Palladium-catalyzed cross-coupling reactions of potassium alkenyltrifluoroborates with organic halides in aqueous media

Article abstract of DOI:10.1021/jo802356n

Potassium vinyl and alkenyltrifluoroborates are cross-coupled with aryl and heteroaryl bromides using 1 mol % Pd loading of 4-hydroxyacetophenone oxime derived palladacycle or Pd(OAc)₂ as precatalysts, K ₂CO₃ as base, and TBAB as additive and water reflux under conventional or microwave heating to afford styrenes, stilbenoids, and alkenylbenzenes. These borates can be cross-coupled diastereoselectively with allyl and benzyl chlorides using KOH as base in acetone-water (3:2) at 50°C and 0.1 mol % Pd loading, giving the corresponding 1,4-dienes and allylarenes, respectively. These simple phosphine-free reaction conditions allow the palladium recycling from the aqueous phase during up to five runs by extractive separation of the products, which contain 58-105 ppm of Pd.

Full text of DOI:10.1021/jo802356n

Palladium-Catalyzed Cross-Coupling Reactions of Potassium
Alkenyltrifluoroborates with Organic Halides in Aqueous Media†
Emilio Alacid and Carmen Na´jera*
Departamento de Qu´ımica Orga´nica, Facultad de Ciencias, and Instituto de S´ıntesis Orga´nica (ISO),
UniVersidad de Alicante, Apdo. 99, 03080-Alicante, Spain
cnajera@ua.es
ReceiVed October 21, 2008
Potassium vinyl and alkenyltrifluoroborates are cross-coupled with aryl and heteroaryl bromides using 1
mol % Pd loading of 4-hydroxyacetophenone oxime derived palladacycle or Pd(OAc)2 as precatalysts,
K2CO3 as base, and TBAB as additive and water reflux under conventional or microwave heating to
afford styrenes, stilbenoids, and alkenylbenzenes. These borates can be cross-coupled diastereoselectively
with allyl and benzyl chlorides using KOH as base in acetone-water (3:2) at 50 °C and 0.1 mol % Pd
loading, giving the corresponding 1,4-dienes and allylarenes, respectively. These simple phosphine-free
reaction conditions allow the palladium recycling from the aqueous phase during up to five runs by
extractive separation of the products, which contain 58-105 ppm of Pd.
Introduction
notin,5 organosilane,6 and organoboron7 derivatives. The
Suzuki-Miyaura reaction of organoboron compounds is nowa-
days the most widely used cross-coupling reaction because of
its low toxicity as well as the possibility of being carried out in
water or aqueous solvents. Several types of alkenylboron
derivatives, such as boronic acids or anhydrides,8 related esters,9
and trifluoroborates10 have been coupled with aryl iodides,
bromides, and triflates. In recent years, potassium organotri-
fluoroborates have become very useful organoboron reagents
in cross-coupling reactions.11 They are crystalline compounds
Palladium-catalyzed vinylation of aromatic halides is an
important strategy for the synthesis of styrenes1 and stilbenes.2
The Heck reaction using ethylene (or its equivalents) and
styrenes allows the preparation of this type of compound.3 A
second approach involves the cross-coupling reaction of aryl
halides with alkenylmetals, such as organomagnesium,4 orga-
† Dedicated to Professor Ryoji Noyori on occasion of his 70th birthday.
(1) For reviews about applications of styrenes, see: (a) Agbossou, F.;
Carpentier, J.-F.; Mortreux, A. Chem. ReV. 1995, 95, 2485–2506. (b) Modern
Styrenic Polymers: Polystyrenes and Styrenic Copolymers; Scheirs, J., Priddy,
D. B., Eds.; John Wiley: Chichester, 2003. (c) De Meijere, A.; von Zezchwitz,
P.; Bra¨se, S. Acc. Chem. Res. 2005, 38, 413–422. (d) Palladium-Catalyzed
Coupling Reactions for Industrial Fine Chemical Syntheses; John Wiley & Sons:
Hoboken, 2002; Vol. 1.
(2) Stilbenoids are very important compounds exhibiting many biological
activities: Ferre´-Filmon, K.; Delaude, L.; Demonceau, A.; Noels, A. F. Coord.
Chem. ReV. 2004, 248, 2323–2336.
(3) For recent reviews, see: (a) Alonso, F.; Beletskaya, I. P.; Yus, M.
Tetrahedron 2005, 61, 11711–11835. (b) Polshettiwar, V.; Molna´r, A. Tetra-
hedron 2007, 63, 6949–6976.
(4) Bumagin, N. A.; Luzikova, E. V. J. Organomet. Chem. 1997, 532, 271–
273.
(5) (a) McKean, D. R.; Parrinello, G.; Renaldo, A. F.; Stille, J. K. J. Org.
Chem. 1987, 52, 422–424. (b) Grasa, G. A.; Nolan, S. P. Org. Lett. 2001, 3,
119–122. (c) Littke, A. F.; Schwartz, L.; Fu, G. C. J. Am. Chem. Soc. 2002,
124, 6343–6348.
(6) For recent publications, see: (a) Alacid, E.; Na´jera, C. J. Org. Chem.
2008, 73, 2315–2322. (b) Denmark, S. E.; Butler, C. R. J. Am. Chem. Soc. 2008,
130, 3690–3704. (c) Gordillo, A.; de Jesu´s, E.; Lo´pez-Mardomingo, C. Chem.
Commun. 2007, 4056–4058. (d) Nakao, Y.; Imanaka, H.; Chen, J.; Yada, A.;
Hiyama, T. J. Organomet. Chem. 2007, 692, 585–603.
(7) For recent reviews, see: (a) Alonso, F.; Beletskaya, I. P.; Yus, M.
Tetrahedron 2008, 64, 3047–3101. (b) Yin, L.; Liebscher, J. Chem. ReV. 2007,
107, 133–173. (c) Corbet, J. P.; Mignani, G. Chem. ReV. 2006, 106, 2651–2710.
(d) Boronic Acids; Hall, D. G., Ed., Wiley-VCH: Weinheim, 2005. (e) Leadbeater,
N. E. Chem. Commun. 2005, 2881–2902.
(8) (a) Kerins, F.; O’Shea, D. F. J. Org. Chem. 2002, 67, 4968–4971. (b)
Peyroux, E.; Berthiol, F.; Doucet, H.; Santelli, M. Eur. J. Org. Chem. 2004,
1075–1082. (c) Barder, T. E.; Walker, S. D.; Martinelli, J. R.; Buchwald, S. L.
J. Am. Chem. Soc. 2005, 127, 4685–4696. (d) Mantel, M. L. H.; Sobjerg, L. S.;
Huynh, T. H. V.; Ebran, J.-P.; Lindhart, A. T.; Nielsen, N. C.; Skrydstrup, T. J.
Org. Chem. 2008, 73, 3570–3573.
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10.1021/jo802356n CCC: $40.75
Published on Web 02/13/2009
2009 American Chemical Society
J. Org. Chem. 2009, 74, 2321–2327 2321

Alacid and Na´jera
more stable to air and moisture than boronic acids. Alkenyltri-
fluoroborates can be prepared by reaction of alkenylboron
compounds with KHF2 starting from organolithium and mag-
nesium compounds10d and also by hydroboration of alkynylpi-
nacolborates,12 nowadays some of them being commercially
available. The typical cross-coupling conditions for the synthesis
of styryl and other alkenylborates from aryl iodides, bromides,
and triflates used PdCl2 (2 mol %), a phosphine (6 mol %) such
as PPh3 or bis(diphenylphosphino)ferrocene (dppf), and an
amine as base in aqueous isopropanol.10f,k Similar reaction
conditions have been used for the reaction between allyl
chlorides and styryltrifluoroborates at 100 °C under microwave
(MW) heating.13 For the preparation of styrenes, potassium
vinyltrifluoroborate has been coupled with aryl and heteroaryl
bromides and triflates in THF-H2O (9:1) at 85 °C using Cs2CO3
as base during 22 h.10e,f,i†
The only report about the use of neat water as solvent was
the cross-coupling of potassium (E)-styryltrifluoroborate with
aryl bromides under MW heating (150 °C) using Na2CO3 as
base, tetra-n-butylammonium (TBAB) as additive, and ultralow
Pd loading.10h However, under these reaction conditions isomer-
ization of the C-C double bond occurred, affording a ca. 5:1
trans/cis mixture of stilbenes. We have recently described the
first cross-coupling of potassium aryltrifluoroborates with aryl
chlorides under water reflux using 4-hydroxyacetophenone
oxime derived palladacycle 1 as precatalyst, K2CO3 as base,
and TBAB as additive.14 The same palladacycle was able to
catalyze the coupling with allyl and benzyl chlorides using KOH
as base in acetone-H2O as solvent at 50 °C.14 We describe
here that these reaction conditions can also be used for the cross-
coupling of aryl bromides and allyl and benzyl chlorides with
potassium vinyl- and alkenyltrifluoroborates in the synthesis of
styrenes, stilbenes, alkenylbenzenes, allyl benzenes, and 1,4-
dienes. Attempts for easy product separation and also Pd
recycling experiments under these reaction conditions would
be considered.
water reflux using TBAB (1 equiv)15 and 3 and 2 equiv of
K2CO3, respectively (Table 1). Initial studies on the reaction of
4-bromoacetophenone with 1.5 equiv of potassium vinyltri-
fluoroborate gave product 2aa in 93% crude yield (Table 1,
entry 1). However, when 1.01 equiv of potassium vinyltrifluo-
roborate was used, 72% yield of 2aa was obtained together with
15% of 4,4′-diacetylstilbene (Table 1, entry 2). The vinylation
of 4-bromoacetophenone performed under conventional thermal
(in a pressure tube) or MW conditions showed that palladacycle
1 afforded 4-acetylstyrene (2aa) in higher yields and lower
reaction times than Pd(OAc)2 (Table 1, compare entries 1 with
3 and 4 with 5). Parallel studies were performed with potassium
(E)-styryltrifluoroborate using 2 equiv of K2CO3, providing
regio- and stereoselectively stilbene (E)-2ba in higher yields
using palladacycle 1 than Pd(OAc)2 (Table 1, compare entries
6 with 7 and 8 with 9). However, when potassium (Z)-
styryltrifluoroborate12 was cross-coupled with 4-bromoacetophe-
none, a lower stereoselectivity than in the case of the E-isomer
was obtained, affording product 2ba in a 80:20 Z/E ratio (Table
1, entries 10 and 11). In case of the cross-coupling of potassium
(E)-dec-1-enyltrifluoroborate with 4-bromoacetophenone, (E)-
dec-1-enylbenzene 2ca was isolated in a regio- and stereose-
lective manner with high yields under conventional or MW
heating (Table 1, entries 12 and 13).
Vinylation reactions of alkenyltrifluoroborates with deacti-
vated aryl bromides, such as 2-bromotoluene, 1-bromonaph-
thalene, 4-bromoanisole, and 6-methoxy-2-bromonaphthalene,
were carried out using palladacycle 1 as precatalyst under
conventional and MW heating, providing styrenes 2ab-ae,
stilbenes 2bb-2be, and (E)-1-(dec-1-enyl)-4-methoxybenzene
(2cd) in good yields but with longer reaction times than previous
mentioned examples (Table 1, entries 14-31). Only in the case
of the preparation of styrenes 2ac and 2ad under MW conditions
was the formation of the Heck products 1,2-di(1-naphthyl)eth-
ylene (21%) and 4,4′-dimethoxystilbene (11%) observed (Table
1, entries 19 and 23). The alkenylation of 4-bromoanisole with
potassium (E)-styryl and (E)-dec-1-enyltrifluoroborates afforded
mainly stilbene 2bd and 1-decenyl-4-methoxybenzene 2 cd, as
well as the corresponding regioisomeric compounds resulting
from the arylation at the R-position (Table 1, entries 24-27).
6-Methoxy-2-bromonaphthalene reacted with vinyltrifluorobo-
rate to provide in good yield 6-methoxy-2-vinylnaphthalene
(2ae), a precursor of the antiinflamatory naproxene (Table 1,
entries 28 and 29). When the cross-coupling was performed with
(E)-styryltrifluoroborate, the corresponding stilbene 2be was
obtained regio- and stereoselectively (Table 1, entries 30 and
31).
Results and Discussion
The reaction of aryl bromides with potassium vinyl-, styryl-,
and dec-1-enyltrifluoroborates (1.5 equiv) was performed under
(10) (a) Puentener, K.; Scalone, M.;Hoffmann-La Roche AG, Patent 1057831,
2000; CAN 134:17683. (b) Darses, S.; Geneˆt, J.-P.; Brayer, J.-L.; Demoute, J.-
P. Tetrahedron Lett. 1997, 38, 4393–4396. (c) Darses, S.; Michaud, G.; Geneˆt,
J.-P. Tetrahedron Lett. 1998, 39, 5045–5048. (d) Darses, S.; Michaud, G.; Geneˆt,
J.-P. Eur. J. Org. Chem. 1999, 1875–1883. (e) Molander, G. A.; Rivero, M. R.
Org. Lett. 2002, 4, 107–109. (f) Molander, G. A.; Bernardi, C. R. J. Org. Chem.
2002, 67, 8424–8429. (g) Molander, G. A.; Felix, L. A. J. Org. Chem. 2005,
70, 3950–3956. (h) Arvela, R. K.; Leadbeater, N. E.; Mack, T. L.; Kormos,
C. M. Tetrahedron Lett. 2006, 47, 217–220. (i) Kabalka, G. W.; Al-Masum,
M.; Mereddy, A. R.; Dadush, E. Tetrahedron Lett. 2006, 47, 1133–1136. (j)
Carter, R. R.; Wyatt, J. K. Tetrahedron Lett. 2006, 47, 6091–6094. (k) Molander,
G. A.; Brown, A. R. J. Org. Chem. 2006, 71, 9681–9686. (l) Joucha, L.; Cusati,
G.; Pinel, C.; Djakovitch, L. Tetrahedron Lett. 2008, 49, 4738–4741.
(11) For reviews, see: (a) Darses, S.; Geneˆt, J.-P. Chem. ReV. 2008, 108,
288–325. (b) Doucet, H. Eur. J. Org. Chem. 2008, 2013–2030. (c) Molander,
G. A.; Ellis, N. Acc. Chem. Res. 2007, 40, 275–286. (d) Stefani, H. A.; Cella,
R.; Vieira, A. S. Tetrahedron 2007, 63, 3623–3658. (e) Molander, G. A.;
Figueroa, R. Aldrichimica Acta 2005, 38, 49–56. (f) Darses, S.; Geneˆt, J.-P.
Eur. J. Org. Chem. 2003, 4313–4327.
These aqueous conditions were tolerated by easily hydroliz-
able aryl bromides such as ethyl 4-bromobenzoate and 4-bro-
mobenzonitrile (Table 1, entries 32-35). Both electrophiles were
cross-coupled with potassium vinyltrifluoroborate under con-
ventional thermal conditions using palladacycle 1 as precatalyst,
affording styrenes 2af and 2ag, respectively, in good yields
(Table 1, entries 32 and 34). Under the same reaction conditions
potassium (E)-styryltrifluoroborate gave steroselectively the
corresponding stilbenes 2bf and 2bg in 81% and 84% yield,
respectively (Table 1, entries 33 and 35).
Heterocyclic bromides, such as 5-bromothiophene-2-carbox-
aldehyde and 3-bromopyridine, afforded the corresponding vinyl
(12) Molander, G. A.; Ellis, N. M. J. Org. Chem. 2008, 73, 6841–6844.
(13) Kabalka, G. W.; Dadush, E.; Al-Masum, M. Tetrahedron Lett. 2006,
47, 7459–7461.
(15) TBAB can act as phase-transfer catalyst and also can stabilize palladium
nanoparticles, avoiding aggregation: Reetz, M. T.; Westermann, E. Angew. Chem.,
Int. Ed. 2000, 39, 165–168.
(14) Alacid, E.; Na´jera, C. Org. Lett. 2008, 10, 5011–5014.
2322 J. Org. Chem. Vol. 74, No. 6, 2009

Cross-Coupling Reactions of Potassium Alkenyltrifluoroborates
TABLE 1. Alkenylation of Aryl and Heteroaryl Bromides with Potassium Vinyl and Alkenyltrifluoroborates for the Synthesis of Styrenes,
Stilbenoids, and Alkenylbenzenesa
J. Org. Chem. Vol. 74, No. 6, 2009 2323

Alacid and Na´jera
TABLE 1. Continued
a Reactions were performed with ArBr or HetArBr (0.3 mmol), RCHdCHBF3K (0.45 mmol), 1 or Pd(OAc)2 (1 mol % Pd), K2CO3 (0.6 or 0.9 mmol),
and TBAB (97 mg, 0.3 mmol) in H2O (1 mL) in a pressure tube at 120 °C bath temperature. b Isolated yield after flash chromatography. In parenthesis,
yield of the crude product determined by 1H NMR. c 3 equiv of K2CO3. d 1.01 equiv of potassium vinyltrifluoroborate was used. e 15% of
4,4′-diacetylstilbene was also obtained. f Under microwave heating (40 W, 120 °C, 3-5 bar). g 2 equiv of K2CO3. h As 80:20 Z/E stereoisomer ratio.
I Under microwave heating (30 W, 100 °C, 1-3 bar). j 21% of 1,2-di(1-naphthyl)ethylene was also obtained. k 11% of 4,4′-dimethoxystilbene was also
obtained. l 3% of regioisomer 1-(4-methoxyphenyl)-1-phenylethylene was also obtained. m 10% of regioisomer 1-(4-methoxyphenyl)-1-phenylethylene
was also obtained. n 12% of regioisomer 1-(4-methoxyphenyl)-1-octylethylene was also obtained. o 10% of regioisomer 1-(4-methoxyphenyl)-1-octyl-
ethylene was also obtained. p 2% of 4,4′-di(ethoxycarbonyl)stilbene was also obtained. q 3% of 4,4′-dicyanostilbene was also obtained.
derivatives 2ah and 2ai in good yields when reacted with
potassium vinyltrifluoroborate (Table 1, entries 36, 37 and 40,
41, respectively), whereas compounds 2bh and 2bi were
stereoselectively obtained using potassium (E)-styryltrifluo-
roborate (Table 1, entries 38, 39 and 42, 43, respectively).
Although the cross-coupling of aryl chlorides with potassium
aryltrifluoroborates could be achieved under these reactions
conditions,14 the less reactive potassium alkenyltrifluoroborates
could not be cross-coupled with aryl chlorides.
Next, the cross-coupling of potassium vinyltrifluoroborates
with representative allyl and benzyl chlorides was studied using
K2CO3 as base and TBAB as additive in refluxing water.
However, under these reactions conditions the cross-couplings
with cinammyl and benzyl chloride failed. In the case of
cinnamyl chloride a complex mixture of products was observed.
For benzyl chloride the corresponding benzyl alcohol was
exclusively obtained. When KOH was used as base and TBAB
as additive in acetone-H2O (3:2) at 50 °C, allyl and benzyl
chlorides could be successfully cross-coupled with potassium
alkenyltrifluoroborates (Table 2). In these processes only 0.1
mol % Pd loading was necessary to achieve cross-coupled
products in good yields. In general, conventional thermal
conditions afforded higher yields than MW heating. Thus, initial
studies for the coupling with cinnamyl chloride in the presence
of palladacycle 1 afforded 1,4-dienes 3aa and 3ba in higher
yields than when using Pd(OAc)2 (Table 2, entries 1-4).
Therefore, palladacycle 1 was used as precatalyst when per-
forming other couplings. Allyl chloride gave 1,4-dienes 3ab and
3bb in good yields, although volatile 1,4-pentadiene (3ab) was
obtained in 61% yield after distillation (Table 2, entries 5 and
2324 J. Org. Chem. Vol. 74, No. 6, 2009

Cross-Coupling Reactions of Potassium Alkenyltrifluoroborates
TABLE 2. Alkenylation of Allyl and Benzyl Chlorides with Potassium Vinyl and Styryltrifluoroborates for the Synthesis of 1,4-Dienes and
Allylbenzenesa
a Reactions were performed with allyl or benzyl chloride (1 mmol), RCHdCHBF3K (1.5 mmol), 1 or Pd(OAc)2 (0.1 mol % Pd), KOH (112 mg, 2
mmol), and TBAB (192 mg, 0.5 mmol) in acetone-H2O (3:2, 5 mL) at 50 °C bath temperature. b Isolated yield after flash chromatography. In
parenthesis, yield of the crude product determined by 1H NMR. c Isolated by distillation at 30 °C. d 1 mol % Pd loading was used. e 9% of the
regioisomer 3-(prop-1-enyl)anisole was also obtained. f 0.5 mol % Pd loading was used. g 1% of the regioisomer 2-chloro-4-(prop-1-enyl)pyridine was
also obtained.
6). Methallyl chloride was coupled with potassium (E)-styryl-
trifluoroborate, providing 4-methyl-1-phenylpenta-1,4-diene
(3bc) in good yield (Table 2, entry 7). Dienes 3ba-bc were
stereoselectively obtained with E-configuration.
Using the former reaction conditions, benzyl chlorides have
been cross-coupled with potassium alkenyltrifluoroborates for
the first time, affording allylbezenes 4 in good yields.
Palladacycle 1 showed again higher efficiency than Pd(OAc)2
in the reaction of benzyl chloride with vinyl and styryltrif-
luoroborates (Table 2, entries 8-11). 1-(Chloromethyl)naph-
thalene, 3-(chloromethyl)anisole, and 2-chloro-4-(chlorom-
ethyl)pyridine afforded allylic products 4ab, 4ac, and 4ad
J. Org. Chem. Vol. 74, No. 6, 2009 2325

Alacid and Na´jera
TABLE 3. Recycling Experiments of the Palladium-Catalyzed Suzuki-Miyaura Reaction of Potassium Vinyltrifluoroborate with
4-Bromoacetophenone and Cinnamyl and Benzyl Chloride
a Method A: 4-bromoacetophenone (0.5 mmol), CH2dCHBF3K (100 mg, 0.75 mmol), 1 (1 mol % Pd), K2CO3 (207 mg, 1.5 mmol), and TBAB (162
mg, 0.5 mmol) in H2O (1 mL) in a pressure tube at 120 °C bath temperature. Method B: allyl or benzyl chloride (0.5 mmol), CH2dCHBF3K (100 mg,
0.75 mmol), 1 (0.5 mol % Pd), KOH (56 mg, 1 mmol), and TBAB (81 mg, 0.25 mmol) in acetone-H2O (3:2, 2.5 mL) at 50 °C bath temperature.
b Isolated crude yield after flash chromatography. In parenthesis, yield of the crude product determined by 1H NMR. c Determined in the crude product
by ICP-OES.
in good yields, the Pd loading being increased to 0.5 mol %
in the last example (Table 2, entries 12, 14, and 16). Products
4ba-4bd, resulting from the cross-coupling of benzylic
chlorides with potassium styryltrifluoroborate, were obtained
with retention of the C-C double bond configuration (Table
2, entries 10, 11, 13, 15, and 17). In all of these vinylation
reactions with allyl and benzyl chlorides, no isomerization
of the double bond along the chain was observed, except in
the case of the reaction of potassium vinyltrifluoroborates
with 3-(chloromethyl)anisole and 2-chloro-4-(chlorometh-
yl)pyridine (Table 2, entries 14 and 16).
Recycling experiments were carried out for the cross-coupling
of 4-bromoacetophenone and potassium vinyltrifluoroborate
under conventional thermal conditions using method A (Table
3, entries 1-6). After the reaction was finished, the product
was extracted with ethyl acetate, and reagents were added again
to the aqueous phase except palladacycle 1. Four more runs
were performed in 2, 2.5, 4, and 14 h, yielding product 2aa in
91%, 87%, 83%, and 76%. In the sixth cycle, the yield decreased
to 37% after 24 h reaction time. ICP-OES analyses of the
obtained crude products indicated relatively low levels of Pd
in the range of 86.2-103.1 ppm.
Method B was used in the presence of palladacycle 1 (0.5 mol
% Pd) in the case of the recycling experiments for the vinylation
of cinnamyl and benzyl chloride (Table 3). The cross-coupling of
potassium vinyltrifluoroborate and cinnamyl chloride was per-
formed efficiently during 5 runs, giving product 3aa in 91%, 93%,
81%, 78%, and 80% yield in 1.5, 2.5, 5, 10, and 24 h, respectively
(Table 3, entries 7-12). However, lower efficiency was observed
in the case of benzyl chloride. Thus, product 4aa was obtained in
86%, 79%, and 75% yield in 4.5, 10, and 24 h, yield decreasing to
47% in the fourth cycle. Leaching analyses indicated 51.5-109.5
ppm of Pd in the crude products.
Conclusions
The reaction conditions found for the Suzuki-Miyaura
reaction between aryl bromides and potassium alkenyltrifluo-
2326 J. Org. Chem. Vol. 74, No. 6, 2009

Cross-Coupling Reactions of Potassium Alkenyltrifluoroborates
yl)acetophenone (2ca),16 (E)-1-(decen-1-yl)-4-methoxybenzene (2
cd),16 (E)-5-styrylthiophene-2-carbaldehyde (2bh),17 and (E)-2-
methoxy-6-styrylnaphthalene (2be)18 have been previously reported.
General Procedure for the Cross-Coupling of Allyl and
Benzyl Chlorides with Potassium Alkenyltrifluoroborates [(E)-
1-Phenylpenta-1,4-diene (3aa) as Example]. A 1 M solution of
KOH (2 mL, 2 mmol) was added to a solution of allyl/benzyl
chloride (1 mmol), tetrabutylammonium bromide (322 mg, 1 mmol),
potassium alkenyltrifluoroborate (1.5 mmol), and catalyst (0.292
mg, 0.1 mol % Pd) in acetone (3 mL) in a round-bottom flask. The
mixture was stirred and heated at 50 °C, and the reaction was
monitored by GC until completion. Then, the crude reaction was
cooled at room temperature, the product was extracted with diethyl
ether (3 × 15 mL), and the combined organic layers were washed
with water (3 × 15 mL) and dried over magnesium sulfate. The
solvent was removed under slight vacuum, and the products were
purified by flash chromatography on silica gel. For recycling
experiments the product was extracted in situ with ethyl acetate (6
× 5 mL), and the combined organic layers were washed with water
(3 × 15 mL) and dried over magnesium sulfate. The aqueous phase
in the vessel reaction was recharged with 3 mL of acetone and all
reagents except the catalyst.
roborates, aqueous potassium carbonate, and TBAB as additive
under conventional or microwave heating at 120 °C are
appropriate for the preparation of styrenes, unsymmetrical
stilbenes, and alkenylbenzenes. Ligand-less Pd(OAc)2 or the
4-hydroxyacetophenone oxime derived palladacycle, which are
efficient source of Pd nanoparticles, act as precatalyst using 1
mol % Pd loading. In the case of potassium styryl- and dec-1-
enyltrifluoroborates the reaction was faster than with vinyltri-
fluoroborate. The cross-coupling of allyl and benzyl chlorides
was performed using KOH in aqueous acetone at 50 °C,
affording 1,4-dienes and allylbenzenes, respectively. For the
vinylation reactions, the palladacycle was a better precatalyst
than Pd(OAc)2, and a lower Pd loading (0.1 mol % Pd) can be
used. Cross-couplings with alkenyltrifluoroborates took place
in a stereoselective manner without isomerization of the C-C
double bond. In addition, both reaction conditions allow the
separation of the products by extractive workup and the recovery
of Pd in the aqueous basic layer.
Experimental Section
(E)-1-Phenylpenta-1,4-diene (3aa). Colorless oil; Rf ) 0.57
(hexane); IR (film) ν ) 3047, 1636, 1423, 1275 cm-1; H NMR
(CDCl3, 300 MHz) δ 7.36-7.16 (m, 5H), 6.41 8d, 1H, J ) 15.7
Hz), 6.22 (dt, 1H, J ) 15.8 and 6.5 Hz), 5.97-5.83 (m, 1H),
5.14-5.03 (m, 2H), 2.98-2.93 (m, 2H); 13C NMR (CDCl3, 75
MHz) δ 137.7, 136.6, 131.0, 128.6, 128.3, 127.1, 126.2, 115.8,
37.1; MS m/z 145 (M+ + 1, 5), 144 (M+, 39), 143 (M+ - 1, 23),
129 (100), 128 (58), 115 (37), 91 (15).
The compounds 1-phenyl-1,4-pentadiene (3aa), 1,4-pentadiene
(3ab), allylbenzene (4aa), 1-allylnaphthalene (4ab), and 2-ally-
lanisole (4ac) are commercially available. The compounds (E)-1,3-
diphenylpropene (4ba),19 (1E,4E)-1,5-diphenyl-1,4-pentadiene
(3ba),20 and (E)-3-(1-naphthyl)-1-phenylpropene (4bb)21 have been
previously reported.
General Procedure for the Cross-Coupling of Aromatic Bro-
mides with Potassium Alkenyltrifluoroborates [2-Methoxy-6-vi-
nylnaphthalene (2ae) as Example]. A pressure glass vessel (10 mL)
sealed with a septum was charged with the aryl bromide (0.3 mmol),
tetra-n-butylammonium bromide (97 mg, 0.3 mmol), potassium
alkenyltrifluoroborate (0.45 mmol), and catalyst (1 mol % Pd) in
water (1 mL). The mixture was stirred and heated at 120 °C (bath
temperature), and the reaction was monitored by GC until comple-
tion. When the reaction was performed in a microwave reactor,
the mixture was stirred and heated at 30-40 W, 1-5 bar, 100-120
°C, 20-30 min, and 40 psi of air stream cooling. Then, the crude
reaction was cooled at room temperature, the product was extracted
with diethyl ether (3 × 15 mL), and the combined organic layers
were washed with water (3 × 15 mL) and dried over magnesium
sulfate. The solvent was removed under vacuum, and the products
were purified by flash chromatography on silica gel. For recycling
experiments, the product was extracted in situ with ethyl acetate
(6 × 5 mL), and the combined organic layers were washed with
water (3 × 15 mL) and dried over magnesium sulfate. The aqueous
phase in the vessel reaction was recharged with all reagents except
the catalyst.
Acknowledgment. This work was financially supported by
the Direccio´n General de Investigacio´n from the Ministerio de
Educacio´n y Ciencia (MEC) of Spain (Grants CTQ2004-00808/
BQU, CTQ2007-62771/BQU, and Consolider INGENIO 2010,
CSD200700006), the Generalitat Valenciana (GV05/157), and
the University of Alicante. E.A. thanks the MEC for a
predoctoral fellowship.
2-Methoxy-6-vinylnaphthalene.6a White solid; mp 91-93 °C;
Rf 0.60 (hexane/diethyl ether 10/1); IR (KBr) ν ) 3054, 2838,
1
1633, 1597, 1482, 1258 cm-1; H NMR (CDCl3, 300 MHz) δ
Supporting Information Available: Physical and spectral
1
data, as well as the H NMR and 13C NMR spectra of known
7.72-7.68 (m, 3H), 7.62 (d, 1H, J ) 8.5 Hz), 7.14 (d, 2H, J )
8.1 Hz), 6.89 (dd, 1H, J ) 17.6 and 10.9 Hz), 5.85 (d, 1H, J )
17.6 Hz), 5.29 (d, 1H, J ) 10.9 Hz); 13C NMR (CDCl3, 75 MHz)
δ 157.7, 136.9, 134.2, 132.9, 129.5, 128.8, 126.9, 126.1, 123.7,
118.9, 113.0, 105.7, 55.2; MS m/z 184 (M+, 100), 169 (17),
141 (50), 115 (19).
compounds. This material is available free of charge via the
Internet at http://pubs.acs.org.
JO802356N
(16) Santelli, M.; Doucet, H.; Berthiol, F.; Fall, Y. Synthesis 2007, 1683–
1696.
(17) Nam, H.; Buu-Ho¨i, N. G.; Xuong, D. J. Chem. Soc. 1954, 1690–1696.
(18) Geissler, H.; Gross, P.;Aventis Research and Technologies GmbH and
Co. KG, Germany, Patent 9819813402, 1999; CAN 131:257324.
(19) Bokadia, M. M.; Brown, B. R.; Cobern, D.; Roberts, A.; Somerfield,
G. A. J. Chem. Soc. 1962, 1658–1666.
(20) Tsukamoto, H.; Sato, M.; Kondo, Y. Chem. Commun. 2004, 1200–1201.
(21) Tsukamoto, H.; Uchiyama, T.; Suzuki, T.; Kondo, Y. Org. Biomol.
Chem. 2008, 6, 3005–3013.
The following compounds are commercially available: 4-viny-
lacetophenone (2aa), (E)-4-styrylacetophenone (2ba), 2-methyl-
styrene (2ab), (E)-2-methylstilbene (2bb), 1-vinylnaphthalene (2ac),
(E)-4-styrylnaphthalene (2bc), 4-methoxystyrene (2ad), (E)-4-
methoxystilbene (2bd), 2-methoxy-6-vinylnaphthalene (2ae), ethyl
4-vinylbenzoate (2af), 4,4′-di(ethoxycarbonyl)stilbene (2bf), 4-vi-
nylbenzonitrile (2ag), 4,4′-dicyanostilbene (2bg), 3-vinylpyridine
(2ai), and (E)-3-styrylpyridine (2bi). Compounds (E)-4-(decen-1-
J. Org. Chem. Vol. 74, No. 6, 2009 2327