (c) Molander,
G. A.; Biolatto, B. J. Org. Chem. 2003, 68, 4302-4314. (d) Molander, G.
A.; Katona, B. W.; Machrouhi, F. J. Org. Chem. 2002, 67, 8416-8423. (e)
Molander, G. A.; Yun, C. S.; Ribagorda, M.; Biolatto, B. J. Org. Chem.
2003, 68, 5534-5539. (f) Molander, G. A.; Ribagorda, M. J. Am. Chem.
Soc. 2003, 125, 11148-11149. (g) Molander, G. A.; Felix, L. A. J. Org.
Chem. 2005, 70, 3950-3956. (h) Molander, G. A.; Figueroa, R. Ald-
richimica Acta 2005, 38, 49-55.
To test the generality of the method, potassium aryltrifluo-
roborates were chosen that possessed diverse functionalities
(cyano, ether, aldehyde, halogen, and nitro groups, Table 2).
For this aspect of the study, (Z)-(6-bromohex-5-enyloxy)-tert-
(7) (a) Vedejs, E.; Chapman, R. W.; Fields, S. C.; Lin, S.; Schrimpf, M.
R. J. Org. Chem. 1995, 60, 3020-3027. (b) Vedejs, E.; Fields, S. C.;
Hayashi, R.; Hitchcock, S. R.; Powell, D. R.; Schrimpf, M. R. J. Am. Chem.
Soc. 1999, 121, 2460-2470.
(8) (a) Molander, G. A.; Dehmel, F. J. Am. Chem. Soc. 2004, 126,
10313-10318. (b) Skaff, O.; Jolliffe, K. A.; Hutton, C. A. J. Org. Chem.
2005, 70, 7353-7363. (c) Garc´ıa-Fortanet, J.; Debergh, J. R.; De Brabander,
J. K. Org. Lett. 2005, 7, 685-688. (d) Toyota, M.; Asano, T.; Ihara, M.
Org. Lett. 2005, 7, 3929-3932.
(9) Molander, G. A.; Bernardi, C. J. Org. Chem. 2002, 67, 8424-8429.
(10) (a) Batey, R. A.; Quach, T. D. Tetrahedron Lett. 2001, 42, 9099-
9103. (b) Yuen, A. K. L.; Hutton, C. A. Tetrahedron Lett. 2005, 46, 7899-
7903.
5744 J. Org. Chem., Vol. 71, No. 15, 2006

Pd-Catalyzed Suzuki-Miyaura Cross-Coupling Reactions
TABLE 2. Cross-Coupling Reaction of Potassium Aryltrifluoroborates with (Z)-(6-Bromohex-5-enyloxy)-tert-butyldimethylsilane
a Condition A: 2 mol % of Pd(PPh3)4, toluene:H2O (2.6:1), 3 equiv of Cs2CO3, 90 °C, under N2. b The reaction was carried out with K2CO3 instead of
Cs2CO3. c The reaction was carried out with 4.5 mol % of Pd(PPh3)4. d The reaction was carried out with 9 mol % of P(Bu)3. e The reaction was carried out
at 55 °C. f The reaction was carried out with 4.5 mol % of Pd(dppf)‚CH2Cl2. g The reaction was not optimized for time or mol % of catalyst loaded. h The
reaction was carried out with 0.5 mol % of Pd(PPh3)4. i GC purity.
butyldimethylsilane (2a) was again selected as the standard
electrophile. The reactions conducted led to very high yields
of the cross-coupled product, with reaction times varying
between 25 min and 3.5 h (with the exception of entry 11, Table
2). The reaction results confirm the stereospecificity of the
reaction and the compatibility of silyl ether protecting groups
with the reaction conditions. The latter point was previously a
concern because the trifluoroborates represent an obvious source
of fluoride that is often used to deprotect silylated alcohols.
The protecting group stability is perhaps due to the heteroge-
neous nature of the system in which the fluoride is solvated in
the aqueous layer and thus unavailable to deprotect the organic
soluble silyl ether.6g
Electron-neutral potassium aryltrifluoroborates were exam-
ined, starting with potassium 1-naphthyltrifluoroborate 1b. The
reaction was complete in 50 min, affording a quantitative yield
of 3ba (Table 2, entry 2). To begin an evaluation of steric and
electronic effects, potassium 4-tolyl- (1d), potassium 2-tolyl-
(1c), and potassium 2,6-dimethylphenyltrifluoroborate 1f were
examined in which inductively electron-donating substituents
were present. Potassium 4-tolyl-trifluoroborate was the fastest,
with the product 3da being obtained in 93% yield in 25 min
J. Org. Chem, Vol. 71, No. 15, 2006 5745

Molander and Fumagalli
TABLE 3. Cross-Coupling Reaction of Potassium Aryltrifluoroborates with Bromoalkenes
a Condition A: 2 mol % of Pd(PPh3)4, toluene:H2O (2.6:1), 3 equiv of K2CO3, 90 °C, under N2. b The reaction was carried out with 2 mol % of
Pd(dppf)‚CH2Cl2 instead of Pd(PPh3)4.
(Table 2, entry 4). Potassium 2-tolyl-trifluoroborate is more
sterically hindered, and the synthesis of 3ca was realized in
91% yield after 1.5 h (Table 2, entry 3). Potassium 2,6-
dimethylphenyltrifluoroborate, the most sterically hindered of
the trio, required 4.5 mol % of catalyst to achieve an 82% yield
of 3fa in 2.8 h (Table 2, entry 6). An identical reaction charged
with 2 mol % of catalyst resulted in about 64% yield of the
instead of Cs2CO3. Thus, potassium 4-methoxyphenyltrifluo-
roborate 1e and potassium 4-fluorophenyltrifluoroborate 1g were
tested, as these substituents have π-releasing but inductively
electron-withdrawing characteristics. The reaction with 1e was
complete in 40 min, providing a 97% yield of 3ea (Table 2,
entry 5). In a similar manner, product 3ga was obtained in 95%
yield from substrate 1g after 55 min (Table 2, entry 7).
To access the product (3ha, 89% yield, 3 h) from the coupling
between the electron-deficient aryltrifluoroborate 1h and alkenyl
halide 2a, it was necessary to employ 9 mol % of (Bu)3P as the
phosphine ligand (Table 2, entry 8). For the remaining electron-
poor aryltrifluoroborates, 4.5 mol % of the less expensive and
more stable PdCl2(dppf)‚CH2Cl2 was employed, which per-
1
desired product after 5 h as determined by H NMR spectros-
copy. As the steric hindrance of the substrates increased,
protodeborination became more important, leaving some of the
bromoalkene unreacted.
To decrease the reaction cost, all of the remaining reactions
(including 3fa, Table 2, entry 6) were performed with K2CO3
5746 J. Org. Chem., Vol. 71, No. 15, 2006

Pd-Catalyzed Suzuki-Miyaura Cross-Coupling Reactions
formed better than 4.5 mol % of Pd(PPh3)4 (Table 2, entry 8).
In this manner, potassium 4-nitrophenyltrifluoroborate 1i pro-
vided the cross-coupled product 3ia in 90% yield (Table 2, entry
9), which was g87% pure by capillary GC analysis. Unfortu-
nately in this case, it was not possible to remove an unknown
byproduct by silica gel column chromatography. Other electron-
deficient arylborons worked equally well under these conditions.
Thus, potassium 4-trifluoroboratobenzaldehyde 1j yielded the
product 3ja in 89% yield (Table 2, entry 10), and potassium
3-cyanophenyltrifluoroborate 1k gave the product 3ka in 86%
yield (Table 2, entry 11).
Potassium heteroaryltrifluoroborates were examined using the
same catalyst [Pd(PPh3)4] as that employed for electron-rich
aryltrifluoroborates (1l, 1m, and 1n). Thus, 3-trifluorobora-
tothiophene 1l was cross-coupled with 2a, and after 2.5 h, 3la
was generated in quantitative yield (Table 2, entry 12). To
demonstrate that the method is suitable for large-scale reactions,
where the amount of catalyst is a concern, the same reaction
was performed with a lower catalyst loading [0.5 mol % of Pd-
(PPh3)4]. Under these conditions, the reaction took longer (3.5
h as opposed to 2.5 h with 2 mol % of catalyst), but still gave
a 93% yield of product 3la (Table 2, entry 13). Cross-coupling
of potassium 2-trifluoroboratothiophene 1m and alkenyl bromide
2a yielded 3ma in 80% yield (Table 2, entry 14). Potassium
3-trifluoroboratofuran afforded 98% of the cross-coupled product
in 2.5 h (Table 2, entry 15).
Conclusions
In summary, the palladium-catalyzed cross-coupling reactions
of potassium aryl- and heteroaryltrifluoroborates with alkenyl
halides were achieved in good to excellent yields. The procedure
possesses several advantages when compared with other meth-
ods. The potassium aryltrifluoroborates can be prepared easily
by different routes, and the ease of isolation, purification,
handling, and long-term storage makes them attractive inter-
mediates for large scale use as well. The cross-coupling can be
carried out rapidly using as little as 0.5 mol % of catalyst loading
along with an inexpensive inorganic base. For electron-neutral
and electron-rich aryltrifluoroborates, Pd(PPh3)4 is suitable for
the cross-coupling, while PdCl2(dppf)‚CH2Cl2 has proven to be
more efficient in the coupling of electron-deficient aryltrifluo-
roborates.
When (Z)-bromoalkenes are employed, the (Z)-styryl moiety
is achieved stereospecifically, and silyl protecting groups for
alcohols are tolerated even though a fluoride source is present.
Moreover, a variety of other functional groups (aldehydes,
ketones, enones, nitriles, and nitro groups) and substitution
patterns are tolerated in both coupling partners.
Experimental Section
General Procedure for Suzuki-Miyaura Cross-Coupling
Reactions. Preparation of tert-Butyldimethyl[(Z)-6-(phenyl)hex-
5-enyloxy]silane (3aa). In a 13 × 100 mm test tube were weighed
Cs2CO3 (1.13 mmol, 366.0 mg), 1a (0.42 mmol, 80.0 mg), Pd-
(PPh3)4 (0.0074 mmol, 8.6 mg, 2 mol %), and 2a (0.38 mmol, 116.2
mg). A septa was placed on the test tube which then was purged
with N2 for 2 min. The solvents (1 mL of toluene and 0.375 mL of
H2O) were added, and the test tube was put in an oil bath previously
set at 90 °C. The reaction was monitored by TLC with hexanes as
eluent. After 35 min, when the reaction was complete, it was diluted
with hexanes, and MgSO4 was added. The organic layer was
removed, and the remaining MgSO4 paste was triturated five times
with hexanes. The combined organic extracts were added directly
to a plug of silica gel to remove the catalyst, thus yielding the crude
product. Further purification was accomplished via column chro-
matography (SiO2, hexanes), yielding a colorless oil (107.1 mg,
97%).
Continuing with the investigation, the scope of the reaction
with regard to the bromoalkenes was examined. Haloalkenes
containing a variety of functional groups (R,â-unsaturated
ketones, R,â-unsaturated aldehydes, R,â-unsaturated amides),
as well as substitution patterns (trisubstituted bromoalkenes,
tetrasubstituted bromoalkenes, and ω-halogenobromoalkenes),
all proved to be successful coupling partners (Table 3).
The products resulting from coupling of 1a with (E)-2,3-
diphenylpropenal, 3-methyl-2-phenyl-2-cyclopent-2-enone, 6-flu-
oro-3-phenylchromen-4-one, and 1,3-dimethyl-5-phenyl-1H-
pyrimidine-2,4-dione (3ac, 3ad, 3ae, 3af, respectively) were all
obtained as white solids. R-Bromocinnamaldehyde 2c was
coupled with 1a, leading to the desired product 3ac in 94%
yield in 30 min (Table 3, entry 1). The reaction of 2-bromo-
3-methyl-2-cyclopenten-1-one 2d afforded the product 3ad in
87% yield after a longer period of time (1.8 h, Table 3, entry
2). Products 3ae and 3af were recrystallized and obtained in
87 (1 h) and 88% yield (3 h), respectively (Table 3, entries 3
and 4). The cross-coupling reaction between (Z)-1-bromo-6-
chlorohex-1-ene 2b and potassium 1-naphthalenetrifluoroborate
1b yielded, without further purification, 94% of product 3bb
in 1 h (Table 3, entry 5). The reaction with R-bromostyrene 2g
was carried out with 1a, using 2 mol % of Pd(PPh3)4 to give a
crude product that was difficult to separate from the biphenyl
byproduct. However, utilizing 4-trifluoroboratobenzaldehyde 1j
in conjunction with 2g and 2 mol % of PdCl2(dppf)‚CH2Cl2 as
the catalyst allowed access to the corresponding product in 89%
yield in 3 h. This product, 3jg, possessed higher polarity and
silica gel affinity than the biphenyl from 1a, and so it proved
possible to separate it cleanly from the minor homocoupling
byproduct formed. Finally, trisubstituted and tetrasubstituted
bromoalkenes (2h, 2i, 2j) were explored. The product from the
tetrasubstituted bromoalkene, 3jh, required a longer reaction
time compared to that of 3oi and 3oj (Table 3, entries 7-9),
but yields for all three were excellent.
IR (neat): ν 3009.4, 1600.2, 1494.1, 1471.8, 1462.31, 1255.4,
1
1104.3 cm-1. H NMR (CDCl3, 360 MHz): δ 7.30 (m, 5H), 6.46
(d, J ) 11.7 Hz, 1H), 5.70 (dt, J ) 11.7, 7.3 Hz, 1H), 3.64 (t, J )
6.1 Hz, 2H), 2.39 (m, 2H), 1.56 (m, 4H), 0.93 (s, 9H), 0.08 (s,
6H). 13C NMR (CDCl3, 90 MHz): δ 137.7, 132.9, 128.9, 128.7,
128.1, 126.4, 62.9, 32.5, 28.3, 26.2, 25.9, 18.3, -5.3. HRMS (CI):
m/z calcd for C18H31OSi (MH+) 291.2144, found 291.2141.
Acknowledgment. The Ministero per l’Istruzione e la
Ricerca (MIUR) supported this research through a fellowship
to T.F. We thank the National Institutes of Health (GM35249),
Merck Research Laboratories, and Amgen for their generous
support, along with Johnson Matthey and Frontier Scientific
for donations of the catalysts.
Supporting Information Available: Experimental details and
structural data for all new compounds. This material is available
free of charge via the Internet at http://pubs.acs.org.
JO0608366
J. Org. Chem, Vol. 71, No. 15, 2006 5747