Synthesis of enantiomerically pure substituted tetrahydrofurans from epoxides and phenylselenium reagents

Article abstract of DOI:10.1016/j.tetasy.2003.10.042

Starting from commercially available enantiomerically pure epoxides, enantiomerically pure substituted tetrahydrofurans were prepared using simple conversions promoted by organoselenium reagents. The first step consisted in the opening of the epoxides with phenylselenolate anions to afford hydroxyalkyl phenyl selenides. The PhSe group was then substituted by an allyl group by treatment with allyltributyltin and AIBN. The reaction of these allylic derivatives with electrophilic phenylselenium reagents afforded selenium containing tetrahydrofurans as the result of a stereospecific 5-exo-trig cyclization. The tetrahydrofuran derivatives thus obtained were finally deselenenylated with triphenyltin hydride and AIBN.

Full text of DOI:10.1016/j.tetasy.2003.10.042

Tetrahedron:
Asymmetry
Tetrahedron: Asymmetry 15 (2004) 405–412
Synthesis of enantiomerically pure substituted tetrahydrofurans
from epoxides and phenylselenium reagents
Marcello Tiecco,* Lorenzo Testaferri, Luana Bagnoli, Valentina Purgatorio,
Andrea Temperini, Francesca Marini and Claudio Santi
Dipartimento di Chimica e Tecnologia del Farmaco, Sezione di Chimica Organica, Universitꢀa di Perugia, Perugia I-06123, Italy
Received 9October 2003; accepted 30 October 2003
Abstract—Starting from commercially available enantiomerically pure epoxides, enantiomerically pure substituted tetrahydrofurans
were prepared using simple conversions promoted by organoselenium reagents. The first step consisted in the opening of the
epoxides with phenylselenolate anions to afford hydroxyalkyl phenyl selenides. The PhSe group was then substituted by an allyl
group by treatment with allyltributyltin and AIBN. The reaction of these allylic derivatives with electrophilic phenylselenium
reagents afforded selenium containing tetrahydrofurans as the result of a stereospecific 5-exo-trig cyclization. The tetrahydrofuran
derivatives thus obtained were finally deselenenylated with triphenyltin hydride and AIBN.
Ó 2003 Elsevier Ltd. All rights reserved.
1. Introduction
diastereoselectivities were observed in most cases.
Recently, two new enantiomerically pure diselenides, the
di-2-[(1S)-1-(methylthio)ethyl]phenyl diselenide and the
di-2-methoxy-6-[(1S)-1-methylthio)ethyl]phenyl diselen-
ide, have been prepared.14;15 The electrophilic reagents
produced from them have been employed to effect
asymmetric selenocyclization reactions. Thus, tetra-
hydrofurans,16 lactones, lactams, N-protected pyrrol-
idines,16 1,2-oxazines, and cyclic nitrones have been
prepared.17 The transfer of chirality was very efficient
and the diastereoselectivities observed are comparable
or better than those obtained with the most efficient
diselenides previously described in the literature. The
efficiency of these reagents has been attributed to the
presence of a sulfur atom linked to the stereogenic center
and close to the selenium atom.
Owing to the great importance of heterocyclic com-
pounds as final products or as reaction intermediates
several methods have been described for their con-
struction. Among these, the use of selenium reagents to
effect ring closure reactions has recently gained
increasing popularity. This is due to the ready avail-
ability of the reagents, the numerous chemical manipu-
lations, which can be effected on the selenium moiety
before or during its removal and to the mild reaction
conditions required in the various steps. Selenium pro-
moted cyclization reactions thus provide an easy access
to a wide variety of heterocyclic compounds in general
and to those containing oxygen and/or nitrogen het-
eroatoms in particular.1–3
An important new finding is that optically active het-
erocyclic compounds can be prepared using electrophilic
selenium reagents RSeX in which R is a chiral group.
Several enantiomerically pure diselenides have been
employed as precursor to promote the cyclization of
alkenes containing internal nucleophiles.4–13 Satisfactory
We now report that the versatile chemical behavior of
organoselenium compounds allows the preparation of
enantiomerically pure heterocyclic compounds to be
effected using an alternative approach. This consists in
the reaction of the achiral phenylselenium reagent with
an enantiomerically pure easily available substrate. As a
first example we describe the synthesis of substituted
tetrahydrofurans starting from enantiomerically pure
epoxides. The stereoselective synthesis18;19 of substituted
cyclic ether is important since cyclic ether units are fre-
quently found in polyether antibiotics, C-glycosides, and
other biologically active natural products.20
* Corresponding author. Tel.: +39-075-5855100; fax: +39-075-58551-
16; e-mail: tiecco@unipg.it
0957-4166/$ - see front matter Ó 2003 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2003.10.042

406
M. Tiecco et al. / Tetrahedron: Asymmetry 15 (2004) 405–412
2. Results and discussion
starting from the alkenol 4 an almost equimolar mixture
of the two enantiomerically pure diastereoisomeric 2,5-
disubstituted tetrahydrofurans 5 and 6 was formed.
These were separated by column chromatography.
Finally, 5 and 6 were deselenenylated with triphenyltin
hydride and AIBN and afforded the enantiomerically
pure 2-methyl-5-phenyl tetrahydrofurans 7 and 8,
respectively.
As illustrated in Scheme 1, the opening of the epoxide
(R)-phenyloxirane 1 (ee equal or greater than 98%) with
the phenylselenolate anions, produced in situ by diphe-
nyl diselenide and sodium borohydride in ethanol, was
not regiospecific and the two enantiomerically pure
b-hydroxyalkyl phenyl selenides 2 and 3 were obtained.
The two regioisomers were easily separated by column
chromatography and the b-hydroxy selenide 2 was
treated with allyltributyltin and AIBN.21 The enantio-
merically pure alkenol 4 was formed in reasonably good
yields. Its absolute configuration was confirmed by
comparison of its specific rotation with that reported in
the literature.22
2R,5S
2S,5S
b
5
2
Ph
Ph
Me
O
O
SePh
7 (85%)
[α]D = -57.1
5 (35%)
[α]D = -59.6
a
Ph
OH
4 (1S)
2S,5R
2S,5S
PhSe
Ph
HO
Ph
b
PhSeSePh
O
5 2
O
Ph
O
+
Ph
Me
NaBH4, EtOH
SePh
Ph
1 (R)
OH
SePh
40 o
C
6 (32%)
[α]D = -26.8
8 (80%)
[α]D = -26.6
2 (1R) (45%)
[α]D = -14.6
3 (2R) (32%)
[α]D = +130.0
Scheme 3. Reagents and conditions: (a) PhSeSePh, (NH4)2S2O8,
CF3SO3H, MeCN, rt; (b) Ph3SnH, AIBN, C6H6, 80 °C.
SnBu3
AlBN, C6H6, 80 oC
2 (1R)
The same cyclization procedure applied to the alkenol
ent-4, gave rise to the two diastereoisomeric tetra-
hydrofurans ent-5 and ent-6 and, after deselenylation,
the two enantiomerically pure 2-methyl-5-phenyl tetra-
hydrofurans ent-7 and ent-8 were obtained (Scheme 4).
Ph
OH
4 (1S) (66%)
[α]D = -31.0
Scheme 1.
2S,5R
2R,5R
b
Following the same procedures (Scheme 2), the (S)-
phenyloxirane ent-1 (ee equal or greater than 98%) gave
a mixture of the two regioisomers ent-2 and ent-3.
Compound ent-2 was then converted into the enantio-
merically pure alkenol ent-4.
5
O
2
Ph
Ph
Me
O
SePh
ent-7 (85%)
[α]D = +56.6
ent-5 (35%)
[α]D = +59.0
a
Ph
OH
2R,5S
2R,5R
ent-4 (1R)
b
HO
Ph
PhSe
Ph
5
O
2
O
PhSeSePh
Ph
O
+
Ph
Me
SePh
Ph
NaBH4, EtOH
40 oC
SePh
OH
ent-6 (32%)
[α]D = +26.0
ent-8 (80%)
[α]D = +27.4
ent-1 (1S)
ent-2 (1S)
ent-2 (1S) (52%)
[α]D = +14.2
ent-3 (2S) (40%)
[α]D = -132.8
Scheme 4. Reagents and conditions: (a) PhSeSePh, (NH4)2S2O8,
CF3SO3H, MeCN, rt; (b) Ph3SnH, AIBN, C6H6, 80 °C.
SnBu3
AlBN, C6H6, 80 oC
The relative configurations within 2-methyl-5-phenyl
tetrahydrofurans 7 (2R,5S) and 8 (2S,5S), ent-7 (2S,5R)
and ent-8 (2R,5R) were determined by NMR spectro-
scopy on the basis of the results of NOESY experiments.
In compounds 7 and ent-7 a strong dipolar interaction
was observed between the methyl in the 2-position and
the proton in the 5-position whereas in compounds 8
and ent-8 the NOE effect was observed between the
proton in the 2- and the proton in the 5-positions. The
relative configurations within the selenides 5, 6, ent-5,
and ent-6 were deduced from those of the corresponding
deselenenylated compounds. The enantiomeric excess of
the tetrahydrofurans 7, 8, ent-7, ent-8 was confirmed by
GC–MS experiments using a Chirasildex column.
Ph
OH
ent-4 (1R) (55%)
[α]D = +31.2
Scheme 2.
The following step of the sequence was the 5-exo-trig
cyclization reaction promoted by the electrophilic phe-
nylselenenyl sulfate, generated by the reaction of the
diphenyl diselenide with ammonium persulfate in the
presence of trifluoromethanesulfonic acid (Scheme 3).23
This ring closure reaction was not stereoselective. Thus,

M. Tiecco et al. / Tetrahedron: Asymmetry 15 (2004) 405–412
407
2R,3S,5S
2R,3S,5R
Thus, starting from the (R)-phenyloxirane 1 and the (S)-
Ph
Ph
phenyloxirane ent-1 and using the simple reaction
sequence described above, all the four 2-methyl-5-phenyl
tetrahydrofurans 7, 8, ent-7, and ent-8 could be obtained
in an enantiomerically pure form.
b
Me
O
Me
Me
O
SePh
17 (95%)
13 (47%)
[α]D = +66.9
[α]D = +16.8
Ph
The same synthetic sequence described above for (R)
and (S)-phenyloxirane was then applied to the com-
mercially available (1R,2R)-1-phenylpropylene oxide 9
(99% ee) and (1S,2S)-1-phenylpropylene oxide ent-9
(99% ee). In the present case the stereospecific opening
of the chiral epoxides 9 and ent-9 by sodium phenyl-
selenolate was regiospecific and afforded exclusively the
enantiomerically pure 1-phenyl-1-(phenylseleno)propan-
2-ols 10 and ent-10, respectively, in high yields (Scheme
5).24
a
Me
OH
2R,3S,5R
2R,3S,5S
Ph
11 (2R,3S)
Ph
b
Me
O
Me
Me
O
SePh
14 (29%)
[α]D = +120.0
18 (95%)
[α]D = +113.0
2R,3R,5R
2R,3R,5S
Ph
Ph
b
Ph
PhSe
Me
Ph
PhSeSePh
Me
O
Me
Me
O
O
SePh
NaBH4, EtOH
40 oC
OH
Me
15 (45%)
19 (85%)
[α]D = +34.9
[α]D = +8.2
Ph
9 (1R,2R)
10 (1S,2R) (92%)
[α]D = +255.1
a
Me
OH
2R,3R,5R
2R,3R,5S
Ph
Ph
12 (2R,3R)
b
Ph
PhSe
Me
Ph
Me
O
PhSeSePh
Me
Me
O
O
SePh
NaBH4, EtOH
40 oC
OH
Me
20 (90%)
16 (25%)
[α]D = +15.3
[α]D = -55.4
ent-9 (1S,2S)
ent-10 (1R,2S) (92%)
[α]D = -250.2
a: PhSeSePh, (NH4)2S2O8, MeCN, r.t.:
b: Ph2SnH, AlBN, C6H6, 80oC
Scheme 5.
Scheme 7. Reagents and conditions: (a) PhSeSePh, (NH4)2S2O8,
CF3SO3H, MeCN, rt; (b) Ph3SnH, AIBN, C6H6, 80 °C.
Owing to its radical nature, the substitution of the PhSe
with the allyl group produced the epimerization of the
stereogenic center at the 1-position and gave rise to the
diasteroisomeric mixtures of the alkenols 11, 12 and ent-
11, ent-12 (Scheme 6). These could be easily separated
by column chromatography and hence obtained in an
enantiomerically pure form. The absolute configurations
of the alkenols 11 and 12 were established by compari-
son of their specific rotations with those reported in the
literature.25
As indicated in Scheme 7, by cyclization with phenyl-
selenenyl sulfate, the alkenol 11 afforded a mixture of
the two diastereoisomers 13 and 14 and the alkenol 12
gave a mixture of 15 and 16. In both cases the two
diastereoisomers could be easily separated by column
chromatography and hence obtained in an enantiomer-
ically pure form. Their deselenenylations eventually
afforded the four enantiomerically pure 2,5-dimethyl-3-
phenyltetrahydrofurans 17, 18, 19, and 20.
In the same way, the cyclization (Scheme 8) of the
alkenols ent-11 and ent-12 gave rise to the enantiomeric
tetrahydrofurans ent-13–ent-16. These were then dese-
lenenylated and afforded the four enantiomeric 2,3,5-
trisubstituted tetrahydrofurans ent-17–ent-20.
SnBu3
PhSe
Me
Ph
Ph
Ph
+
AlBN C6H6, 80 oC
OH
Me
OH
Me
OH
10 (1S,2R)
11 (2R,3S) (32%)
[α]D = +23.2
12 (2R,3R) (32%)
[α]D = -33.8
In this case also, using the simple reaction sequence
described herein, all the eight 2,5-dimethyl-3-phenyl-
tetrahydrofurans could be obtained in an enantiomeri-
cally pure form.
SnBu3
PhSe
Me
Ph
OH
Ph
Ph
+
oC
AlBN,C6H6, 80
Me
OH
Me
OH
ent-11 (2S,3R) (28%)
[α]D = -22.7
ent-10 (1R,2S)
ent-12 (2S,3S) (28%)
[α]D = +32.1
The relative configurations indicated in the Schemes 7
and 8 for the tetrahydrofurans 17–20 and ent-17–ent-20
were determined by NMR on the basis of the results of
NOESY experiments.The configurations of the carbon
Scheme 6.

408
M. Tiecco et al. / Tetrahedron: Asymmetry 15 (2004) 405–412
13–16 and ent-13–ent-16 were deduced from those of
2S,3R,5R
2S,3R,5S
Ph
Ph
the corresponding deselenenylated compounds. The
enantiomeric excess of the 2,5-dimethyl-3-phenyl-
tetrahydrofurans was determined by GC–MS experi-
ments using a Chirasildex column.
b
Me
O
Me
Me
O
SePh
ent-17 (95%)
[α]D = -65.4
ent-13 (47%)
[α]D = -15.9
Ph
a
Me
OH
3. Conclusions
2S,3R,5S
2S,3R,5R
Ph
ent-11 (2S,3R)
Ph
b
Starting from commercially available chiral epoxides, all
the possible isomers of 2-methyl-5-phenyl tetra-
hydrofurans and of 2,5-dimethyl-3-phenyltetrahydrofu-
rans were synthesized in an enantiomerically pure form,
using simple conversions promoted by the versatile
organoselenium reagents. All the steps of the synthetic
sequence occurred with satisfactory to good chemical
yields. The present procedure seems to be of general
application and favorably compares with other methods
described in the literature. Further experiments are now
in progress in order to find useful applications of this
new methodology for the preparation of more complex
tetrahydrofurans as well as of other type of heterocyclic
compounds.
Me
O
Me
Me
O
SePh
ent-14 (29%)
[α]D = -121.0
ent-18 (95%)
[α]D = -111.5
2S,3S,5S
2S,3S,5R
Ph
Ph
b
Me
O
Me
Me
O
SePh
ent-15 (45%)
ent-19 (85%)
[α]D = -8.9
[α]D = -36.2
Ph
a
Me
OH
2S,3S,5S
2S,3S,5R
Ph
Ph
ent-12 (2S,3S)
4. Experimental
b
Me
O
1
Me
Me
O
All new compounds were characterized by MS, H, and
SePh
13C NMR spectroscopy. GC analyses and MS spectra
were carried out with an HP 6890 gas chromatograph
(25 m dimethyl silicone capillary column) equipped with
an HP 5973 Mass Selective Detector; for the ions con-
taining selenium only the peaks arising from the sele-
nium-80 isotope is given. GC chiral analyses and MS
spectra were carried out with an HP 5890 gas chro-
matograph (25 m Chirasildex capillary column) equip-
ent-20 (90%)
[α]D = -15.3
ent-16 (25%)
[α]D = +56.9
Scheme 8. Reagents and conditions: (a) PhSeSePh, (NH4)2S2O8,
CF3SO3H, MeCN, rt; (b) Ph3SnH, AIBN, C6H6, 80 °C.
1
atoms in the 2- and 3-positions were obviously un-
changed in respect to those of the starting alkenols 11–
12. This was also confirmed by the strong dipolar
interactions observed between the protons in the 2- and
in the 3-positions in compounds 17–18 and ent-17–ent-
18 and between the methyl in the 2- and the proton in
the 3-position in the cases of compounds 19–20 and ent-
19–ent-20. Further support was obtained by the obser-
vation of the chemical shift of the methyl group in the
1H NMR spectrum. In fact, in compounds 17–18 and
ent-17–ent-18, the methyl in the 2-position and the
phenyl group have a cis relationship and the methyl
group lies in the shielding cone of the aromatic ring. In
these compounds, the absorption due to the methyl
group was observed at 0.8 ppm whereas in compounds
19–20 and ent-19–ent-20 this absorption occurred at
1.2 ppm. NOE experiments allowed the relative config-
uration of the carbon atom in the 5-position to be
determined. In fact, in compounds 17, 20, ent-17, ent-20
a dipolar interaction between the proton at 2 and methyl
at 5 was observed. In compounds 18, 19, ent-18, ent-19
instead the interaction occurred between the methyls as
well as between the protons at the 2- and in the 5-
positions. The relative configurations of the selenides
ped with an HP 5971 Mass Selective Detector. H and
13C NMR spectra were recorded at 400 and
100.62 MHz, respectively, on a Bruker DRX 400
instrument; unless otherwise specified, CDCl3 was used
as solvent and TMS as standard. Optical rotations were
measured with a Jasco DIP-1000 digital polarimeter.
Elemental analyses were carried out on a Carlo Erba
1106 Elemental Analyzer.
4.1. Starting products
The starting epoxides 1, ent-1, 9, and ent-9 were com-
mercial products and were used without further purifi-
cation.
4.2. Conversion of epoxides into b-hydroxyalkyl phenyl
selenides. General procedure
Sodium borohydride (6 mmol) was added to a solution
of diphenyl diselenide (3 mmol) in ethanol (8 mL) at
40 °C. After 45 min a solution of the epoxides 1, ent-1, 9,
ent-9 (4 mmol) in ethanol (8 mL) was added. The pro-

M. Tiecco et al. / Tetrahedron: Asymmetry 15 (2004) 405–412
409
gress of the reaction was monitored by TLC and by
4.3. Conversion of b-hydroxyalkyl phenyl selenides
into alkenols. General procedure
GC–MS. After 2 h the reaction mixture was poured into
aqueous NH4Cl solution and extracted with diethyl
ether. The organic layer was dried over Na2SO4, filtered,
and evaporated under vacuum. Reaction products were
obtained in a pure form after column chromatography
of the residue on silica gel with a 3:7 mixture of diethyl
ether and light petroleum as eluant. The products
obtained and the reaction yields are reported in Schemes
1, 2, and 5. Physical and spectral data are reported
below.
A catalytic amount of AIBN and allyltributylstannane
(7 mmol) were added to a solution of b-hydroxyalkyl
phenyl selenide 2, ent-2, 10, and ent-10 (1 mmol) in
refluxing dry benzene (8 mL) under nitrogen. A second
portion of allyltributylstannane (7 mmol) and a catalytic
amount of AIBN was then added after 1 h. The progress
of the reaction was monitored by TLC and 1H NMR. In
the case of compounds 4 and ent-4 the reactions were
stirred for 5 h and then directly evaporated under vac-
uum. The reaction products were obtained in a pure
form after column chromatography of the residue on
silica gel using dichloromethane as eluant. In the case of
compounds 11, 12, ent-11, ent-12 the reactions were
stirred for 23 h, and the purification of the products
required a first column chromatography on silica gel
using dichloromethane as eluant and a second medium
pressure chromatography on a silica gel column (Merck,
LiChroprepâ Si60, 40–63 lm) using a 1:9mixture of
diethyl ether and light petroleum as eluant. The prod-
ucts obtained and the reaction yields are reported in
Schemes 1, 2, and 6. Physical and spectral data are
reported below.
24
D
4.2.1. (1R)-1-Phenyl-2-(phenylseleno)ethanol, 2. Oil; ½aŠ
¼
1
À14:6 (c 1.70, CHCl3). H NMR: d 7.65–7.55 (m, 2H),
7.45–7.20 (m, 8H), 4.75 (dd, 1H, J ¼ 3:7, 9.3Hz), 3.35
(dd, 1H, J ¼ 3:7, 12.8 Hz), 3.17 (dd, 1H, J ¼ 9:3,
12.8 Hz), 2.91 (br s, 1H); 13C NMR: d 142.5, 133.0 (two
carbons), 129.3, 129.2 (two carbons), 128.5 (two carbons),
127.9, 127.3, 125.8 (two carbons), 72.3, 38.4; MS m=z (rel
int): 278 (37), 172 (100), 157 (38), 121 (53), 107 (48), 103
(54), 91 (67), 77 (92), 51 (32). Anal. Calcd for C14H14OSe:
C, 60.66; H, 5.09. Found: C, 60.73; H, 5.19.
4.2.2.
(1S)-1-Phenyl-2-(phenylseleno)ethanol,
ent-2.
25
D
C14H14OSe: C, 60.66; H, 5.09. Found: C, 60.81; H, 5.17.
½aŠ ¼ þ14:2 (c 1.02, CHCl3). Anal. Calcd for
24
4.3.1. (1S)-1-Phenylpent-4-en-1-ol, 4. Oil; ½aŠ ¼ À31:0
D
(c 3.37, CHCl3).22 1H NMR: d 7.48–7.15 (m, 5H), 5.89
(ddt, 1H, J ¼ 6:4, 10.1, 16.6 Hz), 5.24–4.97 (m, 2H), 4.73
(dd, 1H, J ¼ 5:8, 7.4 Hz), 2.50 (br s, 1H), 2.23–2.15 (m,
2H), 2.0–1.80 (m, 2H); 13C NMR: d 144.6, 138.2, 128.4
(two carbons), 127.5, 125.9 (two carbons), 114.9, 73.9,
38.0, 30.0; MS m=z (rel int): 162 (1), 144 (7), 120 (33),
107 (100), 105 (16), 79(70), 77 (40), 55 (3), 51(9). Anal.
Calcd for C11H14O: C, 81.44; H, 8.70. Found: C, 81.32;
H, 8.63.
4.2.3. (2R)-2-Phenyl-2-(phenylseleno)ethanol, 3. Oil;
26
D
1
½aŠ ¼ þ130:0 (c 2.20, CHCl3). H NMR: d 7.60–7.45
(m, 2H), 7.38–7.20 (m, 8H), 4.41 (dd, 1H, J ¼ 6:5,
7.7 Hz), 4.03 (dd, 1H, J ¼ 7:7, 11.6 Hz), 3.94 (dd, 1H,
J ¼ 6:5, 11.6 Hz), 2.20 (br s, 1H); 13C NMR: d 139.3,
135.3 (two carbons), 129.0 (two carbons), 128.8, 128.7
(two carbons), 128.1, 127.9(two carbons), 127.5, 65.0,
50.8; MS m=z (rel int): 278 (33), 158 (40), 121 (100), 103
(73), 91 (40), 77 (38), 51 (10). Anal. Calcd for
C14H14OSe: C, 60.66; H, 5.09. Found: C, 60.70; H, 5.11.
23
4.3.2. (1R)-1-Phenylpent-4-en-1-ol, ent-4. ½aŠ ¼ þ31:2
D
(c 2.86, CHCl3). Anal. Calcd for C11H14O: C, 81.44; H,
8.70. Found: C, 81.51; H, 8.75.
4.2.4. (2S)-2-Phenyl-2-(phenylseleno)ethanol, ent-3. Oil;
25
D
C14H14OSe: C, 60.66; H, 5.09. Found: C, 60.69; H, 5.00.
½aŠ ¼ À132:8 (c 1.35, CHCl3). Anal. Calcd for
21
D
4.3.3. (2R,3S)-3-Phenylhex-5-en-2-ol, 11. Oil; ½aŠ
¼
þ23:2 (c 2.05, CHCl3).25 1H NMR: d 7.40–7.25 (m, 2H),
7.24–7.17 (m, 3H), 5.66 (dddd, 1H, J ¼ 6:5, 7.2, 10.1,
16.8 Hz), 5.08–4.85 (m, 2H), 3.98 (ddq, 1H, J ¼ 3:8, 5.8,
6.2 Hz), 2.66 (ddd, 1H J ¼ 5:6, 5.8, 9.3 Hz), 2.57 (dddt,
1H, J ¼ 1:2, 5.6, 7.2, 12.5 Hz), 2.47 (dddt, 1H, J ¼ 1:3,
6.5, 9.3, 12.5 Hz), 1.39 (d, 1H, J ¼ 3:8 Hz), 1.21 (d, 3H,
J ¼ 6:2 Hz); 13C NMR: d 140.7, 136.6, 128.9(two car-
bons), 128.5 (two carbons), 126.8, 116.2, 69.2, 53.4, 36.7,
21.2; MS m=z (rel int): 176 (1), 132 (87), 117 (81), 91
(100), 78 (26), 65 (8), 54 (13). Anal. Calcd for C12H16O:
C, 81.77; H, 9.15. Found: C, 81.67; H, 9.20.
4.2.5. (1S,2R)-1-Phenyl-1-(phenylseleno)propan-2-ol, 10.
20
D
1
Oil; ½aŠ ¼ þ255:1 (c 1.96, CHCl3). H NMR: d 7.58–
7.48 (m, 2H), 7.30–7.24 (m, 8H), 4.26 (d, 1H,
J ¼ 5:6 Hz), 4.19(ddq, 1H, J ¼ 3:4, 5.6, 6.0 Hz), 2.35 (d,
1H, J ¼ 3:4 Hz), 1.26 (d, 3H, J ¼ 6:0 Hz); 13C NMR: d
140.4, 134.7 (two carbons), 129.0, 128.6 (two carbons),
128.5 (two carbons), 128.1 (two carbons), 127.6, 127.0,
68.9, 56.9, 20.4; MS m=z (rel int): 292 (25), 248 (7), 167
(26), 135 (100), 115 (14), 91 (38), 77 (19), 57 (17). Anal.
Calcd for C15H16OSe: C, 61.86; H, 5.54. Found: C,
61.80; H, 5.33.
19
4.3.4. (2S,3R)-3-Phenylhex-5-en-2-ol, ent-11. Oil; ½aŠ ¼
4.2.6. (1R,2S)-1-Phenyl-1-(phenylseleno)propan-2-ol, ent-
10. Oil; ½aŠ ¼ À250:2 (c 1.57, CHCl3). Anal. Calcd for
D
22
D
C15H16OSe: C, 61.86; H, 5.54. Found: C, 61.70; H, 5.32.
À22:7 (c 1.51, CHCl3). Anal. Calcd for C12H16O: C,
81.77; H, 9.15. Found: C, 81.85; H, 9.06.

410
M. Tiecco et al. / Tetrahedron: Asymmetry 15 (2004) 405–412
21
D
4.3.5. (2R,3R)-3-Phenylhex-5-en-2-ol, 12. Oil; ½aŠ
¼
1H, J ¼ 6:2, 7.4 Hz), 4.37–4.28 (m, 1H), 3.28 (dd, 1H,
J ¼ 5:1, 12.2 Hz), 3.12 (dd, 1H, J ¼ 7:2, 12.2 Hz), 2.40–
2.25 (m, 1H), 2.18–2.08 (m, 1H), 1.90–1.71 (m, 2H); 13C
NMR: d 142.7, 132.5 (two carbons), 130.3, 129.0 (two
carbons), 128.2 (two carbons), 127.2, 126.8, 125.7 (two
carbons), 81.5, 78.9, 34.4, 33.1, 31.4; MS m=z (rel int):
318 (69), 171 (20), 161 (30), 147 (100), 129 (47), 117 (42),
105 (27), 91 (96), 77 (29), 55 (10). Anal. Calcd for
C17H18OSe: C, 64.35; H, 5.72. Found: C, 64.21; H, 5.69.
1
À33:8 (c 2.0, CHCl3). H NMR: d 7.40–7.20 (m, 5H),
5.68 (dddd, 1H, J ¼ 6:2, 6.6, 10.1, 16.9Hz), 5.10–4.78
(m, 2H), 3.96 (dq, 1H, J ¼ 6:2, 6.4 Hz), 2.75–2.67 (m,
2H), 2.49(dddt, 1H, J ¼ 1:3, 6.2, 9.6, 12.5 Hz), 1.60 (br
s, 1H), 1.07 (d, 3H, J ¼ 6:2 Hz); 13C NMR: d 141.5,
136.8, 128.8 (two carbons), 128.4 (two carbons), 126.4,
115.8, 71.3, 53.3, 35.7, 21.0; MS m=z (rel int): 176 (1),
132 (89), 117 (82), 91 (100), 78 (24), 54 (12). Anal. Calcd
for C12H16O: C, 81.77; H, 9.15. Found: C, 81.81; H, 9.23.
4.4.4. (2R,5S)-2-Phenyl-5-[(phenylseleno)methyl]tetrahy-
23
D
25
D
4.3.6. (2S,3S)-3-Phenylhex-5-en-2-ol, ent-12. Oil; ½aŠ
¼
drofuran, ent-6. Oil; ½aŠ ¼ þ26:0 (c 0.99, CHCl3). Anal.
þ32:1 (c 1.13, CHCl3). Anal. Calcd for C12H16O: C,
Calcd for C17H18OSe: C, 64.35; H, 5.72. Found: C,
64.40; H, 5.80.
81.77; H, 9.15. Found: C, 81.66; H, 9.22.
4.4. Synthesis of tetrahydrofurans. General procedure
for the cyclofunctionalization reactions
4.4.5. (2R,3S,5S)-2-Methyl-3-phenyl-5-[(phenylseleno)-
24
D
methyl]tetrahydrofuran, 13. Oil; ½aŠ ¼ þ16:8 (c 1.61,
1
CHCl3). H NMR: d 7.52–7.50 (m, 2H), 7.32–7.10 (m,
A mixture of diphenyl diselenide (0.5 mmol), ammonium
persulfate (0.5 mmol), and trifluoromethanesulfonic acid
(1 mmol) in acetonitrile (5 mL) was stirred at room
temperature for 15 min. The solution of an alkenol
(1 mmol) was then added and the mixture was stirred for
2 h. The progress of the reaction was monitored by TLC
and GC–MS. The reaction mixtures were poured into a
10% solution of NaHCO3 and extracted with dichloro-
methane. The combined organic layers were washed
with brine, dried over sodium sulfate, filtered, and
evaporated. The reaction products were separated by
medium pressure chromatography on a silica gel column
(Merck, LiChroprepâ Si60, 40–63 lm) using a 1:9mix-
ture of diethyl ether and light petroleum as eluant. The
products obtained and the reaction yields are reported
in Schemes 3, 4, 7, and 8. Physical and spectral data are
reported below.
8H), 4.60–4.54 (m, 1H), 4.42 (dq, 1H, J ¼ 6:2, 6.4 Hz),
3.43 (ddd, 1H, J ¼ 5:2, 6.2, 8.0 Hz), 3.24 (dd, 1H,
J ¼ 5:5, 12.1 Hz), 3.05 (dd, 1H, J ¼ 7:4, 12.1 Hz), 2.41
(ddd, 1H, J ¼ 5:2, 7.8, 12.8 Hz), 2.20 (ddd, 1H, J ¼ 5:6,
8.0, 12.8 Hz), 0.84 (d, 3H, J ¼ 6:4 Hz); 13C NMR: d
140.7, 132.5 (two carbons), 130.1, 129.0 (two carbons),
128.2 (four carbons), 126.8, 126.4, 77.8, 77.0, 48.9, 37.9,
34.2, 16.7; MS m=z (rel int): 332 (26), 330 (14), 157 (25),
143 (18), 131 (100), 117 (23), 91 (62), 77 (14), 55 (6).
Anal. Calcd for C18H20OSe: C, 65.25; H, 6.08. Found:
C, 65.12; H, 6.18.
4.4.6. (2S,3R,5R)-2-Methyl-3-phenyl-5-[(phenylseleno)-
25
D
methyl]tetrahydrofuran, ent-13. Oil; ½aŠ ¼ À15:9
(c 2.40, CHCl3). Anal. Calcd for C18H20OSe: C, 65.25; H,
6.08. Found: C, 65.07; H, 6.14.
4.4.1. (2S,5S)-2-Phenyl-5-[(phenylseleno)methyl]tetrahy-
4.4.7. (2R,3S,5R)-2-Methyl-3-phenyl-5-[(phenylseleno)-
25
D
25
D
drofuran, 5. Oil; ½aŠ ¼ À59:6 (c 0.69, CHCl3). 1H
methyl]tetrahydrofuran, 14. Oil; ½aŠ ¼ þ120:0 (c 2.37,
1
NMR: d 7.60–7.50 (m, 2H), 7.40–7.10 (m, 8H), 5.07 (dd,
1H, J ¼ 6:0, 7.9Hz), 4.50–4.43 (m, 1H), 3.26 (dd, 1H,
J ¼ 5:1, 12.1 Hz), 3.06 (dd, 1H, J ¼ 7:6, 12.1 Hz), 2.43–
2.35 (m, 1H), 2.28–2.20 (m, 1H), 1.93–1.77 (m, 2H); 13C
NMR: d 144.0, 133.5 (two carbons), 130.1, 129.9 (two
carbons), 129.2 (two carbons), 128.1, 127.7, 126.5 (two
carbons), 81.8, 79.9, 36.2, 34.2, 33.2; MS m=z (rel int):
318 (33), 281 (10), 207 (30), 171 (15), 161 (42), 147 (66),
129 (37), 117 (51), 91 (100), 77 (35), 55 (19). Anal. Calcd
for C17H18OSe: C, 64.35; H, 5.72. Found: C, 64.30; H,
5.59.
CHCl3). H NMR: d 7.60–7.50 (m, 2H), 7.30–7.10 (m,
8H), 4.30 (dq, 1H, J ¼ 6:4, 7.2 Hz), 4.24–4.16 (m, 1H),
3.51 (ddd, 1H, J ¼ 7:2, 7.9, 8.3 Hz), 3.33 (dd, 1H,
J ¼ 5:6, 12.1 Hz), 3.15 (dd, 1H, J ¼ 7:0, 12.1 Hz), 2.51
(ddd, 1H, J ¼ 6:1, 7.9, 12.7 Hz), 1.97 (ddd, 1H, J ¼ 8:3,
9.3, 12.7 Hz), 0.84 (d, 3H, J ¼ 6:4 Hz); 13C NMR: d
141.0, 132.5 (two carbons), 130.3, 129.0 (two carbons),
128.4 (two carbons), 128.2 (two carbons), 126.9, 126.4,
78.5, 78.0, 48.6, 38.3, 32.8, 18.0; MS m=z (rel int): 332
(17), 157 (10), 131 (100), 117 (12), 91 (38), 77 (9). Anal.
Calcd for C18H20OSe: C, 65.25; H, 6.08. Found: C,
65.31; H, 6.15.
4.4.2. (2R,5R)-2-Phenyl-5-[(phenylseleno)methyl]tetrahy-
22
D
drofuran, ent-5. ½aŠ ¼ þ59:0 (c 5.11, CHCl3). Anal.
4.4.8. (2S,3R,5S)-2-Methyl-3-phenyl-5-[(phenylseleno)-
20
D
Calcd for C17H18OSe: C, 64.35; H, 5.72. Found: C,
64.28; H, 5.63.
methyl]tetrahydrofuran, ent-14. Oil; ½aŠ ¼ À121:0
(c 2.25, CHCl3). Anal. Calcd for C18H20OSe: C, 65.25;
H, 6.08. Found: C, 65.19; H, 6.21.
4.4.3. (2S,5R)-2-Phenyl-5-[(phenylseleno)methyl]]tetrahy-
26
D
drofuran, 6. Oil; ½aŠ ¼ À26:8 (c 1.51, CHCl3). 1H
4.4.9. (2R,3R,5R)-2-Methyl-3-phenyl-5-[(phenylseleno)-
methyl]tetrahydrofuran, 15. Oil; ½aŠ ¼ þ34:9 (c 1.33,
22
D
NMR: d 7.61–7.50 (m, 2H), 7.40–7.10 (m, 8H), 4.92 (dd,

M. Tiecco et al. / Tetrahedron: Asymmetry 15 (2004) 405–412
411
1
CHCl3). H NMR: d 7.55–7.50 (m, 2H), 7.35–7.15 (m,
NMR: d 143.9, 128.0 (two carbons), 126.9, 125.4 (two
carbons), 80.1, 75.8, 35.5, 34.1, 21.4; MS m=z (rel int):
162 (100), 161 (70), 147 (9), 117 (54), 105 (80), 91 (35), 77
(34), 56 (40). Anal. Calcd for C11H14 O: C, 81.44; H,
8.70. Found: C, 81.37; H, 8.60.
8H), 4.43–4.37 (m, 1H), 3.92 (dq, 1H, J ¼ 6:0, 8.9Hz),
3.21 (dd, 1H, J ¼ 5:2, 12.2 Hz), 3.09(dd, 1H, J ¼ 7:1,
12.2 Hz), 2.90 (q, 1H, J ¼ 8:9Hz), 2.32–2.20 (m, 2H),
1.23 (d, 3H, J ¼ 6:0); 13C NMR: d 141.1, 132.5 (two
carbons), 130.3, 129.0 (two carbons), 128.6 (two car-
bons), 127.6 (two carbons), 126.8, 126.7, 82.9, 77.6, 52.4,
40.5, 33.7, 19.0; MS m=z (rel int): 332 (30), 161 (37), 143
(25), 131 (100), 117 (30), 105 (10), 91 (70), 77 (15), 55 (7).
Anal. Calcd for C18H20OSe: C, 65.25; H, 6.08. Found:
C, 65.09; H, 6.10.
4.5.2. (2S,5R)-2-Methyl-5-phenyltetrahydrofuran, ent-7.
24
D
C11H14O: C, 81.44; H, 8.70. Found: C, 81.59; H, 8.65.
Oil; ½aŠ ¼ þ56:6 (c 1.04, CHCl3). Anal. Calcd for
4.4.10. (2S,3S,5S)-2-Methyl-3-phenyl-5-[(phenylseleno)-
4.5.3. (2S,5S)-2-Methyl-5-phenyltetrahydrofuran, 8. Oil;
18
D
23
D
methyl]tetrahydrofuran, ent-15. Oil; ½aŠ ¼ À36:2
½aŠ ¼ À26:6 (c 0.57, CHCl3). 1H NMR: d 7.45–7.15 (m,
(c 1.02, CHCl3). Anal. Calcd for C18H20OSe: C, 65.25; H,
6.08. Found: C, 65.11; H, 6.17.
5H), 4.91 (dd, 1H, J ¼ 7:1, 7.4 Hz), 4.20 (ddq, 1H,
J ¼ 6:0, 6.2, 7.4 Hz), 2.34 (dddd, 1H, J ¼ 6:4, 7.1, 8.2,
12.3 Hz), 2.12 (dddd, 1H, J ¼ 6:1, 6.2, 8.2, 12.0 Hz), 1.88
(dddd, 1H, J ¼ 6:1, 7.4, 9.1, 12.3 Hz), 1.64 (dddd, 1H,
J ¼ 6:4, 7.4, 9.1, 12.0 Hz), 1.41 (d, 3H, J ¼ 6:0 Hz); 13C
NMR: d 143.4, 128.1 (two carbons), 127.0, 125.7 (two
carbons), 80.9, 75.9, 34.5, 33.0, 21.2; MS m=z (rel int):
162 (100), 161 (77), 147 (10), 117 (49), 107 (45), 105 (77),
91 (29), 77 (32), 56 (36). Anal. Calcd for C11H14O: C,
81.44; H, 8.70. Found: C, 81.29; H, 8.78.
4.4.11. (2R,3R,5S)-2-Methyl-3-phenyl-5-[(phenylseleno)-
24
D
methyl]tetrahydrofuran, 16. Oil; ½aŠ ¼ À55:4 (c 2.45,
1
CHCl3). H NMR: d 7.54–7.50 (m, 2H), 7.38–7.10 (m,
8H), 4.44–4.37 (m, 1H), 4.09(dq, 1H, J ¼ 5:9, 9.4 Hz),
3.27 (dd, 1H, J ¼ 5:1, 12.2 Hz), 3.13 (dd, 1H, J ¼ 7:2,
12.2 Hz), 2.90 (ddd, 1H, J ¼ 7:1, 9.4, 11.7 Hz), 2.54
(ddd, 1H, J ¼ 6:7, 7.1, 12.3 Hz), 2.01 (ddd, 1H, J ¼ 9:1,
11.7, 12.3 Hz), 1.19(d, 3H, J ¼ 5:9Hz); 13C NMR: d
140.1, 132.5 (two carbons), 130.2, 129.0 (two carbons),
128.6 (two carbons), 127.5 (two carbons), 126.8 (two
carbons), 81.6, 77.4, 54.0, 41.7, 33.7, 19.1; MS m=z (rel
int): 332 (42), 161 (43), 143 (27), 131 (100), 117 (31), 105
(10), 91 (69), 77 (15), 55 (7). Anal. Calcd for C18H20OSe:
C, 65.25; H, 6.08. Found: C, 65.22; H, 6.13.
4.5.4. (2R,5R)-2-Methyl-5-phenyltetrahydrofuran, ent-8.
21
D
C11H14O: C, 81.44; H, 8.70. Found: C, 81.43; H, 8.72.
Oil; ½aŠ ¼ þ27:4 (c 1.62, CHCl3). Anal. Calcd for
4.5.5. (2R,3S,5R)-2,5-Dimethyl-3-phenyltetrahydrofuran,
26
D
17. Oil; ½aŠ ¼ þ66:9 (c 1.29, CHCl3). 1H NMR: d 7.30–
4.4.12. (2S,3S,5R)-2-Methyl-3-phenyl-5-[(phenylseleno)-
7.15 (m, 5H), 4.51 (ddq, 1H, J ¼ 5:7, 6.2, 7.7 Hz), 4.38
(dq, 1H, J ¼ 6:3, 6.4 Hz), 3.41 (ddd, 1H, J ¼ 5:2, 6.3,
8.1 Hz), 2.37 (ddd, 1H, J ¼ 5:2, 7.7, 12.8 Hz), 1.98 (ddd,
1H, J ¼ 5:7, 8.1, 12.8 Hz), 1.31 (d, 3H, J ¼ 6:2 Hz), 0.85
(d, 3H, J ¼ 6:4 Hz); 13C NMR: d 141.1, 128.3 (two
carbons), 128.2 (two carbons), 126.2, 76.9, 73.6, 48.9,
39.5, 22.7, 16.8; MS m=z (rel int): 176 (1), 132 (52), 117
(100), 91 (17), 77 (5). Anal. Calcd for C12H16O: C, 81.77;
H, 9.15. Found: C, 81.67; H, 9.10.
22
D
methyl]tetrahydrofuran, ent-16. Oil; ½aŠ ¼ þ56:9
(c 0.94, CHCl3). Anal. Calcd for C18H20OSe: C, 65.25;
H, 6.08. Found: C, 65.19; H, 6.01.
4.5. Reductive deselenenylation. General procedure
A catalytic amount of AIBN and triphenyltin hydride
(0.5 mmol) were added to a solution of the tetra-
hydrofurans (0.3 mmol) in dry benzene (3 mL) and the
mixture refluxed under nitrogen. The reaction was stir-
red and refluxed for 2 h and, after removal of the solvent
under reduced pressure, the residue was purified by
chromatography on silica gel with a 1:9mixture of
diethyl ether and light petroleum as eluant. The prod-
ucts obtained and the reaction yields are reported in
Schemes 3, 4, 7, and 8. Physical and spectral data are
reported below.
4.5.6. (2S,3R,5S)-2,5-Dimethyl-3-phenyltetrahydrofuran,
24
D
for C12H16O: C, 81.77; H, 9.15. Found: C, 81.71; H, 9.21.
ent-17. Oil; ½aŠ ¼ À65:4 (c 0.56, CHCl3). Anal. Calcd
4.5.7. (2R,3S,5S)-2,5-Dimethyl-3-phenyltetrahydrofuran,
24
D
18. Oil; ½aŠ ¼ þ113:0 (c 0.76, CHCl3). 1H NMR: d
7.32–7.15 (m, 5H), 4.20 (dq, 1H, J ¼ 6:4, 7.2 Hz), 4.06
(ddq, 1H, J ¼ 6:1, 6.2, 9.3 Hz), 3.44 (ddd, 1H, J ¼ 7:2,
7.7, 8.4 Hz), 2.47 (ddd, 1H, J ¼ 6:2, 8.4, 12.7 Hz), 1.77
(ddd, 1H, J ¼ 7:7, 9.3, 12.7 Hz), 1.42 (d, 3H,
J ¼ 6:1 Hz), 0.83 (d, 3H, J ¼ 6:4); 13C NMR: d 142.1,
128.5 (two carbons), 128.1 (two carbons), 126.2, 78.1,
74.7, 49.0, 40.9, 20.8, 17.7; MS m=z (rel int): 176 (2), 132
(54), 117 (100), 91 (18), 77 (5). Anal. Calcd for C12H16O:
C, 81.77; H, 9.15. Found: C, 81.70; H, 9.23.
4.5.1. (2R,5S)-2-Methyl-5-phenyltetrahydrofuran, 7. Oil;
25
D
½aŠ ¼ À57:1 (c 1.87, CHCl3). 1H NMR: d 7.50–7.05 (m,
5H), 5.07 (dd, 1H, J ¼ 6:5, 8.0 Hz,), 4.38 (ddq, 1H,
J ¼ 5:9, 6.0, 8.0 Hz), 2.42 (dddd, 1H, J ¼ 3:2, 6.5, 7.3,
12.3 Hz), 2.18 (dddd, 1H, J ¼ 3:2, 5.9, 7.8, 12.0 Hz), 1.91
(dddd, 1H, J ¼ 7:8, 8.0, 9.9, 12.3 Hz), 1.65 (dddd, 1H,
J ¼ 7:3, 8.0, 9.9, 12.0 Hz), 1.35 (d, 3H, J ¼ 6:0 Hz); 13C

412
M. Tiecco et al. / Tetrahedron: Asymmetry 15 (2004) 405–412
4.5.8. (2S,3R,5R)-2,5-Dimethyl-3-phenyltetrahydrofuran,
References and notes
24
D
ent-18. Oil; ½aŠ ¼ À111:5 (c 0.76, CHCl3). Anal. Calcd
1. Tiecco, M. In Electrophilic Selenium, Selenocyclizations;
Wirth, T., Ed.; Topics in Current Chemistry: Organo-
selenium Chemistry: Modern Developments in Organic
Synthesis; Springer: Heidelberg, 2000; pp 7–54.
2. Organoselenium Chemistry––A Pratical Approach; Back,
T. G., Ed.; Oxford: New York, 2000.
3. Selenium Reagents and Intermediates in Organic Synthesis;
Paulmier, C., Ed.; Pergamon: Oxford, 1986.
4. Fragale, G.; Wirth, T. Eur. J. Org. Chem. 1998, 1361–
1369.
5. Deziel, R.; Malenfant, E. J. Org. Chem. 1995, 60, 4660–
4662.
6. Nishibayashi, Y.; Srivastava, S. K.; Takada, H.; Fukuz-
awa, S.; Uemura, S. J. Chem. Soc., Chem. Commun. 1995,
2321–2322.
for C12H16O: C, 81.77; H, 9.15. Found: C, 81.65; H,
9.07.
4.5.9. (2R,3R,5S)-2,5-Dimethyl-3-phenyltetrahydrofuran,
22
D
1
19. Oil; ½aŠ ¼ þ8:2 (c 1.03, CHCl3). H NMR: d 7.30–
7.15 (m, 5H), 4.32–4.24 (m, 1H), 3.85 (dq, 1H, J ¼ 5:9,
8.8 Hz), 2.86 (ddd, 1H, J ¼ 8:0, 8.8, 9.7 Hz), 2.21 (ddd,
1H, J ¼ 7:8, 8.0, 12.7 Hz), 2.01 (ddd, 1H, J ¼ 6:5, 9.7,
12.7 Hz), 1.32 (d, 3H, J ¼ 6:1 Hz), 1.23 (d, 3H,
J ¼ 5:9Hz); 13C NMR: d 142.0, 128.5 (two carbons),
127.6 (two carbons), 126.4, 82.7, 74.6, 52.6, 42.4, 21.9,
19.0; MS m=z (rel int): 176 (3), 132 (63), 117 (100), 91
(19), 77 (5). Anal. Calcd for C12H16O: C, 81.77; H, 9.15.
Found: C, 81.65; H, 9.14.
7. Back, T. G.; Dyck, B. P.; Nan, S. Tetrahedron 1999, 55,
3191–3208.
8. Takada, H.; Nishibayashi, Y.; Uemura, S. J. Chem. Soc.,
Perkin Trans. 1 1999, 1511–1516.
9. Fujita, K.; Murata, K.; Iwaoka, M.; Tomoda, S. J. Chem.
Soc., Chem. Commun. 1995, 1641–1642.
10. Fujita, K.; Murata, K.; Iwaoka, M.; Tomoda, S. Tetra-
hedron 1997, 53, 2029–2048.
11. Deziel, R.; Malenfant, E.; Thibault, C.; Frechette, S.;
Gravel, M. Tetrahedron Lett. 1997, 38, 4753–4756.
12. Wirth, T. Tetrahedron 1999, 55, 1–28.
13. Wirth, T. Angew. Chem., Int. Ed. 2000, 39, 3740–3749.
14. Tiecco, M.; Testaferri, L.; Bagnoli, L.; Marini, F.;
Temperini, A.; Tomassini, C.; Santi, C. Tetrahedron Lett.
2000, 41, 3241–3245.
15. Tiecco, M.; Testaferri, L.; Santi, C.; Tomassini, C.;
Marini, F.; Bagnoli, L.; Temperini, A. Chem. Eur.
J. 2002, 8, 1118–1124.
16. Tiecco, M.; Testaferri, L.; Marini, F.; Sternativo, S.;
Bagnoli, L.; Santi, C.; Temperini, A. Tetrahedron: Asym-
metry 2001, 12, 1493–1502.
17. Tiecco, M.; Testaferri, L.; Bagnoli, L.; Purgatorio, V.;
Temperini, A.; Marini, F.; Santi, C. Tetrahedron: Asym-
metry 2001, 12, 3297–3304.
4.5.10. (2S,3S,5R)-2,5-Dimethyl-3-phenyltetrahydrofu-
20
D
ran, ent-19. Oil; ½aŠ ¼ À8:9 (c 1.76, CHCl3). Anal.
Calcd for C12H16O: C, 81.77; H, 9.15. Found: C, 81.68;
H, 9.11.
4.5.11. (2R,3R,5R)-2,5-Dimethyl-3-phenyltetrahydrofu-
23
D
1
ran, 20. Oil; ½aŠ ¼ þ15:3 (c 1.0, CHCl3). H NMR: d
7.34–7.15 (m, 5H), 4.30 (ddq, 1H, J ¼ 5:5, 6.0, 9.4 Hz),
4.04 (dq, 1H, J ¼ 6:0, 9.0 Hz), 2.91 (ddd, 1H, J ¼ 7:0,
9.0, 11.7 Hz), 2.43 (ddd, 1H, J ¼ 5:5, 7.0, 12.2 Hz), 1.76
(ddd, 1H, J ¼ 9:4, 11.7, 12.2 Hz), 1.35 (d, 3H,
J ¼ 6:0 Hz), 1.21 (d, 3H, J ¼ 6:0 Hz); 13C NMR: d
140.4, 128.1 (two carbons), 127.1 (two carbons), 126.2,
80.6, 74.0, 54.0, 43.3, 21.2, 19.0; MS m=z (rel int): 176
(1), 132 (53), 117 (100), 91 (17), 77 (5). Anal. Calcd for
C12H16O: C, 81.77; H, 9.15. Found: C, 81.66; H, 9.16.
18. Angle, S. R.; White, S. L. Tetrahedron Lett. 2000, 41,
8059–8062, and references cited therein.
19. Harmange, J.-C.; Figadere, B. Tetrahedron: Asymmetry
1993, 4, 1711–1754.
20. Miura, K.; Okajima, S.; Hondo, T.; Nakagawa, T.;
Takahashi, T.; Hosomi, A. J. Am. Chem. Soc. 2000, 122,
11348–11357, and references cited therein.
4.5.12. (2S,3S,5S)-2,5-Dimethyl-3-phenyltetrahydrofu-
22
D
ran, ent-20. Oil; ½aŠ ¼ À15:3 (c 0.86, CHCl3). Anal.
Calcd for C12H16O: C, 81.77; H, 9.15. Found: C, 81.64;
H, 9.12.
21. Olivier, A.; Laurent, D.; Landais, Y.; Planchenault, D.;
Weber, V. Tetrahedron 1997, 53, 4339–4352.
22. Von dem Bussche-Hunnefeld, J. L.; Seebach, D. Tetrahe-
dron 1992, 48, 5719–5730.
Acknowledgements
23. Tiecco, M.; Testaferri, L.; Santi, C.; Tomassini, C.;
Marini, F.; Bagnoli, L.; Temperini, A. Tetrahedron:
Asymmetry 2002, 13, 429–435.
24. Bernardi, L.; Bonini, B. M.; Comes-Franchini, M.; Fochi,
M.; Mazzanti, G.; Ricci, A.; Varchi, G. Eur. J. Org. Chem.
2002, 2776–2784.
Financial support from MIUR, National Project
ÔStereoselezione in Sintesi Organica. Metodologie ed
ApplicazioniÕ, FIRB Project ÔProgettazione, Preparazione
e Valutazione Biologica e Farmacologica di Nuove
Molecole Organiche Quali Potenziali Farmaci Innov-
ativiÕ, Consorzio CINMPIS and University of Perugia,
Progetti di Ateneo, is gratefully acknowledged.
25. Abenhaim, D.; Namy, J. L.; Boireau, G. Bull. Soc. Chim.
Fr. 1971, 9, 3254–3258.