A highly effective (Triphenyl phosphite)palladium catalyst for a cross-coupling reaction of allylic alcohols with organoboronic acids

Article abstract of DOI:10.1002/ejoc.200400621

The cross coupling reaction of aryl and vinyl boronic acids and allylic alcohols proceeded smoothly in toluene or dioxane in the presence of a (triphenyl phosphite)palladium catalyst to give the corresponding allylbenzene derivatives and 1,4-dienes. Neither cocatalysts for promoting C-O bond cleavage of allylic alcohols nor bases for activation of organoboron reagents are required for promoting the coupling process. Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004.

Full text of DOI:10.1002/ejoc.200400621

SHORT COMMUNICATION
A Highly Effective (Triphenyl phosphite)palladium Catalyst for a
Cross؊Coupling Reaction of Allylic Alcohols with Organoboronic Acids
Yoshihito Kayaki,[a] Takashi Koda,[b] and Takao Ikariya*[b]
Keywords: Allylation / Boranes / CϪC coupling / Green chemistry / Palladium
The cross coupling reaction of aryl and vinyl boronic acids
and allylic alcohols proceeded smoothly in toluene or diox-
ane in the presence of a (triphenyl phosphite)palladium cata-
lyst to give the corresponding allylbenzene derivatives and
1,4-dienes. Neither cocatalysts for promoting C−O bond
cleavage of allylic alcohols nor bases for activation of organo-
boron reagents are required for promoting the coupling
process.
( Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2004)
Introduction
with organoboron reagents. The PdϪOH species possibly
activates
the
boron
center
to
facilitate
transmetallation.[8Ϫ10]
Metal-catalyzed cross-coupling reactions between or-
ganic halides and organometallic reagents have been devel-
oped as a versatile and efficient tool for formation of
carbonϪcarbon bonds in organic synthesis.[1] The pal-
ladium-catalyzed reaction with organoboron compounds
(SuzukiϪMiyaura coupling) has emerged as being advan-
tageous in light of its low toxicity, operational simplicity,
and broad functional group tolerance.[2] Recent marked
progress in ligand design allows for the utilization of a vari-
ety of electrophilic substrates including less reactive aryl
chlorides.[3] However, the use of stoichiometric amounts of
a base or an activator for boron reagents with relatively
poor nucleophilicity has generally been required for ef-
ficient SuzukiϪMiyaura coupling reactions.[4]
We have recently developed a highly effective Pd catalyst
that has a P(OC6H5)3 ligand for dehydrative substitution of
allylic alcohols with O-, N-, and C-nucleophiles; the
PdϪP(OC6H5)3 catalyst facilitated the CϪO bond cleavage
to generate a PdϪOH intermediate without additional pro-
moters thus leading to a greener allylic alkylation, free from
salt wastes [Equation (1)].[5Ϫ7] In this allylation, the
PdϪOH species generated from the oxidative addition of
allylic alcohols presumably has sufficient basicity to depro-
tonate the nucleophiles, liberating water. We utilize the po-
tential basicity of the possible intermediate, the PdϪOH
species, in the SuzukiϪMiyaura coupling reaction and
found that the PdϪP(OC6H5)3 catalyst system efficiently
promotes the cross-coupling reaction of allylic alcohols
(1)
Results and Discussion
The reaction of allyl alcohol (1) (2.5 mmol) and phe-
nylboronic acid (3.0 mmol) in the presence of
Pd2(dba)3·CHCl3 (1.25 ϫ 10Ϫ2 mmol/Pd, S/C ϭ 200) was
carried out in dioxane at 80 °C [Equation (2)]. As listed in
Table 1, control of the molar ratio of Pd to P(OC6H5)3 li-
gand is crucial for optimal catalyst performance. The use of
an equimolar amount of the ligand with respect to Pd pro-
vided the desired allylbenzene (2) in 71% yield after 1 h (En-
try 2), whereas no coupling product was obtained in the
absence of P(OC6H5)3 (Entry 1).[11] An increase in the P/Pd
ratio resulted in a significant loss in the yield of coupled
product, along with the formation of diallyl ether through
dehydrative allylation of 1 as observed in our previous
paper.[5] Other phenylboranes (Entries 6 and 7) gave satis-
factory results except for the reaction with a catecholborane
derivative (Entry 8). The choice of solvent proved to be cru-
cial for determining the outcome of the reaction. The use
of toluene gave a satisfactory result, the yield reaching 81%
after a 1-h reaction, while polar solvents, acetonitrile, and
DMF led to no conversion possibly because of their strong
coordination ability. Dioxane can be used when boronic ac-
ids that have a poor solubility in toluene are employed for
this reaction.
[a]
PRESTO, Japan Science and Technology Agency,
2-12-1 O-okayama, Meguro-ku, Tokyo, 152-8552, Japan
[b]
Graduate School of Science and Engineering and Frontier
Collaborative Research Center, Tokyo Institute of Technology,
2-12-1 O-okayama, Meguro-ku, Tokyo, 152-8552, Japan
Fax: (internat.) ϩ81-3-5734-2637
E-mail: tikariya@apc.titech.ac.jp
Eur. J. Org. Chem. 2004, 4989Ϫ4993
DOI: 10.1002/ejoc.200400621
 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
4989

Y. Kayaki, T. Koda, T. Ikariya
SHORT COMMUNICATION
alcohols with boronic acids by using a (PPh3)Pd catalyst
was reported independently by Tsukamoto et al.; however,
higher catalyst loadings (S/C ϭ20) with PPh3 and longer
reaction times were required for the coupling.[13,14]
Table 1. Cross-coupling of 1 with phenylborane derivatives
Table 2. Ligand effects on the formation of 2
Entry[a]
Ligand[b]
Yield of 2[c] [%]
1
2
3
4
5
6
7
8
9
P(OC6H5)3
As(C6H5)3
P(2-furyl)3
P(C6H5)3
P(OC2H5)3
P(C6H11)3
P(nC4H9)3
DPPB[d]
81
53
20
9
5
0
0
0
0
P[N(C2H5)2]3
[a]
Reaction conditions:
1 (2.5 mmol), phenylboronic acid
(3.0 mmol), and Pd2(dba)3·CHCl3 (5.0 ϫ 10Ϫ3 mmol/Pd) at 80 °C
for 1 h in toluene (2.5 mL) under argon.
Determined by GC.
ane.
[a]
Reaction conditions: 1 (2.5 mmol), boron reagent (3.0 mmol),
[b]
[c]
Pd2(dba)3·CHCl3 (1.25 ϫ 10Ϫ2 mmol/Pd), and P(OC6H5)3 (0Ϫ5.0
P (or As)/Pd ϭ 1.
[d]
ϫ 10Ϫ2 mmol) at 80 °C for 6 h in dioxane (2.5 mL) under argon.
DPPB ϭ 1,4-bis(diphenylphosphanyl)but-
[b]
[c]
[d]
9-BBN ϭ 9-borabicyclo[3,3,1]nonane. Determined by GC.
Reactions conducted for 1 h.
A variety of ring-substituted boronic acids can be con-
verted into the coupling products with 1 by using
PdϪP(OC6H5) (P/Pd ϭ 1) in toluene or dioxane, as shown
in Table 3 [Equation (3)]. The reaction between arylboronic
acids that have 4-methyl, 4-methoxy, and 4-vinyl groups and
1 gave the allylbenzene derivatives in good to excellent
yields (Entries 1Ϫ3), while the coupling with congested 2-
methylphenylboronic acid gave the product in a slightly
(2)
The markedly beneficial effect of the P(OC6H5)3 ligand lower yield, and the reaction with the more sterically de-
on catalyst activity was observed by comparing with other manding (2,6-dimethylphenyl)boronic acid provided unsat-
ligands. Triphenylarsane and tris(2-furyl)phosphane, which isfactory results even under forced conditions (Entries 5 and
are known to be efficient ligands for Stille coupling,[12] gave 6). At a higher reaction temperature (100 °C) and with a
lower yields of 53% and 20%, respectively (Entries 2 and 3 higher concentration of the catalyst (S/C ϭ 100), the reac-
in Table 2). Little or no reaction took place in the case of tion of boronic acids bearing electron-deficient groups pro-
other phosphorus ligands including triphenylphosphane ceeded smoothly to give the desired product in reasonably
under the reaction conditions described in Table 2 (Entries high yields as shown in Table 3 (Entries 7Ϫ13). It should
4Ϫ9). Recently, a closely related coupling reaction of allylic be noted that the reaction tolerated the carbonϪchlorine
Table 3. Cross-coupling of 1 with various organoboronic acids
Entry[a]
R
S/C
Temp. [°C]
Solvent
Time [h]
Yield[b] [%]
1
2
3
4
5
6
7
8
9
10
11
12
13
4-CH3C6H4
4-CH3OC6H4
4-vinylphenyl
2-naphthyl
2-CH3C6H4
2,6-(CH3)2C6H3
4-FC6H4
4-ClC6H4
4-BrC6H4
4-IC6H4
500
500
500
500
500
50
100
500
100
100
100
100
100
80
80
80
80
80
toluene
dioxane
toluene
dioxane
toluene
toluene
dioxane
dioxane
dioxane
dioxane
dioxane
dioxane
dioxane
2
2
2
2
2
7
3
3
3
3
3
3
3
89
89
92
(79)
84
19
95
72
(82)
0
(89)
(100)
85
80
100
100
100
100
100
100
100
4-CHOC6H4
4-CH3COC6H4
4-CF3C6H4
[a] Reaction conditions: 1 (2.5 mmol) and RB(OH)2 (3.0 mmol), under argon. P/Pd ϭ 1. [b] Determined by 1H NMR spectroscopy. Isolated
yields are in parenthesis.
4990
 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
Eur. J. Org. Chem. 2004, 4989Ϫ4993

A Highly Effective (Triphenyl phosphite)palladium Catalyst
SHORT COMMUNICATION
and carbonϪbromine bonds in the arylboronic acids under
the reaction conditions. However, 4-iodophenylboronic acid
gave neither the corresponding substituted allylbenzene nor
diallyl ether formed by dehydrative allylation of 1, possibly
because facile oxidative addition of the carbonϪiodine
bond to a Pd0 intermediate consequently prevented CϪO
bond activation of 1 (Entry 10).
(4)
(3)
A possible mechanism for the formation of allylbenzene
from 1 and phenylboronic acid is outlined in Scheme 3. Ac-
cording to previous results from the stoichiometric reaction
of 1 with Pd0, we predicted that an η3-allyl(hydroxo)pallad-
ium complex A would be generated by oxidative addition
of the alcohol.[15,16] The subsequent transmetallation of
phenylboronic acids affords allyl(phenyl)palladium species
B, the PdϪOH species might interact with the organoboron
reagents to accelerate the reaction. The coupling products,
allylbenzenes, are obtained by reductive elimination from
intermediate B. In the step from A to B, excess ligand mol-
ecules would block an available coordination site for the
incoming phenyl group. Indeed, a decrease in the catalyst
activity was observed when excess P(OC6H5)3 ligand or co-
ordinating polar solvents were added, as mentioned above.
Substituted allylic alcohols can successfully be used for
the SuzukiϪMiyaura coupling by using the PdϪP(OC6H5)3
catalyst system. Cinnamyl alcohol (3) and 2-methallyl al-
cohol (4) reacted smoothly with phenylboronic acid to give
the desired products in good to excellent yields (Scheme 1).
The reaction of crotyl alcohol (5) with the phenylborane
reagent provided a mixture of phenylbutenes (7 and 8). As
shown in Scheme 2, products 7 and 8 were obtained in com-
parable ratios from the reaction of the regioisomeric sub-
strate, 1-methyl-2-propen-1-ol (6), and this implies that the
products from 5 and 6 may be derived from an identical η3-
allylpalladium intermediate. The catalyst system based on
the P(OC6H5)3 ligand was also effective for the formation of
1,4-dienes when styrylboronic acid was used as a coupling
partner. A single stereoisomer was obtained from the reac-
tion of 1 or 3 [Equation (4)].
The stereochemical course of the coupling process was
investigated at an early stage of the reaction of the cyclo-
hexenol derivative (9) (cis/trans ϭ 99%). To suppress the
stereochemical scrambling of the η3-allylpalladium inter-
mediates,[17] the reaction of 9 with phenylboronic acid was
performed at 50 °C and with a low catalyst loading (S/C ϭ
Scheme 1. SuzukiϪMiyaura coupling of substituted allylic alcohols
by the PdϪP(OC6H5)3 catalyst
Scheme 2. Stereochemical results of the cross-coupling of 5 or 6 with phenylboronic acid
www.eurjoc.org
Eur. J. Org. Chem. 2004, 4989Ϫ4993
 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
4991

Y. Kayaki, T. Koda, T. Ikariya
SHORT COMMUNICATION
400). The product, trans-10, was found to have 92% stereo-
isomeric purity at 6% conversion by 1H NMR spectroscopy
[Equation (5)], and this implies that the reaction may pro-
ceed through the widely accepted mechanism involving oxi-
dative addition to Pd0 with inversion of configuration, and
subsequent transmetallation and reductive elimination steps
with retention of stereochemistry.[18]
Acknowledgments
This work was financially supported by a Grant-in-Aid from the
Ministry of Education, Science, Sports, and Culture of Japan (No.
14078209, Reaction Control of Dynamic Complexes). This work
was partly supported by the 21st Century COE Program.
[1] [1a]
J. Tsuji, Palladium Reagents and Catalysts, 2nd ed., Wiley,
[1b]
Chichester, 2004.
Handbook of Organopalladium Chemistry
for Organic Synthesis (Ed.: E.-i. Negishi), John Wiley & Sons,
New York, 2002, vol. 2, p. 1669. [1c] S. A. Godleski, in: Compre-
hensive Organic Synthesis (Eds.: B. M. Trost, I. Fleming), Per-
gamon, Oxford, 1991, vol. 4, p. 585. [1d]B. M. Trost, D. L. Van
Vranken, Chem. Rev. 1996, 96, 395Ϫ422.
[2] [2a]
N. Miyaura, A. Suzuki, Chem. Rev. 1995, 95, 2457Ϫ2483.
N. Miyaura, Top. Curr. Chem. 2002, 219, 11Ϫ59.
[2b]
[3]
[3a] A. F. Littke, G. C. Fu, Angew. Chem. 2002, 114, 4350Ϫ4386;
Angew. Chem. Int. Ed. 2002, 41, 4176Ϫ4211.
[3b]
M. Miura,
Angew. Chem. 2004, 116, 2251Ϫ2253; Angew. Chem. Int. Ed.
2004, 43, 2201Ϫ2203 and references cited therein.
[4]
A base-free cross-coupling reaction of acid anhydrides with or-
Scheme 3. Possible mechanism of SuzukiϪMiyaura coupling of al-
lylic alcohol with phenylboronic acid
ganoboron reagents: [4a] R. Kakino, H. Narahashi, I. Shimizu,
[4b]
A. Yamamoto, Chem. Lett. 2001, 30, 1242Ϫ1243.
R. Kak-
ino, I. Shimizu, A. Yamamoto, Bull. Chem. Soc., Jpn. 2002, 75,
[4c]
137Ϫ148.
L. J. Gooßen, K. Ghosh, Angew. Chem. 2001,
113, 3566Ϫ3568; Angew. Chem. Int. Ed. 2001, 40, 3458Ϫ3460.
Y. Kayaki, T. Koda, T. Ikariya, J. Org. Chem. 2004, 69,
2595Ϫ2597.
[5]
[6]
Conclusion
Reviews of CϪO bond cleavage reactions by transition metal
[6a]
complexes:
34, 111.
A. Yamamoto, Adv. Organomet. Chem. 1992,
In summary, we have demonstrated a facile CϪC bond
forming reaction by using allylic alcohols catalyzed by the
PdϪP(OC6H5)3 system. The present process requires ne-
ither cocatalysts for promoting CϪO bond cleavage of al-
lylic alcohols nor bases for activation of organoboron re-
agents. Although allylic compounds have generally been
considered to be inert for cross-coupling reactions relative
to aryl and alkenyl substrates,[9,19] the present catalyst sys-
tem is characterized by high activity (S/C ϭ 100Ϫ500) and
high functional group tolerance as well as operational sim-
plicity. Further studies on the reaction mechanism and
other applications will be forthcoming.
[6b]
Y. S. Lin, A. Yamamoto, Topics in Organometallic
Chemistry (Ed.: S. Murai), Springer, Berlin, 1999, vol. 3, pp.
161Ϫ192.
[7]
[8]
Pd-promoted direct conversion of allylic alcohols without co-
catalysts: F. Ozawa, H. Okamoto, S. Kawagishi, S. Yamamoto,
T. Minami, M. Yoshifuji, J. Am. Chem. Soc. 2002, 124,
10968Ϫ10969, and references cited therein.
Bouyssi, et al. investigated the palladium catalyzed coupling of
arylboronic acids with allylic acetates under neutral conditions,
but addition of a stoichiometric amount of fluoride anion was
essential; D. Bouyssi, V. Gerusz, G. Balme, Eur. J. Org. Chem.
2002, 2445Ϫ2448.
[9]
RhCl3-catalyzed reaction in ionic liquid; G. W. Kabalka, G.
Dong, B. Venkataiah, Org. Lett. 2003, 5, 893Ϫ895.
Ni-catalyzed reaction; K.-G. Chung, Y. Miyake, S. Uemura, J.
Chem. Soc., Perkin Trans. 1 2000, 15Ϫ18.
[10]
[11]
There have been a number of reports on the application of
aryl phosphite ligands to SuzukiϪMiyaura coupling. [11a] D.A.
Experimental Section
Albisson, R. B. Bedford, S. E. Lawrence, P. N. Scully, Chem.
[11b]
Commun. 1998, 2095Ϫ2096.
S. Zhang, D. Marshall, L. S.
Typical Procedure for the Coupling Reactions: P(OC6H5)3 (1.3 µL,
5.0 ϫ 10Ϫ3 mmol) and 1 (0.17 mL, 2.5 mmol) was added success-
ively to a mixture of Pd2(dba)3·CHCl3 (2.6 mg, 5.0 ϫ 10Ϫ3 mmol/
Pd) and 2-naphthylboronic acid (516.0 mg, 3.0 mmol) in dioxane
(3.0 mL) under argon. After stirring at 80 °C for 2 h, the reaction
mixture was cooled to room temperature, poured into diethyl ether,
and washed with brine. The organic layer was dried with MgSO4,
filtered, and concentrated under reduced pressure. The crude prod-
uct was purified by chromatography on silica gel to afford 2-allyl-
naphthalene with a yield of 79% (334 mg). 1H NMR (300.04 MHz,
[11c]
Liebeskind, J. Org. Chem. 1999, 64, 2796Ϫ2804.
M. Beller, Chem. Eur. J. 2000, 6, 1830Ϫ1833.
A. Zapf,
[11d]
R. B.
Bedford, C. S. J. Cazin, S. L. Hazelwood, Angew. Chem. 2002,
114, 4294Ϫ4296; Angew. Chem. Int. Ed. 2002, 41, 4120Ϫ4122.
[11e]
R. B. Bedford, S. L. Hazelwood, M. E. Limmert, Chem.
[11f]
Commun. 2002, 2610Ϫ2611.
R. B. Bedford, S. L. Hazel-
wood, M. E. Limmert, J. M. Brown, S. Ramdeehul, A. R.
Cowley, S. J. Coles, M. B. Hursthouse, Organometallics 2003,
[11g]
22, 1364Ϫ1371.
R. B. Bedford, S. L. Hazelwood, P. N.
Horton, M. B. Hursthouse, Dalton Trans. 2003, 4164Ϫ4174.
V. Farina, B. Krishnan, J. Am. Chem. Soc. 1991, 113,
9585Ϫ9595.
H. Tsukamoto, M. Sato, Y. Kondo, Chem. Commun. 2004,
1200Ϫ1201.
[12]
[13]
[14]
3
CDCl3): δ ϭ 3.55Ϫ3.57 (d, JH,H ϭ 6.6 Hz, 2 H, CH2), 5.06Ϫ5.12
(m, 1 H, terminal CH2), 5.14Ϫ5.18 (ddt, 3JH,H ϭ 9.0, 3JH,H ϭ 1.7,
4JH,H ϭ 1.7 Hz, 1 H), 6.00Ϫ6.13 (m, 1 H, terminal CH2),
7.32Ϫ7.50 (m, 4 H, arene), 7.77Ϫ7.86 (m, 3 H, arene) ppm. 13C
NMR (75.45 MHz, CDCl3): δ ϭ 40.3, 116.1, 125.3, 125.9, 126.7,
127.4, 127.5, 127.6, 127.9, 132.1, 133.6, 137.3, 137.5 ppm. EIMS:
m/z ϭ 169 [Mϩ].
Related works on the coupling of propargylic alcohols with
[14a]
boronic acids.
M. Yoshida, T. Gotou, M. Ihara, Tetra-
[14b]
hedron Lett. 2004, 45, 5573Ϫ5575.
M. Ihara, Chem. Commun. 2004, 1124Ϫ1125.
M. Yoshida, T. Gotou,
4992
 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
Eur. J. Org. Chem. 2004, 4989Ϫ4993

A Highly Effective (Triphenyl phosphite)palladium Catalyst
SHORT COMMUNICATION
[15]
[19b]
T. Yamamoto, M. Akimoto, O. Saito, A. Yamamoto, Or-
Chem. Soc. 1985, 107, 972Ϫ980.
M. Moreno-Man˜as, F.
Pajuelo, R. Pleixats, J. Org. Chem. 1995, 60, 2396Ϫ2397.
[19c]
ganometallics 1986, 5, 1559Ϫ1567.
Attempts to confirm the allyl(hydroxo)palladium species by
[16]
Y. Uozumi, H. Danjo, T. Hayashi, J. Org. Chem. 1999, 64,
[19d]
NMR experiments were unsuccessful, possibly due to instability.
K. L. Granberg, J.-E. Bäckvall, J. Am. Chem. Soc. 1992, 114,
6858Ϫ6863.
3384Ϫ3388.
H. Chen, M.-Z. Deng, J. Org. Chem. 2000,
[17]
65, 4444Ϫ4446. [19e] J.-Y. Legros, J.-C. Fiaud, Tetrahedron Lett.
1990, 31, 7453Ϫ7456. [19f] Y. Kobayashi, R. Mizojiri, E. Ikeda,
[18]
[19g]
F. K. Sheffy, J. P. Godschalx, J. K. Stille, J. Am. Chem. Soc.
J. Org. Chem. 1996, 61, 5391Ϫ5399.
koro, K. Watatani, Eur. J. Org. Chem. 2000, 3825Ϫ3834.
Y. Kobayashi, Y. To-
1984, 106, 4833Ϫ4840.
[19] [19a]
N. Miyaura, K. Yamada, H. Suginome, A. Suzuki, J. Am.
Received September 1, 2004
Eur. J. Org. Chem. 2004, 4989Ϫ4993
www.eurjoc.org
 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
4993