Conformational control on remote stereochemistry in the intramolecular Pauson-Khand reactions of enynes tethered to homoallyl and homopropargyl alcohols

Article abstract of DOI:10.1016/j.tetasy.2006.11.012

An intramolecular Pauson-Khand reaction of enynes derived from homoallyl and homopropargyl alcohols is described. 2-Furyl substituted homoallyl and homopropargyl alcohols are easily and efficiently resolved through enzymatic resolution in a high ee (93-99%) with a known stereochemistry. Each enantiomerically enriched enyne affords the conformationally most stable diastereomeric cyclopenta[c]pyran ring system.

Full text of DOI:10.1016/j.tetasy.2006.11.012

Tetrahedron: Asymmetry 17 (2006) 2981–2986
Conformational control on remote stereochemistry in the
intramolecular Pauson–Khand reactions of enynes tethered
to homoallyl and homopropargyl alcohols
a
b
c
a,
*
¨
Serdar Sezer, Devrim Ozdemirhan, Ertan Sßahin and Cihangir Tanyeli
aDepartment of Chemistry, Middle East Technical University, 06531 Ankara, Turkey
b
_
Department of Chemistry, Abant Izzet Baysal University, 14280 Bolu, Turkey
cDepartment of Chemistry, Ataturtk University, 25240 Erzurum, Turkey
Received 29 September 2006; accepted 9 November 2006
Abstract—An intramolecular Pauson–Khand reaction of enynes derived from homoallyl and homopropargyl alcohols is described. 2-
Furyl substituted homoallyl and homopropargyl alcohols are easily and efficiently resolved through enzymatic resolution in a high ee
(93–99%) with a known stereochemistry. Each enantiomerically enriched enyne affords the conformationally most stable diastereomeric
cyclopenta[c]pyran ring system.
ꢀ 2006 Elsevier Ltd. All rights reserved.
1. Introduction
1997, we reported the first enzyme-catalyzed resolution of
racemic furylcarbinols with high enantiomeric purity and
in good total yields.6 This approach was used recently by
some other groups.7
Heterocyclic natural products having a-heterocyclic carbi-
nol moieties, are exceptionally valuable compounds for
biomedical and pharmaceutical research, owing to their
structural features and diverse medicinal values. A number
of heterocyclic natural products exhibiting useful biological
activities have been isolated from natural sources.1 Brown
et al.2 accomplished the highly stereoselective synthesis of
furyl-, thiophenyl-, pyridyl-, and other heterocyclic carbi-
nols, which are useful for the stereoselective synthesis of
many other important heterocyclic compounds,3 by the
asymmetric allylboration of heterocyclic aldehydes with
diterpenylallylboranes. However, catalytic enantioselective
methods hold tremendous appeal in synthetic organic
chemistry. A significant progress in the development of cat-
alytic enantioselective allylation and propargylation has
been recorded in recent years.4
The Pauson–Khand reaction (PKR)8 has been established
as a powerful method for the synthesis of the cyclopente-
none framework by a cobalt-mediated reaction performed
by joining an alkyne, an olefin, and carbon monoxide.
The intramolecular version of the reaction has gained
much popularity because it can afford cyclopentenone-
fused ring systems, which are difficult to construct.9
Although the application of this useful method to the con-
struction of chiral cyclopentenone–pyran ring skeletons
using carbohydrate templates has been well documented,10
little attention has been focused on the PKR of chiral en-
yne systems.11 Recent reports from our laboratory have
demonstrated the utility of biocatalysts in the resolution
of racemic a-heterocyclic carbinols6,12 as a potentially use-
ful scaffold for carrying out intramolecular PKRs. The
important characteristics of this scaffold are the availability
of the starting material, easy enzymatic resolution of the
products, and the easy construction of enyne systems on
it. Herein we report, a brief study on the PKR of enyne sys-
tems tethered to a chiral 2-furylcarbinol scaffold affording
chiral cyclopenta-pyran fused ring systems with an excel-
lent diastereoselectivity.
Since biocatalysts have become popular and powerful in
organic synthesis,5 enzymatic resolution can sometimes
be very useful if it works well for individual alcohols. In
*
Corresponding author. Tel.: +90 312 210 3222; fax: +90 312 210 3200;
e-mail: tanyeli@metu.edu.tr
0957-4166/$ - see front matter ꢀ 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2006.11.012

2982
S. Sezer et al. / Tetrahedron: Asymmetry 17 (2006) 2981–2986
2. Results and discussion
none–pyran products (+)-7:cis and (+)-8:trans were
obtained (Scheme 2).15
The parent homoallylic alcohol ( )-1 and homopropargy-
lic alcohol ( )-2 were prepared by the addition of allylmag-
nesium bromide and propargyl bromide in the presence of
a zinc–copper couple to the commercially available furfural
in ether and THF, respectively, as shown in Scheme 1. The
enantiomeric resolution of ( )-1 and 2 catalyzed by PS-C
Amano II13 using vinyl acetate as an acyl donor and
THF as solvent afforded (S)-(ꢀ)-1 (99% ee) and (S)-(+)-2
(93% ee) after the reaction was stopped at 55% and 52%
conversions, respectively. To obtain alcohols (R)-(+)-1
and (R)-(ꢀ)-2, acetates (R)-(+)-3 and (R)-(+)-4 were
hydrolyzed quantitatively with NaOH in methanol. More-
over, the enzymatic hydrolysis of ( )-3 catalyzed by PLE
also afforded alcohol (R)-(+)-1 (93% ee) in a pH = 7 phos-
phate buffer system.14 All the results are summarized in Ta-
ble 1. The enyne systems were built on enantiomerically
enriched homoallylic and homopropargylic alcohol skele-
tons by O-propargylation and O-allylation using TMS–
propargyl bromide and allyl bromide with NaH in THF,
respectively.
X-ray structures of the cyclopentenone–pyran products cis-
(+)-7 and trans-(+)-8 provided an explanation as to why
enynes (S)-(+)-5 and (S)-(ꢀ)-6, respectively, afforded single
diastereomers (Fig. 1). In compound (+)-7, C1–H and C3–
H are cis, whereas C1–H and C4–H are trans in compound
(+)-8. In both cases, the pyran rings are in the most
favored chair conformation and the furyl substituents
are in equatorial orientation, as expected.
3. Conclusion
New enantiomerically enriched 2-furyl substituted enynes
tethered to homoallyl and homopropargyl backbones have
been synthesized. Their intramolecular PKR showed a high
conformational control on the remote stereocenter formed
on the cyclopentenone–pyran ring system. We are currently
studying the role of conformational control of similar
homoallyl and homopropargyl enynes having diverse
substituents. This work may be applicable to other easily
prepared chiral homoallyl and homopropargyl type
compounds.
To study the applicability of the intramolecular PKR of
enynes tethered to chiral 2-furylcarbinols and to explore
the control of remote stereochemistry in the synthesis of
cyclopentenone–pyran ring skeletons, we submitted com-
pounds (S)-5 and (S)-6 to the most common conditions
for PKR.
4. Experimental
All experiments were carried out in pre-dried glassware
(1 h, 150 ꢁC) under an inert atmosphere of argon. The fol-
lowing reaction solvents were distilled from the indicated
drying agents: dichloromethane (P2O5), tetrahydrofuran
In this protocol, cobalt alkyne complexes were prepared
using enyne–dicobalt octacarbonyl in a molar ratio of
1.0:1.3 in DCM, and then N-methylmorpholine N-oxide
monohydrate was added as a promoter.
1
(sodium, benzophenone). H NMR and 13C NMR spectra
were recorded in CDCl3 on a Bruker Spectrospin Avance
DPX-400 spectrometer and the chemical shift as were ex-
pressed in ppm relative to CDCl3 (d 7.26 and 77.0 for H
The reaction was monitored by thin layer chromatography
(TLC). In both cases, single diastereomers of cyclopente-
1
O
O
H
b
a
OH
OH
O
O
( )-1
2
( )-
c
c
OH
OAc
OH
OAc
O
O
O
O
+
+
(
R
)-(+)-3
e, d
(S)-(-)-1
(
R
)-(+)-4
e, f
(S)-(+)-2
d
f
O
O
O
O
O
O
O
O
6
(S)-(-)-
(R)-(+)-5
(S)-(-)-5
(R)-(+)-6
Scheme 1. Reagents and conditions: (a) allylbromide, Mg, dry ether; (b) Zn, Cu, propargylbromide, THF; (c) PS-C Amano II, vinylacetate, THF; (d)
NaH, TMS–propargylbromide, THF; (e) NaOH, MeOH; (f) NaH, allylbromide, THF.

S. Sezer et al. / Tetrahedron: Asymmetry 17 (2006) 2981–2986
2983
Table 1. Enzymatic hydrolysis of 1–3a,e
29
Entry
Substrate
Enzyme
Temperature (ꢁC)
Time (h)
Conv. (%)
eeb (%)
½aꢁD (c, solvent)
Absolute conf.c
1
2
3d
(
(
(
)-1
)-2
)-3
PS-C Amano II
PS-C Amano II
PLE
24
24
15
4
1.5
4.5
55
52
47
99
93
93
ꢀ40.0 (c 5.0, CH2Cl2)
+6.7 (c 3.1, MeOH)
+37.1 (c 0.76, CHCl3)
S
S
R
a All data given for the alcohols isolated as a result of enzymatic resolution.
b Determined by HPLC analysis employing a Daicel Chiralcel OD–H and OJ–H column.
c The absolute configurations of (S)-(ꢀ)-1,7a (S)-(+)-2,4t (R)-(+)-1,6 (R)-(ꢀ)-24t were found to be (S) or (R) according to the specific rotations reported in
Refs. 6, 7a and 4t.
d Compound ( )-3 was resolved by PLE.14
e Compound (R)-(+)-4 was chemically hydrolyzed to obtain (R)-(ꢀ)-2.
O
O
Daicel Chiralcel OD-H, OJ-H and Regis technologies
Inc., Whelk O1 chiral columns.
H
a
a
a
O
3
O
O
1
(S
)
H
Flash column chromatography was performed by using
thick-walled glass columns with a flash grade (Merc Silica
Gel 60). The reactions were monitored by thin layer chro-
matography using pre-coated silica gel plates (Merc Silica
Gel PF-254), visualized by UV-light and polymolybden
phosphoric acid in ethanol as appropriate. All extracts
were dried over anhydrous magnesium sulfate and solu-
tions were concentrated under vacuum by using rotary
evaporator.
7
(+)- (cis-1,3)
H
O
O
4
H
O
O
O
O
1
(
S
)
8
(+)- (trans-1,4)
O
O
H
O
3
O
1
(R
)
H
4.1. Synthesis of homopropargyl alcohol ( )-2
7
(-)- (cis-1,3)
A Zn–Cu couple preparation was formed in an oxygen-free
environment. Zinc dust (6.5 g, 100 mmol) was suspended in
distilled water (10 mL). Acidic cupric chloride solution
(0.15 M in 5% hydrochloric acid, 22 mL) was then added
with vigorous magnetic stirring. When the evolution of
gas ceased the suspension was filtered and the black solid
was washed with water until the wash gave a negative test
with 6% silver nitrate solution. The Zn–Cu was then
washed twice with acetone.12,18
H
O
O
4
a
H
O
O
O
1
(R)
8
(-)- (trans-1,4)
Scheme 2. Reagents and conditions: (a) Co2CO8, DCM, NMO.
and 13C NMR, respectively) as the internal standard. Stan-
dard COSY, HETCOR, and DEPT experiments were per-
formed to establish NMR assignments. Infrared spectra
were recorded on a Varian 1000 FT-IR spectrophotometer.
High-resolution mass spectral data were obtained with a
Varian MAT 212. Optical rotations were measured
employing a Rudolph research analytical, Autopol III
automatic polarimeter. Melting points were determined
on an Electrothermal (Mel-Temp) apparatus (Model No:
1002D) on are uncorrected. High performance liquid chro-
matography (HPLC) was done with a Thermo Separation
Products, Inc., P1500-SN-4000-UV2000 instrument using
To a stirred mixture of 2-furaldehyde (6.90 g, 72 mmol)
and freshly prepared Zn–Cu couple (1.03 g, 79.6 mmol)
in THF (20 mL), propargyl bromide (0.21 g, 79.6 mmol,
80% solution in toluene) was added dropwise at 0 ꢁC.
The mixture was then refluxed for 6 h (TLC monitoring).
The resultant mixture was hydrolyzed with 1 M HCl
(8 mL) and extracted with ether (3 · 30 mL), dried over
MgSO4, and evaporated in vacuo. The crude product was
purified by flash column chromatography (EtOAc–hexane,
1:10), (7.83 g, 80% yield). All spectroscopic data are in
accordance with that in the literature.4t
Figure 1. X-ray structure of compounds cis-(+)-7 and trans-(+)-8.

2984
S. Sezer et al. / Tetrahedron: Asymmetry 17 (2006) 2981–2986
4.2. General procedure for enzymatic resolution
4.2.6. (R)-(ꢀ)-1-(Furan-2-yl)but-3-yn-1-ol, (R)-(ꢀ)-2. To a
solution of (R)-(+)-4 (500 mg, 2.7 mmol) in methanol
(30 mL) and water (10 mL), 1 M solution of NaOH
(2.7 mL) was added and stirred at room temperature until
the hydrolysis was complete (TLC). The solution was ex-
tracted with chloroform (3 · 25 mL), dried over MgSO4,
and evaporated under vacuum (495 mg, 99% yield).
To a solution of ( )-1–2 (1 mmol) in anhydrous THF
(1 mL) and vinyl acetate (0.9 mL, 10 mmol) in a 25 mL
round-bottomed flask, was added lipase (1 equiv w/w).
The reaction mixture was stirred at constant temperature
(24 1 ꢁC) and monitored by TLC and recorded on
HPLC. On achieving the desired conversion the reaction
was stopped by filtering the enzyme on a sintered glass fun-
nel. The filtrate was concentrated and purified by column
chromatography on silica gel using mixtures of hexane
and ethyl acetate as eluents to afford (R)-acetates and
(S)-alcohols.
4.3. General procedure for O-allylation and O-
propargylation
To a solution of (S)-(ꢀ)-1 or (S)-(+)-2 (1.4 mmol) in dry
THF (10 mL) was added NaH (0.62 g, 60% dispersion in
oil, 1.54 mmol) under argon. Allylbromide or TMS–propa-
rgylbromide (1.54 mmol) was then added dropwise. The
mixture was refluxed for 1 h and hydrolyzed by the cau-
tious addition of water (15 mL). The aqueous layer was ex-
tracted with ether (3 · 20 mL). The combined organic
phase was dried over MgSO4 and evaporated in vacuo.
The crude product mixture was separated by flash column
chromatography using ethylacetate/hexane (1:9) as the elu-
ent to afford the product.
4.2.1. (S)-(ꢀ)-1-(2-Furyl)but-3-en-1-ol, (S)-(ꢀ)-1. This is a
29
yellow oil; ½aꢁD ¼ ꢀ40:0 (c 5.0, CH2Cl2) for 99% ee. The
absolute configuration and enantiomeric purity of the
product were determined by HPLC analysis (Daicel Chiral-
cel OJ-H, hexane/i-PrOH 96:4, flow rate = 1 mL minꢀ1
,
k = 230 nm, tR = 11.20 min [(R)-isomer], tR = 12.64 min
[(S)-isomer] in comparison with the racemic sample).
4.2.2. (R)-(+)-1-(2-Furyl)but-3-en-1-yl acetate, (R)-(+)-
29
4.3.1. (S)-(ꢀ)-2-(1-(Prop-2-ynyloxy)but-3-enyl)furan, (S)-
3. This is a yellow oil; ½aꢁD ¼ þ22:2 (c 1.02, CH2Cl2)
29
(ꢀ)-5. This is a yellow oil (0.20 g, 83% yield). ½aꢁD ¼ ꢀ67:5
for 96% ee. The absolute configuration and enantiomeric
purity of the product were determined by HPLC analysis
1
(c 2.7, CH2Cl2). H NMR (CDCl3): d 7.24 (d, J = 0.8 Hz,
1H), 6.32–6.38 (m, 2H), 5.70–5.83 (m, 1H), 4.93 (dd,
J = 1.2 and 17.1 Hz, 1H), 4.88 (d, J = 1.2 and 10.2 Hz,
1H), 4.42 (t, J = 7.0 Hz, 1H), 3.98 (dd, J = 2.2 and
J = 15.8 Hz, 1H), 3.78 (dd, J = 2.2 and 15.8 Hz, 1H),
2.36–2.56 (m, 2H), 2.23 (t, J = 2.2 Hz, 1H). 13C NMR
(CDCl3): d 152.4, 142.1, 133.3, 116.8, 109.5, 108.5, 79.2,
73.8, 72.5, 55.0, 37.8. Anal. Calcd: C, 74.98; H, 6.86. Found:
C, 74.36; H, 6.81.
(Whelk, hexane/i-PrOH 96:4, flow rate = 1 mL minꢀ1
,
k = 230 nm, tR = 5.49 min, tR = 6.25 in comparison with
the racemic sample).
4.2.3. (R)-(+)-1-(2-Furyl)but-3-en-1-ol, (R)-(+)-1. To a
stirred solution of ( )-3 (500 mg, 2.7 mmol) in 0.1 M phos-
phate buffer (pH 7.00, 75 mL), was added PLE (100 lL) at
one portion and the reaction mixture was stirred at 15 ꢁC
for 4.5 h. The reaction mixture was extracted with ethyl
acetate (3 · 50 mL), dried over MgSO4 and then evapo-
rated under vacuum. The crude product was separated by
flash column chromatography (EtOAc/hexane, 1:4)
(0.24 g, 47% yield).6
4.3.2. (R)-(+)-2-(1-(Prop-2-ynyloxy)but-3-enyl)furan. (R)-
29
(+)-5: ½aꢁD ¼ þ66:4 (c 2.6, CH2Cl2).
4.3.3.
(S)-(ꢀ)-2-(1-Allyloxy)but-3-ynyl)furan,
(S)-(ꢀ)-
29
6. This is a yellow oil (0.19 g, 80% yield). ½aꢁD ¼ ꢀ8:5
(c 0.5, MeOH). 1H NMR (CDCl3): d 7.34 (br s, 1H),
6.28–6.29 (overlapped br s, 2H), 5.77–5.86 (m, 1H), 5.20
(dd, J = 1.2 and 17.2 Hz, 1H), 5.11 (dd, J = 1.2 and
10.4 Hz, 1H), 4.48 (t, J = 6.9 Hz, 1H), 3.96 (dd, J = 5.1
and 12.8 Hz, 1H), 3.86 (dd, J = 5.1 and 12.8 Hz, 1H),
2.65–2.77 (m, 2H), 1.90 (t, J = 2.6 Hz, 1H). 13C NMR
(CDCl3): d 153.3, 143.0, 134.7, 117.8, 110.4, 108.9, 80.6,
72.8, 70.3, 70.2, 24.9. Anal. Calcd: C, 74.98; H, 6.86.
Found: C, 74.52; H, 6.74.
4.2.4. (S)-(+)-1-(Furan-2-yl)but-3-yn-1-ol, (S)-(+)-2. This
29
is a yellow oil; ½aꢁD ¼ þ6:7 (c 3.1, MeOH) for 93% ee.
The absolute configuration and enantiomeric purity of
the product were determined by HPLC analysis (Daicel
Chiralcel OD-H, hexane/i-PrOH 96:4, flow rate = 1 -
mL minꢀ1, k = 230 nm), tR = 16.842 min, tR = 23.15 in
comparison with an authentic sample).
4.2.5. (R)-(+)-1-(Furan-2-yl)but-3-ynyl acetate, (R)-(+)-
29
4.3.4. (R)-(+)-2-(1-(Allyloxy)but-3-ynyl)furan. (R)-(+)-6:
½aꢁD ¼ þ8:2 (c 0.5, MeOH).
4. This is a yellow oil; ½aꢁD ¼ þ54:6 (c 4.0, MeOH)
29
for 90% ee. The absolute configuration and enantiomeric
purity of the product were determined by HPLC analysis
(Whelk, hexane/i-PrOH 96:4, flow rate = 1 mL minꢀ1
,
4.4. General procedure for the Pauson–Khand reaction
k = 230 nm), tR = 5.89 min, tR = 6.11 in comparison with
the authentic sample. H NMR (CDCl3): d 7.32 (s, 1H),
6.34 (d, J = 3.2 Hz, 1H), 6.27 (d, J = 1.79 Hz, 1H), 5.89
(t, J = 6.9, 1H), 2.73 (dd, J = 7.69 and 7.67 Hz, 2H), 2.00
(s, 3H), 1.91 (s, 1H). 13C NMR (CDCl3): d 169.9, 151.2,
142.8, 110.3, 109.1, 78.9, 70.6, 66.5, 23.0, 20.9. Anal. Calcd:
C, 67.41; H, 5.66. Found: C, 67.13; H, 5.46.
1
To a solution of (S)-(ꢀ)-5 (0.204 g, 1.16 mmol) or (S)-(ꢀ)-6
(0.197 g, 1.12 mmol) in CH2Cl2 (10 mL) was added
Co2(CO)8 (0.683 g, 2.0 mmol), and stirred for 2 h (TLC
monitoring). Then, NMO (1.56 g, 11.6 mmol) was added
and stirred for 24 h. The crude product was purified by
flash column chromatography (EtOAc–hexane, 2:1).

S. Sezer et al. / Tetrahedron: Asymmetry 17 (2006) 2981–2986
2985
4.4.1. (3S,4aR)-(+)-3-(Furan-2-yl)-3,4,4a,5-tetrahydrocyclo-
penta[c]pyran-6(1H)-one, (+)-7. This is a white solid
correction for Lorentz and polarization effects and cell
refinement were performed using CrystalClear software.16
The structures were solved by direct methods (SHELXS-97)
and non-H atoms were refined by full-matrix least-squares
method with anisotropic temperature factors (SHELXL-
97).17
29
(0.18 g, 75% yield); mp 89 ꢁC. ½aꢁD ¼ þ35:5 (c 1.7,
1
CH2Cl2); H NMR (CDCl3): d 7.33 (d, J = 1.0 Hz, 1H),
6.29 (m, 1H), 6.24 (d, J = 3.2 Hz, 1H) 5.94 (s, 1H), 4.74
(d, J = 13.5 Hz, 1H), 4.63 (dd, J = 1.3 and 11.5 Hz, 1H),
4.35 (d, J = 13.5 Hz, 1H), 2.97–3.00 (m, 1H), 2.62 (dd,
J = 6.5 and 18.8 Hz, 1H), 2.36 (dd, J = 5.8 and 13.0 Hz,
1H), 2.08 (dd, J = 2.8 and 18.6 Hz, 1H), 1.80 (dd,
J = 12.2 and 24.4 Hz, 1H); 13C NMR (CDCl3): d 207.4,
174.2, 153.0, 142.6, 127.8, 110.3, 107.1, 72.2, 67.0, 41.8,
39.0, 37.9. IR (KBr): 1702, 1622, 1403 cmꢀ1. Anal. Calcd:
C, 70.57; H, 5.92. Found: C, 70.36; H, 5.78.
4.6.1. Crystal data for compound cis-(+)-7. C12H12O3,
crystal system, space group: monoclinic, P21/c; (no:14);
unit cell dimensions: a = 5.5093(3), b = 18.8250(6), c =
3
˚
˚
10.2240(5) A, b = 105.466(2)ꢁ; volume: 1021.96(6) A ;
Z = 4; calculated density: 1.33 mg/m3; absorption coeffi-
cient:
0.095 mmꢀ1
;
F(000):
432;
crystal
size:
0.031 · 0.025 · 0.012 mm3; h range for data collection
2.2–30.5ꢁ; completeness to h: 30.5ꢁ, 99.8%; refinement
method: full-matrix least-square on F2; data/restraints/
parameters: 3117/0/160; goodness-of-fit on F2: 1.386; final
R indices [I > 2r(I)]: R1 = 0.073, wR2 = 0.183; R indices
4.4.2. (3R,4aS)-(ꢀ)-3-(Furan-2-yl)-3,4,4a,5-tetrahydrocyclo-
29
penta[c]pyran-6(1H)-one, (ꢀ)-7. ½aꢁD ¼ ꢀ34:4 (c 1.8, CH2Cl2).
4.4.3. (3S,7aR)-(+)-3-(Furan-2-yl)-3,4,7,7a-tetrahydrocyclo-
penta[c]pyran-6(1H)-one, (+)-8. This is a white solid
(all data): R1 = 0.074, wR2 = 0.183; extinction coefficiꢀen3t:
29
˚
(0.19 g, 81% yield); mp 81–82 ꢁC. ½aꢁD ¼ þ99:1 (c 3.6,
0.00; largest diff. peak and hole: 0.226 and ꢀ0.239 e A
.
1
MeOH). H NMR (CDCl3): d 7.37 (br s, 1H), 6.31 (br s,
2H), 5.95 (s, 1H), 4.32–4.39 (m, 3H), 3.21 (t, J = 11.0 Hz,
1H), 2.98 (d, J = 13.3 Hz, 1H), 2.86 (t, J = 12.4 Hz, 1H),
2.45 (dd, J= 6.6 and 18.8 Hz, 1H), 1.89 (d, J = 18.8 Hz,
1H). 13C NMR (CDCl3): d 207.5, 178.4, 152.7, 142.9,
128.1, 110.4, 107.6, 73.3, 73.2, 40.9, 37.0, 35.3. IR (KBr):
1704, 1618, 1381 cmꢀ1. Ion mode; FAB+ MS (m/z) exact
mass; 205.0786 (M+1); observed; 205.0802 (M+1).
4.6.2. Crystal data for compound trans-(+)-8. C12H12O3,
crystal system, space group: orthorhombic, P212121; (no:
14); unit cell dimensions: a = 7.8398(8), b = 11.4097(8),
3
˚
˚
c = 11.9476(9) A, b = 90ꢁ; volume: 1068.71(2) A ; Z = 4;
calculated density: 1.27 mg/m3; absorption coefficient:
0.091 mmꢀ1; F(000): 432; crystal size: 0.021 · 0.015 ·
0.012 mm3; h range for data collection 2.5–30.6ꢁ; complete-
ness to h: 30.6ꢁ, 99.7%; refinement method: full-matrix
least-square on F2; data/restraints/parameters: 3275/0/
4.4.4. (3R,7aS)-(+)-3-(Furan-2-yl)-3,4,7,7a-tetrahydrocyclo-
29
penta[c]pyran-6(1H)-one, (ꢀ)-8. ½aꢁD ¼ ꢀ95:7 (c 3.6,
138; goodness-of-fit on F2: 1.139; final
R indices
MeOH).
[I > 2r(I)]: R1 = 0.076, wR2 = 0.150; R indices (all data):
R1 = 0.130, wR2 = 0.171; extinction coefficient: 0.0090;
4.5. General procedure for the chemical hydrolysis of (R)-
acetates
ꢀ3
˚
largest diff. peak and hole: 0.132 and ꢀ0.123 e A
.
Crystallographic data (excluding structure factors) for the
structures of cis-(+)-7: and trans-(+)-8: in this paper have
been deposited with the Cambridge Crystallographic Data
center as supplementary publication numbers CCDC
622252 and 622253, respectively. Copies of the data can
be obtained, free of charge, on application to CCDC, 12
Union Road, Cambridge CB2 1EZ, UK [fax: +44 1223
336033 or e-mail: deposit@ccdc.cam.ac.uk].
To a solution of acetates (R)-3–4 (0.2 mmol) in methanol
(4 mL) and water (1 mL), a 1 M solution of NaOH
(0.2 mL, 0.2 mmol) was added. The mixture was stirred
at room temperature until the hydrolysis was completed
(TLC). The solution was extracted with chloroform, dried
with anhydrous Na2SO4, and evaporated to give respective
(R)-alcohols, which were purified with column chromato-
graphy eluting with a hexane–ethyl acetate mixture and
the specific rotation of these alcohols was determined.
Acknowledgement
4.6. X-ray structure analysis
¨
We thank the OYP project (BAP-08-11-DPT2002K120510)
For the crystal structure determination, the single-crystal
of compounds cis-(+)-7 (C12H12O3) and C12H12O3 trans-
(+)-8 was used for data collection on a four-circle Rigaku
R-AXIS RAPID-S diffractometer equipped with a two-
dimensional area IP detector. The graphite-monochroma-
for financial support.
References
˚
tized Mo Ka radiation (k = 0.71073 A) and oscillation
1. (a) Wu, Y.; Chang, F. R.; Duh, C. Y.; Wang, S. K.
scans technique with Dx = 5ꢁ for one image were used
for data collection. The images for cis-(+)-7 and trans-
(+)-8 were taken successfully by varying x with three sets
of different v and u values. For each compound the 108
images for six different runs covering about 99.8% of the
Ewald spheres were performed. The lattice parameters were
determined by the least-squares methods on the basis of all
reflections with F2 > 2r(F2). Integration of the intensities,
Heterocycles 1992, 34, 667; (b) Myint, S. H.; Cortes, A.;
Laurens, A.; Hocquemiller, R.; Leboeuf, M.; Cave, A.; Cotte,
J.; Quero, A. M. Phytochemistry 1991, 30, 3335; (c) Joesang,
A.; Dubaele, B.; Cave, A.; Bartoli, M. H.; Beriel, H. J. Nat.
Prod. 1991, 54, 967; (d) Cow, D.; Myint, S. H.; Hocque-
miUer, R. Tetrahedron 1991, 47, 8195; (e) Scholz, G.;
Tochtermann, W. Tetrahedron Lett. 1991, 32, 5535; (f)
Wakabaywhi, N.; Spencer, S. L.; Waters, R. M.; Lusby, W.
´
´
´
´

2986
S. Sezer et al. / Tetrahedron: Asymmetry 17 (2006) 2981–2986
R. J. Nat. Prod. 1991, 54, 1419; (g) Rieser, M. J.; Kozolowski,
90, 1; (f) Enzyme Catalysis in Organic Synthesis; Drauz, K.,
Waldmann, H., Eds.; VCH: New York, 1995; (g) Santaniello,
E.; Ferraboschi, P.; Grisenti, P.; Manzocchi, A. Chem. Rev.
1992, 92, 1071.
J. F.; Wood, K. V.; McLaughlin, J. L. Tetrahedron Lett.
1991, 32, 1137; (h) Fang, X. P.; Rupprecht, J. K.; Alkofahi,
A.; Hui, Y. H.; Liu, Y. M.; Smith, D. L.; Wood, K. V.;
McLaughlin, J. L. Heterocycles 1991, 32, 11; (i) Myint, S. H.;
6. Tanyeli, C.; Demir, A. S.; Arkın, H.; Akhmedov, I. M.
Enantiomer 1997, 2, 433.
´
Laurens, A.; Hocquemiller, R.; Cave, A.; Davoust, D.;
Cortse, D. Heterocycles 1990, 31, 861; (j) Fukuzawa, A.;
Aye, M.; Nakamura, M.; Tamura, M.; Murai, A. Tetrahe-
dron Lett. 1990, 31, 4895; (k) Hisham, A.; Pieters, L. A. C.;
Claeys, M.; Esmans, E.; Dommisse, R.; Wetinck, A. J.
Tetrahedron Lett. 1990, 31, 4649; (l) Ojika, M.; Yoehida, Y.;
Nakayama, Y.; Yamada, K. Tetrahedron Lett. 1990, 31, 4907;
(m) Otsuka, M.; Nishio, T.; Oshitari, T.; Owa, T.; Sugiura,
Y.; Maeda, K.; Ohno, M.; Kobayaahi, S. Heterocycles 1992,
33, 27; (n) Barrett, A. G. M.; Lebold, S. A. J. Org. Chem.
1991, 56, 4875; (o) Funayama, S.; Ishibashi, M.; Komiyama,
K.; Omura, S. J. Org. Chem. 1990, 55, 1132; (p) Kogen, H.;
Kadokawa, H.; Kurabayshi, M. J. Chem. Soc., Chem.
Commun. 1990, 1240; (q) Paquette, L. A.; Sweeney, T. J. J.
Org. Chem. 1990, 55, 1703; (r) Commercon, A.; Poesinet, G.
Tetrahedron Lett. 1990, 31, 3871.
7. (a) Sing, S.; Kumar, S.; Chimni, S. Tetrahedron: Asymmetry
2002, 13, 2679; (b) Bierstedt, A.; Sto¨lting, J.; Fro¨hlich, R.;
Metz, P. Tetrahedron: Asymmetry 2001, 12, 3399; (c) Holm-
berg, P.; Karlsson, J.; Gogoll, A. Tetrahedron: Asymmetry
2005, 16, 2397; (d) Krishna, U. M.; Srikanth, G. S. C.;
Trivedi, G. K. Tetrahedron: Asymmetry 2003, 44, 8227.
8. (a) Khand, I. U.; Knox, G. R.; Pauson, P. L.; Watts, W. E. J.
Chem. Soc., Perkin Trans. 1 1973, 975; Recent reviews of the
Pauson–Khand reaction: (b) Schore, N. E. In Comprehensive
Organometallic Chemistry II; Hegedus, L. S., Ed.; Pergamon:
Oxford, 1995; Vol. 12, p 703; (c) Geis, O.; Schmalz, H. G.
Angew. Chem., Int. Ed. 1998, 37, 911; (d) Jeong, N. In
Transition Metals in Organic Synthesis; Beller, M., Bolm, C.,
Eds.; Wiley-VCH: Weinheim, Germany, 1998; Vol. 1, p 560;
(e) Brummond, K. M.; Kent, J. L. Tetrahedron 2000, 56,
3263; (f) Bonaga, L. V. R.; Krafft, M. E. Tetrahedron 2004,
60, 9795.
2. (a) Brown, H. C.; Randad, R. S.; Bhat, K. S.; Zaidelwicz, M.;
Racheria, U. S. J. Am. Chem. Soc. 1990, 112, 2389; (b)
Racheria, U. S.; Brown, H. C. J. Org. Chem. 1991, 56, 401; (c)
Racheria, U. S.; Liao, Y.; Brown, H. C. J. Org. Chem. 1992,
57, 6614.
3. (a) Deeter, J.; Frazier, J.; Staten, G.; Staszak, M.; Wiegel, L.
Tetrahedron Lett. 1990, 31, 7101; (b) Farr, R. A.; Peet, N. P.;
Kang, M. S. Tetrahedron Lett. 1990, 31, 7109; (c) Soai, K.;
Hori, H.; Niwa, S. Heterocycles 1989, 29, 2065; (d) Kusakabe,
M.; Kitano, Y.; Kobayashi, Y.; Sato, F. J. Org. Chem. 1989,
54, 2085; (e) Kametani, T.; Tsubuki, M.; Tatsuzaki, Y.;
Honda, T. J. Chem. Soc., Perkin Trans. 1 1990, 639; (f) Jian-
Xin, G.; Zu-Yi, L.; Guo-Qiang, L. Tetrahedron 1993, 49,
5805; (g) Kobayashi, Y.; Kusakabe, M.; Kitano, Y.; Sato, F.
J. Org. Chem. 1988, 53, 1586; (h) Soai, K.; Kawase, Y. J.
Chem. Soc., Perkin Trans. 1 1990, 3214.
4. (a) Denmark, S. E.; Fu J. Chem. Rev. 2003, 103, 2763, and
references cited therein; (b) Kwiatkowski, P.; Chaladaj, W.;
Jurczak, J. Tetrahedron 2006, 62, 5116; (c) Malkov, A.; Bell,
M.; Castelluzzo, F.; Kocovsky, P. Org. Lett. 2005, 7, 3219;
(d) Zhu, S.; Yang, Y.; Wang, L.; Liu, B.; Zhou, Q. Org. Lett.
2005, 7, 2333; (e) Teo, Y.; Tan, K.; Loh, T. Chem. Commun.
2005, 10, 1318; (f) Xia, G.; Shibatomi, K.; Yamamoto, H.
Synlett 2004, 13, 2437; (g) Kina, A.; Shimada, T.; Hayashi, T.
Adv. Synth. Catal. 2004, 346, 1169; (h) Wong, W.; Lee, C.;
Leung, H.; Kwong, H. Org. Biomol. Chem. 2004, 2, 1967; (i)
Yanagisawa, A.; Nakamura, Y.; Arai, T. Tetrahedron:
Asymmetry 2004, 15, 1909; (j) Malkov, A.; Bell, M.; Orsini,
M.; Pernazza, D.; Massa, A.; Herrmann, P.; Kocovsky, P. J.
Org. Chem. 2003, 68, 9659; (k) Massa, A.; Malkov, A.;
Kocovsky, P.; Scettri, A. Tetrahedron Lett. 2003, 44, 9067; (l)
Shimada, T.; Kina, A.; Hayashi, T. J. Org. Chem. 2003, 68,
6329; (m) Malkov, A.; Bell, M.; Vassieu, M.; Bugatti, V.;
Kocovsky, P. J. Mol. Catal. A: Chem. 2003, 196, 179; (n) Yin,
Y.; Zhao, G.; Qian, Z.; Yin, W. J. Fluor. Chem. 2003, 120,
117; (o) Hernandez, E.; Soderquist, J. Org. Lett. 2005, 7,
5397; (p) Hyland, C.; Hegedus, L. J. Org. Chem. 2005, 70,
8628; (q) Inoue, M.; Nakada, M. Org. Lett. 2004, 6, 2977; (r)
Konishi, S.; Hanawa, H.; Maruoka, K. Tetrahedron: Asym-
metry 2003, 14, 1603; (s) Loh, T.; Lin, M.; Tan, K.
Tetrahedron Lett. 2002, 44, 507; (t) Soderquist, A.; Lai, C.
Org. Lett. 2005, 7, 799.
9. (a) Schore, N. E.; Croudace, M. C. J. Org. Chem. 1981, 46,
5436; (b) Exon, C.; Magnus, P. J. Am. Chem. Soc. 1983, 105,
2477; (c) Sugihara, T.; Yamada, M.; Yamaguchi, M.;
Nishizawa, M. Synlett 1999, 771; (d) Sugihara, T.; Yamada,
M.; Ban, H.; Yamaguchi, M.; Kaneko, C. Angew. Chem., Int.
´
Ed. 1997, 36, 2801; (e) Perez-Serrano, L.; Casarrubios, L.;
´
´
Domınguez, G.; Perez-Castells, J. Org. Lett. 1999, 1, 1187; (f)
´
´
Blanco-Urogoiti, J.; Casarrubios, L.; Domınguez, G.; Perez-
Castells, J. Tetrahedron Lett. 2002, 43, 5763; (g) Krafft, M. E.;
Bonaga, L. V. R.; Hirosawa, C. J. Org. Chem. 2002, 67, 1233;
˜
(h). Chem. Soc. Rev. 2004, 33, 32–42, and references cited
therein.
10. (a) Leeuwenburgh, M. A.; Appeldoorn, C. C. M.; Hooft, A.
V.; Overkleeft, H. S.; van der Marel, G. A.; Van Boom, J. H.
Eur. J. Org. Chem. 2000, 873; (b) Pai, A.; Bhattacharjya, A. J.
Org. Chem. 2001, 66, 9071; (c) Hotha, S.; Maurya, S. K.;
Gurjar, M. K. Tetrahedron Lett. 2005, 46, 5329.
11. (a) Ghosh, S. K.; Hsung, R. P.; Liu, J. J. Am. Chem. Soc.
2005, 127, 8260; (b) Pal, A.; Bhattacharjya, A. J. Org. Chem.
2001, 66, 9071; (c) Subburaj, K.; Okamoto, S.; Sato, F. J.
Org. Chem. 2002, 67, 1024; (d) Brummond, K. M.; Kerekes,
A. D.; Wan, H. J. Org. Chem. 2002, 67, 5156, and references
cited therein; (e) Marchueta, I.; Montenegro, E.; Panov, D.;
`
Poch, M.; Verdaguer, X.; Moyano, A.; Pericas, M. A.; Riera,
A. J. Org. Chem. 2001, 66, 6400; (f) Rivero, M. R.; Adrio, J.;
Carretero, J. C. Eur. J. Org. Chem. 2002, 2881.
¨
12. Tanyeli, C.; Akhmedov, I. M.; Ozdemirhan, D. Enantiomer
2001, 259.
13. Enzymatic resolution of compound ( )-1 was carried out by
using the procedure given in Ref. 7a. The same conditions
were applied to substrate ( )-2. The absolute configurations
of (ꢀ)-1 and (+)-2 were found to be (S) as reported.7a,4t
14. We applied the conditions given in Ref. 6.
15. Final compounds were identified and characterized by 1H
NMR, 13C NMR, FTIR, COSY, HMBC, HMQC and
HRMS, and/or elemental analysis. The new chiral center on
the final products can be discerned in the X-ray structure
relative to homoallylic and homopropargylic alcohols.
16. Rigaku, CrystalClear, Version 1.3.6. Rigaku American Cor-
poration, 9009 New Trails Drive, The Woodlands, TX 77381-
5209, USA; 2005.
5. Reviews: (a) Faber, K. Biotransformations in Organic Chem-
istry; Springer: Berlin, 1992; (b) Sih, C. J.; Wu, S. H. Top.
Stereochem. 1989, 19, 63; (c) Chen, C. S.; Sih, C. Angew.
Chem., Int. Ed. Engl. 1989, 28, 695; (d) Klibanov, A. M. Acc.
Chem. Res. 1990, 23, 114; (e) Ward, S. C. Chem. Rev. 1990,
17. Sheldrick, G. M. SHELXS97 and SHELXL97; University of
Go¨ttingen: Germany, 1997.
18. Stephenson, L. M.; Gemmer, R. V.; Current, S. P. J. Org.
Chem. 1977, 42, 1977.