Synthesis of optically active 9-oxabicyclo[3.3.1]nona-2,6-diene as a cycloocta-1,5-diene equivalent and the corresponding tetrol

Article abstract of DOI:10.1016/S0040-4020(00)00089-2

Highly enantio- and diastereo-selective synthesis of C₂-symmetric 9- oxabicyclo[3.3.1]nona-2,6-diene and the corresponding C₂-symmetric 2,3,6,7- tetrol has been achieved starting from optically active 5-cyclooctene-1,2- diol prepared by an enzymatic procedure. (C) 2000 Elsevier Science Ltd.

Full text of DOI:10.1016/S0040-4020(00)00089-2

TETRAHEDRON
Pergamon
Tetrahedron 56 (2000) 1999±2006
Synthesis of Optically Active 9-Oxabicyclo[3.3.1]nona-2,6-diene as
a Cycloocta-1,5-diene Equivalent and the Corresponding Tetrol
*
Akira Takahashi, Mariko Aso, Masakazu Tanaka and Hiroshi Suemune
Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka 812-8582, Japan
Received 22 September 1999; accepted 31 January 2000
AbstractÐHighly enantio- and diastereo-selective synthesis of C2-symmetric 9-oxabicyclo[3.3.1]nona-2,6-diene and the corresponding
C2-symmetric 2,3,6,7-tetrol has been achieved starting from optically active 5-cyclooctene-1,2-diol prepared by an enzymatic procedure.
q 2000 Elsevier Science Ltd. All rights reserved.
Recently, numerous optically active phosphines and
amines have been used as a chiral ligand for developing
catalytic asymmetric reactions with various metals such as
palladium, rhodium and so on. In the procedure for prepara-
tion of these metal complexes, cycloocta-1,5-diene was
commonly used as a bidentate ole®nic ligand.1 In this report,
we wish to describe the synthesis of optically active 9-oxa-
bicyclo[3.3.1]nona-2,6-diene2 15 as a chiral cycloocta-1,5-
diene equivalent and the corresponding tetrol 26. The ®nal
aim of this work is to develop an asymmetric reaction using a
metal complex with these compounds as a chiral ligand.
previously reported by us.3 First, diastereoselective addition
of bromine to (2)-1 was studied. Reaction of (2)-1 with
bromine in CHCl3 at 2408C unexpectedly afforded a
mixture of bicyclic ether-bridged products4 2 and 3 (72%
yield) in the ratio of 7 to 1. This mixture was submitted to
dehydrobromination with 1,8-diazabicyclo[5.4.0]undec-7-
ene (DBU) and subsequent acetylation to afford an insepar-
able mixture of 4 and 5 (55% yield) in the same ratio of 7 to
1
1. In the H±1H COSY spectrum of the major part of this
mixture, the connections in the order of C2-H, C3-2H, C4-H
and C5-H of 4 were observed, which suggests that the major
product has
a 9-oxabicyclo[4.2.1]non-2-ene skeleton
The synthetic route to 15 was planned as follows: (i)
diastereoselective addition of bromine to optically active
cyclooctene derivatives; (ii) an ether bridge formation to
construct the 9-oxabicyclo[3.3.1]nonane skeleton; (iii) intro-
duction of double bonds at the C2- and C6-positions of 15.
(Scheme 1). The ether bond formation from (2)-1 might
proceed with complete diastereoselectivity via bromonium
cation (A), and 5-exo ring closure is favored over 6-exo
ring closure in terms of regioselectivity. Details for the
determination of the stereochemistry of the initial products
2 and 3 are given below.
Both enantiomers of 5-cyclooctene-1,2-diol 1 as the starting
material were prepared by an enzymatic procedure
Next, addition of bromine to the acetonide 6, prepared from
Scheme 1.
Keywords: chiral ligand; bidentate ole®nic ligand; 5-cyclooctene-1,2-diol.
* Corresponding author. E-mail: suemune@lyra.phar.kyushu-u.ac.jp
0040±4020/00/$ - see front matter q 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020(00)00089-2

2000
A. Takahashi et al. / Tetrahedron 56 (2000) 1999±2006
Scheme 2.
Scheme 3.
Scheme 4.

A. Takahashi et al. / Tetrahedron 56 (2000) 1999±2006
2001
identical with that of 2, and subsequent basic treatment of 12
with DBU gave an achiral bis-ether 13 with s-symmetry in
57% yield. For the reactions from 7 and 8, ether bond forma-
tion might proceed via an intramolecular SN2 process.
Taking the results mentioned above into consideration, the
structures of 2±5, 7±10 and 12 were determined as depicted
in Schemes 1 and 2.
Next, dehydroxylation of 10 was studied to synthesize the
target molecule (R,R)-15. Compound 10 was converted into
the corresponding N,N-dimethylthiocarbamate 14 (95%) in
the usual manner. Elimination reaction of 14 under thermal
conditions gave the desired (R,R)-15 in reasonable yields
(47% as isolated yield). In this reaction, not so many
by-products were observed, but the volatility of 15 might
cause the slightly decreased yield. 1H and 13C NMR spectra
Figure 1. ORTEP-diagram of 19.
(2)-1 in 94% yield in the usual manner, was examined. This
reaction afforded two diastereomers of trans-addition
products 7 (89%) and 8 (9%) with C2-axis. The structure
of these products was determined by the following chemical
transformations. Acidic treatment of 7 gave 9 in 99% yield,
1
of the (R,R)-15 showed its C2-symmetric property; the H
1
whose H NMR spectrum was not identical with that of 3.
NMR spectrum showed ®ve kinds of protons and the 13C
NMR spectrum four kinds of carbons. Compound (S,S)-15
was also synthesized starting from (S,S)-(1)-1.
Subsequent dehydrobromination of 9 under basic conditions
afforded the desired 10 and the optically active D2-
symmetric 2,7-dioxatwistan 11 ([a]2D7ˆ2221 (c 0.67,
CHCl3); lit.5 [a]Dˆ2225 (c 0.285, CHCl3)). Among several
reaction conditions employed, NaH in dimethylsulfoxide
(DMSO) gave the best result in terms of the yield of 10
(70%). Furthermore, the yield of 11 was raised up to 35%
in the case of using DBU in re¯uxing toluene. This process
might be interesting as a novel procedure to prepare the
optically active dioxatwistan 11. After quantitative acetyl-
ation of 10 into 5, the skeleton of 5 could be determined by
its 1H±1H COSY spectrum, in which the connections in the
order of C2-H, C1-H, C8-2H, C7-H, C6-H and C5-H were
observed. On the other hand, similar acid treatment of 8
As a preliminary study for the application of optically active
15, synthesis of the complex with rhodium trichloride was
performed. According to the method for preparation of
RhCl(cycloocta-1,5-diene)2, a mixture of RhCl3 and (S,S)-
15 in EtOH was re¯uxed for 2 h. The resulting crude yellow
precipitate 16 (60%) was collected. The high-resolution
mass spectrum of 16 supported Rh2Cl2(15)2 as a molecular
1
mass, and its H NMR spectrum suggested its structure as
depicted in Scheme 3. To our regret, racemization of (S,S)-
15, which might be caused through the shift of both double
bonds, was observed during this complex formation; a
ligand exchange of 16 with PPh3 in CHCl3 gave (S,S)-15
1
gave 12 in 99% yield, whose H NMR spectrum was not
Scheme 5.

2002
A. Takahashi et al. / Tetrahedron 56 (2000) 1999±2006
Scheme 6.
of 11% ee. In addition, a preliminary study of silylformyla-
tion6 of benzaldehyde using 16 did not afford satisfactory
results; this reaction afforded a hydroxy aldehyde 17, which
might be obtained via a desired product B, in only 15%
yield. As a result, a further molecular design might be
required to use 15-type of compound as a chiral ligand.
IR spectra were taken on a JASCO IR A-100 infrared spec-
trophotometer. Speci®c rotations were measured on a
JASCO DIP-360 digital polarometer. Column chromato-
graphy was carried out on silica gel 70±230 mesh (Merck,
Kieselgel 60).
A mixture of (1R,2R,5S,6S)-5-bromo-9-oxabicyclo[4.2.1]-
nonan-2-ol (2) and (1R,2R,5R,6R)-6-bromo-9-oxabicyclo-
[3.3.1]nonan-2-ol (3). To a solution of (R,R)-(2)-1
(462 mg, 3.25 mmol) in CHCl3 (6 ml) was added dropwise
a solution of Br2 (0.2 ml, 3.9 mmol) in CHCl3 (5 ml) at
2408C and the mixture was stirred for 1 h. The reaction
mixture was allowed to warm to room temperature, and
saturated aqueous sodium hydrogen sul®te was added to
the reaction mixture. The mixture was extracted with
CHCl3. The organic layer was washed with saturated
aqueous NaHCO3 and brine, and dried over Na2SO4. After
removal of solvent in vacuo, the residue was puri®ed by
silica gel column chromatography. Elution with hexane±
AcOEtˆ2:1 to 1:1 gave 2 and 3 as an inseparable mixture
(517 mg; 72%) in the ratio of 7 to 1; EIMS (m/z) 221
Synthesis of C2-symmetric 9-oxabicyclo[3.3.1]nonane-
2,3,6,7-tetrol
Two synthetic plans of (1S,2R,3R,5S,6R,7R)-9-oxabi-
cyclo[3.3.1]nonane-2,3,6,7-tetrol 26 were considered. One
was a stepwise process starting from (1)-10 via 23 (Path A),
and the other was a direct one-step process from (S,S)-15
(Path B) (Scheme 4).
At ®rst, the hydroxy group of (1)-10 was protected as
tert-butyldimethylsilyl (TBDMS) ether 18 (98%) and sub-
sequent OsO4-catalyzed cis-dihydroxylation gave the syn-
diol 19 (82%) with complete diastereoselectivity. The
stereochemical structure of 19 was ®nally determined by
X-ray analysis (Fig. 1). Protection of cis-diol functions of
19 as an acetonide 20 (95%) and further cleavage of
TBDMS ether linkage gave 21 (98%).
1
[M1H]1, 223 [M1H12]1; 2: H NMR (d, CDCl3) 4.60±
4.51 (m, 2H), 4.26±4.11 (m, 2H), 2.40±1.05 (m, 9H); 13C
NMR (d, CDCl3) 82.0 (d), 80.9 (d), 71.1 (d), 54.3 (d), 32.1
1
(t), 29.7 (t), 26.6 (t), 24.8 (t); 3: H NMR (d, CDCl3) 4.55
(m, 1H), 4.20±4.03 (m, 2H), 3.89 (m, 1H).
Subsequent mesylation of 21 and elimination of mesylate
gave the desired 23 (56% from 21). The OsO4-catalyzed cis-
dihydroxylation of 23 afforded the desired syn,syn-24 in
79% yield. The structure of 24 was con®rmed by conversion
into bisacetonide 25 of C2-symmetry. Acidic treatment of 24
afforded the target molecule 26 in 72% yield and its spectro-
scopic analyses supported the structure (Scheme 5). The
synthetic route from 10 to the mesylate 22 (Scheme 6)
could be shortened by direct mesylation of 10 into 27 and
subsequent similar transformation via 28.7
A mixture of (1R,2R,6S)-9-oxabicyclo[4.2.1]non-4-en-2-
yl acetate (4) and (1R,2R,5R)-9-oxabicyclo[3.3.1]non-6-
en-2-yl acetate (5). To a solution of a mixture of 2 and 3
(100 mg, 0.45 mmol) in toluene (2 ml) was added DBU
(0.68 ml, 4.54 mmol) and the whole was re¯uxed for 30 h.
After cooling, H2O was added to the reaction mixture and
the whole was extracted with Et2O. The organic layer was
washed with brine, dried over Na2SO4, and concentrated in
vacuo. The residue was dissolved in CH2Cl2 (2 ml), and
(CH3CO)2O (42 ml, 0.45 mmol), pyridine (36 ml,
0.45 mmol) and 4-dimethylaminopyridine (10 mg) were
added. The mixture was stirred at room temperature for
16 h. After addition of H2O, the whole was extracted with
CH2Cl2. The organic layer was washed with saturated
aqueous NaHCO3 and brine, and dried over Na2SO4. After
removal of solvent in vacuo, the residue was puri®ed by
silica gel column chromatography. Elution with hexane±
AcOEtˆ5:1 gave 4 and 5 as an inseparable mixture
(45 mg; 55%) in the ratio of 7 to 1; IR (CHCl3) 2945,
The syn-selectivity of OsO4-catalyzed cis-dihydroxylation8
of 18, 27 and 23 strongly encouraged us to undertake direct
synthesis of 26 from (S,S)-15 (Path B). In accordance with
our expectation, OsO4-catalyzed cis-dihydroxylation of
(S,S)-15 afforded 26 in 72% yield in a completely diastereo-
selective manner.
Experimental
1
1735 cm21; 4; H NMR (d, CDCl3) 5.94 (ddd, Jˆ11.6,
5.6, 3.0 Hz, 1H), 5.48 (ddd, Jˆ11.6, 6.9, 3.6 Hz, 1H), 5.03
(ddd, Jˆ9.6, 5.6, 4.0 Hz, 1H), 4.59 (dd, Jˆ7.6, 5.6 Hz, 1H),
4.50 (m, 1H), 2.67 (dt, Jˆ16.8, 6.3 Hz, 1H), 2.25 (m, 1H),
Melting points were taken on a Yanagimoto melting point
apparatus and are not corrected. H NMR spectra were
1
obtained on a JEOL GX-270 (270 MHz) or a JEOL JMN-
GX-500 (500 MHz) spectrometer. 13C NMR spectra were
taken on a JEOL GX-270 (68 MHz) spectrometer. Mass
spectra and high-resolution mass spectra were measured
on a JEOL JMS-610H or a JEOL JMS-SX 102 spectrometer.
1
2.05 (s, 3H), 2.16±1.95 (m, 3H), 1.83 (m, 1H). 5; H
NMR (d, CDCl3) 5.98 (ddd, Jˆ10.2, 4.0, 3.0 Hz, 1H),
5.73 (ddt, Jˆ10.2, 4.6, 2.3 Hz, 1H), 5.00 (dt, Jˆ11.6,
5.6 Hz, 1H), 4.25 (m, 1H), 4.19 (m, 1H), 2.44 (dm,

A. Takahashi et al. / Tetrahedron 56 (2000) 1999±2006
2003
Jˆ18.8 Hz, 1H), 2.13 (ddd, Jˆ18.8, 4.3, 2.3 Hz, 1H), 2.52
(s, 3H), 2.00 (m, 1H), 1.85±1.74 (m, 2H), 1.59 (dm,
Jˆ13.2 Hz, 1H).
(1R,2R,5R)-9-Oxabicyclo[3.3.1]non-6-en-2-ol (10) and (1R,
3R,6R,8R)-2,7-dioxatricyclo[4.4.0.03,8]decane ((2)-2,7-Dioxa-
twistan) (11). With DBU in toluene: To a solution of 9
(132 mg, 597 mmol) in toluene (14 ml) was added DBU
(0.9 ml, 5.97 mmol) and the mixture was re¯uxed for
1 day. H2O was added to the reaction mixture and the
whole was extracted with Et2O. The organic layer was
washed with brine, dried over Na2SO4, and concentrated
in vacuo. The residue was puri®ed by silica gel column
chromatography. Elution with hexane±AcOEtˆ2:1 to 1:1
gave 10 (38 mg, 46%) and 11 (30 mg, 35%). 10: a colorless
oil; [a]2D8ˆ 298.8 (c 0.63, CHCl3); IR (neat) 3400, 2920,
(1R,8R)-10,10-Dimethyl-9,11-dioxabicyclo[6.3.0]undec-
4-ene (6). A mixture of (R,R)-(2)-(1) (3.25 g, 22.9 mmol),
2,2-dimethoxypropane (4.2 ml, 34.4 mmol) and catalytic
amount of PPTS in acetone (30 ml) was stirred at room
temperature for 5 h. After the addition of saturated aqueous
NaHCO3 (10 ml), the whole was concentrated in vacuo and
the aqueous residue was extracted with ether. The ether
extract was washed with brine, dried over Na2SO4, and
concentrated in vacuo. The residue was puri®ed by silica
gel column chromatography. Elution with hexane±
AcOEtˆ10:1 gave 6 (3.90 g, 94%) as a colorless oil;
1
1060, 1040, 1020 cm21; H NMR (d, CDCl3) 5.97 (dt,
Jˆ9.9, 3.3 Hz, 1H), 5.72 (ddt, Jˆ10.2, 4.6, 2.3 Hz, 1H),
4.23 (t, Jˆ4.6 Hz, 1H), 4.09 (t, Jˆ6.3 Hz, 1H), 3.97 (m,
1H), 2.45±2.18 (m, 2H), 2.00±1.55 (m, 5H); 13C NMR (d,
CDCl3) 127.6 (d), 126.4 (d), 70.4 (d), 69.2 (d), 66.0 (d), 28.8
(t), 24.0 (t), 22.2 (t); MS (m/z) 140 [M1]; HRMS calcd for
C8H12O2 [M]1 140.0837, found 140.0845. 11: colorless
solid; mp 110±1128C (Et2O); [a]2D7ˆ2221 (c 0.67,
CHCl3), lit.5 [a]Dˆ 2225 (c 0.285, CHCl3); IR (CHCl3)
[a]2D7ˆ298.9 (c 1.89, CHCl3); IR (neat) 2940, 1050 cm21
;
1H NMR (d, CDCl3) 5.67±5.63 (m, 2H), 3.95±3.91 (m, 2H),
2.31±2.07 (m, 6H), 1.52±1.42 (m, 2H), 1.37 (s, 6H); MS
(m/z) 182 [M1]; HRMS calcd for C11H18O2 [M1] 182.1306,
found 182.1311.
1
(1R,4S,5S,8R)-4,5-Dibromo-10,10-dimethyl-9,11-dioxa-
bicyclo[6.3.0]undecane (7) and (1R,4R,5R,8R)-4,5-
dibromo-10,10-dimethyl-9,11-dioxabicyclo[6.3.0]unde-
cane (8). To a solution of 6 (814 mg, 4.47 mmol) in CHCl3
(10 ml) was added dropwise a solution of Br2 (345 ml,
6.70 mmol) in CHCl3 (7 ml) at 2408C. Similar treatment
to that described for 2 and 3 afforded crude products, which
were puri®ed by silica gel column chromatography. Elution
with hexane±AcOEtˆ10:1 gave 7 (1.35 g; 89%) and 8
(137 mg, 9%). 7: a colorless oil; [a]2D8ˆ124.7 (c 1.32,
CHCl3); IR (neat) 3000, 2940, 2860, 1440, 1380, 1220,
3020, 2980, 2880, 1460, 1320, 1090, 1020 cm21; H NMR
(d, CDCl3) 3.86 (d, Jˆ4.0 Hz, 4H), 2.13±1.99 (m, 4H),
1.78±1.67 (m, 4H); 13C NMR (d, CDCl3) 72.4 (d), 22.9
(t); MS (m/z) 140 [M1].
With NaH in DMSO: To a solution of 9 (545 mg,
2.46 mmol) in dry DMSO (10 ml) was added NaH
(400 mg, 9.84 mmol) under an Ar atmosphere and the
mixture was stirred at room temperature for 3 h. After
addition of saturated aqueous ammonium chloride solution,
the whole was extracted with AcOEt. The organic layer was
washed with brine, dried over Na2SO4, and concentrated in
vacuo. Puri®cation by silica gel column chromatography
gave 10 (239 mg; 70%) and 11 (73 mg; 21%).
1
1050 cm21; H NMR (d, CDCl3) 4.72 (bs, 2H), 3.64 (bs,
2H), 2.55 (bs, 2H), 2.18 (bs, 2H), 2.15 (bs, 4H), 1.38 (s, 6H);
13C NMR (d, CDCl3) 105.9 (s), 82.6 (d), 57.0 (d), 29.1 (t),
27.4 (t), 27.0 (q); MS (m/z) 343 [M1H]1; HRMS calcd for
C8H19O2Br2 [M1H]1 342.9732, found 342.9745. 8: color-
less solid; mp 115±1168C (Et2O); [a]2D9ˆ287.4 (c 0.97,
CHCl3); IR (CHCl3) 3000, 2950, 2860, 1460, 1380, 1250,
1060 cm21; 1H NMR (d, CDCl3) 4.34±4.32 (m, 2H), 3.90±
3.88 (m, 2H), 2.44±2.35 (m, 4H), 2.14±2.09 (m, 2H), 1.69±
1.63 (m, 2H), 1.39 (s, 6H); 13C NMR (d, CDCl3) 107.9 (s),
78.1 (d), 60.1 (d), 31.3 (t), 31.2 (t), 26.9 (q); MS (m/z) 343
[M1H]1; HRMS calcd for C8H19O2Br2 [M1H]1 342.9732,
found 342.9738.
(1R,2R,5R,6S)-5-Bromo-9-oxabicyclo[4.2.1]nonan-2-ol
(12). A mixture of 8 (95 mg, 279 mmol) and 1N HCl (3 ml)
in THF (3 ml) was heated at 508C for 7 h. The reaction
mixture was neutralized with saturated aqueous NaHCO3
and extracted with AcOEt. The organic layer was washed
with brine, dried over Na2SO4, and concentrated in vacuo.
The residue was puri®ed by silica gel column chromato-
graphy. Elution with hexane±AcOEtˆ1:1 gave 12 (61 mg;
99%) as colorless solids; [a]2D8ˆ124.3 (c 1.15, CHCl3); IR
(CHCl3) 3400, 2940, 1470, 1440, 1200, 1060, 1030 cm21
;
(1R,2R,5R,6S)-6-Bromo-9-oxabicyclo[3.3.1]nonan-2-ol (9).
A mixture of 7 (1.32 g, 3.86 mmol) and 1N HCl (5 ml) in
THF (5 ml) was heated at 508C for 9 h. After cooling, the
reaction mixture was neutralized with saturated aqueous
NaHCO3 and extracted with AcOEt. The combined organic
layers were washed with brine, dried over Na2SO4, and
concentrated in vacuo. The residue was puri®ed by silica
gel column chromatography. Elution with hexane±
AcOEtˆ1:1 gave 9 (852 mg, 99%) as a colorless oil;
[a]2D8ˆ23.1 (c 0.95, CHCl3); IR (neat) 3400, 2940, 1080,
1H NMR (d, CDCl3) 4.79 (dd, Jˆ9.2, 2.6 Hz, 1H), 4.46 (m,
1H), 4.13±4.03 (m, 2H), 2.33±1.83 (m, 6H), 1.76±1.35 (m,
3H); 13C NMR (d, CDCl3) 85.1 (d), 81.4 (d), 71.9 (d), 58.3
(d), 32.4 (t), 30.8 (t), 30.7 (t), 23.1 (t); MS (m/z) 221
([M1H]1); HRMS calcd for C8H14O2Br [M1H]1
221.0177, found 221.0171.
cis-transoid-cis-9,10-Dioxatricyclo[4.2.1.12,5]decane (13)
To a solution of 12 (84.0 mg, 380 mmol) in dry toluene
(10 ml) was added DBU (0.28 ml, 1.90 mmol) and the
mixture was re¯uxed for 20 h. After dilution with H2O,
the whole was extracted with AcOEt. The organic layer
was washed with brine, dried over Na2SO4, and concen-
trated in vacuo. The residue was puri®ed by silica gel
column chromatography. Elution with hexane±
AcOEtˆ2:1 gave 13 (30 mg; 57%) as colorless solids; IR
1
1030 cm21; H NMR (d, CDCl3) 4.33 (m, 1H), 4.13±
4.05 (m, 2H), 3.93 (t, Jˆ5.9 Hz, 1H), 2.50±2.17 (m,
2H), 2.14±1.96 (m, 4H), 1.89±1.68 (m, 3H); 13C
NMR (d, CDCl3) 71.9 (d), 69.9 (d), 68.1 (d), 52.9
(d), 29.0 (t), 27.5 (t), 27.4 (t), 18.0 (t); MS (m/z) 221
[M1H]1; HRMS calcd for C8H14O2Br [M1H]1
221.0177, found 221.0189.
1
(CHCl3) 2960, 2860, 1460, 1140, 1100 cm21; H NMR (d,

2004
A. Takahashi et al. / Tetrahedron 56 (2000) 1999±2006
CDCl3) 3.93±3.91 (m, 4H), 2.23±2.16 (m, 4H), 1.84±1.79
(m, 4H); MS (m/z) 140 [M1]; HRMS calcd for C8H12O2
[M1] 140.0837, found 140.0842.
(m, 2H), 2.29±2.27 (m, 2H), 1.89 (m, 1H), 1.68±1.60 (m,
2H), 1.50 (m, 1H), 0.85 (s, 9H), 0.04 (s, 3H), 0.02 (s, 3H);
MS (m/z) 254 [M1]; HRMS calcd for C14H26O2Si [M1]
254.1702, found 254.1708.
(1R,2R,5R)-9-Oxabicyclo[3.3.1]non-6-en-2-yl N,N-dimethyl-
thiocarbamate (14). To a solution of (2)-10 (267 mg,
1.91 mmol) in DMF (3 ml) were successively added
NaH (92 mg, 2.3 mmol) and N,N-dimethylthiocarbamoyl
chloride (354 mg, 2.86 mmol) under an Ar atmosphere,
and the whole was stirred at room temperature for 5 h.
After addition of H2O, the mixture was extracted with
ether and the organic layer was washed with brine, dried
over Na2SO4, and concentrated in vacuo. The residue was
puri®ed by silica gel column chromatography. Elution with
hexane±AcOEtˆ3:1 gave 14 (411 mg; 95%) as a colorless
oil; [a]2D4ˆ294.8 (c 2.0, CHCl3); IR (neat) 2940, 1510,
(1S,2R,3R,5S,6S)-6-t-Butyldimethylsilyloxy-9-oxabicyclo-
[3.3.1]nonane-2,3-diol (19). To a mixed solution of 18
(50 mg, 197 mmol) in acetone (10 ml) and H2O (5 ml)
were successively added 50% aqueous N-methylmorpholine
N-oxide solution (0.14 ml, 0.59 mmol) and 0.5% aqueous
OsO4 solution (0.2 ml, 3.94 mmol) at 08C. The whole was
stirred at room temperature for 12 h. Saturated aqueous
sodium hydrogen sul®te solution and ¯orisil were added
and the resulting mixture was stirred for further 30 min
and passed through a celite pad. The ®ltrate was concen-
trated in vacuo and the residue was extracted with AcOEt.
The organic layer was washed with brine, dried over
Na2SO4, and concentrated in vacuo. The residue was puri-
®ed by silica gel column chromatography. Elution with
hexane±AcOEtˆ1:1 gave 19 (47 mg; 82%) as colorless
needles. mp 78±818C (hexane); [a]2D3ˆ115.3 (c 0.55,
CHCl3); IR (CHCl3) 3500, 3380, 2900, 2800, 1220,
1
1390, 1280, 1180, 1050 cm21; H NMR (d, CDCl3) 5.99
(dt, Jˆ10.2, 3.6 Hz, 1H), 5.75 (ddt, Jˆ10.2, 4.3, 2.3 Hz,
1H), 5.61 (dt, Jˆ11.5, 5.9 Hz, 1H), 4.34 (t, Jˆ6.3 Hz,
1H), 4.27 (t, Jˆ4.6 Hz, 1H), 3.36 (s, 3H), 3.11 (s, 3H),
2.49 (dddt, Jˆ19.1, 7.6, 2.3, 2.0 Hz, 1H), 2.14±1.96 (m,
3H), 1.82 (m, 1H), 1.61 (m, 1H); MS (m/z) 228.1 [M1H1].
1
1080 cm21; H NMR (d, CDCl3) 4.12 (bs, 1H), 3.98 (dd,
(1R,5R)-9-Oxabicyclo[3.3.1]nona-2,6-diene (R,R)-(15). A
solution of 14 (161 mg, 0.71 mmol) in HMPA (3 ml) was
heated at 2508C for 4.5 h in a sealed tube. After dilution
with H2O, the whole was extracted with pentane. The
organic layer was washed with brine, dried over Na2SO4,
and concentrated in vacuo. The residue was puri®ed by
silica gel column chromatography. Elution with pentane±
etherˆ8:1 gave (R,R)-15 (40 mg; 47%) as colorless solids;
mp 348C (pentane); [a]2D8ˆ2216 (c 0.40, CHCl3); IR
(CHCl3) 3000, 2930, 2840, 1410, 1380, 1320, 1270, 1180,
1050 cm21; 1H NMR (d, CDCl3) 5.86±5.73 (m, 4H), 4.50±
4.46 (m, 2H), 2.60±2.49 (m, 2H), 1.76 (dd, Jˆ16.8, 4.3 Hz,
2H); 13C NMR (d, CDCl3) 129.7 (d), 122.7 (d), 66.4 (d),
28.3 (t); MS (m/z) 122 [M1]; HRMS calcd for C8H10O [M]1
122.0731, found 122.0726. (S,S)-(15) ([a]2D8ˆ1210 (c 0.35,
CHCl3)) was also synthesized starting from (S,S)-(1)-1.
Jˆ6.9, 2.0 Hz, 1H), 3.93 (m, 1H), 3.85 (t, Jˆ5.6 Hz, 1H),
3.63 (bs, 1H), 2.53 (bs, D2O exchangeable, 1H), 2.47 (bs,
D2O exchangeable, 1H), 2.27 (dd, Jˆ13.9, 6.6 Hz, 2H), 2.00
(dt, Jˆ13.9, 6.6 Hz, 1H), 1.90 (m, 1H), 1.77±1.64 (m, 2H),
1.44 (dd, Jˆ13.5, 10.6, 5.9 Hz, 1H), 0.87 (s, 9H), 0.05 (s,
3H), 0.04 (s, 3H); 13C NMR (d, CDCl3) 72.3 (d), 72.1 (d),
71.3 (d), 67.9 (d), 64.8 (d), 28.7 (t), 28.5 (t), 25.7 (q), 24.4 (t),
17.9 (s), 24.6 (q), 24.9 (q); MS (m/z) 289 [M1H]1; HRMS
calcd for C14H29O4Si [M1H]1 289.1835, found 289.1817.
X-Ray structure determination of compound 19. Crystal
data: C14H28O4Si, Mˆ288.46. Orthorhombic, aˆ7.131(2),
Ê
Ê 3
bˆ36.972(3), cˆ6.409(2) A, Vˆ1689.7(5) A (from center-
ing angles for 25 re¯ections (40.6#2u#49.38, lˆ
Ê
1.54178 A, Tˆ296 K), space group P212121 (No. 19),
Zˆ4, Dcˆ1.134 g cm23, colorless needle 0.40£0.10£
0.10 mm, m(Cu-Ka)ˆ12.95 cm21. Data collection and
processing: Rigaku AFC5R four-circle diffractometer,
v22u scans with v scan width (1.0510.30 tan u)8, ®ltered
Rhodium complex (16; Rh2Cl2(15)2). To a solution of
(S,S)-15 (280 mg, 2.28 mmol) in EtOH (5 ml) was added
RhCl3´3H2O (100 mg, 0.38 mmol) and the mixture was
re¯uxed for 3 days. The resulting precipitate was collected
by ®ltration to give crude 16 (60 mg; 60%) as brown
Cu-Ka X-radiation; 1526 re¯ections measured (2umax
ˆ
1208), giving 746 with I$3.00s(I). No crystal decay was
observed. Structure solution and re®nement: the structure
was solved by direct methods using SIR929 and expanded
using Fourier techniques.10 All non-hydrogen atoms were
given anisotropic thermal parameters and hydrogen atoms
included in calculated positions given isotropic thermal
parameters. The ®nal cycle of full-matrix least-squares
re®nement based on 746 re¯ections gave a conventional R
1
powder; H NMR (d, CDCl3) 4.91±4.86 (m, 2H), 4.12 (s,
4H), 2.64±2.61 (m, 2H), 2.39±2.36 (m, 2H); MS (m/z) 520
[M1]; HRMS calcd for C16H20O2Cl2Rh2 [M]1 519.8950,
found 519.8928.
(1S,2S,5S)-2-t-Butyldimethylsilyloxy-9-oxabicyclo[3.3.1]-
non-6-ene (18). A mixture of (1)-10 (1.13 g, 8.07 mmol),
imidazole (824 mg, 12.1 mmol), and t-butyldimethylsilyl
chloride (1.80 g, 12.1 mmol) in CH2Cl2 (10 ml) was stirred
at room temperature for 6 h. After dilution with H2O, the
whole was extracted with CH2Cl2. The organic layer was
washed with brine, dried over Na2SO4, and concentrated in
vacuo. The residue was puri®ed by silica gel column chro-
matography. Elution with hexane±AcOEtˆ50:1 gave 18
(2.00 g; 98%) as a colorless oil; [a]2D4ˆ142.6 (c 0.86,
factor of 0.059 (Rwˆ0.053). The largest peak and hole in
Ê 23
the ®nal difference Fourier map were 0.12 and 20.12 e A
.
All calculations were performed using the teXsan11 crystal-
lographic package of Molecular Structure Corporation.
(1S,2S,6R,8S,9S)-9-t-Butyldimethylsilyloxy-4,4-
dimethyl-3,5,12-trioxatricyclo[6.3.1.02,6]dodecane (20). A
mixture of 19 (213 mg, 0.74 mmol), 2,2-dimethoxypropane
(0.14 ml, 1.11 mmol) and catalytic amount of p-toluene-
sulfonic acid in acetone (5 ml) was stirred at room tempera-
ture for 3 h. The reaction mixture was neutralized with
saturated aqueous NaHCO3 and the mixture was concentrated
1
CHCl3); IR (neat) 2930, 2850, 1470, 1250, 1100 cm21; H
NMR (d, CDCl3) 5.93 (dt, Jˆ10.2, 3.6 Hz, 1H), 5.66 (ddt,
Jˆ10.2, 4.6, 2.3 Hz, 1H), 4.17 (t, Jˆ4.6 Hz, 1H), 3.95±3.83

A. Takahashi et al. / Tetrahedron 56 (2000) 1999±2006
2005
in vacuo. The residue was extracted with ether. The organic
layer was washed with brine, dried over Na2SO4, and
concentrated in vacuo. The residue was puri®ed by silica
gel column chromatography. Elution with hexane±
AcOEtˆ10:1 gave 20 (231 mg; 95%) as a colorless oil;
[a]2D6ˆ130.9 (c 1.60, CHCl3); IR (neat) 2900, 2820, 1440,
1.5 h. Saturated aqueous ammonium chloride was added
to the reaction mixture and the whole was extracted with
ether. The organic layer was washed with brine, dried over
Na2SO4, and concentrated in vacuo. The residue was
puri®ed by silica gel column chromatography. Elution
with hexane±AcOEtˆ5:1 gave 23 (91 mg; 57%) as color-
less needles; mp 62±638C (hexane); [a]2D4ˆ1154 (c 0.83,
CHCl3); IR (CHCl3) 3000, 2940, 1380, 1360, 1050 cm21; 1H
NMR (d, CDCl3) 5.84 (m, 1H), 5.72 (m, 1H), 4.53 (d,
Jˆ7.3 Hz, 1H), 4.32 (m, 1H), 4.29 (dt, Jˆ8.6, 5.3 Hz,
1H), 3.92 (d, Jˆ5.3 Hz, 1H), 2.73 (m, 1H), 1.88 (ddt,
Jˆ18.1, 5.0, 0.7 Hz, 1H), 1.85 (dd, Jˆ8.6, 3.6 Hz, 1H),
1.56 (s, 3H), 1.37 (s, 3H); 13C NMR (d, CDCl3) 128.6 (d),
123.9 (d), 107.8 (s), 76.7 (d), 69.9 (d), 68.8 (d), 66.9 (d),
31.6 (t), 28.4 (q), 28.2 (t), 26.5 (q); MS (m/z) 197 [M1H]1;
HRMS calcd for C11H17O3 [M1H]1 197.1178, found
197.1155.
1
1360, 1220, 1080 cm21; H NMR (d, CDCl3) 4.46 (dt,
Jˆ8.6, 5.9 Hz, 1H), 4.19 (d, Jˆ5.3 Hz, 1H), 4.14±3.87
(m, 3H), 2.27 (dd, Jˆ13.9, 8.3 Hz, 1H), 2.17±1.63 (m,
4H), 1.56 (s, 3H), 1.35 (s, 3H), 1.25 (m, 1H), 0.86 (s, 9H),
0.04 (s, 3H), 0.03 (s, 3H); MS (m/z) 329 [M1H]1; HRMS
calcd for C17H33O4Si [M1H]1 329.2148, found 329.2160.
(1S,2S,6R,8S,9S)-4,4-Dimethyl-3,5,12-trioxatricyclo-
[6.3.1.02,6]dodecan-9-ol (21). To a solution of 20 (57 mg,
172 mmol) in THF (3 ml) was added 1.0 M TBAF in THF
(345 ml, 345 mmol) and the whole was stirred at room
temperature for 5 h. After removal of the solvent in
vacuo, H2O was added to the residue and the mixture was
extracted with AcOEt. The organic layer was washed with
brine, dried over Na2SO4, and concentrated in vacuo. The
residue was puri®ed by silica gel column chromatography.
Elution with hexane±AcOEtˆ1:2 gave 21 (36 mg; 98%) as
colorless needles; mp 115±1168C (Et2O); [a]2D3ˆ146.5 (c
0.86, CHCl3); IR (CHCl3) 3600, 3450, 3000, 2950, 1380,
(1S,2S,6R,8S,9R,10R)-4,4-Dimethyl-3,5,12-trioxatricyclo-
[6.3.1.02,6]dodecane-9,10-diol (24). By the similar proce-
dure to that described for preparation of 19 from 18,
compound 23 (82 mg, 416 mmol) was converted to 24
(76 mg; 79%). Colorless solids; [a]2D4ˆ195.9 (c 0.56,
CHCl3); IR (CHCl3) 3570, 3420, 3000, 2950, 1380,
1
1060 cm21; H NMR (d, CDCl3) 4.38 (d, Jˆ5.9 Hz, 1H),
1
1100, 1050 cm21; H NMR (d, CDCl3) 4.46 (dt, Jˆ8.6,
4.28 (dt, Jˆ8.6, 5.9 Hz, 1H), 4.17 (d, Jˆ7.3 Hz, 1H), 3.98
(d, Jˆ5.9 Hz, 1H), 3.72 (m, 1H), 2.34 (d, Jˆ5.3 Hz, D2O
exchangeable, 1H), 2.31 (d, Jˆ4.3 Hz, D2O exchangeable,
1H), 2.12±1.81 (m, 4H), 1.55 (s, 3H), 1.35 (s, 3H); 13C
NMR (d, CDCl3) 108.7 (s), 74.6 (d), 72.8 (d), 71.4 (d),
69.7 (d), 68.8 (d), 64.6 (d), 32.0 (t), 30.9 (t), 28.2 (q), 26.3
(q); MS (m/z) 231 [M1H]1; HRMS calcd for C11H19O5
[M1H]1 231.1232, found 231.1245.
5.9 Hz, 1H), 4.21 (d, Jˆ5.6 Hz, 1H), 4.04±3.95 (m, 2H),
3.89 (t, Jˆ5.9 Hz, 1H), 2.25 (dd, Jˆ14.5, 8.3 Hz, 1H),
2.09±1.94 (m, 2H), 1.85 (ddd, Jˆ14.5, 8.6, 7.3 Hz, 1H),
1.79±1.66 (m, 2H), 1.57 (s, 3H), 1.35 (s, 3H), 1.26 (m,
1H); 13C NMR (d, CDCl3) 107.2 (s), 74.6 (d), 71.3 (d),
69.5 (d), 68.5 (d), 69.7 (d), 28.3 (q), 28.0 (t), 27.9 (t), 27.7
(t), 26.4 (q); MS (m/z) 215 [M1H]1; Anal. calcd for
C11H18O4: C 61.65, H 8.47; found: C 61.62, H 8.44.
(1S,2S,6R,8S,9S,13R)-4,4,11,11-Tetramethyl-3,5,10,12,
15-pentaoxatetracyclo[6.6.1.02,6.09,13]pentadecane (25).
By the similar procedure to that described for preparation
of 20 from 19, compound 24 (17 mg, 75 mmol) was
converted to 25 (19 mg; 93%). Colorless solids; mp 190±
1928C (Et2O); [a]2D2ˆ188.7 (c 0.53, CHCl3); IR (CHCl3)
(1S,2S,6R,8S,9S)-9-Methanesulfonyloxy-4,4-dimethyl-
a
3,5,12-trioxatricyclo[6.3.1.02,6]dodecane (22). To
mixture of 21 (1.22 g, 5.70 mmol) and NEt3 (1.2 ml,
8.55 mmol) in dry CH2Cl2 (10 ml) was added methane-
sulfonyl chloride (0.66 ml, 8.55 mmol) and the mixture
was stirred at room temperature for 20 h. The reaction
was stopped by addition of H2O and the mixture was
extracted with CH2Cl2. The organic layer was washed
with brine, dried over Na2SO4, and concentrated in vacuo.
The residue was puri®ed by silica gel column chromato-
graphy. Elution with hexane±AcOEtˆ1:1 gave 22 (1.65 g;
99%) as colorless needles; mp 153±1558C (Et2O);
[a]2D7ˆ131.6 (c 0.57, CHCl3); IR (CHCl3) 3000, 2950,
1
2980, 2940, 1380, 1360, 1060, 1040 cm21; H NMR (d,
CDCl3) 4.38±4.36 (m, 2H), 4.19±4.11 (m, 2H), 3.93 (d,
Jˆ5.3 Hz, 2H), 2.04 (ddd, Jˆ13.9, 10.2, 5.9 Hz, 2H), 1.88
(ddd, Jˆ13.9, 7.6, 2.0 Hz, 2H), 1.55 (s, 6H), 1.35 (s, 6H);
13C NMR (d, CDCl3) 108.8 (s), 74.6 (d), 69.7 (d), 68.7 (d),
32.3 (t), 28.4 (q), 26.5 (q); MS (m/z) 271 [M1H]1; Anal.
calcd for C14H22O5: C 62.19, H 8.21; found: C 62.13, H
8.25.
1
1360, 1170, 1050 cm21; H NMR (d, CDCl3) 4.87 (dt,
Jˆ11.9, 5.9 Hz, 1H), 4.47 (dt, Jˆ8.6, 5.9 Hz, 1H), 4.25
(d, Jˆ5.6 Hz, 1H), 4.20 (t, Jˆ5.9 Hz, 1H), 3.92 (d,
Jˆ5.9 Hz, 1H), 3.03 (s, 3H), 2.24±2.05 (m, 3H), 2.03±
1.89 (m, 1H), 1.83±1.75 (m, 1H), 1.62±1.50 (m, 5H), 1.35
(s, 3H); 13C NMR (d, CDCl3) 108.2 (s), 76.2 (d), 74.3 (d),
69.0 (d), 68.8 (d), 68.5 (d), 38.6 (q), 28.5 (t), 28.2 (q), 26.8
(t), 26.4 (q), 26.0 (t); MS (m/z) 293 [M1H]1; HRMS calcd
for C12H21O6S [M1H]1 293.1059, found 293.1051.
(1S,2R,3R,5S,6R,7R)-9-Oxabicyclo[3.3.1]nonane-2,3,6,7-
tetraol (26). 26 from 24: To a solution of 24 (17 mg,
72 mmol) in MeOH (2 ml) was added 10% HCl (0.5 ml)
and the mixture was re¯uxed for 2 days. The solvent was
evaporated in vacuo and the residue was puri®ed by
preparative TLC (CHCl3±MeOHˆ7:3), which gave 26
(11.9 mg, 72%) as colorless solids; mp. 159±1608C
(MeOH2H2O); [a]2D2ˆ188.7 (c 0.53, H2O); IR (KBr)
1
3400, 3270, 2930, 1460, 1370, 1220, 1190, 1040 cm21; H
(1S,2S,6R,8S)-4,4-Dimethyl-3,5,12-trioxatricyclo-
[6.3.1.02,6]dodec-9-ene (23). To a solution of K2CO3
(168 mg, 1.21 mmol) in HMPA (2 ml) was added a solution
of 22 (236.2 mg. 809 mmol) in HMPA (4 ml) at 1808C under
an Ar atmosphere. The mixture was stirred at 1808C for
NMR (d, d-DMSO) 4.42 (d, Jˆ6.6 Hz, 2H), 4.24 (d,
Jˆ4.3 Hz, 2H), 3.85 (d, Jˆ6.9 Hz, 2H), 3.79±3.69 (m,
2H), 3.43±3.39 (m, 2H), 1.75 (ddd, Jˆ13.5, 11.6, 6.9 Hz,
2H), 1.54 (dd, Jˆ13.5, 6.6 Hz, 2H); 13C NMR (d, d-DMSO)
73.1 (d), 70.0 (d), 63.3 (d), 30.8 (t); MS (m/z) 191 [M1H]1;

2006
A. Takahashi et al. / Tetrahedron 56 (2000) 1999±2006
Anal. calcd for C8H14O5: C 50.50, H 7.42; found: C 50.53, H
7.48.
3.69 (bs, 1H), 3.05 (s, 3H), 2.50 (bs, 2H), 2.27±2.05 (m,
3H), 1.96±1.71 (m, 3H).
26 from (S,S)-15: To a solution of (S,S)-15 (164 mg,
1.34 mmol) in a mixture of acetone and H2O (3:1; 4 ml)
were added 50% aqueous N-methylmorpholine N-oxide
solution (1.90 ml, 8.04 mmol), then 0.5% aqueous OsO4
solution (2.0 ml, 0.04 mmol) and the mixture was stirred
at room temperature for 30 h. The resulting precipitate
was collected by ®ltration and recrystallized from
MeOH2H2O gave 26 (183 mg, 72%).
References
1. Miyashita, A.; Yasuda, A.; Takaya, H.; Toriumi, K.; Ito, T.;
Souchi, T.; Noyori, R. J. Am. Chem. Soc. 1980, 102, 7932±7934.
Hayashi, T.; Katsumura, A.; Konishi, M.; Kumada, M. Tetrahedron
Lett. 1979, 20, 425±428. Ojima, I.; Kogure, T.; Kumagai, M. J. Org.
Chem. 1977, 42, 1671±1679.
2. For the synthesis of (dl)-15; Eaton, P. S.; Millikan, P. Synthesis
1990, 483±484.
(1RS,2RS,5RS)-2-Methanesulfonyloxy-9-oxabicyclo-
[3.3.1]non-6-ene (dl)-(27). To a solution of (dl)-10 (5.06 g,
36.1 mmol) in CH2Cl2 (100 ml) were added NEt3 (7 ml,
50.5 mmol) and methanesulfonyl chloride (3.9 ml,
50.5 mmol) and the whole was stirred at room temperature
for 9 h. After addition of saturated aqueous ammonium
chloride, the mixture was extracted with CH2Cl2 and the
organic layer was washed with brine, dried over Na2SO4,
and concentrated in vacuo. The residue was puri®ed by
silica gel column chromatography. Elution with hexane±
AcOEtˆ2:1 gave (dl)-27 (7.32 g; 93%) as colorless solids;
3. Horikawa, T.; Tanaka, M.; Sakai, K.; Suemune, H. Chem.
Pharm. Bull. 1998, 46, 17±21.
4. Davies, S. G.; Polywka, M. E. C.; Thomas, S. E. Tetrahedron
Lett. 1985, 26, 1461±1464.
5. Ackermann, P.; Ganter, C. Helv. Chim. Acta 1976, 59, 2531±
2535.
6. Wright, M. E.; Cochran, B. B. Organometallics 19, 15, 317±
324 (and references cited therein).
7. The synthetic procedure from 10 to 22 via 27 and 28 was
developed by using racemic compounds.
1
IR (CHCl3) 3030, 2950, 1360, 1335, 1175, 1170 cm21; H
8. Noyori, R.; Sato, T.; Hayakawa, Y. J. Am. Chem. Soc. 1978,
100, 2561±2563.
NMR (d, CDCl3) 5.99 (dt, Jˆ10.2, 3.6 Hz, 1H), 5.73 (ddd,
Jˆ10.2, 4.3, 2.3 Hz, 1H), 4.88 (m, 1H), 4.32±4.24 (m, 2H),
3.03 (s, 3H), 2.50 (dm, Jˆ19.1 Hz, 1H), 2.21 (ddd, Jˆ19.1,
4.3, 2.0 Hz, 1H), 2.08±1.98 (m, 2H), 1.69±1.64 (m, 1H).
9. Altomare, A.; Burla, M. C.; Camalli, M.; Cascarano, M.;
Giacovazzo, C.; Guagliardi, A.; Polidori, G. J. Appl. Crystallogr.
(SIR92) 1994, 27, 435.
10. Beurskens, P. T.; Admiraal, G.; Beurskens, G.; Bosman, W. P.;
de Gelder, R.; Israel, R.; Smits, J. M. M. The DIRDIF-94 program
system, Technical Report of the Crystallography Laboratory,
University of Nijmegen, The Netherlands, 1994.
11. Molecular Structure Corporation, 3200 Research Forest Drive,
The Woodlands, TX 77381, USA: TEXSAN Crystal Structure
Analysis Package, 1985 and 1992.
(1RS,2SR,3SR,5RS,6RS)-6-Methanesulfonyloxy-9-oxabi-
cyclo[3.3.1]nonane-2,3-diol (dl)-(28). By the similar proce-
dure to that described for preparation of 19 from 18,
compound (dl)-27 (139 mg, 637 mmol) was converted to
(dl)-28 (144 mg; 90%). Colorless solids; 1H NMR (d,
CDCl3) 4.93 (m, 1H), 4.23±4.14 (m, 2H), 4.06 (m, 1H),