Palladium-catalyzed asymmetric allylic substitution reactions using new chiral phosphinite-oxazoline ligands derived from D-glucosamine

Article abstract of DOI:10.1021/jo990901u

Novel 2-alkyl- or 2-aryl-4,5-(4,6-O-benzylidene-3-O-(diphenylphosphino)- 1,2-dideoxy-α-D-glucopyrano)-[2,1-d]-2-oxazolines (5a-f) have been prepared from D-glucosamine hydrochloride. They work effectively as chiral ligands and provide a high level of enantiomeric excess in palladium-catalyzed allylic alkylation and amination reactions. The allylic alkylation of 1,3-diphenyl-3- acetoxyprop-1-ene with dimethyl malonate proceeds smoothly in the presence of 0.25 mol % [Pd(η³C₃H₅)Cl]₂ and the chiral ligand 5a having the smallest substituent on oxazoline at 0 °C within 6 h to furnish the highest enantiomeric excess (96% ee). The ligand 5a is also effective for the Pd- catalyzed amination of ethyl 1,3-diphenylprop-2-enyl carbonate, leading to the corresponding allylic amine in 94% ee. The full scope and limitations using ligands 5a-f in the allylic substitution reactions are described.

Full text of DOI:10.1021/jo990901u

9374
J . Org. Chem. 1999, 64, 9374-9380
P a lla d iu m -Ca ta lyzed Asym m etr ic Allylic Su bstitu tion Rea ction s
Usin g New Ch ir a l P h osp h in ite-Oxa zolin e Liga n d s Der ived fr om
D-Glu cosa m in e
Koji Yonehara, Tomohiro Hashizume, Kenji Mori, 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 J une 2, 1999
Novel 2-alkyl- or 2-aryl-4,5-(4,6-O-benzylidene-3-O-(diphenylphosphino)-1,2-dideoxy-R-D-gluco-
pyrano)-[2,1-d]-2-oxazolines (5a -f) have been prepared from D-glucosamine hydrochloride. They
work effectively as chiral ligands and provide a high level of enantiomeric excess in palladium-
catalyzed allylic alkylation and amination reactions. The allylic alkylation of 1,3-diphenyl-3-
acetoxyprop-1-ene with dimethyl malonate proceeds smoothly in the presence of 0.25 mol % [Pd(η3-
C3H5)Cl]2 and the chiral ligand 5a having the smallest substituent on oxazoline at 0 °C within 6 h
to furnish the highest enantiomeric excess (96% ee). The ligand 5a is also effective for the Pd-
catalyzed amination of ethyl 1,3-diphenylprop-2-enyl carbonate, leading to the corresponding allylic
amine in 94% ee. The full scope and limitations using ligands 5a -f in the allylic substitution
reactions are described.
In tr od u ction
Palladium-catalyzed allylic substitution reactions are
known as an efficient synthetic tool for the construction
of carbon-carbon and carbon-heteroatom bonds.1 Vari-
ous C2- and C1-symmetric bidentate chiral ligands have
been applied to palladium-catalyzed allylic substitution
reactions to provide high enantioselectivities.1b The chiral
phosphine-oxazoline ligands were first developed by
Pfaltz,2 Helmchen,3 and Williams4 as effective non-C2-
symmetric ligands for these reactions. Other types of
oxazoline ligands which have not only the central chiral-
ity but also the planar5 or axial6 chirality on the backbone
of ligands have emerged for the past few years.
F igu r e 1.
deal of interest in the synthesis of chiral ligands for the
following reasons: (1) They exist widely in nature, and
thus they are commercially available at a reasonable
price. (2) These carbohydrates have many chiral centers
and many hydroxy groups in their skeletons, and there-
fore the regio- and stereoselective introduction of func-
tionality might be possible. Recently, a phosphine-
oxazoline ligand having a sugar backbone has been
reported by Kunz9 as illustrated in Figure 1. In this
ligand a phosphorus atom is attached to the aromatic ring
in the 2-position of oxazoline. In most phosphine-
oxazoline ligands a phosphorus atom is introduced to the
alkyl chain3a,10 or aromatic ring2-4 in the 2-position of
oxazoline. To prepare a chiral P-N ligand, an amino-
sugar D-glucosamine having a nitrogen atom in its
structure is suitable for the starting material. We have
prepared new chiral ligands 5a -f from the commercially
available D-glucosamine (Figure 1). These ligands have
Recently, the carbohydrates such as D-glucose,7 R,R-
trehalose,8 and D-glucosamine7b,9 have attracted a great
(1) (a) Tsuji, J . Palladium Reagents and Catalysis, Innovations in
Organic Synthesis; Wiley: New York, 1995. (b) Trost, B. M.; Van
Vranken, D. L. Chem. Rev. 1996, 96, 395. (c) J ohannsen, M.; J ørgensen,
K. A. Chem. Rev. 1998, 98, 1689. (d) Hayashi, T. J . Organomet. Chem.
1999, 576, 195. (e) Helmchen, G. J . Organomet. Chem. 1999, 576, 203.
(2) (a) Von Matt, P.; Pfaltz, A. Angew. Chem., Int. Ed. Engl. 1993,
32, 566. (b) Pre´toˆt, R.; Pfaltz, A. Angew. Chem., Int. Ed. 1998, 37, 323.
(3) (a) Sprinz, J .; Helmchen, G. Tetrahedron Lett. 1993, 34, 1769.
(b) Steinhagen, H.; Reggelin, M.; Helmchen, G. Angew. Chem., Int. Ed.
Engl. 1997, 36, 2108.
(4) (a) Dawson, G. J .; Frost, C. G.; Williams, J . M. J . Tetrahedron
Lett. 1993, 34, 3149. (b) Williams, J . M. J . Synlett 1993, 509. (c) Bower,
J . F.; J umnah, R.; Williams, A. C.; Williams, J . M. J . J . Chem. Soc.,
Perkin Trans. 1 1997, 1411.
(5) (a) Nishibayashi, Y.; Uemura, S. Synlett 1995, 79. (b) Nishiba-
yashi, Y.; Segawa, K.; Arikawa, Y.; Ohe, K.; Hidai, M.; Uemura, S. J .
Organomet. Chem. 1997, 545-546, 381. (c) Sammakia, T.; Latham, H.
A.; Schaad, D. R. J . Org. Chem. 1995, 60, 10. (d) Sammakia, T.;
Latham, H. A. J . Org. Chem. 1996, 61, 1629. (e) Stangeland, E. L.;
Sammakia, T. Tetrahedron 1997, 53, 16503. (f) Richards, C. J .;
Damalidis, T.; Hibbs, D. E.; Hursthouse, M. B. Synlett 1995, 74. (g)
Richards, C. J .; Mulvaney, A. W. Tetrahedron: Asymmetry 1996, 7,
1419. (h) Park, J .; Lee, S.; Ahn, K. H.; Cho, C.-W. Tetrahedron Lett.
1995, 36, 7263. (i) Ahn, K. H.; Cho, C.-W.; Baek, H.-H.; Park, J .; Lee,
S. J . Org. Chem. 1996, 61, 4937. (j) Zhang, W.; Adachi, Y.; Hirao, T.;
Ikeda, I. Tetrahedron: Asymmetry 1996, 7, 451. (k) Zhang, W.; Hirao,
T.; Ikeda, I. Tetrahedron Lett. 1996, 37, 4545. (l) Kudis, S.; Helmchen,
G. Angew. Chem., Int. Ed. 1998, 37, 3047.
(7) (a) Nomura, N.; Mermet-Bouvier, Y. C.; RajanBabu, T. V. Synlett
1996, 745. (b) RajanBabu, T. V.; Ayers, T. A.; Halliday, G. A.; You, K.
K.; Calabrese, J . C. J . Org. Chem. 1997, 62, 6012. (c) Barbaro, P.;
Currao, A.; Herrmann, J .; Nesper, R.; Pregosin, P. S.; Salzmann, R.
Organometallics 1996, 15, 1879. (d) Albinati, A.; Pregosin, P. S.; Wick,
K. Organometallics 1996, 15, 2419. (e) Boog-Wick, K.; Pregosin, P. S.;
Trabesinger, G. Organometallics 1998, 17, 3254. (f) Boog-Wick, K.;
Pregosin, P. S.; Wo¨rle, M.; Albinati, A. Helv. Chim. Acta 1998, 81, 1622.
(g) Selke, R.; Ohff, M.; Riepe, A. Tetrahedron 1996, 52, 15079.
(8) (a) Brown, J . M.; Cook, S. J .; Kent, A. G. Tetrahedron 1986, 42,
5097. (b) Brown, J . M.; Cook, S. J .; Kahn, R. Tetrahedron 1986, 42,
5105. (c) Gilbertson, S. R.; Chang, C.-W. T. J . Org. Chem. 1995, 60,
6226. (d) Yonehara, K.; Hashizume, T.; Ohe, K.; Uemura, S. Bull.
Chem. Soc. J pn. 1998, 71, 1967. (e) Yonehara, K.; Hashizume, T.; Mori,
K.; Ohe, K.; Uemura, S. J . Org. Chem. 1999, 64, 5593.
(6) (a) Imai, Y.; Zhang, W.; Kida, T.; Nakatsuji, Y.; Ikeda, I.
Tetrahedron Lett. 1998, 39, 4343. (b) Ogasawara, M.; Yoshida, K.;
Kamei, H.; Kato, K.; Uozumi, Y.; Hayashi, T. Tetrahedron: Asymmetry
1998, 9, 1779.
(9) Gla¨ser, B.; Kunz, H. Synlett 1998, 53.
(10) Gilbertson, S. R.; Chang, C.-W. T. J . Org. Chem. 1998, 63, 8424.
10.1021/jo990901u CCC: $18.00 © 1999 American Chemical Society
Published on Web 12/04/1999

Palladium-Catalyzed Allylic Substitution Reactions
J . Org. Chem., Vol. 64, No. 26, 1999 9375
Sch em e 1a
a
Reagents and conditions: (a) (RCO)2O, NaOMe/MeOH, rt, 1 d, or RCOCl, NaHCO3(aq), rt, 1 d; (b) PhCHO, ZnCl2, rt, 6 h; (c) Ac2O,
pyridine, rt, 1 d; (d) SnCl4, CH2Cl2, rt, 2 h; (e) K2CO3, MeOH, rt, 1 h; (e) Ph2PCl, catalytic 4-(dimethylamino)pyridine, Et3N-THF, -40
°C, 15 min.
an alkyl or aryl group at the 2-position of oxazoline and
a phosphorus atom attached to a sugar backbone through
the phosphinite linkage. Since the substituent at the
2-position in our ligand is variable, some kind of steric
effect is expected in the asymmetric induction. In this
paper, we report the synthesis of such novel phosphinite-
oxazoline chiral ligands from D-glucosamine hydrochlo-
ride (2-amino-2-deoxy-D-glucopyranoside hydrochloride),
which has been less frequently used as a source of chiral
ligands, and their application to the palladium-catalyzed
allylic substitution of allylic acetates and an allylic
carbonate.11
treated with Ph2PCl and a catalytic amount of 4-(di-
methylamino)pyridine in THF-Et3N at -40 °C to give
the desired phosphinite-oxazoline ligands 5.
Asym m etr ic Allylic Alk yla tion . We investigated the
palladium-catalyzed allylic substitution of 1,3-diphenyl-
3-acetoxyprop-1-ene (6) and ethyl 1,3-diphenylprop-2-enyl
carbonate (7) as test substrates with dimethyl malonate
using the chiral phosphinite-oxazoline ligands 5a -f (eq
1), the results being summarized in Table 1. The reaction
Resu lts a n d Discu ssion
Syn th esis of P h osph in ite-Oxazolin e Ligan ds fr om
D-Glu cosa m in e Hyd r och lor id e. The sequence of ligand
synthesis is illustrated in Scheme 1. The acylation of the
D-glucosamine hydrochloride suspended in NaOMe/
MeOH12 with (PriCO)2O, (BuiCO)2O, and (ButCO)2O
afforded the amides 1b, 1c, and 1d , respectively. N-Acyl-
D-glucosamines 1e and 1f were also prepared from the
D-glucosamine hydrochloride and PhCOCl or PhCH2COCl
in aqueous NaHCO3, respectively. Then, the protection
of hydroxy groups of the 4,6-positions and 1,3-positions
of the acylated D-glucosamines 1 with PhCHO13 and
Ac2O, respectively, gave the protected N-acyl-D-glu-
cosamines 2 as a mixture of R- and â-anomers. They were
converted to the corresponding oxazolines 3 in the
presence of anhydrous SnCl4 without affecting the ben-
zylidene acetal.14,15 Deacetylation of 3 with K2CO3 in
MeOH gave the hydroxy compounds 4, which were
Ta ble 1. P a lla d iu m -Ca ta lyzed Asym m etr ic Allylic
Alk yla tion of 6 a n d 7 Usin g Ch ir a l Liga n d s 5a -fa
sub-
strate
time
(h)
%
%
entry
L*
solvent
toluene
yieldb
eec
1
2
3
4
5
6
7
8d
6
6
6
6
6
6
7
6
5a
5b
5c
5d
5e
5f
6
6
6
6
6
18
6
0.5
81
99
82
91
74
88
84
98
96 (S)
90 (S)
95 (S)
83 (S)
94 (S)
78 (S)
95 (S)
93 (S)
toluene
toluene
toluene
toluene
toluene
toluene
toluene/
5a
5a
THFe (1:1)
a
Reactions were carried out under Ar using 6 or 7 (1.0 mmol),
dimethyl malonate (3.0 mmol), BSA [bis(trimethylsilyl)acetamide]
(3.0 mmol), KOAc (0.05 mmol), solvent (2 mL), [Pd(η3-C3H5)Cl]2
b
(0.25 mol %), and L* (0.55 mol %). Isolated yield. c The values
were measured by HPLC, and the absolute configuration was
d
determined by optical rotation.3a Carried out at rt with tetra-
(11) The preliminary results were partly reported: Yonehara, K.;
Hashizume, T.; Mori, K.; Ohe, K.; Uemura, S. Chem. Commun. 1999,
415.
(12) Inoue, Y.; Onodera, K.; Kitaoka, S.; Hirano, S. J . Am. Chem.
Soc. 1956, 78, 4722.
(13) Roth, W.; Pigman, W. J . Am. Chem. Soc. 1960, 82, 4608.
(14) Srivastava, V. K. Carbohydr. Res. 1982, 103, 286.
(15) Kiso, M.; Anderson, L. Carbohydr. Res. 1985, 136, 309. When
FeCl3, used in this reference, was employed instead of SnCl4, the
benzylidene group was deprotected before the formation of the oxazo-
line ring.
butylammonium fluoride (3 mmol) as a base instead of BSA and
KOAc. e Solvent (6 mL).
was carried out in toluene unless otherwise noted using
a catalyst generated in situ by mixing 0.25 mol % [Pd(η3-
C3H5)Cl]2 with 0.55 mol % chiral ligand. The ligands 5a -f
were effective in the allylic alkylation of the acetate 6
with the malonate in the presence of N,O-bis(trimethyl-

9376 J . Org. Chem., Vol. 64, No. 26, 1999
Yonehara et al.
silyl)acetamide (BSA)16 (entries 1-6). The best result
(96% ee) was achieved using the ligand 5a having the
smallest alkyl group (R) on the oxazoline (entry 1). The
chiral ligands 5c and 5e also gave good enantioselectivi-
ties, 95% and 94% ee, respectively (entries 3 and 5). The
ligands 5d and 5f having bulky substituents gave lower
ee’s (83% and 78%) (entries 4 and 6). The sterically less
demanding substituents such as Me and Bui on the
oxazoline are most effective in this reaction. The reaction
of the carbonate 7 instead of 6 gave almost the same
enantioselectivity (95% ee) in the presence of the ligand
5a (entry 7). Tetrabutylammonium fluoride instead of
BSA can promote the reaction,17 albeit with slightly lower
selectivity (entry 8).18
It is known to be more difficult to control the enantio-
selective substitution of cyclic and 1,3-dimethylallylic
systems.19 Although the highest enantioselectivity in such
systems has been reported by Trost21 and Osborn,22 the
development of enantioselective catalysts for this class
of substrates remains challenging. We applied the chiral
ligands 5a -f to the palladium-catalyzed allylic alkylation
of 3-acetoxycyclohexene (8) (eq 2). The reaction proceeded
F igu r e 2. Schematic structure of the metal complex of the
phosphinite-oxazoline ligand.
cyclic substrates. Next, the alkylation of 4-acetoxypent-
2-ene (9) was investigated (eq 3). The results are listed
Ta ble 3. P a lla d iu m -Ca ta lyzed Asym m etr ic Allylic
Alk yla tion of 9 Usin g Ch ir a l Liga n d sa
entry
L*
time (h)
% yieldb
% eec
1
2
3
5a
5d
5f
12
24
12
69
21
84
57
57
48
a
Reactions were carried out under Ar using 9 (1.0 mmol),
dimethyl malonate (3.0 mmol), BSA [bis(trimethylsilyl)acetamide]
(3.0 mmol), KOAc (0.05 mmol), THF (2 mL), [Pd(η3-C3H5)Cl]2 (0.5
Ta ble 2. P a lla d iu m -Ca ta lyzed Asym m etr ic Allylic
Alk yla tion of 8 Usin g Ch ir a l Liga n d sa
b
mol %), and L* (1.1 mol %). Isolated yield. c The values were
entry
L*
time
% yieldb
% eec
measured by 1H NMR with Eu(hfc)3.
1
2
3
4
5a
5b
5c
5f
7 h
1 d
1 d
4 d
88
85
62
47
74 (R)
70 (R)
68 (R)
72 (R)
in Table 3. Among the ligands examined, 5a afforded
moderate selectivity (57% ee). The enantioselectivity
obtained here does not exceed the reported value in the
same substrate using previously developed phosphine-
oxazoline ligands.2a,9
a
Reactions were carried out under Ar using 8 (1.0 mmol),
dimethyl malonate (3.0 mmol), BSA [bis(trimethylsilyl)acetamide]
(3.0 mmol), KOAc (0.05 mmol), THF (2 mL), [Pd(η3-C3H5)Cl]2 (0.5
mol %), and L* (1.1 mol %). Isolated yield. c The values were
b
To explain the stereoselectivity obtained, a schematic
structure of the coordination center is shown in Figure
2. The second quadrant is most sterically occupied by the
phenyl group, and the fourth quadrant is the second most
sterically occupied by the substituent on the oxazoline
ring. The extent of the steric hindrance in these quad-
rants has an influence on the enantioselectivity. We
suppose that a nucleophilic attack occurs predominantly
at the allyl terminus trans to the Pd-P bond in a
π-allylpalladium intermediate.3b,23 Since the alkylated
product (S)-10 was obtained as a major enantiomer in
the reaction of 6 and 7 with the malonate, the reaction
probably proceeds through intermediate A rather than
intermediate B in the equilibrium as shown in Figure
3.24 The steric repulsion in the intermediate A between
a phenyl moiety on the phosphorus atom and a phenyl
group of the π-allyl moiety seems to be smaller than that
in B. Therefore, the major contribution of the intermedi-
measured by 1H NMR with Eu(hfc)3, and the absolute configura-
tion was determined by optical rotation.20
in THF at 0 °C using 0.5 mol % [Pd(η3-C3H5)Cl]2 and 1.1
mol % chiral ligand. Typical results are shown in Table
2. The chiral ligand 5a gave the highest enantiomeric
excess (74% ee). Other chiral ligands, 5b, 5c, and 5f, gave
almost the same enantioselectivity (68-72% ee). In the
case of 5f, the reaction was not complete even after 4
days. The chiral ligands 5d and 5e were also examined,
but the reactions were sluggish. These results show that
our ligand structure having no additional chiral auxil-
iaries can effectively control the enantioselectivity in
(16) Trost, B. M.; Murphy, D. J . Organometallics 1985, 4, 1143.
(17) Clark, J . H. Chem. Rev. 1980, 80, 429.
(18) This reaction did not proceed at 0 °C.
(19) It was reported that the original chiral diphenylphosphino-
oxazolines (refs 2-4) gave almost racemic products in allylic substitu-
tion of 3-acetoxycyclohexene. The reasonable enantioselectivity in the
reaction was achieved by employing chiral diarylphosphinooxazoline
with a stereogenic phosphorus center20 or with a planar chirality.5l
(20) Sennhenn, P.; Gabler, B.; Helmchen, G. Tetrahedron Lett. 1994,
35, 8595.
(21) (a) Trost, B. M.; Breit, B.; Peukert, S.; Zambrano, J .; Ziller, J .
W. Angew. Chem., Int. Ed. Engl. 1995, 34, 2386. (b) Trost, B. M.;
Krueger, A. C.; Bunt, R. C.; Zambrano, J . J . Am. Chem. Soc. 1996,
118, 6520. (c) Trost, B. M.; Bunt, R. C. J . Am. Chem. Soc. 1994, 116,
4089.
(23) The phosphorus atom is known as a better π-acceptor than the
nitrogen atom in a π-allylpalladium complex bearing a P-N bidentate
ligand. For examples, see: (a) Åkermark, B.; Krakenberger, B.;
Hansson, S.; Vitagliano, A. Organometallics 1987, 6, 620. (b) Blo¨chl
P. E.; Togni, A. Organometallics 1996, 15, 4125. (c) Pen˜a-Cabrera, E.;
Norrby, P.-O.; Sjo¨gren, M.; Vitagliano, A.; De Felice, V.; Oslob, J .; Ishii,
S.; O’Neill, D.; Åkermark, B.; Helquist, P. J . Am. Chem. Soc. 1996,
118, 4299.
(24) The equilibrium between A and B should include not only π-σ-
π-allyl rotation but also the ligand rotation through the dissociation
of the coordinated nitrogen; for an example, see: Gogoll, A.; O¨ rnebro,
J .; Grennberg, H.; Ba¨ckvall, J .-E. J . Am. Chem. Soc. 1994, 116, 3631.
(22) Dierkes, P.; Ramdeehul, S.; Barloy, L.; De Cian, A.; Fischer,
J .; Kamer, P. C. J .; Van Leeuwen, P. W. N. M.; Osborn, J . A. Angew.
Chem., Int. Ed. 1998, 37, 3116.

Palladium-Catalyzed Allylic Substitution Reactions
J . Org. Chem., Vol. 64, No. 26, 1999 9377
Ta ble 4. P a lla d iu m -Ca ta lyzed Asym m etr ic Allylic
Alk yla tion of 13 Usin g Ch ir a l Liga n d sa
entry
L*
% yieldb
14:15c,d
% eee
1
2
5a
5d
74
85
25:75
11:89
75 (S)
90 (S)
a
Reactions were carried out under Ar using 13 (1.0 mmol),
dimethyl malonate (3.0 mmol), BSA [bis(trimethylsilyl)acetamide]
(3.0 mmol), KOAc (0.05 mmol), THF (2 mL), [Pd(η3-C3H5)Cl]2 (0.5
b
mol %), and L* (1.1 mol %). Isolated yield of 14 and 15. c The
d
ratios were determined by 1H NMR. For 1H NMR data, see ref
27. e The values and absolute configuration were determined by
HPLC.28i
F igu r e 3. A plausible reaction course in the reaction of 6 and
7.
experimental details on the ratio of intermediates C and
D and the reactivity of C and D were obtained, its ratio
and the formation of the olefin-palladium complex via
the nucleophilic attack followed by the rotation of the
cyclohexenyl26 group might be crucial in enantiodiffer-
entiation.
Next, we examined the regio- and stereoselective allylic
alkylation of cinnamyl acetate (13) with dimethyl mal-
onate in the presence of the palladium catalyst and chiral
ligands, the products being a mixture of regioisomers of
14 and 15 (eq 4). There are several reports28 on the regio-
ate A might be established in the equilibrium. In the
intermediate A, however, there is an unfavorable inter-
action between R on the oxazoline ring and another
phenyl group of the π-allyl moiety. The larger the R group
on the oxazoline ring, the less favorable is intermediate
A. Thereby, the ratio of two diastereomeric intermediates,
A to B, is decreased to give a lower enantioselectivity.
In the reaction of 3-acetoxycyclohexene (8), the result-
ing cyclic allyl ligand has anti,anti-configuration as in
intermediates C and D shown in Figure 4. Different from
and stereoselective reaction of this substrate using a
variety of catalysts, but the regioselectivity for 14 is quite
low using a Pd catalyst and P,N-bidentate ligands27,29
except a recent report by Pfaltz and a co-worker.2b They
claimed that both the electronegative substituents at the
coordinating P atom and the steric interaction which
affects the ratio of π-allylpalladium intermediates are
important to obtain the product in high regioselectivity
(14:15 ) 76:24).2b In our phosphinite-oxazoline ligands
the P atom seems more electropositive than that of
phosphine-oxazoline ligands. We performed the reaction
in THF at room temperature using 0.5 mol % [Pd(η3-
C3H5)Cl]2 and 1.1 mol % chiral ligands. As shown in Table
4, unfortunately, the regioselectivity for 14 was not high
in our case. Thus, the chiral ligand 5a which was
expected to give the highest branch:normal ratio gave
products 14 with 75% ee and 15 in a ratio of 25:75. The
F igu r e 4. A plausible reaction course in the reaction of 8.
the diphenyl-substituted case of 6 and 7, this anti,anti-
configuration lacks the steric interaction from both the
phenyl ring on the P atom and the R group on the
oxazoline ring in both intermediates. In fact, the observed
enantioselectivities of the product are in the range of 68-
74% ee irrespective of the nature of R as shown in Table
2. The R configuration of the major enantiomeric product
shows that the product can arise by reaction at the allylic
carbon trans to the P atom in the intermediate C, which
is also postulated in the case of the acyclic substrate. The
intermediates C and D might be produced by the oxida-
tive addition (ionization step) via four diastereomeric
olefin-palladium complexes, respectively.25 Although no
(26) The hydrogen atom on the sp3 carbon center formed by
nucleophilic attack should sterically interact with the R group in
clockwise rotational motion of the cyclohexenyl group from intermedi-
ate B. There is no such interaction in the counterclockwise motion via
intermediate C. The importance of the rotational motion has been
suggested by Brown,27 Osborn,22 and Helmchen.5l
(27) Brown, J . M.; Hulmes, D. I.; Guiry, P. J . Tetrahedron 1994,
50, 4493.
(28) [Mo]: (a) Trost, B. M.; Lautens, M. Tetrahedron 1987, 43, 4817.
(b) Trost, B. M.; Hachiya, I. J . Am. Chem. Soc. 1998, 120, 1104. (c)
Glorius, F.; Pfaltz, A. Org. Lett. 1999, 1, 141. [Ru]: (d) Kondo, T.; Ono,
H.; Satake, N.; Mitsudo, T.; Watanabe, Y. Organometallics 1995, 14,
1945. [Pd]: Reference 2b. (e) Hayashi, T.; Kawatsura, M.; Uozumi, Y.
J . Am. Chem. Soc. 1998, 120, 1681. [W]: (f) Lehmann, J .; Lloyd-J ones,
G. C. Tetrahedron 1995, 51, 8863. (g) Lloyd-J ones, G. C.; Pfaltz, A.
Angew. Chem., Int. Ed. Engl. 1995, 34, 462. [Ir]: (h) Takeuchi, R.;
Kashio, M. J . Am. Chem. Soc. 1998, 120, 8647. (i) J anssen, J . P.;
Helmchen, G. Tetrahedron Lett. 1997, 38, 8025. (j) Bartels, B.;
Helmchen, G. Chem. Commun. 1999, 741.
(25) Two of the four diastereomeric complexes lead to complex C,
and the others to complex D. Trost et al. suggested the importance of
such ionization steps for the enantioselection in the allylic substitution
of cyclic substrates; see: Trost, B. M.; Van Vranken, D. L.; Bingel, C.
J . Am. Chem. Soc. 1992, 114, 9327.
(29) Vyskocˇil, Sˇ.; Smrcˇina, M.; Hanusˇ, V.; Pola´sˇek, M.; Kocˇovsky´,
P. J . Org. Chem. 1998, 63, 7738.

9378 J . Org. Chem., Vol. 64, No. 26, 1999
Yonehara et al.
chiral ligand 5d which has a bulky substituent gave a
lower ratio of 14 to 15 (11:89), but with a higher level of
enantioselectivity in 14 (90% ee). The plausible interme-
diates in the alkylation of 13 are illustrated in Figure 5.
The predominant formation of the linear product 15
might suggest that intermediate F is most favored. The
absolute configuration of the branched product 14 was
(S), which appeared to stem from an intermediate E1.
As in the case of 3-acetoxycyclohexene, the hydrogen
atom on the sp3 carbon of an alkene-Pd complex formed
by nucleophilic attack on the intermediate E2 followed
by the clockwise rotation of cinnamyl group should
sterically interact with the R group of the oxazoline ring,
while there is no such interaction in the alkene-Pd
complex obtained from the intermediate E1 with the
counterclockwise rotation. Thus, the (S) product becomes
predominant.
Asym m etr ic Allylic Am in a tion . Finally, we carried
out the palladium-catalyzed allylic amination of the
carbonate 7 (eq 5). Typical results are shown in Table 5.
Ta ble 5. P a lla d iu m -Ca ta lyzed Asym m etr ic Allylic
Am in a tion of 7 Usin g Ch ir a l Liga n d s 5a -fa
entry
L*
% yield
% eeb
1
2
3
4
5
6
5a
5b
5c
5d
5e
5f
78
57
72
48
86
47
94 (R)
87 (R)
95 (R)
69 (R)
86 (R)
87 (R)
a
Reactions were carried out under Ar using 7 (0.33 mmol),
benzylamine (1.0 mmol), toluene (2 mL), [Pd(η3-C3H5)Cl]2 (1.5 mol
F igu r e 5. A plausible reaction course in the reaction of 13.
%), and L* (3.3 mol %). The value was measured by HPLC,34
b
and the absolute configuration was determined by optical rota-
strate. The rigidity of an oxazoline moiety in our ligands
presumably influences the enantiodifferential course of
reactions. Further application of the ligands 5a -f and
other ligands without benzylidene protection to other
asymmetric catalytic reactions will be reported in due
course.
tion.30
When benzylamine was used as a nucleophile, the
highest enantiomeric excess (95% ee) was observed using
the chiral ligand 5c (R ) Bui). Almost the same level of
enantioselectivity (94% ee) was observed using the chiral
ligand 5a . The absolute stereochemistry is consistent
with the case of a carbon nucleophile. The absolute
configuration of the amination product 16 lends support
to the mechanism of this allylic substitution via the
intermediate A (see Figure 3).
Exp er im en ta l Section
Gen er a l P r oced u r es. Tetrahydrofuran (THF) and diethyl
ether were distilled from sodium benzophenone ketyl under
argon. Dichloromethane, N,N-dimethylformamide (DMF), and
triethylamine were distilled from calcium hydride. The NMR
spectra were measured for solutions in CDCl3 with Me4Si as
an internal standard (1H and 13C) or with P(OMe)3 as an
external standard (31P). Melting points are uncorrected. Ele-
mental analyses were performed at the Microanalytical Center
of Kyoto University. N-Acetyl-D-glucosamine (1a ) is com-
mercially available. N-Isopropyl-D-glucosamine (1b ), N-iso-
valeryl-D-glucosamine (1c), N-trimethylacetyl-D-glucosamine
(1d ), N-benzoyl-D-glucosamine (1e), and N-phenylacetyl-D-
glucosamine (1f) were prepared by N-acylation of commercial
D-glucosamine hydrochloride with acid anhydride or acid
chloride according to literature procedures.12 1,3-Diphenyl-3-
acetoxyprop-1-ene (6),30 ethyl 1,3-diphenylprop-2-enyl carbon-
ate (7),30 and 4-acetoxypent-2-ene (9)31 were prepared accord-
Con clu sion
We were successful in the preparation of the novel
chiral phosphinite-oxazoline ligands 5a -f from a natu-
ral D-glucosamine hydrochloride. These were effective
ligands for the palladium-catalyzed enantioselective al-
lylic alkylation and amination reactions. In previously
reported phosphine-oxazoline ligands, a phosphorus
atom is bound to an alkyl chain or an aromatic ring in
the 2-position of oxazoline. In our ligands, the substitu-
ents at the 2-position are variable, and the steric effect
of the substituents is remarkable. Although the enantio-
selectivities reported here are almost comparable to the
level of ee achieved by original chiral phosphine-oxazo-
line ligands, it is noted that our ligands without further
modification furnish good selectivity in the cyclic sub-
(30) Hayashi, T.; Yamamoto, A.; Ito, Y.; Nishioka, E.; Miura, H.;
Yanagi, K. J . Am. Chem. Soc. 1989, 111, 6301.
(31) Von Matt, P.; Loiseleur, O.; Koch, G.; Pfaltz, A.; Lefeber, C.;
Feucht, T.; Helmchen, G. Tetrahedron: Asymmetry 1994, 5, 573.

Palladium-Catalyzed Allylic Substitution Reactions
J . Org. Chem., Vol. 64, No. 26, 1999 9379
ing to literature procedures. 3-Acetoxycyclohexene (8) was
prepared by the reduction of 2-cyclohexen-1-one with NaBH4
and CeCl3‚7H2O in MeOH32 and acetylation with Ac2O. The
spectral data of alkylated products 10,33 11,33 12,33 14,27 and
1527 and aminated product 1630 are reported in previous
papers.
ppm; 13C NMR (75 MHz, CDCl3) δ 63.7, 68.5, 69.0, 74.3, 79.0,
102.1, 103.6, 126.4, 128.3, 128.4, 128.5, 129.3, 132.3, 137.1,
164.5 ppm; IR (KBr) 1637 cm-1. Anal. Calcd for C20H19NO5:
C, 67.98; H, 5.42; N, 3.96. Found: C, 67.70; H, 5.43; N, 4.08.
2-Ben zyl-4,5-(4,6-O-b en zylid en e-1,2-d id eoxy-r-D-glu -
cop yr a n o)-[2,1-d ]-2-oxa zolin e (4f): 92% yield, a white solid;
mp 156.0-157.0 °C; [R]20 ) +114.3° (c ) 0.25, CHCl3); 1H
Gen er a l P r oced u r e for th e Syn th esis of 2-Alk yl- or
-Ar yl-4,5-(4,6-O-ben zyliden e-1,2-dideoxy-r-D-glu copyr an o)-
[2,1-d ]-2-oxa zolin e (4). To a solution of 3a (0.552 g, 1.65
mmol) in MeOH (30 mL) and CHCl3 (10 mL) was added K2CO3
(140 mg, 1 mmol), and the mixture was stirred for 1 h. After
the solvent was removed under reduced pressure, the residue
was subjected to column chromatography on SiO2 with CHCl3/
acetone (v/v, 1:3) as an eluent to give 2-methyl-4,5-(4,6-O-
benzylidene-1,2-dideoxy-R-D-glucopyrano)-[2,1-d]-2-oxazoline
(4a ) (0.441 g, 1.51 mmol, 93%) as a white solid: mp 168.1-
169.0 °C; [R]20D ) +29.2° (c ) 0.25, CHCl3); 1H NMR (300 MHz,
CDCl3) δ 1.91 (d, J ) 2.9 Hz, 3H), 3.59-3.76 (m, 4H), 3.94 (dt,
J ) 2.9, 6.5 Hz, 1H), 4.37 (dd, J ) 3.1, 9.0 Hz, 1H), 5.59 (s,
1H), 5.97 (d, J ) 6.5 Hz, 1H), 7.30-7.49 (m, 5H) ppm; 13C NMR
(67.5 MHz, CDCl3) δ 13.9, 63.9, 68.3, 68.8, 73.9, 78.5, 101.7,
103.6, 126.2, 128.0, 129.0, 137.7, 166.5 ppm; IR (KBr) 1654
cm-1; HRMS (FAB) calcd for C15H18NO5 (M + H+) 292.1185,
found 292.1192. Anal. Calcd for C15H17NO5: C, 61.85; H, 5.88;
N, 4.81; O, 27.46. Found: C, 61.23; H, 5.92; N, 4.82; O, 27.08.
2-Isop r op yl-4,5-(4,6-O-ben zylid en e-1,2-d id eoxy-r-D-glu -
cop yr a n o)-[2,1-d ]-2-oxa zolin e (4b): 73% yield, a white solid;
mp 173.0-173.9 °C; [R]20D ) +97.8° (c ) 0.25, CHCl3); 1H NMR
(300 MHz, CDCl3) δ 1.11 (d, J ) 7.0 Hz, 3H), 1.13 (d, J ) 7.0
Hz, 3H), 2.59 (sept, J ) 7.0 Hz, 1H), 3.61-3.76 (m, 4H), 3.96
(dd, J ) 5.1, 7.7 Hz, 1H), 4.38 (dd, J ) 4.2, 10.3 Hz, 1H), 5.59
(s, 1H), 5.96 (d, J ) 7.7 Hz, 1H), 7.33-7.50 (m, 5H) ppm; 13C
NMR (67.5 MHz, CDCl3) δ 19.0, 19.2, 28.4, 63.0, 68.4, 68.7,
74.0, 78.8, 101.6, 103.2, 126.2, 128.1, 129.0, 137.1, 173.2 ppm;
IR (KBr) 1653 cm-1; HRMS (FAB) calcd for C17H22NO5 (M +
H+) 320.1498, found 320.1499. Anal. Calcd for C17H21NO5: C,
63.94; H, 6.63; N, 4.39; O, 25.05. Found: C, 63.43; H, 6.60; N,
4.41; O, 25.43.
D
NMR (300 MHz, CDCl3) δ 3.44-3.72 (m, 6H), 3.95 (dd, J )
5.9, 7.3 Hz, 1H), 4.34 (dd, J ) 2.8, 9.5 Hz, 1H), 5.58 (s, 1H),
5.93 (d, J ) 7.3 Hz, 1H), 7.23-7.43 (m, 10H) ppm; 13C NMR
(67.5 MHz, CDCl3) δ 35.0, 64.0, 68.3, 68.5, 74.2, 78.4, 101.7,
104.0, 126.1, 127.1, 128.1, 128.6, 128.9, 129.0, 134.1, 136.9,
167.8 ppm; IR (KBr) 1648 cm-1. Anal. Calcd for C21H21NO5:
C, 68.65; H, 5.76; N, 3.81; O, 21.77. Found: C, 68.37; H, 5.71;
N, 3.78; O, 21.77.
Gen er al P r ocedu r e for th e Syn th esis of Diph en ylph os-
p h in ite 5. To a solution of 4a (0.291 g, 1 mmol) and a catalytic
amount of 4-(dimethylamino)pyridine (10 mg) in 10 mL of
degassed THF/Et3N (v/v, 2:1) was slowly added chlorodiphen-
ylphosphine (0.2 mL, 1.1 mmol) at -40 °C, and the mixture
was stirred at this temperature. After 15 min, the mixture
was concentrated to dryness, and the residue was subjected
to column chromatography on Al2O3 with degassed toluene/
CH2Cl2 (v/v, 1:2) as an eluent to give 2-methyl-4,5-(4,6-O-
benzylidene-3-O-(diphenylphosphino)-1,2-dideoxy-R-D-glucopy-
rano)-[2,1-d]-2-oxazoline (5a ) (0.301 g, 0.633 mmol, 63%) as a
white solid: mp 169.1-169.6 °C; [R]20 ) - 75.7° (c ) 0.25,
D
CHCl3); 1H NMR (270 MHz, CDCl3) δ 2.05 (d, J ) 1.1 Hz, 3H),
3.61-3.69 (m, 2H), 3.76 (t, J ) 8.5 Hz, 1H), 4.23-4.32 (m, 2H),
4.36 (dd, J ) 3.3, 8.5 Hz, 1H), 5.35 (s, 1H), 5.98 (d, J ) 7.4
Hz, 1H), 7.23-7.53 (m, 15H) ppm; 13C NMR (67.5 MHz, CDCl3)
δ 14.3, 62.9, 68.6, 69.4 (d, J ) 5.2 Hz), 79.6 (d, J ) 3.6 Hz),
82.3 (d, J ) 20.2 Hz), 101.2, 102.2, 126.0-136.9 (16 carbons),
141.9 (d, J ) 21.3 Hz), 142.2 (d, J ) 16.4 Hz), 165.0 ppm; 31
P
NMR (161.9 MHz, CDCl3) δ 114.5 ppm; IR (KBr) 1665, 1433
cm-1. Anal. Calcd for C27H26NO5P: C, 68.20; H, 5.51; N, 2.95;
P, 6.51. Found: C, 68.12; H, 5.61; N, 2.69; P, 6.69.
2-Isop r op yl-4,5-(4,6-O-ben zylid en e-3-O-(d ip h en ylp h os-
p h in o)-1,2-d id e oxy-r-D-glu cop yr a n o)-[2,1-d ]-2-oxa zo-
2-Isobu tyl-4,5-(4,6-O-ben zylid en e-1,2-d id eoxy-r-D-glu -
lin e (5b): 54% yield, a white solid; mp 169.0-169.5 °C; [R]20
cop yr a n o)-[2,1-d ]-2-oxa zolin e (4c): 80% yield, a white solid;
D
) -49.4° (c ) 0.25, CHCl3); 1H NMR (400 MHz, CDCl3) δ 1.209
(d, J ) 6.8 Hz, 3H), 1.213 (d, J ) 6.8 Hz, 3H), 2.63 (sept, J )
6.8 Hz, 1H), 3.57 (dt, J ) 4.9, 9.8 Hz, 1H), 3.64 (t, J ) 9.8 Hz,
1H), 3.74 (t, J ) 9.8 Hz, 1H), 4.22-4.43 (m, 2H), 4.37 (dd, J )
4.9, 9.8 Hz, 1H), 5.33 (s, 1H), 5.96 (d, J ) 7.3 Hz, 1H), 7.23-
7.58 (m, 15H) ppm; 13C NMR (100 MHz, CDCl3) δ 19.2, 19.3,
28.5, 62.9, 68.6, 69.1 (d, J ) 5.0 Hz), 79.9 (d, J ) 3.7 Hz), 82.3
(d, J ) 19.9 Hz), 101.1, 102.0, 126.0-136.9 (16 carbons), 142.0
(d, J ) 19.9 Hz), 142.3 (d, J ) 14.3 Hz), 171.9 ppm; 31P NMR
mp 138.0-139.5 °C; [R]20 ) +101.3° (c ) 0.25, CHCl3); 1H
D
NMR (270 MHz, CDCl3) δ 0.86 (d, J ) 6.9 Hz, 3H), 0.88 (d, J
) 7.1 Hz, 3H), 2.00 (m, 1 H), 2.16 (d, J ) 7.4 Hz, 2H), 3.56-
3.77 (m, 2H), 3.94 (dd, J ) 5.5, 7.7 Hz, 1H), 4.38 (dd, J ) 3.6,
9.6 Hz, 1H), 5.59 (s, 1H), 5.96 (d, J ) 7.7 Hz, 1H), 7.33-7.50
(m, 5H) ppm; 13C NMR (75 MHz, CDCl3) δ 21.1, 22.2, 26.0,
37.1, 64.0, 68.5, 68.8, 74.2, 78.6, 101.8, 103.5, 126.3, 128.2,
129.1, 137.2, 168.8 ppm; IR (KBr) 1654 cm-1; HRMS (FAB)
calcd for C18H24NO5 (M + H+) 334.1654, found 334.1654. Anal.
Calcd for C18H23NO5: C, 64.85; H, 6.95; N, 4.20; O, 24.00.
Found: C, 64.43; H, 7.05; N, 4.24; O, 24.00.
(161.9 MHz, CDCl3) δ 114.8 ppm; IR (KBr) 1658, 1433 cm-1
.
Anal. Calcd for C29H30NO5P: C, 69.17; H, 6.01; N, 2.78; P, 6.15.
Found: C, 69.08; H, 6.08; N, 2.76; P, 6.44.
2-ter t-Bu tyl-4,5-(4,6-O-ben zylid en e-1,2-d id eoxy-r-D-glu -
cop yr a n o)-[2,1-d ]-2-oxa zolin e (4d ): 97% yield, a white solid;
mp 138.0-139.0 °C; [R]20D ) +75.1° (c ) 0.25, CHCl3); 1H NMR
(270 MHz, CDCl3) δ 1.23 (s, 9H), 3.61-3.77 (m, 4H), 3.95 (dd,
J ) 5.2, 7.7 Hz, 1H), 4.39 (dd, J ) 4.1, 10.4 Hz, 1H), 5.59 (s,
1H), 5.94 (d, J ) 7.7 Hz, 1H), 7.35-7.51 (m, 5H) ppm; 13C NMR
(67.5 MHz, CDCl3) δ 27.3, 33.6, 63.3, 68.5, 69.1, 74.1, 79.2,
101.6, 103.0, 126.2, 128.1, 129.0, 137.0, 174.9 ppm; IR (KBr)
1647 cm-1; HRMS (FAB) calcd for C18H24NO5 (M + H+)
334.1654, found 334.1649. Anal. Calcd for C18H23NO5: C,
64.85; H, 6.95; N, 4.20; O, 24.00. Found: C, 64.24; H, 6.89; N,
3.84; O, 24.05.
2-Isobu tyl-4,5-(4,6-O-ben zylid en e-3-O-(d ip h en ylp h os-
p h in o)-1,2-d id e oxy-r-D-glu cop yr a n o)-[2,1-d ]-2-oxa zo-
lin e (5c): 28% yield, a white solid; mp 142.8-143.2 °C; [R]20
D
) -28.1° (c ) 0.25, CHCl3); 1H NMR (300 MHz, CDCl3) δ 0.98
(d, J ) 6.7 Hz, 3H), 0.99 (d, J ) 6.7 Hz, 3H), 2.08 (sept, J )
6.7 Hz, 1H), 2.20-2.23 (m, 2H), 3.59-3.69 (m, 2H), 3.75 (t, J
) 8.6 Hz, 1H), 4.21-4.31 (m, 2H), 4.35 (dd, J ) 3.6, 9.3 Hz,
1H), 5.34 (s, 1H), 5.96 (d, J ) 7.3 Hz, 1H), 7.24-7.53 (m, 15H)
ppm; 13C NMR (75 MHz, CDCl3) δ 22.5, 26.1, 37.3, 63.1, 68.6,
69.2 (d, J ) 5.0 Hz), 79.9 (d, J ) 3.7 Hz), 82.6 (d, J ) 19.9
Hz), 101.2, 102.0, 126.0-136.9 (16 carbons), 142.0 (d, J ) 19.9
Hz), 142.3 (d, J ) 14.3 Hz), 167.4 ppm; 31P NMR (161.9 MHz,
CDCl3) δ 114.7 ppm; IR (KBr) 1658, 1434 cm-1. Anal. Calcd
for C30H32NO5P: C, 69.62; H, 6.23; N, 2.71; P, 5.98. Found:
C, 69.31; H, 6.23; N, 2.60; P, 5.80.
2-P h en yl-4,5-(4,6-O-b en zylid en e-1,2-d id eoxy-r-D-glu -
cop yr a n o)-[2,1-d ]-2-oxa zolin e (4e). This compound was
recrystallized from CHCl3 and hexane: 81% yield, a white
solid; mp 228.0-229.0 °C; [R]20 ) +141.7° (c ) 0.25, CHCl3);
D
1H NMR (300 MHz, CDCl3) δ 3.70-3.84 (m, 3H), 3.96 (dd, J
) 5.5, 8.4 Hz, 1H), 4.24 (dd, J ) 5.5, 7.7 Hz, 1H), 4.43 (m,
1H), 5.63 (s, 1H), 6.17 (d, J ) 7.7 Hz, 1H), 7.14-7.97 (m, 10H)
2-ter t-Bu tyl-4,5-(4,6-O-ben zylid en e-3-O-(d ip h en ylp h os-
p h in o)-1,2-d id e oxy-r-D-glu cop yr a n o)-[2,1-d ]-2-oxa zo-
lin e (5d ): 68% yield, a white solid; mp 168.1-169.0 °C; [R]20
D
) -26.5° (c ) 0.25, CHCl3); 1H NMR (400 MHz, CDCl3) δ 1.24
(s, 9H), 3.57 (dt, J ) 4.7, 9.8 Hz, 1H), 3.64 (t, J ) 9.8 Hz, 1H),
3.73 (dd, J ) 8.3, 9.8 Hz, 1H), 4.20-4.30 (m, 2H), 4.36 (dd, J
) 4.7, 9.8 Hz, 1H), 5.32 (s, 1H), 5.95 (d, J ) 7.3 Hz, 1H), 7.24-
7.53 (m, 15H) ppm; 13C NMR (75 MHz, CDCl3) δ 27.3, 33.5,
(32) Luche, J .-L.; Rodriguez-Hahn, L.; Crabbe´, P. J . Chem. Soc.,
Chem. Commun. 1978, 601.
(33) Kang, J .; Cho, W. O.; Cho, H. G. Tetrahedron: Asymmetry 1994,
5, 1347.

9380 J . Org. Chem., Vol. 64, No. 26, 1999
Yonehara et al.
63.0, 68.7, 69.2 (d, J ) 5.6 Hz), 80.0 (d, J ) 3.1 Hz), 82.5 (d,
J ) 20.6 Hz), 101.1, 102.3, 126.0-136.9 (16 carbons), 142.0
(d, J ) 19.3 Hz), 142.3 (d, J ) 14.9 Hz), 174.0 ppm; 31P NMR
Allylic Alk yla tion of 3-Acetoxycycloh exen e (8). The
chiral ligand 5a (5.24 mg, 11 × 10-3 mmol) and [Pd(η3-C3H5)-
Cl]2 (1.82 mg, 5.0 × 10-3 mmol) were dissolved in degassed
THF (0.5 mL) under Ar, and the solution was stirred at room
temperature. After 30 min, the acetate 8 (0.14 g, 1.0 mmol) in
THF (1.5 mL) was added, and the solution was stirred for 30
min. N,O-Bis(trimethylsilyl)acetamide (0.74 mL, 3 mmol),
dimethyl malonate (0.35 mL, 3 mmol), and KOAc (5 mg) were
added in this order at 0 °C, and the stirring was continued at
this temperature. After 7 h the reaction mixture was added
to saturated NH4Cl(aq) and extracted with Et2O three times,
and the extract was dried over MgSO4. Solvent was removed
under 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 compound 11 (0.17 g, 0.88 mmol,
88%). The enantiomeric excess was determined by Eu(hfc)3.
The absolute configuration was determined by optical rota-
tion.20
(161.9 MHz, CDCl3) δ 115.4 ppm; IR (KBr) 1648, 1434 cm-1
.
Anal. Calcd for C30H32NO5P: C, 69.62; H, 6.23; N, 2.71; P, 5.98.
Found: C, 69.37; H, 6.20; N, 2.73; P, 6.25.
2-P h en yl-4,5-(4,6-O-b en zylid en e-3-O-(d ip h en ylp h os-
p h in o)-1,2-d id e oxy-r-D-glu cop yr a n o)-[2,1-d ]-2-oxa zo-
lin e (5e): 62% yield, a white solid; mp 176.0-176.6 °C; [R]20
D
) +37.6° (c ) 0.25, CHCl3); 1H NMR (400 MHz, CDCl3) δ 3.65-
3.75 (m, 2H), 3.80 (t, J ) 8.8 Hz, 1H), 4.39-4.47 (m, 3H), 5.36
(s, 1H), 6.17 (d, J ) 7.3 Hz, 1H), 7.27-8.00 (m, 20H) ppm; 13
C
NMR (100 MHz, CDCl3) δ 63.2, 68.6, 69.6 (d, J ) 5.5 Hz), 79.8
(d, J ) 3.6 Hz), 82.5 (d, J ) 22.0 Hz), 101.3, 102.7, 126.0-
136.9 (22 carbons), 141.9 (d, J ) 18.4 Hz), 142.3 (d, J ) 16.5
Hz), 163.7 ppm; 31P NMR (161.9 MHz, CDCl3) δ 115.9 ppm;
IR (KBr) 1634, 1434 cm-1. Anal. Calcd for C32H28NO5P: C,
71.50; H, 5.25; N, 2.61; P, 5.76. Found: C, 71.48; H, 5.14; N,
2.41; P, 6.04.
Allylic Alk yla t ion of 4-Acet oxyp en t -2-en e (9). The
acetate 9 (0.13 g, 1.0 mmol) was used instead of 8, and the
product was purified by column chromatography on silica gel
with hexanes/Et2O (v/v, 5:1) as an eluent to give compound
12 (0.14 g, 0.69 mmol, 69%). The enantiomeric excess was
2-Ben zyl-4,5-(4,6-O-b en zylid en e-3-O-(d ip h en ylp h os-
p h in o)-1,2-d id e oxy-r-D-glu cop yr a n o)-[2,1-d ]-2-oxa zo-
lin e (5f): 56% yield, a white solid; mp 154.6-155.0 °C; [R]20
D
) -29.3° (c ) 0.25, CHCl3); 1H NMR (400 MHz, CDCl3) δ 3.53
(dt, J ) 5.0, 9.7 Hz, 1H), 3.61 (t, J ) 9.7 Hz, 1H), 3.67 (s, 2H),
3.74 (t, J ) 9.7 Hz 1H), 4.24-4.31 (m, 3H), 5.33 (s, 1H), 5.95
(d, J ) 7.8 Hz, 1H), 7.22-7.52 (m, 20H) ppm; 13C NMR (75
MHz, CDCl3) δ 35.2, 63.0, 68.5, 69.3 (d, J ) 5.0 Hz), 79.6 (d,
J ) 3.7 Hz), 82.3 (d, J ) 19.9 Hz), 101.2, 102.5, 126.0-136.9
(22 carbons), 141.9 (d, J ) 23.0 Hz), 142.2 (d, J ) 18.1 Hz),
166.4 ppm; 31P NMR (161.9 MHz, CDCl3) δ 114.9 ppm; IR
(KBr) 1657, 1434 cm-1. Anal. Calcd for C33H30NO5P: C, 71.86;
H, 5.48; N, 2.54; P, 5.62. Found: C, 71.74; H, 5.36; N, 2.45; P,
6.01.
1
determined by H NMR with Eu(hfc)3.
Typ ica l P r oced u r e of Allylic Alk yla tion of Cin n a m yl
Aceta te (13). The chiral ligand 5d (5.70 mg, 11 × 10-3 mmol)
and [Pd(η3-C3H5)Cl]2 (1.81 mg, 5.0 × 10-3 mmol) were dissolved
in degassed toluene (0.5 mL) under Ar, and the solution was
stirred at room temperature. After 30 min the acetate 13 (0.176
g, 1.0 mmol) in toluene (1.5 mL) was added to the above
solution, and the mixture was stirred for 30 min. N,O-Bis-
(trimethylsilyl)acetamide (0.74 mL, 3 mmol), dimethyl mal-
onate (0.35 mL, 3 mmol), and KOAc (5 mg) were added to the
mixture in this order at room temperature, and the mixture
was stirred at this temperature. After 2 h, the reaction mixture
was added to saturated NH4Cl(aq) and extracted with Et2O
(10 mL × 3), and the extract was dried over MgSO4. The crude
product (1H NMR, 14:15 ) 11:89)27 was purified by column
chromatography on silica gel with hexane/AcOEt (v/v, 5:1) as
an eluent to afford a mixture of 14 and 15 (0.21 g, 0.85 mmol,
85%). The enantiomeric excess of 14 and the absolute config-
uration were determined by HPLC (Chiralcel OJ column).28i
Gen er a l P r oced u r e of Allylic Am in a tion of Eth yl 1,3-
Dip h en ylp r op -2-en yl Ca r bon a te (7). The chiral ligand 5a
(5.24 mg, 11 × 10-3 mmol) and [Pd(η3-C3H5)Cl]2 (1.82 mg, 5.0
× 10-3 mmol) were dissolved in degassed toluene (0.5 mL)
under Ar, and the solution was stirred at room temperature.
After 30 min, the solution of the carbonate 7 (94 mg, 0.33
mmol) and benzylamine (BnNH2) (107 mg, 1.0 mmol) in
toluene (1.5 mL) was added to the above solution, and the
solution was stirred at room temperature. After 24 h, solvent
was removed under 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 compound 16 (79 mg, 0.26
mmol, 78%). The enantiomeric excess was determined by
HPLC (Chiralcel OJ column, 1.0 mL/min, hexane:2-propanol
) 95:5).34 The absolute configuration was determined by
optical rotation.30
Typ ica l P r oced u r e of Allylic Alk yla tion of 1,3-Dip h en -
yl-3-a cetoxyp r op -1-en e (6). The chiral ligand 5a (2.62 mg,
5.5 × 10-3 mmol) and [Pd(η3-C3H5)Cl]2 (0.91 mg, 2.5 × 10-3
mmol) were dissolved in degassed toluene (0.5 mL) under Ar,
and the solution was stirred at room temperature. After 30
min the acetate 6 (0.25 g, 1.0 mmol) in toluene (1.5 mL) was
added, and the mixture was stirred for 30 min. N,O-Bis-
(trimethylsilyl)acetamide (0.74 mL, 3 mmol), dimethyl mal-
onate (0.35 mL, 3 mmol), and KOAc (5 mg) were added to the
above mixture in this order at 0 °C, and the mixture was
stirred at this temperature. After 6 h the reaction mixture was
added to saturated NH4Cl(aq) and extracted with Et2O (10 mL
× 3), and the extract was dried over MgSO4. Solvent was
removed under reduced pressure, and the residue was sub-
jected to column chromatography on silica gel with hexane/
AcOEt (v/v, 5:1) as an eluent to give compound 10 (0.27 g, 0.81
mmol, 81%). The enantiomeric excess was determined by
HPLC (Chiralcel AD column, 1.0 mL/min, hexane:2-propanol
) 95:5). The absolute configuration was determined by optical
rotation.3a
Typ ica l P r oced u r e of Allylic Alk yla tion of 1,3-Dip h en -
yl-3-a cetoxyp r op -1-en e (6) in th e P r esen ce of Tetr a bu tyl-
a m m on iu m F lu or id e. The chiral ligand 5a (2.62 mg, 5.5 ×
10-3 mmol) and [Pd(η3-C3H5)Cl]2 (0.91 mg, 2.5 × 10-3 mmol)
were dissolved in degassed toluene (0.5 mL) under Ar, and
the solution was stirred at room temperature. After 30 min
the acetate 6 (0.25 g, 1.0 mmol) in toluene (1.5 mL) was added
to the above solution, and the mixture was stirred for 30 min.
Dimethyl malonate (0.35 mL, 3 mmol) and 1 M tetrabutyl-
ammonium fluoride in THF (3 mL, 3 mmol) were added at
room temperature, and the mixture was stirred for 2 h at this
temperature. Purification and determination of ee were the
same as those described above.
Su p p or tin g In for m a tion Ava ila ble: Spectral and ana-
lytical data for new compounds 2a -f and 3a -f. This material
is available free of charge via the Internet at http://pubs.acs.org.
J O990901U
(34) Sudo, A.; Saigo, K. J . Org. Chem. 1997, 62, 5508.