Diastereoselective reactions of 1,1′-bihaphthyl ester enolates with carbonyl electrophiles

Article abstract of DOI:10.1039/a706673b

Diastereoselectivity in the aldol and the conjugate additions of 2′-hydroxy-1,1′-binaphthyl ester enolates with a variety of carbonyl electrophiles has been examined. The ester enolate generated by BuLi reacts with several aldehydes to give the threo products preferentially with high diastereoselectivity and in good yield. Satisfactory diastereoselectivity has also been observed in the minor erythro derivatives. A mechanistic interpretation of the results is made on the basis of the absolute stereochemistry of the products.

Full text of DOI:10.1039/a706673b

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Diastereoselective reactions of 1,1Ј-binaphthyl ester enolates with
carbonyl electrophiles
Mija Ahn, Kiyoshi Tanaka and Kaoru Fuji*
Institute for Chemical Research, Kyoto University, Uji, Kyoto 611, Japan
Diastereoselectivity in the aldol and the conjugate additions of 2Ј-hydroxy-1,1Ј-binaphthyl ester enolates
with a variety of carbonyl electrophiles has been examined. The ester enolate generated by BuLi reacts
with several aldehydes to give the threo products preferentially with high diastereoselectivity and in good
yield. Satisfactory diastereoselectivity has also been observed in the minor erythro derivatives. A
mechanistic interpretation of the results is made on the basis of the absolute stereochemistry of the
products.
Introduction
O
Carbon–carbon bond-forming reactions, such as aldol and
Michael reactions, play an important role in synthetic organic
chemistry, and their directed versions have been widely used for
Ph
O
OH
the selective construction of the carbon skeleton of a variety of
1
useful compounds. Earlier, we reported the highly diastereo-
selective alkylation of the ester anion of 2Ј-hydroxy-1,1Ј-
(S)-1
binaphthalene as the result of complex-induced proximity
effects (CIPE) in enolate formation, and demonstrated that the
2
Base / RCHO
78 °C, for 2 h
-
2
Ј-hydroxy-1,1Ј-binaphthalene acts as an effective stereochemi-
3
cal controller in stoichiometric reactions. These approaches
were successfully applied to the asymmetric synthesis of clinic-
ally important drugs as well as non-racemic uncommon α-
O
OH
O
OH
4
5
O
R
O
R
amino acid derivatives. As an extension to the alkylation of
+
OH
Ph
OH
Ph
binaphthyl ester enolates, we have examined the diastereoselec-
tive aldol and Michael-type reactions of binaphthyl ester eno-
lates with a variety of carbonyl electrophiles. Despite the
numerous methods available for asymmetric aldol reactions,
including enolates of ketones, amides and imides, very few
approaches involving enolates of carboxylic esters have been
2
a-m
3a-m
6
reported.
O
OH
O
OH
O
R
O
R
Results and discussion
The aldol reaction of the anion of optically active (S)-2Ј-
hydroxy-1,1Ј-binaphthyl phenylacetate (S)-1 with benzalde-
+
+
OH
Ph
OH
Ph
2
hyde was first examined under a variety of reaction conditions,
the chemical yield and the syn/anti ratio of the products being
studied. Of the bases evaluated, BuLi gave the best result with
respect to both chemical yield and diastereoselectivity in THF†
at Ϫ78 ЊC a mixture of 2–5a (Table 1) being obtained. With
BuLi as a base, increased chemical yields were observed with
the solvent systems THF–toluene, THF–DME† and THF–
ether.† The addition of HMPA,† which has a strong ligating
ability, interfered with the reaction. Diastereoselectivity was
4a-m
5a-m
Scheme 1 R = a = Phenyl; b = 1-naphthyl; c = 2-naphthyl; d = styryl;
e = 4-methoxyphenyl; f = ethyl; g = isopropyl; h = 2-furyl; i = 3-furyl;
j = 5-methyl-2-furyl; k = 2-thienyl; l = 3-pyridyl; m = 4-pyridyl
field, while the β-proton and both hydroxy protons shifted to
lower field (Table 7 in Experimental section). These observ-
ations also suggested that the stereostructure of the major
products was as shown in 2 and 3.
1
determined by HPLC and/or H NMR analysis. Despite a few
exceptions, it has been well documented for aldol reactions that
a small vicinal coupling constant of 3–6 Hz is attributable to an
erythro (syn) relationship, while a larger one of 7–9 Hz is attrib-
The aldol reactions of the anion of 1 with several aromatic
and aliphatic aldehydes other than benzaldehyde were carried
out (Scheme 1), and these results are given in Table 2. In gen-
eral, satisfactory chemical yields of more than 90% were
obtained with aromatic aldehydes, but not with aliphatic alde-
hydes. Again, the syn/anti ratio increased slightly when toluene
was added to THF. The stereoselectivity depended on the struc-
ture of the aldehydes used. Thus, a relatively high syn/anti ratio
was observed for 2-naphthaldehyde, trans-cinnamaldehyde and
p-anisaldehyde (entries 3 to 5), and a lower selectivity was
obtained with the less bulky propionaldehyde (entry 6 vs. 7).
The selectivity of the adducts of 3-furaldehyde and thiophene-
carbaldehyde was superior to those of 2-furaldehyde and 5-
methyl-2-furaldehyde (entries 8 to 11), and the adducts from
7
utable to a threo (anti) relationship. Consequently, the syn/anti
stereochemistry of the adducts was deduced by comparing the
1
vicinal coupling constants of the adducts by H NMR spec-
trometry (see Table 6 in Experimental section); this assignment
was later supported by chemical transformation and an X-ray
analysis (vide infra). Of the anti products 2a and 3a, the α-
proton of the major diastereoisomer 2a appeared at higher
†
THF = tetrahydrofuran, DME = dimethyl ether, ether = diethyl
ether, HMPA = hexamethylphosphoramide, LDA = lithium diiso-
propylamide.
J. Chem. Soc., Perkin Trans. 1, 1998
185

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pyridinecarbaldehydes showed low selectivity (entries 12 and
3). threo Products were generally obtained with good diastereo-
selectivity in preference to erythro adducts. The diastereo-
selectivity of the minor erythro adducts 4 and 5 could not be
determined at that time, but was evaluated later by the chemical
transformations described below.
To confirm the absolute stereochemistry of the aldol prod-
ucts 2–5a–m, we next tried to remove the chiral auxiliary to give
the β-hydroxy carboxylates 6,7a–m. Under hydrolytic condi-
tions using NaOH or LiOH in aqueous MeOH, the retro-aldol
reaction took place to give recovery of binaphthol and the cor-
responding aldehyde. On the other hand, under the conditions
used for the ester exchange, LiOMe–MeOH, the aldol products
2–5a–m were converted into a separable syn/anti diastereoiso-
1
meric mixture of the methyl esters 6a–m and 7a–m in satisfac-
tory yield, together with binaphthol without any loss of optical
purity (Scheme 2).
O
OH
*
*
O
R
OH
Ph
2
-5a-m
LiOMe–MeOH
Table 1 Reaction conditions for the aldol reaction of 1 with benz-
aldehyde
0
°C, 1-2 h
a
b,c
Base
Solvent
Yield (%)
anti:syn
O
OH
O
OH
d
BuLi
BuLi
BuLi
BuLi
BuLi
LDA
LTMP
KDA
LHMDS
BuLi–MgBr2
NaH
THF
97
93
97
88
28
70
32
47
62
93:7
MeO
R
MeO
R
THF–toluene (3:1)
THF–DME (2:1)
THF–ether (2:1)
THF–HMPA (3%)
THF
THF
THF
THF
THF
THF
94:6
92:8
96:4
87:13
88:12
85:15
90:10
90:10
53:47
—
Ph
+
Ph
syn
+
2,2'-BINOL
anti
6
a-m
7
a-m
Scheme 2
e
39
—
The anti stereochemistry of the major diastereoisomers 6
from 2 was confirmed by comparison with the physical data in
f
8
the literature, and the absolute stereostructure of 6a was proven
a
b
c
Isolated yield. 2a ϩ 3a:4a ϩ 5a. Determined by HPLC using a
d
to be 2S,3R by comparison with the sign of the reported spe-
Puresil C18 column. A crystalline compound of 100:1 ratio was
obtained after one recrystallization. A 33% yield of 2,2Ј-BINOL was
recovered. 1 and 2,2Ј-BINOL were recovered.
9
e
cific rotation. Authentic samples of the racemic mixture of the
f
syn and anti diastereoisomers 6 and 7 were prepared independ-
Table 2 The aldol reaction of 1 with RCHO
HPLC cond.
a
b
c,d
e
Entry
RCHO
Solvent
Prod.
Yield (%)
anti:syn
% de (anti)
(MeOH–H O)
2
1
2
3
a
b
c
THF
THF
THF
2–5 a
2–5 b
2–5 c
97
95
98
61
80
91
59
91
94
85
78f
71
58
99
89
95
99
84
97
92
97:3
60:40
94:6
76
70
68
60
48
82
80
68
64
70
55
75:25
70:30
75:25
THF–toluene = 2:1
THF–ether = 3:1
THF
THF–toluene = 3:1
THF–ether = 3:1
THF
THF–toluene = 3:1
THF–ether = 3:1
THF
THF
THF
THF–toluene = 3:1
THF
THF
THF–toluene = 3:1
THF
THF–toluene = 3:1
THF
THF
99:1
89:11
87:13
88:12
87:13
94:6
100:0
99:1
4
5
d
e
2–5 d
2–5 e
72:28
75:25
g
6
7
8
f
g
h
2–5 f
2–5 g
2–5 h
62:38
98:2
—
75:25
75:25
70:30
70
30
30
72
34
33
60
62
37:63
46:54
86:14
79:21
69:31
89:11
95:5
9
0
i
j
2–5 i
2–5 j
70:30
72:28
1
1
1
k
2–5 k
70:30
h
i
j
1
1
2
3
l
m
2–5 l
2–5 m
91
54:46
30:70
48 (74)
27 (60)
—
—
h
i
j
90
a
CHO
CHO
CHO
OMe
CHO
CHO
a;
b;
c;
d;
j;
e;
f; C2H5CHO
CHO
N
CHO
CHO
h;
i;
k;
l;
m;
g; (CH3)2CHCHO
O
CHO
O
O
CHO
S
CHO
N
b
c
d
e
Combined isolated yield. 2 ϩ 3:4 ϩ 5. Determined by HPLC analysis using a Puresil C column. The % de of the minor syn products was not
1
8
f
g
h
i
1
j
determined. Reacted for 7 h. Not determined. Reacted for 5 min. Determined by H NMR (400 MHz). The % de of syn products.
1
86
J. Chem. Soc., Perkin Trans. 1, 1998

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Table 3 Transesterification of 2–5a–m with lithium methoxide
Starting from 2–5
Major prod.
(% ee)
Minor prod.
(% ee)
Cond. for HPLC analysis
b c
a
Entry
Compd.
anti:syn
Yield (%)
(chiral column, eluent )
1
2
3
4
5
6
7
8
9
0
1
2
3
a
b
c
d
e
f
g
h
i
93:7
60:40
94:6
87:13
94:6
62:38
98:2
37:63
86:14
69:31
89:11
54:46
30:70
75
71
67
72
68
82
79
60
85
72
74
75
83
anti (77)
anti (70)
anti (67)
anti (79)
anti (65)
anti (69)
anti (67)
syn (94)
anti (70)
anti (32)
anti (60)
anti (47)
syn (60)
syn (65)
syn (90)
—
syn (64)
—
syn (88)
—
anti (22)
syn (83)
syn (94)
syn (85)
syn (73)
anti (26)
anti (OD, 10), syn (AD, 8)
anti (AD, 15), syn (OJ, 30)
anti (AS, 10), syn (AD, 15)
anti (AD, 15), syn (AS, 8)
anti (AS, 12), syn (AS, 15)
d
d
anti (AD, 1) , syn (AD, 2)
d
d
anti (AD, 3) , syn (AD, 3)
d
d
d
anti (OJ, 10) , syn (AD, 15)
d
d
anti (OJ, 10) , syn (AD, 5)
d
1
1
1
1
j
k
l
anti (OJ, 10) , syn (AD, 20)
d
d
anti (OJ, 15) , syn (OJ, 20)
e
e
anti (OJ, 12) syn (OJ, 15)
e
e
m
anti (OJ, 15) syn (OJ, 15)
a
b
c
i
d
e
Combined isolated yield. Daicel Chem. Ind. LTD. % of Pr OH in hexane. Detected at 235 nm. Diethylamine (0.01%) was added.
Ph
R
O
O
Li
O
O
H
H
Li
O
Li
O
Li
Li
O
Li
Ph
H
Ph
H
O
O
H
O
E+
H
Boc
Boc
TS-A
si-approach
TS-B
re-re-approach
TS-A'
Fig. 2 Mechanistic explanation for observed stereochemistry in the
aldol and related reactions
Earlier we reported the asymmetric alkylation of the ester
enolate of (S)-1 with alkyl halides in which the E-enolate forms
preferentially by the action of BuLi or LDA in THF and the
approach of the electrophiles is directed from the less-hindered
si-face of the enolate (TS-A in Fig. 2) to give the S,S-product
selectively. According to this hypothesis, the rigidly fixed lith-
ium enolate influences the direction of the approach of the
electrophile such that the combination of the si-face of the E-
enolate of (S)-1 and the si-face of the aldehyde carbonyl would
lead to the anti product of S,R,S-conformation (S,R,R for 2f
and g). However, the observed stereochemistry of the major
anti product, S,S,R, is inconsistent with the proposed TS-A.
Furthermore, even the six-membered transition state, which is
generally accepted for the aldol reaction, can not account for
the observed stereochemistry. Consequently, we proposed an
acyclic TS of chelated lithium enolate involving the aldehyde
carbonyl and a 2Ј-hydroxy group (TS-B in Fig. 2). The re-re
approach in TS-B may explain the stereochemical course of
the present aldol reaction. The π-face of the aldehyde to be
attacked, i.e. the syn or anti stereochemistry of the products,
depends on the identity of the group R. Generally, an approach
to the re-face of the aldehyde might be favourable due to gauche
interaction between R and the phenyl ring of the enolate, if
R lacks heteroatoms with lone-pair electrons. The reverse may
also occur to give the syn product, when R bearing hetero-
atoms occupies a position gauche to the phenyl group to avoid
repulsive interaction between ester oxygens or the naphthalene
ring.
Fig. 1 Crystal structure of (S,S,R)-2e
ently by reaction of the enolate of methyl phenylacetate and
the corresponding aldehyde, and the enantiomeric excess (ee)
of each diastereoisomer was determined by HPLC analysis on
a chiral stationary phase. These HPLC analyses also indicated
that no significant racemization occurred during the ester
exchange reaction. These results are summarized in Table 3.
In addition, the absolute structure of one of the major anti-
diastereoisomers 2e was unambiguously determined by X-ray
analysis (Fig. 1).
2
When 2Ј-methoxy-1,1Ј-binaphthalen-2-yl phenylacetate 8
was used as a substrate for the aldol reaction with benzaldehyde
under the same reaction conditions as above, no aldol adducts
formation was detectable, probably because of lack of effective
2
CIPE in the enolate formation. However, the reaction using
LDA as a base provided the aldol adducts in a much lower yield
(
9%) with an anti/syn ratio of 89:11 (Scheme 3). The diastereo-
O
O
OH
LDA
PhCHO
Ph
O
O
Ph
THF
78 °C for 2 h
OMe
OMe Ph
-
8
9
CH2N2
The selectivity in the reaction of the ester enolate of 1,1Ј-
binaphthyl-2,2Ј-diol (BINOL) with electrophiles other than
aldehydes or alkyl halides was examined next. The ester enolate
failed to react with alkyl or aryl ketones such as benzophenone
and cyclohexanone in satisfactory yield under the same reac-
tion conditions as those used for the aldol reaction mentioned
above, probably because of steric constraints. No significant
reactivity of the enolate was observed in the Michael reaction
with methyl acrylate, methyl vinyl ketone and acrylonitrile, and
no noticeable diastereoselectivity was observed with cyclopent-
2-enone as a Michael acceptor. On the other hand, the lithium
2
a
Scheme 3
selectivity of the major anti adduct 9 was deduced by com-
parison of the HPLC analysis with that of an authentic sample
9
1
obtained by treatment of 2a with CH N , which gave only
2 2
2% de of 9. These experiments clearly suggest that the free
hydroxy group at the 2Ј position plays a crucial role in both the
reactivity and the induction of diastereoselectivity.
2
J. Chem. Soc., Perkin Trans. 1, 1998
187

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Table 4 The Michael reaction of 1 with methylenemalonate
Table 5 Conjugate addition of the anion of (S)-1 with DBAD
a
b
a
b
c
Solvent
Yield (%)
de (%)
Solvent
Yield (%)
de (%)
Config. at C-2
THF
Ether
Toluene
DME
THF–ether (2:1)
THF–toluene (2:1)
THF–DME (2:1)
63
51
6
57
81
96
82
63
38
—
41
66
56
THF
THF–ether (2:1)
THF–toluene (2:1)
97
99
99
75
68
61
S
S
S
c
a
b
Isolated yield. Determined by HPLC analysis using a Puresil C18
c
c
column. Determined by the [α]D of the methyl ester 13.
c
65
a
c
b
in an excellent yield of up to 99%, and the results are summar-
ized in Table 5. Thus, a diastereoselectivity of 61–75% was
observed by reversed-phase HPLC analysis of the products. The
S configuration at the position α to the carbonyl was confirmed
by chemical transformation to the known methyl ester 13.
Unlike the situation with the aldol or Michael products,
removal of the chiral auxiliary group proved to be troublesome,
and led to significant racemization. Thus, hydrolysis of 12 of
Isolated yield. 1 Determined by HPLC using a silica gel column.
Determined by H NMR (400 MHz) for the C-2Ј hydroxy signal.
enolate of (S)-1 underwent conjugate addition with an acti-
vated Michael acceptor, di-tert-butyl methylenemalonate, in
good yield (85%) and with moderate diastereoselectivity (65%
de) (Scheme 4). The reactions were carried out under different
n
75% de by LiOH–MeOH–H O followed by methylation with
Bu Li
2
O
CH2=C(Boc)2
CH N gave the methyl ester 13 (79%). However, the ee fell to
2
2
CH2CH(Boc)2
O
26%. Furthermore, the ester exchange with LiOMe–MeOH
could not prevent racemization (from 64% de to 6% ee).
Conversion of the methyl ester 13 to phenylglycine has already
(S)-1
OH
Ph
–
1
78 °C
.5 h
10
been reported by Evans and his co-workers. The si-approach
in a transition state analogous to TS-A leads to an absolute
stereostructure of S,S for the product 12, and this was con-
firmed by comparing the sign of the specific rotation of the
1
0
O
LiOMe
MeOH
CH2CH(Boc)2
10
methyl ester 13 with that which has been previously reported.
MeO
(
S)-2,2'-BINOL
In conclusion, we have investigated diastereoselectivity in the
reaction of a chiral ester enolate with achiral carbonyl electro-
philes. The ester enolate of BINOL generated by BuLi reacted
with several aldehydes to give the threo products preferentially
with high diastereoselectivity in good yield. Satisfactory dia-
stereoselectivity was also found in the minor erythro derivatives.
With axially chiral binaphthol as an auxiliary in the stoichio-
metric transformation, the present study demonstrates that
non-racemic β-hydroxy carboxylic acid derivatives can be pre-
pared with some degree of stereochemical prediction. Since β-
hydroxy carboxylic acids often occur as a structural unit in bio-
logically important compounds such as natural products, this
method may be used to prepare these compounds. Use of this
auxiliary was also extended to Michael-type reactions. Regard-
ing the mechanisms of these reactions, the remaining hydroxy
group at the 2Ј position of the auxiliary may play an important
role in bringing about the high degree of diastereoselectivity.
Related reactions with other types of electrophiles as well as
elucidation of the precise mechanism are in progress.
+
Ph
0
1
°C
h
1
1
84% yield
4% ee
82% yield
~100% ee
6
Scheme 4
reaction conditions and the diastereoisomer ratio was deter-
1
mined by H NMR (at 400 MHz) analysis. These results are
listed in Table 4. Among the solvents examined, a combination
of THF with ether, toluene or DME gave better chemical yield
and selectivity. The Michael adduct 10 was converted into the
methyl ester 11 in a manner similar to the transformation of
the aldol product by LiOMe in 84% yield. HPLC analysis on a
reverse chiral stationary phase showed that the methyl ester of
6
4% ee was obtained starting from 10 of 65% de. While the
absolute stereostructure of 11 has yet to be determined, it is
believed to be S from mechanistic considerations having been
formed via a transition state of type TS-AЈ (Fig. 2).
Electrophilic amination is an efficient synthetic strategy for
the construction of α-amino acid derivatives, including those
that are non-proteinogenic. DBAD (di-tert-butyl azodicarb-
oxylate) is an electrophilic amine source. As an extension of
the Michael-type reaction of the binaphthyl ester enolate, the
conjugate addition of the anion to DBAD was investigated
Experimental
General
1
Unless otherwise specified, all H NMR spectra were taken at
(
Scheme 5). The reactions proceeded quite smoothly to give 12
200 or 400 MHz in CDCl with chemical shifts being reported
3
at δ ppm from tetramethylsilane as an internal standard; coup-
ling constants are expressed in Hz. IR spectra were measured
n
O
Bu Li
BocN=NBoc
Ph
in CHCl . THF, Ether, DME and toluene were distilled from
3
O
sodium benzophenone ketyl, and CH Cl2 was from calcium
(S)-1
2
-78 °C, 2 h
OH
hydride and MeOH was from magnesium. Unless otherwise
noted, all reactions were run under an argon or a nitrogen
atmosphere. All extracted organic solutions were dried over
BocN
NHBoc
1
2
75% de
anhydrous MgSO . Flash column chromatography was carried
4
out with silica gel 60 spherical (150–325 mesh) and silica gel 60
F254 plates (Merck) were used for preparative TLC (pTLC).
O
Ph
Diastereoisomeric excesses (de) were determined by HPLC on a
1
) LiOH
MeO
+
(S)-2,2'-BINOL
1
Puresil C18 column (Waters Co.) with MeOH–H O or H NMR
2
BocN
2
) CH2N2
(400 MHz). The enantiomeric excess (ee) of methyl propanoate
derivatives was determined by HPLC on Chiralpak AS, AD,
NHBoc
i
1
3
79% yield
6% ee
99% yield
~100% ee
OD, or OJ column (Daicel Co.) with hexane–Pr OH, or on
2
Ceramospher (chiral) Ru-1 column (Shiseido Co.) with MeOH.
Scheme 5
The analysis of the recovered (S)-(Ϫ)-binaphthol was carried
1
88
J. Chem. Soc., Perkin Trans. 1, 1998

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i
out in a Chiralpak AS column with hexane–Pr OH (80:20). [α]
2Ј-Hydroxy-1,1Ј-binaphthalen-2-yl 3-hydroxy-2-phenylpent-
Ϫ1
D
Ϫ1
2
Ϫ1
Values recorded in units of 10 deg cm g
.
anoate 2–5f. 71% Yield; amorphous solid; νmax/cm 3534,
080–2880, 1734 and 1150; δ (400 MHz) 0.68 (t, J 7.3; 4,5f),
3
H
General procedure for the aldol reaction of the anion of 1
0.72 (3H, t, J 7.3; 2f), 0.93 (m; 4,5f), 1.07 (2H, m; 2f), 2.12
(br d; 3f), 2.17 (1H, br d; 2f), 3.40 (d, J 7.3; 4,5f), 3.42 (1H, d,
J 8.8; 2f), 3.48 (d, J 9.3; 3f), 3.68 (m; 4,5f), 3.75 (m; 3f), 3.81
(1H, m; 2f), 5.17 (s; 3f), 5.23 (1H, s; 2f), 6.77–8.05 (17H, m;
2
The preparation of 2a is typical. To a solution of (S)-1 (200
3
mg, 0.50 mmol) in THF (8 cm ) was added butyllithium (1.62 
in hexane; 642 µl, 1.04 mmol, 2.1 equiv.) at Ϫ78 ЊC. After being
stirred for 5 min, the above enolate solution was treated with
benzaldehyde (52.8 µl, 0.52 mmol, 1.05 equiv.), added dropwise,
and the resulting mixture was stirred at Ϫ78 ЊC for 2 h. The
reaction mixture was then poured into cold 10% aqueous
ϩ
ϩ
2–5f); m/z (EI) 462 (M ) (Found: M , 462.1860. C H O
31
26
4
requires 462.1831).
2Ј-Hydroxy-1,1Ј-binaphthalen-2-yl
methylpentanoate 2–5g. 58% Yield; amorphous solid; νmax/cm
3-hydroxy-2-phenyl-4-
Ϫ1
NH Cl, and extracted with AcOEt. The extracts were washed
3535, 3060–2880, 1732 and 1170–1150; δ (400 MHz) 0.66 (3H,
4
H
with water, dried and evaporated under reduced pressure. The
residual products of 2–5a were analyzed by HPLC (for condi-
tions, see Table 3) and purified by pTLC (hexane–CH Cl –
AcOEt = 4:1:1, 2 times) to give 2–5a (246 mg, 97%) as
amorphous solids.
d, J 6.8; 2g), 0.67 (d, J 6.8; 3g), 0.69 (3H, d, J 6.8; 2g), 0.72 (d, J
6.8; 3g), 1.13 (1H, m; 2g), 1.96 (br d; 3g), 2.03 (1H, d, J 5.9; 2g),
3.58 (1H, d, overlapped; 2g), 3.60 (d, overlapped; 3g), 3.69 (1H,
m; 2g), 5.14 (s; 3g), 5.20 (1H, s; 2g) and 6.79–8.05 (17H, m;
2
2
ϩ
ϩ
2–5g); m/z (EI) 476 (M ) (Found: M , 476.1995. C H O
32 28 4
2
Ј-Hydroxy-1,1Ј-binaphthalen-2-yl 3-hydroxy-2,3-diphenyl-
requires 476.1987).
2Ј-Hydroxy-1,1Ј-binaphthalen-2-yl 3-hydroxy-3-(2-furyl)-2-
phenylpropanoate 2–5h. 99% Yield; amorphous solid; νmax/cm
propanoate 2a and 3–5a. Compound 2a: mp 169–170 ЊC; plates
from hexane and ether); [α]D Ϫ86.0 (c 1.1, in CHCl ) (Found:
20
Ϫ1
(
3
C, 82.28; H, 5.00. Calc. for C H O : C, 82.34; H, 5.13%); νmax/
3675, 3540, 3080–2900, 1747 and 1170–1150; δ (400 MHz) 1.96
35
26
4
H
Ϫ1
cm 3550, 3080–2920, 1740 and 1170–1140; δ (400 MHz) 2.55
(1H, d, J 4.4; 4h), 2.63 (d, J 5.5; 2h), 4.01 (1H, d, J 8.4; 4h), 4.05
(d, J 9.5; 2h), 4.09 (d, J 9.2; 3h), 4.94 (dd, J 9.2 and 5.5; 3h), 5.01
(dd, J 9.3 and 5.7; 2h), 5.06 (1H, dd, J 8.4 and 4.0; 4h), 5.09
(1H, s; 4h), 5.18 (s; 3h), 5.22 (s; 2h), 5.85–6.31 (2H, m; 2–5f) and
H
(
1H, d, J 4.0), 3.70 (1 H, d, J 9.7), 4.95 (1H, dd, J 9.7 and 3.9),
5
.23 (1H, s), and 6.64–8.05 (22H, m).
Compounds 3–5a IR spectra the same as above for 2a;
ϩ
ϩ
δH(200 MHz) 2.12 (br d; 4,5a), 2.49 (br d; 3a), 3.72 (d, J 7.3;
,5a), 3.74 (d, J 9.7; 3a), 4.83 (overlapped; 4a), 4.84 (over-
lapped; 3a), 5.01 (1H, s; 4,5a), 5.21 (1H, s; 3a) and 6.64–8.05
6.67–8.07 (18H, m; 2–5h); m/z (EI) 500 (M ) (Found: M ,
4
500.1650. C H O requires 500.1623).
33
24
5
2Ј-Hydroxy-1,1Ј-binaphthalen-2-yl 3-hydroxy-3-(3-furyl)-2-
Ϫ1
(
22H, m; 3–5a).
Ј-Hydroxy-1,1Ј-binaphthalen-2-yl 3-hydroxy-3-(1-naphthyl)-
-phenylpropanoate 2–5b. 95% Yield; amorphous solid; ν
phenylpropanoate 2–5i. 95% Yield; amorphous solid; νmax/cm
2
3535, 3080–2900, 1735 and 1150; δ (400 MHz) 1.94 (br d; 4,5i),
H
2
/
ϩ
2.47 (br d; 3i), 2.53 (br d, 1H; 2i), 3.68 (1H, d, J 9.5; 2i), 3.69
(d, J 7.7; 4,5i), 3.73 (d, J 9.5; 3i), 4.90 (d, J 7.7; 4,5i), 4.98 (1H, d,
J 9.2; 2i), 5.10 (s; 4,5i), 5.18 (s; 3i), 5.22 (1H, s; 2i), 5.94 (br s;
4,5i), 5.95 (1H, br s; 2i), 6.15 (br s; 3i) and 6.68–8.07 (19H,
max
Ϫ1
cm 3530, 3070–2840, 1735 and 1150–1070; m/z 560 (M );
δH(400 MHz) 2.64 (br s; 4,5b), 2.74 (br s; 3b), 2.82 (1H, br s;
2
3
b), 3.92 (d, J 4.4; 4,5b), 4.16 (1H, d, J 9.5; 2b), 4.23 (d, J 8.8;
b), 5.28 (1H, s; 2b), 5.40 (d, J 4.0; 4,5b), 5.55 (d, J 9.2; 3b), 5.59
ϩ
ϩ
m; 2–5i); m/z (EI) 500 (M ) (Found: M , 500.1631. C H O
33
24
5
(
(
1H, d, J 9.5; 2b), and 6.61–8.06 (24H, m; 2–5b); m/z (EI) 560
requires 500.1624).
2Ј-Hydroxy-1,1Ј-binaphthalen-2-yl 3-hydroxy-3-(5-methyl-2-
ϩ
ϩ
M ) (Found: M , 560.2021. C H O requires 560.1988).
39
28
4
2
Ј-Hydroxy-1,1Ј-binaphthalen-2-yl 3-hydroxy-3-(2-naphthyl)-
furyl)-2-phenylpropanoate 2–5j. 99% Yield; amorphous solid;
Ϫ1
2
-phenylpropanoate 2–5c. 98% Yield; amorphous solid; νmax/
νmax/cm
3690, 3535, 3080–2840, 1746 and 1170–1150;
Ϫ1
cm 3535, 3080–2840, 1743 and 1150; δ (400 MHz) 2.20 (d,
δH(400 MHz) 1.86 (br s; 4,5j), 2.04 (s; 3j), 2.15 (3H, s; 2j),
2.27 (s; 4,5j), 2.59 (1H, br s; 2,3j), 4.00 (d, J 9.2; 4,5j), 4.05 (1H,
d, J 9.5; 2j), 4.08 (d, J 9.5; 3j), 4.88 (d, J 9.5; 3j), 4.95 (1H, d,
J 9.5; 2j), 5.02 (d, J 9.2; 4,5j), 5.11 (s; 4,5j), 5.20 (s; 3j), 5.24 (1H,
s; 2j), 5.64–6.02 (2H, m; 2–5j) and 6.67–8.07 (17H, m; 2–5j);
H
no resolution; 4,5c), 2.59 (d, J 4.0; 3c), 2.69 (1H, d, J 4.0; 2c),
3
4
2
2
.83 (d, J 7.0; 4,5c), 3.84 (1H, d, J 9.5; 2c), 3.89 (d, J 9.5; 3c),
.97 (1H, s; 4,5c), 5.02 (m; 3–5c), 5.13 (1H, dd, J 9.5 and 4.0;
c), 5.22 (1H, s; 3c), 5.23 (1H, s; 2c) and 6.61–8.06 (24H, m;
ϩ
ϩ
ϩ
ϩ
–5c); m/z (EI) 560 (M ) (Found: M , 560.2008. C H O
m/z (EI) 514 (M ) (Found: M , 514.1755. C H O requires
39
28
4
34 26 5
requires 560.1988).
514.1780).
2
Ј-Hydroxy-1,1Ј-binaphthalen-2-yl
(E)-3-hydroxy-2,5-di-
2Ј-Hydroxy-1,1Ј-binaphthalen-2-yl 3-hydroxy-3-(2-thienyl)-2-
phenylpropanoate 2–5k. 97% Yield; amorphous solid; νmax/cm
Ϫ1
phenylpent-4-enoate 2–5d. 91% Yield; amorphous solid; ν
/
max
ϩ
Ϫ1
cm 3530, 3080–2840, 1740 and 1170–1150; m/z 536 (M );
δH(400 MHz) 1.85 (br s; 4,5d), 2.31 (br s; 3d), 2.38 (1H, br s; 2d),
3540, 3080–2900, 1740 and 1150; δ (400 MHz) 2.14 (d, J 3.3;
H
4,5k), 2.74 (d, J 4.8; 3k), 2.77 (1H, d, J 4.4; 2k), 3.80 (1H, d, J
9.5; 2k), 3.82 (d, no resolution; 4,5k), 3.83 (d, J 9.5; 3k), 5.03 (s;
4,5k), 5.18 (s; 3k), 5.19 (1H, s; 2k), 5.20 (no resolution; 3–5k),
5.25 (1H, dd, J 9.3 and 4.6; 2k) and 6.43–8.07 (20H, m; 2–5k);
3
4
4
5
6
.58 (1H, d, J 9.2; 2d), 3.62 (d, J 7.3; 4,5d), 3.63 (d, J 9.2; 3d),
.47 (br t; 4,5d), 4.61 (1H, br t, J 7.3; 2d), 4.57 (br t; 3d), 5.15 (s;
,5d), 5.21 (s; 3d), 5.24 (1H, s; 2d), 5.76 (dd, J 16.1 and 5.9; 3d),
.79 (1H, dd, J 15.8 and 6.2; 2d), 5.97 (dd, J 16.1 and 7.0; 4,5d),
.34 (1H, d, J 15.4; 2d), 6.49 (d, J 16.1; 3d), 6.77 (d, J 7.3; 4,5d)
ϩ
ϩ
m/z (EI) 516 (M ) (Found: M , 516.1436. C H O S requires
33
24
4
516.1396).
ϩ
ϩ
and 6.92–8.05 (22H, m; 2–5d); m/z (EI) 536 (M ) (Found: M ,
36.2036. C H O requires 536.1987).
2Ј-Hydroxy-1,1Ј-binaphthalen-2-yl 3-hydroxy-3-(3-pyridyl)-2-
Ϫ1
5
phenylpropanoate 2–5l. 91% Yield; amorphous solid; νmax/cm
37
28
4
2
Ј-Hydroxy-1,1Ј-binaphthalen-2-yl 3-hydroxy-3-(4-methoxy-
3542, 3080–2970, 1733 and 1150; δ (400 MHz) 3.60 (d, J 6.3;
4,5l), 3.63 (1H, d, J 9.8; 2l), 3.72 (d, J 9.8; 3l), 4.80 (d, J 5.9; 4l),
H
phenyl)-2-phenylpropanoate 2–5e. 94% Yield; 2e: mp 159–
60 ЊC; plates (from hexane and ether); [α]D Ϫ99.9 (c 1.02, in
CHCl ) (Found: C, 78.63; H, 5.26. Calc. for C H O ؒ1/2H O:
C, 78.67; H, 5.32%); νmax/cm 3540, 3080–2840, 1735 and
170–1150; δ (400 MHz) 2.45 (1H, d, J 3.7), 3.67 (3H, s), 3.70
20
1
4.83 (d, J 9.8; 3l), 4.96 (1H, d, J 9.8; 2l), 5.00 (d, J 6.4; 5l) and
ϩ
ϩ
6.55–8.54 (21H, m; 2–5l); m/z (EI) 511 (M ) (Found: M ,
3
36 28
5
2
Ϫ1
511.1815. C H NO requires 511.1783).
34
25
4
1
(
6
2Ј-Hydroxy-1,1Ј-binaphthalen-2-yl 3-hydroxy-3-(4-pyridyl)-2-
H
Ϫ1
1H, d, J 9.9), 4.90 (1H, dd, J 9.9 and 3.3), 5.24 (1H, s) and
.58–8.07 (21H, m); m/z (EI) 540 (M ) (Found: M , 540.1956.
phenylpropanoate 2–5m. 90% Yield; amorphous solid; νmax/cm
ϩ
ϩ
3536, 3080–2920, 1732 and 11.50; δ (400 MHz) 3.58 (1H,
H
C H O requires 540.1937).
d, J 5.6; 4m), 3.65 (d, J 6.3; 5m), 3.66 (d, J 9.4; 2m), 3.71 (d, J
9.4; 3m), 4.74 (d, J 5.6; 4m), 4.81 (d, J 9.4; 3m), 4.92 (d, J 9.4;
2m), 4.97 (d, J 6.3; 5m) and 6.55–8.38 (21H, m; 2–5m); m/z
36
28
5
Compounds 3–5e: IR the same as 2e; δ (400 MHz) 2.38
d, J 3.8; 3e), 3.66 (s; 3e), 3.73 (d, J 7.8; 4,5e), 3.74 (d, J 9.7; 3e),
H
(
ϩ
ϩ
3
5
.81 (s; 4,5e), 4.80 (dd, J 9.5 and 3.7; 3e), 4.81 (d, J 7.4; 4,5e),
.20 (s; 3e) and 6.58–8.07 (21H, m; 3–5e).
(EI) 511 (M ) (Found: M , 511.1811. C H NO requires
34 25 4
511.1783).
J. Chem. Soc., Perkin Trans. 1, 1998
189

View Article Online
X-Ray analysis of 2e
General procedure for transesterification of 2–5a–m to methyl
esters 6,7a–m
Crystal data. C H O , M = 540.61, Monoclinic, Noncent,
3
6
28
5
a = 17.563(11), b = 9.554(3), c = 18.330(8) Å, β = 112.62(4)Њ,
V = 2839.1 Å (by least squares refinement for 25 reflections
The transformation of 2a to 6a and 7a is typical. A solution of
3
3
2a (139 mg, 0.26 mmol) in MeOH (3 cm ) was treated with
3
with 15.08 < θ < 24.20, λ = 0.7107 Å, T = 295 K) space group
LiOMe (1.17  in MeOH, 0.67 cm ; 0.86 mmol, 3 equiv.) at
Ϫ3
C2 (no. 5), Z = 4, D = 1.265 g cm , dimension 0.4 × 0.3 × 0.1
0 ЊC. The mixture was stirred at 0 ЊC for 1 h after which it
c
Ϫ1
mm, µ(Mo-Kα) = 0.138 mm , F(000) = 1136. Full crystallo-
was poured into cold 10% aqueous NH Cl and extracted with
4
graphic details, excluding structure factor tables, have been
deposited at the Cambridge Crystallographic Data Centre
AcOEt. The extract was washed with water, dried and evapor-
ated under reduced pressure. The residual product was purified
by pTLC (hexane–acetone = 3:1, 2 times) to give (S)-(Ϫ)-
binaphthol (71 mg, 95%, >99% ee) and 6a and 7a (50.4 mg,
75%). The diastereoisomeric mixture was separated by pTLC
(hexane–AcOEt = 3:1) and the enantiomeric excess was ana-
lyzed by HPLC analysis on a chiral stationary phase with the
(
CCDC). For details of the deposition scheme, see ‘Instructions
for Authors’, J. Chem. Soc., Perkin Trans. 1, available via the
RSC Web pages (http://www.rsc.org/authors). Any request to
the CCDC for this material should quote the full literature
citation and the reference number 207/168.
i
solvent system of Pr OH and hexane (see Table 3).
Data collection and processing
Rigaku AFC-5 diffractometer, graphite monochromated Mo-
Kα radiation; ω–2θ scan method. 2589 Reflections measured
Methyl 3-hydroxy-2,3-diphenylpropanoate 6a
18
70% Yield; amorphous solid; [α] Ϫ122.6 (c 1.22, in MeOH,
D
Ϫ1
(
4.56 < 2θ < 50.0, h, k, ±l) 2499 unique (Rint = 0.0149), giving
77% ee); νmax/cm 3600, 3080–2840, 1725 and 1160; δ (200
H
2
298 observed [F > 3.00 σ(F)] which were used in all further
MHz) 3.16 (d, 1H, d, J 4.0), 3.73 (3H, s), 3.88 (1H, d, J 9.4),
5.18 (1H, dd, 9.4 and 3.8) and 7.07–7.26 (10H, m); m/z (EI) 256
calculations.
ϩ
ϩ
(
M ) (Found: M , 256.1102. C H O requires 256.1099).
16 16 3
Structure solution and refinement
Methyl 3-hydroxy-3-(1-naphthyl)-2-phenylpropanoate 6b. 55%
The structure was solved by direct methods with the program
18
Yield; amorphous solid; [α]D Ϫ79.4 (c 2.7, in CHCl , 70% ee);
3
11
MULTAN88. The positional parameters and anisotropic ther-
mal factors of the non-H atoms were refined by the full-matrix
Ϫ1
νmax/cm 3600, 3080–2840, 1726 and 1160; δ (200 MHz) 3.60
H
(
1H, d, J 5.2), 3.73 (3H, s), 4.34 (1H, d, J 8.3), 5.88 (1H, dd, J
least-squares method R = 0.068, R = 0.086. Maximum peak in
w
8.4 and 5.1), 7.11 (5H, s), 7.26–7.46 (4H, m), 7.69–7.83 (2H, m)
Ϫ3
the final ∆F was 0.27 e Å . All calculations were carried out
ϩ
ϩ
and 8.14 (1H, m); m/z (EI) 306 (M ) (Found: M , 306.1225.
12
using the KPPXRAY package in the Data Processing Center
of Kyoto University.
C H O requires 306.1256).
20
18
3
Methyl 3-hydroxy-3-(1-naphthyl)-2-phenylpropanoate 7b. 16%
1
8
Yield: amorphous solid; [α] Ϫ189 (c 0.4, in CHCl , 90% ee);
D
3
Table 6 Comparison of the vicinal coupling constants J of the aldol
ab
Ϫ1
1
a
νmax/cm 3570, 3080–2840, 1730 and 1220–1160; δ (200 MHz)
adducts in the H NMR spectra (400 MHz)
H
3
.17 (1H, br d, J 2.6), 3.60 (3H, s), 4.24 (1H, d, J 5.6), 6.16 (1H,
ϩ
anti (2 or 3)
syn (4 or 5)
dd, J 5.5 and 1.9) and 7.08–8.21 (12H, m); m/z (EI) 306 (M )
Compd.
ϩ
(
Found: M , 306.1261. C H O requires 306.1256).
20 18 3
2
–5
major (minor)
major (minor)
Methyl 3-hydroxy-3-(2-naphthyl)-2-phenylpropanoate 6c. 63%
18
b
Yield; amorphous solid; [α] Ϫ135.6 (c 1.01, in CHCl , 67% ee);
D
3
a
b
c
d
e
f
g
h
i
9.7 (9.7)
9.5 (9.2)
9.5 (9.5)
9.2 (9.2)
9.9 (9.7)
8.8 (9.3)
9.5 (9.5)
9.5 (9.2)
9.5 (9.5)
9.5 (9.5)
9.5 (9.5)
9.8 (9.8)
9.4 (9.4)
7.3 (—)b
Ϫ1
νmax/cm 3600, 3080–2840, 1730 and 1160; δ (200 MHz) 3.35
4.0 (—)b
H
7.0 (—)b
7.3 (—)
(1H, br s), 3.72 (3H, s), 3.99 (1H, d, J 9.2), 5.34 (1H, dd, J 9.2
ϩ
and 3.4) and 7.08–7.77 (12H, m); m/z (EI) 306 (M ) (Found:
b
7.8 (—)b
ϩ
M , 306.1232. C H O requires 306.1256).
20
18
3
7.3 (—)
Methyl (E)-3-hydroxy-2,5-diphenylpent-4-enoate 6d. 63%
b
b
— (—)
b
1
8
Yield; amorphous solid; [α]
Ϫ146.2 (c 1.1, in CHCl
, 79% ee);
D
3
8.4 (—)b
Ϫ1
νmax/cm 3600, 3080–2840, 1730 and 1195–1170; δ (200 MHz)
7.7 (—)b
H
j
k
l
9.2 (—)
3.06 (1H, d, J 4.8), 3.72 (3H, s), 3.77 (1H, d, no resolution), 4.86
(1H, m), 6.01 (1H, dd, J 15.9 and 5.9), 6.52 (1H, d, J 16.0), 7.24
b
b
— (—)
5.9 (6.4)
5.6 (6.3)
ϩ
ϩ
(
2
5H, s) and 7.32 (5H, s); m/z (EI) 282 (M ) (Found: M ,
82.1229. C H O requires 282.1256).
m
18
18
3
a
b
Methyl(E)-3-hydroxy-2,5-diphenylpent-4-enoate7d.9%Yield;
Measured in CDCl . Chemical shifts in ppm downfield from Me Si.
Could not be determined because of poor resolution or because only
3
4
1
8
Ϫ
1
colourless oil; [α]D Ϫ57.2 (c 0.46, in CHCl , 64% ee); νmax/cm
3
trace amounts were obtained.
3580, 3080–2840, 1730 and 1160; δ (200 MHz) 2.41 (1H, d, J
H
1
a
Table 7 Comparison of the chemical shifts of the anti isomers 2a–m and 3a–m in the H NMR spectra (400 MHz)
β-OH
α-Proton
β-Proton
2Ј-OH
Compd.
2
and 3
major
minor
major
minor
major
minor
major
minor
5.21
a
b
c
d
e
f
g
h
i
2.55
2.82
2.69
2.38
2.45
2.17
2.03
2.63
2.53
2.15
2.77
2.49
2.74
2.59
2.31
2.38
2.12
1.96
3.70
4.16
3.84
3.58
3.70
3.42
3.58
4.05
3.68
4.05
3.80
3.63
3.66
3.74
4.23
3.89
3.63
3.74
3.48
3.60
4.09
3.73
4.08
3.83
3.72
3.71
4.95
5.59
5.13
4.61
4.90
3.81
3.69
5.01
4.98
4.95
5.25
4.96
4.92
4.84
5.55
5.02
4.57
4.80
3.75
5.23
5.28
5.23
5.24
5.24
5.23
5.20
5.22
5.22
5.24
5.19
b
—
5.22
5.21
5.20
5.17
5.14
5.18
5.18
5.20
5.18
b
—
b
—
4.94
b
2.47
2.04
2.74
—
j
k
l
4.88
b
—
b
b
b
b
—
—
—
—
4.83
4.81
—
—
—
—
b
b
b
b
m
a
b
Measured in CDCl . Chemical shifts in ppm downfield from Me Si. Not assigned.
3
4
1
90
J. Chem. Soc., Perkin Trans. 1, 1998

View Article Online
2
.5), 3.67 (3H, s), 3.78 (1H, d, J 7.2), 4.86 (1H, m), 6.19 (1H, dd,
Methyl 3-hydroxy-3-(2-thienyl)-2-phenylpropanoate 6k. 66%
18
J 15.9 and 6.8), 6.66 (1H, d, J 15.8) and 7.24–7.40 (10H, m);
m/z (EI) 282 (M ) (Found: M , 282.1219. C H O requires
Yield; amorphous solid; [α] Ϫ103.0 (c 1.16, in CHCl , 60% ee);
D
3
ϩ
ϩ
Ϫ1
νmax/cm 3600, 3080–2900, 1727 and 1160; δ (200 MHz) 3.41
18
18
3
H
2
82.1256).
Methyl 3-hydroxy-3-(4-methoxyphenyl)-2-phenylpropanoate
(1H, d, J 4.6), 3.73 (3H, s), 3.95 (1H, d, J 9.2), 5.47 (1H, dd, J
9.1 and 4.4), 6.59 (1H, br d, J 3.5), 6.78 (1H, dd, J 5.1 and 3.5)
and 7.15–7.26 (6H, m); m/z (EI) 262 (M ) (Found: M ,
18
ϩ
ϩ
6
e. 64% Yield; colourless oil; [α] Ϫ116.7 (c 2.5, in CHCl , 65%
D
3
Ϫ1
ee); νmax/cm 3600, 3080–2840, 1727 and 1170; δ (200 MHz)
262.0654. C H O S requires 262.0664).
H
14 14
3
3
.07 (1H, d, J 3.8), 3.73 (6H, s), 3.86 (1H, d, J 9.5), 5.15 (1H,
Methyl 3-hydroxy-3-(2-thienyl)-2-phenylpropanoate 7k. 8%
Yield; amorphous solid; νmax/cm 3585, 2840–3080, 1730 and
Ϫ1
dd, J 9.5 and 3.6), 6.69–6.75 (2H, m) and 7.00–7.26 (7H, m);
m/z (EI) 286 (M ) (Found: M , 286.1203. C H O requires
ϩ
ϩ
1160; δ (200 MHz) 2.64 (1H, d, J 2.9), 3.58 (3H, s), 3.94 (1H,
17
18
4
H
2
86.1205).
Methyl 3-hydroxy-2-phenylpentanoate 6f. 51% Yield;
d, J 8.1), 5.58 (1H, dd, J 8.1 and 2.3), 6.92–7.01 (2H, m) and
7.23–7.44 (6H, m); m/z (EI) 262 (M ) (Found: M , 262.0643.
ϩ
ϩ
20
amorphous solid; [α] Ϫ61.6 (c 0.70, in CHCl , 69% ee); νmax/
cm 3590, 3080–2840, 1721 and 1170; δ (200 MHz) 0.92 (3H,
C H O S requires 262.0664).
D
3
14 14
3
Ϫ1
Methyl 3-hydroxy-3-(3-pyridyl)-2-phenylpropanoate 6l,7l.
H
t, J 7.3), 1.29 (2H, m), 2.79 (1H, br d, J 4.8), 3.59 (1H, d, J 9.1),
75% Combined yield; mixture of inseparable diastereoisomers;
amorphous solid; νmax/cm 3595, 3080–2920, 1728 and 1165;
Ϫ1
3
.69 (3H, s), 4.10 (1H, m) and 7.25–7.36 (5H, m); m/z (EI) 208
ϩ
ϩ
(
M ) (Found: M , 208.1124. C H O requires 208.1099).
δH(200 MHz) 3.58 (s; 7l), 3.74 (3H, s; 6l), 3.84 (1H, d, J 9.6; 6l),
3.85 (d, J 6.7; 7l), 5.23 (1H, d, J 9.6; 6l), 5.35 (1H, d, J 7.0;
7l), 7.03–7.72 (7H, m; 6,7l) and 8.19–8.51 (2H, m; 6,7l); m/z
12
16
3
Methyl 3-hydroxy-2-phenylpentanoate 7f. 31% Yield; colour-
2
0
Ϫ1
less oil; [α] Ϫ84.2 (c 0.87, in CHCl , 88% ee); νmax/cm 3586,
D
3
ϩ
ϩ
3
080–2840, 1729 and 1160; δ (200 MHz) 1.00 (3H, t, J 7.3),
(EI) 257 (M ) (Found: M , 257.1045. C H NO requires
H
15 15 3
1
.42 (2H, m), 2.41 (1H, br d, J 2.3), 3.61 (1H, d, J 6.3), 3.69
257.1052).
ϩ
(
(
3H, s), 4.13 (1H, m) and 7.36 (5H, s); m/z (EI) 208 (M )
Found: M , 208.1106. C H O requires 208.1099).
Methyl 3-hydroxy-3-(4-pyridyl)-2-phenylpropanoate 6m,7m.
83% Combined yield; mixture of inseparable diastereoisomers;
amorphous solid; νmax/cm 3580, 3080–2960, 1728 and 1165;
δH(200 MHz) 3.62 (3H, s; 7m), 3,73 (s; 6m), 3.79 (d, J 9.2; 6m),
3.83 (1H, d, J 6.2; 7m), 5.17 (d, J 9.2; 6m), 5.34 (1H, d, J 6.2;
7m), 6.95–7.33 (7H, m; 6,7m), 8.38 (d, J 5.9; 6m) and 8.49 (2H,
ϩ
12
16
3
Ϫ1
Methyl 3-hydroxy-2-phenyl-4-methylpentanoate 6g. 77%
1
8
Yield; amorphous solid; [α] Ϫ60.6 (c 0.79, in CHCl , 67% ee);
νmax/cm 3600, 3080–2880, 1724, 1170 and 750; δ (200 MHz)
0
br d, J 3.3), 3.68 (3H, s), 3.74 (1H, d, J 9.4), 4.07 (1H, m)
and 7.32 (5H, s); m/z (EI) 222 (M ) (Found: M , 222.1258.
D
3
Ϫ1
H
.87 (3H, d, J 6.8), 0.94 (3H, d, J 6.9), 1.45 (1H, m), 2.61 (1H,
ϩ
ϩ
d, J 6.0; 7m); m/z (EI) 257 (M ) (Found: M , 257.1091.
ϩ
ϩ
C H O N requires 257.1052).
15
15
3
C H O requires 222.1256).
13
18
3
Methyl 3-hydroxy-3-(2-furyl)-2-phenylpropanoate 6h. 22%
Aldol reaction of the anion of 8
In a similar way to the preparation of 2a except for the usage of
LDA (628 µl, 0.31 mmol) in place of BuLi, 2Ј-methoxy-1,1Ј-
19
Yield; amorphous solid; [α] Ϫ29.2 (c 1.74, in CHCl , 22% ee);
D
3
Ϫ1
νmax/cm 3600, 3080–2840, 1727 and 1170; δ (200 MHz) 3.33
H
(
1H, d, J 5.5), 3.72 (3H, s), 4.20 (1H, d, J 9.1), 5.21 (1H, dd,
binaphthalen-2-yl 3-hydroxy-2,3-diphenylpropanoate 9 was
2
J 9.1 and 5.5), 6.04 (1H, br d, J 2.9), 6.18 (1H, dd, J 3.3 and
1
2
obtained from 2Ј-methoxy-1,1Ј-binaphthyl phenylacetate 8
(125 mg, 0.30 mmol) and benzaldehyde (31.9 µl, 0.31 mmol,
1.05 equiv.) in 9% yield as a mixture of diastereoisomers. HPLC
ϩ
ϩ
.8) and 7.20–7.31 (6H, m); m/z (EI) 246 (M ) (Found: M ,
46.0885. C H O requires 246.0892).
14
14
4
Methyl 3-hydroxy-3-(2-furyl)-2-phenylpropanoate 7h. 38%
analysis of the mixture (on a Puresil C18 column with 22%
19
Ϫ1
Yield; amorphous solid; [α] Ϫ115.8 (c 1.15, in CHCl , 94% ee);
H O–MeOH at a flow rate of 0.5 ml min ) suggested a ratio of
D
3
2
Ϫ1
νmax/cm 3585, 3080–2840, 1732 and 1160; δ (200 MHz) 2.51
50:39:11 for anti:anti:syn.
H
(
1H, br d, J 3.7), 3.60 (3H, s), 4.13 (1H, d, J 8.2), 5.33 (1H, dd,
Compound 9: 9% combined yield; mixture of diastereo-
isomers; amorphous solid; νmax/cm 3587, 3080–2840, 1746
Ϫ1
J 8.1 and 2.9), 6.25 (1H, br d, J 3.3), 6.31 (1H, br d, J 3.3 and
1
ϩ
ϩ
.8) and 7.26–7.39 (6H, m); m/z (EI) 246 (M ) (Found: M ,
and 1150; δ (400 MHz) 2.19 (br d; syn), 2.36 (d, J 5.1; anti-
H
2
46.0875. C H O requires 246.0892).
minor), 2.79 (1H, d, J 3.9; anti-major), 3.51 (s; syn), 3.56 (3H, s;
anti-major), 3.58 (s; anti-minor), 3.64 (d, J 9.4; anti-minor),
3.73 (d, J 8.5; syn), 3.74 (1H, d, J 9.4; anti-major), 4.73 (dd,
J 9.3 and 3.8; anti-minor), 4.80 (1H, dd, J 9.3 and 3.5; anti-
major), 4.87 (br d, J 7.5; syn) and 6.43–7.98 (22H, m); m/z (EI)
14
14
4
Methyl 3-hydroxy-3-(3-furyl)-2-phenylpropanoate 6i. 73%
1
8
Yield; amorphous solid; [α] Ϫ87.2 (c 3.6, in CHCl , 70% ee);
νmax/cm 3600, 3080–2840, 1725 and 1200–1170; δ (200 MHz)
3
8
2
D
3
Ϫ1
H
.27 (1H, br s), 3.71 (3H, s), 3.85 (1H, d, J 9.2), 5.21 (1H, br d, J
ϩ
ϩ
.9), 6.13 (1H, s), 7.09 (1H, s) and 7.18–7.25 (7H, m); m/z (EI)
524 (M ) (Found: M , 524.1995. C H O requires 524.1988).
36
28
4
ϩ
ϩ
46 (M ) (Found: M , 246.0894. C H O requires 246.0892).
14
14
4
Methyl 3-hydroxy-3-(3-furyl)-2-phenylpropanoate 7i. 12%
Michael reaction of the anion of (S)-1 with di-tert-butyl
methylenemalonate
18
Yield; amorphous solid; [α] Ϫ89.7 (c 0.48, in CHCl , 83% ee);
D
3
Ϫ1
νmax/cm 3580, 3080–2840, 1730 and 1160; δ (200 MHz) 2.47
In the same manner as the preparation of 2a, 2Ј-hydroxy-1,1Ј-
binaphthalen-2-yl 2-phenyl-4,4-di-tert-butoxycarbonylbutan-
oate 10 was furnished in the yields shown in Table 4 from
(S)-1 and di-tert-butyl methylenemalonate (1.2 equiv.) with
the action of BuLi (2.1 equiv.) as a mixture of two diastereo-
isomers. The products were analyzed by HPLC with silica gel
column.
H
(
6
(
1H, br s), 3.61 (3H, s), 3.84 (1H, d, J 7.9), 5.29 (1H, d, J 7.8),
ϩ
.34 (1H, br s) and 7.32–7.38 (7H, m); m/z (EI) 246 (M )
ϩ
Found: M , 246.0893. C H O requires 246.0892).
14 14 4
Methyl 3-hydroxy-3-(5-methyl-2-furyl)-2-phenylpropanoate
1
8
6
3
j. 50% Yield; amorphous solid; [α] Ϫ50.2 (c 2.67, in CHCl3,
D
Ϫ1
2% ee); νmax/cm 3598, 3080–2840, 1728 and 1170; δ (200
H
19
MHz) 2.23 (3H, s), 3.20 (1H, d, J 5.5), 3.73 (3H, s), 4.19 (1H, d,
J 9.2), 5.14 (1H, dd, J 9.1 and 5.4), 5.75 (1H, m), 5.90 (1H, d, J
Compound 10: amorphous solid; [α]D Ϫ37.0 (c 1.1, in CHCl3,
65% de) (Found: C, 75.96; H, 6.40. Calc. for C H O : C, 75.93;
4
0
40
7
ϩ
ϩ
Ϫ1
2
.9) and 7.23 (5H, s); m/z (EI) 260 (M ) (Found: M , 260.1048.
H, 6.37%); νmax/cm 3530, 3080–2880, 1760, 1740 and 1220–
C H O requires 260.1049).
1140; δ (400 MHz) 1.39 (d, J 5.5; minor), 1.41 (18H, s; major),
15
16
4
H
Methyl 3-hydroxy-3-(5-methyl-2-furyl)-2-phenylpropanoate
2.04 (1H, m; major), 2,04 (m; minor), 2.25 (m; minor),
2.33 (1H, m; major), 2.80 (dd, J 8.2 and 6.8; minor), 2.85 (1H,
dd, J 8.4 and 7.0; major), 3.51 (t, J 7.9; minor), 3.85 (1H, t,
J 7.9; major), 5.24 (1H, s; major), 5.30 (s; minor) and 6.63–8.05
(17H, m).
18
7
9
j. 22% Yield; amorphous solid; [α] Ϫ102.5 (c 0.65, in CHCl3,
D
Ϫ1
4% ee); νmax/cm 3586, 3080–2840, 1732 and 1160; δ (200
H
MHz) 2.22 (1H, d, J 3.7), 2.29 (1H, s), 3.61 (3H, s), 4.11 (1H, d,
J 8.7), 5.26 (1H, dd, J 8.8 and 3.4), 5.89 (1H, m), 6.16 (1H, d, J
ϩ
ϩ
3
2
.2) and 7.27–7.41 (5H, m); m/z (EI) 260 (M ) (Found: M ,
Methyl 2-phenyl-4,4-di-tert-butoxycarbonylbutanoate 11.
According to the general procedure for the transesterification
60.1011. C H O requires 260.1049).
15
16
4
J. Chem. Soc., Perkin Trans. 1, 1998
191

View Article Online
ϩ
mentioned above, the methyl ester 11 was obtained in 84% yield
from 10 of 65% de as an amorphous solid together with (S)-
BINOL (82% yield, Ϫ100% ee). The optical yield of 11 was
determined by HPLC using a reversed-phase chiral column of
6.43 (1H, br s) and 7.31 (5H, s); m/z (EI) 380 (M ) (Found:
ϩ
M , 380.1956. C H N O requires 380.1948).
19
28
2
6
Ϫ1
Acknowledgements
Ceramospher chiral Ru-1 under the conditions of 0.5 ml min 1
9
D
of flow rate of MeOH detected at 235 nm. Compound 11; [α]
The authors are grateful to Dr Y. Miwa and Prof T. Taga
for performance of the X-ray analysis. We also thank Mr
T. Furuta for assistance with the crystallographic investigations.
Ϫ1
ϩ35.1 (c 0.9 CHCl , 64% ee); νmax/cm 3040–2950, 1732 and
3
1
160–1140; δ (200 MHz) 1.44 (9H, s), 1.47 (9H, s), 2.29 (1H,
H
m), 2.54 (1H, m), 3.02 (1H, dd, J 8.3 and 7.0), 3.65 (1H, m, no
resolution), 3.66 (3H, s) and 7.28–7.34 (5H, m); m/z (EI) 378
ϩ
ϩ
References
(
M ) (Found: M , 378.2032. C H O requires 378.2043).
21 30 6
1
2
3
For example: see K. C. Nicolaou and E. J. Sorensen, Classics in
Total Synthesis, VCH, Weinheim, 1996.
K. Fuji, F. Tanaka, M. Node, K. Tanaka and M. Mizuchi, J. Am.
Chem. Soc., 1995, 117, 12 159.
(a) K. Fuji, K. Tanaka, M. Mizuchi and S. Hosoi, Tetrahedron Lett.,
Conjugate addition of the anion of 1 to DBAD
In the same manner as the preparation of 2a, 2Ј-hydroxy-1,1Ј-
binaphthalen-2-yl
N,NЈ-bis(tert-butoxycarbonyl)hydrazino-
phenylacetate 12 (310 mg, 75% de) was furnished from (S)-1 (204
mg, 0.5 mmol) and di-tert-butyl azodicarboxylate (581 mg, 2.52
mmol, 5 equiv.) by the action of BuLi (2.1 equiv.) as a mixture
of two diastereoisomers. The products were analyzed by
1
991, 32, 7277; (b) K. Fuji, K. Tanaka, M. Ahn and M. Mizuchi,
Chem. Pharm. Bull., 1994, 42, 957; (c) K. Fuji, M. Node, F. Tanaka
and S. Hosoi, Tetrahedron Lett., 1989, 30, 2825; (d) K. Fuji,
M. Node and F. Tanaka, Tetrahedron Lett., 1990, 31, 6553.
3
Ϫ1
4 K. Fuji, F. Tanaka and M. Node, Tetrahedron Lett., 1991, 32, 7281.
5
reversed-phase HPLC using a flow rate of 0.5 cm min of 15%
K. Fuji, K. Tanaka, M. Ahn and Y. Watanabe, Tetrahedron:
Asymmetry, 1996, 7, 1771.
H O in MeOH.
2
2
0
Compound 12: 97% yield; amorphous solid; [α] ϩ6.7 (c 1.5,
D
6 (a) M. Nógrádi, Stereoselective Synthesis, VCH, Weinheim, 1995,
pp. 177–211; (b) Comprehensive Organic Synthesis, ed. B. M. Trost
and I. Fleming, Pergamon Press, Oxford, 1991, vol. 2, ch. 1;
Ϫ1
in CHCl , 75% de); νmax/cm 3550, 3400, 3070–2930, 1750–
3
1
700 and 1160; δ (400 MHz, in C D , at 70 ЊC) 1.12 (br s;
H 6 6
(
c) C. H. Heathcock, Asymmetric Synthesis, ed. J. D. Morrison,
minor), 1.15 (9H, br s; major), 1.40 (s; minor), 1.41 (9H, s;
major), 5.15 (s; minor), 5.31 (1H, br s; major), 6.03 (br s;
minor), 6.17 (1H, br s; major), 6.40 (1H, s) and 6.70–7.70 (17H,
Academic Press, New York, 1984, vol. 3, part B, ch. 2.
D. A. Evans, J. V. Nelson and T. R. Taber, Top. Stereochem., 1982,
7
1
3, 1.
ϩ
ϩ
m); m/z (EI) 634 (M ) (Found: M , 643.2734. C H N O
38
38
2
7
8 (a) S. L. Spassov, Tetrahedron, 1969, 25, 3631; (b) N. A. Kirtchev
and H. G. Kratchanov, Dokl. Bolg. Akad. Nauk, 1978, 31, 59;
(c) J. Mulzer, M. Zippel, G. Brüntrup, J. Segner and J. Finkle,
Liebigs Ann. Chem., 1980, 1108; (d) J. Mulzer and G. Brüntrup,
Chem. Ber., 1982, 2057; (e) J. Mulzer, P. Lasalle, A. Chucholowski,
U. Blaschek and G. Brüntrup, Tetrahedron, 1984, 40, 2111; ( f )
J. Dubac, C. L. Roux and H. Gaspard-Iloughmane, Bull. Soc. Chim.
Fr., 1993, 832.
requires 643.2679).
Methyl N,NЈ bis(tert-butoxycarbonyl)hydrazinophenylacetate
3. A mixture of 12 (200 mg, 0.32 mmol; 75% de), LiOHؒH O
1
2
3
(
27 mg, 0.63 mmol, 2 equiv.) and THF–H O (3:1; 10 cm ) was
2
stirred for 8 h at 0 ЊC and for 14 h at room temperature. After
additional LiOHؒH O (27 mg, 0.63 mmol, 2 equiv.) had been
2
added, the resulting mixture was further stirred for 3 h at room
temperature and then poured into cold 1  aq. HCl. The mix-
ture was extracted with AcOEt, washed with water, dried and
evaporated under reduced pressure. Without isolation and
purification, the residual carboxylic acid was immediately
9 T. Hayashi, Y. Ito and A. Hosomi, Tetrahedron Lett., 1988. 29, 5667.
10 D. A. Evans, T. C. Britton, R. L. Dorow and J. F. Dellaria, Jr.,
Tetrahedron, 1988, 44, 5525.
1 P. Main, S. E. Hull, L. Lessinger, G. Germain, J.-P. Declecq,
M. M. Woolfson, MULTAN88, A System of Computer Programs
for the Automatic Solution of Crystal Structures from X-ray
Diffraction Data. Universities of York, England, and Louvain,
Belgium, 1988.
1
methylated with an excess of CH N in ether at 0 ЊC to give 13
2
2
(
95 mg; 26% ee) in 79% yield concomitant with (S)-BINOL (97
mg, 99% yield; 100% ee). The optical yield of 13 was deter-
12 T. Taga, K. Masuda, T. Higashi and H. Iizuka, KPPXRAY, Kyoto
Program Package for X-ray Crystal Structure Analysis, Kyoto
University, Japan, 1991.
mined by HPLC using a reversed-phase chiral column of Cera-
Ϫ1
mospher chiral Ru-1 under the conditions of 0.5 ml min of
flow rate of MeOH detected at 225 nm. Compound 13:
22
amorphous solid; [α] ϩ52.5 (c 1.26, in CHCl , 26% ee); νmax/
Paper 7/06673B
Received 15th September 1997
Accepted 13th October 1997
D
3
Ϫ1
cm 3400, 3040–2950, 1745, 1710 and 1160; δ (200 MHz, at
H
6
0 ЊC) 1.19 (9H, br s), 1.48 (9H, s), 3.74 (3H, s), 5.96 (1H, br s),
1
92
J. Chem. Soc., Perkin Trans. 1, 1998