Enantioselective microbial hydrolysis of dissymmetrical cyclic carbonates with disubstitution

Article abstract of DOI:10.1016/j.tet.2006.09.066

Enantioselective microbial hydrolysis of C₁ and C₂ dissymmetrical cyclic carbonates with disubstitution (methyl and another groups) has been developed. Pseudomonas diminuta (FU0090), a bacterium, efficiently catalyzes the hydrolysis of five-membered cyclic carbonates. While the trans-substrates are hydrolyzed with low enantioselectivities and/or reactivities, the microbe hydrolyzes the cis-substrates with very high enantioselectivities to afford the corresponding almost optically pure anti-(2R,3S)-diols. On the other hand, six-membered trans-cyclic carbonates are enantioselectively hydrolyzed to afford the corresponding optically active syn-(2R,4R)-diols, although the hydrolysis of the cis-substrates gives racemic compounds. In all cases, the enzyme prefers the (R)-enantiomer for the carbon atom bearing a methyl group.

Full text of DOI:10.1016/j.tet.2006.09.066

Tetrahedron 62 (2006) 12071–12083
Enantioselective microbial hydrolysis of dissymmetrical
cyclic carbonates with disubstitution
Masaki Nogawa,a Satomi Sugawara,a Rie Iizuka,a Megumi Shimojo,a Hiromichi Ohta,b
Minoru Hatanakac and Kazutsugu Matsumotoa,
*
aDepartment of Chemistry, Meisei University, Hodokubo 2-1-1, Hino, Tokyo 191-8506, Japan
bDepartment of Biosciences and Informatics, Keio University, Hiyoshi 3-14-1, Yokohama 223-8522, Japan
cDepartment of Applied Chemistry and Biotechnology, University of Fukui, Bunkyo 3-9-1, Fukui 910-8507, Japan
Received 28 August 2006; revised 13 September 2006; accepted 19 September 2006
Available online 27 October 2006
Abstract—Enantioselective microbial hydrolysis of C1 and C2 dissymmetrical cyclic carbonates with disubstitution (methyl and another
groups) has been developed. Pseudomonas diminuta (FU0090), a bacterium, efficiently catalyzes the hydrolysis of five-membered cyclic
carbonates. While the trans-substrates are hydrolyzed with low enantioselectivities and/or reactivities, the microbe hydrolyzes the cis-
substrates with very high enantioselectivities to afford the corresponding almost optically pure anti-(2R,3S)-diols. On the other hand,
six-membered trans-cyclic carbonates are enantioselectively hydrolyzed to afford the corresponding optically active syn-(2R,4R)-diols,
although the hydrolysis of the cis-substrates gives racemic compounds. In all cases, the enzyme prefers the (R)-enantiomer for the carbon
atom bearing a methyl group.
Ó 2006 Elsevier Ltd. All rights reserved.
1. Introduction
meso- and C2-symmetrical compounds. Recently, the kinetic
resolution of cyclic carbonates with hydrolytic enzymes is
one of the attractive methods for preparing optically active
diols.4 We have already reported the enzyme-mediated
hydrolysis of cyclic carbonates, and have accomplished
the efficient preparation of various kinds of optically active
diols.5,6 Commercially available porcine pancreas lipase
(PPL, Type II from Sigma) catalyzes the hydrolysis of mono-
substituted cyclic carbonates to afford the corresponding
optically active 1,2- and 1,3-diols.5 On the other hand,
Pseudomonas diminuta (FU0090), which is a bacterium
isolated from the soil and classified by NCIMB Japan Co.
Ltd, hydrolyzes the C2-symmetrical five- and six-membered
cyclic carbonates with a dimethyl group, and then optically
active 2,3-butanediol and 2,4-pentanediol were obtained.6a
This type of reaction proceeds irreversibly because the
acyl moiety of the substrate leaves the reaction system as
carbon dioxide. The enzyme, however, has a high substrate
specificity for the side chain of the substrate, and the reaction
of the substrate bearing a diethyl group was not hydrolyzed
at all. During our studies on this microbial reaction, we
observed that even C1- and C2-dissymmetrical disubstituted
substrates could be enantioselectively hydrolyzed when one
of the substituent was a methyl group. Herein, we reported
the application of the microbial hydrolysis to various five-
and six-membered cyclic carbonates bearing methyl and
another groups, and then prepared the corresponding opti-
cally active 1,2- and 1,3-diols with two chiral centers
Optically active diols are important intermediates for the
synthesis of natural products, and many synthetic procedures
for such compounds have been developed. Although the
asymmetric dihydroxylation of olefins is one of the most
popular ways to prepare chiral 1,2-diols,1 this method does
not always satisfactorily work in terms of the enantioselec-
tivity in some cases. For example, the oxidation of (Z)-disub-
stituted olefins is not a suitable tool for the preparation of
optically active anti-1,2-diols.2 On the other hand, optically
active 1,3-diols are not easily synthesized by direct prepara-
tion methods.
The use of enzymes in the preparation of such optically ac-
tive compounds is especially attractive due to the remarkable
stereoselectivity and its benign effect on the environment.
Enzymatic hydrolysis of diacetates and esterification of diols
are the representative biochemical methods to prepare such
compounds.3 The reactions, however, produce a mixture of
more than two compounds (diol, diacetate, and two mono-
acetates), which causes difficulty with the purification, and
the almost examples have been limited to the reaction of
Keywords: Cyclic carbonates; Enantioselective hydrolysis; Enzymes;
Microbial reaction; Optically active diols.
* Corresponding author. Tel./fax: +81 42 591 7360; e-mail: mkazu@chem.
meisei-u.ac.jp
0040–4020/$ - see front matter Ó 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2006.09.066

12072
M. Nogawa et al. / Tetrahedron 62 (2006) 12071–12083
(Scheme 1). In particular, the optically pure anti-1,2-diols
were obtained from the five-membered cis-substrates with
high enantioselectivities.6b
respectively) as the representative substrates. After the reac-
tion of (ꢀ)-4 (ca. 84 mg, 10 mM) with P. diminuta in 50 mL
of glucose medium at 30 ꢁC, the bacterium catalyzed
the hydrolysis of both substrates, and the corresponding
anti- and syn-6-benzyloxy-2,3-diols (3a and 3b, respec-
tively) were obtained, as expected (Scheme 5). The trans-
form substrate ((ꢀ)-4b) was enantioselectively hydrolyzed
to give the optically active (2R,3R)-3b ([a]2D2 +11.5
(c 0.72, MeOH), 75% ee) in 23% yield and the remaining
(4S,5S)-4b ([a]2D2 ꢂ10.0 (c 0.35, MeOH), 54% ee) in 44%
yield. In this case, the enzyme preferentially hydrolyzed
the (4R,5R)-form in the same stereoselective manner as in
the case of the C2-symmetrical (ꢀ)-trans-4,5-dimethyl-1,3-
dioxolan-2-one (38b) bearing a dimethyl group.6a The
hydrolysis, however, proceeded with moderate enantio-
selectivity, and the conversion and E value of the reaction
for 48 h were 0.42 and 12, respectively,7 while 38b was
hydrolyzed with high enantioselectivity (E value¼70). To
determine the stereochemistry of the resulting (2R,3R)-3b,
the sign of the optical rotation was compared with that of
the authentic sample (2S,3S)-3b ([a]2D7 ꢂ13.8 (c 1.16,
MeOH), 77% ee), which was transformed from (E)-2b
by the asymmetric dihydroxylation method with AD-mix-a
and CH3SO2NH2 in t-BuOH/H2O (Scheme 6).1
O
O
Pseudomonas diminuta
O
*
O
*
O
O
OH OH
FU0090
+
Me
R
Me
R
Me
R
*
*
n
n
n
R
≠
H, Me
cis- and trans-form
n = 0, 1
Enzyme
Enzyme
O
HO
O
O
H2O
OH OH
O
O
n
O
OH
Me
R
n
Me
R
Me
R
n
CO2
Acyl-Enzyme Intermediates
Scheme 1.
2. Results and discussion
The diastereomeric anti- and syn-racemic diols, which were
the precursors of cyclic carbonates, were readily synthe-
sized. The compounds 1,2-diols are selectively prepared
starting from (Z)- and (E)-olefins, respectively, as shown in
Schemes 2 and 3. On the other hand, selective reduction of
b-hydroxy ketones followed by separation with column
chromatography on silica gel afforded anti- and syn-1,3-
diols (Scheme 4). In all cases, successive treatment of the
diols with pyridine and bis(trichloromethyl)carbonate (tri-
phosgene) resulted in the corresponding racemic substrates.
On the other hand, the enantioselectivity of the hydrolysis
of the cis-substrate ((ꢀ)-4a) was almost perfect. The reac-
tion of (ꢀ)-4a for 48 h produced the remaining cyclic
carbonate (4R,5S)-4a ([a]2D6 +10.9 (c 1.68, MeOH), 97%
ee) in 43% yield and the resulting optically pure diol
(2R,3S)-3a ([a]2D5 ꢂ14.0 (c 2.54, MeOH)) in 40% yield
(conv.¼0.49, E value3¼>200). Although, we have already
reported the hydrolysis of cis-4,5-dimethyl-1,3-dioxolan-
2-one (38a; the meso-cyclic carbonate bearing a dimethyl
group) as the C1-symmetrical substrate,6a this is the first
First, we selected the racemic five-membered cyclic
carbonates, diastereomers of the cis- and trans-4-(3-benzyl-
oxy)propyl-5-methyl-1,3-dioxolan-2-ones ((ꢀ)-4a and 4b,
i
OBn
OH
Me
OH
Me
(Z)-1a
(Z)-2a
O
ii
iii
Me
OBn
O
O
OBn
OBn
OH
Me
( )-3a (anti)
( )-4a (cis)
i
Me
OBn
Me
OH
(E)-1b
(E)-2b
O
OH
ii
iii
Me
OBn
O
O
OH
Me
( )-3b (syn)
( )-4b (trans)
O
OH
: R = butyl
5a, 8a, 11a
ii
iii
O
O
Me
: R = pentyl
: R = heptyl
6a, 9a, 12a
R
Me
R
7a, 10a, 13a
Me
R
OH
(Z)-5a, 6a, 7a
( )-8a, 9a, 10a
( )-11a, 12a, 13a
(anti)
(cis)
O
OH
ii
iii
O
O
Me
Me
Me
OH
( )-8b (syn)
(E)-5b
( )-11b (trans)
Scheme 2. (i) BnBr, NaH/THF, reflux ((E)-2b, 98%); (ii) cat. OsO4, NMO/acetone/H2O, rt (3a, 86% from 1a; 3b, 63%; 8a, 49%; 8b, 87%; 9a, 82%; 10a, 55%);
(iii) triphosgene, Py/CH2Cl2, ꢂ78/0 ꢁC (4a, 92%; 4b, 96%; 11a, 78%; 11b, 85%; 12a, 60%; 13a, 97%).

M. Nogawa et al. / Tetrahedron 62 (2006) 12071–12083
12073
O
O
Me
Me
i
iii
N
Ethyl ( )-lactate
O
OMPM
OR
( )-16
( )-14:
R = H
ii
( )-15: R = MPM
O
OH
OH
iv
v
vi
Me
Me
O
O
OMPM
( )-17
OH
( )-18a (anti
Me
)
( )-19a (cis)
Scheme 3. (i) Morpholine, reflux (69%); (ii) MPMCl, NaH/THF, rt (87%); (iii) CH2]CHCH2CH2MgBr/THF, rt (74%); (iv) ZnBH4/Et2O (48%); (v) cat.
p-TsOH/MeOH (76%); (vi) triphosgene, Py/CH2Cl2, ꢂ78/0 ꢁC (51%).
OH
O
OH
R2
O
O
vi
O
Me
O
O
Me
O
iv or v
i
R1
R2
Me
( )-26, 27
Me
OEt
21: R1 = CO2Et
( )-24, 25
20
ii
22: R1 = CH2OH
23: R1 = CHO
iii
OMOM
O
O
OH
vii
x
O
Me
( )-24
OBn
R2
Me
( )-28: R2 = allyl
( )-31
viii
ix
: R2 = CH2CH2CH2OH
: R2 = CH2CH2CH2OBn
( )-29
( )-30
O
OH OH
xiii
O
O
xi or xii
Me
R2
Me
R2
( )-35a, 36a, 37a
(cis)
( )-32a, 33a, 34a
: R2 = allyl
(syn)
( )-24, 26, 32, 35
( )-25, 27, 33, 36
( )-31, 34, 37
( )-26, 27, 31
xi or xii
O
: R2= propyl
: R2= CH2CH2CH2OBn
OH OH
O
O
xiii
R2
Me
R2
Me
( )-32b, 33b, 34b
(anti)
( )-35b, 36b, 37b
(trans)
Scheme 4. (i) cat. p-TsOH, ethylene glycol/benzene, reflux (73%); (ii) LiAlH4/THF, rt (91%); (iii) (COCl)2, DMSO, Et3N/CH2Cl2, ꢂ78 ꢁC/rt (75%); (iv)
CH2]CHCH2MgBr/THF, rt (24, 88%); (v) propylmagnesium bromide/THF, rt (25, 76%); (vi) 2 M HCl aq/THF (26, 71%; 27, 79%); (vii) MOMCl,
i-Pr2NH/CH2Cl2 (89%); (viii) BH3$THF/THF then 2 M NaOH aq, H2O2 (90%); (ix) BnBr, NaH/THF (88%); (x) 2 M HCl aq/THF (71%); (xi) Procedure A,
NaBH4/MeOH (32a (56%)+32b (28%); 33a (64%)+33b (32%); 34a (50%)+34b (34%)); (xii) Procedure B, MeNB(OAc)3H/AcOH/CH3CN (32a (24%)+32b
(73%); 33a (16%)+33b (78%); 34a (37%)+34b (56%)); (xiii) triphosgene, Py/CH2Cl2, ꢂ78 ꢁC/rt (35a, 78%; 35b, 55%; 36a, 30%; 36b, 42%; 37a, 79%;
37b, 76%).
example of the enantioselective hydrolysis of the cis-
disubstituted carbonates. The absolute configuration of the
anti-diol was determined by comparing the optical rotation
with that of the optically active authentic (2S,3R)-3a
([a]2D5 +12.9 (c 1.34, MeOH)), which was prepared from
ethyl (S)-lactate in seven steps (Scheme 7). In the case of
anti-1,2-diol, the asymmetric dihydroxylation of (Z)-2a
with AD-mix-a proceeded with very low enantioselectivity
to give (2R,3S)-3a in only 18% ee. These show that the
microbial hydrolysis apparently has some advantage
for the preparation of optically active anti-1,2-diol with
high ee.
O
O
OH
O
O
O
O
3
P. diminuta
Me
2
OBn
OBn
+
+
OBn
OBn
OBn
OBn
5
4
Me
Me
30 °C, 48 h
Me
OH
( )-4a (cis)
(4R,5S)-4a
(2R,3S)-3a (anti)
Conv. = 0.49
43%, 97% ee
40%, >99% ee
E value = >200
O
O
OH
O
O
O
O
P. diminuta
Me
Me
30 °C, 48 h
OH
( )-4b (trans)
(4S,5S)-4b
44%, 54% ee
(2R,3R)-3b (syn)
Conv. = 0.42
23%, 75% ee
E value = 12
Scheme 5.

12074
M. Nogawa et al. / Tetrahedron 62 (2006) 12071–12083
OH
Then, we applied the microbial reaction to several five-
membered cis-cyclic carbonates (Scheme 9, Table 1). As
expected, all the substrates were hydrolyzed with high enan-
tioselectivity. The reaction of the substrate bearing an unsat-
urated substituent (R¼3-butenyl, (ꢀ)-19a, entry 3) gave
a result similar to that of (ꢀ)-11a, which has the correspond-
ing saturated group. The bacterium smoothly catalyzed the
hydrolysis of (ꢀ)-19a for 48 h to give the optically active
(4R,5S)-19a (63% ee) and (2R,3S)-18a (95% ee) in 46 and
42% yields, respectively (conv.¼0.40, E value¼75). The
optically active 18a is an important precursor for the synthe-
sis of a biologically active deoxysugar, D-amicetose.8 On the
other hand, the substrates bearing a longer chain, (ꢀ)-12a
(R¼pentyl, entry 1) and 13a (R¼heptyl, entry 2) showed
excellent enantioselectivities, although the reactivities
were low. For the reactions going for 96 h, the resulting
(2R,3S)-9a and 10a were obtained in their optically pure
forms, and the E values were over 200.
AD-mix- α
Me
OBn
Me
OBn
t-BuOH-H2O
CH3SO2NH2
OH
(E)-2b
(2S,3S)-3b
63%, 77% ee
Scheme 6.
OH
OTHP
4 steps
i
Me
Me
Ethyl (S)-lactate
OMPM
(2S,3R)-39
OMPM
(2S,3R)-40
OH
OTHP
iv
ii
Me
OBn
Me
OR
OH
OMPM
R = H
(4R,5S)-41:
(2S,3R)-3a
iii
R = Bn
(4R,5S)-42:
Scheme 7. (i) DHP, p-TsOH/CH2Cl2 (64%); (ii) BH3$THF/THF then 2 M
NaOH aq, H2O2 (62%); (iii) BnBr, NaH/THF (81%); (iv) p-TsOH/MeOH
(38%).
O
O
OH
O
O
O
O
S
R
P. diminuta
Me
R
+
The difference in the reactivity between the diastereomers is
noticeably observed during the hydrolysis of the substrates
bearing a butyl group ((ꢀ)-11a and 11b) as a substituent
(Scheme 8). The hydrolysis of the cis-substrate (ꢀ)-11a
smoothly proceeded to give optically active compounds,
(4R,5S)-11a (92% ee, [a]2D2 +14.6 (c 1.04, MeOH)) in 31%
yield and (2R,3S)-8a (93% ee, [a]2D3 ꢂ22.0 (c 0.82,
MeOH)) in 40% yields (reaction for 48 h; conv.¼0.50,
E value¼91). Interestingly, in the case of the trans-isomer
(ꢀ)-11b, the enzyme scarcely catalyzed the substrate at all.
S
R
R
30 °C
Me
R
Me
OH
anti-form
( )-cis-form
Scheme 9.
Next, our attention focused on the ring size of the substrate,
and we tried the reaction of racemic six-membered cyclic
carbonates (Scheme 10, Table 2). As expected, P. diminuta
catalyzed the hydrolysis of all the substrates examined to
afford the corresponding 1,3-diols. The stereoselective
manner, however, was quite different from that of the five-
membered substrates. In the case of the trans-substrate bear-
ing an allyl group (35b, entry 1), the substrate was smoothly
hydrolyzed with good enantioselectivity to give the optically
active remaining (4S,6S)-35b (72% ee) in 39% yield and
the resulting (2R,4R)-32b (84% ee, [a]2D1 ꢂ29.7 (c 0.66,
CHCl3)) in 26% yield (reaction for 48 h; conv.¼0.46,
E value¼25). The absolute configuration of the diol 32b
was determined by comparing the optical rotation with
that reported; (2R,4R)-32b (96% ee), lit.9 [a]D23 ꢂ34.1 (c
1.13, CHCl3). The reaction for 72 h (entry 2) gave optically
pure (4S,6S)-35b in 27% yield. It is noteworthy that the
enzyme preferentially catalyzes the hydrolysis of (R)-enan-
tiomer at the asymmetric center bearing a methyl group as
O
O
OH
O
O
O
O
P. diminuta
Me
+
Me
Me
Me
30 °C, 48 h
OH
( )-11a (cis)
(4R,5S)-11a
(2R,3S)-8a (anti)
Conv. = 0.50
31%, 92% ee
40%, 93% ee
E value = 91
O
O
OH
O
O
O
O
P. diminuta
Me
+
Me
30 °C, 48 h
OH
( )-11b (trans)
11b
80%, racemic
8b (syn)
trace
Scheme 8.
Table 1. Microbial hydrolysis of several five-membered (ꢀ)-cis-cyclic carbonatesa
Entry
R
Time (h)
Carbonate
Diol
Conv.b
Ec
Yield (%)
ee (%)
Yield (%)
ee (%)
1
2
3
Pentyl
Heptyl
3-Butenyl
96
96
48
12a
13a
19a
77
84
46
18d
13f
63h
9a
10a
18a
14
11
42
>99e
>99g
95i
0.15
0.12
0.40
>200
>200
75
a
The reaction was performed using 10 mM of the substrate.
Calculated by ee(carbonate)/[ee(carbonate)+ee(diol)].
b
c
d
e
f
Calculated by ln[(1ꢂconv.)(1ꢂee(carbonate))]/ln[(1ꢂconv.)(1+ee(carbonate))].
[a]2D8 +6.10 (c 1.08, MeOH).
[a]2D8 ꢂ20.4 (c 0.89, MeOH).
[a]2D9 +3.58 (c 0.79, MeOH).
[a]2D4 ꢂ10.1 (c 0.39, MeOH).
g
h
i
[a]2D3 +7.93 (c 1.20, MeOH).
[a]2D3 ꢂ19.1 (c 1.31, MeOH).

M. Nogawa et al. / Tetrahedron 62 (2006) 12071–12083
12075
O
O
well as that in the case of the five-membered substrates.
Changing the substituent from allyl to propyl (36b, entry
3) and 3-benzyloxypropyl (37b, entry 4) decreased the reac-
tivity and the enantioselectivity. For example, the reaction of
36b for 48 h gave the optically active (2R,4R)-33b in 84%
ee, but the conversion and E value were only 0.10 and 13, re-
spectively. The longer reaction time scarcely improved the
conversion at all. Interestingly, although the enzyme acceler-
ated the hydrolysis of the cis-substrates and the reactions for
48 h gave the remaining carbonates (35a, 37%; 36a, 48%;
37a, 47%) and the corresponding diols (32a, 31%; 33a,
28%; 34a, 18%), all of the products were almost racemates.
O
O
O
O
H
R3
R3
1
5
4
H
5
4
R
H
R1
R2
R2
L
S
slow
fast
R1 = H or Me
Figure 1.
O
O
O
O
O
O
Me
OBn
O
O
43
44
O
O
O
O
OH OH
P. diminuta
Figure 2.
+
30 °C
Me
R
Me S
S
R
Me R
R
R
( )-trans-form
anti-form
O
Scheme 10.
O
O
4
6
H
H
Based on all of our observations, we can formulate an empir-
ical rule for predicting the enantioselectivity in this micro-
bial reaction.10 For the rigid five-membered substrates, the
active site model is illustrated in Figure 1. First, a methyl
group at C-5 position of the substrates is necessary for the
enantioselective reaction because we have also found that
monosubstituted cyclic carbonates (R1¼H), such as 4-methyl-
1,3-dioxolan-2-one (43) and 4-(2-benzyloxy)ethyl-1,3-
dioxolan-2-one (44) in Figure 2, are smoothly hydrolyzed
without enantioselectivity. Second, the enzyme prefers
(5R)-substrates in all cases. These results indicate that the
enzyme apparently distinguishes the stereochemistry at the
asymmetric center substituted with a methyl group and
the cis-(5R)-substrate is most suitable for the active site of
the enzyme (R1¼Me, R2¼alkyl, R3¼H). In the case of the
fast reactive enantiomer, the methyl group would locate at
the S (small)-pocket, with hydrogen in H-site, and with R2
group in L (large)-pocket. In the reaction of trans-substrates,
the elongation of the substituent (R3) at the C-4 position
decreases both the reactivity and the enantioselectivity.
Because the introduction of a benzyloxy group on the side
chain could improve the reactivity, the oxygen atom of the
substrates could play an important role for the interaction
between the substrates and the enzyme.
H
R
Me
L
S
trans-(6R)-form
Figure 3.
at the S-pocket (Fig. 3). This indicates that the trans-(6R)-
substrate might be a most preferable isomer. But, it is
difficult to understand the stereoselective mode because
the six-membered ring is very flexible in comparison with
the five-membered ring. Consequently, the enantio- and
diastereoselectivity of the hydrolysis was lower than those
in the case of the five-membered substrates.
3. Conclusion
In this paper, we have established the microbial enantio-
selective hydrolysis of five- and six-membered cyclic car-
bonates bearing two substituents, which are methyl and
another groups, as a new route to optically active diols. In
particular, this is the first report for the enantioselective
hydrolysis of five-membered cis-cyclic carbonates, which
are favorably hydrolyzed with high enantioselectivity to
give the corresponding optically pure anti-1,2-diols. Fur-
thermore, we can postulate the active site model for the hy-
drolase through the microbial reaction for various substrates.
On the other hand, for the six-membered trans-cyclic car-
bonates, R group at the pseudo-equatorial position could
turn to L-pocket when the pseudo-axial methyl group locates
Table 2. Microbial hydrolysis of several six-membered (ꢀ)-trans-cyclic carbonatesa
Entry
R
Time (h)
Carbonate
Diol
Conv.b
Ec
Yield (%)
ee (%)
Yield (%)
ee (%)
1
2
3
4
Allyl
Allyl
Propyl
–(CH2)3OBn
48
72
48
48
35b
35b
36b
37b
39
27
80
71
72
>99d
10
32b
32b
33b
34b
26
29
16
7
84
61
84e
84
0.46
0.62
0.10
0.07
25
>20
13
6
12
a
The reaction was performed using 10 mM of the substrate.
Calculated by ee(carbonate)/[ee(carbonate)+ee(diol)].
b
c
d
e
Calculated by ln[(1ꢂconv.)(1ꢂee(carbonate))]/ln[(1ꢂconv.)(1+ee(carbonate))].
[a]2D0 ꢂ75.7 (c 1.00, CHCl3).
[a]2D2 ꢂ8.91 (c 0.63, CHCl3).

12076
M. Nogawa et al. / Tetrahedron 62 (2006) 12071–12083
4. Experimental
(2b, 1.90 g, 98%) as a colorless oil. Then, (E)-2b
(56.5 mg, 0.30 mmol) was converted to (ꢀ)-3b as a colorless
oil (41.7 mg, 63%); IR (neat) 3399, 2926, 2857, 1454, 1098,
1072, 737, 698 cmꢂ1; 1H NMR (300 MHz, CDCl3) d¼1.18
(d, J¼6.0 Hz, 3H), 1.45–1.52 (m, 1H), 1.62 (br s, 2H),
1.64–1.72 (m, 1H), 1.79 (td, J1¼J2¼6.0 Hz, 1H), 3.34
(ddd, J1¼3.0 Hz, J2¼6.5 Hz, J3¼9.5 Hz, 1H), 3.54 (t, J¼
6.0 Hz, 2H), 3.56–3.62 (m, 1H), 4.23 (s, 2H), 7.26–7.38
(m, 5H); 13C NMR (75 MHz, CDCl3) d¼19.3, 26.0, 30.9,
70.5, 70.9, 73.2, 75.8, 127.8, 128.5, 137.9; MS m/z (rel inten-
sities) 224 (M+, 1.7%), 206 (0.6), 107 (34), 91 (100); HRMS
m/z 224.1412 (224.1413 calcd for C6H14O2, M+).
4.1. General
1H (300 or 500 MHz) and 13C (75 or 125 MHz) NMR spec-
tra were measured on a JEOL JNM AL-300 and a-500 with
tetramethylsilane (TMS) as the internal standard. IR spectra
were recorded with Shimadzu FTIR-8300 and IR Prestige-
21 spectrometers. Mass spectra were obtained with
a JEOL EI/FAB mate BU25 Instrument by the EI method.
Optical rotations were measured with a Jasco DIP-1000
polarimeter. HPLC data were obtained on Shimadzu
LC-10ADVP, SPD-10AVP, and sic 480II data station (System
Instruments Inc.). GLC data were taken on GL Sciences GC
353B and sic 480II data station (System Instruments Inc.).
E. Merck Kieselgel 60 F254 Art. 5715 was used for analytical
TLC. Preparative TLC was performed on E. Merck Kiesel-
gel 60 F254 Art. 5744. Column chromatography was per-
formed with Silica Gel 60N (63–210 mm, Kanto Chemical
Co. Inc.). Melting points were obtained on a Yanako melting
point apparatus and were not corrected. All other chemicals
were also obtained from commercial sources.
4.2.3. (2RS,3SR)-Heptane-2,3-diol (( )-8a (anti)). Accord-
ing to the procedure for the preparation of 3a described
above, (Z)-2-heptene (5a, 564 mg, 5.75 mmol) was con-
verted to (ꢀ)-8a as a colorless oil (375 mg, 49%); IR
1
(neat) 3379, 2932, 1462, 1379, 1055, 984, 737 cmꢂ1; H
NMR (300 MHz, CDCl3) d¼0.92 (t, J¼7.0 Hz, 3H), 1.14
(d, J¼6.5 Hz, 3H), 1.24–1.43 (m, 5H), 1.43–1.53 (m, 1H),
2.39 (br s, 2H), 3.54–3.65 (m, 1H), 3.79 (qd, J1¼3.0 Hz,
J2¼6.5 Hz, 1H); 13C NMR (75 MHz, CDCl3) d¼14.0,
16.5, 22.7, 28.2, 31.4, 70.4, 74.9; MS m/z (rel intensities)
132 (M+, 5.6%), 113 (37), 104 (28), 83 (46), 71 (90), 57
(100); HRMS m/z 132.1137 (132.1150 calcd for C7H16O2,
M+).
4.2. Preparation of 1,2-diols
4.2.1. (2RS,3SR)-(6-Benzyloxy)hexane-2,3-diol (( )-3a
(anti)). Under an argon atmosphere, to a suspension of
NaH (60% in oil, 900 mg, 22 mmol) in THF (10 mL) was
added a solution of (Z)-4-hexen-1-ol (1a, 2.0 g, 20 mmol)
in THF (15 mL) and benzyl bromide (2.9 mL, 24 mmol) at
0 ꢁC. The mixture was stirred for 6 h under reflux, and the
reaction was quenched with 0.1 M phosphate buffer (pH
6.5). The products were extracted with AcOEt (ꢃ3), and
the organic layer was washed with brine, and dried over
Na2SO4. After evaporation under reduced pressure, the
residue was purified by flash column chromatography on
silica gel (hexane/AcOEt¼2/1) to give (Z)-(6-benzyloxy)-
2-hexene (2a) as a colorless oil (3.7 g).
4.2.4. (2RS,3RS)-Heptane-2,3-diol (( )-8b (syn)). Accord-
ing to the procedure for the preparation of 3a described
above, (E)-2-heptene (5b, 1.01 g, 10.4 mmol) was converted
to ((ꢀ)-8b as a colorless oil (1.18 g, 87%); IR (neat) 3370,
2957, 2934, 2872, 1458, 1375, 1057 cmꢂ1 1H NMR
;
(300 MHz, CDCl3) d¼0.92 (t, J¼7.0 Hz, 3H), 1.20 (d, J¼
6.0 Hz, 3H), 1.33–1.52 (m, 6H), 2.29 (br s, 2H), 3.31–3.36
(m, 1H), 3.60 (qd, J1¼J2¼6.0 Hz, 1H); 13C NMR
(75 MHz, CDCl3) d¼14.0, 19.5, 22.7, 27.7, 33.1, 70.9,
76.2; MS m/z (rel intensities) 132 (M+, 12%), 114 (11),
107 (31), 91 (100), 71 (51); HRMS m/z 132.1151
(132.1150 calcd for C7H16O2, M+).
To a solution of (Z)-2a (3.7 g, 19.6 mmol) in acetone (7 mL)
and H2O (3 mL) were added 4-methylmorpholine N-oxide
(10.0 g, 80 mmol), t-BuOH (0.3 mL), and a catalytic amount
of OsO4, and the mixture was stirred for 2 h at room temper-
ature. After addition of NaS2O4, stirring for 30 min, and fil-
tration through a Celite pad, the products were extracted
with AcOEt (ꢃ3), and the organic layer was washed with
brine, and dried over Na2SO4. After evaporation under re-
duced pressure, the residue was purified by flash column
chromatography on silica gel (hexane/AcOEt¼1/1) to give
(ꢀ)-3a as a colorless oil (3.9 g, 86% from 1a); IR (neat)
4.2.5. (2RS,3SR)-Octane-2,3-diol (( )-9a (anti)). Accord-
ing to the procedure for the preparation of 3a described
above, (Z)-2-octene (6a, 2.02 g, 18.1 mmol) was converted
to (ꢀ)-9a as a colorless oil (2.15 g, 82%); IR (neat) 3285,
2955, 2940, 2916, 2857, 1485, 1069, 1055 cmꢂ1; 1H NMR
(500 MHz, CDCl3) d¼0.90 (t, J¼7.0 Hz, 3H), 1.15 (d, J¼
6.5 Hz, 3H), 1.25–1.36 (m, 5H), 1.37–1.43 (m, 2H), 1.46–
1.55 (m, 1H), 1.70 (br s, 1H), 1.98 (br s, 1H), 3.61–3.64
(m, 1H), 3.77–3.83 (m, 1H); 13C NMR (125 MHz, CDCl3)
d¼14.0, 16.6, 22.6, 25.7, 31.7, 31.9, 70.4, 74.9; MS m/z
(rel intensities) 146 (M+, 6.9%), 128 (18), 110 (16), 101
(100), 99 (42), 85 (39); HRMS m/z 146.1361 (146.1307
calcd for C8H18O2, M+).
1
3399, 2930, 1714, 1454, 1277, 1099, 714 cmꢂ1; H NMR
(500 MHz, CDCl3) d¼1.15 (d, J¼6.5 Hz, 3H), 1.41–1.85
(m, 4H), 3.50–3.82 (m, 4H), 4.53 (s, 2H), 7.28–7.38 (m,
5H); 13C NMR (125 MHz, CDCl3) d¼17.0, 26.5, 28.9,
70.3, 70.5, 73.1, 74.7, 127.7, 128.4, 129.5, 137.9; MS m/z
(rel intensities) 224 (M+, 5.6%), 206 (2.5), 107 (100), 91
(100); HRMS m/z 224.1419 (224.1413 calcd for
C13H20O3, M+).
4.2.6. (2RS,3SR)-Decane-2,3-diol (( )-10a (anti)). Accord-
ing to the procedure for the preparation of 3a described
above, (Z)-2-decene (7a, 656 mg, 4.68 mmol) was converted
to (ꢀ)-10a as a colorless oil (446 mg, 55%); IR (neat) 3293,
2955, 2916, 2853, 1487, 1468, 1069 cmꢂ1 1H NMR
;
4.2.2. (2RS,3RS)-(6-Benzyloxy)hexane-2,3-diol (( )-3b
(syn)). According to the procedure for the preparation
method described above, (E)-4-hexen-1-ol (1b, 1.02 g,
10.2 mmol) was converted to (E)-(6-benzyloxy)-2-hexene
(500 MHz, CDCl3) d¼0.88 (t, J¼7.0 Hz, 3H), 1.15 (d, J¼
6.5 Hz, 3H), 1.21–1.51 (m, 12H), 1.82 (br s, 2H), 3.59–
3.64 (m, 1H), 3.76–3.83 (m, 1H); 13C NMR (125 MHz,
CDCl3) d¼14.1, 16.6, 22.6, 26.0, 29.2, 29.6, 31.8, 70.4,

M. Nogawa et al. / Tetrahedron 62 (2006) 12071–12083
12077
74.9; MS m/z (rel intensities) 174 (M+, 7.6%), 156 (4.8), 138
(6.3), 129 (100), 113 (14), 99 (15); HRMS m/z 174.1625
(174.1620 calcd for C10H22O2, M+).
0.2 M phosphate buffer (pH 6.5). The products were ex-
tracted with AcOEt (ꢃ4), and the organic layer was washed
with brine, and dried over Na2SO4. After evaporation under
reduced pressure, the residue was purified by flash column
chromatography on silica gel (hexane/AcOEt¼10/1) to
give (2RS,3SR)-2-(4-methoxybenzyloxy)-6-hepten-3-one
((ꢀ)-17) as a colorless oil (962 mg, 48%). The diastereo-
selectivity was not determined, but the amount of the minor
isomer was very small; IR (neat) 3447, 2928, 2855, 1613,
4.2.7. (2RS,3SR)-6-Heptene-2,3-diol (( )-18a (anti)). To
ethyl (ꢀ)-lactate (10.0 g, 0.08 mol) was added morpholine
(14.8 g, 0.17 mol), and the mixture was stirred overnight un-
der reflux. After removal of the excess morpholine in vacuo,
the residue was purified by distillation under reduced pres-
sure to afford (ꢀ)-2-hydroxy-1-morpholinopropan-1-one
(14) as a colorless oil (9.35 g, 69%); bp 109–110 ꢁC/
3 mmHg; IR (neat) 3420, 2858, 2341, 1643, 1439, 1273,
1115, 845, 571 cmꢂ1; 1H NMR (300 MHz, CDCl3) d¼1.33
(d, J¼6.5 Hz, 3H), 3.38–3.76 (m, 8H), 3.87 (br s, 1H),
4.45 (q, J¼6.5 Hz, 1H); 13C NMR (75 MHz, CDCl3)
d¼21.1, 42.6, 45.2, 63.9, 66.2, 66.6, 173.6.
1514, 1248, 1080, 1036 cmꢂ1
;
1H NMR (300 MHz,
CDCl3) d¼1.15 (d, J¼6.5 Hz, 3H), 1.41–1.59 (m, 2H),
1.63 (br s, 1H), 2.03–2.18 (m, 1H), 2.20–2.34 (m, 1H),
3.49 (dq, J1¼3.5 Hz, J2¼6.5 Hz, 1H), 3.69–3.78 (m, 1H),
3.80 (s, 3H), 4.44 (d, J¼11.5 Hz, 1H), 4.53 (d, J¼11.5 Hz,
1H), 4.94–5.07 (m, 2H), 5.83 (tdd, J1¼6.5 Hz, J2¼
10.5 Hz, J3¼17.0 Hz, 1H), 6.85–6.90 (m, 2H), 7.23–7.28
(m, 2H); 13C NMR (75 MHz, CDCl3) d¼14.2, 22.6, 31.6,
55.3, 60.4, 70.3, 72.4, 113.8, 114.8, 129.2, 138.4, 157.8.
Under an argon atmosphere, to a suspension of NaH
(553 mg, 13.8 mmol, 60% in oil) in THF (20 mL) was added
a solution of (ꢀ)-14 (2.0 g, 12.6 mmol) in THF (10 mL) and
p-methoxybenzyl chloride (1.9 mL, 2.2 g, 13.8 mmol) at
0 ꢁC. After the mixture was stirred for 24 h at room temper-
ature, the reaction was stopped with 0.2 M phosphate buffer
(pH 6.5). The products were extracted with AcOEt (ꢃ3), and
the organic layer was washed with brine, and dried over
Na2SO4. After evaporation under reduced pressure, the resi-
due was purified by flash column chromatography on silica
gel (hexane/AcOEt¼1/1) to give (ꢀ)-2-(4-methoxybenzyl-
oxy)-1-morpholinopropan-1-one (15) as a colorless oil
(3.06 g, 87%); IR (neat) 2961, 2903, 2857, 1647, 1514,
To a solution of (ꢀ)-17 (195 mg, 0.78 mmol) in MeOH
(30 mL) was added a catalytic amount of p-TsOH at room
temperature, and stirred overnight. The reaction was stopped
with satd NaHCO3 aqueous solution, and the products were
extracted with AcOEt (ꢃ3), and dried over Na2SO4. After
evaporation under reduced pressure, the residue was purified
by flash column chromatography on silica gel (hexane/
AcOEt¼5/1) to give (ꢀ)-18a (anti) as a colorless oil
(77.4 mg, 76%); IR (neat) 3377, 3077, 2974, 2926, 2855,
1
1641, 1449, 1065, 910 cmꢂ1; H NMR (300 MHz, CDCl3)
d¼1.16 (d, J¼6.5 Hz, 3H), 1.52 (dt, J1¼6.5 Hz, J2¼
7.5 Hz, 2H), 1.96 (br s, 2H), 2.04–2.30 (m, 2H), 3.64 (dt,
J1¼3.5 Hz, J2¼6.5 Hz, 1H), 3.81 (qd, J1¼3.5 Hz,
J2¼6.5 Hz, 1H), 5.07 (tdd, J1¼J2¼1.5 Hz, J3¼17.0 Hz,
2H), 5.85 (tdd, J1¼6.5 Hz, J2¼10.5 Hz, J3¼17.0 Hz, 1H);
13C NMR (75 MHz, CDCl3) d¼16.7, 30.2, 30.7, 70.4,
74.4, 115.1, 138.3; MS m/z (rel intensities) 130 (M+,
2.0%), 112 (6.1), 94 (4.4), 85 (8.4), 83 (15), 73 (13);
HRMS m/z 130.0946 (130.0994 calcd for C7H14O2, M+).
1464, 1437, 1248 cmꢂ1 1H NMR (300 MHz, CDCl3)
;
d¼1.43 (d, J¼7.0 Hz, 3H), 3.60–3.67 (m, 8H), 3.80 (s,
3H), 4.30 (q, J¼7.0 Hz, 1H), 4.40 (d, J¼11.5 Hz, 1H),
4.52 (d, J¼11.5 Hz, 1H), 6.88 (d, J¼8.5 Hz, 2H), 7.25 (dd,
J1¼2.5 Hz, J2¼8.5 Hz, 2H); 13C NMR (75 MHz, CDCl3)
d¼17.8, 42.4, 45.6, 55.2, 66.7, 67.0, 70.8, 75.0, 113.8,
129.4, 129.5, 159.4, 170.7.
Under an argon atmosphere, to a solution of (ꢀ)-15 (4.6 g,
16.5 mmol) in THF (40 mL) was added 3-butenylmagne-
sium bromide (90 mL, 2.2 M in THF) at 0 ꢁC and stirred
for 24 h at room temperature. After the reaction was stopped
with satd NH4Cl aqueous solution, the products were ex-
tracted with AcOEt (ꢃ3), and the organic layer was washed
with brine, and dried over Na2SO4. After evaporation under
reduced pressure, the residue was purified by flash column
chromatography on silica gel (hexane/AcOEt¼10/1) to
give (ꢀ)-2-(4-methoxybenzyloxy)-6-hepten-3-one (16) as
a colorless oil (3.03 g, 74%); IR (neat) 2978, 2936, 2837,
4.3. Preparation of 1,3-diols
4.3.1. (2RS,4SR)- and (2RS,4RS)-6-Heptene-2,4-diol (( )-
32a (syn) and ( )-32b (anti)). To a solution of ethyl 3-oxo-
butanoate (20, 30.0 g, 231 mmol) in benzene (60 mL) were
added a solution of ethylene glycol (42.9 g, 691.6 mmol)
in benzene (60 mL) and a catalytic amount of p-TsOH at
room temperature. After the mixture was stirred for 20 h un-
der reflux, the reaction was stopped with satd NaHCO3 aque-
ous solution at 0 ꢁC. The organic layer was washed with satd
NaHCO3 aqueous solution (ꢃ3) and brine, and dried over
Na2SO4. After evaporation under reduced pressure, the
residue was purified by distillation to give ethyl (2-methyl-
1,3-dioxolan-2-yl)acetate (21) as a colorless oil (29.4 g,
73%); bp 90–120 ꢁC (23 mmHg); IR (neat) 3468, 2889,
1717, 1514, 1250, 1111 cmꢂ1
;
1H NMR (300 MHz,
CDCl3) d¼1.32 (d, J¼7.0 Hz, 3H), 2.28–2.35 (m, 2H),
2.63 (td, J1¼7.5 Hz, J2¼17.5 Hz, 1H), 2.67 (td, J1¼
7.5 Hz, J2¼17.5 Hz, 1H), 3.80 (s, 3H), 3.91 (q, J¼6.5 Hz,
1H), 4.44 (d, J¼11.5 Hz, 1H), 4.47 (d, J¼11.5 Hz, 1H),
4.91–5.07 (m, 2H), 5.81 (tdd, J1¼6.5 Hz, J2¼10.5 Hz,
J3¼17.0 Hz, 1H), 6.86–6.91 (m, 2H), 7.23–7.29 (m, 2H);
13C NMR (75 MHz, CDCl3) d¼17.4, 27.2, 36.5, 55.3,
71.6, 80.3, 113.9, 115.2, 129.4, 129.6, 137.2, 159.4, 212.2.
1744, 1377, 1225, 1049 cmꢂ1
;
1H NMR (500 MHz,
CDCl3) d¼1.27 (t, J¼7.0 Hz, 2H), 1.51 (s, 3H), 2.67 (s,
2H), 3.99 (s, 4H), 4.16 (q, J¼7.0 Hz, 2H); 13C NMR
(75 MHz, CDCl3) d¼14.2, 24.5, 44.2, 60.5, 64.8, 107.6.
Under an argon atmosphere, to a solution of (ꢀ)-16 (2.0 g,
8.06 mmol) in Et2O (30 mL) was slowly added Zn(BH4)2
(120 mL, ca. 0.13 M in Et2O) at ꢂ30 ꢁC, and the mixture
was stirred for 24 h. The reaction was quenched with
Under an argon atmosphere, to a suspension of LiAlH4
(15.0 g, 86.2 mmol) in THF (150 mL) was added a solution
of 21 (3.30 g, 86.2 mmol) in THF (90 mL) at 0 ꢁC. The mix-
ture was stirred for 1 h. The reaction was quenched slowly

12078
M. Nogawa et al. / Tetrahedron 62 (2006) 12071–12083
with H2O (3.3 mL), 15% NaOH (3.3 mL), H2O (6.6 mL) at
0 ꢁC, and the mixture was stirred for 24 h. After filtration
through a Celite pad and evaporation under reduced
pressure, the residue was purified by distillation to give
2-(2-methyl-1,3-dioxolan-2-yl)ethanol (22) as a colorless
oil (10.3 g, 91%); bp 100–114 ꢁC (24 mmHg); IR (neat)
J2¼17.5 Hz, 1H), 3.13 (br s, 1H), 4.05–4.20 (m, 1H), 5.02–
5.20 (m, 2H), 5.70–5.90 (m, 1H); 13C NMR (75 MHz,
CDCl3) d¼30.7, 40.8, 49.1, 66.9, 118.0, 134.1, 209.6.
Procedure A: to a solution of (ꢀ)-26 (810 mg, 6.33 mmol) in
MeOH (40 mL) was added sodium borohydride (479 mg,
12.7 mmol) at 0 ꢁC. After the mixture was stirred for 2 h
at room temperature, the reaction was stopped with brine
at 0 ꢁC. The products were extracted with AcOEt (ꢃ3),
and the organic layer was washed with brine, and dried
over Na2SO4. After evaporation under reduced pressure,
the residue was purified by flash column chromatography
on silica gel (hexane/AcOEt¼3/1) to give (ꢀ)-32a (syn)
and (ꢀ)-32b (anti) as colorless oils (32a, 446 mg, 56%;
32b, 223 mg, 28%).
1
3383, 1651, 1381, 1150, 1016 cmꢂ1; H NMR (500 MHz,
CDCl3) d¼1.37 (s, 3H), 1.95 (t, J¼5.5 Hz, 2H), 2.94
(t, J¼5.5 Hz, 1H), 3.76 (dt, J1¼J2¼5.5 Hz, 2H), 4.0
(s, 4H); 13C NMR (75 MHz, CDCl3) d¼23.8, 40.3, 59.0,
64.5, 110.0.
Under an argon atmosphere, to a solution of oxalyl chloride
(5.77 g, 45.5 mmol) in CH2Cl2 (30 mL) was added a solution
of DMSO (7.09 g, 90.1 mmol) in CH2Cl2 (30 mL) at
ꢂ78 ꢁC. After 5 min, a solution of 22 (5.01 g, 37.9 mmol)
in THF (40 mL) was added to the mixture at ꢂ78 ꢁC, and
the mixture was stirred for 10 min. After an addition of
triethylamine (13.8 g, 136.4 mmol) to the solution at
ꢂ78 ꢁC, the mixture was warmed up to 0 ꢁC. The reaction
was stopped with 0.1 M phosphate buffer (pH 6.5). The
products were extracted with AcOEt (ꢃ3), and the organic
layer was washed with brine, and dried over Na2SO4. After
evaporation under reduced pressure, the residue was purified
by flash column chromatography on silica gel (hexane/
AcOEt¼6/1/5/1/3/1) to give 3-(1,3-dioxolan-2-yl)-
butanal (23) as a colorless oil (3.71 g, 75%); IR (neat)
Procedure B: under an argon atmosphere, to Me4NBH4
(1.07 g, 12.0 mol) were slowly added AcOH (4 mL) at
0 ꢁC and CH3CN (11 mL) at room temperature, and the mix-
ture was stirred for 30 min. After the addition of (ꢀ)-26
(699 mg, 5.46 mmol) in CH3CN (10 mL) at 0 ꢁC and stirring
for 3 h, the reaction was quenched with 0.5 M C4H4KNaO6
aqueous solution (10 mL). The products were extracted with
AcOEt (ꢃ3), and the organic layer was washed with satd
NaHCO3 aqueous solution, brine, and dried over Na2SO4.
After evaporation under reduced pressure, the residue was
purified by flash column chromatography on silica gel (hex-
ane/AcOEt¼3/1) to give (ꢀ)-32a (syn) and (ꢀ)-32b (anti) as
colorless oils (32a, 172 mg, 24%; 32b, 516 mg, 73%).
1715, 1418, 1385, 1360, 1132, 1047 cmꢂ1 1H NMR
;
(300 MHz, CDCl3) d¼1.43 (s, 3H), 2.72 (d, J¼3.0 Hz,
2H), 3.93–4.07 (m, 4H), 9.76 (t, J¼3.0 Hz, 1H); 13C NMR
(75 MHz, CDCl3) d¼25.0, 52.5, 64.8, 107.6, 200.2.
Compound (ꢀ)-32a (syn): IR (neat) 3339, 3077, 2969, 2932,
1641, 1418, 1375, 1325 cmꢂ1; 1H NMR (500 MHz, CDCl3)
d¼1.21 (d, J¼6.0 Hz, 3H), 1.51 (td, J1¼10.0 Hz, J2¼
14.5 Hz, 1H), 1.61 (td, J1¼2.5 Hz, J2¼14.0 Hz, 1H), 2.17–
2.25 (m, 2H), 3.10 (br s, 1H), 3.29 (br s, 1H), 3.83–3.97
(m, 1H), 3.98–4.17 (m, 1H), 5.10–5.20 (m, 2H), 5.76–5.88
(m, 1H); 13C NMR (75 MHz, CDCl3) d¼24.0, 42.6, 44.1,
68.9, 71.8, 118.3, 134.2; MS m/z (rel intensities) 131
(M++H, 11%), 112 (36), 94 (41), 89 (100), 87 (69), 73
(28); HRMS m/z 131.1060 (131.1072 calcd for C7H15O2,
M++H).
Under an argon atmosphere, to a solution of 23 (610 mg,
4.69 mmol) in THF (80 mL) was added a solution of allyl-
magnesium bromide (9.38 mL, 1.0 M THF solution) at
0 ꢁC. After the mixture was stirred for 1 h, the reaction
was stopped with satd NH4Cl aqueous solution at 0 ꢁC.
The products were extracted with AcOEt (ꢃ3), and the
organic layer was washed with brine, and dried over
Na2SO4. After evaporation under reduced pressure, the
residue was purified by flash column chromatography on
silica gel (hexane/AcOEt¼5/1) to give (ꢀ)-2-methyl-2-(2-
hydroxy-4-penten)-1,3-dioxolane (24) as a colorless oil
(700 mg, 88%); IR (neat) 2982, 1641, 1217, 1107,
Compound (ꢀ)-32b (anti): IR (neat) 3368, 3077, 2970,
1
2932, 1641, 1412, 1375, 1350 cmꢂ1; H NMR (500 MHz,
1
1045 cmꢂ1; H NMR (300 MHz, CDCl3) d¼1.37 (s, 3H),
CDCl3) d¼1.24 (d, J¼6.0 Hz, 3H), 1.62 (dd, J1¼J2¼6.0 Hz,
2H), 2.18–2.32 (m, 2H), 2.64 (br s, 2H), 4.00 (tt,
J1¼J2¼6.0 Hz, 1H), 4.16 (tq, J1¼J2¼6.0 Hz, 1H), 5.05–
5.20 (m, 2H), 5.74–5.90 (m, 1H); 13C NMR (75 MHz,
CDCl3) d¼23.5, 41.9, 43.5, 65.4, 68.1, 118.3, 134.6; MS
m/z (rel intensities) 130 (M+, 5.5%), 112 (20), 94 (13), 89
(11), 85 (54), 71 (95); HRMS m/z 130.0995 (130.0994 calcd
for C7H14O2, M+).
1.70–1.95 (m, 2H), 2.10–2.35 (m, 2H), 3.57 (s, 1H), 3.92–
4.03 (m, 1H), 3.98–4.03 (s, 4H), 5.02–5.18 (m, 2H), 5.85
(tdd, J1¼7.0 Hz, J2¼10 Hz, J3¼17 Hz, 1H); 13C NMR
(75 MHz, CDCl3) d¼24.1, 41.7, 44.2, 64.3, 64.7, 67.5,
110.4, 117.3, 134.8.
To a solution of (ꢀ)-24 (1.00 g, 5.83 mmol) in THF (20 mL)
was added a solution of 2 M HCl aq (20 mL) at 0 ꢁC. The
mixture was stirred for 6 h and the reaction was stopped
with H2O at 0 ꢁC. The products were extracted with AcOEt
(ꢃ3), and the organic layer was washed with brine, and dried
over Na2SO4. After evaporation under reduced pressure, the
residue was purified by flash column chromatography on
silica gel (hexane/AcOEt¼5/1) to give (ꢀ)-4-hydroxy-
6-hepten-2-one (26) as a colorless oil (530 mg, 71%); IR
4.3.2. (2RS,4SR)- and (2RS,4RS)-heptane-2,4-diol (( )-
33a (syn) and ( )-33b (anti)). According to the procedure
for the preparation of 24 described above, the aldehyde 23
(1.15 g, 8.82 mmol) was converted to (ꢀ)-1-(2-methyl-1,3-
dioxolan-2-yl)-2-pentanol (25) as a colorless oil (1.17 g,
76%); IR (neat) 3526, 2957, 2934, 2874, 1377, 1256,
1219, 1044 cmꢂ1 1H NMR (300 MHz, CDCl3) d 0.93
;
1
(neat) 3429, 2924, 1709, 1420, 1167, 997 cmꢂ1; H NMR
(t, J¼7.0 Hz, 3H), 1.22–1.60 (m, 4H), 1.37 (s, 3H), 1.76
(dd, J1¼9.0 Hz, J2¼14.5 Hz, 1H), 1.82 (dd, J1¼2.0 Hz,
J2¼14.5 Hz, 1H), 3.56 (s, 1H), 3.85–3.95 (m, 1H),
(300 MHz, CDCl3) d¼2.18 (s, 3H), 2.20–2.33 (m, 2H), 2.58
(dd, J1¼8.5 Hz, J2¼17.5 Hz, 1H), 2.63 (dd, J1¼4.0 Hz,

M. Nogawa et al. / Tetrahedron 62 (2006) 12071–12083
12079
3.95–4.06 (m, 4H); 13C NMR (75 MHz, CDCl3) d¼14.1,
4.68 (d, J¼7.0 Hz, 1H), 5.02–5.14 (m, 2H), 5.84 (tdd,
J1¼7.0 Hz, J2¼10.0 Hz, J3¼17.0 Hz, 1H); 13C NMR
(75 MHz, CDCl3) d¼24.3, 40.1, 43.1, 55.7, 64.3, 64.4,
73.6, 95.6, 109.0, 117.3, 134.7.
18.6, 24.1, 39.5, 44.8, 64.2, 64.7, 67.7, 110.4.
According to the procedure for the preparation of 26
described above, 25 (602 mg, 3.46 mmol) was converted
to (ꢀ)-4-hydroxy-2-heptanone (27) as a colorless oil
(356 mg, 79%); IR (neat) 3441, 2959, 2932, 2874, 1713,
Under an argon atmosphere, to a solution of (ꢀ)-28 (1.00 g,
4.63 mol) in THF (15 mL) was added BH3$THF (9.3 mL,
9.26 mol) at 0 ꢁC. The mixture was stirred for 40 min and
the reaction was quenched with 2 M NaOH (9.3 mL) and
H2O2 (9.3 mL). After 1 h, the products were extracted with
Et2O (ꢃ3), and the organic layer was washed with brine,
and dried over Na2SO4. After evaporation under reduced
pressure, the residue was purified by flash column chro-
matography on silica gel (hexane/AcOEt¼1/1) to give
(ꢀ)-4-methoxymethoxy-5-(2-methyl-1,3-dioxolan-2-yl)-1-
pentanol (29) as a colorless oil (900 mg, 90%); IR (neat)
1418, 1362, 1167 cmꢂ1 1H NMR (300 MHz, CDCl3)
;
d¼0.93 (t, J¼7.0 Hz, 3H), 1.20–1.57 (m, 4H), 2.18 (s,
3H), 2.54 (dd, J1¼9.0 Hz, J2¼17.5 Hz, 1H), 2.61 (dd,
J1¼3.0 Hz, J2¼17.5 Hz, 1H), 2.97 (br s, 1H), 3.90–4.10
(m, 1H); 13C NMR (75 MHz, CDCl3) d¼13.9, 18.6, 30.7,
38.5, 49.9, 67.3, 210.0.
Procedure A: according to the procedure for the preparation
of 32 described above, (ꢀ)-27 (645 mg, 4.96 mmol) was
converted to (ꢀ)-33a (syn) and (ꢀ)-33b (anti) as colorless
oils (33a, 420 mg, 64%; 33b, 210 mg, 32%).
3476, 2886, 1036 cmꢂ1 1H NMR (300 MHz, CDCl3)
;
d¼1.35 (s, 3H), 1.55–2.05 (m, 7H), 3.40 (s, 3H), 3.66 (t,
J¼7.0 Hz, 2H), 3.75–3.85 (m, 1H), 3.86–4.01 (m, 4H),
4.63 (d, J¼7.0 Hz, 1H), 4.72 (d, J¼7.0 Hz, 1H); 13C NMR
(75 MHz, CDCl3) d¼24.3, 28.1, 32.0, 43.5, 55.7, 62.9,
64.3, 64.5, 73.9, 95.5, 108.9.
Procedure B: according to the procedure for the preparation
of 32 described above, (ꢀ)-27 (566 mg, 4.35 mmol) was
converted to (ꢀ)-33a (syn) and (ꢀ)-33b (anti) as colorless
oils (33a, 89.0 mg, 16%; 33b, 445 mg, 78%).
Under an argon atmosphere, to a solution of NaH (890 mg,
22.2 mmol) in THF (30 mL) was added a solution of
(ꢀ)-29 (2.59 g, 11.1 mmol) in THF (25 mL) and benzyl bro-
mide (1.3 mL, 11.1 mmol) at 0 ꢁC. The mixture was stirred
for 48 h under reflux and the reaction was stopped with
0.1 M phosphate buffer (pH 6.5) at 0 ꢁC. The products
were extracted with AcOEt (ꢃ3), and the organic layer
was washed with brine, and dried over Na2SO4. After evap-
oration under reduced pressure, the residue was purified
by flash column chromatography on silica gel (hexane/
AcOEt¼10/1) to give (ꢀ)-2-(5-benzyloxy-2-methoxy-
methoxypentyl)-2-methyl-1,3-dioxolane (30) as a colorless
oil (3.2 g, 88%); IR (neat) 2932, 2880, 1454, 1375, 1038,
Compound 33a (syn): IR (neat) 3349, 2961, 2932, 2872,
1418, 1375, 1323 cmꢂ1 1H NMR (500 MHz, CDCl3)
;
d¼0.93 (t, J¼7.0 Hz, 3H), 1.21 (d, J¼6.5 Hz, 3H), 1.29–
1.62 (m, 6H), 2.97 (br s, 2H), 3.86–3.88 (m, 1H), 4.01–
4.10 (m, 1H); 13C NMR (125 MHz, CDCl3) d¼14.0, 18.4,
24.2, 40.4, 44.6, 69.2, 72.8; MS m/z (rel intensities) 132
(M+, 6.1%), 114 (100), 101 (6.7), 96 (41), 87 (20), 71
(100); HRMS m/z 132.1119 (132.1150 calcd for C7H16O2,
M+).
Compound 33b (anti): IR (neat) 3348, 2961, 2932, 2872,
1456, 1418, 1377, 1325 cmꢂ1
;
1H NMR (300 MHz,
CDCl3) d¼0.94 (t, J¼7.0 Hz, 3H), 1.24 (d, J¼6.0 Hz, 3H),
1.10–1.81 (m, 4H), 1.61 (dd, J1¼5.0 Hz, J2¼6.0 Hz, 2H),
2.50 (br s, 2H), 3.90–4.01 (m, 1H), 4.08–4.25 (m, 1H); 13C
NMR (75 MHz, CDCl3) d¼14.0, 18.9, 23.5, 39.5, 43.9,
65.5, 69.1; MS m/z (rel intensities) 132 (M+, 2.0%), 114
(28), 101 (17), 96 (25), 87 (13), 71 (90); HRMS m/z
132.1141 (132.1150 calcd for C7H16O2, M+).
947, 916, 737, 698 cmꢂ1 1H NMR (300 MHz, CDCl3)
;
d¼1.35 (s, 3H), 1.50–2.05 (m, 6H), 3.37 (s, 3H), 3.49 (t,
J¼6.0 Hz, 2H), 3.70–3.81 (m, 1H), 3.82–4.00 (m, 4H),
4.50 (s, 2H), 4.62 (d, J¼7.0 Hz, 1H), 4.70 (d, J¼7.0 Hz,
1H), 7.20–7.40 (m, 5H); 13C NMR (75 MHz, CDCl3)
d¼24.3, 25.1, 32.2, 43.6, 55.7, 64.3, 64.4, 70.3, 72.8, 73.8,
95.4, 108.9, 127.4, 127.5, 128.3, 138.6.
4.3.3. (2RS,4SR)- and (2RS,4RS)-7-benzyloxyheptane-
2,4-diol (( )-34a (syn) and ( )-34b (anti)). Under an argon
atmosphere, to a solution of (ꢀ)-24 (2.00 g, 11.6 mmol) in
CH2Cl2 (30 mL) was added a solution of diisopropylamine
(6.1 mL, 34.9 mmol) and chloromethylmethylether (1.8 mL,
23.3 mmol). The mixture was stirred for 17 h at room
temperature and the reaction was stopped with 0.1 M
phosphate buffer (pH 6.5) at 0 ꢁC. The products were
extracted with AcOEt (ꢃ3), and the organic layer was
washed with brine, and dried over Na2SO4. After evapora-
tion under reduced pressure, the residue was purified by flash
column chromatography on silica gel (hexane/AcOEt¼
10/1/7/1/4/1) to give (ꢀ)-2-(2-methoxymethoxypent-
4-enyl)-2-methyl-1,3-dioxolane (28) as a colorless oil (2.2 g,
To a solution of (ꢀ)-30 (1.00 g, 3.09 mmol) in THF (50 mL)
was added a solution of 2 M HCl aq (20 mL) at 0 ꢁC. The
mixture was stirred for 24 h and the reaction was stopped
with 0.2 M phosphate buffer (pH 6.5) at 0 ꢁC. The products
were extracted with Et2O (ꢃ3), and the organic layer was
washed with brine, and dried over Na2SO4. After evapora-
tion under reduced pressure, the residue was purified by flash
column chromatography on silica gel (hexane/AcOEt¼5/1)
to give (ꢀ)-7-benzyloxy-4-hydroxy-heptan-2-one (31) as
a colorless oil (510 mg, 71%); IR (neat) 3433, 2926, 2859,
1711, 1454, 1362, 1099, 739, 698 cmꢂ1
;
1H NMR
(300 MHz, CDCl3) d¼1.45–1.85 (m, 4H), 2.17 (s, 3H),
2.53–2.63 (m, 2H), 3.29 (br s, 1H), 3.51 (t, J¼6.0 Hz, 2H),
4.00–4.10 (m, 1H), 4.51 (s, 2H), 7.27–7.35 (m, 5H); 13C
NMR (125 MHz, CDCl3) d¼25.9, 30.8, 33.5, 50.1, 67.4,
70.2, 73.0, 127.6, 127.7, 128.4, 138.3, 209.7.
1
89%); IR (neat) 2934, 1639, 1377, 1146, 1040 cmꢂ1; H
NMR (300 MHz, CDCl3) d¼1.36 (s, 3H), 1.86 (dd,
J1¼5.0 Hz, J2¼14.5 Hz, 1H), 1.91 (dd, J1¼6.0 Hz,
J2¼14.5 Hz, 1H), 2.25–2.48 (m, 2H), 3.39 (s, 3H), 3.79–
3.87 (m, 1H), 3.89–3.98 (m, 4H), 4.67 (d, J¼7.0 Hz, 1H),
Procedure A: according to the procedure for the preparation
of 32 described above, (ꢀ)-31 (500 mg, 2.12 mmol) was

12080
M. Nogawa et al. / Tetrahedron 62 (2006) 12071–12083
converted to (ꢀ)-34a (syn) and (ꢀ)-34b (anti) as colorless
oils (34a, 252 mg, 50%; 34b, 168 mg, 34%).
(m, 2H), 4.22 (ddd, J1¼2.0 Hz, J2¼6.5 Hz, J3¼12.0 Hz,
1H), 4.38 (dq, J1¼J2¼6.5 Hz, 1H), 4.50 (s, 2H), 7.27–7.38
(m, 5H); 13C NMR (125 MHz, CDCl3) d¼19.5, 25.1, 30.2,
69.1, 73.0, 78.4, 83.3, 127.6, 127.7, 128.4, 138.1, 154.5;
MS m/z (rel intensities) 250 (M+, 28%), 173 (19), 71 (22),
43 (100); HRMS m/z 250.1200 (250.1205 calcd for
C7H12O3, M+).
Procedure B: according to the procedure for the preparation
of 32 described above, (ꢀ)-31 (315 mg, 1.34 mmol) was
converted to (ꢀ)-34a (syn) and (ꢀ)-34b (anti) as colorless
oils (34a, 118 mg, 37%; 34b, 177 mg, 56%).
Compound 34a (syn): IR (neat) 3383, 2928, 2857, 1454,
1406, 1323, 1099, 737, 698 cmꢂ1 1H NMR (300 MHz,
;
4.4.3. (4RS,5SR)-4-Butyl-5-methyl-1,3-dioxolan-2-one
(( )-11a (cis)). According to the procedure for the prepara-
tion of 4a described above, (ꢀ)-8a (375 mg, 2.84 mmol) was
converted to (ꢀ)-11a (cis) as a colorless oil (350 mg, 78%);
IR (neat) 2959, 1788, 1462, 1371, 1190, 1070, 777 cmꢂ1; 1H
NMR (300 MHz, CDCl3) d¼0.93 (t, J¼7.0 Hz, 3H), 1.30–
1.42 (m, 3H), 1.36 (d, J¼6.5 Hz, 3H), 1.49–1.60 (m, 2H),
1.67–1.78 (m, 1H), 4.64 (ddd, J1¼3.5 Hz, J2¼7.0 Hz,
J3¼10.0 Hz, 1H), 4.84 (qd, J1¼J2¼7.0 Hz, 1H); 13C NMR
(75 MHz, CDCl3) d¼13.8, 14.5, 22.3, 28.4, 75.9, 79.9,
154.7; MS m/z (rel intensities) 159 (M++H, 4.5%), 101
(46), 85 (100), 72 (100), 57 (100); HRMS m/z 159.1046
(159.1021 calcd for C8H15O3, M++H).
CDCl3) d¼1.18 (d, J¼6.0 Hz, 3H), 1.43–1.80 (m, 6H),
3.52 (t, J¼6.0 Hz, 2H), 3.66 (br s, 2H), 3.80–3.92 (m, 1H),
3.97–4.09 (m, 1H), 4.53 (s, 2H), 7.22–7.39 (m, 5H); 13C
NMR (75 MHz, CDCl3) d¼23.0, 25.2, 33.8, 44.8, 68.9,
70.0, 72.3, 72.8, 127.6, 127.8, 128.3, 138.5; MS m/z (rel
intensities) 238 (M+, 4.9%), 179 (9.2), 149 (100), 107
(66), 99 (43), 91 (100); HRMS m/z 238.1570 (238.1569
calcd for C14H22O3, M+).
Compound 34b (anti): IR (neat) 3377, 2928, 2857, 1454,
1408, 1312, 1099, 737, 698 cmꢂ1 1H NMR (300 MHz,
;
CDCl3) d¼1.22 (d, J¼6.0 Hz, 3H), 1.50–1.82 (m, 6H),
2.80 (br s, 1H), 3.42 (br s, 1H), 3.46–3.59 (m, 2H), 3.90–
4.00 (m, 1H), 4.08–4.21 (m, 1H), 4.53 (s, 2H), 7.24–7.39
(m, 5H); 13C NMR (125 MHz, CDCl3) d¼23.4, 26.5, 34.9,
44.0, 65.4, 69.2, 70.5, 73.1, 127.7, 127.8, 128.4, 137.9;
MS m/z (rel intensities) 238 (M+, 7.7%), 179 (79), 147
(21), 131 (77), 107 (100), 91 (100); HRMS m/z 238.1572
(238.1569 calcd for C14H22O3, M+).
4.4.4. (4RS,5RS)-4-Butyl-5-methyl-1,3-dioxolan-2-one
(( )-11b (trans)). According to the procedure for the prepa-
ration of 4a described above, (ꢀ)-8b (1.07 g, 8.10 mmol)
was converted to (ꢀ)-11b (trans) as a colorless oil (1.09 g,
85%); IR (neat) 2959, 2934, 2872, 1798, 1454, 1377,
1
1188, 775 cmꢂ1; H NMR (300 MHz, CDCl3) d¼0.93 (t,
J¼6.5 Hz, 3H), 1.31–1.55 (m, 4H), 1.46 (d, J¼6.5 Hz,
3H), 1.60–1.83 (m, 2H), 4.19 (dt, J1¼5.0 Hz, J2¼6.5 Hz,
1H), 4.38 (dq, J1¼J2¼6.5 Hz, 1H); 13C NMR (125 MHz,
CDCl3) d¼13.8, 19.1, 22.3, 26.7, 32.8, 78.4, 83.5, 154.6;
MS m/z (rel intensities) 159 (M++H, 2.0%), 101 (17), 85
(36), 71 (61), 57 (100); HRMS m/z 159.0966 (159.1021
calcd for C8H15O3, M++H).
4.4. Preparation of five-membered cyclic carbonates
4.4.1. (4RS,5SR)-4-(3-Benzyloxy)propyl-5-methyl-1,3-di-
oxolan-2-one (( )-4a (cis)). Under an argon atmosphere,
pyridine (7.9 g, 0.10 mmol) was added to a solution of
(ꢀ)-3a (3.9 g, 17.2 mmol) in CH2Cl2 (30 mL) at 0 ꢁC, fol-
lowed by addition of a solution of triphosgene (3.1 g,
10.3 mmol) in CH2Cl2 (15 mL) at ꢂ78 ꢁC. The mixture
was then slowly warmed to 0 ꢁC and stirred for 1 h. The re-
action was stopped with a satd NH4Cl aqueous solution and
the products were extracted with CH2Cl2 (ꢃ3). The organic
layer was washed with 1 M HCl (ꢃ2), brine, satd NaHCO3
aqueous solution, and brine, and dried over Na2SO4. After
evaporation, the residue was purified by column chromato-
graphy on silica gel (hexane/AcOEt¼1/1) to give (ꢀ)-4a
as a colorless oil (3.96 g, 92%); IR (neat) 2938, 2859,
4.4.5. (4RS,5SR)-4-Methyl-5-pentyl-1,3-dioxolan-2-one
(( )-12a (cis)). According to the procedure for the prepara-
tion of 4a described above, (ꢀ)-9a (2.08 g, 18.6 mmol) was
converted to (ꢀ)-12a (cis) as a colorless oil (1.63 g, 60%);
IR (neat) 2957, 2932, 2860, 1798, 1466, 1370, 1186,
1071 cmꢂ1
;
1H NMR (300 MHz, CDCl3) d¼0.91 (t,
J¼7.0 Hz, 3H), 1.23–1.45 (m, 5H), 1.36 (d, J¼6.5 Hz,
3H), 1.45–1.64 (m, 2H), 1.64–1.80 (m, 1H), 4.63 (ddd,
J1¼3.5 Hz, J2¼7.0 Hz, J3¼10.0 Hz, 1H), 4.82 (dq,
J1¼J2¼7.0 Hz, 1H); 13C NMR (75 MHz, CDCl3) d¼13.9,
14.5, 22.4, 25.2, 28.8, 31.4, 75.9, 79.9, 154.6; MS m/z (rel
intensities) 173 (M++H, 3.9%), 157 (4.8), 129 (13), 110
(21), 99 (78), 85 (68); HRMS m/z 173.1174 (173.1178 calcd
for C9H17O3, M++H).
1
1798, 1717, 1452, 1368, 1184, 1074, 743 cmꢂ1; H NMR
(500 MHz, CDCl3) d¼1.36 (d, J¼7.0 Hz, 3H), 1.66–1.90
(m, 4H), 3.48–3.53 (m, 1H), 3.53–3.60 (m, 1H), 4.51 (s,
2H), 4.65 (ddd, J1¼4.0 Hz, J2¼5.5 Hz, J3¼7.0 Hz, 1H),
4.82 (dq, J1¼J2¼7.0 Hz, 1H), 7.28–7.38 (m, 5H); 13C
NMR (75 MHz, CDCl3) d¼14.5, 25.9, 69.1, 72.9, 75.9,
79.7, 127.6, 127.7, 128.4, 138.2, 154.6; MS m/z (rel intensi-
ties) 250 (M+, 18%), 173 (15), 107 (56), 91 (100); HRMS
m/z 250.1187 (250.1205 calcd for C14H18O4, M+).
4.4.6. (4RS,5SR)-4-Heptyl-5-methyl-1,3-dioxolan-2-one
(( )-13a (cis)). According to the procedure for the prepara-
tion of 4a described above, (ꢀ)-10a (418 mg, 2.01 mmol)
was converted to (ꢀ)-13a (cis) as a colorless oil (405 mg,
97%); IR (neat) 2953, 2928, 2857, 1798, 1370, 1180,
4.4.2. (4RS,5RS)-4-(3-Benzyloxy)propyl-5-methyl-1,3-di-
oxolan-2-one (( )-4b (trans)). According to the procedure
for the preparation of 4a described above, (ꢀ)-3b (445 mg,
1.99 mmol) was converted to (ꢀ)-4b (trans) as a colorless
oil (478 mg, 96%); IR (neat) 2934, 2859, 1798, 1454,
1072 cmꢂ1
;
1H NMR (300 MHz, CDCl3) d¼0.89 (t,
J¼6.0 Hz, 3H), 1.24–1.44 (m, 9H), 1.36 (d, J¼6.5 Hz,
3H), 1.45–1.64 (m, 2H), 1.64–1.81 (m, 1H), 4.63 (ddd, J1¼
3.5 Hz, J2¼6.5 Hz, J3¼10.0 Hz, 1H), 4.82 (dq, J1¼J2¼
6.5 Hz, 1H); 13C NMR (75 MHz, CDCl3) d¼14.0, 14.5,
22.6, 25.6, 28.8, 29.0, 29.2, 31.7, 75.9, 79.9, 154.7; MS
m/z (rel intensities) 201 (M++H, 2.1%), 156 (1.9), 138
1373, 1186, 1074 cmꢂ1
;
1H NMR (500 MHz, CDCl3)
d¼1.43 (d, J¼6.5 Hz, 3H), 1.59–1.87 (m, 4H), 3.45–3.60

M. Nogawa et al. / Tetrahedron 62 (2006) 12071–12083
12081
(29), 127 (33), 113 (17), 99 (11); HRMS m/z 201.1490
(201.1491 calcd for C11H21O3, M++H).
143 (2.7), 130 (42), 114 (43), 86 (77), 72 (100); HRMS
m/z 159.1022 (159.1021 calcd for C8H15O3, M++H).
4.4.7. (4RS,5SR)-4-(3-Butenyl)-5-methyl-1,3-dioxolan-2-
one (( )-19a (cis)). According to the procedure for the
preparation of 4a described above, (ꢀ)-18a (325 mg,
2.50 mmol) was converted to (ꢀ)-19a (cis) as a colorless
oil (200 mg, 51%); IR (neat) 2982, 2926, 2853, 1798,
4.5.4. (4RS,6RS)-4-Methyl-6-propyl-1,3-dioxan-2-one
(( )-36b (anti)). According to the procedure for the prepara-
tion of 4a described above, (ꢀ)-33b (650 mg, 4.93 mmol)
was converted to (ꢀ)-36b (anti) as a colorless oil (323 mg,
42%); IR (neat) 2961, 2938, 2874, 1746, 1387, 1252,
1
1
1370, 1186, 1074, 916 cmꢂ1; H NMR (500 MHz, CDCl3)
1204, 1134 cmꢂ1; H NMR (500 MHz, CDCl3) d¼0.96 (t,
d¼1.37 (d, J¼6.5 Hz, 3H), 1.55–1.69 (m, 1H), 1.75–1.93
(m, 1H), 2.07–2.24 (m, 1H), 2.24–2.75 (m, 1H), 4.61–4.73
(m, 1H), 4.84 (dq, J1¼J2¼6.5 Hz, 1H), 5.00–5.18 (m, 2H),
5.80 (tdd, J1¼6.5 Hz, J2¼10.5 Hz, J3¼17.0 Hz, 1H);
13C NMR (125 MHz, CDCl3) d¼14.5, 28.1, 29.5,
75.8, 78.9, 116.4, 136.2, 154.5; MS m/z (rel intensities)
156 (M+, 13%), 114 (16), 112 (6.8), 97 (39), 85 (12),
84 (51); HRMS m/z 156.0736 (156.0787 calcd for
C8H12O3, M+).
J¼7.5 Hz, 3H), 1.41 (d, J¼6.5 Hz, 3H), 1.42–1.79 (m,
6H), 4.39–4.49 (m, 1H), 4.49–4.61 (m, 1H); 13C NMR
(75 MHz, CDCl3) d¼13.7, 18.2, 20.8, 32.4, 36.9, 72.7,
75.9, 149.4; MS m/z (rel intensities) 159 (M++H, 51%),
129 (6.1), 115 (12), 99 (6.1), 86 (7.1), 71 (100); HRMS
m/z 159.1047 (159.1021 calcd for C8H15O3, M++H).
4.5.5. (4RS,6SR)-4-(3-Benzyloxypropyl)-6-methyl-1,3-di-
oxan-2-one (( )-37a (syn)). According to the procedure for
the preparation of 4a described above, (ꢀ)-34a (100 mg,
0.42 mmol) was converted to (ꢀ)-37a (syn) as a colorless
oil (87.8 mg, 79%); IR (neat) 2932, 2857, 1746, 1042,
4.5. Preparation of six-membered cyclic carbonates
4.5.1. (4RS,6SR)-4-Allyl-6-methyl-1,3-dioxan-2-one (( )-
35a (cis)). According to the procedure for the preparation
of 4a described above, (ꢀ)-32a (100 mg, 0.77 mmol) was
converted to (ꢀ)-35a (cis) as a colorless oil (93.2 mg,
78%); IR (neat) 2980, 2936, 1748, 1643, 1400, 1248,
1244, 1194, 1113, 737, 700 cmꢂ1 1H NMR (300 MHz,
;
CDCl3) d¼1.39 (d, J¼6.0 Hz, 3H), 1.50–1.90 (m, 4H),
1.98–2.10 (m, 2H), 3.44–3.58 (m, 2H), 4.38–4.58 (m, 2H),
4.50 (s, 2H), 7.24–7.40 (m, 5H); 13C NMR (75 MHz,
CDCl3) d¼21.2, 24.7, 32.3, 34.7, 69.4, 72.9, 75.1, 78.6,
127.6, 128.4, 138.3, 149.1; MS m/z (rel intensities) 264 (M+,
4.2%), 221 (5.8), 160 (100), 130 (15), 107 (96), 91 (100);
HRMS m/z 264.1373 (264.1362 calcd for C15H20O4, M+).
1
1229, 1117 cmꢂ1; H NMR (500 MHz, CDCl3) d¼1.42 (d,
J¼6.0 Hz, 3H), 1.64 (td, J1¼12.0 Hz, J2¼14.0 Hz, 1H),
2.07 (td, J1¼3.0 Hz, J2¼14.0 Hz, 1H), 2.38–2.45 (m, 1H),
2.49–2.56 (m, 1H), 4.48 (ddt, J1¼3.0 Hz, J2¼J3¼6.0 Hz,
1H), 4.56 (ddq, J1¼3.0 Hz, J2¼6.0 Hz, J3¼11.5 Hz, 1H),
5.12–5.22 (m, 2H), 5.76–5.84 (m, 1H); 13C NMR
(75 MHz, CDCl3) d¼21.1, 33.9, 75.1, 77.9, 119.4, 131.2,
149.1; MS m/z (rel intensities) 157 (M++H, 3.7%), 141
(3.2), 129 (4.4), 112 (5.0), 97 (15), 87 (8.8); HRMS m/z
157.0864 (157.0865 calcd for C8H13O3, M++H).
4.5.6. (4RS,6RS)-4-(3-Benzyloxy-propyl)-6-methyl-1,3-
dioxan-2-one (( )-37b (anti)). According to the procedure
for the preparation of 4a described above, (ꢀ)-34b
(520 mg, 2.19 mmol) was converted to (ꢀ)-37b (anti) as
a colorless oil (437 mg, 76%); IR (neat) 2934, 2859, 1746,
1387, 1252, 1207, 1115, 737, 698 cmꢂ1
;
1H NMR
(300 MHz, CDCl3) d¼1.40 (d, J¼6.5 Hz, 3H), 1.65–2.10
(m, 6H), 3.44–3.60 (m, 2H), 4.44–4.60 (m, 1H), 4.50 (s,
2H), 4.62–4.74 (m, 1H), 7.24–7.42 (m, 5H); 13C NMR
(75 MHz, CDCl3) d¼20.7, 25.2, 31.9, 32.4, 69.3, 72.7,
72.9, 75.9, 127.6, 128.4, 138.2, 149.3; MS m/z (rel intensi-
ties) 264 (M+, 6.9%), 173 (6.5), 159 (4.6), 107 (46), 91
(100), 71 (100); HRMS m/z 264.1336 (264.1362 calcd for
C15H20O4, M+).
4.5.2. (4RS,6RS)-4-Allyl-6-methyl-1,3-dioxan-2-one (( )-
35b (anti)). According to the procedure for the preparation
of 4a described above, (ꢀ)-32b (403 mg, 3.10 mmol) was
converted to (ꢀ)-35b (anti) as a colorless oil (265 mg,
55%); IR (neat) 2980, 2938, 1746, 1643, 1387, 1254,
1
1202, 1119 cmꢂ1; H NMR (500 MHz, CDCl3) d¼1.45 (d,
J¼6.0 Hz, 3H), 1.90 (ddd, J1¼4.5 Hz, J2¼6.0 Hz, J3¼
9.0 Hz, 1H), 2.03 (ddd, J1¼4.5 Hz, J2¼7.0 Hz, J3¼
14.0 Hz, 1H), 2.38–2.44 (m, 1H), 2.57–2.63 (m, 1H),
4.56–4.61 (m, 1H), 4.68–4.74 (m, 1H), 5.16–5.23 (m, 2H),
5.75–5.84 (m, 1H); 13C NMR (75 MHz, CDCl3) d¼20.8,
31.5, 39.0, 77.0, 77.3, 119.5, 131.5, 149.2; MS m/z (rel inten-
sities) 157 (M++H, 30%), 141 (2.1), 129 (4.4), 112 (11), 97
(26), 84 (13); HRMS m/z 157.0873 (157.0865 calcd for
C8H13O3, M++H).
4.6. Typical procedure for the hydrolysis of cyclic
carbonates with P. diminuta
The basal medium for the microbial reaction consists of glu-
cose (10 g), polypeptone (7 g), and yeast extract (5 g) in 1 L
of 0.1 M phosphate buffer (pH 6.5). A 500-mL Erlenmeyer
flask each containing 100 mL of sterilized basal medium
was inoculated with a loopful of P. diminuta, and incubated
for 48 h at 30 ꢁC. To the broth was added 80 mL (84 mg) of
(ꢀ)-4a (cis) and the cultivation was continued. After 50 mL
of acetone was added to the mixture followed by saturation
with NaCl and filtration through a Celite pad, the products
were extracted with AcOEt, and the organic layer was dried
over Na2SO4. After evaporation, the residue was purified by
column chromatography on silica gel (hexane/AcOEt¼5/1)
to afford (4R,5S)-4a (36.1 mg, 43%; 97% ee) and (2R,3S)-
3a (30.1 mg, 40%; >99% ee) as colorless oils. The ee of
(2R,3S)-3a was determined by HPLC analysis of the
4.5.3. (4RS,6SR)-4-Methyl-6-propyl-1,3-dioxan-2-one
(( )-36a (cis)). According to the procedure for the prepara-
tion of 4a described above, (ꢀ)-33a (383 mg, 2.9 mmol) was
converted to (ꢀ)-36a (cis) as a colorless oil (139 mg, 30%);
IR (neat) 2961, 2936, 2874, 1744, 1400, 1248, 1198,
1
1115 cmꢂ1; H NMR (300 MHz, CDCl3) d¼0.96 (t, J¼
7.0 Hz, 3H), 1.35–1.83 (m, 6H), 1.42 (d, J¼6.0 Hz, 3H),
4.30–4.49 (m, 1H), 4.49–4.70 (m, 1H); 13C NMR
(75 MHz, CDCl3) d¼13.7, 17.7, 21.2, 34.8, 37.3, 75.1,
78.6, 149.4; MS m/z (rel intensities) 159 (M++H, 34%),

12082
M. Nogawa et al. / Tetrahedron 62 (2006) 12071–12083
corresponding bis-(+)-MTPA ester. Conditions of the HPLC
analysis: column, Zorbax-Sil (0.46 mmꢃ25 cm, DuPont
Instruments); eluent, hexane/AcOEt¼90/10; flow rate,
0.5 mL/min; retention time, 30 (2R,3S) and 32 (2S,3R) min.
To determine the ee of (4R,5S)-4a, the cyclic carbonate
was hydrolyzed with K2CO3 to afford the corresponding
(2S,3R)-3a. The absolute configuration was confirmed by
comparing its optical rotation sign with that of the authentic
sample (2S,3R)-3a, and the preparation method is described
in the following section.
Compound 33b: HPLC analysis of the corresponding bis-
(+)-MTPA ester. Conditions of the HPLC analysis: column,
Zorbax-Sil (0.46 mmꢃ25 cm); eluent, hexane/AcOEt¼
90/10; flow rate, 0.5 mL/min; retention time, 13 (2R,4R)
and 14 (2S,4S) min.
Compound 34a: HPLC analysis of the corresponding bis-
(+)-MTPA ester. Conditions of the HPLC analysis: column,
Zorbax-Sil (0.46 mmꢃ25 cm); eluent, hexane/AcOEt¼
90/10; flow rate, 0.5 mL/min; retention time, 30 and 32 min.
Enantioselective reactions of the other substrates were car-
ried out by the same procedure. The results were shown in
the text. All the spectral data (1H and 13C NMR, IR, and
MS) were in full agreement with those of the racemates.
Compound 34b: HPLC analysis of the corresponding bis-
(+)-MTPA ester. Conditions of the HPLC analysis: column,
Zorbax-Sil (0.46 mmꢃ25 cm); eluent, hexane/AcOEt¼
90/10; flow rate, 0.5 mL/min; retention time, 26 (2R,4R)
and 32 (2S,4S) min.
1
The ee’s of diols were determined by HPLC or H NMR
analysis. The ee’s of cyclic carbonates were determined by
similar analyses of the corresponding diols derived from
the carbonates with K2CO3. The methods and the conditions
are given below:
4.7. Preparation of the authentic sample (2S,3R)-3a
According to the procedure described above for the prepara-
tion of (ꢀ)-17, (2S,3R)-2-(4-methoxybenzyloxy)-5-hexen-
3-ol (39) was prepared from ethyl (S)-lactate in four steps.
Compound 3b: HPLC analysis of the corresponding bis-(+)-
MTPA ester. Conditions of the HPLC analysis: column,
Zorbax-Sil (0.46 mmꢃ25 cm, Agilent Technologies); elu-
ent, hexane/AcOEt¼90/10; flow rate, 0.5 mL/min; retention
time, 36 (2S,3S) and 39 (2R,3R) min.
Under an argon atmosphere, to a solution of (2S,3R)-39
(502 mg, 2.13 mmol) in CHCl2 (10 mL) were added 3,4-di-
hydro-2H-pyran (2.0 mL, 1.8 g, 21 mmol) and a catalytic
amount of p-TsOH at 0 ꢁC, and stirred overnight at room
temperature. The reaction was stopped with satd NaHCO3
aqueous solution, and the products were extracted with
CHCl2 (ꢃ3). The organic layer was washed with brine and
dried over Na2SO4. After evaporation under reduced pressure,
the residue was purified by flash column chromatography
on silica gel (hexane/AcOEt¼10/1/5/1) to give (4R,5S)-
5-(4-methoxybenzyloxy)-4-tetrahydropyranyloxy-1-hexene
(40) as a colorless oil (433 mg, 64%). This compound
included some impurity, but this was used without further
purification.
1
Compound 8a: H NMR (500 MHz) analysis of the cor-
responding bis-(+)-MTPA ester. Signals at d 3.42 (d,
J¼1.0 Hz)+3.50 (d, J¼1.0 Hz) (CH3Oꢃ2, (2S,3R)) and
3.46 (t, J¼1.0 Hz) (CH3Oꢃ2, (2R,3S)).
1
Compound 9a: H NMR (500 MHz) analysis of the cor-
responding bis-(+)-MTPA ester. Signals at d 3.42 (s)+3.50
(d, J¼1.0 Hz) (CH3Oꢃ2, (2S,3R)) and 3.45 (s)+3.46 (s)
(CH3Oꢃ2, (2R,3S)). The absolute configuration was
confirmed by comparing its optical rotation sign with that
reported; (2S,3R)-9a, lit.11 [a]1D8 +22.73 (c 1.10, MeOH).
Under an argon atmosphere, to a solution of (2S,3R)-40
(400 mg, 1.25 mmol) in THF (10 mL) was added BH3$THF
(1.25 mL, 2.0 M in THF) at 0 ꢁC and stirred for 4 h at room
temperature. The reaction was quenched with a drop of
water, followed by the addition of 2 M NaOH aqueous solu-
tion (2.5 mL) and 35% H2O2 (2.5 mL), and the mixture was
stirred overnight at room temperature. After the mixture was
saturated with NaCl, products were extracted with Et2O
(ꢃ3), and the organic layer was dried over Na2SO4. After
evaporation under reduced pressure, the residue was purified
by flash column chromatography on silica gel (hexane/
AcOEt¼1/1/AcOEt) to give (4R,5S)-5-(4-methoxybenzyl-
oxy)-4-tetrahydropyranyloxy-1-hexanol (41) as a colorless
oil (262 mg, 62%).
Compound 10a: 1H NMR analysis of the corresponding bis-
(+)-MTPA ester. Signals at d 3.42 (d, J¼1.0 Hz)+3.50 (s)
(CH3Oꢃ2, (2S,3R)) and 3.45 (d, J¼1.0 Hz)+3.46 (s)
(CH3Oꢃ2, (2R,3S)).
Compound 18a: 1H NMR analysis of the corresponding bis-
(+)-MTPA ester. Signals at d 3.42 (s)+3.49 (s) (CH3Oꢃ2,
(2S,3R)) and 3.45 (s)+3.46 (s) (CH3Oꢃ2, (2R,3S)).
Compound 32a: HPLC analysis of the corresponding bis-
(+)-MTPA ester. Conditions of the HPLC analysis: column,
Zorbax-Sil (0.46 mmꢃ25 cm); eluent, hexane/AcOEt¼
90/10; flow rate, 0.5 mL/min; retention time, 16 and 17 min.
Compound 32b: HPLC analysis of the corresponding bis-
(+)-MTPA ester. Conditions of the HPLC analysis: column,
Zorbax-Sil (0.46 mmꢃ25 cm); eluent, hexane/AcOEt¼
90/10; flow rate, 0.5 mL/min; retention time, 14 (2R,4R)
and 16 (2S,4S) min.
According to the procedure for the preparation of (Z)-2a
described above, (4R,5S)-41 (329 mg, 0.973 mmol) was
converted to (4R,5S)-1-benzyloxy-5-(4-methoxybenzyl-
oxy)-4-tetrahydropyranyloxyhexane (42, 337 mg, 81%) as
a colorless oil.
Compound 33a: HPLC analysis of the corresponding bis-(+)-
MTPA ester. Conditions of the HPLC analysis: column,
Zorbax-Sil (0.46 mmꢃ25 cm); eluent, hexane/AcOEt¼
90/10; flow rate, 0.5 mL/min; retention time, 13.6and 14.4 min.
According to the procedure for the preparation of (ꢀ)-18a
described above, (4R,5S)-42 (259 mg, 0.605 mmol) was
converted to (2S,3R)-3a (51.6 mg, 38%) as a colorless oil;
[a]2D5 +12.9 (c 1.34, MeOH). All the spectral data (1H and

M. Nogawa et al. / Tetrahedron 62 (2006) 12071–12083
12083
13C NMR, IR, and MS) of (2S,3R)-3a were in full agreement
with those of (ꢀ)-3a.
3. For representative examples, see: (a) Caron, G.; Kazlauskas,
R. J. Tetrahedron: Asymmetry 1993, 4, 1995–2000; (b) Bisht,
K. S.; Parmar, V. S. Tetrahedron: Asymmetry 1993, 4, 957–
958; (c) Kim, M.-J.; Choi, G.-B.; Kim, J.-Y. Tetrahedron
Lett. 1995, 36, 6253–6256; (d) Liu, R.; Hogberg, H.-E.
Tetrahedron: Asymmetry 2001, 12, 771–778.
4. (a) Barton, P.; Page, M. I. Tetrahedron 1992, 48, 7731–7734;
(b) Kawashima, M.; Horikawa, Y. Biotechnol. Lett. 1993, 15,
1039–1042; (c) Kojima, T.; Ando, T. JP07031497; Chem.
Abstr. 1995, 122, 263703.
5. (a) Matsumoto, K.; Fuwa, S.; Kitajima, H. Tetrahedron Lett.
1995, 36, 6499–6502; (b) Matsumoto, K.; Fuwa, S.; Shimojo,
M.; Kitajima, H. Bull. Chem. Soc. Jpn. 1996, 69, 2977–2987;
(c) Matsumoto, K.; Shimojo, M.; Kitajima, H.; Hatanaka, M.
Synlett 1996, 1085–1086; (d) Matsumoto, K.; Shimojo, M.;
Hatanaka, M. Chem. Lett. 1997, 1151–1152; (e) Shimojo, M.;
Matsumoto, K.; Hatanaka, M. Tetrahedron 2000, 56, 9281–
9288; (f) Matsumoto, K.; Nakamura, Y.; Shimojo, M.;
Hatanaka, M. Tetrahedron Lett. 2002, 43, 6933–6936.
6. (a) Matsumoto, K.; Sato, Y.; Shimojo, M.; Hatanaka, M.
Tetrahedron: Asymmetry 2000, 11, 1965–1973; (b) Nogawa,
M.; Shimojo, M.; Matsumoto, K.; Ohta, H.; Hatanaka, M.
Heterocycles 2006, 68, 1329–1334.
4.8. Preparation of the authentic sample (2S,3S)-3b
Under an argon atmosphere, to a solution of (2S,3R)-24
(400 mg, 1.25 mmol) in t-BuOH (5 mL)/H2O (5 mL) mixed
solvent was added AD-mix-a (1.4 g), and the mixture was
stirred at room temperature. After the mixture changed to
a biphasic clear solution, to the solution were added
CH3SO2NH2 (95 mg) and (E)-2b (190 mg, 1.0 mmol) at
0 ꢁC, and stirred overnight at room temperature. After addi-
tion of NaS2O4 and stirring for 30 min, the products were ex-
tracted with AcOEt (ꢃ4), and the organic layer was washed
with 2 M NaOH aqueous solution (ꢃ2). After the organic
layer was dried over Na2SO4 and evaporated under reduced
pressure, the residue was purified by flash column chromato-
graphy on silica gel (hexane/AcOEt¼1/1) to give (2S,3S)-3b
as a colorless oil (148 mg, 66%); [a]2D7 ꢂ13.8 (c 1.16,
MeOH); [a]2D3 ꢂ8.0 (c 1.87, CHCl3). All the spectral data
(1H and 13C NMR, IR, and MS) of (2S,3S)-3b were in full
agreement with those of (ꢀ)-3b.
7. Chen, C.-S.; Fujimoto, Y.; Girdaukas, G.; Sih, C. J. J. Am.
Chem. Soc. 1982, 104, 7294–7299.
8. Itoh, T.; Yoshinaka, A.; Sato, T.; Fujisawa, T. Chem. Lett. 1985,
1679–1680.
9. Yamazaki, T.; Kuboki, A.; Ohta, H.; Mitzel, T. S.; Paquette,
L. A.; Sugai, T. Synth. Commun. 2000, 30, 3061–3072.
10. The plural hydrolytic enzymes could probably present in the
microorganisms. However, in all cases, the enantioselectivities
could be explained by the participation of a single enzyme.
Furthermore, we already tried to purify the active enzyme
and the data showed that a single enzyme could catalyze the
enantioselective hydrolysis of the cyclic carbonates, although
the purification have not completely finished.12
11. Kawabata, J.; Tahara, S.; Mizutani, J. Agric. Biol. Chem. 1978,
42, 89–94.
12. Kondo, D.; Uchida, H.; Matsumoto, K.; Shimojo, M.;
Hatanaka, M.; Uwajima, T. Abstracts of Papers, 5th Japanese
Symposium on the Chemistry of Biocatalysis, Okayama,
Japan, Dec 13–14, 2001; 2P-25.
Acknowledgements
M.S. was supported by a grant from Research Fellowships of
the Japan Society for the Promotion of Science (JSPS) for
Young Scientists. We thank Material Science Research
Center (Meisei university) for NMR analysis.
References and notes
1. (a) Sharpless, K. B.; Amberg, W.; Bennani, Y. L.; Crispino,
G. A.; Hartung, J.; Jeong, K.-S.; Kwong, H.-L.; Morikawa,
K.; Wang, Z.-M.; Xu, D.; Zhang, X.-L. J. Org. Chem. 1992,
57, 2768–2771; (b) Kolb, H. C.; VanNieuwenhze, M. S.;
Sharpless, K. B. Chem. Rev. 1994, 94, 2483–2547.
2. Wang, L.; Sharpless, K. B. J. Am. Chem. Soc. 1992, 114, 7568–
7570.