Synthesis and application of novel chiral phosphino-oxazoline ligands with 1,1'-binaphthyl skeleton

Article abstract of DOI:10.1016/S0957-4166(98)00136-0

C₁-Symmetric phosphino-oxazolines, (S,S)- and (S,R)-2-[4- (isopropyl)oxazol-2-yl]-2'-diphenylphosphino-1, 1'-binaphthyl, which possess both phosphine and oxazoline moieties, were prepared from racemic binaphthol and enantiomerically pure (S)-(+

Full text of DOI:10.1016/S0957-4166(98)00136-0

TETRAHEDRON:
ASYMMETRY
Pergamon
Tetrahedron: Asymmetry 9 (1998) 1779–1787
Synthesis and application of novel chiral phosphino-oxazoline
ligands with 1,10-binaphthyl skeleton
Masamichi Ogasawara, Kazuhiro Yoshida, Hiroaki Kamei, Kazuhiko Kato, Yasuhiro Uozumi
and Tamio Hayashi ∗
Department of Chemistry, Graduate School of Science, Kyoto University, Sakyo, Kyoto 606-8502, Japan
Received 27 March 1998; accepted 31 March 1998
Abstract
C1-Symmetric phosphino-oxazolines, (S,S)- and (S,R)-2-[4-(isopropyl)oxazol-2-yl]-20-diphenylphosphino-1,10-
binaphthyl, which possess both phosphine and oxazoline moieties, were prepared from racemic binaphthol and
enantiomerically pure (S)-(+)-2-amino-3-methyl-1-butanol in high yields. Reaction of 1,3-diphenyl-2-propenyl
acetate with dimethyl sodiomalonate in the presence of 2 mol% of palladium catalysts bearing the new chiral
ligands proceeded with high enantioselectivity to give allylic alkylation products of up to 91% ee. © 1998 Published
by Elsevier Science Ltd. All rights reserved.
1. Introduction
The progress of transition metal-catalyzed asymmetric synthesis has been linked closely with the
development of chiral ligands.1 The idea of C2-symmetric bidentate ligands, which was originated by
Kagan in the form of diop in 1971,2 was an epoch-making concept, since their symmetry can greatly
simplify the structure of their transition metal complexes and reduce the number of possible species. C2-
Symmetry is important for the design of efficient chiral ligands, and high enantioselectivity has actually
been observed with the C2-symmetric bidentate ligands.1 However, as consumer demand grows for steric
control in asymmetric reactions, a more elaborate design of chiral ligands is required in some cases.
Recently, several new C1-symmetric ligands have been reported to show fairly promising results.3–5 One
example is the monodentate phosphine ligand MOP, which has the axially chiral binaphthyl backbone
and displays several unique features in catalytic asymmetric reactions.6 The 1,10-binaphthyl backbone
has also been applied to several chiral ligands and used successfully in a wide range of reactions.
Representative examples are binap,7 binaphos,5c and boxax.8
∗
Corresponding author. E-mail: thayashi@kuchem.kyoto-u.ac.jp
0957-4166/98/$19.00 © 1998 Published by Elsevier Science Ltd. All rights reserved.
PII: S0957-4166(98)00136-0

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M. Ogasawara et al. / Tetrahedron: Asymmetry 9 (1998) 1779–1787
On the other hand, another approach to the C1-symmetric chiral ligands can be seen in the development
of so-called P–N ligands, which include phosphinophenyloxazolines3 and their ferrocene analogues.4
The phosphine (P donor) and the oxazoline (N donor) moieties in those ligands possess completely
different electronic characteristics to each other, and they produce two distinctive coordination sites in
the transition metal complexes upon their coordination. Based on this historical background, we designed
and synthesized the new chiral phosphino-oxazoline ligands with binaphthyl skeletons 1a and 1b. Here
we report their synthetic procedures and their application to the palladium-catalyzed asymmetric allylic
alkylation.9
2. Results and discussion
2.1. Synthesis and characterization of phosphino-oxazoline ligands
A successful synthetic route to the new phosphino-oxazoline ligands is outlined in Scheme 1. All the
reactions proceeded in excellent isolated yields and the final products were obtained readily from the
known racemic compound, 2-methoxycarbonyl-20 -diphenylphosphinyl-1,10 -binaphthyl 2,10 on a multi-
gram scale in 81% (for (S,S)-isomer 1a) and 62% (for (S,R)-isomer 1b) overall yield. The synthetic
strategy described in Scheme 1 possesses several advantageous features: (1) it can furnish both (S,S)- and
(S,R)-diastereomers at the same time; (2) the starting binaphthyl building block is racemic binaphthol, i.e.
one can avoid using expensive enantiomerically pure binaphthyl compounds; (3) the synthetic procedures
were performed on the compounds substituted with a diphenylphosphinyl group (phosphine oxide) as a
phosphorus containing moiety until the final stage of the synthetic route. Thus, most of the intermediary
products can be handled in air without loss of their purity and/or yield. This characteristic is especially
important for scale-up of the reactions.
The starting methyl ester 2, which was reported by us previously in an enantiomerically pure form, was
obtained as a racemic compound from racemic binaphthol according to the reported procedures.10 The
racemic ester was hydrolyzed by a methanolic KOH solution to give racemic carboxylic acid 3 in 94%
yield after recrystallization from hot chloroform. The carboxylic acid 3 was condensed with enantiomer-
ically pure (S)-(+)-2-amino-3-methyl-1-butanol ((S)-valinol) in the presence of 1-hydroxylbenzotriazole
(HOBt) and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDCI) in DMF, which is a
standard method widely used for peptide synthesis,11 to give a mixture of a pair of diastereoisomeric
amides 4a and 4b almost quantitatively. The diastereoisomers were readily separated by column chrom-
atography on silica gel (eluent: hexane/EtOAc=1/5), and their absolute configurations were determined
as (S,S) for 4a (eluted first) and (S,R) for 4b (eluted second) in comparison with the amide which was
independently synthesized from enantiomerically pure (S)-2 and (S)-valinol. The separated amides 4a and
4b were subjected to the oxazoline ring formation by treatment with triethylamine and methanesulfonyl
chloride in the presence of a catalytic amount of 4-dimethylaminopyridine in dichloromethane. Both of
the crude phosphinyl-oxazoline ligands 5a and 5b could be purified by silica gel column chromatography
with hexane–EtOAc–NEt3 as an eluent, and obtained in an analytically pure form in 98% and 97%

M. Ogasawara et al. / Tetrahedron: Asymmetry 9 (1998) 1779–1787
1781
Scheme 1.
isolated yields, respectively. Addition of triethylamine to the eluent was essential for the protection of
the oxazoline rings, which were sensitive to ring-opening under acidic conditions. The reduction of the
phosphine-oxide in 5a and 5b was achieved by a standard silane reduction using trichlorosilane and
triethylamine in refluxing toluene. Successive column chromatography under nitrogen and recrystalliza-
tion from absolute ethanol (for 1a) or Et2O–CH2Cl2 (for 1b) afforded the analytically pure phosphino-
oxazoline ligands (S,S)-1a and (S,R)-1b in 92% and 83% yield, respectively.
2.2. Palladium-catalyzed asymmetric allylic alkylation
Both of the diastereomeric ligands were examined in the enantioselective allylic substitution reaction
catalyzed by palladium complexes.9 It was found that a palladium complex generated in situ from
[PdCl(π-C3H5)]2 and 1b (1.25 equiv. to Pd) was an effective catalyst for asymmetric allylic alkylation
of racemic 1,3-diphenyl-2-propenyl acetate 6 with the sodium salt of dimethyl malonate (Scheme 2).
The alkylation proceeded smoothly, even at −20°C, with high enantioselectivity to afford the product 7
whose enantiomeric excess was 91% (entry 6 in Table 1). The absolute configuration (R) was determined
20
by comparison of the specific rotation ([α]D +14.7 (c 1.10, EtOH) for the product from entry 4) with
that reported for (S)-712 and the enantiomeric excess was determined by HPLC analysis using a chiral
stationary phase column (Chiralcel OD-H, hexane/2-propanol=98/2). The catalyst coordinated with 1a
showed slightly better catalytic activity (i.e. a faster reaction) than with 1b, but the enantioselectivity was
much lower. Interestingly, ligand 1a has (S) axial chirality on the binaphthyl induced (S) configuration in
product 7 (entry 1–3), while its diastereomeric ligand 1b has (R) axial chirality induced (R) configuration
(entry 4–6). This observation indicates that the axial chirality in ligands 1a and 1b is the more influential
factor determining the stereochemical outcome in the allylic alkylation than the central chirality in the
oxazoline unit.

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M. Ogasawara et al. / Tetrahedron: Asymmetry 9 (1998) 1779–1787
Scheme 2.
Table 1
Asymmetric allylic alkylation of rac-6 catalyzed by phosphino-oxazoline–palladium complexesa
3. Experimental
3.1. General
The reactions, which required anaerobic conditions, were carried out with standard Schlenk techniques
under predried (P2O5; Merck, SICAPENT) nitrogen. Reaction progress was monitored by analytical thin-
layer chromatography (TLC) using 0.25 mm Merck F-254 silica gel glass plates. Visualization of the
TLC plates was achieved by an UV illumination. NMR spectra were recorded on a JEOL JNM LA500
1
spectrometer (1H, 500 MHz; 13C, 125 MHz; 31P, 202 MHz). H NMR chemical shifts are reported in
ppm downfield of internal tetramethylsilane. 13C NMR chemical shifts are relative to tetramethylsilane
with the use of solvent resonances (CDCl3, δ 77.05) as internal standards. 31P NMR chemical shifts are
externally referenced to 85% H3PO4. Optical rotations were measured on a JASCO DIP-370 polarimeter.
3.2. Materials
Compounds 2,11 [PdCl(π-C3H5)]2,13 and 614 were prepared according to previous reports. Diethyl
ether (Et2O) and tetrahydrofuran (THF) were distilled from sodium/benzophenone ketyl under N2 prior to
use. Dichloromethane was distilled from calcium hydride under nitrogen prior to use. Methanol (MeOH)
was dried over magnesium methoxide, distilled, and stored over 4 Å molecular sieves. All other solvents
were used as received. (S)-(+)-2-Amino-3-methyl-1-butanol (S-valinol) was prepared from (S)-valine
and LiAlH4. 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride, 1-hydroxybenzotriazole,

M. Ogasawara et al. / Tetrahedron: Asymmetry 9 (1998) 1779–1787
1783
4-dimethylaminopyridine, methanesulfonyl chloride, and triethylamine were purchased from Nacalai
Tesque, Japan, and used without purification. Trichlorosilane was purchased from Tokyo Chemical
Industry Co. and used as received.
3.3. rac-20-Diphenylphosphinyl-1,10 -binaphthyl-2-carboxylic acid 3
To a methanol solution of 2 (5.00 g, 9.76 mmol in 150 mL) was added 30 mL of an aqueous KOH
solution (40%), and the mixture was refluxed for 12 h. After cooling to 0°C, the reaction mixture was
acidified to ca. pH=2 with conc HCl. The separated solid was extracted with CHCl3 three times, and the
combined organic layer was dried over anhydrous Na2SO4. After filtration, the filtrate was evaporated to
dryness to give a slightly yellow residue. The crude material was recrystallized from hot chloroform to
give the analytically pure compound as a white solid. Yield: 4.56 g (9.15 mmol, 94%). 1H NMR (CDCl3,
23°C): δ 6.21 (d, J=8.4 Hz, 1H), 6.66 (t, J=7.7 Hz, 1H), 6.98 (dt, J=3.0 and 7.7 Hz, 2H), 7.11–7.19
(m, 5H), 7.29 (t, J=8.4 Hz, 1H), 7.32 (dd, J=8.7 and 12.4 Hz, 1H), 7.52–7.55 (m, 3H), 7.63–7.66 (m,
2H), 7.72–7.78 (m, 3H), 7.90 (d, J=8.1 Hz, 1H), 7.93 (d, J=8.7 Hz, 1H), 7.94 (dd, J=2.7 and 8.7 Hz,
1H), 14.66 (br, 1H). 13C{1H} NMR (CDCl3, 23°C): δ 123.8 (s), 126.0 (s), 126.4 (d, JCP=23.9 Hz), 126.9
(s), 127.1 (s), 127.5 (d, JCP=9.2 Hz), 127.6 (s), 127.8 (s), 127.9 (d, JCP=1.1 Hz), 128.1 (d, JCP=13.0
Hz), 128.1 (d, JCP=1.1 Hz), 128.2 (s), 128.8 (d, JCP=12.5 Hz), 128.9 (s), 128.9 (d, JCP=11.9 Hz), 129.6
(s), 129.8 (d, JCP=4.9 Hz), 130.1 (s), 130.9 (d, JCP=9.8 Hz), 131.5 (s), 131.8 (d, JCP=3.3 Hz), 132.3 (d,
J
CP=9.8 Hz), 132.7 (d, JCP=2.7 Hz), 132.9 (s), 133.7 (d, JCP=11.4 Hz), 134.9 (d, JCP=2.2 Hz), 135.5 (s),
142.4 (d, JCP=8.1 Hz), 171.5 (s). 31P{1H} NMR (CDCl3, 22°C): δ 35.1 (s). Anal. calcd for C33H23O3P:
C, 79.51; H, 4.65. Found: C, 79.42; H, 4.58.
3.4. (S,S)- and (S,R)-N-(1-Hydroxymethyl-2-methylpropyl)-20 -diphenylphosphinyl-1,10 -binaphthyl-
2-carboxylamide 4a and 4b
A mixture of 3 (4.49 g, 9.01 mmol), (S)-(+)-2-amino-3-methyl-1-butanol (1.86 g, 18.0 mmol),
1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (5.18 g, 27.0 mmol), and 1-hydroxy-
benzotriazole (4.87 g, 36.0 mmol) in N,N-dimethylformamide (500 mL) was stirred at 0°C for 30 min,
and then at room temperature for 4 h. Most of the solvent was removed from the flask under reduced
pressure. The resulting residue was diluted with CHCl3, and washed with saturated NaCl solution twice.
The organic layer was dried over anhydrous Na2SO4 and concentrated in vacuo to leave a slightly
yellow viscous oil, which contained both 4a and 4b as the main products. The two diastereomers were
separated by column chromatography on silica gel (hexane/EtOAc=1/5 as an eluent). The (S,S)-isomer
4a, which was eluted first, was further purified by recrystallization from chloroform/hexane, yielding
colorless needles. Although the (S,R)-isomer 4b was obtained as a colorless viscous oil after a second
chromatography on silica gel (eluent: chloroform/acetone), an analytically pure compound could not be
obtained because of the low crystallinity. 4a: Yield: 2.53 g (4.34 mmol, 48%), mp 202–205°C. 1H NMR
(CDCl3, 21°C): δ 0.96 (d, J=6.8 Hz, 3H), 1.03 (d, J=6.8 Hz, 3H), 1.95–2.05 (m, 1H), 3.14 (ddd, J=2.7,
5.9 and 11.7 Hz, 1H), 3.34 (ddd, J=4.9, 8.1 and 11.7 Hz, 1H), 3.54 (ddt, J=2.7, 4.6 and 8.8 Hz, 1H), 3.63
(br, 1H), 6.56 (d, J=8.5 Hz, 1H), 6.76 (dt, J=3.2 and 8.1 Hz, 2H), 6.85 (ddd, J=1.2, 6.8 and 8.5 Hz, 1H),
6.94 (dt, J=1.5 and 7.3 Hz, 1H), 7.07 (d, J=12.2, 1H), 7.09 (d, J=12.2 Hz, 1H), 7.17 (ddd, J=1.0, 6.8
and 8.3 Hz, 1H), 7.23 (d, J=8.5 Hz, 1H), 7.30 (ddd, J=1.2, 6.8 and 8.5 Hz, 1H), 7.47–7.58 (m, 6H), 7.66
(d, J=8.5 Hz, 1H), 7.78 (d, J=8.5 Hz, 1H), 7.82 (dd, J=1.5 and 11.5 Hz, 1H), 7.84 (d, J=11.5 Hz, 1H),
7.89 (d J=8.1 Hz, 1H), 7.94 (dd, J=2.4 and 8.8 Hz, 1H), 8.40 (d, J=9.0 Hz, 1H). 13C{1H} NMR (CDCl3,
22°C): δ 19.7 (s), 19.7 (s), 29.0 (s), 57.6 (s), 63.0 (s), 124.2 (s), 125.8 (s), 126.1 (s), 127.0 (s), 127.4 (d,

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M. Ogasawara et al. / Tetrahedron: Asymmetry 9 (1998) 1779–1787
JCP=13.0 Hz), 127.7 (d, JCP=16.8 Hz), 127.7 (s), 127.9 (d, JCP=13.0 Hz), 128.0 (s), 128.2 (d, JCP=12.5
Hz), 128.6 (s), 128.7 (d, JCP=11.9 Hz), 128.7 (s), 129.1 (s), 129.4 (s), 130.2 (d, JCP=9.8 Hz), 130.7 (d,
J
CP=2.7 Hz), 131.1 (d, JCP=4.9 Hz), 131.5 (s), 132.0 (s), 132.1 (d, JCP=9.2 Hz), 132.2 (s), 132.3 (s),
132.8 (s), 133.8 (d, JCP=11.4 Hz), 134.5 (d, JCP=2.2 Hz), 137.8 (s), 143.3 (d, JCP=8.1 Hz), 170.1 (s).
31P{1H} NMR (CDCl3, 22°C): δ 30.1 (s). [α]20 −62.7 (c 1.01, CHCl3). Anal. calcd for C38H34O3NP:
D
C, 78.20; H, 5.87; N, 2.40. Found: C, 77.90; H, 5.76; N, 2.48. 4b: Yield: 2.17 g (3.72 mmol, 41%), mp
1
117–120°C. H NMR (CDCl3, 21°C): δ −0.10 (d, J=6.8 Hz, 3H), 0.53 (d, J=6.8 Hz, 3H), 1.16–1.25
(m, 1H), 3.51–3.59 (m, 2H), 3.71–3.74 (m, 1H), 4.24 (br, 1H), 6.58 (d, J=8.3 Hz, 1H), 6.73 (dt, J=3.2
and 7.8 Hz, 2H), 6.90–6.95 (m, 2H), 7.08–7.12 (m, 2H), 7.16 (d, J=8.8 Hz, 1H), 7.20 (t, J=7.1 Hz, 1H),
7.29 (t, J=7.1 Hz, 1H), 7.51–7.60 (m, 6H), 7.74 (d, J=8.5 Hz, 1H), 7.87 (d, J=11.5 Hz, 1H), 7.89 (d,
J=11.5 Hz, 1H), 7.92 (d, J=8.3 Hz, 1H), 7.97 (d, J=8.8 Hz, 1H), 7.98 (dd, J=2.2 and 8.8 Hz, 1H), 8.28
(d, J=8.1 Hz, 1H). 13C{1H} NMR (CDCl3, 23°C): δ 18.4 (s), 19.1 (s), 29.2 (s), 57.9 (s), 63.3 (s), 126.1
(s), 126.1 (d, JCP=1.6 Hz), 127.0 (s), 127.3 (s), 127.3 (d, JCP=12.5 Hz), 127.7 (s), 127.8 (s), 128.1 (s),
128.2 (d, JCP=13.0 Hz), 128.6 (d, JCP=11.9 Hz), 128.8 (d, JCP=11.9 Hz), 128.9 (s), 129.0 (d, JCP=9.8
Hz), 129.4 (s), 129.8 (s), 130.2 (d, JCP=9.8 Hz), 130.7 (d, JCP=3.3 Hz), 130.8 (d, JCP=4.9 Hz), 131.2 (s),
132.0 (s), 132.1 (d, JCP=9.2 Hz), 132.2 (s), 132.2 (d, JCP=17.4 Hz), 133.3 (s), 133.3 (d, JCP=11.4 Hz),
135.0 (d, JCP=2.2 Hz), 136.3 (s), 143.0 (d, JCP=8.7 Hz), 168.5 (s). 31P{1H} NMR (CDCl3, 23°C): δ 30.2
(s). [α]20 +39.8 (c 1.01, CHCl3). Anal. calcd for C38H34O3NP: C, 78.20; H, 5.87; N, 2.40. Found: C,
D
77.19; H, 5.97; N, 2.15.
3.5. (S,S)-2-[4-(Isopropyl)oxazol-2-yl]-20 -diphenylphosphinyl-1,10 -binaphthyl 5a
To a mixture of 4a (2.27 g, 3.89 mmol), 4-dimethylaminopyridine (5.0 mg, 0.041 mmol), and
triethylamine (791 mg, 1.09 mL, 7.82 mmol) in dichloromethane (50 mL) was added methanesulfonyl
chloride (888 mg, 0.60 mL, 7.75 mmol) at 0°C, and the solution was stirred for 30 min at this temperature.
Then another portion of triethylamine (3.56 g, 4.91 mL, 35.2 mmol) was added to the solution, and it
was refluxed until the initially formed mesylate disappeared (checked by TLC). On cooling to room
temperature, the reaction mixture was diluted with CHCl3 and washed with an aqueous NaHCO3
solution. The organic layer was dried over anhydrous Na2SO4 and filtered. The filtrate was concentrated
under reduced pressure to give a slightly yellow residue, which was chromatographed on silica gel
(elution with hexane/EtOAc/Et3N=7/14/1) to give 5a in pure form. Yield: 2.16 g (3.82 mmol, 98%),
mp 221–225°C. 1H NMR (CDCl3, 21°C): δ 0.37 (d, J=6.8 Hz, 3H), 0.54 (d, J=6.8 Hz, 3H), 1.14–1.20
(m, 1H), 3.67–3.73 (m, 2H), 3.89–3.95 (m, 1H), 6.99 (dt, J=2.9 and 7.8 Hz, 2H), 7.02 (d, J=9.0 Hz, 1H),
7.15–7.22 (m, 4H), 7.24–7.29 (m, 4H), 7.37 (dt, J=1.5 and 7.3 Hz, 1H), 7.41 (ddd, J=2.0, 5.9 and 8.1 Hz,
1H), 7.45–7.48 (m, 1H), 7.60 (dd, J=1.2 and 11.7 Hz, 1H), 7.61 (d, J=11.7 Hz, 1H), 7.68 (d, J=8.5 Hz,
1H), 7.72 (d, J=8.3 Hz, 1H), 7.77 (dd, J=8.8 and 11.7 Hz, 1H), 7.84 (d, J=8.5 Hz, 1H), 7.87 (d, J=8.1
Hz, 1H), 7.92 (dd, J=1.7 and 8.8 Hz, 1H). 13C{1H} NMR (CDCl3, 23°C): δ 17.8 (s), 18.6 (s), 32.8 (s),
69.7 (s), 72.9 (s), 125.6 (s), 126.4 (s), 126.6 (d, JCP=3.6 Hz), 126.9 (s), 127.0 (d, JCP=12.4 Hz), 127.1
(s), 127.2 (s), 127.6 (d, JCP=3.1 Hz), 127.7 (s), 127.8 (d, JCP=2.1 Hz), 128.5 (s), 128.9 (s), 128.9 (d,
J
J
CP=11.4 Hz), 129.7 (s), 130.7 (d, JCP=3.1 Hz), 131.0 (d, JCP=3.1 Hz), 131.7 (d, JCP=9.8 Hz), 132.1 (d,
CP=9.8 Hz), 132.6 (s), 133.0 (s), 133.1 (s), 133.5 (s), 133.6 (s), 134.0 (s), 134.5 (d, JCP=2.1 Hz), 134.8
(s), 136.4 (d, JCP=4.7 Hz), 143.3 (d, JCP=7.8 Hz), 162.3 (s). 31P{1H} NMR (CDCl3, 23°C): δ 27.5 (s).
[α]20D −254 (c 1.01, CHCl3). Anal. calcd for C38H32O2NP: C, 80.69; H, 5.70; N, 2.48. Found: C, 80.44;
H, 5.59; N, 2.33.

M. Ogasawara et al. / Tetrahedron: Asymmetry 9 (1998) 1779–1787
1785
3.6. (S,R)-2-[4-(Isopropyl)oxazol-2-yl]-20 -diphenylphosphinyl-1,10 -binaphthyl 5b
This compound was prepared from 4b (2.17 g, 3.72 mmol), 4-dimethylaminopyridine (4.5 mg, 0.037
mmol), triethylamine (753 mg, 1.04 mL, 7.44 mmol), methanesulfonyl chloride (1.49 g, 1.01 mL, 13.0
mmol), and an additional portion of triethylamine (3.39 g, 4.67 mL, 33.5 mmol) in dichloromethane as
described above. The final purification was performed by column chromatography on silica gel (elution
1
with hexane/EtOAc/Et3N=5/15/1). Yield: 2.03 g (3.59 mmol, 97%), mp 232–235°C. H NMR (CDCl3,
21°C): δ 0.54 (d, J=6.6 Hz, 3H), 0.59 (d, J=6.8 Hz, 3H), 1.44–1.53 (m, 1H), 3.45 (t, J=8.1 Hz, 1H),
3.69–3.74 (m, 1H), 3.96 (dd, J=8.3 and 9.8 Hz, 1H), 7.08–7.14 (m, 7H), 7.21 (ddd, J=1.0, 6.6 and 8.5
Hz, 1H), 7.24–7.27 (m, 2H), 7.36 (ddd, J=1.5, 6.6 and 8.1 Hz, 1H), 7.39–7.43 (m, 4H), 7.48 (t, J=7.1 Hz,
1H), 7.68 (d, J=8.5 Hz, 2H), 7.74 (dd, J=8.8 and 11.5 Hz, 1H), 7.88 (d, J=8.3 Hz, 1H), 7.91 (d, J=8.8
Hz, 1H), 7.93 (dd, J=2.0 and 8.5 Hz, 1H). 13C{1H} NMR (CDCl3, 23°C): δ 17.7 (s), 18.8 (s), 32.3 (s),
69.9 (s), 72.3 (s), 126.2 (d, JCP=15.0 Hz), 126.7 (s), 126.8 (s), 126.8 (s), 127.2 (d, JCP=11.9 Hz), 127.3
(s), 127.5 (d, JCP=15.5 Hz), 127.5 (s), 127.7 (d, JCP=2.6 Hz), 127.7 (d, JCP=4.7 Hz), 128.6 (s), 128.8 (d,
J
CP=11.9 Hz), 129.4 (s), 130.8 (s), 130.8 (d, JCP=5.2 Hz), 131.6 (d, JCP=15.5 Hz), 131.7 (d, JCP=15.0
Hz), 132.9 (s), 133.2 (s), 133.3 (s), 133.5 (s), 133.5 (s), 133.7 (s), 133.9 (s), 134.0 (s), 134.2 (d, JCP=2.6
Hz), 135.5 (d, JCP=5.2 Hz), 143.2 (d, JCP=7.8 Hz), 163.9 (s). 31P{1H} NMR (CDCl3, 22°C): δ 28.0 (s).
[α]20D +98.1 (c 1.00, CHCl3). Anal. calcd for C38H32O2NP: C, 80.69; H, 5.70; N, 2.48. Found: C, 80.13;
H, 5.64; N, 2.51.
3.7. (S,S)-2-[4-(Isopropyl)oxazol-2-yl]-20 -diphenylphosphino-1,10 -binaphthyl 1a
To a mixture of 5a (2.00 g, 3.54 mmol) and triethylamine (10.7 g, 14.8 mL, 106 mmol) in toluene (60
mL) was added trichlorosilane (4.79 g, 3.57 mL, 35.4 mmol) at 0°C, and the solution was stirred for 30
min at this temperature. It was then refluxed for 2 h (checked with TLC) under nitrogen. After cooling
to 0°C, the reaction mixture was diluted with Et2O and quenched with a small amount of saturated
aqueous NaHCO3 solution. The resulting suspension was filtered through a pad of Celite and the filter
cake was washed with Et2O, then the filtrate was concentrated under reduced pressure. The crude product
was chromatographed on silica gel (pretreated with an Et2O/Et3N solution) under a nitrogen atmosphere
using Et2O as an eluent to give analytically pure 1a. Yield: 1.80 g (3.27 mmol, 92%), mp 152–155°C. 1H
NMR (CDCl3, 22°C): δ 0.44 (d, J=6.6 Hz, 3H), 0.52 (d, J=6.8 Hz, 3H), 1.17–1.24 (m, 1H), 3.54 (t, J=7.8
Hz, 1H), 3.61 (ddd, J=6.6, 7.8 and 9.5 Hz, 1H), 3.78 (dd, J=7.8 and 9.5 Hz, 1H), 6.94 (d, J=8.1 Hz, 1H),
6.97 (ddd, J=1.2, 6.6 and 8.5 Hz, 1H), 7.06–7.28 (m, 12H), 7.37–7.43 (m, 2H), 7.49 (dd, J=2.9 and 8.5
Hz, 1H), 7.84 (d, J=8.5 Hz, 2H), 7.89 (d, J=8.3 Hz, 1H), 8.00 (d, J=8.8 Hz, 1H), 8.16 (d, J=8.5 Hz, 1H).
13C{1H} NMR (CDCl3, 23°C): δ 18.0 (s), 18.5 (s), 32.8 (s), 69.8 (s), 72.7 (s), 125.7 (d, JCP=2.6 Hz),
126.1 (s), 126.1 (s), 126.5 (s), 126.7 (d, JCP=2.6 Hz), 126.9 (s), 127.5 (s), 127.6 (d, JCP=1.9 Hz), 127.8
(s), 127.8 (d, JCP=5.7 Hz), 128.0 (d, JCP=10.9 Hz), 128.1 (d, JCP=7.2 Hz), 128.2 (s), 130.5 (d, JCP=2.6
Hz), 133.0 (d, JCP=8.3 Hz), 133.2 (s), 133.4 (s), 133.5 (d, JCP=2.6 Hz), 133.5 (s), 133.8 (d, JCP=20.2
Hz), 134.2 (s), 135.0 (d, JCP=9.3 Hz), 137.7 (s), 137.8 (s), 138.5 (s), 138.7 (d, JCP=18.6 Hz), 138.9 (s),
145.3 (d, JCP=35.2 Hz), 162.7 (s). 31P{1H} NMR (CDCl3, 23°C): δ −14.2 (s). [α]20 −142 (c 1.00,
D
CHCl3). Anal. calcd for C38H32ONP: C, 83.04; H, 5.87; N, 2.55. Found: C, 83.07; H, 5.95; N, 2.44.
3.8. (S,R)-2-[4-(Isopropyl)oxazol-2-yl]-20 -diphenylphosphino-1,10 -binaphthyl 1b
This compound was prepared from 5b (1.80 g, 3.18 mmol), triethylamine (10.3 g, 14.2 mL, 102 mmol)
and trichlorosilane (4.32 g, 3.22 mL, 31.9 mmol) in toluene (55 mL) and purified as described above.

1786
M. Ogasawara et al. / Tetrahedron: Asymmetry 9 (1998) 1779–1787
An analytically pure sample was obtained by recrystallization from Et2O–CH2Cl2. Yield: 1.45 g (2.64
1
mmol, 83%), mp 165–167°C. H NMR (CDCl3, 22°C): δ 0.51 (d, J=6.8 Hz, 3H), 0.57 (d, J=6.8 Hz,
3H), 1.31–1.41 (m, 1H), 3.32 (t, J=8.1 Hz, 1H), 3.57 (ddd, J=6.3, 7.8 and 9.8 Hz, 1H), 3.69 (dd, J=8.1
and 9.8 Hz, 1H), 6.95 (d, J=8.5 Hz, 1H), 6.99–7.04 (m, 3H), 7.10–7.14 (m, 2H), 7.16–7.27 (m, 8H), 7.39
(ddd, J=1.2, 6.6 and 8.3 Hz, 1H), 7.43 (ddd, J=1.5, 6.3 and 8.3 Hz, 1H), 7.48 (dd, J=2.9 and 8.5 Hz,
1H), 7.84 (d, J=8.5 Hz, 2H), 7.89 (d, J=8.1 Hz, 1H), 7.99 (d, J=8.8 Hz, 1H), 8.13 (d, J=8.5 Hz, 1H).
13C{1H} NMR (CDCl3, 23°C): δ 17.7 (s), 18.6 (s), 32.4 (s), 70.0 (s), 72.0 (s), 126.2 (d, JCP=8.8 Hz),
126.5 (d, JCP=22.2 Hz), 126.8 (d, JCP=2.6 Hz), 126.8 (s), 127.3 (d, JCP=2.6 Hz), 127.6 (s), 127.6 (s),
127.7 (s), 127.9 (s), 128.0 (s), 128.0 (s), 128.0 (s), 128.0 (s), 128.1 (s), 128.2 (s), 130.2 (d, JCP=2.1 Hz),
133.2 (d, JCP=1.0 Hz), 133.3 (d, JCP=2.6 Hz), 133.4 (d, JCP=7.8 Hz), 133.5 (d, JCP=20.2 Hz), 133.5 (d,
J
CP=19.1 Hz), 134.1 (s), 134.8 (d, JCP=10.9 Hz), 138.0 (s), 138.1 (s), 138.1 (s), 138.2 (d, JCP=8.8 Hz),
144.9 (d, JCP=34.7 Hz), 164.3 (s). 31P{1H} NMR (CDCl3, 23°C): δ −14.7 (s). [α]20 +15.2 (c 1.00,
D
CHCl3). Anal. calcd for C38H32ONP: C, 83.04; H, 5.87; N, 2.55. Found: C, 82.88; H, 6.12; N, 2.49.
3.9. Palladium-catalyzed asymmetric allylic alkylation of 6: typical procedure
To a mixture of [PdCl(π-C3H5)]2 (1.0 mg, 2.7 µmol), 1b (3.7 mg, 6.7 µmol) and rac-6 (66.6 mg,
264 µmol) in THF (0.1 mL) was added a solution of the sodium salt of dimethyl malonate prepared
from dimethyl malonate (66.1 mg, 0.50 mmol) and sodium hydride in THF (2 mL) at −78°C under
nitrogen. The flask was then immersed in a bath maintained at −20°C and the solution was stirred
for 48 h. The reaction mixture was quenched with a small amount of 5% HCl aqueous solution and
evaporated to dryness under reduced pressure. The crude product was purified by preparative TLC on
silica gel (eluent: hexane/EtOAc=4/1) to give 7 in pure form, quantitatively. The enantiomeric purity
was detemined to be 91% ee by HPLC analysis with a chiral stationary phase column, Chiralcel OD-H
(hexane/2-propanol=98/2).
Acknowledgements
This work was supported by ‘Research for the Future’ Program, the Japan Society for the Promotion
of Science and a Grant-in-Aid for Scientific Research, the Ministry of Education, Japan.
References
1. (a) Brunner, H. Synthesis 1988, 645. (b) Noyori, R.; Kitamura, M., In Modern Synthetic Methods, Schefford, R., Ed.
Springer-Verlag: New York, 1989, Vol. 5; p. 115. (c) Ojima, I.; Clos, N.; Bastos, C. Tetrahedron 1989, 45, 6901. (d) Ojima,
I. Catalytic Asymmetric Synthesis, VCH: New York, 1993. (e) Noyori, R. Asymmetric Catalysis in Organic Synthesis,
Wiley: New York, 1994.
2. (a) Dang, T. P.; Kagan, H. B. J. Chem. Soc., Chem. Commun. 1971, 481. (b) Kagan, H. B.; Dang, T. P. J. Am. Chem. Soc.
1972, 94, 6429.
3. (a) von Matt, P.; Pfaltz, A. Angew. Chem., Int. Ed. Engl. 1993, 32, 566. (b) Sprinz, J.; Helmchen, G. Tetrahedron Lett.
1993, 34, 1769. (c) Dawson, G. J.; Frost, C. G.; Williams, J. M. J.; Coote, S. J. Tetrahedron Lett. 1993, 34, 3149.
4. (a) Richards, C. J.; Dmalidis, T.; Hibbs, D. E.; Hursthouse, M. B. Synlett 1995, 74. (b) Sammakia, T.; Latham, H. A.;
Schaad, D. R. J. Org. Chem. 1995, 60, 10. (c) Nishibayashi, Y.; Uemura, S. Synlett 1995, 79.
5. (a) Giardello, M. A.; Conticello, V. P.; Brard, L.; Sabat, M.; Rheingold, A. L.; Stern, C. L.; Marks, T. J. J. Am. Chem.
Soc. 1994, 116, 10212. (b) Hayashi, T.; Niizuma, S.; Kamikawa, T.; Suzuki, N.; Uozumi, Y. J. Am. Chem. Soc. 1995, 117,
9101. (c) Nozaki, K.; Sakai, N.; Nanno, T.; Higashijima, T.; Mano, S.; Horiuchi, T.; Takaya, H. J. Am. Chem. Soc. 1997,
119, 4413.

M. Ogasawara et al. / Tetrahedron: Asymmetry 9 (1998) 1779–1787
1787
6. (a) Uozumi, Y.; Hayashi, T. J. Am. Chem. Soc. 1991, 113, 9887. (b) Uozumi, Y.; Tanahashi, A.; Lee, S.-Y.; Hayashi, T. J.
Org. Chem. 1993, 58, 1945. (c) Hayashi, T.; Iwamura, H.; Naito, M.; Matsumoto, Y.; Uozumi, Y. J. Am. Chem. Soc. 1994,
116, 775. (d) Hayashi, T.; Kawatsura, M.; Uozumi, Y. Chem. Commun. 1997, 561. (e) Hayashi, T. J. Synth. Org. Chem.,
Jpn 1994, 52, 900.
7. (a) Takaya, H.; Mashima, K.; Koyano, K.; Yagi, M.; Kumobayashi, H.; Taketomi, T.; Akutagawa, S.; Noyori, R. J. Org.
Chem. 1986, 51, 629. (b) Noyori, R. Chem. Soc. Rev. 1989, 18, 187 and references cited therein. (c) Noyori, R.; Takaya,
H. Acc. Chem. Res. 1990, 23, 345 and references cited therein.
8. (a) Uozumi, Y.; Kyota, H.; Kishi, E.; Kitayama, K.; Hayashi, T. Tetrahedron: Asymmetry 1996, 7, 1603. (b) Uozumi, Y.;
Kato, K.; Hayashi, T. J. Am. Chem. Soc. 1997, 119, 5063. (c) Nelson, T. D.; Meyers, A. I. J. Org. Chem. 1994, 59, 2655.
9. (a) Trost, B. M.; Van Vranken, D. L. Chem. Rev. 1996, 96, 395. (b) Hayashi, T., In Catalytic Asymmetric Synthesis; Ojima,
I., Ed. VCH: New York, 1993; p. 325. (c) Frost, C. G.; Howarth, J.; Williams, J. M. J. Tetrahedron: Asymmetry 1992, 3,
1089. (d) Consiglio, G.; Waymouth, R. M. Chem. Rev. 1989, 89, 257.
10. Uozumi, Y.; Suzuki, N.; Ogiwara, A.; Hayashi, T. Tetrahedron 1994, 50, 4293.
11. (a) König, W.; Geiger, R. Chem. Ber. 1970, 103, 788. (b) König, W.; Geiger, R. Chem. Ber. 1970, 103, 2024.
12. (a) Hayashi, T.; Yamamoto, A.; Hagihara, T.; Ito, Y. Tetrahedron Lett. 1986, 27, 191. (b) Hayashi, T.; Yamamoto, A.; Ito,
Y.; Nishioka, E.; Miura, H.; Yanagi, K. J. Am. Chem. Soc. 1989, 111, 6301.
13. Tatsuno, A.; Yoshida, T.; Otsuka, S. Inorg. Synth. 1979, 19, 220.
14. Trost, B. M.; Strege, P. E. J. Am. Chem. Soc. 1977, 99, 1649.