Remarkable solvent effect on Pd(0)-catalyzed deprotection of allyl ethers using barbituric acid derivatives: Application to selective and successive removal of allyl, methallyl, and prenyl ethers

Article abstract of DOI:10.1055/s-2007-992352

Pd(0)-catalyzed deprotection of allyl ethers using barbituric acid derivatives in protic polar solvent such as MeOH and aqueous 1,4-dioxane proceeds at room temperature without affecting a wide variety of functional groups. Control of the reaction temperature allows selective and successive cleavage of allyl, methallyl, and prenyl ethers. A study of ligand effects on the deprotection reveals that the improved reactivity in MeOH results from the accelerated oxidative addition to Pd(O). Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-2007-992352

LETTER
3131
Remarkable Solvent Effect on Pd(0)-Catalyzed Deprotection of Allyl Ethers
Using Barbituric Acid Derivatives: Application to Selective and Successive
Removal of Allyl, Methallyl, and Prenyl Ethers
Solvent
E
ffec
t
on
P
i
d(0)-C
r
atalyzed
o
D
eprotectio
k
n
of Allyl Et
a
hers zu Tsukamoto,* Takamichi Suzuki, Yoshinori Kondo
Graduate School of Pharmaceutical Sciences, Tohoku University, Aramaki-aza aoba 6-3, Aoba-ku, Sendai 980-8578, Japan
Fax +81(22)7953906; E-mail: hirokazu@mail.pharm.tohoku.ac.jp
Received 5 September 2007
solvent effect on the deallylation of 2a because acidity is
Abstract: Pd(0)-catalyzed deprotection of allyl ethers using barbi-
strongly affected by solvent polarity (Table 1). For exam-
turic acid derivatives in protic polar solvent such as MeOH and
ple, the pKa of acetic acid in MeCN, DMSO, MeOH, and
aqueous 1,4-dioxane proceeds at room temperature without affect-
ing a wide variety of functional groups. Control of the reaction tem-
water is reported to be 21.6, 12.5, 9.7, and 4.8, respective-
perature allows selective and successive cleavage of allyl, ly.4 Therefore, use of protic polar solvents could optimize
methallyl, and prenyl ethers. A study of ligand effects on the depro-
tection reveals that the improved reactivity in MeOH results from
the accelerated oxidative addition to Pd(0).
Brønsted acidity intrinsic to 1a. As expected, the use of 1a
in polar solvent facilitated the cleavage (entries 1–13).5
Methanol as the most protic polar organic solvent was su-
perior to the others and completed the deallylation of 2a
in the presence of Pd(PPh3)4 (5 mol%) within one hour at
Key words: barbituric acid, Pd(0)-catalyzed deprotection, allyl
ethers, protic polar solvent, methallyl ethers, prenyl ethers
room temperature to give the parent alcohol 3a in excel-
lent yield (entries 1–12 vs. 13).6 Furthermore, water as co-
solvent greatly enhanced the reactivity of the deallylation
(entries 2 vs. 11)
The allyl group is one of the most useful protecting groups
for alcohols due to its stability under both acidic and basic
conditions.1 Although its palladium-catalyzed removal
had been a problem owing to poor leaving ability of the
ether group, LiBHEt3,2a p-toluenesulfinic acid,2b,c poly-
methylhydrosiloxane–ZnCl2,2d K2CO3–MeOH,2e and bar-
bituric acid derivatives2f,g were found to scavenge the allyl
group from allylic alkyl ethers in the presence of
Pd(PPh3)4 as an available catalyst. Our own deallylation
method using 1,3-dimethylbarbituric acid [DMBA (1a)]
and polymer-supported barbituric acid [PSBA (1b)] as
soft carbonucleophiles has advantages of commercial
availability of reagents, compatibility with a wide variety
of functional groups, high yields, and simple operation
over other methods (Figure 1).2a–e,3 However, its sluggish-
ness requiring high reaction temperature and long reaction
time, appeared to make the process of no practical use.2f
Therefore, there is still a need to improve the reaction con-
ditions.
Table 1 Solvent Effect on Cleavage of Allyl Ether 2a Using 1a
1a (2 equiv)
Pd(PPh3)4 (5 mol%)
O
OH
BnO
BnO
r.t.
2a
3a
Entry
1
Solvent
Time (h) Yield (%)
MeCN
120
120
72
48
24
24
8
86
2
1,4-dioxane
MeNO2
MeOAc
CH2Cl2
87
3
94
4
90
5
89
6
THF
92
7
t-BuOH
DMF
93
O
8
6
92
R1
O
R2
O
1a: R1 = R2 = Me, R3 = H (DMBA)
1b: R1 = polystyrene, R2 = Pr, R3 = H (PSBA)
1c: R1 = R2 = R3 = Me (TMBA)
N
N
9
i-PrOH
6
99
10
11
12
13
EtOH
4
99
R3
1,4-dioxane–H2O (3:1)
DMSO
3
quant.
93
Figure 1 DMBA, PSBA, and TMBA (1,3,5-trimethylbarbituric
acid) as allyl scavengers
2
MeOH
1
quant.
The key feature of our deallylation method is employing
the Brønsted acid character of 1a to activate the ether ox-
ygen. To improve the sluggish reaction, we examined the
The lower reaction temperature and shorter reaction time
offer compatibility with a wide variety of functional
groups (Table 2). In spite of the weak acidic conditions,
acid-labile benzyl and silyl ethers in 2b–d and acetal func-
tionalities in 2e–f were stable under the present protocol
(entries 1–6). Other functionalities including aryl, substi-
tuted allyl and propargyl ethers in 2g–j, esters in 2k–u,
SYNLETT 2007, No. 20, pp 3131–3136
Advanced online publication: 08.11.2007
DOI: 10.1055/s-2007-992352; Art ID: U08107ST
© Georg Thieme Verlag Stuttgart · New York
x
x
.x
x
.2
0
0
7

3132
H. Tsukamoto et al.
LETTER
alkyl chloride in 2l, ketone in 2m, nitro in 2o, and nitrile lation of 3d because the scavenger itself and the allylated
in 2p also survived the reaction conditions (entries 7–21). by-products could be readily removed by filtration.
Although aryl iodide in 2u underwent competitive oxida-
Other allyl ethers of primary, secondary, and tertiary alco-
tive addition to the catalyst leading to no deallylation, aryl
hols were also cleaved smoothly (Table 3). When the sub-
chloride, bromide, and trifluoromethanesulfonate in 2r, 2s
strate was insoluble in MeOH or attached to cross-linked
polystyrene resin, CH2Cl2 had to be employed as co-sol-
and 2t, respectively, did not hinder the reaction (entries
18–21). It is worth noting that use of 1,3,5-trimethylbarbi-
vent to dissolve or swell it, respectively (entries 1 and 7).
turic acid [TMBA (1c)]7 instead of 1a in aqueous 1,4-di-
Thioether moiety in 4d did not poison the catalyst (entry
oxane could prevent the most labile aldehyde group in 2q
4). The deallylation of 4e and 4f proceeded without acyl
from undergoing Knoevenagel condensation with 1a and
migration (entries 5 and 6). Use of excess reagents en-
abled the deallylation of polymer-bound substrate 4g (en-
try 7). The four allyl ethers in 4h could be removed
altogether (entry 8).
acetalization with MeOH under the normal conditions
(entry 17). Furthermore, the deprotection of 2d employing
polymer-supported barbituric acid [PSBA (1b)]2g instead
of 1a required CH2Cl2–MeOH (1:1) solvent system to
swell 1b and longer reaction time, but facilitated the iso-
Table 3 Cleavage of Allyl Ethers 4a–ha
O
O
Table 2 Cleavage of Allyl Ethers 2b–u Containing Various Protect-
ing Groups
OR
O
1a (2 equiv)
Pd(PPh3)4 (5 mol%)
O
OH
O
RO
RO
O
MeOH, r.t.
2b–u
3b–u
OR
RO
Entry
1
Substrate
2b
2c
R
Product
3b
3c
Yield (%)
90
4a: R = allyl
5a: R = H
4b: R = allyl
5b: R = H
4c: R = allyl
5c: R = H
PMB
Tr
Ph
2
94
O
AcO
AcO
OR
O
OAc
O
O
3
2d
2d
2e
TBDMS
3d
3d
3e
89
O
PMBO
SEt AcO
OMP RO
OMP
4a
5
TBDMS
81
OR
OBn
OAc
4d: R = allyl
5d: R = H
4e: R = allyl
5e: R = H
4f: R = allyl
5f: R = H
THP
92
6
2f
MOM
3f
78
OR
O
Tr
BzO
BnO
O
7
2g
PMP
3g
3h
3i
96
RO
O
RO
OMP
8
2h
2i
methallyl
prenyl
87
OR
RO OMe
9
84
4g: R = allyl
5g: R = H
4h: R = allyl
5h: R = H
10
11
12
13
14
15
16
17b
18
19
20
21
2j
PhC≡CCH2
Ac
3j
94
Entry
1b
Substrate
Product
Yield (%)
95
2k
2l
3k
3l
93
4a
4b
4c
4d
4e
4f
5a
5b
5c
5d
5e
5f
chloroacetyl
levulinoyl
Bz
100
100
93
2
81
2m
2n
2o
3m
3n
3o
3p
3q
3r
3c
100
99
4c
p-O2NC6H4CO
p-NCC6H4CO
p-OHCC6H4CO
p-ClC6H4CO
p-BrC6H4CO
p-TfOC6H4CO
p-IC6H4CO
88
5c
96
2p
2q
2r
98
6c
80
96
7b,d
8f
4g
5g
95e
96
4h
5h
94
2s
3s
91
a Reaction was performed with 1a (2 equiv) and Pd(PPh3)4 (5 mol%)
in MeOH at r.t.
2t
3t
97
b Reaction was performed in CH2Cl2–MeOH (3:1).
c Reaction was performed at 40 °C.
2u
3u
0
d Reaction was performed with 1a (12 equiv) and Pd(PPh3)4 (30
mol%).
a Reaction was performed with PSBA (1b; 2 equiv) in CH2Cl2–MeOH
(1:1) for 24 h.
e Isolated yield of the cleaved residue from solid-support.
f Reaction was performed with 1a (8 equiv) and Pd(PPh3)4 (20 mol%).
b Reaction was performed with TMBA (1c; 3 equiv) in 1,4-dioxane–
H2O (3:1).
Synlett 2007, No. 20, 3131–3136 © Thieme Stuttgart · New York

LETTER
Solvent Effect on Pd(0)-Catalyzed Deprotection of Allyl Ethers
3133
As shown in Table 2, we have achieved selective cleavage Combination of these deprotecting methods would make
of allyl ethers in the presence of substituted allyl ethers, orthogonal deprotection strategy for substituted allyl pro-
i.e., methallyl and prenyl ethers (Table 2, entries 8 and 9). tecting groups feasible.
We, then examined the cleavage of these less reactive
General mechanism for the Tsuji–Trost reaction is shown
ethers (Scheme 1). To the best of our knowledge, there is
in Scheme 4.12 The reaction begins by the oxidative addi-
no report on the Pd(0)-catalyzed cleavage of these
tion of the allylic substrate 15 to the Pd(0) catalyst leading
ethers.8,9 Whereas methallyl ether in 6 could also be re-
to the h3-allyl complex 16 (a). In base-free conditions, the
moved by 1a on heating at 60 °C for 12 hours under the
palladium catalysis, the cleavage of prenyl ether in 7 re-
quired heating over 80 °C for 24 hours. It is worth noting
that methallyl ether in 8 could be cleaved selectively with-
counteranion derived from the leaving group itself depro-
tonates the pronucleophile 19 to give a cationic p-allylpal-
ladium(II) 17 with a nucleophile anion (b). Finally, the
generated nucleophile anion attacks the cationic p-al-
lylpalladium(II) from the face opposite to the metal (c) to
out affecting prenyl ether (Scheme 2).
produce the allylated nucleophile 18, and to regenerate
Pd(0) to reenter the catalytic cycle.
1a (2 equiv)
Pd(PPh3)4 (5 mol%)
OR
3a
BnO
MeOH
Nu
RO
Pd(0)L2
a
6: R = methallyl
7: R = prenyl
89% from 6
100% from 7
60 °C, 12 h for 6
80–110 °C, 24 h for 7
18
15
c
Scheme 1 Cleavage of methallyl and prenyl ethers
b
1a (2 equiv)
Pd+
Pd+
Pd(PPh3)4 (5 mol%)
Nu–
RO–
L
OMethallyl
L
L
L
3i (80%)
PrenylO
MeOH, 60 °C, 12 h
17
16
8
Nu– + H+
↑↓
Nu-H 19
RO-H
Scheme 2 Cleavage of methallyl ether in the presence of prenyl
ether
Scheme 4 General mechanism for Tsuji–Trost reaction: (a) oxida-
tive addition; (b) counteranion exchange; (c) reductive elimination.
Selective and successive cleavage of allyl, methallyl, and
prenyl ethers on the galactopyranoside 9 was achieved by
control of the reaction temperature (Scheme 3).10 Selec-
tive deprotection and functionalization of hydroxyl
groups on sugar scaffolds is very important for the combi-
natorial synthesis of sugar-based library for pharmaceuti-
cal drugs and chiral ligands for metal-catalyzed
asymmetric reactions.11 This method is complementary to
the recently reported selective and successive cleavage of
prenyl and methallyl ethers in the presence of allyl ethers.8
In this catalytic cycle, the p-allylpalladium(II) formation
(oxidative addition) and the alkylation (reductive elimina-
tion) would be hindered by electron-accepting and elec-
tron-donating
phosphine
ligands,
respectively.13
Although a protic polar solvent, such as MeOH, was ex-
pected to increase the acidity of DMBA and accelerate the
counteranion-exchange step, we studied the electronic ef-
fect of the phosphine ligands to determine the rate-limit-
ing step of the deallylation in both THF and MeOH
(Table 4). Triarylphosphines bearing methoxy and trifluo-
romethyl groups at their para positions were employed as
electron-donating and -accepting phosphines, respective-
ly. The Pd catalysts ligated with these phosphines were
prepared in situ by mixing Pd(OAc)2 (5 mol%) and phos-
phines (15 mol%). The in situ prepared catalyst ligated
with triphenylphosphine as well as Pd(PPh3)4 promoted
the deallylations in both solvents (entries 1 and 4). The
use of electron-donating phosphine retarded the deallyla-
tion in MeOH and promoted that in THF (entries 2 and 5).
In contrast, the use of electron-accepting phosphine hin-
dered the deallylation in THF and promoted that in MeOH
(entries 3 and 6). These results indicate that the deallyla-
tions in THF and MeOH involve p-allylpalladium(II) for-
mation and alkylation as the rate-limiting steps,
respectively. The acceleration of oxidative addition step
in protic polar solvent is in agreement with the recent re-
ports on Tsuji–Trost reaction using allyl alcohols as ally-
lating reagents in aqueous media.14–16 It is still unclear
whether the protic solvent itself or the Brønsted acidity of
BnO
O
BnO
RO
O
O
a
O
O
O
O
OMP
OMP
9
10: R = H
11: R = Bz
b
BnO
BzO
BnO
OH
O
c
e
O
O
OMP
BzO
OMP
OR
OAc
14
12: R = H
13: R = Ac
d
Scheme 3 Selective and successive removal of allyl, methallyl, and
prenyl ethers on galactopyranoside 9. Reagents and conditions: (a) 1a
(2 equiv), Pd(PPh3)4 (5 mol%), MeOH, r.t., 84%; (b) BzCl, TMEDA,
cat. DMAP, CH2Cl2, r.t., 93%; (c) 1a (2 equiv), Pd(PPh3)4 (5 mol%),
MeOH, 60 °C, 83%; (d) Ac2O, Et3N, cat. DMAP, CH2Cl2, r.t., 100%;
(e) 1a (2 equiv), Pd(PPh3)4 (5 mol%), MeOH, 110 °C, 86%.
Synlett 2007, No. 20, 3131–3136 © Thieme Stuttgart · New York

3134
H. Tsukamoto et al.
LETTER
Thongsornkleeb, C.; Teng, L. Org. Lett. 2000, 2, 489.
Table 4 Ligand Effect on Deallylation of 2a in THF and MeOHa
(h) Taniguchi, T.; Ogasawara, K. Angew. Chem. Int. Ed.
1998, 37, 1136. (i) Dahlen, A.; Sundgren, A.; Lahmann, M.;
Oscarson, S.; Hilmersson, C. Org. Lett. 2003, 5, 4085.
(j) Thomas, R. M.; Mohan, G. H.; Iyengar, D. S.
Tetrahedron Lett. 1997, 38, 4721. (k) Chary, K. P.; Mohan,
G. H.; Iyengar, D. S. Chem. Lett. 1999, 28, 1223.
(l) RajaRam, S.; Chary, K. P.; Salahuddin, S.; Iyengar, D. S.
Synth. Commun. 2002, 30, 133. (m) Tanaka, S.; Saburi, H.;
Ishibashi, Y.; Kitamura, M. Org. Lett. 2004, 6, 1873.
(n) Tanaka, S.; Saburi, H.; Kitamura, M. Adv. Synth. Catal.
2006, 348, 375. (o) Murakami, H.; Minami, T.; Ozawa, F.
J. Org. Chem. 2004, 69, 4482.
1a (2 equiv)
Pd(OAc)2 (5 mol%)
ligand (15 mol%)
3a
2a
THF or MeOH, r.t.
Entry
Solvent
THF
Ligand
PPh3
Time (h) Yield (%)
1
2
3
4
5
6
48
48
48
4
86
82
nda
88
90
91
THF
P(C6H4-p-OMe)3
P(C6H4-p-CF3)3
PPh3
THF
(4) (a) Bartnicka, H.; Bojanowska, I.; Kalinowski, M. K. Aust.
J. Chem. 1991, 44, 1077. (b) Headly, A. D.; Starnes, S. D.;
Wilson, L. Y.; Famini, G. R. J. Org. Chem. 1994, 59, 8040.
(c) Mollin, J.; Pavelek, Z.; Navrátilová, J.; Recmanová, A.
Coll. Czech. Chem. Commun. 1985, 50, 2670.
MeOH
MeOH
MeOH
P(C6H4-p-OMe)3
P(C6H4-p-CF3)3
18
3
(5) In this time, the deallylation of 2a in THF proceeded even at
room temperature, but required 24 hours for its completion
(Table 1, entry 6). Use of Pd(PPh3)4 prepared according to
the following literature procedure instead of commercially
available one might improve the reactivity: Coulson, D. R.
Inorg. Synth. 1972, 13, 121.
(6) Representative Procedure for Deprotection of Allyl
Ether: To a test tube containing 2a (0.13 mmol), 1a (0.27
mmol), and Pd(PPh3)4 (7 mmol) was added MeOH (0.4 mL)
under argon. The resulting mixture was sealed with a screw
cap and agitated at r.t. for 1 h. The mixture was partitioned
between EtOAc and sat. aq Na2CO3 and the aqueous layer
was extracted with EtOAc (2 ×). The combined organic
layers were washed with brine, dried over MgSO4, and
concentrated in vacuo. The residue was purified by silica gel
chromatography to yield the deallylated product 3a.
(7) (a) Jursic, B. S.; Neumann, D. M. Tetrahedron Lett. 2001,
42, 4103. (b) Jursic, B. S.; Stevens, E. D. Tetrahedron Lett.
2003, 44, 2203.
a A trace of 3a was observed by 1H NMR.
1a increased by using protic polar solvent accelerates the
oxidative addition step.17,18
The present study has disclosed that the use of a protic po-
lar solvent instead of THF can dramatically accelerate the
deallylation using barbituric acid derivatives 1a–c. The
mild reaction conditions compatible with a wide variety of
functional groups (including the most sensitive aldehyde
group) would make this method the first choice for the
deprotection of allyl ethers. The improved reactivity also
allows selective and successive cleavage of allyl, methal-
lyl, and prenyl ethers. Furthermore, study of ligand effects
reveals that oxidative addition step should not be a rate-
limiting step in the deallylation in MeOH anymore. Fur-
ther studies on the details of the reaction mechanism are
underway in our laboratory.
(8) For sulfone-catalyzed selective and successive cleavage of
prenyl and methallyl ethers in the presence of allyl ethers,
see: (a) Markovic, D.; Vogel, P. Org. Lett. 2004, 6, 2693.
(b) Markovic, D.; Steunenberg, P.; Ekstrand, M.; Vogel, P.
Chem. Commun. 2004, 2444.
Acknowledgment
(9) For cleavage of prenyl ethers in the presence of allyl ethers,
see: (a) Sharma, G. V. M.; Ilangovan, A.; Mahalingam, A.
K. J. Org. Chem. 1998, 63, 9103. (b) Sharma, G. V. M.;
Reddy, C. G.; Krishna, P. R. Synlett 2003, 1728.
This work was partly supported by a Grant-in-Aid from the Japan
Society for Promotion of Sciences (No. 18790003).
References and Notes
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4-Methoxyphenyl 3-O-Allyl-4-O-benzyl-2-O-methallyl-6-
O-prenyl-b-D-galactopyranoside (9): 1H NMR (400 MHz,
CDCl3): d = 7.25–7.40 (m, 5 H), 6.99 (d, J = 8.8 Hz, 2 H),
6.78 (d, J = 8.8 Hz, 2 H), 5.93 (ddt, J = 5.6, 10.4, 17.2 Hz, 1
H), 5.33 (d, J = 17.2 Hz, 1 H), 5.27 (t, J = 6.8 Hz, 1 H), 5.18
(d, J = 10.4 Hz, 1 H), 5.01 (s, 1 H), 4.96 (d, J = 11.6 Hz, 1
H), 4.87 (s, 1 H), 4.77 (d, J = 7.6 Hz, 1 H), 4.67 (d, J = 11.6
Hz, 1 H), 4.33 (d, J = 12.0 Hz, 1 H), 4.23 (d, J = 12.0 Hz, 1
H), 4.19 (d, J = 5.6 Hz, 2 H), 3.82–3.95 (m, 4 H), 3.75 (s, 3
H), 3.51–3.61 (m, 3 H), 3.44 (dd, J = 2.8, 9.6 Hz, 1 H), 1.78
(s, 3 H), 1.72 (s, 3 H), 1.62 (s, 3 H). 13C NMR (100 MHz,
C6D6): d = 155.8, 152.4, 143.3, 139.6, 136.2, 135.7, 128.5,
128.1, 127.6, 122.0, 119.2, 116.0, 114.9, 111.7, 103.9, 82.5,
Synlett 2007, No. 20, 3131–3136 © Thieme Stuttgart · New York

LETTER
Solvent Effect on Pd(0)-Catalyzed Deprotection of Allyl Ethers
3135
79.3, 77.1, 75.2, 74.5, 74.0, 71.9, 68.5, 68.0, 55.2, 25.8, 19.9,
CDCl3): d = 8.01 (d, J = 7.8 Hz, 2 H), 7.57 (t, J = 7.8 Hz, 1
H), 7.43 (dd, J = 7.8, 7.8 Hz, 2 H), 7.16–7.28 (m, 5 H), 6.98
(d, J = 9.0 Hz, 2 H), 6.80 (d, J = 9.0 Hz, 2 H), 5.79 (dd, J =
7.6, 10.4 Hz, 1 H), 5.29 (t, J = 6.8 Hz, 1 H), 5.21 (dd, J = 3.2,
10.4 Hz, 1 H), 4.98 (d, J = 7.6 Hz, 1 H), 4.71 (d, J = 11.6 Hz,
1 H), 4.56 (d, J = 11.6 Hz, 1 H), 4.20 (dd, J = <1.0, 3.2 Hz,
1 H), 3.96 (dd, J = 7.2, 11.6 Hz, 1 H), 3.89 (dd, J = 7.2, 11.6
Hz, 1 H), 3.87 (ddd, J = 1.0, 7.2, 7.2 Hz, 1 H), 3.76 (s, 3 H),
3.58–3.66 (m, 2 H), 1.98 (s, 3 H), 1.72 (s, 3 H), 1.63 (s, 3 H).
13C NMR (100 MHz, CDCl3): d = 169.3, 165.7, 155.3, 151.2,
137.7, 137.3, 133.4, 129.8, 129.0, 128.5, 128.1, 127.9,
127.5, 120.6, 118.5, 114.4, 100.8, 75.0, 74.5, 73.8, 73.8,
69.5, 67.8, 67.7, 55.6, 25.8, 20.8, 18.0. IR (neat): 2935,
2869, 1752, 1719, 1507, 1272, 1212, 1067, 1027, 828, 749,
714 cm–1. MS (EI): m/z (%) = 590 [M]+ (0.26), 467 (3.7), 399
(54), 339 (5.0), 277 (30), 249 (27), 175 (8.5), 124 (30), 91
(100). HRMS (EI): m/z [M]+ calcd for C34H38O9: 590.2516;
found: 590.2518.
4-Methoxyphenyl 2-O-Acetyl-3-O-benzoyl-4-O-benzyl-b-
D-galactopyranoside (14): 1H NMR (400 MHz, CDCl3): d =
8.05 (dd, J = 1.2, 8.0 Hz, 2 H), 7.60 (tt, J = 1.2, 8.0 Hz, 1 H),
7.47 (dd, J = 8.0, 8.0 Hz, 2 H), 7.23–7.26 (m, 5 H), 6.96 (d,
J = 9.2 Hz, 2 H), 6.81 (d, J = 9.2 Hz, 2 H), 5.81 (dd, J = 8.0,
10.4 Hz, 1 H), 5.22 (dd, J = 2.8, 10.4 Hz, 1 H), 5.01 (d, J =
8.0 Hz, 1 H), 4.76 (d, J = 11.6 Hz, 1 H), 4.48 (d, J = 11.6 Hz,
1 H), 4.13 (dd, J = <1.0, 2.8 Hz, 1 H), 3.84–3.90 (m, 1 H),
3.73–3.78 (m, 4 H), 3.55–3.62 (m, 1 H), 2.00 (s, 3 H), 1.58–
1.65 (br s, 1 H). 13C NMR (100 MHz, CDCl3): d = 169.4,
165.8, 155.3, 151.0, 137.1, 133.6, 129.8, 128.9, 128.6,
128.4, 128.3, 128.0, 118.3, 114.5, 100.5, 75.2, 72.7, 74.6,
73.1, 69.4, 61.6, 55.6, 20.8. IR (neat): 3350–3600 (br), 2935,
2883, 1752, 1719, 1507, 1272, 1212, 1069, 1027, 828, 749,
698 cm–1. MS (EI): m/z (%) = 522 [M]+ (0.35), 399 (22), 339
(3.0), 277 (9.5), 249 (18), 217 (3.5), 175 (8.5), 124 (25), 91
(100). HRMS (EI): m/z [M]+ calcd for C29H30O9: 522.189;
found: 522.1868.
18.0. IR (neat): 2914, 2875, 1507, 1233, 1102, 1054, 1027,
822, 746 cm–1. MS (FAB): m/z = 538 [M]+. HRMS (FAB):
m/z [M]+ calcd for C32H42O7: 538.2928; found: 538.2916.
4-Methoxyphenyl 4-O-Benzyl-2-O-methallyl-6-O-prenyl-
1
b-D-galactopyranoside (10): H NMR (600 MHz, CDCl3):
d = 7.39 (d, J = 7.2 Hz, 2 H), 7.35 (dd, J = 7.2, 7.2 Hz, 2 H),
7.30 (t, J = 7.2 Hz, 1 H), 6.99 (d, J = 9.0 Hz, 2 H), 6.80 (d,
J = 9.0 Hz, 2 H), 5.29 (t, J = 6.3 Hz, 1 H), 5.01 (s, 1 H), 4.89
(s, 1 H), 4.85 (d, J = 11.7 Hz, 1 H), 4.77 (d, J = 7.2 Hz, 1 H),
4.75 (d, J = 11.7 Hz, 1 H), 4.40 (d, J = 12.0 Hz, 1 H), 4.18
(d, J = 12.0 Hz, 1 H), 3.96 (dd, J = 7.2, 11.4 Hz, 1 H), 3.88–
3.92 (m, 2 H), 3.76 (s, 3 H), 3.68–3.71 (m, 3 H), 3.56–3.63
(m, 2 H), 2.39–2.43 (br s, 1 H), 1.77 (s, 3 H), 1.72 (s, 3 H),
1.63 (s, 3 H). 13C NMR (150 MHz, CDCl3): d = 155.2, 151.5,
142.4, 138.5, 137.5, 128.4, 128.1, 127.8, 120.7, 118.3,
114.5, 112.5, 102.8, 79.6, 76.7, 75.5, 75.1, 74.1, 73.9, 68.2,
67.8, 55.6, 25.8, 19.7, 18.0. IR (neat): 3300–3600 (br), 2914,
2865, 1507, 1453, 1378, 1214, 1061, 826, 747 cm–1. MS
(EI): m/z (%) = 498 [M]+ (0.45), 430 (0.36), 374 (1.9), 307
(5.6), 262 (2.6), 214 (5.3), 192 (15), 145 (15), 124 (100), 91
(94). HRMS (EI): m/z [M]+ calcd for C29H38O7: 498.2615;
found: 498.2616.
4-Methoxyphenyl 3-O-Benzoyl-4-O-benzyl-2-O-methallyl-
6-O-prenyl-b-D-galactopyranoside (11): 1H NMR (400
MHz, CDCl3): d = 8.04 (dd, J = 1.2, 8.0 Hz, 2 H), 7.56 (tt,
J = 1.2, 8.0 Hz, 1 H), 7.43 (dd, J = 8.0, 8.0 Hz, 2 H), 7.20–
7.30 (m, 5 H), 7.03 (d, J = 9.2 Hz, 2 H), 6.81 (d, J = 9.2 Hz,
2 H), 5.24 (t, J = 6.8 Hz, 1 H), 5.24 (dd, J = 3.4, 10.2 Hz, 1
H), 4.92 (d, J = 7.6 Hz, 1 H), 4.89 (s, 1 H), 4.76 (s, 1 H), 4.72
(d, J = 11.8 Hz, 1 H), 4.58 (d, J = 11.8 Hz, 1 H), 4.31 (d, J =
11.6 Hz, 1 H), 4.13 (dd, J = <1.0, 3.4 Hz, 1 H), 4.12 (d, J =
11.6 Hz, 1 H), 4.08 (dd, J = 7.6, 10.2 Hz, 1 H), 3.95 (dd, J =
6.8, 11.4 Hz, 1 H), 3.88 (dd, J = 6.8, 11.4 Hz, 1 H), 3.82 (ddd,
J = <1.0, 6.8, 6.8 Hz, 1 H), 3.76 (s, 3 H), 3.56–3.64 (m, 2 H),
1.72 (s, 3 H), 1.62 (s, 3 H), 1.58 (s, 3 H). 13C NMR (100
MHz, CDCl3): d = 165.6, 155.1, 151.4, 142.1, 137.9, 137.2,
133.1, 129.7, 129.7, 128.3, 128.1, 127.9, 127.5, 120.7,
118.4, 114.4, 112.6, 103.0, 77.0, 76.8, 75.7, 75.0, 74.3, 73.5,
67.9, 67.8, 55.6, 25.8, 19.6, 18.1. IR (neat): 2931, 2867,
1719, 1507, 1451, 1270, 1216, 1067, 903, 826, 749, 710
cm–1. MS (EI): m/z (%) = 602 [M]+ (1.3), 479 (8.7), 411 (21),
393 (5.7), 339 (6.2), 303 (4.6), 249 (20), 214 (15), 192 (18),
149 (22), 91 (100). HRMS (EI): m/z [M]+ calcd for
(11) (a) Wunberg, T.; Kallus, C.; Opatz, T.; Henke, S.; Schmidt,
W.; Kunz, H. Angew. Chem. Int. Ed. 1998, 37, 2503.
(b) Kallus, C.; Opatz, T.; Wunberg, T.; Schmidt, W.; Henke,
S.; Kunz, H. Tetrahedron Lett. 1999, 40, 7783.
(12) Frost, C. G.; Howarth, J.; Williams, J. M. J. Tetrahedron:
Asymmetry 1992, 3, 1089.
(13) (a) Sakaki, S.; Nishikawa, M.; Ohyoshi, A. J. Am. Chem.
Soc. 1980, 102, 4062. (b) Åkermark, B.; Zetterberg, K.;
Hansson, S.; Krakenberger, B.; Vitagliano, A.
C36H42O8: 602.2877; found: 602.2867.
4-Methoxyphenyl 3-O-Benzoyl-4-O-benzyl-6-O-prenyl-b-
D-galactopyranoside (12): 1H NMR (400 MHz, CDCl3): d =
8.05 (dd, J = 1.2, 8.0 Hz, 2 H), 7.56 (tt, J = 1.2, 8.0 Hz, 1 H),
7.42 (dd, J = 8.0, 8.0 Hz, 1 H), 7.20–7.30 (m, 5 H), 7.03 (d,
J = 9.2 Hz, 2 H), 6.80 (d, J = 9.2 Hz, 2 H), 5.28 (t, J = 6.8
Hz, 1 H), 5.22 (dd, J = 3.2, 10.4 Hz, 1 H), 4.86 (d, J = 8.0 Hz,
1 H), 4.73 (d, J = 11.6 Hz, 1 H), 4.59 (d, J = 11.6 Hz, 1 H),
4.35 (dd, J = 8.0, 10.4 Hz, 1 H), 4.15 (dd, J = <1.0, 3.2 Hz,
1 H), 3.96 (dd, J = 7.2, 11.6 Hz, 1 H), 3.88 (dd, J = 7.2, 11.6
Hz, 1 H), 3.85 (ddd, J = <1.0, 7.2, 7.2 Hz, 1 H), 3.76 (s, 3 H),
3.56–3.65 (m, 2 H), 2.49–2.55 (br s, 1 H), 1.72 (s, 3 H), 1.62
(s, 3 H). 13C NMR (100 MHz, CDCl3): d = 166.0, 155.3,
151.1, 137.9, 137.3, 133.2, 129.8, 129.5, 128.4, 128.1,
127.8, 127.6, 120.6, 118.5, 114.4, 102.6, 75.8, 75.1, 74.2,
73.8, 69.7, 67.8, 67.8, 55.6, 25.8, 18.1. IR (neat): 3250–
3600(br), 2912, 2836, 1717, 1507, 1451, 1273, 1216, 1065,
1027, 827, 748, 712 cm–1. MS (EI): m/z (%) = 548 [M]+
(0.34), 425 (8.5), 357 (34), 249 (4.0), 214 (11), 192 (13), 124
(100), 91 (97). HRMS (EI): m/z [M]+ calcd for C32H36O8:
548.2410; found: 548.2411.
J. Organomet. Chem. 1987, 335, 133. (c) Åkermark, B.;
Krakenberger, B.; Hansson, S.; Vitagliano, A.
Organometallics 1987, 6, 620. (d) Szabó, K. J.
Organometallics 1996, 15, 1128. (e) Szabó, K. J. J. Am.
Chem. Soc. 1996, 118, 7818. (f) Ross, J.; Chen, W.; Xu, L.;
Xiao, J. Organometallics 2001, 20, 138.
(14) For Pd(0)-catalyzed direct allylation of 1,3-dicarbonyl
compounds with allyl alcohols in aqueous media, see:
(a) Manabe, K.; Kobayashi, S. Org. Lett. 2003, 5, 3241.
(b) Kinoshita, H.; Shiokubo, H.; Oshima, K. Org. Lett. 2004,
6, 4085. (c) Kinoshita, H.; Shiokubo, H.; Oshima, K. Angew.
Chem. Int. Ed. 2005, 44, 2097.
(15) For Pd(0)-catalyzed direct allylation of 1,3-dicarbonyl
compounds with allylic alcohols in nonaqueous media, see:
(a) Tamaru, Y.; Horino, Y.; Araki, M.; Tanaka, S.; Kimura,
M. Tetrahedron Lett. 2000, 41, 5705. (b) Kimura, M.;
Mukai, R.; Tanigawa, N.; Tanaka, S.; Tamaru, Y.
Tetrahedron 2003, 59, 7767. (c) Ozawa, F.; Okamoto, H.;
Kawagishi, S.; Yamamoto, S.; Minami, T.; Yoshifuji, M. J.
Am. Chem. Soc. 2002, 124, 10968. (d) Ozawa, F.; Ishiyama,
T.; Yamamoto, S.; Kawagishi, S.; Murakami, H.; Yoshifuji,
M. Organometallics 2004, 23, 1698. (e) Kayaki, Y.; Koda,
4-Methoxyphenyl 2-O-Acetyl-3-O-benzoyl-4-O-benzyl-6-
O-prenyl-b-D-galactopyranoside (13): 1H NMR (400 MHz,
Synlett 2007, No. 20, 3131–3136 © Thieme Stuttgart · New York

3136
H. Tsukamoto et al.
LETTER
T.; Ikariya, T. J. Org. Chem. 2004, 69, 4989. (f)Hou, R.-S.;
Wang, H.-M.; Huang, H.-Y.; Chen, L.-C. Heterocycles
2005, 65, 1917. (g) Patil, N. T.; Yamamoto, Y. Tetrahedron
Lett. 2004, 45, 3101. (h) Yang, S.-C.; Hsu, Y.-C.; Gan, K.-
H. Tetrahedron 2006, 62, 3949.
(17) There are a few reports on carboxylic acids promoted Tsuji–
Trost reaction.14a,15g,h In our systems, barbituric acids play
dual roles as acids and nucleophiles.
(18) Less acidic acyclic 1,3-dicarbonyl compounds did not
scavenge the allyl group of 2a in aqueous 1,4-dioxane at
room temperature. This result is quite different from the
aqueous biphasic Tsuji–Trost reaction developed by
Shinokubo and Oshima.14b Our system does not require
biphasic systems, water-soluble TPPTS [trisodium salt of
tri(m-sulfophenyl)phosphine] as a ligand, and additional
base.
(16) The following reports also suggested that alcoholic solvents
would promote the oxidative addition to Pd(0) catalyst:
(a) Tsukamoto, H.; Suzuki, R.; Kondo, Y. J. Comb. Chem.
2006, 8, 289. (b) Yokogi, M.; Kuwano, R. Tetrahedron Lett.
2007, 48, 6109.
Synlett 2007, No. 20, 3131–3136 © Thieme Stuttgart · New York

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