Palladium-catalysed coupling reaction of allenic alcohols with aryl- and alkenylboronic acids

Article abstract of DOI:10.1039/b402047b

The direct coupling of aryl- and alkenylboronic acids with allenic alcohols has been achieved using a palladium catalyst to yield various substituted dienes and trienes in high yields.

Full text of DOI:10.1039/b402047b

Palladium-catalysed coupling reaction of allenic alcohols with aryl- and
alkenylboronic acids
Masahiro Yoshida,* Takahiro Gotou and Masataka Ihara*
Department of Organic Chemistry, Graduate School of Pharmaceutical Sciences, Tohoku University,
Aobayama, Sendai, 980-8578, Japan. E-mail: mihara@mail.pharm.tohoku.ac.jp; Fax: +81-22-217-6877
Received (in Cambridge, UK) 10th February 2004, Accepted 11th March 2004
First published as an Advance Article on the web 6th April 2004
The direct coupling of aryl- and alkenylboronic acids with
allenic alcohols has been achieved using a palladium catalyst to
yield various substituted dienes and trienes in high yields.
studies of transition metal-catalysed reactions using allenic alco-
hols,6 we found the palladium-catalysed direct coupling with
boronic acids (Scheme 1). We wish to report here our preliminary
results describing this coupling reaction.
Organoboronic acids are widely used reagents in organic synthesis
because of their commercial availability, stability and nontoxicity.
Various kinds of reactions using organoboronic acids have been
Initial attempts were made using 1-(1,2-propadienyl)cyclohex-
anol (1a) as a substrate (Table 1). When 1a was subjected to
reaction with 2-methylphenylboronic acid (2a) in the presence of
1
developed to construct a carbon–carbon bond. Among them,
3 4
10 mol% Pd(PPh ) in dioxane at 80 °C, the reaction was completed
palladium-catalysed coupling reactions of organoboronic acids
within 1 h to afford a coupled diene 3aa in 99% yield (entry 1 in
Table 1).† The reaction can be performed in the presence of 2 mol%
palladium catalyst without loss of the reactivity (entry 2), and the
product is efficiently obtained even in the presence of 0.5 mol% of
catalyst (88% yield, entry 3). A series of substituted boronic acids
were then subjected to the reaction (entries 4–12). Similar reactivity
has been observed in the reactions with other methyl- and methoxy-
substituted phenylboronic acids 2b–2d to lead to the corresponding
products 3ab–3ad in high yields (entries 4–6). Phenyl- and
1-naphthaleneboronic acids (2e and 2f) also give good results
(entries 7 and 8). Arylboronic acids 2g and 2h having an electron-
withdrawing group tolerate the reaction to produce the products 3ag
and 3ah in moderate yields (entries 9 and 10). When the reactions
with alkenylboronic acids 2i and 2j are carried out, the correspond-
2
3
4
with allylic, propargylic and allenic compounds are one of the
useful reactions to produce a variety of synthetically useful
unsaturated compounds. In these reactions, halides, esters and
carbonates are used as a leaving group of the substrates, which are
normally prepared by conversion from the corresponding alcohols.
The ability to use the alcohol itself in the coupling reactions would
be highly beneficial from the viewpoint of atom economy although
hydroxide is generally regarded as having poor reactivity as a
5
leaving group. Recently, the direct coupling reaction of boronic
acids with allylic alcohols catalysed by a rhodium complex has
been reported, in which the allylic alcohol can be effectively
5f
activated by carrying out the reaction in ionic liquids. However, to
the best of our knowledge, direct coupling of allenic alcohols with
boronic acids has not been reported. During the course of our
Table 2 Reactions of various substituted allenic alcohols 1b–1i with
2
-methylphenylboronic acid 2aa
Yield (%)
(E : Z)
Entry
1
Substrate
Productb
1b
3ba
95
Scheme 1
2
1c
3ca
3da
97
98
Table 1 Palladium-catalysed coupling of allenic alcohol 1a with boronic
a
acids 2a–2j
3c
1d
(1.5 : 1)
4d
99
1e
3ea
(9 : 1)
5
6
7
1f
3fa
3ga
3ha
91
Yield
(%)
Entry
1
Boronic acid
Product
96
1g
1h
2-methylphenylboronic acid (2a)
2a
2a
3aa
3aa
3aa
3ab
3ac
3ad
3ae
3af
3ag
3ah
3ai
99
99
88
87
99
90
83
97
67
63
84
93
(16 : 1)
b
2
3
c
91
4
5
6
7
8
9
4-methylphenylboronic acid (2b)
2-methoxyphenylboronic acid (2c)
4-methoxyphenylboronic acid (2d)
phenylboronic acid (2e)
1-naphthaleneboronic acid (2f)
4-acetylphenylboronic acid (2g)
3-nitrophenylboronic acid (2h)
trans-1-hexenylboronic acid (2i)
trans-2-phenylvinylboronic acid (2j)
8e
1i
3ia
97
(
> 20 : 1)
a
3 4
Reactions were carried out in the presence of 10 mol% Pd(PPh )
in
1
1
1
a
0
1
2
dioxane at 80 °C for 1–2 h. b Ar = 2-methylphenyl. The stereochemistry
of each product was tentatively assigned by the H-NMR shift of the methyl
proton on the dienyl group. d The stereochemistry of each product was
determined by using the NOESY technique. The stereochemistry of each
product was tentatively assigned by comparison with the known
1,2-diphenylbutadiene.
c
1
3aj
e
Reactions were carried out using Pd(PPh
)
3 4
(10 mol%) in dioxane at 80 °C
b
c
for 1 h. 2 mol% of Pd(PPh
used.
)
3 4
was used. 0.5 mol% of Pd(PPh
)
3 4
was
1
124
C h e m . C o m m u n . , 2 0 0 4 , 1 1 2 4 – 1 1 2 5
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

ing coupled trienes 3ai and 3aj are produced in good yields (entries
which is subsequently subjected to transmetalation with boronic
acid 2 to lead to the intermediate 5. Reductive elimination of
palladium from 5 produces the coupled product 3 and regenerates
palladium catalyst.
In conclusion, we have developed a palladium-catalysed cou-
pling reaction of allenic alcohols with aryl- and alkenylboronic
acids. Various aryl- and alkenyl-substituted dienes can be directly
synthesized from the corresponding allenic alcohols, and neither
carbonates nor esters are required as a leaving group. Synthetic
applications of the obtained dienes are being investigated and
further studies of this type of reaction are now in progress.
11 and 12).
Some results of palladium-catalysed reactions of various allenic
alcohols 1b–1i with 2-methylphenylboronic acid 2a are summa-
rized in Table 2. The reactions of 1b–1d, which have a cyclopentyl,
dipropyl and methylphenyl substituent, respectively, successfully
proceed to afford the corresponding products 3ba–3da in high
yields (entries 1–3). When substrates 1e and 1f possessing a methyl
group on the allenyl group are subjected to the reactions, the
substituted dienes 3ea and 3fa are obtained in 99% and 91% yield,
respectively (entries 4 and 5). A substrate 1g containing a
secondary hydroxyl group is uneventfully transformed to the
product 3ga in 96% yield (entry 6). Furthermore, it is clear that the
reactions of primary allenic alcohols 1h and 1i also proceed to
produce the dienes 3ha and 3ia in 91% and 97% yields (entries 7
and 8). All coupled products 3ba–3ia are obtained in over 90%
yields, and the corresponding (E)-products are predominantly
produced with moderate to high stereoselectivities from the
reactions of the unsymmetrical substrates 1d, 1e, 1g and 1i (entries
Notes and references
†
1
Typical procedure: To a stirred solution of 1a (50.0 mg, 0.362 mmol) in
,4-dioxane (3.6 mL) was added 2-methylphenylboronic acid (2a) (98.4 mg,
0.724 mmol), Pd(PPh3)4 (41.8 mg, 0.036 mmol) at rt, and stirring was
continued for 1 h at 80 °C. After filtration of the reaction mixture using
AcOEt with a small amount of silica gel followed by evaporation of the
eluate, the residue was chromatographed on silica gel with hexane as eluent
3, 4, 6 and 8).
to give 3aa (76.1 mg, 99%) as a colorless oil; R
f
= 0.49 (in hexane); IR
H-NMR (400 MHz, CDCl ) d
.18–7.12 (4H, m), 5.86 (1H, s), 5.21 (1H, m), 4.99 (1H, d, J = 2.8 Hz), 2.23
A plausible mechanism for the reaction is shown in Scheme 2. It
21
1
(neat) 2926, 2853, 1639, 1448 cm
;
3
is proposed that the substrate 1 is activated by a hydrogen bond
interaction with boronic acid 2 to form the reactive species 1·2. S 2A
attack of palladium on 1·2 affords the allylpalladium hydroxide 4,
7
N
(
3H, s), 2.14 (2H, t, J = 5.8 Hz), 1.96 (2H, t, J = 5.8 Hz), 1.61–1.33 (6H,
13
m); C-NMR (400 MHz, CDCl
3
) d 146.9, 143.3, 142.8, 135.2, 129.8,
1
2
28.6, 126.8, 125.5, 123.2, 117.0, 38.2, 29.3, 28.8, 27.6, 26.7, 20.1; MS m/z
12 (M ); HRMS m/z calcd for C16H20 212.1565 (M ), found 212.1568.
+
+
1
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2
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3
4
5
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S. Tanaka and M. Kimura, Tetrahedron Lett., 2000, 41, 5705; (b) Y.
Horino, M. Naito, M. Kimura, S. Tanaka and Y. Tamaru, Tetrahedron
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Y. Tamaru, J. Am. Chem. Soc., 2001, 123, 10401; (d) F. Ozawa, H.
Okamoto, S. Kawagishi, S. Yamamoto, T. Minami and M. Yoshifuji, J.
Am. Chem. Soc., 2002, 124, 10968; (e) K. Manabe and S. Kobayashi,
Org. Lett., 2003, 5, 3241; (f) G. W. Kabalka, G. Dong and B. Venkataiah,
Org. Lett., 2003, 5, 893.
6
(a) H. Nemoto, M. Yoshida and M. Ihara, J. Org. Chem., 1997, 62, 6450;
(b) M. Yoshida, K. Sugimoto and M. Ihara, Tetrahedron Lett., 2000, 41,
5
2
089; (c) M. Yoshida, K. Sugimoto and M. Ihara, Tetrahedron Lett.,
001, 42, 3877; (d) M. Yoshida, T. Gotou and M. Ihara, Tetrahedron
Scheme 2 Proposed reaction mechanism.
Lett., 2003, 44, 7151.
C h e m . C o m m u n . , 2 0 0 4 , 1 1 2 4 – 1 1 2 5
1125