Stereoselective synthesis of optically active cyclopenta[c]pyrans and cyclopenta[c]furans by the intramolecular Pauson-Khand reaction

Article abstract of DOI:10.1016/j.tetasy.2010.02.016

An intramolecular Pauson-Khand reaction of enynes derived from homoallyl, homopropargyl, and allyl alcohols is described. 2-Heteroaryl-substituted homoallyl, homopropargyl, and allyl alcohols are easily and efficiently resolved through enzymatic resolution in high ee (91-99%) and with a known stereochemistry. Each enantiomerically enriched enyne derived from homoallyl and homopropargyl alcohols affords the conformationally most stable diastereomeric cyclopenta[c]pyran ring system as the sole product, whereas enantiomerically enriched enynes derived from allyl alcohols give a diastereomeric cis:trans mixture of the cyclopenta[c]furan ring system.

Full text of DOI:10.1016/j.tetasy.2010.02.016

Tetrahedron: Asymmetry 21 (2010) 476–485
Contents lists available at ScienceDirect
Tetrahedron: Asymmetry
journal homepage: www.elsevier.com/locate/tetasy
Stereoselective synthesis of optically active cyclopenta[c]pyrans and
cyclopenta[c]furans by the intramolecular Pauson–Khand reaction
Serdar Sezer a, Ertan Sßahin b, Cihangir Tanyeli a,
*
a Department of Chemistry, Middle East Technical University, 06531 Ankara, Turkey
b Department of Chemistry, Atatürk University, 25240 Erzurum, Turkey
a r t i c l e i n f o
a b s t r a c t
Article history:
An intramolecular Pauson–Khand reaction of enynes derived from homoallyl, homopropargyl, and allyl
alcohols is described. 2-Heteroaryl-substituted homoallyl, homopropargyl, and allyl alcohols are easily
and efficiently resolved through enzymatic resolution in high ee (91–99%) and with a known stereochem-
istry. Each enantiomerically enriched enyne derived from homoallyl and homopropargyl alcohols affords
the conformationally most stable diastereomeric cyclopenta[c]pyran ring system as the sole product,
whereas enantiomerically enriched enynes derived from allyl alcohols give a diastereomeric cis:trans
mixture of the cyclopenta[c]furan ring system.
Received 25 January 2010
Accepted 19 February 2010
Available online 16 March 2010
Ó 2010 Elsevier Ltd. All rights reserved.
1. Introduction
of enantioselective processes because of the fact that mild and
environmentally friendly conditions are applied to the production
The investigation of new methods for the synthesis of chiral
complex molecules of natural or synthetic origin remains a chal-
lenge.1 Amongst these methods, the Pauson–Khand reaction
(PKR)2 is widely used for the construction of cyclopentenone ring
systems.3 The intramolecular version of the reaction has gained
much popularity since it can afford cyclopentenone-fused ring sys-
tems, which are difficult to construct.4 It has also been used as a
key step in the synthesis of a number of natural products including
hirsutene,5 kainic acid,6 pentalenene,7 epoxydicytymene,8 incarvil-
line,9 paecilomycine A,10 magellanine, magellaninone, and panicul-
atine.11 Asymmetric versions of the PKR have been carried out by
the use of chiral auxiliaries,12 chiral metal complexes,13 and chiral
cyclization precursors.14
Chiral allylic, homoallylic, and homopropargylic alcohols are all
good candidates for preparing chiral enyne systems because of
their oxygen-anchoring site.15 The development of convenient
synthetic routes to prepare enantiomerically enriched heteroaryl-
substituted allyl, homoallyl, and homopropargyl alcohols has
attracted considerable attention because these compounds consti-
tute advanced intermediates for many natural compounds.16
Although a wide range of synthetic procedures including the
asymmetric allyl boration of heterocyclic aldehydes with diterpe-
nylallylboranes,17 and catalytic enantioselective allylation and
propargylation methods18 has been reported, the most convenient
synthesis of enantiomerically enriched alcohols is carried out with
biocatalysts.19 Biocatalytic approaches have emerged over the last
few decades as a powerful and alternative tool for the development
of chiral compounds. In many cases, enzymatic resolution can be
very useful if it works well for individual alcohols. We reported
the first enzyme-catalyzed resolution of racemic furyl20 and thie-
nylcarbinols21 with high enantiomeric purity and good total yields.
This approach was used recently by some other groups.22
As part of our continuing series of studies to study the effect of
conformational control on remote stereochemistry in the intramo-
lecular PKR, we recently reported the intramolecular PKR results of
chiral enyne systems anchored to a chiral 2-furylcarbinol23 and
camphor24 scaffolds. In particular, the excellent conformational
control property of pyran rings formed in the aforementioned
works prompted us toward the development of diastereomerically
enriched heteroaryl-substituted cyclopenta-pyran and furan units.
To the best of our knowledge, the intramolecular PKR has not been
utilized for the synthesis of heteroaryl-substituted cyclo-
penta[c]pyran and cyclopenta[c]furan units using enantiomerically
enriched allylic, homoallylic, and homopropargylic alcohol tem-
plates. Herein, we report a simple route to synthesize
a-heteroa-
rylcarbinol-anchored chiral cyclopentenone-pyran I–II and furan
systems III–IV with excellent and acceptable diastereoselectivities,
respectively (Fig. 1).
2. Results and discussion
The addition of vinylic, allylic, and propargylic nucleophiles to
carbonyl groups is one of the most effective methods for the con-
struction of allylic, homoallylic, and homopropargylic alcohols,
respectively. In the same manner, the parent allylic alcohols
rac-4a–c and homoallylic alcohols rac-2a–b were synthesized by
the addition of vinylmagnesium bromide and allylmagnesium
* Corresponding author. Tel.:+90 312 210 3222; fax: +90 312 210 3200.
E-mail address: tanyeli@metu.edu.tr (C. Tanyeli).
0957-4166/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2010.02.016

S. Sezer et al. / Tetrahedron: Asymmetry 21 (2010) 476–485
477
the complexation of nitrogen with the Zn–Cu couple. In order
to overcome this problem, we applied another procedure as de-
scribed in our previous work24 in which catalytic amount of HgCl2
is added to the mixture of propargyl bromide and Mg in dry
ether.
H
O
H
O
H
R
R
O
O
O
O
H
H
II
I
Initially, the enantiomeric resolutions of homoallylic rac-2a–b
and homopropargylic alcohols rac-3a–b were performed by using
Pseudomonas cepacia lipase (PS-C II) and vinyl acetate as an acyl
donor and THF as a solvent at 24 °C according to the procedure gi-
ven in the literature22a and in our related work.23 All the reactions
were carried out by using a substrate/enzyme ratio 1:1 (w/w) and
afforded excellent enantioselectivities which varied between 95%
and 99% ee (Table 1, entries 1, 3, 5, and 7, respectively). We also
planned to study the enzyme-mediated resolution of the same sub-
strates with immobilized lipases from Thermomyces lanuginosus li-
pase (Lipozyme TL IM) and Candida antarctica lipase B (CAL-B,
Novozym 435). Lipozyme TL IM also gave excellent enantioselec-
tivities which varied between 85% and 99% ee by using vinyl ace-
tate as an acyl donor and DIPE as solvent at 30 °C (Table 1,
entries 2, 4, 6, and 8, respectively). Although the enantioselectivi-
ties were very similar, the resolutions with Lipozyme TL IM
required longer reaction times compared with PS-C II resolutions.
CAL-B, as a biocatalyst, was not an adequate lipase and the results
are not given in Table 1, since all the resolutions did not reach 50%
conversion value.
H
H
H
R
R
O
O
III
IV
R = Furyl, Thienyl, Pyridyl
Figure 1. Higly diastereoselective PKR products.
bromide to the commercially available 2-heteroarylcarbaldehy-
des, respectively, as shown in Scheme 1. However, homopropar-
gylic alcohols rac-3a–b could not be obtained with the same
procedure. We have recently reported a procedure in which the
addition of propargyl bromide to a carbonyl group proceeds
readily by using a Zn–Cu couple.21,23 Although the synthesis of
homopropargyl alcohol rac-3a was achieved in high yield with
this strategy, pyridyl-substituted homopropargylic alcohol
rac-3b could not be synthesized. This was presumably due to
O
1
R
R
R
R
R
b or c
R
a
e
e
R
H
+
+
OH
OAc
OH
OH
OAc
OH
rac-2a-b
rac-3a-b
d
(S)-3a-b
(R)-6a-b
(S)-2a-b
(R)-5a-b
R
OH
S
S
N
N
rac-4a-c
OH
OH
OH
OH
e
(S)-(-)-2a
(S)-(-)-2b
(S)-(-)-3b
(S)-(+)-3a
R
R
+
S
S
N
O
N
O
OH
(S)-4a-c
OAc
(R)-7a-c
O
O
O
(R)-(+)-6a
O
O
O
(R)-(+)-5a
(R)-(+)-5b
(R)-(+)-6b
O
S
N
OH
OH
OH
(S)-(+)-4a
(S)-(-)-4b
(S)-(+)-4c
R=
,
,
O
S
N
S
O
N
O
O
O
(R)-7b
(R)-7a
O
O
O
(R)-(+)-7c
Decomposed on silica
Scheme 1. Reagents: (a) allylbromide, Mg, I2, dry ether; (b) propargyl bromide, Zn–Cu, dry THF for 3a; (c) propargyl bromide, HgCl2, Mg, I2, dry ether for 3b; (d)
vinylmagnesium bromide (1 M in THF), dry ether; (e) lipase, vinyl acetate, THF.

478
S. Sezer et al. / Tetrahedron: Asymmetry 21 (2010) 476–485
Table 1
Enzymatic kinetic resolution of homoallylic and homopropargylic alcohols rac-2a–b and rac-3a–b
Entry
Substrate
Enzyme
Time (h)
Estersd
eep (%)
Alcoholsd
ees (%)
cb (%)
Ec
a
a
1
2
3
4
5
6
7
8
rac-2a
rac-2a
rac-2b
rac-2b
rac-3a
rac-3a
rac-3b
rac-3b
PS-C Amona IIe
Lipozyme IMf
PS-C Amona IIe
Lipozyme IMf
PS-C Amona IIe
Lipozyme IMf
PS-C Amona IIe
Lipozyme IMf
20
23
30
49
2.5
24
25
43
40 (R)
91 (R)
95 (R)
98 (R)
92 (R)
80 (R)
92 (R)
75 (R)
99 (S)
85 (S)
98 (S)
94 (S)
99 (S)
99 (S)
95 (S)
98 (S)
71
48
51
49
52
56
51
57
11
67
154
327
116
41
82
30
a
b
c
d
e
f
Determined by HPLC analysis employing Diacel Chiralcel OD-H and OJ-H columns.
c = ees/(ees + eep).
E = ln[(1 ꢀ c)(1 ꢀ ees)]/ln[(1 ꢀ c)(1 + ees)].25
The absolute configurations were found to be (S) for alcohols and (R) for esters according to the specific rotations reported in the literature.
The reactions were carried out at 24 °C.
The reactions were carried out at 30 °C.
In the second part, the enzymatic kinetic resolution of allylic
cisely the applicability of the intramolecular PKR of enynes
anchored to chiral 2-heteroarylcarbinols and to support the data
given in our previous study23 on the control of remote stereo-
chemistry in the synthesis of cyclopentenone-pyran ring
systems, compounds (S)-8–11 were subjected to the most com-
mon conditions for PKR (Scheme 2). In this protocol, cobalt
alkyne complexes were prepared using enyne-dicobalt octacar-
bonyl in a molar ratio of 1.0:1.7 in DCM, and then N-methyl-
morpholine N-oxide monohydrate was added as a promoter.
The reactions were monitored by thin layer chromatography
(TLC). In all cases, single diastereomers of cyclopentenone-pyran
products (+)-12–15 were obtained as established by NMR spec-
troscopy (Scheme 2).26
The relative configuration of (+)-12 was determined by differen-
tial NOE experiments. The characteristic methine proton attached
to the stereogenic carbon of the pyran ring at 4.82 ppm and the
methine proton of cyclopentenone-pyran-fused position carbon
at 3.00–3.03 ppm showed significant NOE enhancements, which
indicate the cis-relationship between the stereogenic center pro-
tons. The configuration of (+)-13 was also determined by differen-
tial NOE experiments. In the differential NOE experiments of (+)-
13, we observed significant NOE enhancement between the
methine proton attached to the stereogenic carbon of the pyran
ring at 4.68 ppm and the methine proton of the newly created ste-
reogenic carbon center at 3.03–3.09 ppm; we hence decided that
the methine protons were in a cis-relationship (Fig. 2). Thus, the
absolute configurations of (+)-12 (cis-1,3) and (+)-13 (cis-1,3) were
determined as (3S,4aR).
alcohols rac-4a–c was performed by PS-C II and CAL-B using the
procedure given above. The results of these studies are summa-
rized in Table 2. As can be seen in Table 2, rac-4a was first tested
with PS-C II in vinyl acetate used both as an acyl donor and as
the solvent at 27 °C and afforded (S)-4a in 51% ee (entry 1). When
the resolution was carried out in THF under the same conditions,
we observed a substantial increase in the ee and conversion values
as 77% and 48%, respectively (entry 2). Based on these results, the
conversions were 54% and 60% and the alcohol (S)-4a was isolated
with excellent ee values of 92% and 99%, respectively (entries 3 and
4). These results show that the increase in conversion had an effect
on the ee value of the alcohol. When substrate rac-4a was sub-
jected to CAL-B-mediated acetylation under the same reaction con-
ditions, similar excellent results were obtained in terms of
enantioselectivity (99% ee, entry 5). In the case of rac-4b, PS-C II-
mediated acetylation afforded (S)-4b with 83% ee (entry 6),
whereas CAL-B showed the highest ee value (97%, entry 7). As a re-
sult of the decomposition during the chromatographic separation
of acetylated products (R)-7a and (R)-7b, we could not determine
their ee values. In the PS-C II-mediated resolution of rac-4c, the
conversion did not exceed 10%, while on the other hand, CAL-B-
mediated acetylation afforded the alcohol (S)-4c with 48% conver-
sion and 91% ee after 13 h under the same conditions applied to the
other substrates (entry 8).
The enyne systems were first built on enantiomerically
enriched homoallylic (S)-2a–b and homopropargylic alcohol
(S)-3a–b backbones by O-propargylation and O-allylation using
propargyl bromide and allylbromide with NaH and tetrabutyl-
ammonium iodide (TBAI) in THF, respectively. To evaluate pre-
X-ray diffraction analysis of the products (+)-14 (trans-1,4) and
(+)-15 (trans-1,4) confirmed the absolute configuration of the
Table 2
Enzymatic kinetic resolution of allylic alcohols rac-4a–c
Entry
Substrate
Enzyme
Time
Temp
Conva (%)
Alcoholsd
ees (%)
Solvent
b
1
2
3
4
5
6
7
8
rac-4a
rac-4a
rac-4a
rac-4a
rac-4a
rac-4b
rac-4b
rac-4c
PS-C II
PS-C II
PS-C II
PS-C II
CAL-B
PS-C II
CAL-B
CAL-B
55 min
55 min
65 min
70 min
75 min
75 min
65 min
13 h
27
27
27
26
26
26
26
30
40
48
54
60
56
47
56
48
51 (S)
77 (S)
92 (S)
99 (S)
99 (S)
83 (S)
97 (S)
91c (S)
—
THF
THF
THF
THF
THF
THF
THF
a
b
c
Determined by HPLC and NMR.
Determined by HPLC analysis employing a Diacel Chiralcel OD-H and OJ-H columns.
Ee was calculated after transformation to the corresponding acetate.
d
The absolute configurations were found to be (S) for alcohols according to the specific rotations reported in the literature.

S. Sezer et al. / Tetrahedron: Asymmetry 21 (2010) 476–485
479
H
H
a
c
c
O
O
3
1
S
S
S
O
O
OH
(+)-12 (cis-1,3)
(S)-(-)-8
(S)-2a
a
b
H
H
N
N
N
S
1
3
O
O
OH
(+)-13 (cis-1,3)
(S)-(-)-9
(S)-2b
H
c
c
O
S
1
S
4
O
O
OH
H
(S)-(-)-10
(S)-3a
(+)-14 (trans-1,4)
b
H
N
N
N
1
O
4
O
OH
O
H
(S)-3b
(S)-(-)-11
(+)-15 (trans-1,4)
single diastereomers of the
desired products
Scheme 2. Reagents: (a) propargyl bromide, NaH, TBAI, THF; (b) allylbromide, NaH, TBAI, THF; (c) Co2(CO)8, NMO, CH2Cl2.
question of why enynes (3S,4aR)-(+)-12, (3S,4aR)-(+)-13, (3S,7aR)-
(+)-14, and (3S,7aR)-(+)-15, respectively, afforded single diastereo-
mers. In all products, the new stereogenic centers located at the
fused position of cyclopentenone-pyran rings possess an (R)-con-
figuration, since the pyran rings are in the most favored chair con-
formation as expected.
On the basis of our observations given above, we decided to ex-
plore the diastereoselectivity in the construction of cyclopente-
none-furan ring systems. For this purpose, the enyne systems
were constructed on enantiomerically enriched allylic alcohol
(S)-4a–c backbones by O-propargylation using propargyl bromide
with NaH and tetrabutylammonium iodide (TBAI) in THF. The eny-
ne compounds (S)-16–18 were subsequently subjected to intramo-
lecular PKR following the procedure given above. In contrast to
pyran-based cyclic systems, chiral enynes leading to furan-fused
cyclopentenone frameworks afforded diastereomeric mixtures
(Scheme 3). This was presumably due to the reduced conforma-
tional effect of the furan rings on the diastereoselectivity compared
NOE
H
NOE
H
H
H
Ha
Hb
H
Ha
Hb
H
S
N
H
O
H
O
O
O
H
H
H
H
H
H
(+)-13 (cis-1,3)
(+)-12 (cis-1,3)
Figure 2. NOE correlations observed between Ha and Hb protons of (+)-12 (cis-1,3)
and (+)-13 (cis-1,3).
newly created stereogenic centers at the fused position of cyclo-
pentenone-pyran rings as (3S,7aR) (Fig. 3).
The differential NOE results of cyclopentenone-pyran products
(+)-12 (cis-1,3) and (+)-13 (cis-1,3) and X-ray structures of (+)-14
(trans-1,4) and (+)-15 (trans-1,4) provided an explanation to the
H
H
O
O
N
S
O
O
H
H
(3S,7aR)-(+)-14
(3S,7aR)-(+)-15
Figure 3. X-ray structures of (3S,7aR)-(+)-14 and (3S,7aR)-(+)-15. Displacement ellipsoids are shown at the 40% probability level.

480
S. Sezer et al. / Tetrahedron: Asymmetry 21 (2010) 476–485
O
H
O
H
H
H
a
a
b
O
+
O
O
O
O
OH
O
O
(+)-19 (trans-1,2)
(-)-19 (cis-1,2)
major isomer
dr: 3:1
(S)-(+)-4a
(S)-(-)-16
minor isomer
O
O
H
H
H
H
b
b
+
S
S
S
S
O
OH
O
O
(+)-20 (trans-1,2)
(-)-20 (cis-1,2)
dr: 3:1
(S)-(-)-4b
(S)-(-)-17
minor isomer
major isomer
O
O
a
H
H
N
O
H
H
N
O
+
N
N
OH
O
(S)-(-)-18
(+)-21 (trans-1,2)
(-)-21 (cis-1,2)
dr: 3.5:1.5
(S)-(+)-4c
minor isomer
major isomer
Scheme 3. Reagents: (a) propargyl bromide, NaH, TBAI, THF; (b) Co2(CO)8, NMO, CH2Cl2. Diastereomeric ratios (drs) were determined by 1H NMR.
to the more favored chair conformation of the pyran rings. The
diastereomeric mixture of (ꢀ)-19 and (+)-19 was separated by
flash column chromatography and isolated as major and minor
products, respectively. The relative configurations of (ꢀ)-19 and
(+)-19 were determined by comparing the coupling constant val-
ues (J) of the methine protons attached to the stereogenic centers.
The 1H NMR spectrum of (ꢀ)-19 shows a doublet at 4.36 ppm with
J = 10.7 Hz for the methine proton of furan ring and a multiplet at
3.50–3.54 for the methine proton of cyclopentenone-furan-fused
position carbon, whereas the minor product (+)-19 possesses a
doublet at 5.24 ppm with J = 8.3 Hz and a multiplet at 3.54–
3.59 ppm for the corresponding methine protons, respectively.
These coupling constant values are in accordance with the litera-
ture data indicated as J = 10.7 and J = 8.3 Hz for the cis- and
trans-coupling of methine protons, respectively.27 Thus, the abso-
lute configurations of (ꢀ)-19 (cis-1,2) and (+)-19 (trans-1,2) were
determined as (3S,3aR) and (3S,3aS), respectively. We followed
the same route for the determination of the relative configurations
of (ꢀ)-20 and (+)-20 diastereomers. The 1H NMR spectrum of (ꢀ)-
20 showed a doublet at 4.56 ppm with J = 10.3 Hz for the methine
proton of furan ring and a multiplet at 3.23–3.28 for the methine
proton attached to the newly formed stereogenic carbon center,
whereas the minor (+)-20 gave a doublet at 5.55 ppm with
J = 8.3 Hz and a multiplet at 3.60–3.64 ppm for the corresponding
methine protons, respectively. According to these results, the abso-
lute configurations of (ꢀ)-20 (cis-1,2) and (+)-20 (trans-1,2) were
determined as (3S,3aR) and (3S,3aS), respectively. In contrast to
the intramolecular PKR results of (S)-(ꢀ)-16 and 17, pyridine-
substituted substrate (S)-(ꢀ)-18 afforded the (+)-21 (trans-1,2)
isomer as the major and (ꢀ)-21 (cis-1,2) as the minor product with
a diastereomeric ratio of 3.5:1.5. This result can be attributed to
the high coordination tendency of the pyridine ring nitrogen to
the alkyne–Co2(CO)6 complex and may predominantly direct the
trans-isomer formation as the major over the cis-isomer. The pre-
ferred conformers of the alkyne–Co2(CO)6 complex can be regarded
as A and B, with and without nitrogen coordination, respectively,
as shown in Figure 4. In the 1H NMR spectrum of (+)-21, the
methine proton of the furan ring and the newly generated stereo-
genic center methine proton resonate at 5.39 ppm as a doublet
with J = 8.3 Hz and at 3.74–3.80 ppm as a multiplet, respectively,
O
Hcis
O
Htrans
Hcis
N
Htrans
Co2(CO)6
N
Co
B
A
Figure 4. Conformers of the intermediates in the Pauson–Khand reactions.
whereas, the same set of (ꢀ)-21 protons resonate at 4.48 ppm as
doublet with J = 10.4 Hz and at 3.30–3.37 ppm as multiplet, respec-
tively. Depending upon these results, we determined the relative
configurations of (+)-21 and (ꢀ)-21 as trans-1,2 and cis-1,2, respec-
tively. Thus, the absolute configurations of (+)-21 (trans-1,2) and
(ꢀ)-21 (cis-1,2) were determined as (3S,3aS) and (3S,3aR),
respectively.
3. Conclusion
New enantiomerically enriched 2-thiophenyl- and pyridinyl-
substituted enynes anchored to homoallyl and homopropargyl
alcohol backbones have been synthesized. Their intramolecular
PKR showed a high conformational control on the new stereocen-
ter formed in the cyclopentenone-pyran ring system. The absolute
configurations of the products synthesized from homoallylic- and
homopropargylic-based enynes have been determined by differen-
tial NOE experiments and X-ray analysis, respectively. We have
also synthesized new enantiomerically enriched 2-heteroaryl-
substituted enynes tethered to allyl alcohol backbones, which were
subjected to intramolecular PKR. In contrast to the cyclopente-
none-pyran-fused ring systems, the resultant cyclopentenone-fur-
an-fused ring systems were isolated as cis:trans isomers with
acceptable diastereoselectivities. The absolute configurations of
them have been determined by 1H NMR. The role of the conforma-
tional control of pyrans was found to have a drastic influence on
the diastereoselectivity in comparison with the furan ring systems.

S. Sezer et al. / Tetrahedron: Asymmetry 21 (2010) 476–485
481
4.1.3. (S)-(+)-1-(Thiophen-2-yl)but-3-yn-1-ol, (S)-(+)-3a
4. Experimental
This is a yellow oil; ½a D28
¼ þ26:5 (c 1, EtOH) for 99% ee. The
ꢁ
enantiomeric purity of the product was determined by HPLC anal-
ysis (Daicel Chiralcel OJ-H, hexane/i-PrOH 96:4, flow rate = 1 -
mL minꢀ1, k = 230 nm), tR = 35.56 min [(R)-isomer], tR = 41.75 min
(S isomer) in comparison with the racemic sample.
All experiments were carried out in pre-dried glassware (1 h,
150 °C) under an inert atmosphere of argon. The following reac-
tion solvents were distilled from the indicated drying agents:
dichloromethane (P2O5), tetrahydrofuran (sodium, benzophe-
none). 1H NMR and 13C NMR spectra were recorded in CDCl3 on
Bruker Spectrospin Avance DPX-400 spectrometer. 1H (400 MHz)
and 13C NMR were recorded in CDCl3 and the chemical shifts
were expressed in ppm relative to CDCl3 (d 7.26 and 77.0 for 1H
and 13C NMR, respectively) as the internal standard. Standard
COSY, HETCOR, and DEPT experiments were performed to estab-
lish NMR assignments. Infrared spectra were recorded on a Ther-
mo Nicolet IS10 ATR-FT-IR spectrophotometer. The mass spectra
were recorded on Thermo Scientific DSQ II Single Quadrupole
GC/MS. HRMS data were obtained via LC–MS analysis performed
with APCI-Q-TOF II (Waters, Milford, MA, USA) at Mass Spectrom-
etry Facility Center for Functional Genomics University at Albany.
Optical rotations were measured employing a Rudolph research
analytical, autopol III automatic polarimeter. Melting points were
obtained on a Thomas Hoover capillary melting point apparatus
and are uncorrected.
4.1.4. (R)-(+)-1-(Thiophen-2-yl)but-3-ynyl acetate, (R)-(+)-6a
This is a yellow oil; ½a D29
¼ þ73:4 (c 1, EtOH) for 93% ee. The
ꢁ
enantiomeric purity of the product was determined by HPLC anal-
ysis (Daicel Chiralcel OJ-H, hexane/i-PrOH 96:4, flow rate = 1 -
mL minꢀ1, k = 230 nm), tR = 11.53 min [(S)-isomer], tR = 14.31 min
[(R)-isomer] in comparison with the racemic sample.
4.1.5. (S)-(ꢀ)-1-(Pyridin-2-yl)but-3-en-1-ol, (S)-(ꢀ)-2b
This is a yellow oil; ½a D29
¼ ꢀ42:9 (c 0.86, CH2Cl2) for 98% ee. The
ꢁ
enantiomeric purity of the product was determined by HPLC anal-
ysis (Daicel Chiralcel OJ-H, hexane/i-PrOH 99:1, flow rate = 0.3 -
mL minꢀ1, k = 254 nm), tR = 58.75 min [(S)-isomer], tR = 63.74 min
[(R)-isomer] in comparison with the racemic sample.
4.1.6. (R)-(+)-1-(Pyridin-2-yl)but-3-enyl acetate, (R)-(+)-5b
This is a yellow oil; ½a D30
¼ þ49:7 (c 0.5, CH2Cl2) for 95% ee. The
ꢁ
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 chromatography using pre-
coated silica gel plates (Merc Silica Gel PF-254), visualized by UV-
light and polymolybdenum phosphoric acid in ethanol as appropri-
ate. All extracts were dried over anhydrous magnesium sulfate and
the solutions were concentrated in vacuo by using a rotary
evaporator.
enantiomeric purity of the product was determined by HPLC anal-
ysis after conversion to alcohol.
4.1.7. (S)-(ꢀ)-1-(Pyridin-2-yl)but-3-yn-1-ol, (S)-(ꢀ)-3b
This is a yellow oil but after a short time turned black;
½
a 2D8
ꢁ
¼ ꢀ6:7 (c 1, CH2Cl2)30a for 99% ee. The enantiomeric purity
of the product was determined by HPLC analysis (Daicel Chiralcel
OJ-H, hexane/i-PrOH 99:1, flow rate = 0.3 mL minꢀ1, k = 254 nm),
tR = 90.56 min [(R)-isomer] tR = 97.90 min (S isomer) in comparison
with the racemic sample. The absolute configuration of the com-
All the racemic secondary alcohols 2a,21 2b,21 3a,21 3b,24 4a,20
4b,21 and 4c,20 were prepared by reported procedures. The abso-
lute configurations were found to be (S) for alcohols (S)-(ꢀ)-2a,21
(S)-(ꢀ)-2b,22a (S)-(+)-3a,21 (S)-(ꢀ)-3b,22a,30b (S)-(+)-4a,20 (S)-(ꢀ)-
4b,21 and (S)-(+)-4c28 according to the specific rotations reported
in references.
pound was determined by comparing
a value after conversion to
its saturated form.30b
4.1.8. (R)-(+)-1-(Pyridin-2-yl)but-3-ynyl acetate, (R)-(+)-6b
This is a yellow oil but after a short time turned black;
4.1. General procedure for enzymatic resolution
½
a 2D7
ꢁ
¼ þ44:0 (c 0.5, CH2Cl2) for 75% ee. The enantiomeric purity
of the product was determined by HPLC analysis (Daicel Chiralcel
OJ-H, hexane/i-PrOH 97:3, flow rate = 1 mL minꢀ1, k = 254 nm),
tR = 11.20 min [(R)-isomer], tR = 12.64 min [(S)-isomer] in compar-
ison with the racemic sample.
To a solution of the ( )-2a–b, 3a–b, and 4a–c (3 mmol) in anhy-
drous co-solvent (THF for PS-C II and CAL-B, DIPE for Lipozyme)
(3 mL) and vinyl acetate (2.7 mL) in a 25 mL round-bottomed flask
was added lipase (1 equiv w/w). The reaction mixture was stirred
at a constant temperature29 and monitored by TLC and recorded
on HPLC. At the desired conversion, the reaction mixture was fil-
tered off, the solid was washed with Et2O, and the solvent was
evaporated in vacuo to give a residue which was purified by col-
umn chromatography on silica gel. The experiments were repeated
at least twice.
4.1.9. (S)-(+)-1-(Furan-2-yl)prop-2-en-1-ol, (S)-(+)-4a
This is a yellow oil; ½a D28
¼ þ1:1 (c 2.24, CHCl3) for 98% ee. The
ꢁ
enantiomeric purity of the product was determined by HPLC anal-
ysis (Daicel Chiralcel OJ-H, hexane/i-PrOH 96:4, flow rate = 1 -
mL minꢀ1, k = 230 nm), tR = 18.26 min [(S)-isomer], tR = 19.75 min
[(R)-isomer] in comparison with the racemic sample.
4.1.1. (S)-(ꢀ)-1-(Thiophen-2-yl)but-3-en-1-ol, (S)-(ꢀ)-2a
4.1.10. (S)-(ꢀ)-1-(Thiophen-2-yl)prop-2-en-1-ol, (S)-(ꢀ)-4b
This is a yellow oil; ½a D27
¼ ꢀ17:1 (c 1.2, CH2Cl2) for 99% ee. The
ꢁ
This is a yellow oil; ½a D28
¼ ꢀ2:7 (c 1, CHCl3) for 97% ee. The
ꢁ
enantiomeric purity of the product was determined by HPLC anal-
ysis (Daicel Chiralcel OJ-H, hexane/i-PrOH 96:4, flow rate = 1 -
mL minꢀ1, k = 230 nm), tR = 12.98 min [(S)-isomer], tR = 15.01 min
[(R)-isomer] in comparison with the racemic sample.
enantiomeric purity of the product was determined by HPLC anal-
ysis (Daicel Chiralcel OJ-H, hexane/i-PrOH 96:4, flow rate = 1 -
mL minꢀ1, k = 230 nm), tR = 20.93 min [(S)-isomer], tR = 27.14 min
[(R)-isomer] in comparison with the racemic sample.
4.1.2. (R)-(+)-1-(Thiophen-2-yl)but-3-enyl acetate, (R)-(+)-5a
4.1.11. (S)-(+)-1-(Pyridin-2-yl)prop-2-en-1-ol, (S)-(+)-4c
This is a yellow oil; ½a D29
¼ þ84:0 (c 1, CH2Cl2) for 91% ee. The
ꢁ
This is a yellow oil; ½a D29
¼ þ54:8 (c 1.84, CHCl3) for 91% ee. The
ꢁ
enantiomeric purity of the product was determined by HPLC
enantiomeric purity of the product was determined by HPLC anal-
ysis after conversion to an acetate (Daicel Chiralcel OJ-H, hexane/i-
PrOH 99:1, flow rate = 1 mL minꢀ1, k = 254 nm), tR = 34.23 min
[(R)-isomer], tR = 35.90 min [(S)-isomer] in comparison with the
racemic sample.
analysis (Daicel Chiralcel OJ-H, hexane/i-PrOH 96:4, flow
rate = 1 mL minꢀ1
,
k = 230 nm),
tR = 8.58 min
[(S)-isomer],
tR = 19.86 min [(R)-isomer] in comparison with the racemic
sample.

482
S. Sezer et al. / Tetrahedron: Asymmetry 21 (2010) 476–485
4.1.12. (R)-(+)-1-(Pyridin-2-yl)allyl acetate, (R)-(+)-7c
4.2.4. (S)-(ꢀ)-2-(1-(Allyloxy)but-3-ynyl)pyridine, (S)-(ꢀ)-11
This is a yellow oil; ½a D27
ꢁ
¼ þ36:4 (c 1.84, CHCl3) for 99% ee. The
This is a yellow oil (0.23 g, 90% yield). ½a D29
¼ ꢀ63:6 (c 0.9,
ꢁ
enantiomeric purity of the product was determined by HPLC anal-
ysis after conversion to acetate (Daicel Chiralcel OJ-H, hexane/i-
PrOH 99:1, flow rate = 1 mL minꢀ1, k = 254 nm), tR = 32.40 min
[(R)-isomer], tR = 35.10 min [(S)-isomer] in comparison with the
racemic sample.
CH2Cl2). 1H NMR (CDCl3): d 8.49 (d, J = 4.61 Hz, 1H), 7.63 (t,
J = 7.5 Hz, 1H), 7.41 (d, J = 7.84 Hz, 1H), 7.06–7.18 (m, 1H), 5.85
(ddd, J = 5.5, 10.8 and 16.3 Hz, 1H), 5.19–5.23 (dm, J = 17.2 Hz,
1H), 5.08–5.11 (dm, J = 10.4 Hz, 1H), 4.57 (t, J = 6.0 Hz, 1H),
3.99 (dd, J = 5.2 and 12.8 Hz, 1H), 3.91 (dd, J = 5.7 and 12.8 Hz,
1H), 2.73 (ddd, J = 2.5, 5.5 and 16.8 Hz, 1H), 2.64 (dd, J = 6.4
4.2. General procedure for O-allylation and O-propargylation
and 16.8 Hz, 1H), 1.86 (s, 1H). 13C NMR (CDCl3):
d 160.2,
149.1, 136.5, 134.3, 122.7, 121.0, 117.2, 80.5, 80.0, 70.5, 70.1,
26.1. Anal. Calcd C, 76.98; H, 7.00; N, 7.48. Found: C, 77.12; H,
7.21; N, 7.33.
To a solution of (S)-(ꢀ)-2a and (S)-(ꢀ)-2b or (S)-(+)-3a and (S)-
(ꢀ)-3b, or (S)-(+)-4a, (S)-(ꢀ)-4b, and (S)-(+)-4c (1.4 mmol) in dry
THF (15 mL) was added NaH (0.62 g, 60% dispersion in oil,
1.54 mmol) under argon. The solution was heated at reflux until
H2 gas was removed completely (nearly 45 min). Allylbromide or
propargyl bromide (1.54 mmol) was then added dropwise followed
by tetrabutylammonium iodide (0.5 mmol). The mixture was re-
fluxed for another 2 h and hydrolyzed by the cautious addition of
water (15 mL). The aqueous layer was extracted with ether
(3 ꢂ20 mL). The combined organic phase was dried over MgSO4
and evaporated in vacuo. The crude product mixtures were sepa-
rated by flash column chromatography using ethylacetate/hexane
solvent as eluent (1:6) system for compounds (S)-(ꢀ)-8, (S)-(ꢀ)-
10, (S)-(ꢀ)-16, and (S)-(ꢀ)-17 and (1:1) system for compounds
(S)-(ꢀ)-9, (S)-(ꢀ)-11, and (S)-(ꢀ)-18. The products (S)-(ꢀ)-8, (S)-
(ꢀ)-9, (S)-(ꢀ)-10, (S)-(ꢀ)-11, (S)-(ꢀ)-16, (S)-(ꢀ)-17, and (S)-(ꢀ)-
18 were obtained with 80%, 89%, 82%, 90%, 78%, 80%, and 41% yield,
respectively.
4.2.5. (S)-(ꢀ)-2-(1-(Prop-2-ynyloxy)allyl)furan, (S)-(ꢀ)-16
This is a yellow oil (0.18 g, 78% yield). ½a D20
¼ ꢀ7:1 (c 1, CH2Cl2).
ꢁ
1H NMR (CDCl3): d 7.31–7.33 (m, 1H,), 6.21–6.83 (m, 2H), 5.93
(ddd, J = 6.8, 10.3 and 17.2 Hz, 1H), 5.29–5.34 (dm, J = 17.2 Hz,
1H), 5.23–5.25 (dm, J = 10.3 Hz, 1H), 5.00 (d, J = 6.7 Hz, 1H), 4.09
(dd, JAB = 2.4 and 15.8 Hz, 1H), 4.01 (dd, JAB = 2.4 and 15.8 Hz,
1H), 2.34 (t, J = 2.4 Hz, 1H). 13C NMR (CDCl3): d 151.5, 141.6,
133.4, 117.4, 109.1, 107.5, 78.4, 73.6, 73.0, 54.1. IR (neat): 2960,
1092, 799 cmꢀ1. MS (EI) m/z (rel. intensity) 162 (M+, 4), 107 (62),
95 (base). Anal. Calcd C, 74.06; H, 6.21. Found: C, 74.02; H, 6.18.
4.2.6. (S)-(ꢀ)-2-(1-(Prop-2-ynyloxy)allyl)thiophene, (S)-(ꢀ)-17
This is a yellow oil (0.2 g, 80% yield). ½a D22
¼ ꢀ13:4 (c 1, CH2Cl2).
ꢁ
1H NMR (CDCl3): d 7.19 (dd, J = 1.2 and 5.0 Hz, 1H), 6.91–6.92 (dm,
J = 3.4 Hz, 1H), 6.87–6.89 (m, 1H), 5.91 (ddd, J = 6.8, 10.2 and
17.0 Hz, 1H), 5.27–5.33 (dm, J = 17.1 Hz, 1H), 5.20–5.23 (m, 2H),
4.10 (dd, JAB = 2.4 and 15.9 Hz, 1H), 4.02 (dd, JAB = 2.4 and
15.9 Hz, 1H), 2.33 (t, J = 2.3 Hz, 1H). 13C NMR (CDCl3): d 143.8,
137.4, 126.8, 126.0, 125.9, 118.0, 79.8, 76.7, 75.0, 55.3. IR (neat):
1264, 736 cmꢀ1. MS (EI) m/z (rel. intensity) 151 (M+ꢀ27(+CH@CH2),
base), 111 (30). Anal. Calcd C, 67.38; H, 5.65; S, 17.99. Found: C,
67.37; H, 5.65; S, 17.97.
4.2.1. (S)-(ꢀ)-2-(1-(Prop-2-ynyloxy)but-3-enyl)thiophene, (S)-
(ꢀ)-8
This is a yellow oil (0.21 g, 80% yield). ½a D28
¼ ꢀ97:6 (c 1.3,
ꢁ
CH2Cl2). 1H NMR (CDCl3): d 7.22 (d, J = 4.9 Hz, 1H), 6.88–6.94 (m,
2H), 5.66–5.76 (m, 1H), 4.97–5.05 (m, 2H), 4.76 (t, J = 6.8 Hz, 1H),
4.08 (dd, JAB = 2.4 and 15.8 Hz, 1H), 3.86 (dd, JAB = 2.3 and
15.8 Hz, 1H), 2.60–2.67 (m, 1H), 2.44–2.51 (m, 1H), 2.34 (s, 1H).
13C NMR (CDCl3): d 144.1, 134.0, 126.4, 126.3, 125.5, 117.5, 79.7,
75.5, 74.4, 55.3, 42.4. IR (neat): 2973, 1088, 1047, 880 cmꢀ1. MS
(EI) m/z (rel. intensity) 151 (M+ꢀ41(+CH2CH@CH2), base). Anal.
Calcd C, 68.71; H, 6.29; S, 16.68. Found: C, 68.69; H, 6.24; S, 16.63.
4.2.7. (S)-(ꢀ)-2-(1-(Prop-2-ynyloxy)allyl)pyridine, (S)-(ꢀ)-18
This is a yellow oil (0.1 g, 41% yield). ½a D15
¼ ꢀ7:0 (c 1, CH2Cl2).
ꢁ
1H NMR (CDCl3): d 8.51 (d, J = 4.8 Hz, 1H), 7.64 (td, J = 1.8 and
7.7 Hz, 1H), 7.40 (d, J = 7.9 Hz, 1H), 7.12–7.15 (m, 1H), 5.90
(ddd, J = 7.1, 10.3 and 17.3 Hz, 1H), 5.37–5.41 (dm, J = 17.2 Hz,
1H), 5.25–5.28 (dm, J = 10.3 Hz, 1H), 5.08 (d, J = 7.1 Hz, 1H), 4.17
(d, J = 2.4 Hz, 2H), 2.37 (t, J = 2.4 Hz, 1H). 13C NMR (CDCl3): d
158.8, 148.2, 135.9, 135.4, 121.7, 120.2, 117.5, 81.4, 78.5, 73.6,
54.8. IR (neat): 2958, 1069, 803 cmꢀ1. MS (EI) m/z (rel. intensity)
134 (M+ꢀ39(+CH2C„CH), 78), 118 (M+ꢀ45(+OCH2C„CH), base).
Anal. Calcd C, 76.28; H, 6.40; N, 8.09. Found: C, 76.26; H, 6.38;
N, 8.08.
4.2.2. (S)-(ꢀ)-2-(1-(Prop-2-ynyloxy)but-3-enyl)pyridine, (S)-
(ꢀ)-9
This is a yellow oil (0.23 g, 89% yield). ½a D26
¼ ꢀ136:9 (c 3,
ꢁ
CH2Cl2). 1H NMR (CDCl3): d 8.50 (d, J = 4.4 Hz, 1H), 7.62 (t,
J = 7.6 Hz, 1H), 7.34 (d, J = 7.8 Hz, 1H), 7.11–7.14 (m, 1H), 5.69–
5.79 (m, 1H), 4.93–5.00 (m, 2H), 4.64 (t, J = 6.4 Hz, 1H), 4.12 (d,
JAB = 15.8 Hz, 1H), 3.94 (d, JAB = 15.8 Hz, 1H), 2.51–2.55 (m, 2H),
2.33 (s, 1H). 13C NMR (CDCl3): d 160.7, 149.2, 136.6, 134.0, 122.6,
120.9, 117.3, 81.4, 79.6, 74.4, 56.5, 40.6. IR (neat): 2961, 1084,
797 cmꢀ1. MS (EI) m/z (rel. intensity) 146 (M+ꢀ41(+CH2CH@CH2),
base). Anal. Calcd C, 76.98; H, 7.00; N, 7.48. Found: C, 76.94; H,
6.98; N, 7.39.
4.3. General procedure for the Pauson–Khand reaction
To a solution of (S)-(ꢀ)-8, (S)-(ꢀ)-9, (S)-(ꢀ)-10, (S)-(ꢀ)-11, (S)-
(ꢀ)-16, (S)-(ꢀ)-17, and (S)-(ꢀ)-18 (1 mmol) in CH2Cl2 (10 mL)
was added Co2(CO)8 (1.7 mmol) and stirred for 2 h (TLC monitor-
ing). Then, NMO (9 mmol) was added and stirred for 24 h. The
products (+)-12–15 and diastereomeric couples of (+)-19/(ꢀ)-19,
(+)-20/(ꢀ)-20, and (+)-21/(ꢀ)-21 were purified by flash column
chromatography using ethylacetate/hexane solvent as eluent (1:1
system for compounds (+)-12 and (+)-14 and 10:1 system for com-
pounds (+)-13 and (+)-15). The products (+)-12–15 were obtained
with 80%, 76%, 80%, and 81% yields, respectively. Diastereomeric
mixtures obtained from compounds (S)-(ꢀ)-16–18 were purified
by flash column chromatography using ethylacetate/hexane sol-
vent as eluent (1:1 system for couples (+)-19/(ꢀ)-19 and (+)-20/
(ꢀ)-20 and 10:1 system for couple (+)-21/(ꢀ)-21). The total yields
4.2.3. (S)-(ꢀ)-2-(1-(Allyloxy)but-3-ynyl)thiophene, (S)-(ꢀ)-10
This is a yellow oil (0.22 g, 82% yield). ½a D29
¼ ꢀ33:1 (c 1.3,
ꢁ
CH2Cl2). 1H NMR (CDCl3): d 7.17–7.24 (m, 1H), 6.94–6.96 (m, 1H),
6.89–6.91 (m, 1H), 5.77–5.87 (m, 1H), 5.18–5.22 (dm, J = 15.7 Hz,
1H), 5.10–5.12 (dm, J = 10.3 Hz, 1H), 4.68 (t, J = 6.6 Hz, 1H), 3.97
(dd, JAB = 5.0 and 12.8 Hz, 1H), 3.83 (dd, JAB = 6.3 and 12.8 Hz,
1H), 2.72 (ddd, JAB = 2.8, 6.5 and 16.5 Hz, 1H), 2.59 (ddd, JAB = 2.8,
6.7 and 16.7 Hz, 1H), 1.92 (t, JAB = 2.5 Hz, 1H). 13C NMR (CDCl3): d
144.6, 134.4, 126.5, 125.7, 125.3, 117.5, 80.4, 75.0, 70.4, 69.7,
28.5. IR (neat): 2972, 1081, 1039, 879 cmꢀ1. MS (EI) m/z (rel. inten-
sity) 153 (M+ꢀ39(+CH2C„CH), base). Anal. Calcd C, 68.71; H, 6.29;
S, 16.68. Found: C, 68.68; H, 6.26; S, 16.64.

S. Sezer et al. / Tetrahedron: Asymmetry 21 (2010) 476–485
483
of couples (+)-19/(ꢀ)-19, (+)-20/(ꢀ)-20, and (+)-21/(ꢀ)-21 are 74%,
4.3.6. (3S,3aS)-(+)-3-(Furan-2-yl)-3a,4-dihydro-1H-
cyclopenta[c]furan-5(3H)-one, (3S,3aS)-(+)-19
77%, 50% yield, respectively.
This is a viscous liquid. ½a D20
ꢁ
¼ þ39:8 (c 0.83, CH2Cl2). 1H NMR
(CDCl3): d 7.23 (d, J = 1.1 Hz, 1H), 6.22 (dd, J = 1.8 and 3.2 Hz, 1H),
6.10 (d, J = 3.2 Hz, 1H), 6.04 (br s, 1H), 5.24 (d, J = 8.3 Hz, 1H),
4.71 (d, J = 6.4 Hz, 2H), 3.54–3.59 (m, 1H), 2.45 (dd, JAB = 6.5 and
17.8 Hz, 1H), 1.78 (dd, JAB = 3.8 and 17.8 Hz, 1H). 13C NMR (CDCl3):
d 207.4, 180.9, 151.1, 141.7, 123.6, 109.1, 107.5, 73.2, 64.4, 47.9,
37.0. IR (neat): 2916, 1011, 748 cmꢀ1. MS (EI) m/z (rel. intensity)
190 (M+, 31), 94 (base), 66 (50). HRMS, Calculated [M]+ 191.0708,
Measured [M]+ 191.0700.
4.3.1. (3S,4aR)-(+)-3-(Thiophen-2-yl)-3,4,4a,5-
tetrahydrocyclopenta[c]pyran-6(1H)-one, (3S,4aR)-(+)-12
This is a white solid. Mp: 104–105 °C (0.17 g, 80% yield).
½
a 2D9
ꢁ
¼ þ53:4 (c 1.6, CH2Cl2). 1H NMR (CDCl3): d 7.19–7.20 (m,
1H), 6.90–6.93 (m, 2H), 5.94 (s, 1H), 4.82 (d, J = 11.1 Hz, 1H), 4.77
(d, JAB = 13.5 Hz, 1H), 4.36 (d, JAB = 13.5 Hz, 1H), 3.00–3.03 (m,
1H), 2.61 (dd, J = 6.5 and 18.6 Hz, 1H), 2.44 (dd, J = 5.5 and
13.0 Hz, 1H), 2.06 (dd, J = 2.7 and 18.6 Hz, 1H), 1.70 (q,
J = 12.3 Hz, 1H). 13C NMR (CDCl3): d 206.2, 173.1, 142.8, 126.8,
125.6, 124.1, 123.0, 73.9, 66.2, 40.9, 40.7, 38.2. IR (neat): 1708,
1629, 1072, cmꢀ1. HRMS, Calculated [M]+ 221.0636, Measured
[M]+ 221.0632.
4.3.7. (3S,3aR)-(ꢀ)-3-(Thiophen-2-yl)-3a,4-dihydro-1H-
cyclopenta[c]furan-5(3H)-one, (3S,3aR)-(ꢀ)-20
[0.15 g, 77% total yield for (ꢀ)-20 and (+)-20]. This is a viscous
liquid. ½a 2D2
ꢁ
¼ ꢀ32:0 (c 1, CH2Cl2). 1H NMR (CDCl3): d 7.25 (dd,
J = 1.2 and 5.0 Hz, 1H), 6.98 (dm, J = 3.4 Hz, 1H), 6.91 -6.95 (m,
1H), 6.03 (dd, J = 2.1 and 3.6 Hz, 1H), 4.84 (dm, J = 15.9 Hz, 1H),
4.64 (d, J = 1.2 Hz, 1H), 4.56 (d, J = 10.3 Hz, 1H), 3.23–3.28 (m,
1H), 2.56 (dd, J = 6.4 and 17.7 Hz, 1H), 2.17 (dd, J = 3.61 and
17.7 Hz, 1H). 13C NMR (CDCl3): d 206.4, 181.7, 140.8, 125.7,
124.6, 124.2, 124.1, 79.6, 65.2, 52.2, 37.5. HRMS, Calculated [M]+
207.0480, Measured [M]+ 207.0470.
4.3.2. (3S,4aR)-(+)-3-(Pyridin-2-yl)-3,4,4a,5-
tetrahydrocyclopenta[c]pyran-6(1H)-one, (3S,4aR)-(+)-13
This is a yellow viscous liquid (0.16 g, 76% yield). ½a D29
¼ þ33:6
ꢁ
(c 1, CH2Cl2). 1H NMR (CDCl3): d 8.48 (d, J = 4.07 Hz, 1H), 7.63 (t,
J = 7.3 Hz, 1H), 7.38 (d, J = 7.8 Hz, 1H), 7.12–7.15 (m, 1H), 5.95 (s,
1H), 4.83 (d, JAB = 13.4 Hz, 1H), 4.68 (d, J = 11.1 Hz, 1H), 4.39 (d,
JAB = 13.4 Hz, 1H), 3.03–3.09 (m, 1H), 2.54–2.64 (m, 2H), 2.03 (dd,
J = 2.2 and 18.7 Hz, 1H), 1.45–1.46 (q, J = 12.1 Hz, 1H). 13C NMR
(CDCl3): d 207.5, 174.6, 160.0, 148.9, 136.8, 127.6, 122.7, 120.1,
79.6, 67.1, 41.8, 40.7, 39.4. HRMS, Calculated [M]+ 216.1024, Mea-
sured [M]+ 216.1021.
4.3.8. (3S,3aS)-(+)-3-(Thiophen-2-yl)-3a,4-dihydro-1H-
cyclopenta[c]furan-5(3H)-one, (3S,3aS)-(+)-20
This is a viscous liquid. ½a D22
ꢁ
¼ þ128:2 (c 1, CH2Cl2). 1H NMR
(CDCl3): d 7.13 (d, J = 5.0 Hz, 1H), 6.87–6.89 (m, 1H), 6.76 (d,
J = 3.4 Hz, 1H), 6.08 (s, 1H), 5.55 (d, J = 8.3 Hz, 1H), 4.77 (d,
JAB = 15.6 Hz, 1H), 4.69 (d, JAB = 15.8 Hz, 1H), 3.60–3.64 (m, 1H),
2.54 (dd, J = 6.6 and 17.6 Hz, 1H), 1.80 (dd, J = 3.6 and 17.9 Hz,
1H). 13C NMR (CDCl3): d 207.3, 179.5, 140.0, 125.7, 124.8, 124.3,
76.2, 64.1, 48.5, 37.1, 28.7. IR (neat): 2360, 1091, 798 cmꢀ1. MS
(EI) m/z (rel. intensity) 206 (M+, 34), 94 (base), 66 (48). HRMS, Cal-
culated [M]+ 207.0480, Measured [M]+ 207.0470.
4.3.3. (3S,7aR)-(+)-3-(Thiophen-2-yl)-3,4,7,7a-
tetrahydrocyclopenta[c]pyran-6(1H)-one, (3S,7aR)-(+)-14
This is a white solid. Mp: 132–133 °C (0.17 g, 80% yield).
½
a 2D9
ꢁ
¼ þ250 (c 0.45, MeOH). 1H NMR (CDCl3): d 7.19–7.25 (m,
1H), 6.93–6.97 (m, 2H), 5.95 (s, 1H), 4.58 (d, J = 11.0 Hz, 1H), 4.37
(dd, J = 6.4 and 10.7 Hz, 1H), 3.23 (t, J = 11.0 Hz, 1H), 3.10 (d,
J = 13.5 Hz, 1H), 2.95–3.05 (m, 1H), 2.71 (t, J = 11.8 Hz, 1H), 2.45
(dd, J = 6.6 and 18.8 Hz, 1H), 1.89 (d, JAB = 18.8 Hz, 1H). 13C NMR
(CDCl3): d 206.7, 177.5, 143.3, 127.4, 126.2, 124.9, 123.7, 75.6,
73.1, 40.3, 38.8, 36.5. IR (neat): 2926, 1691, 1000, 706 cmꢀ1. MS
(EI) m/z (rel intensity) 220 (base). HRMS, Calculated [M]+
221.0636, Measured [M]+ 221.0632.
4.3.9. (3S,3aS)-(+)-3-(Pyridin-2-yl)-3a,4-dihydro-1H-
cyclopenta[c]furan-5(3H)-one, (3S,3aS)-(+)-21
[0.1 g, 50% total yield for (+)-21 and (ꢀ)-21]. This is a viscous li-
quid. ½a 2D4
ꢁ
¼ þ85:5 (c 1, CH2Cl2). 1H NMR (CDCl3): d 8.47 (dm,
J = 4.7 Hz, 1H), 7.58 (td, J = 1.7 and 7.7 Hz, 1H), 7.10 (dd, J = 4.8
and 6.6 Hz, 1H), 7.05 (bd, J = 7.8 Hz, 1H), 5.98 (s, 1H), 5.39 (d,
J = 8.3 Hz, 1H), 4.94 (d, JAB = 15.4 Hz, 1H), 4.80 (d, JAB = 15.4 Hz,
1H), 3.74–3.80 (m, 1H), 2.49 (dd, JAB = 6.6 and 18.2 Hz, 1H), 1.78
(dd, JAB = 3.7 and 18.2 Hz, 1H). 13C NMR (CDCl3): d 207.6, 179.7,
157.5, 148.2, 135.5, 123.8, 121.5, 119.8, 79.4, 65.2, 48.3, 37.1.
HRMS, Calculated [M]+ 201.0790, Measured [M]+ 201.0784.
4.3.4. (3S,7aR)-(+)-3-(Pyridin-2-yl)-3,4,7,7a-
tetrahydrocyclopenta[c]pyran-6(1H)-one, (3S,7aR)-(+)-15
This is
a white solid. Mp: 90–92 °C (0.17 g, 81% yield).
½
a 2D9
ꢁ
¼ þ126:1 (c 1, MeOH). 1H NMR (CDCl3): d 8.52 (d, J = 4.3 Hz,
1H), 7.67 (t, J = 7.6 Hz, 1H), 7.43 (d, J = 7.8 Hz, 1H), 7.16–7.21 (m,
1H), 5.97 (s, 1H), 4.41–4.45 (m, 2H), 3.26 (t, J = 11.0 Hz, 1H), 3.20
(bd, J = 13.8 Hz, 1H), 2.98–3.04 (m, 1H), 2.60 (t, J = 12.3 Hz, 1H),
2.45 (dd, J = 6.7 and 18.7 Hz, 1H), 1.90 (bd, JAB = 18.7 Hz, 1H). 13C
NMR (CDCl3): d 207.3, 179.1, 159.5, 149.1, 136.9, 127.9, 123.0,
120.5, 80.6, 73.7, 40.9, 37.6, 37.1. IR (neat): 2917, 1082,
796 cmꢀ1. MS (EI) m/z (rel intensity) 215 (M+, 4), 106 (base). HRMS,
Calculated [M]+ 216.1024, Measured [M]+ 216.1021.
4.3.10. (3S,3aR)-(ꢀ)-3-(Pyridin-2-yl)-3a,4-dihydro-1H-
cyclopenta[c]furan-5(3H)-one, (3S,3aR)-(ꢀ)-21
This is a viscous liquid. ½a D18
ꢁ
¼ ꢀ27:6 (c 0.5, CH2Cl2) 1H NMR
(CDCl3): d 8.52 (d, J = 4.3 Hz, 1H), 7.67 (td, J = 1.3 and 7.7 Hz, 1H),
7.43 (d, J = 7.7 Hz, 1H), 7.18–7.21 (m, 1H), 6.06 (s, 1H), 4.89 (d,
JAB = 15.7 Hz, 1H), 4.69 (d, JAB = 15.7 Hz, 1H), 4.48 (d, J = 10.4 Hz,
1H), 3.30–3.37 (m, 1H), 2.61 (dd, JAB = 6.4 and 17.9 Hz, 1H), 2.63
(dd, JAB = 3.5 and 17.9 Hz, 1H). 13C NMR (CDCl3): d 207.0, 181.9,
157.5, 148.2, 135.7, 124.1, 122.1, 119.7, 83.9, 65.3, 50.7, 38.4.
HRMS, Calculated [M]+ 201.0790, Measured [M]+ 201.0784.
4.3.5. (3S,3aR)-(ꢀ)-3-(Furan-2-yl)-3a,4-dihydro-1H-
cyclopenta[c]furan-5(3H)-one, (3S,3aR)-(ꢀ)-19
[0.14 g, 74% total yield for (ꢀ)-19 and (+)-19]. This is a viscous
liquid. ½a 1D8
ꢁ
¼ ꢀ30:1 (c 1, CH2Cl2). 1H NMR (CDCl3): d 7.38 (d,
4.4. X-ray structure determination
J = 1.03 Hz, 1H), 6.30–6.34 (m, 2H), 6.04 (br s, 1H), 4.80 (d,
JAB = 15.7 Hz, 1H), 4.60 (d, JAB = 15.8 Hz, 1H), 4.36 (d, J = 10.7 Hz,
1H), 3.50–3.54 (m, 1H), 2.56 (dd, J = 6.5 and 17.9 Hz, 1H), 2.13
(dd, J = 3.5 and 17.8 Hz, 1H). 13C NMR (CDCl3): d 207.7, 182.7,
150.9, 143.2, 125.1, 110.5, 109.1, 76.7, 66.0, 49.1, 38.7. HRMS, Cal-
culated [M]+ 191.0708, Measured [M]+ 191.0700.
For the crystal structure determination, the single crystals of
the compounds (3S,7aR)-(+)-14 and (3S,7aR)-(+)-15 were used
for data collection on a four-circle Rigaku R-AXIS RAPID-S dif-
fractometer (equipped with a two-dimensional area IP detector).

484
S. Sezer et al. / Tetrahedron: Asymmetry 21 (2010) 476–485
6. Takano, S.; Inomata, K.; Ogasawara, K. J. Chem. Soc., Chem. Commun. 1992, 169.
7. (a) Rowley, E. G.; Schore, N. E. J. Org. Chem. 1992, 57, 6853; (b) Pallerla, M. K.;
Fox, J. M. Org. Lett. 2007, 26, 5625.
8. Jamison, T. F.; Shambayati, S.; Crowe, W. E.; Schreiber, S. L. J. Am. Chem. Soc.
1997, 119, 4353.
9. Honda, T.; Kaneda, K. J. Org. Chem. 2007, 72, 6541.
The graphite-monochromatized Mo K
a
radiation (k = 0.71073 Å)
and oscillation scan technique with
Dx = 5° for one image were
used for data collection. The lattice parameters were determined
by the least-squares methods on the basis of all reflections with
F2 > 2 (F2). Integration of the intensities, correction for Lorentz
r
10. Min, S. J.; Danishefsky, S. J. Angew. Chem., Int. Ed. 2007, 46, 2199.
11. Kozaka, T.; Miyakoshi, N.; Mukai, C. J. Org. Chem. 2007, 72, 10147.
12. (a) Poch, M.; Valenti, E.; Moyano, A.; Pericas, M. A.; Castro, J.; DeNicola, A.;
Greene, A. E. Tetrahedron Lett. 1990, 31, 7505; (b) Verdaguer, X.; Moyano, A.;
Pericas, M. A.; Riera, A.; Greene, A. E.; Piniella, J. F.; Alvarez-Larena, A. J.
Organomet. Chem. 1992, 433, 305; (c) Castro, J.; Moyano, A.; Pericas, M. A.;
Riera, A.; Greene, A. E. Tetrahedron: Asymmetry 1994, 5, 307; (d) Bernardes, V.;
Verdaguer, X.; Kardos, N.; Riera, A.; Moyano, A.; Pericas, M. A.; Greene, A. E.
Tetrahedron Lett. 1994, 35, 575; (e) Verdaguer, X.; Moyano, A.; Pericas, M. A.;
Riera, A.; Bernardes, V.; Greene, A. E.; Alvarez-Larena, A.; Piniella, J. F. J. Am.
Chem. Soc. 1994, 116, 2153; (f) Fonquerna, S.; Moyano, A.; Pericas, M. A.; Riera,
A. Tetrahedron 1995, 51, 4239; (g) Fonquerna, S.; Moyano, A.; Pericas, M. A.;
Riera, A. J. Am. Chem. Soc. 1997, 119, 10225; (h) Montenegro, E.; Poch, M.;
Moyano, A.; Pericas, M. A.; Riera, A. Tetrahedron Lett. 1998, 39, 335; (i)
Verdaguer, X.; Vazquez, J.; Fuster, G.; Bernardes-Genisson, V.; Greene, A. E.;
Moyano, A.; Pericas, M. A.; Riera, A. J. Org. Chem. 1998, 63, 7037; (j) Fonquerna,
S.; Rios, R.; Moyano, A.; Pericas, M. A.; Riera, A. Eur. J. Org. Chem. 1999, 3459; (k)
Marchueta, I.; Montenegro, E.; Panov, D.; Poch, M.; Verdaguer, X.; Moyano, A.;
Pericas, M. A.; Riera, A. J. Org. Chem. 2001, 66, 6400; (l) Rios, R.; Paredes, S.;
Pericas, M. A.; Moyano, A. J. Organomet. Chem. 2005, 690, 358.
13. (a) Hicks, F. A.; Buchwald, S. L. J. Am. Chem. Soc. 1996, 118, 11688; (b) Hicks, F.
A.; Buchwald, S. L. J. Am. Chem. Soc. 1999, 121, 7026; (c) Sturla, S. J.; Buchwald,
S. L. J. Org. Chem. 1999, 64, 5547; (d) Hiroi, K.; Watanabe, T.; Kawagishi, R.; Abe,
I. Tetrahedron Lett 2000, 41, 891; (e) Hiroi, K.; Watanabe, T.; Kawagishi, R.; Abe,
I. Tetrahedron: Asymmetry 2000, 11, 797; (f) Shibata, T.; Takagi, K. J. Am. Chem.
Soc. 2000, 122, 9852; (g) Jeong, N.; Sung, B. K.; Choi, Y. K. J. Am. Chem. Soc. 2000,
122, 6771; (h) Jeong, N.; Sung, B. K.; Kim, J. S.; Park, S. B.; Seo, S. D.; Shin, J. Y.;
In, K. Y.; Choi, Y. K. Pure Appl. Chem. 2002, 74, 85; (i) Sturla, S. J.; Buchwald, S. L.
J. Org. Chem. 2002, 67, 3398; (j) Gibson, S. E.; Lewis, S. E.; Loch, J. A.; Steed, J. W.;
Tozer, M. J. Organometallics 2003, 22, 5382; (k) Schmid, T. M.; Consiglio, G.
Tetrahedron: Asymmetry 2004, 15, 2205.
14. (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; (d) Ghosh, S. K.; Hsung, R. P.; Liu,
J. J. Am. Chem. Soc. 2005, 127, 8260; (e) Pal, A.; Bhattacharjya, A. J. Org. Chem.
2001, 66, 9071; (f) Subburaj, K.; Okamoto, S.; Sato, F. J. Org. Chem. 2002, 67,
1024; (g) Brummond, K. M.; Kerekes, A. D.; Wan, H. J. Org. Chem. 2002, 67,
5156; (h) Rivero, M. R.; Adrio, J.; Carretero, J. C. Eur. J. Org. Chem. 2002, 2881.
15. (a) Son, S. U.; Yoon, Y. A.; Choi, D. S.; Park, J. K.; Kim, B. M.; Chung, Y. K. Org. Lett.
2001, 3, 1065; (b) Son, S. U.; Paik, S.-J.; Lee, S. I.; Chung, Y. K. J. Chem. Soc., Perkin
Trans. 1 2000, 141; (c) Hong, S. H.; Kim, J. W.; Choi, D. S.; Chung, Y. K.; Lee, S.-G.
J. Chem. Soc., Chem. Commun. 1999, 2099; (d) Son, S. U.; Choi, D. S.; Chung, Y. K.
Org. Lett. 2000, 2, 2097; (e) Lee, S. I.; Son, S. U.; Choi, M. R.; Chung, Y. K.; Lee, S.-
G. Tetrahedron Lett. 2003, 44, 4705; (f) Son, S. U.; Park, K. H.; Lee, S. J.; Kim, B.
M.; Chung, Y. K. Synlett 2003, 110; (g) Muto, R.; Ogasawara, K. Tetrahedron Lett.
2001, 42, 4143; (h) Tamao, K.; Kobayashi, T.; Ito, Y. Synlett 1992, 539.
16. (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.
and polarization effects, and cell refinement was performed
using CrystalClear (Rigaku/MSC Inc., 2005) software.31 The struc-
tures were solved by direct methods using SHELXS-9732 and re-
fined by
a
full-matrix least-squares procedure using the
atoms were positioned geometrically
program SHELXL-97.32
H
and refined using a riding model, fixing the aromatic C–H dis-
tances at 0.93 Å, methine C–H distances at 0.98 Å, and methy-
lene C–H distances at 0.97 Å [Uiso(H) = 1.2Ueq(C)]. The final
difference Fourier maps showed no peaks of chemical
significance.
Crystal data for compound: (3S,7aR)-(+)-14: C12H12O2S, crystal
system, space group: monoclinic, P21; (no:4); unit cell dimensions:
a = 9.1316(4), b = 6.8573(3), c = 9.3837(4) Å,
a = 90°, b = 111.46(2)°,
c
=90°; volume: 546.86(4) Å3; Z = 2; calculated density: 1.34 mg/
m3; absorption coefficient: 0.272 mmꢀ1; F(0 0 0): 232; h range for
data collection 2.3–30.6°; refinement method: full-matrix least-
square on F2; data/parameters: 2594/137; goodness-of-fit on F2:
1.114; final R indices [I > 2r(I)]: R1 = 0.047, wR2 = 0.117; R indices
(all data): R1 = 0.061, wR2 = 0.140; largest diff. peak and hole:
0.166 and ꢀ0.231 e Åꢀ3; CCDC-762198.
Crystal data for compound: (3S,7aR)-(+)-15: C13H13NO2, crystal
system, space group: orthorhombic, P212121; (no:19); unit cell
dimensions: a = 7.0938(2), b = 7.0233(2), c = 44.0534(9) Å,
a = 90°,
b = 90°,
c
= 90°; volume: 2194.82(2) Å3; Z = 8; calculated density:
1.30 mg/m3; absorption coefficient: 0.088 mmꢀ1; F(0 0 0): 912; h
range for data collection 2.8–26.5°; refinement method: full-ma-
trix least-square on F2; data/parameters: 4500/289; goodness-of-
fit on F2: 1.039; final R indices [I > 2
r(I)]: R1 = 0.070, wR2 = 0.144;
R indices (all data): R1 = 0.140, wR2 = 0.173; largest diff. peak and
hole: 0.232 and ꢀ0.187 e Åꢀ3; CCDC-762052.
Acknowledgments
We are grateful to the Turkish Scientific and Technical Research
Council for a grant (No. TBAG-108T072). We thank Professor Cavit
Kazaz for NOE measurements. We are also grateful to Novozymes
A/S (Bagsvaerd, Denmark) for the generous gift of lipases Novozym
435 and Lipozyme TL IM.
References
1. (a) Huang, H. W.; Sun, J. X.; Frontier, A. J. J. Am. Chem. Soc. 2007, 129, 498; (b)
Ko, H. M.; Lee, D. G.; Kim, M. A.; Kim, H. J.; Park, J.; Lah, M. S.; Lee, E. Org. Lett.
2007, 9, 141; (c) Su, Q.; Dakin, L. A.; Panek, J. S. J. Org. Chem. 2007, 72, 2.
2. (a) Khand, I. U.; Knox, G. R.; Pauson, P. L.; Watts, W. E. J. Chem. Soc., Chem.
Commun. 1971, 36; (b) Khand, I. U.; Knox, G. R.; Pauson, P. L.; Watts, W. E.;
Foreman, M. I. J. Chem. Soc., Perkin Trans. 1 1973, 977; (c) Pauson, P. L.; Khand, I.
U. Ann. N.Y. Acad. Sci. 1977, 295, 2.
3. For selected reviews, see: (a) Ingate, S. T.; Contelles, M. Org. Prep. Proced. Int.
1998, 30, 121; (b) Geis, O.; Schmalz, H. G. Angew. Chem., Int. Ed. 1998, 37, 911;
(c) Chung, Y. K. Coord. Chem. Rev. 1999, 188, 297; (d) Brummond, K. M.; Kent, J.
L. Tetrahedron 2000, 56, 3263; (e) Gibson, S. E.; Stevanazzi, A. Angew. Chem., Int.
Ed. 2003, 42, 1800; (f) Bonaga, L. V. R.; Krafft, M. E. Tetrahedron 2004, 60, 9795;
(g) Laschat, S.; Becheanu, A.; Bell, T.; Baro, A. Synlett 2005, 2547; (h) Gibson, S.
E.; Mainolfi, N. Angew. Chem., Int. Ed. 2005, 44, 3022; (i) Park, K. H.; Chung, Y. K.
Synlett 2005, 545.
4. (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)
Pérez-Serrano, L.; Casarrubios, L.; Domínguez, G.; Pérez-Castells, J. Org. Lett.
1999, 1, 1187; (f) Blanco-Urgoiti, J.; Casarrubios, L.; Domínguez, G.; Pérez-
Castells, J. Tetrahedron Lett. 2002, 43, 5763; (g) Krafft, M. E.; Boñaga, L. V. R.;
Hirosawa, C. J. Org. Chem. 2002, 67, 1233; (h) Chem. Soc. Rev. 2004, 33, 32.
5. Castro, J.; Sorensen, H.; Riera, A.; Moyano, A.; Pericas, M. A.; Greene, A. E. J. Am.
Chem. Soc. 1990, 112, 9388.
17. (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.
18. (a) Denmark, S. E.; Fu, J. Chem. Rev. 2003, 103, 2763; (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,
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:Asymmetry 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.
19. (a) Faber, K. Biotransformations in Organic Chemistry, 5th ed.; Springer: Berlin
Heidelberg, New York, 2004; (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, 90, 1;

S. Sezer et al. / Tetrahedron: Asymmetry 21 (2010) 476–485
485
(f)Enzyme Catalysis in Organic Synthesis; Drauz, K., Waldmann II, H., Eds.; VCH:
New York, 2002; (g) Santaniello, E.; Ferraboschi, P.; Grisenti, P.; Manzocchi, A.
Chem. Rev. 1992, 92, 1071.
stereogenic center on the final products can be discerned in the X-ray
structure relative to homopropargylic alcohols and by differential NOE
experiments relative to homoallylic alcohols.
20. Tanyeli, C.; Demir, A. S.; Arkın, H.; Akhmedov, I. M. Enantiomer 1997, 2, 433.
21. Tanyeli, C.; Akhmedov, I. M.; Özdemirhan, D. Enantiomer 2001, 259.
22. (a) Sing, S.; Kumar, S.; Chimni, S. Tetrahedron: Asymmetry 2002, 2679, 13; (b)
Bierstedt, A.; Stolting, J.; Frohlich, R.; Metz, P. Tetrahedron: Asymmetry 2001,
3399, 12; (c) Holmberg, P.; Karlsson, J.; Gogoll, A. Tetrahedron: Asymmetry 2005,
2397, 16; (d) Krishna, U. M.; Srikanth, G. S. C.; Trivedi, G. K. Tetrahedron:
Asymmetry 2003, 8227, 44.
27. (a) Abraham, R. J.; Parry, K.; Thomas, W. A. J. Chem. Soc. B 1971, 446; (b)
Günther, H.; Jikeli, G. Chem. Rev. 1977, 77, 599.
28. Uenishi, J.; Hiraoka, T.; Shinichiro, H.; Nishiwaki, K.; Yoemitsu, O.; Nakamura,
K.; Tsukube, H. J. Org. Chem. 1998, 63, 2481.
29. Lipozyme-catalyzed reactions were performed in an incubator with an orbital
shaker at 30 °C. However, PS-C-catalyzed reactions were performed in a water
bath shaker at 24 1 °C. Moreover, CAL-B-catalyzed reactions were performed
in a water bath shaker at different temperatures shown in Table 2.
23. Sezer, S.; Ozdemirhan, D.; Sßahin, E.; Tanyeli, C. Tetrahedron: Asymmetry 2006,
2981, 17.
30. (a) The [a] value of the product was recorded immediately after resolution
24. Sezer, S.; Gümrükçü, Y.; Sßahin, E.; Tanyeli, C. Tetrahedron: Asymmetry 2008,
2705, 19.
because compound (S)-3b had a tendency to darken while in storage.; (b)
Busto, E.; Fernandez, F. G.; Gotor, V. Tetrahedron:Asymmetry 2005, 16,
3427.
25. Chen, C. S.; Fujimoto, Y.; Girdaukas, G.; Sih, C. J. J. Am. Chem. Soc. 1982, 104,
7294.
31. Rigaku/MSC, Inc., 9009 new Trails Drive, The Woodlands, TX 77381.
32. Sheldrick, G. M., SHELXS97 and SHELXL97, University of Göttingen, Germany,
1997.
26. Final compounds were identified and characterized by 1H NMR, 13C NMR, FTIR,
COSY, HMBC, HMQC and HRMS, and/or elemental analysis. The new