A novel amphiphilic chiral ligand derived from D-glucosamine. Application to palladium-catalyzed asymmetric allylic substitution reaction in an aqueous or an organic medium, allowing for catalyst recycling

Article abstract of DOI:10.1021/jo000305w

A novel amphiphilic phosphinite-oxazoline chiral compound, 2-methyl-4,5-[4,6-O-benzylidene-3-O-bis {4-((diethylamino)methyl)phenyl}phosphino-1,2-dideoxy-α-D-gluc opyranosyl]-[2,1-d]-2-oxazo-line (1), has been prepared from natural D-glucosamine hydrochloride. The newly prepared complex, [Pd(2-methyl-4,5-[4,6-O-benzylidene-3-O-bis{(4-((diethyhnethylam monium)methyl)phenyl)}phosphin 1,2-dideoxy-α-D-glucopyranosyl]-[2,1-d]-2-oxazoline)(n³-C₃H₅) ]³⁺·3BF₄^- (3), is soluble in water and an efficient catalyst for asymmetric allylic substitution reaction in water or an aqueous/organic biphasic medium (up to 85% ee). This catalytic system offers an easy separation of the aqueous catalyst phase from the product phase and allows recycling of the catalyst phase. In addition, compound I also works as an effective ligand for the palladium-catalyzed reaction under conventional homogeneous conditions in an organic medium, in which the catalyst (Pd-1 complex) can be recovered by simple acid/base extraction and reused in the second reaction.

Full text of DOI:10.1021/jo000305w

J . Org. Chem. 2000, 65, 5197-5201
5197
A Novel Am p h ip h ilic Ch ir a l Liga n d Der ived fr om D-Glu cosa m in e.
Ap p lica tion to P a lla d iu m -Ca ta lyzed Asym m etr ic Allylic
Su bstitu tion Rea ction in a n Aqu eou s or a n Or ga n ic Med iu m ,
Allow in g for Ca ta lyst Recyclin g
Tomohiro Hashizume, Koji Yonehara, Kouichi Ohe,* and Sakae Uemura*
Department of Energy and Hydrocarbon Chemistry, Graduate School of Engineering, Kyoto University,
Sakyo-ku, Kyoto 606-8501, J apan
Received March 6, 2000
A novel amphiphilic phosphinite-oxazoline chiral compound, 2-methyl-4,5-[4,6-O-benzylidene-3-
O-bis{4-((diethylamino)methyl)phenyl}phosphino-1,2-dideoxy-R-D-glucopyranosyl]-[2,1-d]-2-oxazo-
line (1), has been prepared from natural D-glucosamine hydrochloride. The newly prepared complex,
[
1
Pd(2-methyl-4,5-[4,6-O-benzylidene-3-O-bis{(4-((diethylmethylammonium)methyl)phenyl)}phosphino-
3
3+
-
,2-dideoxy-R-D-glucopyranosyl]-[2,1-d]-2-oxazoline)(η -C
3
H
5
)] ‚3BF
4
(3), is soluble in water and
an efficient catalyst for asymmetric allylic substitution reaction in water or an aqueous/organic
biphasic medium (up to 85% ee). This catalytic system offers an easy separation of the aqueous
catalyst phase from the product phase and allows recycling of the catalyst phase. In addition,
compound 1 also works as an effective ligand for the palladium-catalyzed reaction under
conventional homogeneous conditions in an organic medium, in which the catalyst (Pd-1 complex)
can be recovered by simple acid/base extraction and reused in the second reaction.
In tr od u ction
attention to asymmetric allylic substitution reactions in
an aqueous medium.
Homogeneous chiral catalysts are extensively used in
both organic syntheses and several industrial chemical
processes, mainly because of their high activity and
selectivity.1 Recently, concerns over hazardous waste
generated during catalytic reactions and separation of
products from catalyst increasingly led to the develop-
ment of systems that employ water as solvent.2 The
benefits gained by using aqueous catalytic systems
include easier product separation, decreased cost, in-
creased safety, and more efficient catalyst recycling. In
these catalytic systems, organometallic complexes are
usually soluble in water through the use of chiral
hydrophilic ligands incorporating the charged or polar
substituents, providing fair to good enantioselectivity in
To our knowledge, scarce attention has been paid to
9
asymmetric palladium-catalyzed reaction in an aqueous
medium,10 except for highly enantioselective allylic alky-
(3) (a) Shin, S.; RajanBabu, T. V. Org. Lett. 1999, 1, 1229. (b) Holz,
J .; Heller, D.; St u¨ rmer, R.; B o¨ rner, A. Tetrahedron Lett. 1999, 40, 7059.
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1
(
1
3
4
the hydrogenation and hydroformylation of alkenes, the
5
6
hydrogenolysis of epoxides, and the oxidation of alkenes.
(
Recently, we reported the highly enantioselective hydro-
genation of alkenes in water, an aqueous/organic me-
dium, or an aqueous miceller medium using novel water-
soluble cationic rhodium(I) complexes bearing hydrophilic
ligands derived from R,R- and â,â-trehaloses.7a,b We also
reported that the ligand derived from D-glucosamine was
very effective for enantioselective palladium-catalyzed
allylic substitution reaction in an organic medium (up
3
(4) Eckl, R. W.; Priermeier, T.; Herrmann, W. A. J . Organomet.
Chem. 1997, 532, 243.
(
5) Bakos, J .; Orosz, AÄ .; Cser e´ pi, S.; T o´ th, I.; Sinou, D. J . Mol. Catal.,
A 1997, 116, 85.
8
(6) (a) Hamed, O.; Henry, P. M. Organometallics 1998, 17, 5184.
to 96% ee). These results encouraged us to turn our
(
2
b) El-Qisairi, A.; Hamed, O.; Henry, P. M. J . Org. Chem. 1998, 63,
790.
(7) (a) Yonehara, K.; Ohe, K.; Uemura, S. J . Org. Chem. 1999, 64,
(1) For recent overviews, see: (a) Noyori, R. Asymmetric Catalysis
in Organic Synthesis; J ohn Wiley: New York, 1994. (b) Ojima I.
Asymmetric Synthesis; Verlag: New York, 1993.
9381. (b) Yonehara, K.; Hashizume, T.; Mori, K.; Ohe, K.; Uemura, S.
J . Org. Chem. 1999, 64, 5593. (c) Recently, RajanBabu and a co-worker
have independently reported the synthesis of water-soluble chiral Rh
complex from R,R-trehalose: see ref 3a.
(8) (a) Yonehara, K.; Hashizume, T.; Mori, K.; Ohe, K.; Uemura, S.
J . Org. Chem. 1999, 64, 9374. (b) Yonehara, K.; Hashizume, T.; Mori,
K.; Ohe, K.; Uemura, S. Chem. Commun. 1999, 415. (c) A series of
phosphinite-oxazoline compounds derived from D-glucosamine also
worked as effective chiral ligands for the palladium-catalyzed asym-
metric intermolecular arylation of alkenes. See: Yonehara, K.; Mori,
K.; Hashizume, T.; Chung, K.-G.; Ohe, K.; Uemura, S. J . Organomet.
Chem., in press.
(2) (a) Cornils, B.; Herrmann, W. A. Aqueous-Phase Organometallic
Catalysis; Wiley-VCH: New York, 1998. (b) Cornils, B.; Herrmann,
W. A. Applied Homogeneous Catalysis with Organometallic Com-
pounds; VCH: New York, 1996. (c) Hanson, B. E. Coord. Chem. Rev.
1
3
999, 185-186, 795. (d) J o o´ , F.; Kath o´ , AÄ . J . Mol. Catal., A 1997, 116,
. (e) Papadogianakis, G.; Sheldon, R. A. New J . Chem. 1996, 20, 175.
(
f) Cornils, B. Angew. Chem., Int. Ed. Engl. 1995, 34, 1575. (g) Beller,
M.; Cornils, B.; Frohning, C. D.; Kohlpaintner, C. W. J . Mol. Catal., A
995, 104, 17. (h) Herrmann, W. A.; Kohlpaintner, C. W. Angew. Chem.,
Int. Ed. Engl. 1993, 32, 1524.
1
1
0.1021/jo000305w CCC: $19.00 © 2000 American Chemical Society
Published on Web 07/21/2000

5
198 J . Org. Chem., Vol. 65, No. 17, 2000
Hashizume et al.
F igu r e 1. Phosphinite-oxazoline chiral ligands derived from
D-glucosamine hydrochloride.
lation in an aqueous medium using heterogeneous resin-
supported MOP-palladium catalysts reported by Uozumi
and Hayashi.11 In this paper we report the synthesis of
a new amphiphilic chiral ligand, 1 (Figure 1), incorporat-
ing the diethylaminomethyl group at the 4-position of the
phenyl ring on the phosphorus atom and its application
to palladium-catalyzed asymmetric allylic substitution in
aqueous or organic media, allowing for catalyst recycling.
The amino group can be expected to serve as an ionizable
inducer by quarternization.12 Thus, the catalyst involving
the ligand having such a quarternized functional group
is soluble in water, which facilitates the catalyst recycling
as well as the separation of the catalyst from water-
immiscible organic products. Furthermore, the pH-
controlled quarternization of amino groups and cancel-
F igu r e 2. Catalyst recycling by pH-controlled extraction.
substitution in the conventional organic medium as
shown in Figure 2.
Resu lts a n d Discu ssion
lation of quarternization enable the catalyst to transport
between an aqueous phase and an organic phase.13 This
Syn th eses of P h osp h in ite-Oxa zolin e Liga n d 1
a n d Wa ter -Solu ble P a lla d iu m Com p lex 3. The
preparative methods for 2-methyl-4,5-[4,6-O-benzylidene-3-O-
bis{4-((diethylamino)methyl)phenyl}phosphino-1,2-di-
deoxy-R-D-glucopyranosyl]-[2,1-d]-2-oxazoline (1) and
catalyst transport between two phases is also applicable
to the catalyst recycling for palladium-catalyzed allylic
(9) (a) Tsuji, J . Palladium Reagents and Catalysis, Innovations in
[
Pd(2-methyl-4,5-[4,6-O-benzylidene-3-O-bis{4-((dieth-
Organic Synthesis; Wiley: New York, 1995. (b) Helmchen, G. J .
Organomet. Chem. 1999, 576, 203. (c) Hayashi, T. J . Organomet. Chem.
ylmethylammonium)methyl)phenyl}phosphino-1,2-dide-
1
9
999, 576, 195. (d) Trost, B. M.; Van Vranken, D. L. Chem. Rev. 1996,
6, 395. (e) Dawson, G. J .; Frost, C. G.; Williams, J . M. J . Tetrahedron
3
3+
oxy-R-D-glucopyranosyl]-[2,1-d]-2-oxazoline)(η -C
3
H
5
)] ‚
-
3
BF
4
(3) are shown in Scheme 1. Initially, treatment of
Lett. 1993, 34, 3149. (f) Sprinz, J .; Helmchen, G. Tetrahedron Lett.
1
1
993, 34, 1769. (g) Matt, P.; Pfaltz, A. Angew. Chem., Int. Ed. Engl.
993, 32, 566.
2-methyl-4,5-(4,6-O-benzylidene-1,2-dideoxy-R-D-gluco-
pyranosyl)-[2,1-d]-2-oxazoline (2), prepared from D-glu-
(10) Nonasymmetric allylic substitution reaction catalyzed by pal-
cosamine hydrochloride in five steps,8
a,b
with bis[4-
ladium-tris(sodium-m-sulfonatophenyl)phosphine in an aqueous me-
dium has also been reported: (a) Gen eˆ t, J . P.; Savignac, M. J .
Organomet. Chem. 1999, 576, 305. (b) dos Santos, S.; Tong, Y.;
Quignard, F.; Choplin, A.; Sinou, D.; Dutasta, J . P. Organometallics
1
3a
((diethylamino)methyl)phenyl]phosphinous diethylamide
and 1H-tetrazole in degassed dry tetrahydrofuran (THF)
gave the new chiral phosphinite-oxazoline 1 in 57%
1
2
998, 17, 78. (c) Sigismondi, S.; Sinou, D. J . Mol. Catal., A 1997, 116,
89. (d) Lemaire-Audoire, S.; Savignac, M.; Pourcelot, G.; Gen eˆ t, J .
3
+
-
yield. Next, a palladium complex, [Pd(1)(η -C
3
H
5
)] ‚BF
4
,
P.; Bernard, J .-M. J . Mol. Catal., A 1997, 116, 247. (e) Blart, E.; Gen eˆ t,
J . P.; Safi, M.; Savignac, M.; Sinou, D. Tetrahedron 1994, 50, 505. (f)
Gen eˆ t, J . P.; Blart, E.; Savignac, M.; Lemeune, S.; Lemaire-Audoire,
S.; Paris, J .-M.; Bernard, J .-M. Tetrahedron 1994, 50, 497. (g) Gen eˆ t,
J . P.; Blart, E.; Savignac, M. Synlett 1992, 715. (h) Safi, M.; Sinou, D.
Tetrahedron Lett. 1991, 32, 2025.
3
was prepared in situ by the reaction of [Pd(cod)(η -
with the ligand 1 in degassed acetone
under Ar. The treatment of the solution with Me
+
- 14
C
3
H
5
)] ‚BF
4
3
-
12h,k
OBF
4
2
followed by the addition of degassed dry Et O
afforded a cationic palladium complex, 3, in 88% yield
in which two amino groups were quarternized. As can
be expected, the complex 3 is soluble in water (ca. 1.47
g/100 mL at 20 °C). It is also soluble in polar organic
solvents such as MeOH, MeCN, and acetone, but in-
(
11) Uozumi, Y.; Danjo, H.; Hayashi, T. Tetrahedron Lett. 1998, 39,
303.
12) For the quaternization of the amino group to gain solubility in
water, see: (a) T o´ th, I.; Guo, I.; Hanson, B. E. J . Mol. Catal., A 1997,
1
1
1
8
(
16, 217. (b) Mohr, B.; Lynn, D. M.; Grubbs, R. H. Organometallics
996, 15, 4317. (c) Bitterer, F.; Kucken, S.; Stelzer, O. Chem. Ber. 1995,
28, 275. (d) T o´ th, I.; Hanson, B. E. Organometallics 1993, 12, 1506.
2
soluble in hexane, toluene, and Et O.
(
e) T o´ th, I.; Hanson, B. E.; Davis, M. E. J . Organomet. Chem. 1990,
3
96, 363. (f) T o´ th, I.; Hanson, B. E.; Davis, M. E. Tetrahedron:
P a lla d iu m -Ca ta lyzed Asym m etr ic Allylic Su bsti-
tu tion Rea ction in a n Aqu eou s Med iu m . First, asym-
metric allylic substitution reaction of 1,3-diphenyl-3-
Asymmetry 1990, 1, 913. (g) T o´ th, I.; Hanson, B. E. Tetrahedron:
Asymmetry 1990, 1, 895. (h) T o´ th, I.; Hanson, B. E.; Davis, M. E. Catal.
Lett. 1990, 5, 183. (i) Peiffer, G.; Chhan, S.; Bendayan, A.; Waegell,
B.; Zahra, J .-P. J . Mol. Catal. 1990, 59, 1. (j) Nagel, U.; Kinzel, E.
Chem. Ber. 1986, 119, 1731. (k) Smith, R. T.; Ungar, R. K.; Sanderson,
L. J .; Baird, M. C. Organometallics 1983, 2, 1138.
2
acetoxyprop-1-ene in an MeCN/H O biphasic medium
with various nucleophiles was examined using the cata-
lyst 3. The catalyst 3 was soluble in MeCN as well as in
an aqueous phase. However, after the reaction, all of the
catalyst in MeCN could be transferred into an aqueous
phase by addition of Et O in which the complex 3 is
2
insoluble, thereby being separated from the product
phase. These results are summarized in Table 1. The
(
13) (a) Buhling, A.; Kamer, P. C. J .; van Leeuwen, P. W. N. M.;
Elgersma, J . W.; Goubitz, K.; Fraanje, J . Organometallics 1997, 16,
027. (b) Buhling, A.; Kamer, P. C. J .; van Leeuwen, P. W. N. M.;
3
Elgersma, J . W. J . Mol. Catal., A 1997, 116, 297. (c) Buhling, A.;
Elgersma, J . W.; Nkrumah, S.; Kamer, P. C. J .; van Leeuwen, P. W.
N. M. J . Chem. Soc., Dalton Trans. 1996, 2143. (d) Buhling, A.; Kamer,
P. C. J .; van Leeuwen, P. W. N. M. J . Mol. Catal. 1995, 98, 69. (e)
Bay o´ n, J . C.; Rael, J .; Claver, C.; Polo, A.; Ruiz, A. J . Chem. Soc., Chem.
Commun. 1989, 1056. (f) Kurtev, K.; Ribola, D.; J ones, R. A.; Cole-
Hamilton, D. J .; Wilkinson, G. J . Chem. Soc., Dalton Trans. 1980, 55.
(14) White, D. A. Inorg. Synth. 1972, 13, 61.

A Novel Ciral Ligand Derived from D-Glucosamine
J . Org. Chem., Vol. 65, No. 17, 2000 5199
Sch em e 1a
a
Reagents and conditions: (a) bis[4-((diethylamino)methyl)phenyl]phosphinous diethylamide, 1H-tetrazole, THF, rt, 30 min, 57%; (b)
3
+
-
(
i) [Pd(cod)(η -C3H5)] ‚BF4 , acetone, rt, 30 min; (ii) Me3OBF4, rt, 30 min, 88% (two steps).
Ta ble 1. Asym m etr ic Allylic Su bstitu tion of 1,3-Dip h en yl-3-a cetoxyp r op -1-en e Usin g 3 in a n Aqu eou s Med iu m a
entry
NuH
base
solvent
MeCN
MeCN/H2O ) 4/1
MeCN/H2O ) 4/1
MeCN/H2O ) 4/1
toluene/H2O ) 1/1
MeCN/H2O ) 4/1
H2O
cat. (mol%)
time (h)
yield (%)b
ee (%)c,d
92 (S)
-
83 (S)
77 (R)
80 (R)
84 (R) (77)
85 (R) (60)
1
2
3
4
5
6
7
4
4
5
6
6
7
7
BSA + cat. KOAc
K2CO3
K2CO3
K2CO3
K2CO3
1
5
5
5
5
4
4
1
48
3
12
24
5
95
0
85
66
51
80
73
e
e
K2CO3
K2CO3
18
a
Reactions were carried out under Ar using 1,3-diphenyl-3-acetoxyprop-1-ene (0.80 mmol), NuH (1.6 mmol), base (3.6 mmol), solvent
b
c
(
3.0 mL), and catalyst 4 (1-5 mol %). Isolated yield. The ee (%) values were determined by HPLC. d The absolute configuration was
determined by its optical rotation.
catalyst.
9 e
f,15-17
The enantiomeric excess obtained from the second use of the aqueous solution containing the
reaction with dimethyl malonate (4) using N,O-bis-
trimethylsilyl)acetamide (BSA) proceeded smoothly in
MeCN to give high enantioselectivity (92% ee) (entry 1),
while this reaction did not take place in an MeCN/H
4/1 biphasic system in the presence of K CO (entry
). However, the reaction with acetylacetone (5) in place
of dimethyl malonate gave the corresponding product in
good yield (85%) with 83% ee under the biphasic condi-
tions (entry 3). The lack of reactivity of dimethyl mal-
complex bearing the ligand 1 in an organic medium, the
catalyst could be extracted into an acidic aqueous phase
as an ammonium salt, allowing the simple separation of
the product, and re-extracted into fresh organic solvent
after neutralization of the aqueous phase. Table 2 shows
the results of the catalyst recycling in asymmetric allylic
alkylation. First, the reaction was carried out in toluene
(
2
O
)
2
2
3
using a catalyst generated in situ by mixing 0.25 mol %
3
[Pd(η -C
3
H
5
)Cl]
2
with 0.55 mol % ligand 1 in the presence
onate (pK
is probably due to its higher pK
a
) 13.3) compared to acetylacetone (pK
a
) 8.94)
of BSA at room temperature. After the reaction, 0.48 M
aqueous HBF was added to the mixture to quarternize
a
; the formation of the
4
enol form disfavors the presence of water.1 The reaction
with 3-methyl-2,4-pentanedione (6) also proceeded to give
the corresponding product with 77% ee (entry 4). In a
0c
two amino groups, and the quarternized catalyst was
extracted into an aqueous phase. An organic phase
containing the product (85% yield, 93% ee) was sepa-
rated, and then fresh toluene was added. The acidic
solution was neutralized with saturated aqueous NaH-
2
toluene/H O biphasic medium in which the catalyst was
dissolved only in the aqueous phase, the product was also
obtained with 80% ee, although the yield decreased (entry
3
CO under rapid stirring until the aqueous phase became
5
). When benzylamine (7) was used as a nucleophile, the
colorless. The separated toluene layer containing the
catalyst was placed in the reaction vessel, and again the
reaction was carried out under the same conditions.
However, the second use of the catalyst unfortunately
was frustrated in the conversion of the substrate (5%
yield, 86% ee) (entry 1). Next, the reaction was carried
out in tetrahydrofuran (THF) in place of toluene. After
reaction was complete within 5 h and high enantioselec-
tivity (84% ee) was obtained. After the reaction, the
aqueous phase containing the catalyst was easily sepa-
rated by phase separation as mentioned above and reused
for the same allylic amination to give 77% ee (entry 6).
2
The reaction proceeded even in H O to give the product
with 85% ee, but the reaction was slower compared to
that in the biphasic system. In this case, after the
extraction of the product using hexane, the aqueous
phase containing the catalyst was also reused for the
same reaction to give 60% ee (entry 7).
the first reaction was complete, 0.48 M aqueous HBF
was added and the product (95% yield, 91% ee) was
extracted with hexane. After fresh CH Cl was added to
an acidic aqueous solution, it was neutralized under rapid
stirring with saturated aqueous NaHCO , and then the
organic layer including the catalyst was separated.
Evaporation of organic solvent from the recovered CH
4
2
2
3
P a lla d iu m Ca ta lyst Recyclin g by p H-Con tr olled
Extr a ction . After the reaction was performed using the
2
-

5
200 J . Org. Chem., Vol. 65, No. 17, 2000
Ta ble 2. Resu lts of th e Recyclin g Exp er im en tsa
Hashizume et al.
yield (%)b
ee (%) (S)
c
d
time (h)
entry
base
solvent
1st
2nd
1st
2nd
1st
2nd
1
2
3
BSA + cat. KOAc
BSA + cat. KOAc
NaH
toluene
THF
THF
1
1
2
36
12
12
85
95
97
5
79
90
93
91
89
86
92
89
a
Reactions were carried out under Ar using 1,3-diphenyl-3-acetoxyprop-1-ene (1.0 mmol), dimethyl malonate (2.0 mmol), base (2.0
3
-3
-3
mmol), solvent (3.5 mL), [Pd(η -C3H5)Cl]2 (2.5 × 10 mmol), and ligand (5.5 × 10 mmol). Recycling conditions are as follows: (1)
Extraction of the catalyst with 0.48 M aqueous HBF4. (2) Neutralization of an aqueous phase with HaHCO3 and re-extraction of the
catalyst with an organic solvent. Isolated yield. Determined by HPLC. d Determined by its optical rotation.
b
c
9f
Cl
2
solution gave the yellow residue,15 which was dis-
Daicel Chiralcel AD or OJ column (4.6 × 250 mm) at 40 °C.
Melting points are uncorrected. Elemental analyses were
performed at the Microanalytical Center of Kyoto University.
Compound 2 was prepared according to the reported pro-
cedure.8
solved in degassed dry THF and used again under the
same conditions. This procedure substantially improved
the product yield to 79% without a decrease of enanti-
oselectivity (92% ee) in the second reaction (entry 2).
Moreover, the use of NaH instead of BSA and KOAc did
not cause the unfavorable decrease of the chemical yield
as well as selectivity in the second reaction (entry 3).
a,b
2
-Met h yl-4,5-[4,6-O-b en zylid en e-3-O-b is{4-((d iet h yl-
a m in o)m et h yl)p h en yl}p h osp h in o-1,2-d id eoxy-r-D-glu -
cop yr a n osyl]-[2,1-d ]-2-oxa zolin e (1). To a solution of 2 (0.56
g, 1.9 mmol) in 10 mL of degassed dry THF (25 mL) was added
1
3a
bis[4-((diethylamino)methyl)phenyl]phosphinous diethylamide
1.1 g, 2.5 mmol) followed by the addition of 1H-tetrazole (0.20
(
Su m m a r y
g, 3.0 mmol) at room temperature, and the mixture was stirred
for 30 min. It was concentrated to dryness, and the residue
Starting from natural D-glucosamine, the amphiphilic
phosphinite-oxazoline 1 bearing a diethylaminomethyl
group on the phenyl ring of the phosphinite moiety and
the water-soluble cationic palladium complex 3 were
newly prepared. Complex 3 worked effectively as a
catalyst and provided good enantiomeric excess in allylic
alkylation and amination in water or an aqueous/organic
biphasic medium (up to 85% ee). The product could be
easily separated from the water-soluble catalyst by
simple phase separation. To the best of our knowledge,
these are the first examples of palladium-catalyzed
asymmetric allylic substitution reaction in an aqueous
medium using a homogeneous catalyst. In addition, it
was demonstrated that the palladium complex bearing
the ligand 1 was an effective catalyst for allylic substitu-
tion reaction in an organic medium, and it could be
reused in the second reaction by pH-controlled phase
separation without a decrease of both yield and enanti-
oselectivity.
was subjected to column chromatography on Al
degassed toluene-CH Cl (v/v ) 1/2) containing 1% triethy-
lamine as an eluent to give 2-methyl-4,5-[4,6-O-benzylidene-
-O-bis{(4-((diethylamino)methyl)phenyl}phosphino-1,2-dideoxy-
R-D-glucopyranosyl]-[2,1-d]-2-oxazoline (1) (0.71 g, 1.1 mmol,
2 3
O with
2
2
3
21
5
7%) as a white solid: mp 103.2-104.0 °C; [R]
D
) -55.5 (c
1
) 0.25, CHCl ); H NMR (300 MHz, CDCl ) δ 1.01 (t, J ) 7.1
Hz, 6H), 1.03 (t, J ) 7.1 Hz, 6H), 2.04 (d, J ) 1.1 Hz, 3H),
3
3
2
3
4
(
5
.47 (q, J ) 7.1 Hz, 4H), 2.51 (q, J ) 7.1 Hz, 4H), 3.50 (s, 2H),
.52 (s, 2H), 3.59-3.68 (m, 2H), 3.76 (t, J ) 8.5 Hz, 1H), 4.23-
.40 (m, 3H), 5.35 (s, 1H), 5.97 (d, J ) 7.5 Hz, 1H), 7.20-7.46
m, 13H) ppm; 13C NMR (67.5 MHz, CDCl
) δ 11.7, 14.3, 46.7,
7.3, 62.8, 68.6, 69.5 (d, J ) 5.0 Hz), 79.9 (d, J ) 3.7 Hz), 82.0
3
(
d, J ) 19.9 Hz), 101.1, 102.1, 126.0-130.7 (8 carbons), 140.0
(d, J ) 19.3 Hz), 140.3 (d, J ) 13.7 Hz), 141.28, 141.32, 164.9
ppm; 31P NMR (161.9 MHz, CDCl
) δ 115.0 ppm; IR (KBr)
1455, 1666, 3443 cm . Anal. Calcd for C37 P: C, 68.82;
H, 7.49; N, 6.51; P, 4.80. Found: C, 68.61; H, 7.66; N, 6.42; P,
.91.
P d (2-m eth yl-4,5-[4,6-O-ben zylid en e-3-O-bis{(4-((d ieth -
3
-1
48 3 5
H N O
4
[
ylm eth yla m m on iu m )m eth yl)p h en yl)}p h osp h in o-1,2-d i3 -
d e o x y -r-D -g lu c o p y r a n o s y l]-[2,1-d ]-2-o x a zo lin e )(η -
Exp er im en ta l Section
3+
-
3
+
- 14
4
C
3
H
5
)] ‚3BF
4
(3). [Pd(cod)(η -C
3
H
5
)] ‚BF
(38 mg, 0.11
mmol) and 1 (75 mg, 0.12 mmol) were dissolved in degassed
Gen er a l P r oced u r es. Tetrahydrofuran (THF) and diethyl
ether were distilled from sodium benzophenone ketyl under
argon. Analytical thin-layer chromatographies (TLC) were
performed with silica gel 60 Merck F-254 plates or aluminum
oxide 60 Merck F-254. Column chromatographies were per-
formed with Merck silica gel 60 or ICN Alumina Akt I
acetone (0.60 mL), and the mixture was stirred under Ar. After
3
0 min, Me
solution, and the mixture was stirred for a further 30 min.
Degassed dry Et O (4.0 mL) was added, and the solution was
3 4
OBF (38 mg, 0.26 mmol) was added to the above
2
cooled at 0 °C for 2 h. The supernatant solution was decan-
tated, and a separated yellow syrup was dried under reduced
(
neutral). The NMR spectra were measured for solutions in
-2
pressure to give the product 3 (105 mg, 9.7 × 10 mmol, 88%)
1
CDCl
3
3
or d
6
-acetone with Me
4
Si as an internal standard ( H
3
1
as a pale yellow powder: mp 188.0-191.0 °C; P NMR (161.9
1
31
and C) or with P(OMe) as an external standard ( P). The
3
MHz, d
ppm. Anal. Calcd for C42
6
-acetone) δ 121.9, 122.4 (1:1 mixture of diastereomers)
PPd: C, 46.55; H, 5.49;
following abbreviations are used: s, singlet; d, doublet; t,
triplet; q, quartet; m, multiplet. IR spectra were recorded with
an FT-IR spectrometer. Optical rotations were recorded at 589
nm. Enantiomeric ratios were determined by HPLC with a
59 3 12 3 5
H B F N O
N, 3.88. Found: C, 46.12; H, 5.42; N, 3.97.
A Typ ica l P r oced u r e of Allylic Su bstitu tion Rea ction
2
of 1,3-Dip h en yl-3-a cetoxyp r op -1-en e in a n MeCN/H O
-
2
Bip h a sic Med iu m . To complex 3 (34.8 mg, 3.2 × 10 mmol)
(15) The recovered catalyst weighed 9.0 mg, which was much more
in degassed H O (0.60 mL) was added a solution of (E)-1,3-
2
than the total amount of catalyst and ligand loaded in the first catalytic
reaction. The increase of the amount of catalyst may be due to the
ligand exchange from both simple allyl to 1,3-diphenylallyl and chloride
diphenyl-3-acetoxyprop-1-ene (0.20 g, 0.80 mmol) in degassed
MeCN (2.4 mL) followed by the addition of benzylamine (0.18
to BF
4
or others.
2 3
mL, 1.6 mmol) and K CO (0.51 g, 3.6 mmol) in this order,

A Novel Ciral Ligand Derived from D-Glucosamine
J . Org. Chem., Vol. 65, No. 17, 2000 5201
and the mixture was stirred vigorously under Ar. After the
complete conversion was confirmed by TLC monitoring (5 h),
Et O (3.0 mL) was added, and the mixture was stirred
2
vigorously for 10 min. After the organic phase was separated
by decantation, the solvent was evaporated under reduced
pressure, and the residue was subjected to column chroma-
tography on silica gel with hexane-AcOEt (v/v ) 5/1) as an
eluent to give the product (0.19 g, 0.64 mmol, 80%). The
separation of the racemic mixture under HPLC conditions is
as follows: (E)-1-benzylamino-1,3-diphenylprop-2-ene (OJ , 1.0
for 30 min. A 0.66 M sodium dimethyl malonate/THF solution
(3.0 mL, 2.0 mmol), which was prepared from dimethyl
malonate (0.24 mL, 2.0 mmol) and NaH (48 mg, 2.0 mmol) in
degassed dry THF (3.0 mL), was added to the above mixture,
and the resulting mixture was stirred at this temperature for
2 h. Aqueous HBF4 (0.48 M) (2.3 mL, 1.1 mmol) was added,
then the product was extracted with hexane (3.0 mL × 3), and
the extract was dried over MgSO . Solvent was removed under
4
reduced pressure, and the residue was subjected to column
chromatography on silica gel with hexane-AcOEt (v/v ) 5/1)
as an eluent to give the product (E)-methyl 2-methoxycarbonyl-
3,5-diphenylpent-4-enoate (0.32 g, 0.97 mmol, 97%). The yellow
aqueous layer was poured into a flask, and fresh degassed CH2-
Cl2 was added. The acidic solution was neutralized with
saturated aqueous NaHCO under rapid stirring until the
3
aqueous phase became colorless, and then the organic layer
was separated. The aqueous phase was again extracted with
mL/min, 5% 2-PrOH/hexane, 254 nm), (S), t
1
) 16.3 min; (R),
) 19.1 min; (E)-methyl 2-methoxycarbonyl-3,5-diphenylpent-
-enoate (AD, 1.0 mL/min, 5% 2-PrOH/hexane, 254 nm); (S),
) 11.1 min; (R), t ) 14.2 min; (E)-3-acetyl-4,6-diphenylhex-
-en-2-one (AD, 1.0 mL/min, 1% 2-PrOH/hexane, 254 nm); (S),
) 25.6 min; (R), t ) 32.3 min; (E)-3-acetyl-3-methyl-4,6-
diphenylhex-5-en-2-one (OJ , 1.0 mL/min, 10% 2-PrOH/hexane,
54 nm); (S), t ) 11.3 min; (R), t ) 15.4 min. The absolute
configurations were determined by their optical rotation.
P a lla d iu m Com p lex Recyclin g Exp er im en t. The chiral
t
2
4
t
1
2
5
t
1
2
2
1
2
2 2
CH Cl (3.0 mL), and the combined yellow organic phase was
concentrated to dryness. The residue, which weighed 9.0 mg,
was dissolved in degassed dry THF (0.5 mL), (E)-1,3-diphenyl-
9
f,16-18
-
3
3
ligand 1 (3.6 mg, 5.5 × 10 mmol) and [Pd(η -C
3
H
5
)Cl]
mg, 2.5 × 10 mmol) were dissolved in degassed dry THF
0.50 mL) under Ar, and the solution was stirred at room
2
(0.91
3
-acetoxyprop-1-ene (0.25 g, 1.0 mmol) and then 0.66 M sodium
-
3
dimethyl malonate solution in THF (3.0 mL, 2.0 mmol) were
added, and the mixture was stirred at room temperature. After
(
temperature. After 30 min, (E)-1,3-diphenyl-3-acetoxyprop-1-
ene (0.25 g, 1.0 mmol) was added, and the mixture was stirred
1
2 h, 0.48 M aqueous HBF
the product was extracted with hexane (3.0 mL × 3), and the
extract was dried over MgSO . Solvent was removed under
4
(2.3 mL, 1.1 mmol) was added,
4
(
16) Hayashi, T.; Yamamoto, A.; Ito, Y.; Nishioka, E.; Miura, H.;
Yanagi, K. J . Am. Chem. Soc. 1989, 111, 6301.
17) Hayashi, T.; Yamamoto, A.; Hagihara, T.; Ito, Y. Tetrahedron
Lett. 1986, 27, 191.
18) The absolute configuration of (R)-(E)-3-acetyl-3-methyl-4,6-
reduced pressure, and the residue was subjected to column
chromatography on silica gel with hexane-AcOEt (v/v ) 5/1)
as an eluent to give the product (E)-methyl 2-carbomethoxy-
(
3
,5-diphenylpent-4-enoate (0.29 g, 0.90 mmol, 90%). The
(
diphenylhex-5-en-2-one assigned in ref 11, where the direction of
optical rotation is described as (-), seems to be incorrect. The direction
of optical rotation of (R)-(E)-3-acetyl-3-methyl-4,6-diphenylhex-5-en-
enantiomeric excess (first use, 89% ee; second use, 89% ee)
was determined by HPLC.
2
-one is indeed (+) in our measurement.
J O000305W