Chiral synthesis via organoboranes. 45. Asymmetric hydroboration of 1-cyclopentenol derivatives using diisopinocampheylborane. Synthesis of optically active cyclopentane-1,2-diol derivatives of high optical purity

Article abstract of DOI:10.1016/S0022-328X(99)00047-9

The asymmetric hydroboration of 1-cyclopentenol derivatives, such as ethers, acetate, silyl ether and borinate, was investigated using diisopinocampheylborane, ^dIpc₂BH. The product trialkylboranes were treated with excess of acetalde

Full text of DOI:10.1016/S0022-328X(99)00047-9

Journal of Organometallic Chemistry 581 (1999) 116–121
Chiral synthesis via organoboranes. 45. Asymmetric hydroboration
of 1-cyclopentenol derivatives using diisopinocampheylborane.
Synthesis of optically active cyclopentane-1,2-diol derivatives of
high optical purityꢀ
Herbert C. Brown a, Dhanabalan Murali a,1, Bakthan Singaram b,*
a H.C. Brown and R.B. Wetherill Laboratories, Department of Chemistry, Purdue Uni6ersity, West Lafayette, IN 47907, USA
b Department of Chemistry and Biochemistry, Uni6ersity of California, Santa Cruz, CA 95064, USA
Received 28 April 1998; received in revised form 10 July 1998
Abstract
The asymmetric hydroboration of 1-cyclopentenol derivatives, such as ethers, acetate, silyl ether and borinate, was investigated
using diisopinocampheylborane, dIpc2BH. The product trialkylboranes were treated with excess of acetaldehyde to give the
corresponding diethyl boronate esters. These boronate esters on oxidation using alkaline hydrogen peroxide gave optically active
trans-cyclopentane-1,2-diol derivatives in 50–85% enantiomeric excess and up to 95% overall yield. Some of the optically active
trans-2-alkoxycyclopentanols were converted by ether cleavage to optically active trans-(1R,2R)-cyclopentane-1,2-diol. The
asymmetric hydroboration-oxidation of 3-methoxy-2,5-dihydrofuran gave trans-(3R,4R)-4-methoxytetrahydrofuran-3-ol of 75%
ee in 70% overall yield. © 1999 Elsevier Science S.A. All rights reserved.
Keywords: Asymmetric hydroboration; Enol-ethers; Chiral cyclopentane-1,2-diols; Diisopinocampheylborane; Asymmetric synthesis
1. Introduction
metric hydroborations, we were interested in the asym-
metric hydroboration of oxy-substituted alkenes using
diisopinocampheylborane (dIpc2BH) of \99% ee. The
hydroboration products upon oxidation would then
give optically active 1,2-diol derivatives Eq. (1).
Optically active 1,2-diols are valuable chiral synthons
and are employed as chiral auxiliaries and as chiral
ligands in a wide range of asymmetric catalysts [1].
However, it appears that the asymmetric hydroxylation
of alkenes using osmium reagents [2a] and the enzy-
matic hydrolysis [2b] of racemic 1,2-diacetates are the
only general methods available for the preparation of
optically active 1,2-diols. Achiral hydroboration of oxy-
substituted alkenes, such as enol ethers [3], enol acetates
[3,4], enol silyl ethers [5], and enolates [5e] has already
been reported in the literature to give the corresponding
1,2-diol derivatives. In our continuing study on asym-
(1)
For the present study, we chose 1-cyclopentenol
derivatives 1–7 as substrates for asymmetric hydrobo-
ration using dIpc2BH (Scheme 1). The five-membered
ring compounds were chosen mainly because of their
ease of preparation. Additionally, five-membered cy-
cloalkenes are more reactive [6,7] compared to their
six-membered counterparts towards hydroboration
d
with Ipc2BH and other bulky hydroborating reagents.
ꢀ Boranes in Synthesis. 8.
* Corresponding author.
2. Results and discussions
1 Postdoctoral research associate on Grant GM 10937-27 from the
National Institutes of Health. Present address: Senior Research Scien-
tist, BioNumerik Pharmaceutical, Suite 400, 8122 Datapoint Drive,
San Antonio, TX 78229
The enol derivatives 1–7 were treated with crys-
talline, enantiomerically pure dIpc2BH [8], obtained
0022-328X/99/$ - see front matter © 1999 Elsevier Science S.A. All rights reserved.
PII: S0022-328X(99)00047-9

H.C. Brown et al. / Journal of Organometallic Chemistry 581 (1999) 116–121
117
ceeded at a reasonable rate. In the cases of 1-methoxy-
d
and 1-ethoxycyclopentenes (1 and 2), the solid Ipc2BH
disappeared completely and the 11B-NMR of the reac-
tion mixture showed the presence of only the trialkylb-
oranes, indicating complete hydroboration in these
cases. Oxidation of the corresponding alkylboronates
trans-2-methoxy- and trans-2-ethoxycyclopentanols in
85 and 75% ee, respectively. The hydroboration of 3
was not complete, as indicated by the residual solid
dIpc2BH. Upon oxidation, the product 2-benzyloxycy-
clopentanol was obtained in 77% ee. Similarly,
methoxymethyl-1-cyclopentenyl ether (4), after the hy-
droboration-oxidation reaction, gave the corresponding
mono methoxymethyl ether of trans-cyclopentane-1,2-
diol in 50% ee. In the case of 1-acetoxycyclopentene,
the hydroboration was very slow. Even after 7 days at
Scheme 1. 1-Cyclopentenol derivatives used for the asymmetric hy-
droboration.
from (+)-a-pinene, in THF solvent. (+)-a-Pinene
(15% excess) was added prior to the addition of the
cyclopentenol derivatives to suppress the dissociation of
dIpc2BH to monoisopinocampheylborane (dIpcBH2)
and a-pinene. The reactions were carried out at low
temperatures and were monitored by 11B-NMR spec-
troscopy. Since dIpc2BH is only sparingly soluble in
d
−10°C most of the Ipc2BH remained unreacted. Con-
d
THF, dissolution of the solid Ipc2BH usually indicates
sequently, we did not process this reaction further. We
then extended this asymmetric hydroboration reaction
to the dihydrofuran derivative (7). This enol ether
behaved very similar to the other cyclopentenyl ethers.
Thus, hydroboration–oxidation of the methyl enol
ether 7 gave the methoxy alcohol 12 of 75% ee in 77%
overall yield. The results are summarized in Table 1.
The enol derivatives are related structurally to tri-
alkylsubstituted olefins, where the oxy group is replaced
by an alkyl group. It has been previously reported in
the literature that dIpc2BH reacts sluggishly with trisub-
stituted alkenes and the products are obtained in low
optical purity [7]. The reaction of trisubstituted alkenes
with dIpc2BH proceed with the displacement of one
mole of a-pinene per mole of alkene reacted. It has
been shown previously in our laboratories that dIpc2BH
exists as the dimer, sym-tetraisopinocampheyldiborane
(dIpc2BH)2, in THF or diglyme solution and that there
was a small measurable dissociation of the reagent into
triisopinocampheyldiborane (Ipc3B2H3) and a-pinene
completion of the reaction. The trialkylborane products
were treated with excess of acetaldehyde to eliminate
selectively the isopinocampheyl group as a-pinene
providing the corresponding diethyl boronate esters.
These boronate esters were then oxidized using alkaline
30% hydrogen peroxide to the corresponding alcohols
Eq. (2).
(2)
The enantiomeric purities of the product alcohols
were determined by capillary GC analyses of the corre-
sponding
esters
of
(R)-a-methoxy-a-(trifl-
uoromethyl)phenylacetic acid (MTPA) [10]. In the
present study, the enantiomeric excess (ee) of the
product alcohols were not optimized and the reaction
temperatures were chosen such that the reaction pro-
Table 1
Hydroboration of enol derivatives 1-7, with dIpc2BH.
Subtrate
Hydroboration
Temp
Oxidation product
% eea
% Yield
Time
1b
2c
3d
4f
6
−25°
−25°
−15°
−15°
−10°
−25°
76 h
80 h
5 d
5 d
3 d
(1R,2R)-(–)-2-methoxy-cyclopentanol, 8
(1R,2R)-(–)-2-ethoxy-cyclopentanol, 9
(1R,2R)-(–)-2-benzyloxy-cyclopentanol, 10
(1R,2R)-(–)-2-(methoxy–methoxy)cyclopentanol, 11
(1R,2R)-(–)-cyclopentane-1,2-diol
85
76
77
50
86
75
93
95
75 (95)e
77
40
70
7g
30 h
(3R,4R)-(+)-4-methoxy-tetrahydrofuran-3-ol, 12
a The ee values were determined by capillary GC analysis of the corresponding MTPA esters.
b R. Wohl, Synthesis (1974) 38.
c I. Ryu, T. Aya, S. Otani, S. Murai, N. Senoda, J. Organomet. Chem. 321 (1987) 279.
d Ref. [10].
e Yield given in parentheses was based on alkene reacted.
f Ref. [18].
g S. Hoff, L. Brandsma, J.F. Arens, Recl. Trav. Chim. Pays-Bas 88 (1969) 609.

118
H.C. Brown et al. / Journal of Organometallic Chemistry 581 (1999) 116–121
[9]. Triisopinocampheyldiborane can be considered as a
tane-1,2-diol in 90% yield. The monomethoxymethyl
ether of trans-cyclopentane-1,2-diol 11 was converted
to (1R,2R)-trans-(+)-cyclopentane-1,2-diol in 92%
yield by treatment with HCl in THF, establishing that
absolute configuration of 11 as 1R,2R.
The absolute configuration of the tetrahydrofurane-
diol 16 is available in the literature [14]. Unfortunately,
reaction of the methoxy alcohol 12 with NaI/Me3SiCl
in acetonitrile gave a complex reaction mixture from
which the required diol 16 could not be isolated. Conse-
quently, we converted alcohol 12 to 3-methoxytetrahy-
drofuran 17, easily prepared from the commercially
available 3-hydroxytetrahydrofuran of known absolute
configuration. Thus, the methoxy alcohol 12 was con-
verted to the corresponding tosylate and reduced using
lithium triethylborohydride [15] to afford (S)-(+)-3-
methoxytetrahydrofuran in 50% yield (Eq. (4)).
d
d
1:1 mixture of Ipc2BH and IpcBH2. When the sub-
strate is hindered sufficiently to retard the direct reac-
tion of dIpc2BH, the reaction proceeds partially through
d
an alternate pathway—reaction with IpcBH2, the less
d
bulky dissociation product. It is known that Ipc2BH
and dIpcBH2 exhibit opposite enantiofacial selectivity in
the hydroboration [7,9]. Consequently, low enantiose-
lectivities are realized in the asymmetric hydroboration
of hindered alkenes as a result of the competitive
d
dissociation of Ipc2BH. In the present study, a-pinene
(15% excess) was added prior to the addition of the
cyclopentenol derivatives to retard such dissociation of
dIpc2BH.
Peterson and Stepanian [11] reported that the hy-
droboration-oxidation of 1-methoxy- and 1-benzyloxy-
cyclopentenes using lIpc2BH at 25 °C produced
trans-2-methoxy- and 2-benzyloxycyclopentanols in 29
and 23% ee, respectively. Neither absolute configura-
tion, nor the optical rotation of these products, were
reported. Since these authors carried out the reaction at
a considerably higher temperature (25°C), compared to
the reaction temperature reported in the present study
(−25 and −15°C), and have not added additional
d
a-pinene to suppress the dissociation of Ipc2BH, it is
(4)
most likely that the low asymmetric induction was due
to the participation of mixed hydroborating agents
An authentic sample of (S)-(+)-3-methoxytetrahy-
drofuran was obtained by methylation of commercially
available (S)-(+)-3-hydroxytetrahydrofuran. Chiropti-
cal comparison of these two samples of (S)-(+)-3-
d
arising from the dissociation of Ipc2BH.
2.1. Determination of absolute configuration of the
product alcohols
methoxytetrahydrofuran
confirmed
an
absolute
configuration of 3R,4R for 12.
On the basis of these results, we are schematically
representing the lowest energy transition state structure
proposed [16] for the hydroboration of the 1-cyclopen-
tenol derivatives with Ipc2BH in Fig. 1.
In this model, the Ipc groups attached to the carbon
bearing the boron atom are shown using the symbols S
The absolute configuration of optically active trans-
cyclopentane-1,2-diol has been reported in the literature
[12]. Hence, the absolute configuration of the hydrobo-
ration–oxidation products, the optically active trans-2-
alkoxycyclopentanols, were determined by converting
them to trans-cyclopentane-1,2-diol. The methoxy alco-
hol 8 (85% ee) was silylated using trimethylsilyl chlo-
ride-triethylamine. This silyl ether 13 was converted to
(1R,2R)-trans-(+)-cyclopentane-1,2-diol 15 by reac-
tion with in situ generated trimethylsilyl iodide followed
by hydrolysis of the intermediate bis-silyl ether 14 with
methanol. Thus the absolute configuration of the
methoxy alcohol 8, obtained by the hydroboration–ox-
idation of 1 using dIpc2BH could be determined as
1R,2R (Eq. (3)).
d
(small) for the hydrogen,
M (medium) for the
methylene and L (large) for the methylene attached to
the methyl group. With trisubstituted olefins, the steric
interaction between the inside L group and the alkyl
group is large enough to slow down the reaction con-
(3)
The absolute configuration of the benzyloxy alcohol
10 was established to be 1R,2R by hydrogenating [13] it
over 10% Pd–C to give (1R,2R)-trans-(+)-cyclopen-
Fig. 1. Preferred transition state structure for hydroboration of
olefins with dIpc2BH.

H.C. Brown et al. / Journal of Organometallic Chemistry 581 (1999) 116–121
119
siderably. In the case of simple enol ethers 1–3 and
4.1. Preparation of methoxymethyl-1-cyclopentenyl
ether 4
7, the increased electron density at the b-carbon, due
to the +R effect, increases the coordination between
the b-carbon and the boron atom. This energetically
favorable coordination of the b-carbon of the double
bond to the boron atom apparently overcomes the
steric repulsion between the L-group and the alkoxy
group.
The literature [18] procedure for the O-alkylation
of ketone enolates was modified as follows. To LDA
(prepared from diisopropylamine (2.02 g, 20 mmol)
and 2M n-BuLi in hexane (10 ml, 20 mmol) at 0°C
in THF), at −78°C cyclopentanone (1.68 g, 20
mmol) was added dropwise with stirring. After an
hour at −78°C the mixture was warmed to 25°C.
THF was evaporated under reduced pressure, DMSO
(250 ml) was added to the residue, followed by drop-
wise addition of methoxymethyl chloride (1.77 g, 22
mmol). The mixture was stirred for 5 min. Pentane
(3×75 ml) was then added to the mixture with stir-
ring and the pentane layer was removed using a dou-
ble-ended needle. The pentane solution was distilled
under reduced pressure to give pure 4 (b.p. 50–52°C,
3. Conclusions
Of the several cyclopentyl enol derivatives used in
the present study of asymmetric hydroboration using
dIpc2BH, the simple derivatives, such as methyl, ethyl
and benzyl enol ethers, appear to be the more favor-
able substrates. In these cases, the hydroboration–ox-
idation products were obtained in high optical purity
(75–85% ee) and good overall yield (70–95%), under
unoptimized reaction conditions. Optically active 2-
methoxy- and 2-benzyloxycyclopentanols were con-
verted to optically active trans-(1R,2R)-cyclopentane-
1,2-diol in high enantiomeric purity, thus constituting
a formal synthesis of the latter.
1
14 Torr): yield 1.0 g (40%); H-NMR (CDCl3) l 1.8–
2.0 (m,
2 H, CH2CH2CH2), 2.3–2.4 (m, 4 H,
CH2CH2CH2), 3.4 (s, 3 H, OCH3), 4.7 (m, 1 H, CH),
4.9 (s, 2 H, OCH2). 13C-NMR (CDCl3) l 21.0 (C-4),
29.3 (C-3), 31.8 (C-5), 56.5 (OCH3), 95.2 (OCH2),
97.4 (C-2), 157.4 (C-1).
4.2. General procedure for hydroboration of enol
deri6ati6es 1–7
4. Experimental
The following procedure for the preparation of
(1R,2R)-(-)-trans-2-methoxycyclopentanol is represen-
tative. A slurry of enantiomerically pure dIpc2BH [8]
(5.72 g, 20 mmol) and a-pinene (3 mmol) in THF (10
ml) was cooled to −25°C and 1-methoxycyclopen-
tene (1.96 g, 20 mmol) was added with stirring. The
reaction mixture was stirred for 76 h at −25°C when
all the dIpc2BH completely dissolved. The complete
formation of the intermediate trialkylborane was
confirmed by 11B-NMR spectrum of an aliquot (l
+82, s). Acetaldehyde (4.67 ml, 80 mmol) was added
to the reaction mixture at 0°C, and stirred at 25°C
for 24 h. Most of the unreacted acetaldehyde was
removed under reduced pressure and aqueous NaOH
(3 M, 5 ml)was added to the reaction mixture fol-
lowed careful addition of 30% aq. H2O2 (5 ml). The
reaction mixture was stirred at 25°C for 6 h. After
saturating the aqueous layer of the reaction mixture
with K2CO3 (5 g), the product was extracted with
ether (3×20 ml). The combined organic layers were
dried over anhydrous MgSO4. The solvent was evapo-
rated (25°C, 12 Torr), and residue was purified by
distillation: 2.2g (93%); b.p. 146–148°C (745 Torr)
(lit. [19] b.p. 81–83°C/10 Torr). The product, trans-2-
methoxycyclopentanol, was further purified by prepar-
ative GC: [h]D −17.1° (c, 3.4, EtOH), 85% ee (by
All b.p.s are uncorrected. All operations involving
organoboranes were carried out under an inert atmo-
sphere. Detailed procedures for handling air-sensitive
compounds have been reported elsewhere [17]. The
11B-NMR spectra were obtained at 25.5 MHz on a
Varian FT-80A instrument. The 11B chemical shifts
are given in l units relative to BF3:OEt2. The 1H-
NMR spectra were recorded at 200 MHz (Gemini-
200). The 13C-NMR measurements were made at 50.3
1
MHz (Gemini-200). The H- and 13C-NMR chemical
shifts are reported in l units relative to TMS stan-
dard. Optical rotations were measured on a Rudolph
polarimeter Autopol III, at 25°C. The enantiomeric
excesses of the product alcohols were determined by
capillary GC analysis of the corresponding esters of
(R) - (+) - a - methoxy - a - (trifluoromethyl)phenylacetic
acid [10] (MTPA), on a 50 ft methylsilicone or SPB-5
column using Hewlett–Packard 5890A chro-
matograph. For all the optically active alcohols re-
ported in this paper, the corresponding racemic
alcohols were prepared by known procedures and
their MTPA esters showed 50–50 baseline separation
on capillary GC analysis. THF was distilled over
sodium and benzo-phenone ketyl. Anhydrous ether
obtained from Mallinckrodt, was used with out fur-
ther purification. Dimethyl sulfoxide (DMSO) was
dried by distilling over CaH.
1
capillary GC analysis of MTPA); H-NMR (CCl4) l
1.3–2.2 (m, 6 H, CH2CH2CH2), 3.2 (s, 1 H, OH), 3.3

120
H.C. Brown et al. / Journal of Organometallic Chemistry 581 (1999) 116–121
(s, 3 H, OCH3), 3.4–3.7 (m, 1 H, CH), 3.9–4.2 (m, 1
H, CH). 13C-NMR (CDCl3) l 20.8 (C-4), 29.1 (C-3),
32.4 (C-5), 56.9 (OCH3), 76.7 (C-1), 88.7 (C-2). Anal.
Calc. for C6H12O2: C, 62.04; H, 10.41. Found: C,
61.87; H, 10.78.
(CDCl3) l 57.1 (OCH3), 71.2 (C-3), 73.8 (C-5), 74.7
(C-1), 86.9 (C-2).
4.7. Con6ersion of methoxy alcohol 8 to
(1R,2R)-(–)-cyclopentane-1,2-diol, 15
A mixture of methoxy alcohol 8 (1.74 g, 15 mmol),
triethylamine (8.37 ml, 60 mmol), trimethylsilyl chlo-
ride (3.57 g, 33 mmol) and ether (150 ml) was stirred
at 25°C for 24 h. The precipitated amine hydrochlo-
ride was filtered off and the filtrate was distilled. The
residue after removing volatiles was found to be pure
13, which was used as such for the next step: yield
2.7 g (95%); 1H-NMR (CCl4) l 0.08 (s, 9 H,
Si(CH3)3), 1.2–2.1 (s, 3 H, OCH3), 3.3–3.6 (m, 1 H,
CH), 3.8–4.3 (m, 1 H, CH).
To a mixture of 13 (1.9 g, 10 mmol), NaI (1.5 g,
10 mmol), and acetonitrile (15 ml) was added
trimethylsilyl chloride (1.08 g, 10 mmol), and stirred
at 25°C. The reaction was monitored by GC and af-
ter 6 h most of the starting materials disappeared.
Methanol (5 ml) was added to the reaction mixture
and stirred at 25°C for 6 h. The solids were filtered
off and the filtrate evaporated under reduced pressure
(12 Torr). The residue was purified by prep GC (10%
SE-30 at 140°C), to give pure (1R,2R)-cyclopentane-
1,2-diol [12]: [h]D −20.0° (EtOH); yield 0.3 g (40%);
1H-NMR (CDCl3) l 1.2-2.2 (m, 6 H, CH2CH2CH2),
3.91 (m, 2 H, CHCH), 4.2 (bs, 2 H, 2 OH).
4.3. (1R,2R)-(–)-2-Ethoxycyclopentanol, 9
B.p. 160°C/745 mm (lit. [20] b.p. 182°C/760 Torr).
[h]D −19.6° (c, 4.8, EtOH), 76% ee (by capillary GC
analysis of MTPA ester); 1H-NMR (CCl4) l 1.2 (t,
J=7 Hz, 3 H, CH3), 1.3–2.3 (m, 6 H, CH2CH2CH2),
2.8 (bs, 1 H, OH), 3.5 (q, J=7 Hz, 2 H, CH2CH3),
3.5–3.8 (m, 1 H, CH), 3.9–4.3 (m, 1 H, CH). 13C-
NMR (CDCl3) l 15.6 (CH3), 20.8 (C-4), 29.7 (C-3),
32.3 (C-5), 64.7 (OCH2), 77.0 (C-1), 87.0 (C-2). Anal.
Calc. for C7H14O2: C, 64.58; H, 10.84. Found: C,
64.83; H, 11.12.
4.4. (1R,2R)-(–)-2-Benzyloxycyclopentanol, 10 [21]
B.p. 110°C/1 mm; [h]D −23.3° (c, 2.7, EtOH), 77%
ee (by capillary GC analysis of MTPA ester); 1H-
NMR (CCl4) l 1.3–2.2 (m, 6 H, CH2CH2CH2), 2.0
(bs, 1 H, OH), 3.6–3.9 (m, 1 H, CH), 4.0–4.3 (m, 1
H, CH), 4.6 (s, 2 H, OCH2), 7.3 (s, 5 H, C6H5).
13C-NMR (CDCl3) l 20.6 (C-4), 29.4 (C-3), 32.2 (C-
5), 71.3 (OCH2), 77.1 (C-1), 86.6 (C-2), 127.6 (C-3%,
C-4% and C-5%), 128.3 (C-2% and C-6%), 138.6 (C-1%).
Anal. Calc. for C12H16O2: C, 74.97; H, 8.39. Found:
C, 75.14; H, 8.72.
4.8. Con6ersion of benzyloxy alcohol 10 to
(1R,2R)-(–)-cyclopentane-1,2-diol
4.5. (1R,2R)-(–)- Mono methoxymethyl ether of
trans-cyclopentane-1,2-diol, 11
The benzyloxy alcohol 10 (1.0 g, of 65% ee) was
hydrogenated over 10% Pd–C (0.2 g) in ethanol (20
ml) using a Brown hydrogenator [13]. Hydrogen was
generated by adding aq. NaBH4 to glacial acetic acid.
When the uptake of hydrogen stopped, the mixture
was filtered, solvent removed to give pure (1R,2R)-cy-
clopentane-1,2-diol [12]: yield 0.43 g (90%). The diol
was further purified by prep GC (10% SE-30, 140°C):
[h]D −15.7° (c, 5.3, EtOH).
Purified by prep GC 10% SE-30 at 150°C; [h]D
−11.6° (c, 2.2, MeOH), 50% ee (by capillary GC
analysis of the corresponding cyclopentane-1,2-diol on
SPB-5 column); 1H-NMR (CDCl3) l 1.4–1.7 (m, 4
H, CH2CH2CH2), 1.8–2.2 (m, 2 H, CH2CH2CH2),
3.3 (s, 1 H, OH), 3.4 (s, 3 H, OCH3), 3.7 (dd,
J=5.7 and 12.9 Hz, 1 H, CH), 4.0 (dd, J=5.7 and
12.9 Hz, 1 H, CH), 4.64, 4.68 (ABq, 2 H, J=7 Hz).
13C-NMR (CDCl3) l 19.5 (C-4), 29.6 (C-3), 31.0
(C-5), 55.8 (OCH3), 77.7 (C-1), 88.0 (C-2), 97.2
(OCH2).
4.9. Con6ersion of alcohol 11 to
(1R,2R)-(–)-cyclopentane-1,2-diol
To a mixture of 11 (1 g), THF (5 ml) and water (1
ml) was added conc. HCl (12 M, 0.1 ml), and the
mixture was stirred at 25°C for 12 h. Solid K2CO3
(1g) was added carefully. The supernatant solution
was decanted and the solvent was evaporated to give
(1R,2R)-cyclopentane-1,2-diol [11]: yield 0.6 g (92%).
The product was further purified by preparative GC.
Capillary GC analysis of its MTPA ester (SPB-5,
240°) showed a 50% ee for the diol.
4.6. (3R,4R)-(+)-4-Methoxytetrahydrofuran-3-ol, 12
Purified by prep GC (10% carbowax column at
150°C; [h]D +14.0° (c, 3.2, EtOH), 75% ee (by capil-
lary GC analysis of MTPA ester on SPB-5, 165°C).
1H-NMR (CCl4) l 3.4 (s, 3 H, OCH3), 3.5–4.2 (m, 6
H, CH2CHCHCH2), 4.3 (bs, 1 H, OH). 13C-NMR

H.C. Brown et al. / Journal of Organometallic Chemistry 581 (1999) 116–121
121
4.10. Con6ersion of methoxy alcohol 12 to
References
(S)-(+)-3-methoxytetrahydrofuran 17
[1] (a) In NADH model compounds: J. Inouye, J. Oda, N. Baba, in:
J.D. Morrison (Ed.), Asymmetric Synthesis, vol. 2, Academic
Press, Orlando, 1983, p.117. (b) As LAH chiral modifiers: E.R.
Grandbois, S.I. Howard, J.D. Morrison, in Ref. [1a], p. 74. (c)
As chiral ligands in Grignard reactions: G. Solladie, in Ref. [1a],
p. 158. (d) In asymmetric hydrogenation catalysts: W.R. Jack-
son, Aust. J. Chem. 35 (1982) 2069. (e) In asymmetric polymer-
ization: A. Momtaz, N. Spassky, P. Sigwalt, Nouv. J. Chim. 3
(1979) 669. (f) As chiral auxiliaries in boron chemistry: D.S.
Matteson, P.B. Tripathy, A. Sarkar, K.M. Sadhu, J. Am. Chem.
Soc. 111 (1989) 4399. (g) In chiral crown ethers: R.C. Hayward,
C.H. Overton, G.H. Whitham, J. Chem. Soc. Perkin Trans 1
(1976) 2413.
To a solution of 12 (0.6 g, 5.0 mmol) in ether (15 ml),
n-BuLi in hexane (2.0 ml, 5.0 mmol) was added drop-
wise. To this mixture p-toluenesulfonyl chloride (0.97 g,
5.1 mmol) was added and the mixture stirred at 25°C
for 12 h. The precipitated LiCl was filtered off and the
1
solvent was evaporated from the filtrate. H-NMR of
the residue showed it to be pure tosylate, which was
1
used as such for the next step: H-NMR (CDCl3) l 2.5
(s, 3 H, ArCH3), 3.3 (s, 3 H, OCH3), 3.5–4.2 (m, 5
H,CH2OCH2CHOCH3), 4.9 (m, 1 H, CHOTs), 7.4 (d,
J=8 Hz, 2 H, ArH3 and H5), 7.8 (d, J=8 Hz, 2 H,
ArH4 and H6).
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To a solution of crude tosylate in THF (10 ml) was
added a 1.0 M solution of lithium triethylborohydride
in THF (5 ml). The mixture was stirred at 25°C for 12
h. The precipitated solids were filtered off and the
filtrate was fractionated at atmospheric pressure. The
fraction distilling at 98°C was found to be pure (S)-3-
methoxytetrahydrofuran 17: yield 0.25 g (50%). [h]D
+15.4° (c, 6.0, THF), H-NMR (CCl4) l 1.7–2.3 (m, 2
H,OCH2CH2), 3.3 (s, 3 H, OCH3), 3.7–4.2 (m, 5
H,OCHCH2OCH2).
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1
4.11. Methylation of commercial
(S)-(+)-3-hydroxytetrahydrofuran
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To a slurry of NaH (from 0.45 g, 10 mmol of 60%
NaH emulsion) in ether (15 ml), (S)-(+)-3-hydroxy-
tetrahydrofuran of 95% optical purity (1 g, 11.4 mmol)
in ether (5 ml) was added at such a rate that the ether
was refluxing gently. The mixture was stirred at 25°C
for 1 h. Methyl iodide (1.7 g, 12 mmol) added to the
mixture and stirred at 25°C for 24 h. The ether solution
was filtered and the filtrate was distilled. The fraction
distilling between 100–105° was found to be pure (S)-
(+)-3-hydroxytetrahydrofuran 17: Yield 1.0 g (90%);
[h]D +25.9° (c, 4.5, THF).
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Acknowledgements
We are grateful to the National Institutes of Health
(GM 10937-27) for their generous support of this work.
Acknowledgement is also made to the donors of The
Petroleum Research Fund, administered by the ACS
for partial support of this research.
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K. Winzenberg, J. Am. Chem. Soc. 108 (1986) 3040.
.