Palladium(0)-catalyzed direct cross-coupling reaction of allyl alcohols with aryl- and vinyl-boronic acids

Article abstract of DOI:10.1039/b402256d

Allyl alcohols can be directly used for the palladium-catalyzed allylation of aryl- and vinyl-boronic acids without the aid of a base.

Full text of DOI:10.1039/b402256d

Palladium(0)-catalyzed direct cross-coupling reaction of allyl alcohols
with aryl- and vinyl-boronic acids†
Hirokazu Tsukamoto,* Masanori Sato and Yoshinori Kondo
Graduate School of Pharmaceutical Sciences, Tohoku University, Aobayama, Aoba-ku, Sendai 980-8578,
Japan. E-mail: hirokazu@mail.pharm.tohoku.ac.jp; Fax: +81-22-217-3906; Tel: +81-22-217-3906
Received (in Cambridge, UK) 13th February 2004, Accepted 16th March 2004
First published as an Advance Article on the web 15th April 2004
Allyl alcohols can be directly used for the palladium-catalyzed
allylation of aryl- and vinyl-boronic acids without the aid of a
base.
7–9). The highest yield was obtained in the coupling with
1-naphthylboronic acid 3N (entry 17), whereas the lowest yield was
obtained in the reaction with heteroarylboronic acid 3O (entry 18)
Allylation of trans- and cis-vinylboronic acid 3P and 3Q could be
achieved in moderate yield and stereospecificity with respect to the
boronic reagents (entries 19, 20).
Next, isomeric cinnamyl alcohols 2a,b and substituted cinnamyl
alcohols 1b–e were examined as the allylating reagents for
phenylboronic acid. a-Vinylbenzyl alcohol 2a, a regioisomer of 1a,
gave the same product 4aA in comparable yield (Table 1, entries 21
vs. 4). Although tertiary alcohol 2b had a high reactivity, its parent
cinnamyl alcohol 1b decreased the reaction rate and product yield
(entries 22, 23). Larger substituents at C-1 also resulted in slower
reaction and lower yields (entries 24, 25). Introduction of a methyl
group at the C-2 position in cinnamyl alcohol hindered the reaction
(entry 26).
Palladium-catalyzed cross-coupling reaction with organometallics
containing B, Mg, Zn, Sn, etc. has been a powerful tool for carbon–
carbon bond formation in organic synthesis.1 Among the organo-
metallics, organoboronic reagents have been widely used because
they are generally non-toxic, commercially available, stable and
compatible with various functional groups.2 Compared to the
significant development of their Pd-catalyzed coupling reaction
with aryl- and vinyl-halides or -sulfonates,2 coupling reactions with
allyl derivatives including halides,3 carboxylates4 and phenyl
ethers5 have received only scattered attention. These allyl deriva-
tives are usually prepared from the corresponding allyl alcohols and
their coupling reaction commonly requires stoichiometric amounts
of a base except for allyl phenyl ethers.5 The direct use of allyl
alcohols for the cross-coupling reaction would omit the preparation
steps of allyl derivatives and make the overall process of the
coupling reaction atom economical.6 However, allyl alcohols
themselves are rarely used because hydroxide is a poor leaving
group. Rh-7 and Ni-catalysed8 coupling of allyl alcohols with
arylboronic acids have been reported, but their allylating reagents
are only limited to cinnamyl alcohols and 2-cyclohexen-1-ol,
respectively. We describe here the first palladium(0)-catalyzed
cross-coupling reaction of a wider range of allyl alcohols with aryl-
and vinyl-boronic acids in the absence of a base.
As with allyl alcohols, unsubstituted allyl alcohol 5a and alkyl-
substituted allyl alcohol 5b–g were used for the allylation of
1-naphthylboronic acid (Scheme 2, Table 2). The reaction of
2-propenyl alcohol (5a) gave 6a in good yield (Table 2, entry 1).
The two regioisomers of crotyl alcohol (5b and 5c) were converted
into 6b-E, 6b-Z and 6c with the same regio- and stereo-selectivity
Table 1 Coupling of cinnamyl alcohols and their isomers with organo-
boronic acidsa
Cinnamyl
Entry alcohol
Isolated
Product t/h yield (%)
Boronic acid
First, cinnamyl alcohol 1a was examined as an allylating reagent
for phenylboronic acid in the presence of 5 mol% tetrakis-
(triphenylphosphine)palladium [Pd(PPh3)4] 9 (Scheme 1, Table 1,
entries 1–4). To our surprise, the cross-coupling reaction readily
proceeded upon heating at 80 °C in a sealed tube without any
additive.10 At lower temperature, bis(cinnamyl)ether was formed as
a by-product and no reaction was observed in the absence of the
palladium catalyst (data not shown). Although dichloromethane
was found to be the most effective solvent, toluene, 1,4-dioxane and
THF could be employed as alternatives (entries 1–4). Arylboronic
acids with electron-donating (Table 1, entries 5–9) or -withdrawing
groups (entries 10–16) could also be coupled with 1a in satisfactory
yields. Generally, the former boronic acids required a shorter
reaction time and gave higher yields than the latter. In contrast to
the Rh-catalyzed reaction,7 steric factors did not affect the yield.
Ortho-, meta- and para-tolylboronic acids reacted equally (entries
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
2a
2b
Phenyl 3A
Phenyl 3A
Phenyl 3A
Phenyl 3A
p-Methoxyphenyl 3B
p-Methylthiophenyl 3C
p-Tolyl 3D
o-Tolyl 3E
m-Tolyl 3F
4aA
4aA
4aA
4aA
4aB
4aC
4aD
4aE
4aF
4aG
4aH
3
3
3
3
4
61
68
69
80
78
21 78
6
2
5
76
78
75
p-Chlorophenyl 3G
p-Fluorophenyl 3H
p-(Trifluoromethyl)phenyl 3I 4aT
15 69
11 58
7
63
p-Formylphenyl 3J
p-Acetylphenyl 3K
p-Cyanophenyl 3L
m-Nitrophenyl 3M
1-Naphthyl 3N
3-Thiophene 3O
trans-b-Styryl 3P
cis-Propenyl 3Q
Phenyl 3A
4aJ
15 70
19 78
19 77
19 50
2
6
8
6
4
4
4aK
4aL
4aM
4aN
4aO
4aP
4aQ
4aA
4bA
92
28
53
52
71
70
Phenyl 3A
(E:Z 5:3)b
23
1b
Phenyl 3A
4bA
33 52
(E:Z 3:2)b
24
25
26
1c
1d
1e
Phenyl 3A
Phenyl 3A
Phenyl 3A
4cA
4dA
4eA
33 63
24 36
39 18
Scheme 1 Coupling of cinnamyl alcohols 1a–e and their isomers 2a,b with
organoboronic acids 3A–Q.
(E:Z 5:2)b
a The reaction was carried out in THF (entry 1), 1,4-dioxane (entry 2),
toluene (entry 3) and dichloromethane (entries 4–26). b E:Z ratio was
determined by 1H-NMR.
† Electronic supplementary information (ESI) available: spectral data of
compounds. See http://www.rsc.org/suppdata/cc/b4/b402256d/
1200
C h e m . C o m m u n . , 2 0 0 4 , 1 2 0 0 – 1 2 0 1
T h i s j o u r n a l i s © T h e R o y a l S o c i e t y o f C h e m i s t r y 2 0 0 4

the palladium(0) complex to give 14 which has been approved in
the Tsuji–Trost reaction14 of 1,3-dicarbonyl compounds with allyl
alcohols as allylating agents15 (path B). However, no coupling
products were obtained when cinnamyl alcohol 1a was heated in
THF with boronate complexes such as sodium tetraphenylborate
and potassium phenyltrifluoroborate, which would not work as a
Lewis acid.
The present study offers an extremely facile allylation procedure
for aryl- and vinyl-boronic acids with a wide variey of functional
groups. As for allyl alcohols, cinnamyl alcohols and their isomers,
unsubstituted and alkyl-substituted allyl alcohols could be directly
used. Neither preparation of allyl halides and esters nor addition of
stoichiometric amounts of a base are required. Although the
reaction required heating, it was not accompanied by the elimina-
tion of hydrogen from p-allylpalladium complexes to generate
conjugated 1,3-diene. Further studies on the detailed mechanism of
the cross-coupling reaction and application to deprotection of allyl
ether, one of the most useful protecting groups in organic synthesis,
are underway in our laboratory.
Scheme 2 Coupling of 1-naphthylboronic acid 3N with aliphatic allyl
alcohols 5a–g.
Table 2 Coupling of 1-naphthylboronic acid with aliphatic allyl alcohols
Isolated yield
Entry Allyl alcohol
Product t/h
(%)
1
2
Allyl alcohol (5a)
6a
6b + 6c
11
9
76
78
Crotyl alcohol (5b)
3-Buten-2-ol (5c)
Prenyl alcohol (5d)
2-Methyl-3-buten-2-ol (5e) 6d
Methallyl alcohol (5f)
2-Cyclohexen-1-ol (5g)
Notes and references
(6b-E:6b-Z:6c =
6:1:3)a
1 J. Tsuji, Palladium Reagents and Catalysts, John Wiley & Sons,
Chichester, 1995; Handbook of Organopalladium Chemistry for
Organic Synthesis, E. Negishi, ed., John Wiley & Sons, New York,
2002.
3
6b + 6c
9
81
(6b-E:6b-Z:6c =
6:1:3)a
2 N. Miyaura, Top. Curr. Chem., 2002, 219, 12.
4
5
6
7
6d
48
48
39
24
72
84
37
23
3 M. Moreno-Mañas, F. Pajuelo and R. Pleixats, J. Org. Chem., 1995, 60,
2396; J. Cortés, M. Moreno-Mañas and R. Pleixats, Eur. J. Org. Chem.,
2000, 239; M. Moreno-Mañas, R. Pleixats and S. Villarroya, Organo-
metallics, 2001, 20, 4524; E. Paetzold and G. Oehme, J. Mol. Catal. A,
2000, 152, 69; L. Botella and C. Nájera, J. Organomet. Chem., 2002,
663, 46; D. A. Alonso, C. Nájera and M. Pacheco, J. Org. Chem., 2002,
67, 5588.
6f
6g
a E:Z ratio was determined by 1H-NMR.
(entries 2, 3). Similarly, the reaction of prenyl alcohol 5d and its
isomer 5e gave the same product 6d exclusively (entries 4, 5). The
use of methallyl alcohol 5f with a methyl group at C-2 like 1e or
cyclic allyl alcohol 5g led to a lower yield (entries 6, 7).
4 (a) J.-Y. Legros and J.-C. Fiaud, Tetrahedron Lett., 1990, 31, 7453; (b)
E. Blart, J.-P. Genêt, M. Safi, M. Savignac and D. Sinou, Tetrahedron,
1994, 50, 505; (c) Y. Uozumi, H. Danjo and T. Hayashi, J. Org. Chem.,
1999, 64, 3384; (d) D. Bouyssi, V. Gerusz and G. Balme, Eur. J. Org.
Chem., 2002, 2445.
Formation of the same products from allyl alcohols and their
isomers may suggest the participation of p-allylpalladium inter-
mediates in the reaction process. It is noteworthy that in spite of the
heated reaction conditions, the formation of conjugated 1,3-dienes
caused by Pd–H elimination from p-allylpalladium intermediates
was not observed in the reactions of 1b,c, 2b and 5b–e,g.4c,11
The plausible mechanism for the cross-coupling reaction is
outlined in Scheme 3. Oxidative addition of allyl alcohol 7
activated by the coordination with arylboronic acid 8 to the Pd(0)
species12 leads to a cationic p-allylpalladium intermediate 10 with
an arylborate counter anion (path A, through 9). This intermediate
exists in equilibrium with arylboronic acid 8 and (p-allylhydroxo)-
palladium complex 11, which would smoothly undergo trans-
metalation to give diorganopalladium complex 12.2,5,13 Reductive
elimination of the coupling product 13 from 12 reproduces the
palladium(0) complex. At this time, it is not possible to rule out a
mechanism involving direct oxidative addition of allyl alcohol 7 to
5 N. Miyaura, K. Yamada, H. Suginome and A. Suzuki, J. Am. Chem.
Soc., 1985, 107, 972.
6 B. M. Trost, Angew. Chem., Int. Ed. Engl., 1995, 34, 259; B. M. Trost,
Science, 1991, 254, 1471.
7 G. W. Kabalka, G. Dong and B. Venkataiah, Org. Lett., 2003, 5, 893.
8 B. M. Trost and M. D. Spagnol, J. Chem. Soc., Perkin Trans. 1, 1995,
2083; K.-G. Chung, Y. Miyake and S. Uemura, J. Chem. Soc., Perkin
Trans. 1, 2000, 15.
9 The Pd2(dba)3 (2.5 mol%)–PPh3 (10 mol%) catalytic system could be
used instead of Pd(PPh3)4.
10 Typical procedure: a mixture of substrate (0.30 mmol), organoboronic
acid (0.36 mmol), Pd(PPh3)4 (0.015 mmol) and dry dichloromethane (1
mL) was heated at 80 °C in a sealed tube under argon atmosphere. After
being stirred at the same temperature for the time described in Table 1
and 2, the reaction mixture was evaporated and purified by preparative
thin layer chromatography to give the allylated product.
11 Uozumi et al.4c reported that the Pd(PPh3)4-catalyzed coupling reaction
of acetyl derivative of 1c with phenylboronic acid 3A in the presence of
Na2CO3 gave 4cA and 1-phenylbutadiene in 14 and 38% yield,
respectively. Tsuji et al., reported that no elimination was observed with
allyl alcohol under the Pd(OAc)2–PPh3 catalytic system in the absence
of a base: J. Tsuji, T. Yamakawa, M. Kaito and T. Mandai, Tetrahedron
Lett., 1978, 24, 2075.
12 X. Lu, X. Jiang and X. Tao, J. Organomet. Chem., 1988, 344, 109; I.
Stary, I. G. Stara and P. Kocovsky, Tetrahedron Lett., 1993, 34, 179; I.
Stary, I. G. Stara and P. Kocovsky, Tetrahedron, 1994, 50, 529; Y.
Tamaru, Y. Horino, M. Araki, S. Tanaka and M. Kimura, Tetrahedron
Lett., 2000, 41, 5705; Y. Horino, M. Naito, M. Kimura, S. Tanaka and
Y. Tamaru, Tetrahedron Lett., 2001, 42, 3113; M. Kimura, Y. Horino,
R. Mukai, S. Tanaka and Y. Tamaru, J. Am. Chem. Soc., 2001, 123,
10 401.
13 T. Moriya, N. Miyaura and A. Suzuki, Synlett, 1994, 149.
14 B. M. Trost and D. L. van Vranken, Chem. Rev., 1996, 96, 395; B. M.
Trost, Chem. Pharm. Bull., 2002, 50, 1.
Scheme 3 Possible catalytic cycle for the coupling reaction of allyl alcohols
with arylboronic acids.
15 K. Manabe and S. Kobayashi, Org. Lett., 2003, 5, 3241 and refs. cited
therein.
C h e m . C o m m u n . , 2 0 0 4 , 1 2 0 0 – 1 2 0 1
1201