Palladium(0)-catalyzed direct cross-coupling reaction of allylic alcohols with aryl- and alkenylboronic acids

Article abstract of DOI:10.1039/b804991b

Allylic alcohols can be used directly for the palladium(0)-catalyzed allylation of aryl- and alkenylboronic acids with a wide variety of functional groups. A triphenylphosphine-ligated palladium catalyst turns out to be most effective for the cross-coupling reaction and its low loading (less than 1 mol%) leads to formation of the coupling product in high yield. The Lewis acidity of the organoboron reagents and poor leaving ability (high basicity) of the hydroxyl group are essential for the cross-coupling reaction. The reaction process is atom-economical and environmentally benign, because it needs neither preparation of allyl halides and esters nor addition of stoichiometric amounts of a base. Furthermore, allylic alcohols containing another unsaturated carbon-carbon bond undergo arylative cyclization reactions leading to cyclopentane formation. The Royal Society of Chemistry.

Full text of DOI:10.1039/b804991b

View Article Online / Journal Homepage / Table of Contents for this issue
PAPER
www.rsc.org/obc | Organic & Biomolecular Chemistry
Palladium(0)-catalyzed direct cross-coupling reaction of allylic alcohols with
aryl- and alkenylboronic acids†
Hirokazu Tsukamoto,* Tomomi Uchiyama, Takamichi Suzuki and Yoshinori Kondo
Received 25th March 2008, Accepted 16th May 2008
First published as an Advance Article on the web 27th June 2008
DOI: 10.1039/b804991b
Allylic alcohols can be used directly for the palladium(0)-catalyzed allylation of aryl- and
alkenylboronic acids with a wide variety of functional groups. A triphenylphosphine-ligated palladium
catalyst turns out to be most effective for the cross-coupling reaction and its low loading (less than
1 mol%) leads to formation of the coupling product in high yield. The Lewis acidity of the organoboron
reagents and poor leaving ability (high basicity) of the hydroxyl group are essential for the
cross-coupling reaction. The reaction process is atom-economical and environmentally benign, because
it needs neither preparation of allyl halides and esters nor addition of stoichiometric amounts of a base.
Furthermore, allylic alcohols containing another unsaturated carbon–carbon bond undergo arylative
cyclization reactions leading to cyclopentane formation.
Introduction
The palladium-catalyzed cross-coupling reaction with organo-
metallics containing B, Mg, Zn, Sn, Si, etc. has been a
powerful tool for carbon–carbon bond formation in organic
synthesis.1 Organoboron reagents are less nucleophilic than other
Scheme 1 Cross-coupling of allylic alcohol with organoboronic acid.
organometallics, but have often been used because they are
followed us and pointed out the high catalyst loading of our own
reaction.12,13 Fortunately, our continuing studies on the coupling
reaction have led to the solution of the problem and are described
here.
generally non-toxic, commercially available, stable and compatible
with a wide variety of functional groups.2 Compared to the
significant development of the Pd-catalyzed coupling reaction
with aryl- and alkenyl-halides or sulfonates,2 that with allyl
derivatives including halides,3 carboxylates4 and phenyl ethers5
has received only scattered attention. These allyl derivatives are
usually prepared from the corresponding allylic alcohols and,
except for allyl phenyl ethers, their coupling reaction commonly
requires stoichiometric amounts of a base.5 The direct use of allyl
alcohols for the cross-coupling reaction would avoid the need for
the preparation of allyl derivatives and make the overall process
of the coupling reaction more atom economical.6 However, allylic
alcohols themselves have been rarely used because hydroxide is
a poor leaving group.7 The Rh-8 and Ni-9catalyzed coupling of
allylic alcohols with arylboronic acids has been reported, but their
allylating reagents were limited to only cinnamyl alcohols and
2-cyclohexen-1-ol, respectively. Recently, we developed the first
palladium(0)-catalyzed cross-coupling reaction of a wider range
of allylic alcohols with aryl- and alkenylboronic acids under base-
free conditions (Scheme 1).10 In spite of the less reactive substrates
and reagents, this coupling process is highly active and efficient,
without forming inorganic salts. Furthermore, we applied the Pd-
catalyzed coupling reaction of allylic alcohols to the deprotection
of allylic ethers, which was also difficult owing to their poor leaving
ability.11 Several reports on closely related coupling reactions
Results and discussion
In the preliminary report, we developed reaction conditions
for the cross-coupling reaction of cinnamyl alcohol (4) with
phenylboronic acid (3a) as a model study. Upon heating at 80 ◦C in
the presence of 5 mol% of tetrakis(triphenylphosphine)palladium
[Pd(PPh3)4], 4 underwent the cross-coupling reaction to afford
(E)-1,3-diphenylpropene (5a) in good yield. Although the reaction
proceeded in any solvent such as toluene, 1,4-dioxane, DMF, and
THF, dichloromethane turned out to be the best solvent (Table 1,
entries 1, 3, 5, 7, 9). In dichloromethane, the product yield was
maintained even when the catalyst loading was lowered from 5
to 2 mol% (entries 1 vs. 2). However, the lower catalyst loading
gave higher yields of 5a with other solvents (entries 4, 6, 8, 10)14
and the best solvent became THF. Then, the catalyst loading
effects on the product yield in THF were studied in detail. This
disproportional tendency was closely preserved in the reaction
with 10, 5, 2, 1, 0.5, and 0.2 mol% of the catalyst (entries 9–11,
14–16). Furthermore, the effect of the ratio of phosphine to Pd
on the reaction was investigated to determine whether decreases
in the amount of Pd metal or the phosphine ligand increase
the product yield. Changing the ratio of phosphine to Pd from
4 : 1 to 1 : 115 by using Pd2dba3 as the Pd source instead of
Pd(PPh3)4 revealed that the phosphine quantity seriously affected
the product yield (entries 9 vs. 12, 13). Almost similar values for
the sum of the phosphine quantity and product yield (entries 9–16)
would indicate that an excess of phosphine competitively attacks a
Graduate School of Pharmaceutical Sciences, Tohoku University, Aramaki-
aza aoba 6–3, Aoba-ku, Sendai, 980-8578, Japan. E-mail: hirokazu@
mail.pharm.tohoku.ac.jp; Fax: +81-22-795-3906; Tel: + 81-22-795-3906
† Electronic supplementary information (ESI) available: General experi-
mental procedures, tables of results and spectral data of the cross-coupling
products. See DOI: 10.1039/b804991b
This journal is
The Royal Society of Chemistry 2008
Org. Biomol. Chem., 2008, 6, 3005–3013 | 3005
©

View Article Online
Table 1 Effects of solvent and catalyst loading on the yield of 5aa
Entry
Solvent
[Pd] (mol%)
[PPh3] (mol%)
Time (h)
Yield (%)
Sum of [PPh3] + Yield (%)
1
2
3
4
5
6
7
8
9
10
11
12a
13a
14
15
16
17
CH2Cl2
CH2Cl2
Toluene
Toluene
1,4-Dioxane
1,4-Dioxane
DMF
DMF
THF
THF
THF
THF
THF
THF
THF
THF
tAmOH
5
2
5
2
5
2
5
2
5
2
10
5
5
1
0.5
0.2
0.5
20
8
20
8
20
8
20
8
20
8
40
10
5
4
2
3
10
3
4
3
3
6
10
3
3
3
3
3
3
3
6
3
74
68
66
74
63
80
45
70
66
81
47
83
83
85
87
88
81
94
76
86
82
83
88
65
78
86
89
87
93
88
89
89
89
83
0.8
2
a Reaction with 2.5 mol% of Pd2dba3 and PPh3 instead of Pd(PPh3)4.
p-allylpalladium intermediate (vide infra). Although we could not
observe the formation of the phosphonium salt or phosphorane
directly, there have been several reports of attack by phosphines
on p-allylpalladium complexes.16,17 Consequently, we could not
only reduce the catalyst loading from 5 mol% to 0.2 mol%,
which is comparable to other cross-coupling reactions of allylic
alcohols with arylboronic acids, but also increase the product
yield simultaneously. Although protic polar solvents are reported
to accelerate the oxidative addition to Pd0,18 this reaction could
not be accelerated by using tert-amyl alcohol as the solvent (entry
17).
As with nucleophiles, boroxine as the anhydride of 3a has
the same reactivity as the boronic acid (Table 1, entry 15 vs.
Table 2, entry 1). Boronic esters of 3a dramatically decrease the
product yield, but the more Lewis acidic catechol ester proves to
be better than the pinacol ester (Table 2, entries 2, 3). Lewis acidic
triphenylborane also participates in this process and provides 5a
in better yield than its borate anions (entries 4, 5). These results
indicate that the Lewis acidity of the boron reagents rather than
their Brønsted acidity is essential in this reaction.
As with electrophiles, the methyl ether and carbonate of 4 show
comparable reactivity to the parent alcohol 4 (Table 1, entry 15
vs. Table 3, entries 1, 2). Reaction with the aryl ether of 4 takes a
longer reaction time, but provides 5a in high yield (Table 3, entry
3). In spite of its good leaving ability in the Tsuji–Trost reaction, the
acetate of 4 leads to poor formation of 5a (entry 4). These results
indicate that the high basicity of the leaving group is essential for
the cross-coupling reaction.
We also examined ligand effects on the coupling reaction
(Table 4). The Pd catalysts ligated with these ligands were prepared
in situ by mixing 0.5 mol% of Pd2dba3 and 1 mol% of the ligands.
In contrast to Ikariya et al.’s report,12a,19 triphenylphosphine turns
out to be the best one, but triarylphosphines bearing methoxy and
chloro groups at their para-positions were less effective (entries 1
vs. 2, 3). p-Accepting heteroarylphosphines and phosphites give
much better results than r-donating trialkylphosphines (entries 4–
7 vs. 8, 9). Bisphosphine does not promote the reaction at all (entry
10). Triphenylarsine gives 5a in only moderate yield (entry 11). For
practical use, we decided to employ Pd(PPh3)4 as the catalyst for
the following cross-coupling reactions.
Table 2 Effects of organoboron reagents
Table 3 Effects of leaving groups
Entry
[PhB]
Yield (%)
1a
2
3
4
5
(PhBO)3
73
ndb
26
63
32
PhB(pinacolato)
PhB(catecholato)
Ph3B
Entry
X
Time (h)
Yield (%)
Ph4BNa
1
2
3
4
OMe
3
3
12
12
85
91
81
21
OCO2Me
OC6H4-4-OMe
OAc
a Reaction with 0.4 equiv. of (PhBO)3. b Formation of 5a was not observed
by TLC.
3006 | Org. Biomol. Chem., 2008, 6, 3005–3013
This journal is
The Royal Society of Chemistry 2008
©

View Article Online
Table 4 Ligand effects
acids (3u–v) is dramatically affected by their substitution position
(entries 20, 21).20 Retention of stereochemistry accompanies the
reactions of 4 with alkenylboronic acids 3w–z that afford 1,3-
dienes 5w–z in good yield (entries 22–25). Generally, the newly
developed reaction conditions, i.e. low catalyst loading and THF
solvent, cause both an acceleration of the reaction rate and an
improvement in the product yields.
Entry
Ligand
Yield (%)
Phenylation of (Z)-cinnamyl alcohol (6) has a reaction time
twice as long as that of the (E)-isomer 4, but gives the same (E)-
1,3-diphenylpropene (5a) in comparable yield (Table 6, entry 1 vs.
Table 1, entry 15). 1-Phenyl-2-propen-1-ol (7), as a regioisomer
of 4, can also be coupled with 3a leading to the formation of 5a
(entry 2). Although the reaction of 3-methyl-substituted cinnamyl
alcohol 8 is much more sluggish and requires a higher reaction
temperature than that of its isomeric tertiary alcohol 9, both
reactions provide tri-substituted alkene 14 as a stereoisomeric
mixture in the same ratio (entries 3, 4). The coupling reactions
of 1,3-disubstituted allylic alcohols 10–12 with 3a require a long
reaction time but afford phenyl-conjugated alkenes 15 and 16
in good yields (entries 5–7). Since the introduction of a methyl
group at the C-2 position in cinnamyl alcohol retards the reaction
remarkably, raising the reaction temperature to 110 ◦C and using
1,4-dioxane is necessary to improve the yield of 17 (entry 8). It
is worth noting that the coupling reaction of optically active 10
results in a complete loss of chirality transfer (Table 6, entry 5)21
and proves to be more efficient than that of the corresponding
acetate 18, which forms conjugated 1,3-diene 19 as the major
product via Pd-H elimination from p-allylpalladium intermediates
(Scheme 2).4c,22
1
2
3
4
5
6
7
8
9
P(C6H5)3
P(C6H4-4-OMe)3
P(C6H4-4-Cl)3
P(2-furyl)3
P(2-thienyl)3
P(OPh)3
87
48
49
71
82
86
83
22
nd
nd
53
P(OEt)3
PCy3
PBu3
10
11
dppea
AsPh3
a Reaction with 0.5 mol% of dppe. dppe = 1,2-bis(diphenylphosphino)-
ethane.
Arylboronic acids with electron-donating (Table 5, entries 1–9)
or -withdrawing groups (entries 10–17) serve as nucleophiles in this
process, which leads to the formation of cross-coupling products
5b–r in high yields. Whereas 2-methylphenylboronic acid (3g) has
the same reactivity as 3- and 4-methylphenylboronic acids (3h and
3f), the 2,6-dimethyl substituted version has much lower reactivity
(entries 5–7 vs. 8). Regardless of their substitution position,
naphthaleneboronic acids (3s–t) also participate in this process
(entries 18, 19). However, the reaction with thiopheneboronic
Table 5 Cross-coupling of 4 with aryl- and alkenylboronic acids
Scheme 2 Cross-coupling of allylic acetate 18 with 3a.4c
Entry
R
Product
Time (h)
Yield (%)
Next, unsubstituted allylic alcohol 1 and the alkyl-substituted
analogs 20–25 were used for the allylation of 1-naphthylboronic
acid (3s) (Table 7). The reaction of 2-propen-1-ol (1) gives 2s in high
yield (entry 1). The two regioisomers of butenols (20 and 21) are
converted to 26-E, 26-Z, and 27 in the same regio- and stereoselec-
tivity (entries 2, 3). Thus, alkyl substitution at the 1- or 3-position
of the allylic alcohols leads to the formation of a more complex
mixture than phenyl substitution (Table 6, entries 1, 2 vs. Table 7,
entries 2, 3). Similarly, prenyl alcohol 22 and its isomer 23 are
converted to the trisubstituted alkene 28 and the terminal alkene
29 in almost same ratio (entries 4, 5). The reactions of less reactive
substrates such as methallyl alcohol (24) and 2-cyclohexen-1-ol
(25) require a higher reaction temperature (entries 6, 7).
The Pd(0)-catalyzed reactions of alkyne-containing allylic al-
cohol 32 with arylboronic acids 3f and 3u provide 5-membered
cyclic systems bearing neighboring vinyl and alkylidene groups
(Scheme 3).23 It is worth noting that 2-thiopheneboronic acid
participates not in the cross-coupling process (Table 5, entry 20),
but in the cyclization. These results would indicate that the poor
reactivity of 3u in the cross-coupling reaction should not result
from hindrance of the oxidative addition step in the catalytic
cycle.24
1
2
4-MeO–C6H4
4-MeS-C6H4
4-Me2N-C6H4
4-AcHN-C6H4
4-Me-C6H4
2-Me-C6H4
3-Me-C6H4
5b
5c
5d
5e
5f
5g
5h
5i
5
8
6
6
3
4
4
3
3
4
3
4
4
4
8
8
6
4
3
12
3
3
3
3
3
92
90
77
90
88
90
88
34
85
87
83
84
75
85
83
82
73
86
79
nd
94
89
72
68
76
3
4a
5
6
7
8
9
2,6-diMe-C6H3
=
4-H2C CH-C6H4
5j
5k
5l
10
11
12
13
14
15
16
17
18
19
20b
21b
22
23
24
25
4-F-C6H4
4-Cl-C6H4
4-F3C-C6H4
4-OHC-C6H4
4-EtO2C-C6H4
4-Ac-C6H4
5m
5n
5o
5p
5q
5r
5s
5t
5u
5v
5w
5x
5y
5z
4-NC-C6H4
3-O2N-C6H4
1-naphthalene
2-naphthalene
2-thiophene
3-thiophene
trans-b-styryl
a − styryl
trans-1-propenyl
cis-1-propenyl
a Reaction with 1 mol% of catalyst. b Reaction with 2 equiv. of 3.
This journal is
The Royal Society of Chemistry 2008
Org. Biomol. Chem., 2008, 6, 3005–3013 | 3007
©

View Article Online
Table 6 Cross-coupling of phenyl-substituted allylic alcohols 6–13 with 3aa
Entry
1
Alcohol
Product
Time (h)
6
Yield (%)
90
5a
2
5a
14
4
24
6
89
3b
4
69 (E : Z = 2 : 1)c
80 (E : Z = 2 : 1)c
79d
5
36
6
15
36
32
24
73
7
80
8b
65 (E : Z = 2.5 : 1)d
a Reaction conditions: a solution of 1 equiv. of 6–13, 1.2 equiv. of 3a, and 0.5 mol% of Pd(PPh3)4 in anhydrous THF is agitated at 80 ◦C. b Reaction in
1,4-dioxane at 110 ◦C. c The E : Z ratio was determined by 1H NMR analysis. d A small amount of (E)-1-phenyl-1,3-butadiene (19) was also formed.
Scheme 3 Arylative cyclization of 1,6-enyne 32.
Scheme 5 Arylative cyclization of 1,6-dienes 36a–b.
Although replacement of the alkyne in 32 with a 1-propenyl
group results in failure of the cyclization, the more conforma-
Formation of the same products in the same ratios from isomeric
tionally restricted substrate 36a cyclized efficiently (Scheme 4 vs.
allylic alcohols such as 4, 6, and 7, 8–9, 10–11, 20–21, and 22–
23 suggests that the common p-allylpalladium intermediate 40
participates in the reaction process (Scheme 6).26 The formation
of 40 through oxidative addition of the less reactive allylic alcohol
38 to the Pd(0) species would require not only the coordination of
the Pd(0) to the olefin in 38 but also that of the Lewis acidic
organoboron reagents 3 to the hydroxyl group in 38.27–29 The
inefficient coupling seen with less Lewis acidic borate anions
would support the importance of the latter coordination (Table 2,
entries 4, 5). The following transmetalation between a cationic
p-allylpalladium and an arylborate counteranion would give the
Scheme 5).25 To our surprise, the cyclization of syn-allylic alcohol
36b requires a longer reaction time, but provides the same bicyclic
37 in high yields.
Scheme 4 Arylative cyclization of 1,6-diene 34.
3008 | Org. Biomol. Chem., 2008, 6, 3005–3013
This journal is
The Royal Society of Chemistry 2008
©

View Article Online
Table 7 Cross-coupling of alkyl-substituted allylic alcohols 1, 20–25 with
3sa
Entry Alcohol
1
Product
Yield (%)
80
2
72 (26-E : 26-Z : 27 = 9 : 1 : 6)b
3
4
26 (E,Z) + 27 83 (26-E : 26-Z : 27 = 11 : 1 : 8)b
64 (28 : 29 = 12 : 1)b
Scheme 6 Possible mechanism for the cross-coupling reaction.
pure alcohol 10 to the completely racemic product 15 and that
of anti and syn isomers 36a–b to the same cyclized product 37
would support attack by Pd(0) (Table 6, entry 5 and Scheme 5).
The epimerization of 40 in the presence of less than 1 mol% of
catalyst can be explained by Ba¨ckvall and Grandberg’s report16f
that the Pd(0) catalyst is much more nucleophilic towards the
p-allyl group than the phosphine and that the less reactive allylic
substrate would make the oxidative addition step rate-limiting and
increase the concentration of the Pd(0), leading to the more rapid
epimerization of 40. On the other hand, the strong basicity of the
hydroxyl and alkoxyl groups would promote the transmetalation
step.2,5,30 The much slower reaction with the less basic phenyl ether
and acetate would be due to hindrance of the transmetalation step
(Table 3, entries 1, 2 vs. 3, 4).
5
28 + 29
75 (28 : 29 = 7.4 : 1)b
6c
77
7c
23
a Reaction conditions: a solution of 1 equiv. of 1, 20–25, 1.2 equiv. of 3s,
and 0.5 mol% of Pd(PPh3)4 in anhydrous THF is agitated at 80 ◦C for 24 h.
Ar = 1-naphthyl. b The E : Z ratio was determined by 1H NMR analysis.
c Reaction in 1,4-dioxane at 110 ◦C for 12 h.
Conclusions
The present study offers an extremely facile allylation procedure
for aryl- and alkenylboronic acids with a wide variety of functional
groups. Low catalyst loading, poor leaving ability (high basicity)
of the hydroxyl group, and Lewis acidity of the organoboron
reagents are essential for the efficient cross-coupling reaction.
The effectiveness is shown by suppression of conjugate diene
formation through reaction of allylic alcohols, via b-hydrogen
elimination of the p-allylpalladium intermediates. No longer are
either preparation of allyl halides and esters or addition of
stoichiometric amounts of a base required. Furthermore, allylic
alcohols containing another unsaturated carbon–carbon bond
undergo arylative cyclization reactions leading to the formation of
cyclopentanes. Further studies on Pd-catalyzed organic transfor-
mations using organoboron reagents under base-free conditions
are underway.32
dioorganopalladium complex 41.2,5,30 Reductive elimination of the
coupling product 42 from 41 reproduces the Pd(0) complex.
In this catalytic cycle, the oxidative addition should be the
rate-limiting step because two stereoisomers 4 and 6 and two
regioisomers 8 and 9 react with 3a at quite different rates in
spite of both reactions proceeding via the same p-allylpalladium
intermediates (Table 1, entry 15 vs. Table 6, entry 1 and Table 6,
entries 3 vs. 4).31 Due to steric and electronic reasons, it is difficult
for highly substituted and cyclic allylic alcohols to coordinate
and add oxidatively to the Pd(0) complex. The cationic p-
allylpalladium intermediate 40 generated should be electrophilic
enough to suffer competitive attack on the allylic carbon from
the side opposite the Pd metal, by an excess of phosphine as
well as an external Pd(0) catalyst, leading to the formation of
phosphonium salts (or phosphoranes) and the epimerization of 40,
respectively. Whereas the reduction in the product yield caused by
a high loading of catalyst would support attack by the phosphine
(Table 1, entries 9–16), the conversion of the enantiomerically
Experimental section
General procedure for the cross-coupling reaction between 4
and 3a (Table 1): to a test tube containing cinnamyl alcohol
(4) (1 equiv., see Table 1S in the ESI†), phenylboronic acid
(3a) (1.2 equiv.), and Pd(PPh3)4 (0.2–10 mol%) or Pd2dba3
This journal is
The Royal Society of Chemistry 2008
Org. Biomol. Chem., 2008, 6, 3005–3013 | 3009
©

View Article Online
(2.5 mol%)–PPh3 (5 or 10 mol%) was added anhydrous sol-
vent (CH2Cl2, toluene, 1,4-dioxane, DMF, THF, or tAmOH,
0.3 M) under argon. The resulting mixture was sealed with
a screw cap and agitated at 80 ◦C for the time described in
Table 1. The mixture was cooled down to room temperature, and
GPC repeated four times to afford 5b–z in the yield described in
Table 5.
General procedure for the cross-coupling reaction between 6–13
and 3a (Table 6): to a test tube containing 6–1336 (0.37 mmol, see
Table 6S in the ESI†), 3a (0.45 mmol), and Pd(PPh3)4 (1.8 lmol)
was added anhydrous THF (1 mL) under argon. The resulting
mixture was sealed with a screw cap and agitated at 80 ◦C for
the time described in Table 6. The mixture was cooled down to
room temperature, and then PS-DEAMTM (1.63 mmol g−1, 0.55 g,
0.90 mmol) and THF (5 mL) were added to remove any excess
of 3a. The mixture was agitated at room temperature for 2 h.
The mixture was filtered and thoroughly washed with CHCl3. The
filtrate was concentrated in vacuo and the residue was purified by
GPC repeated several times to afford 5a and 14–17 in the yield
described in Table 6. The optical rotation of 15 prepared from 10
was 0◦.
General procedure for the cross-coupling reaction between 1
or 20–25 and 3s (Table 7): to a test tube containing 1 or 20–
25 (0.45 mmol, see Table 7S in the ESI†), 3s (0.52 mmol), and
Pd(PPh3)4 (1.8 lmol) was added anhydrous THF (1 mL for entries
1–5) or 1,4-dioxane (1 mL, for entries 6, 7) under argon. The
resulting mixture was sealed with a screw cap and agitated at 80
(for entries 1–5) or 110 ◦C (entries 6, 7) for the time described in
Table 7. The mixture was cooled down to room temperature, and
then PS-DEAMTM (1.63 mmol g−1, 0.55 g, 0.90 mmol) and THF
(5 mL) were added to remove any excess of 3s. The mixture was
agitated at room temperature for 2 h. The mixture was filtered and
thoroughly washed with CHCl3. The filtrate was concentrated in
vacuo and the residue was purified by GPC repeated several times
to afford 2s or 26–31 in the yield described in Table 7.
then N,N-diethanolaminomethyl polystyrene33 (PS-DEAMTM
,
1.63 mmol g−1, 2.4 equiv., X g) and THF (10 x X mL) were added
to remove any excess of 3a. The mixture was agitated at room
temperature for 2 h. The mixture was filtered and thoroughly
washed with CHCl3. The filtrate was concentrated in vacuo and
the residue was purified by gel permeation chromatography (GPC)
repeated four times to afford 5a in the yield described in Table 1.
General procedure for the cross-coupling reaction between 4
and the phenylboron reagents (Table 2): to a test tube containing
4 (0.37 mmol, see Table 2S in the ESI†), phenylboron reagent34
(0.45 mmol), and Pd(PPh3)4 (1.8 lmol) was added anhydrous THF
(1 mL) under argon. The resulting mixture was sealed with a screw
◦
cap and agitated at 80 C for 6 h. The mixture was cooled down
to room temperature, and then partitioned between EtOAc and
saturated aqueous Na2CO3. The organic layers were washed with
water, brine, dried over MgSO4, and concentrated in vacuo. The
residue was purified by GPC repeated four times to afford 5a in
the yield described in Table 2.
General procedure for the cross-coupling reaction between the
cinnamyl derivatives and 3a (Table 3): to a test tube containing
cinnamyl derivative35 (0.37 mmol, see Table 3S in the ESI†), 3a
(0.45 mmol), and Pd(PPh3)4 (1.8 lmol) was added anhydrous THF
(1 mL) under argon. Th◦e resulting mixture was sealed with a screw
cap and agitated at 80 C for the time described in Table 3. The
mixture was cooled down to room temperature, and then PS-
DEAMTM (1.63 mmol g−1, 0.55 g, 0.90 mmol) and THF (5 mL)
were added to remove any excess of 3a. The mixture was agitated at
room temperature for 2 h. The mixture was filtered and thoroughly
washed with CHCl3. The filtrate was concentrated in vacuo and
the residue was purified by GPC repeated several times to afford
5a in the yield described in Table 3.
Spectral data of the cross-coupling products are described in
the ESI†
(4Z)-3-Ethenyl-4-[1-(4-methylphenyl)ethylidene]-1,1-cyclopen-
tanedicarboxylic acid dimethyl ester (33f)
General procedure for the cross-coupling reaction between 4
and 3a (Table 4): to a test tube containing 4 (0.30 mmol, see
Table 4S in the ESI†), 3a (0.36 mmol), Pd2dba3 (1.5 lmol), and
ligand (3 lmol) was added anhydrous THF (1 mL) under argon.
The resulting mixture was sealed with a screw cap and agitated at
80 ◦C for 2 h. The mixture was cooled down to room temperature,
and then PS-DEAMTM (1.63 mmol g−1, 0.44 g, 0.72 mmol) and
THF (4 mL) were added to remove any excess of 3a. The mixture
was agitated at room temperature for 2 h. The mixture was filtered
and thoroughly washed with CHCl3. The filtrate was concentrated
in vacuo and the residue was purified by GPC repeated four times
to afford 5a in the yield described in Table 4.
General procedure for the cross-coupling reaction between 4
and the boronic acids 3b–z: to a test tube containing 4 (0.37 mmol,
see Table 5S in ESI†), 3b-z (0.45 mmol), and Pd(PPh3)4 (1.8 lmol)
was added anhydrous THF (1 mL) under argon. The resulting
mixture was sealed with a screw cap and agitated at 80 ◦C for
the time described in Table 5. The mixture was cooled down to
room temperature, and then PS-DEAMTM (1.63 mmol g−1, 0.55 g,
0.90 mmol) and THF (5 mL) were added to remove any excess
of 3b-z. The mixture was agitated at room temperature for 2 h.
The mixture was filtered and thoroughly washed with CHCl3. The
filtrate was concentrated in vacuo and the residue was purified by
To
a
test tube containing 2-butynyl-[(2E)-4-hydroxy-2-
butenyl]propanedioic acid dimethyl ester 3237 (24.2 mg,
0.0952 mmol), 3f (31.5 mg, 0.232 mmol), and Pd(PPh3)4 (1.5 mg,
1.3 lmol) was added anhydrous THF (1 mL) under argon.
The resulting mixture was sealed with a screw cap and agitated
at 80 ◦C for 3 h. The mixture was cooled down to room
temperature, and then partitioned between EtOAc and water. The
aqueous layer was extracted with EtOAc twice. The combined
organic layers were washed with brine, dried over MgSO4, and
concentrated in vacuo. The residue was purified by silica gel
chromatography eluting with 5% EtOAc–hexane to yield 33f
(24.8 mg, 0.0755 mmol, 79%).
Spectral data of 33f: 1H NMR (400 MHz, CDCl3): d 7.28–7.01
(m, 4H), 5.41 (ddd, 1H, J = 17.0, 10.4, 6.6 Hz), 4.69–4.59 (m,
2H), 3.77 (s, 3H), 3.72 (s, 3H), 3.35–3.49 (m, 1H), 3.15 (d, 1H,
J = 16.8 Hz), 3.03 (d, 1H, J = 16.8 Hz), 2.51 (dd, 1H, J = 13.2,
8.0 Hz), 2.31 (s, 3H), 2.16 (dd, 1H, J = 13.1, 5.8 Hz), 1.98 (s, 3H);
13C NMR (100 MHz, CDCl3): d 172.7, 172.4, 140.7, 140.0, 135.9 ×
2, 131.3, 128.6, 127.7, 114.0, 58.7, 52.8, 52.6, 45.2, 40.3, 38.8, 22.0,
21.0; IR (neat): mmax (cm−1) 2952, 1735, 1488, 1252, 830; EI-MS
m/z (relative intensity) 328 (M)+ (70), 268 (100), 209 (81), 119
(31), 107 (70); HRMS calcd for C20H24O4 (M+) 328.1673, found
328.1684.
3010 | Org. Biomol. Chem., 2008, 6, 3005–3013
This journal is
The Royal Society of Chemistry 2008
©

View Article Online
(4Z)-3-Ethenyl-4-[1-(thiophen-2-yl)ethylidene]-1,1-cyclopen-
tanedicarboxylic acid dimethyl ester (33u)
(10 mL) at 0 ◦C. The mixture was stirred at 0 ◦C for 30 min, and
then added to a mixture of cis-1-acetoxy-4-chloro-2-cyclohexene38b
(350 mg, 2.00 mmol), Pd(OAc)2 (11.1 mg, 0.049 mmol), and
PPh3 (54.1 mg, 0.206 mmol). The whole solution was stirred at
rt for 3 h, and then partitioned between EtOAc and saturated
aqueous NH4Cl. The aqueous layer was extracted with EtOAc
twice. The combined organic layers were washed with brine,
dried over MgSO4, and concentrated in vacuo. The residue was
purified by silica gel chromatography eluting with 25% EtOAc–
hexane to yield cis-[4-(acetyloxy)-2-cyclohexen-1-yl](2-methyl-2-
propenyl)-propanedioic acid dimethyl ester (637 mg, 1.96 mmol,
98%).
33u (32.6 mg, 0.102 mmol) was obtained quantitatively from 32
(25.9 mg, 0.102 mmol), 3u (28.1 mg, 0.220 mmol), and Pd(PPh3)4
(2.4 mg, 2.1 lmol) by the same procedure as that described above.
Spectral data of 33u: 1H NMR (400 MHz, CDCl3): d 7.26–6.91
(m, 3H), 5.63 (ddd, 1H, J = 17.3, 10.5, 5.5 Hz), 4.91–4.81 (m,
2H), 3.74 (s, 3H), 3.71 (s, 3H), 3.72–3.64 (m, 1H), 3.29 (d, 1H, J =
17.5 Hz), 3.03 (d, 1H, J = 17.5 Hz), 2.55 (dd, 1H, J = 13.2, 8.2 Hz),
2.35 (dd, 1H, J = 13.2, 4.1 Hz), 2.12 (s, 3H); 13C NMR (100 MHz,
CDCl3): d 172.2, 171.9, 144.8, 138.8, 137.7, 126.4, 124.8, 123.8,
123.6, 114.8, 58.4, 53.0, 52.7, 45.9, 40.5, 39.6, 22.1; IR (neat): mmax
(cm−1) 2952, 1731, 1434, 1254, 1173, 1065; EI-MS m/z (relative
intensity) 320 (M)+ (92), 260 (100), 245 (31), 289 (23), 201 (92);
HRMS calcd for C17H20O4S (M+) 320.1081, found 320.1083.
1
Spectral data of the acetate: H NMR (400 MHz, CDCl3): d
6.09 (d, 1H, J = 10.3 Hz), 5.82–5.77 (m, 1H), 5.12–5.11 (m, 1H),
4.85 (s, 1H), 4.73 (s, 1H), 3.72 (s, 3H), 3.69 (s, 3H), 2.90–2.86 (m,
1H), 2.79 (d, 1H, J = 14.4 Hz), 2.73 (d, 1H, J = 14.4 Hz), 2.01 (s,
3H), 1.91–1.87 (m, 1H), 1.76–1.66 (m, 2H), 1.70 (s, 3H), 1.55–1.47
(m, 1H); 13C NMR (100 MHz, CDCl3): d 170.8, 170.34, 170.31,
141.0, 134.5, 125.1, 115.3, 65.8, 61.0, 52.2, 51.9, 40.7, 40.1, 28.0,
23.6, 21.4, 19.4; IR (neat): mmax (cm−1) 2951, 1725, 1235, 1226, 1198,
1068, 1011, 991, 902; EI-MS m/z (relative intensity) 324 (M)+ (0.3),
265 (32), 205 (46), 194 (34), 176 (55), 145 (100), 79 (34), 43 (34);
HRMS calcd for C17H24O6 (M+) 324.1573, found 324.1566.
trans-[4-(Hydroxy)-2-cyclohexen-1-yl](2-methyl-2-propenyl)-
propanedioic acid dimethyl ester (36a)
To NaH (60%, 214 mg, 5.35 mmol), washed twice with
anhydrous hexane, was added a solution of dimethyl (2-
methylallyl)malonate38a (968 mg, 5.20 mmol) in anhydrous DMF
(6 mL) at 0 ◦C. The mixture was stirred at 0 ◦C for 30 min,
and then a solution of cis-1-acetoxy-4-chloro-2-cyclohexene38b
(698 mg, 4.00 mmol) in anhydrous DMF (4 mL) was added.
The whole solution was stirred at 80 ◦C for 2 h, cooled down
to room temperature, and then partitioned between EtOAc and
saturated aqueous NH4Cl. The aqueous layer was extracted
with EtOAc twice. The combined organic layers were washed
with water and brine, dried over MgSO4, and concentrated
in vacuo. The crude trans-[4-(acetyloxy)-2-cyclohexen-1-yl](2-
methyl-2-propenyl)-propanedioic acid dimethyl ester38c was dis-
solved in MeOH (20 mL) and K2CO3 (553 mg, 4.00 mmol) was
added. The mixture was stirred at room temperature for 2 h, and
then concentrated in vacuo. The residue was partitioned between
CHCl3 and saturated aqueous NH4Cl. The aqueous layer was
extracted with CHCl3 twice. The combined organic layers were
washed with brine, dried over MgSO4, and concentrated in vacuo.
The residue was purified by silica gel chromatography eluting with
40% EtOAc–hexane to yield 36a (1.04 g, 3.68 mmol, 92%).
Spectral data of 36a: 1H NMR (400 MHz, CDCl3): d 5.84 (dd,
1H, J = 10.5, 1.7 Hz), 5.70 (dd, 1H, J = 10.5, 2.4 Hz), 4.84 (s, 1H),
4.71 (s, 1H), 4.18 (m, 1H), 3.71 (s, 3H), 3.68 (s, 3H), 3.00–2.96 (m,
1H), 2.75 (d, 1H, J = 14.5 Hz), 2.69 (d, 1H, J = 14.5 Hz), 2.16–
2.12 (m, 1H), 1.93–1.88 (m, 1H), 1.69 (s, 3H), 1.48–1.36 (m, 3H);
13C NMR (100 MHz, CDCl3): d 170.8, 170.3, 141.1, 132.2, 129.9,
115.1, 67.2, 61.3, 52.1, 52.0, 40.7, 40.2, 32.9, 23.6, 23.1; IR (neat):
mmax (cm−1) 3530–3330 (br), 2950, 1724, 1433, 1255, 1219, 1201,
1176, 1092, 1055, 896, 753, 737; EI-MS m/z (relative intensity)
282 (M)+ (1), 265 (10), 250 (13), 223 (53), 194 (100), 155 (64), 145
(100), 122 (89), 96 (72), 79 (38); HRMS calcd for C15H22O5 (M+)
282.1467, found 282.1474.
cis-[4-(Hydroxy)-2-cyclohexen-1-yl](2-methyl-2-propenyl)-
propanedioic acid dimethyl ester (36b)
The above acetate (309 mg, 0.953 mmol) was dissolved in MeOH
(5 mL) and K2CO3 (146 mg, 1.06 mmol) was added. The mixture
was stirred at room temperature for 2 h, and then concentrated
in vacuo. The residue was partitioned between CHCl3 and sat-
urated aqueous NH4Cl. The aqueous layer was extracted with
CHCl3 twice. The combined organic layers were washed with brine,
dried over MgSO4, and concentrated in vacuo. The residue was
purified by silica gel chromatography eluting with 50% EtOAc–
hexane to yield 36b (272 mg, 0.953 mmol, quant.).
1
Spectral data of 36b: H NMR (400 MHz, CDCl3): d 5.98 (d,
1H, J = 10.3 Hz), 5.88–5.83 (m, 1H), 4.84 (s, 1H), 4.72 (s, 1H),
4.09 (m, 1H), 3.72 (s, 3H), 3.70 (s, 3H), 2.87–2.82 (m, 1H), 2.80 (d,
1H, J = 14.4 Hz), 2.74 (d, 1H, J = 14.4 Hz), 1.88–1.83 (m, 1H),
1.74–1.63 (m, 2H), 1.70 (s, 3H), 1.57–1.50 (m, 1H), 1.42 (br-s, 1H);
13C NMR (100 MHz, CDCl3): d 170.9, 170.4, 141.1, 132.3, 129.0,
115.2, 63.0, 61.0, 52.2, 52.0, 40.9, 40.5, 30.8, 23.6, 18.8; IR (neat):
mmax (cm−1) 3534–3335 (br), 2950, 1724, 1433, 1223, 1197, 1178,
1072, 1000, 950, 898, 737; EI-MS m/z (relative intensity) 282 (M)+
(0.5), 265 (2), 250 (5), 223 (30), 194 (57), 145 (100), 122 (44), 79
(23); HRMS calcd for C15H22O5 (M+) 282.1467, found 282.1460.
(3a,3ab,7ab)-2,3,3a,6,7,7a-hexahydro-3-methyl-3-(phenylmethyl)-
1H-Indene-1,1-dicarboxylic acid dimethyl ester (37)
From 36a: to a test tube containing 36a (31.1 mg, 0.110 mmol),
3a (15.6 mg, 0.128 mmol), and Pd(PPh3)4 (1.3 mg, 1.1 lmol)
was added anhydrous THF (0.5 mL) under argon. The resulting
mixture was sealed with a screw cap and agitated at 80 ◦C for
6 h. The mixture was cooled down to room temperature, and
then PS-DEAMTM (1.63 mmol g−1, 0.16 g, 0.26 mmol) and THF
(2 mL) were added to remove any excess of 3a. The mixture was
agitated at room temperature for 2 h. The mixture was filtered
cis-[4-(Acetyloxy)-2-cyclohexen-1-yl](2-methyl-2-propenyl)-
propanedioic acid dimethyl ester
To NaH (60%, 106 mg, 2.65 mmol), washed twice with
anhydrous hexane, was added a solution of dimethyl (2-
methylallyl)malonate38a (447 mg, 2.40 mmol) in anhydrous THF
This journal is
The Royal Society of Chemistry 2008
Org. Biomol. Chem., 2008, 6, 3005–3013 | 3011
©

View Article Online
and thoroughly washed with CHCl3. The filtrate was concentrated
in vacuo and the residue was purified by preparative TLC eluting
with 20% EtOAc–hexane, repeating two times to yield 37 (34.6 mg,
0.101 mmol, 92%).
7 Recent reports on the Pd(0)-catalyzed direct allylation of 1,3-dicarbonyl
compounds with allyl alcohols: (a) K. Manabe and S. Kobayashi, Org.
Lett., 2003, 5, 3241; (b) H. Kinoshita, H. Shiokubo and K. Oshima,
Org. Lett., 2004, 6, 4085; (c) H. Kinoshita, H. Shiokubo and K. Oshima,
Angew. Chem., Int. Ed., 2005, 44, 2097; (d) Y. Tamaru, Y. Horino, M.
Araki, S. Tanaka and M. Kimura, Tetrahedron Lett., 2000, 41, 5705;
(e) M. Kimura, R. Mukai, N. Tanigawa, S. Tanaka and Y. Tamaru,
Tetrahedron, 2003, 59, 7767; (f) F. Ozawa, H. Okamoto, S. Kawagishi,
S. Yamamoto, T. Minami and M. Yoshifuji, J. Am. Chem. Soc., 2002,
124, 10968; (g) F. Ozawa, T. Ishiyama, S. Yamamoto, S. Kawagishi, H.
Murakami and M. Yoshifuji, Organometallics, 2004, 23, 1698; (h) Y.
Kayaki, T. Koda and T. Ikariya, J. Org. Chem., 2004, 69, 4989; (i) R.-S.
Hou, H.-M. Wang, H.-Y. Huang and L.-C. Chen, Heterocycles, 2005,
65, 1917; (j) N. T. Patil and Y. Yamamoto, Tetrahedron Lett., 2004, 45,
3101.
8 G. W. Kabalka, G. Dong and B. Venkataiah, Org. Lett., 2003, 5, 893.
9 (a) B. M. Trost and M. D. Spagnol, J. Chem. Soc., Perkin Trans. 1,
1995, 2083; (b) K.-G. Chung, Y. Miyake and S. Uemura, J. Chem. Soc.,
Perkin Trans. 1, 2000, 15.
10 H. Tsukamoto, M. Sato and Y. Kondo, Chem. Commun., 2004, 1200.
11 H. Tsukamoto, T. Suzuki, M. Sato and Y. Kondo, Tetrahedron Lett.,
2007, 48, 8438.
From 36b: to a test tube containing 36b (31.6 mg, 0.112 mmol),
3a (16.3 mg, 0.134 mmol), and Pd(PPh3)4 (1.5 mg, 1.3 lmol)
was added anhydrous THF (0.5 mL) under argon. The resulting
mixture was sealed with a screw cap and agitated at 80 ◦C for
15 h. The mixture was cooled down to room temperature, and
then PS-DEAMTM (1.63 mmol g−1, 0.16 g, 0.26 mmol) and THF
(2 mL) were added to remove any excess of 3a. The mixture was
agitated at room temperature for 2 h. The mixture was filtered
and thoroughly washed with CHCl3. The filtrate was concentrated
in vacuo and the residue was purified by preparative TLC eluting
with 20% EtOAc–hexane, repeating two times to yield 37 (34.3 mg,
0.100 mmol, 89%).
Spectral data of 37: 1H NMR (400 MHz, CDCl3): d 7.28–7.17
(m, 5H), 5.89–5.84 (m, 1H), 5.76–5.72 (m, 1H), 3.73 (s, 3H), 3.67
(s, 3H), 3.02–2.95 (m, 1H), 2.90 (d, 1H, J= 14.4 Hz), 2.65–2.61
(m, 1H), 2.63 (d, 1H, J= 13.2 Hz), 2.44 (d, 1H, J= 13.2 Hz),
2.17–2.04 (m, 2H), 1.68 (d, 1H, J= 14.4 Hz), 1.44–1.37 (m, 2H),
0.93 (s, 3H); 13C NMR (100 MHz, CDCl3): d 172.8, 170.5, 139.7,
130.3, 127.6, 127.2, 125.7, 125.4, 63.1, 52.6, 52.4, 49.5, 47.5, 44.2,
43.9, 43.5, 29.2, 24.6, 22.2; IR (neat): mmax (cm−1) 2950, 1730, 1432,
1241, 1199, 1143, 1068, 769, 705; EI-MS m/z (relative intensity)
342 (M)+ (13), 310 (8), 279 (11), 251 (34), 219 (30), 191 (100), 145
(59), 131 (82), 91 (45); HRMS calcd for C21H26O4 (M+) 342.1831,
found 342.1843.
12 (a) Y. Kayaki, T. Koda and T. Ikariya, Eur. J. Org. Chem., 2004, 4989;
(b) K. Manabe, K. Nakada, N. Aoyama and S. Kobayashi, Adv. Synth.
Catal., 2005, 347, 1499.
13 (a) M. Yoshida, T. Gotou and M. Ihara, Chem. Commun., 2004, 1125;
(b) M. Yoshida, T. Gotou and M. Ihara, Tetrahedron Lett., 2004, 45,
5573.
14 This phenomenon was also observed in reference 12b, but the authors
did not point it out.
15 The ratio of phosphine to Pd of 1 : 1 is also recommended by references
12.
16 (a) J. Powell and B. L. Shaw, J. Chem. Soc. A, 1968, 774; (b) Y.
Tsukahara, H. Kinoshita, K. Inomata and H. Kotake, Bull. Chem. Soc.
Jpn., 1984, 57, 3013; (c) T. Yamamoto, O. Saito and A. Yamamoto,
J. Am. Chem. Soc., 1981, 103, 5600; (d) T. Yamamoto, M. Akimoto
and A. Yamamoto, Chem. Lett., 1983, 1725; (e) T. Yamamoto, M.
Akimoto, O. Saito and A. Yamamoto, Organometallics, 1986, 5, 1559;
(f) K. L. Grandberg and J.-E. Ba¨ckvall, J. Am. Chem. Soc., 1992, 114,
6858.
17 Allylphosphorane was proposed to be an intermediate for the Pd(0)-
catalyzed Wittig-type allylidenation of aldehydes using allylic alcohol
derivatives and phosphines. (a) M. Moreno-Man˜as and A. Trius,
Tetrahedron Lett., 1981, 22, 3109; (b) M. Moreno-Man˜as and A. Trius,
Bull. Chem. Soc. Jpn., 1983, 56, 2154; (c) M. Moreno-Man˜as, R. M.
Ortuno, M. Prat and M. A. Galan, Synth. Commun., 1986, 16, 1003;
(d) Y. Inoue, M. Toyofuku and H. Hashimoto, Bull. Chem. Soc. Jpn.,
1986, 59, 1279; (e) N. Okuda, O. Uchikawa and Y. Nakamura, Chem.
Lett., 1988, 1449.
Acknowledgements
This work was partly supported by a Grant-in-Aid from the Japan
Society for Promotion of Sciences (No.18790003).
18 (a) H. Tsukamoto, T. Suzuki and Y. Kondo, Synlett, 2007, 3131; (b) H.
Tsukamoto, R. Suzuki and Y. Kondo, J. Comb. Chem., 2006, 8, 289;
(c) M. Yokogi and R. Kuwano, Tetrahedron Lett., 2007, 48, 6109.
19 The reaction solvent and catalyst loading are different from those in
Ikariya’s report12a
.
Notes and references
20 2-Thiopheneboronic acid did not work well as a nucleophile in the Pd-
catalyzed cyclization of allenyl enones: see reference 32g. The 2-thienyl
group is used as dummy ligand in the Hiyama cross-coupling reaction:
see K. Hosoi, K. Nozaki and T. Hiyama, Chem. Lett., 2002, 138.
21 It was reported that the Pd0-catalyzed cross-coupling reaction of the
chiral propargylic alcohol with arylboronic acid gave the corresponding
1 (a) J. Tsuji, Palladium Reagents and Catalysts, John Wiley & Sons,
Chichester, 1995; (b) Handbook of Organopalladium Chemistry for
Organic Synthesis, ed. E. Negishi, John Wiley & Sons, New York, 2002.
2 N. Miyaura, Top. Curr. Chem., 2002, 219, 12.
3 (a) M. Moreno-Man˜as, F. Pajuelo and R. Pleixats, J. Org. Chem.,
1995, 60, 2396; (b) J. Corte´s, M. Moreno-Man˜as and R. Pleixats,
Eur. J. Org. Chem., 2000, 239; (c) M. Moreno-Man˜as, R. Pleixats and
S. Villarroya, Organometallics, 2001, 20, 4524; (d) E. Paetzold and G.
Oehme, J. Mol. Catal. A: Chem., 2000, 152, 69; (e) L. Botella and C.
Na´jera, J. Organomet. Chem., 2002, 663, 46; (f) D. A. Alonso, C. Na´jera
and M. Pacheco, J. Org. Chem., 2002, 67, 5588.
4 (a) J.-Y. Legros and J.-C. Fiaud, Tetrahedron Lett., 1990, 31, 7453; (b) E.
Blart, J.-P. Geneˆt, 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.
5 N. Miyaura, K. Yamada, H. Suginome and A. Suzuki, J. Am. Chem.
Soc., 1985, 107, 972.
allene with a dramatic loss of chirality13b
.
22 Uozumi et al.4c reported that an amphiphilic resin-supported palladium
catalyst effectively promoted the coupling reaction of 18 with 3a in the
presence of K2CO3 in water. Tsuji et al. reported that no elimination was
observed with allyl alcohol under a 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.
23 (a) G. Zhu and Z. Zhang, Org. Lett., 2003, 5, 3645; (b) G. Zhu, X. Tong,
J. Cheng, Y. Sun, D. Li and Z. Zhang, J. Org. Chem., 2005, 70, 1712;
(c) Murakami et al. reported the Rh(I)-catalyzed arylative cyclization
of 1,6-enynes such as 32: T. Miura, M. Shimada and M. Murakami,
J. Am. Chem. Soc., 2005, 127, 1094; (d) T. Miura, M. Shimada and M.
Murakami, Chem.–Asian J., 2006, 1, 868.
24 The different behavior of 3u between the cross-coupling reaction and cy-
clization reflects the different palladium intermediates, i.e., p-allyl- and
6 (a) B. M. Trost, Angew. Chem., Int. Ed. Engl., 1995, 34, 259; (b) B. M.
Trost, Science, 1991, 254, 1471.
3012 | Org. Biomol. Chem., 2008, 6, 3005–3013
This journal is
The Royal Society of Chemistry 2008
©

View Article Online
r-alkenylpalladium, respectively. Reductive elimination from p-
allylpalladium would be slower than that from r-alkenylpalladium32g
32 (a) H. Tsukamoto, T. Ueno and Y. Kondo, J. Am. Chem. Soc., 2006,
128, 1406; (b) H. Tsukamoto, T. Ueno and Y. Kondo, Org. Lett., 2007,
9, 3033; (c) H. Tsukamoto and Y. Kondo, Org. Lett., 2007, 9, 4227;
(d) H. Tsukamoto, T. Matsumoto and Y. Kondo, J. Am. Chem. Soc.,
2008, 130, 388; (e) H. Tsukamoto, T. Matsumoto and Y. Kondo, Org.
Lett., 2008, 10, 1047; (f) H. Tsukamoto and Y. Kondo, Angew. Chem.,
Int. Ed., 2008, 47, 4851; (g) H. Tsukamoto and Y. Kondo, Org. Lett.,
2008, 10, 2633; (h) H. Tsukamoto, T. Suzuki, T. Uchiyama and Y.
Kondo, Tetrahedron Lett., 2008, 49, 4174.
.
25 R. Grigg, S. Sukirthalingam and V. Sridharan, Tetrahedron Lett., 1991,
32, 2545.
26 (a) F. K. Sheffy, J. P. Godshalx and J. K. Stille, J. Am. Chem. Soc.,
1984, 106, 4833; (b) C. G. Frost, J. Howarth and J. M. J. Williams,
Tetrahedron: Asymmetry, 1992, 3, 1089.
27 (a) X. Lu, X. Jiang and X. Tao, J. Organomet. Chem., 1988, 344, 109;
(b) I. Stary, I. G. Stara and P. Kocovsky, Tetrahedron Lett., 1993, 34, 179;
(c) I. Stary, I. G. Stara and P. Kocovsky, Tetrahedron, 1994, 50, 529;(d) Y.
Tamaru, Y. Horino, M. Araki, S. Tanaka and M. Kimura, Tetrahedron
Lett., 2000, 41, 5705; (e) M. Kimura, R. Mukai, N. Tanigawa, S. Tanaka
and Y. Tamaru, Tetrahedron, 2003, 59, 7767; (f) Y. Horino, M. Naito,
M. Kimura, S. Tanaka and Y. Tamaru, Tetrahedron Lett., 2001, 42,
3113; (g) M. Kimura, M. Futamata, K. Shibata and Y. Tamaru, Chem.
Commun., 2003, 234; (h) M. Kimura, Y. Horino, R. Mukai, S. Tanaka
and Y. Tamaru, J. Am. Chem. Soc., 2001, 123, 10401; (i) M. Kimura, M.
Shimizu and Y. Tamaru, Tetrahedron, 2005, 61, 3709; (j) M. Kimura,
M. Futamata, R. Mukai and Y. Tamaru, J. Am. Chem. Soc., 2005,
127, 4592; (k) M. Kimura, M. Fukasaka and Y. Tamaru, Heterocycles,
2006, 67, 535; (l) M. Kimura, M. Fukasaka and Y. Tamaru, Synthesis,
2006, 3611; (m) Y. Tamaru, Eur. J. Org. Chem., 2005, 2647; (n) S.
Chandrasekhar, V. Jagadeshwar, B. Saritha and C. Narsihmulu, J. Org.
Chem., 2005, 70, 6506; (o) B. M. Trost and J. Quancard, J. Am. Chem.
Soc., 2006, 128, 6314.
28 At this time, it is unclear why the pinacol ester of 3a could not be
coupled with 4. It is reported that the Lewis acid character of glycol
esters of 3a would be almost the same as boronic acid 3a. G. Springsteen
and B. Wang, Tetrahedron, 2002, 58, 5291.
29 Formation of the allyl borate is not necessary for the cross-coupling
reaction because the allylic ether and carbonate as well as the alcohol
serve as allylating reagents.
30 T. Moriya, N. Miyaura and A. Suzuki, Synlett, 1994, 149.
31 Furthermore, electronic effects of the arylboronic acids on the reaction,
which would affect the transmetalation and reductive elimination steps,
were not observed (Table 5, entries 1–17).
33 PS-DEAMTM was purchased from Biotage AB.
34 (a) F.-X. Chen, A. Kina and T. Hayashi, Org. Lett., 2006, 8, 341;
(b) M. J. S. Dewar and D. S. Urch, J. Chem. Soc., 1958, 3079; (c) S.
Morandi, E. Caselli, A. Forni, M. Bucciarelli, G. Torre and F. Prati,
Tetrahedron: Asymmetry, 2005, 16, 2918.
35 (a) G. H. Schmid, A. Modro and K. Yates, J. Org. Chem., 1977, 42,
871; (b) J. Tsuji, I. Shimizu, I. Minami, Y. Ohashi, T. Sugiura and K.
Takahashi, J. Org. Chem., 1985, 50, 1523; (c) W. N. White and B. E.
Norcross, J. Am. Chem. Soc., 1961, 83, 1968.
36 (a) A. B. Charette, C. Molinaro and C. Brochu, J. Am. Chem. Soc.,
2001, 123, 12168; (b) N. Bischofberger, H. Waldmann, T. Saito, E. S.
Simon, W. Lees, M. D. Bednarski and G. M. Whitesides, J. Org. Chem.,
1988, 53, 3457–3465; (c) R. Mart´ın, G. Islas, A. Moyano, M. A. Perica´s
and A. Riera, Tetrahedron, 2001, 57, 6367; (d) C. S. Marvel and R. G.
Woolford, J. Org. Chem., 1968, 23, 1658; (e) K. Burgess and L. D.
Jennings, J. Am. Chem. Soc., 1991, 113, 6129; (f) U. Kazmaier and F. L.
Zumpe, Eur. J. Org. Chem., 2001, 4067; (g) A. Ghanem and V. Schurig,
Tetrahedron: Asymmetry, 2003, 14, 57; (h) P. Dai, T. K. Trullinger, X.
Liu and P. H. Dussault, J. Org. Chem., 2006, 71, 2283–2292; (i) I. D. G.
Watson, S. A. Styler and A. K. Yudin, J. Am. Chem. Soc., 2004, 126,
5086; (j) T. E. Goodwin, D. G. Ratcliff, C. M. Crowder and N. K.
Seitzinger, J. Org. Chem., 1982, 47, 815.
37 L. Zhao, X. Liu and W. Xu, J. Org. Chem., 2005, 70, 4059.
38 (a) A. M. Go´mez, M. D. Company, S. Valverde and J. C. Lo´pez, Org.
Lett., 2002, 4, 383; (b) J.-E. Ba¨ckvall and J. O. Va˚gberg, Org. Synth.,
1990, 69, 38; (c) B. Burns, R. Grigg, V. Santhakumar, V. Sridharan, P.
Stevenson and T. Worakun, Tetrahedron, 1992, 48, 7297.
This journal is
The Royal Society of Chemistry 2008
Org. Biomol. Chem., 2008, 6, 3005–3013 | 3013
©