Nucleophile-selective selenocyclizations

Article abstract of DOI:10.1002/ejoc.200400526

Electrophilic cyclizations are one of the major strategies for cyclofunctionalizations of alkenes. Selective selenocyclizations can be performed by adjusting various factors in such reactions. The nature of the electrophile, the counterion, solvents, and

Full text of DOI:10.1002/ejoc.200400526

FULL PAPER
Nucleophile-Selective Selenocyclizations
Shaista S. Khokhar[a] and Thomas Wirth*[a]
Keywords: Alkenes / Electrophiles / Heterocycles / Selenium / Stereoselective synthesis
Electrophilic cyclizations are one of the major strategies for
lizations with high degrees of efficiency. Our investigations
cyclofunctionalizations of alkenes. Selective selenocycliza- have been extended towards stereoselective reactions using
tions can be performed by adjusting various factors in such
reactions. The nature of the electrophile, the counterion,
solvents, and external additives coordinating to the elec-
chiral selenium electrophiles.
( Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
trophilic species are used to control the course of such cyc- Germany, 2004)
Introduction
Functionalizations of inactivated carbonϪcarbon double
bonds are central transformations and electrophilic selenen-
ylations of alkenes is one important strategy.[1] We and
other research groups have shown that this reaction can
also be employed in cyclizations for the synthesis of differ-
ent heterocyclic compounds. Different electrophilic sel-
enium reagents and a variety of reaction conditions have
been employed and recent reviews are highlighting the
broad scope of this general process.[2] Stereoselective func-
tionalization of alkenes with chiral selenium electrophiles
have been performed as well.[3,4] For the elaboration of
highly functionalized heterocyclic compounds this method-
ology continues to receive methodological as well as syn-
thetic attention. Although standard conditions can be used
for these cyclizations, the interactions between the selenium
electrophile, the counterion, the solvent, and the substrate
are not fully understood, and we describe herein our recent
investigations towards selective cyclizations.
For example, the addition of external nucleophiles to the
reaction can lead to either selenolactonization (addition of
10 equivalents of acetic acid) or to methoxyselenenylation
(addition of 10 equivalents of methanol) as shown in
Scheme 1.[5] Furthermore, the outcome of this reaction is
influenced by the nature of the selenium electrophile used.
The interaction between the selenium electrophile and the
nucleophile is dependent upon the nature of the nucleoph-
ile, and the reactivity of the selenium electrophile also de-
pends on the nature of the counterion. The coordination of
the selenium electrophile to a carboxylic acid seems to be
stronger than to an alcohol, and therefore in 1, methoxyse-
lenenylation to 3 is favored over lactonization if methanol
Scheme 1. Selenenylation of 1 under different reaction conditions
is present. An excess of external acetic acid, which then
competes in coordinating to the selenium electrophile, leads
to the formation of only seleno lactone 2. As a chiral sel-
enium electrophile has been used in both reactions, the
products 2 and 3 are formed in a diastereomeric ratio of
84:16 and 95:5, respectively.
Results and Discussion
Several observations on the effect of counterions in se-
lenenylation reactions have already been reported, but they
do not yet allow a conclusive picture.[3c,6] There are also
several investigations on the interaction of selenium electro-
philes with nearby heteroatoms.[7,8,9] In order to probe in
which way different nucleophiles, solvents, and counterions
affect selenocyclizations, we synthesized compound 5 con-
taining two different nucleophiles, an alcohol and a car-
boxylic acid. Alkene 5 was synthesized by the reaction of
3-bromo-2-phenylpropene[10] with the enolate of methyl 3-
[a]
Department of Chemistry, Cardiff University,
P. O. Box 912, Cardiff, CF10 3TB, UK
Fax: (internat.) ϩ 44-29-2087-6968
E-mail: wirth@cf.ac.uk
Eur. J. Org. Chem. 2004, 4567Ϫ4581
DOI: 10.1002/ejoc.200400526
 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
4567

S. S. Khokhar, T. Wirth
FULL PAPER
hydroxypropionate[11] and subsequent hydrolysis of
ester 4.
Scheme 4. Independent synthesis of tetrahydrofurans 6/7 and lac-
tones 8/9 (E ϭ ArSe, I)
Scheme 2. Synthesis of alkene 5
Depending on the cyclizing nucleophile, electrophilic 5-
exo-cyclizations of alkene 5 can then lead to two different
heterocycles: tetrahydrofurans or lactones. We have recently
reported on the first results of how different interactions
with selenium electrophiles can be used to direct cycliza-
tions either towards tetrahydrofurans 6/7 or towards lac-
tones 8/9.[12] We found that the ratio of tetrahydrofurans to
lactones is indeed strongly dependent upon the various fac-
tors mentioned above. Unfortunately, NOE experiments
could not clarify the relative stereochemistry because of
overlapping signals of tetrahydrofurans and lactones, which
are both obtained as mixtures of cis and trans isomers.
However, treatment of 5 with iodine monochloride led
only to iodo lactones 8a/9a (E ϭ I), and no tetrahydrofuran
derivatives were detected. The mixture of diastereomers
generated in such an iodocyclization could be separated.
The major isomer 8a was recrystallized and X-ray analysis
finally allowed an unambiguous assignment of the NMR
signals.[13] The tetrahydrofurans 6a and 7a (E ϭ I) were
only accessible by iodocyclization of 4 to tetrahydrofuran
10a (93% yield) and subsequent ester hydrolysis to 6a/7a
(94% yield). Interestingly, treatment of 8a with sodium hy-
dride did not result in a second cyclization, but in an elimin-
ation, to generate the α-methylene lactone 12 containing a
structural motif found in many natural products.[14] α-
Methylene lactones are also valuable building blocks in syn-
thesis.[15]
Scheme 5. Iodo lactone 8a as the major isomer in an iodocycliz-
ation of 5 and subsequent elimination
Scheme 3. Electrophilic cyclizations to tetrahydrofurans 6/7 and
lactones 8/9 (E ϭ ArSe, I)
The use of 4 in a cyclization reaction to tetrahydrofuran
10 followed by ester hydrolysis allowed the independent
synthesis of 6/7. A sequence of TBDMS-protection and es-
ter hydrolysis precedes the cyclization to lactone 11, which
can be followed by TBAF-deprotection, and leads solely to
derivatives 8/9. But even after the separate synthesis of
tetrahydrofurans 6/7 and lactones 8/9, the stereochemical
assignment was impossible.
Figure 1. View of the crystal structure of 8a showing a cis relation-
ship between the ϪCH2OH and ϪCH2I substituents; the ellipsoids
represent atomic displacement parameters at the 50% probability
level
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Nucleophile-Selective Selenocyclizations
FULL PAPER
Compound 5 was treated with the phenylselenenyl elec- from the corresponding diselenides,[17] were employed in the
trophile (E ϭ PhSe) using various counterions and different cyclization reaction of 5 under various conditions.
reaction conditions. The products of this cyclization are
tetrahydrofurans 6b and 7b (E ϭ PhSe) and lactones 8b and
9b (E ϭ PhSe). There are two main interactions influencing
the cyclization reaction. The selenium electrophile can in-
teract with one of the internal nucleophiles of the unsatu-
rated substrate and there are interactions with an external
nucleophile or solvent. Both of these interactions will ad-
ditionally be influenced by the counterion.
We already know from previous investigations using chi-
ral selenenyl triflates that small amounts of additional sol-
vents (additives) can influence the course of selenenylation
reactions dramatically.[16] Addition of alcohols alters the re-
activity of the selenium electrophiles, and tetrahydrofurans
are the major products. Carboxylic acids, as weakly coordi-
nating additives, lead to a further shift towards tetrahydro-
Figure 3. Chiral selenium electrophiles
furan products. The addition of 10 equivalents of acetic
acid to phenylselenenyl triflate leads to the exclusive forma-
tion of 6b and 7b (37:63). The ratio indicated that there is
almost no interaction between the electrophile and the al-
cohol/carboxylic acid functionality of the substrate. But if
the electrophileϪacid coordination is disturbed by ad-
ditional water, lactones are formed preferentially.
Phenylselenenyl hexafluorophosphate or phenylselenenyl
sulfate can be used to synthesize exclusively the lactone 8b/
9b under the standard reaction conditions. The addition of
methanol (10 equiv.) in these reactions is important, as its
replacement with acetic acid (10 equiv.) leads to the forma-
tion of a mixture of all four products in low yields.[12] Irres-
pective of the additive used, this behavior is also reflected
in the ratio of 8b/9b, as the alcohol moiety of the substrate
5 coordinates to the selenium electrophile during the cycli-
zation, leading to the cis-isomer 8b as the major lactone.
The additive now seems to have no great influence on the
course of the cyclization, because the internal oxygen atom
in electrophiles 13Ϫ15 coordinates to the selenium moiety.
Even the cis/trans-ratio (8/9) is very similar in these experi-
ments (Table 1, Entries 1Ϫ3). Electrophile 13 has a very
strong oxygenϪselenium interaction, leading to exclusive
formation of lactones 8c/9c irrespective of any additive.
Electrophiles 14 and 15 form almost equal mixtures of
tetrahydrofurans and lactones with low (tetrahydrofurans)
to moderate (lactones) cis/trans selectivities, and again, no
influence of an additive can be observed, as the carboxylic
acid/ester moiety coordinates to the selenium electrophile.
Due to the high polarity of the tetrahydrofuran products
6d/7d and 6e/7e, their purification was impossible. To cor-
rectly assign the NMR spectra, ester 4 was subjected to
cyclization with electrophiles 14 and 15. The cis/trans ratio
of about 1:1 in the products 10d and 10e is similar to that
observed in the reactions mentioned in Table 1. The results
of the cyclizations of 4 are summarized in Table 3.
A series of chiral selenium electrophiles 16Ϫ20 has been
investigated in the cyclization reaction. A hydroxy moiety
in the chiral side-chain as in compound 16 and even a pro-
tected hydroxy moiety in the selenium electrophile 17 is able
to coordinate to the selenium moiety efficiently, leading to
Figure 2. Functionalized selenium electrophiles
We then investigated the internal coordination of an oxy- lactone formation exclusively (Table 2, entries 1 and 2). If a
gen heteroatom to the selenium electrophile more closely. second ortho-substituent is introduced, as in selenium elec-
The selenium electrophiles 13Ϫ15 (Figure 3), generated trophile 18, equal amounts of tetrahydrofuran and lactone
Table 1. Selenocyclizations with different functionalized selenium electrophiles using 10 equivalents of additives (no additive, methanol,
acetic acid)
Entry
Electrophile
Products
6/7
8/9
Tetrahydrofurans/Lactones
Yield [%]
1
2
3
13
14
15
8c, 9c
6dϪ9d
6eϪ9e
Ϫ
80:20
82:18Ϫ84:16
81:19Ϫ84:16
0:100
46:54Ϫ52:48
41:59Ϫ50:50
40Ϫ51[a]
45Ϫ99
74Ϫ91
32:68Ϫ52:48
24:76Ϫ50:50
[a]
These reactions were slow, and a considerable amount (24Ϫ27%) of diselenide was formed.
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S. S. Khokhar, T. Wirth
FULL PAPER
Table 2. Selenocyclizations of 5 with different selenium electrophiles with 10 equivalents of methanol as additive
Entry
Electrophile
Products
Solvent
Tetrahydrofurans
6/7/10
8/9
Tetrahydrofurans/
Lactones
Yield [%]
1
2
3
4
5
6
16
17
18
19
20
20
8f, 9f
8g, 9g
10h, 8h, 9h
6i Ϫ9i
6j Ϫ9j
10j
Et2O
Et2O
Et2O
THF
THF
Et2O
Ϫ
Ϫ
79[b]:21[c]
82[d]:18[e]
85[g]:15[h]
87[i]:13[j]
70[m]:30[n]
Ϫ
0:100
0:100
50:50
55:45
60:40
100:0
40[a]
68
77
55
48
30:70[f]
38:62
41[k]:59[l]
42:58[o]
38
[a]
[c]
These reactions were slow, and a considerable amount (25%) of diselenide was formed. [b] 21: 69:31 e.r. 22: 78:22 e.r. [d] 21: 79:21 e.r.
[e]
[i]
[f]
[g]
[h]
22: 83:17 e.r. Methyl ester 10h was isolated: 10h-cis: 86:14 d.r. (NMR); 10h-trans: 82:18 d.r. (NMR). 21: 88:12 e.r. 22: 89:11 e.r.
21: 60:40 e.r. 22: 87:13 e.r. 66:34 d.r. (NMR). 62:38 d.r. (NMR).[m] 21: 73:27 e.r. 22: 88:12 e.r.[o] Methyl ester 10j was isolated.
[j]
[k]
[l]
[n]
10j-cis: 89:11 d.r. (NMR); 10j-trans: 72:28 d.r. (NMR).
are formed without any preference. The stereoselectivity in
the addition reaction to the double bond is, however, im-
proved with this reagent (up to 89:11 d.r.), as we have found
earlier also with other substrates[5,18] and by calculations.[7]
Interestingly, the tetrahydrofuran cyclization product was
isolated as the methyl ester 10h in this reaction. Tiecco at
al. have shown that sulfur substituted selenium electrophiles
of type 19 and 20 can be added to double bonds with very
high selectivities.[19] The diselenides used for the prep-
aration of the electrophiles 19 and 20 were synthesized in
analogy to the procedure reported by Tiecco et al. When
the cyclization of 5 is performed with these electrophiles
using THF as solvent, almost equal amounts of tetrahydro-
furan and lactone products are formed (Table 2, entries 4
and 5). When diethyl ether was used as solvent for the reac-
tion, only electrophile 20 gave a clean reaction resulting in
the exclusive formation of the corresponding tetrahydrofu-
rans, which were again isolated as the corresponding methyl
esters 10j. This reaction was repeated several times with the
same result; obviously an esterification must have taken
place during the reaction. The low solubility of electrophile
20 in diethyl ether slows down the reaction, but the reason
for the esterification observed with the electrophiles 18 and
20 under these reaction conditions, probably catalyzed by
the triflic acid generated during the reaction, remains un-
clear.
Table 3. Synthesis of tetrahydrofurans 10 from ester 4 and differ-
ent electrophiles
Entry
Electrophile
Products
cis/trans
Yield [%]
1
2
3
4
5
6
7
8
ICl[a]
PhSeOTf
13
10a
10b
10c
10d
10e
10f
10g
10i
42:58
39:61
48:52
50:50
93
68
30
79
79
78
41
40
14
15
48:52
16
30[b]:70[c]
44[d]:56[e]
30[f]:70[g]
17
19
[a]
[b]
[c]
No methanol added as additive. 23: 76:24 e.r. 24: 71:29 e.r.
[g]
[d]
[e]
[f]
80:20 d.r. (NMR). 83:17 d.r. (NMR). 83:17 d.r. (NMR).
75:25 d.r. (NMR).
Scheme 6. Radical cleavage of the selenium moiety from the cycli-
zation products (E ϭ ArSe, I)
The synthesis of tetrahydrofurans can also be achieved
by using ester 4 in the cyclization. We have synthesized a
series of tetrahydrofuran cyclization products 10 as outlined
in Scheme 4. The results are summarized in Table 3. There
Because alkene 5 is chiral, we attempted a racemic resolu-
is almost no interaction of the electrophile and the ester tion in reactions using only 0.5 equivalents of electrophile
moiety of 4 as the cis- and trans-isomers of the tetrahydro- 16. Depending on the presence of 10 equivalents of meth-
furan cyclization products 10 are formed in almost equal anol as additive, the ratio of tetrahydrofurans to lactones
amounts.
varied slightly, and the remaining starting material was iso-
The use of chiral selenium electrophiles in the cycliza- lated as the methyl ester 4. But no racemic resolution was
tions allowed us to determine also the enantioselectivity of observed, and the unchanged alkene was isolated as a ra-
the addition reaction. A rough estimate can be obtained cemic mixture.
from the NMR spectroscopic data, but only radical cleav-
The comparison of exo- and endo-cyclizations was made
age of the selenium moiety of either the lactones 8/9 or the using two different diols, 25 and 28. While 25 is accessible
tetrahydrofurans 10 by tributyltin hydride and subsequent by reduction of 5 with lithium aluminum hydride in 85%
HPLC analysis of the products allows an accurate determi- yield, the diol 28 for endo-cyclizations was synthesized by
nation. The enantiomeric ratios of the cleavage products complete reduction of the carbon dioxide addition product
21Ϫ24 are included in the footnotes of Tables 2 and 3.
to the enolate of methyl 5-phenyl-4-pentenoate. The yield
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Nucleophile-Selective Selenocyclizations
FULL PAPER
for the reduction to 28 is low (32%) because of the high tion of the alkene with an alcohol and a carboxylic acid
tendency of the starting material towards decomposition nucleophile can be directed as desired by the choice of the
by decarboxylation.
electrophile and the additive used in the reaction. The coor-
Cyclization of 25 with various electrophiles leads, prob- dination of the electrophile to the additive and/or to one
ably via a coordination of the second hydroxy moiety in 25 of the internal nucleophiles influences the stereochemical
to the electrophile, to the formation of 26 as the major iso- outcome of the reactions as well. The use of chiral selenium
mer. As shown in Table 3, the cis/trans ratios vary from electrophiles led to enantiomerically enriched heterocycles
59:41 to 81:19. A coordination of the electrophile to the as reaction products.
second hydroxy moiety is much stronger and influences
cyclizations of 28, where the major isomer 29 is formed in
Experimental Section
large excess with ratios (29/30) ranging from 86:14 to 94:6.
Different electrophiles have been investigated in cyclizations
of both substrates and the results are summarized in
Table 4.
General Remarks: All reactions were performed under argon with
anhydrous solvents. Melting points are uncorrected. The 1H- and
13C NMR spectra were measured in CDCl3, with TMS as an in-
ternal standard. In NMR assignments of type ‘‘7a-CH’’ or ‘‘6j-
CH2Se’’ 7a or 6j, respectively, refer to compound numbers 7a, 6j
and not to atom position numbers in a molecule.
Cyclization Reaction with Selenium Electrophiles (GP 1):[20] Under
an inert atmosphere, the diselenide (0.085 mmol) was dissolved in
diethyl ether (3.5 mL), cooled to Ϫ78 °C, and treated with bromine
(0.085 mmol, 0.085 mL of a 1  solution in CCl4). After 10 min a
solution of silver triflate (0.24 mmol, 61 mg) in MeOH (2 mmol,
80 µL) (or the corresponding amount of a silver salt dissolved in
10 equivalents of the additive used) was added at Ϫ78 °C and
stirred for 10 min. The mixture was treated with the substrate
(0.17 mmol) and stirred at Ϫ78 °C for 3 h, and then at room tem-
perature for 1 h. The mixture was treated with sym-collidine
(0.13 mmol, 17 µL) followed by water (3 mL). After extraction with
tert-butyl methyl ether, the organic extracts were combined, dried
with MgSO4, and the solvent was evaporated to produce a crude
product which was purified by flash chromatography on silica gel.
Scheme 7. Cyclization of diols 25 and 28 (E ϭ ArSe, I)
Table 4. Cyclizations of 25 and 28 with different electrophiles and
10 equivalents of methanol as additive
Entry
Starting
material
Electrophile
Products
Ratio
Yield
[%]
Deselenenylation by Radical Cleavage of Aryl Selenides (GP 2):
AIBN (0.25 mmol, 41 mg) and tributyltin hydride (0.25 mmol,
73 mg) were added to a solution of the substrate (83 µmol) in re-
fluxing toluene (3 mL), and the mixture was refluxed for 45 min.
The solvent was evaporated, and the crude product was purified by
flash chromatography on silica gel.
1
2
3
4
5
6
7
8
25
25
25
25
28
28
28
28
ICl[a]
PhSeOTf
16
26a, 27a
66:34
70:30
59:41
81:19
88:12
94:6
43
74
28
33
79
50
64
30
26b, 27b
26f[b], 27f[c]
26i[d], 27i
29a, 30a
19
ICl[a]
PhSeOTf
16
29b, 30b
Methyl 2-(Hydroxymethyl)-4-phenylpent-4-enoate (4): Lithium di-
isopropylamide (LDA), prepared from nBuLi (21.2 mmol, 8.48 mL,
2.5  in hexane) and dry diisopropylamine (21.2 mmol, 3 mL) in
THF (60 mL), was added at Ϫ78 °C to methyl 3-hydroxypropi-
onate[11] (1.0 g, 9.62 mmol) in THF (60 mL) and stirred for 1 h
while warming up to room temperature. The reaction mixture was
cooled to Ϫ78 °C, and 3-bromo-2-phenylpropene[10] (1.90 g,
9.62 mmol) was added dropwise. This mixture was stirred for 4 h
at Ϫ78 °C and then for 1 h at room temperature. The reaction was
29f[e], 30f[f]
29i[g], 30i[h]
93:7
86:14
19
[a]
[b]
[c]
No methanol added as additive.
61:39 d.r. (NMR).
59:41
[d]
[e]
[f]
d.r. (NMR).
78:22 d.r. (NMR). 32: 77:23 e.r. 32: 72:28 e.r.
[g]
[h]
32: 77:23 e.r. 32: 88:12 e.r.
In order to accurately determine the stereoselectivity in
the cyclizations with chiral selenium electrophiles 16 quenched with saturated aqueous NH4Cl and extracted with di-
ethyl ether (3 ϫ 50 mL). The combined organic phases were dried
with MgSO4, and after evaporation of the solvent the crude reac-
tion mixture was purified by flash chromatography on silica gel
with tert-butyl methyl ether/petroleum ether (1:2) as eluent to give
a yellow oil in 60% yield (1.27 g, 5.0 mmol). HPLC conditions: Chi-
racel OD-H, flow rate: 0.5 ml minϪ1, 2-propanol/n-hexane, 10:90,
10 °C, Rf(1) ϭ 17.8 min, Rf(2) ϭ 22.4 min. IR (thin film on NaCl):
ν˜ ϭ 3408, 2952, 1714, 1628, 1495, 1437, 1379, 1170, 1029 cmϪ1. 1H
(Table 4, Entries 3 and 7) and 19 (Table 4, Entries 4 and 8),
the selenium moiety in the corresponding addition products
was cleaved with tributyltin hydride/AIBN as described
above. The resulting products, 31 (from 26/27) and 32 (from
29/30), were analyzed by HPLC on a chiral stationary
phase.
NMR (400 MHz, CDCl3): δ ϭ 2.56Ϫ2.67 (m,
2 H, CH2),
Conclusions
2.80Ϫ2.90 (m, 1 H, CH), 3.54 (s, 3 H, CH3), 3.62 (d, J ϭ 5.2 Hz,
2 H, CH2OH), 5.04 (d, J ϭ 1.0 Hz, 1 H, ϭCH2), 5.23 (d, J ϭ
1.0 Hz, 1 H, ϭCH2), 7.15Ϫ7.33 (m, 5 H, Ar) ppm. 13C NMR
We were able to develop conditions for nucleophileϪ
selective electrophilic cyclizations. The course of the cycliza- (100 MHz, CDCl3): δ ϭ 34.6 (CH2), 46.4 (CH), 52.2 (OCH3), 62.8
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S. S. Khokhar, T. Wirth
FULL PAPER
(CH2OH), 115.4 (ϭCH2), 126.3 (CH-Ar), 126.6 (CH-Ar), 128.2 CDCl3): δ ϭ 2.50Ϫ2.70 (m, 2 H, CH2C), 2.97 (quint, J ϭ 8.4 Hz,
(CH-Ar), 128.9 (CH-Ar), 140.4 (C), 145.7 (C-Ar), 175.6 (Cϭ 1 H, CH), 3.29 (d, J ϭ 12.0 Hz, 1 H, CH2Se), 3.39 (d, J ϭ 12.0 Hz,
O) ppm. MS (EI): m/z (%) ϭ 221 (100) [M ϩ Η]ϩ, 203 (4), 143 (2), 1 H, CH2Se), 4.02 (t, J ϭ 8.4 Hz, 1 H, CH2O), 4.14 (t, J ϭ 7.2 Hz,
118 (13), 52 (7); HRMS: calcd. for C13H16O3 221.1177, found
221.1178.
1 H, CH2O), 7.00Ϫ7.40 (m, 10 H, 2 ϫ Ar) ppm. 13C NMR
(100 MHz, CDCl3): δ ϭ 39.5 (CH2), 39.8 (CH2 Se), 42.8 (CH), 68.0
(CH2O), 86.2 (C), 124.1 (CH-Ar), 125.7 (CH-Ar), 126.4 (CH-Ar),
127.4 (CH-Ar), 128.0 (CH-Ar), 130.0 (C-Ar), 131.6 (CH-Ar), 142.7
(CH-Ar), 178.4 (CϭO) ppm. 77Se NMR (57.3 MHz, CDCl3): δ ϭ
257.5 ppm. IR (thin film on NaCl): ν˜ ϭ 3477, 1705, 1643, 1579,
1478, 1437, 1236, 1058, 738, 702 cmϪ1. MS (EI): m/z (%) ϭ 362 (2)
[M ϩ Η]ϩ, 331 (1), 191 (76), 173 (12), 157 (20), 145 (22), 128 (18),
115 (32), 105 (70), 91 (69), 77 (100), 65 (25), 51 (72), 45 (91);
HRMS: calcd. for C18H18O3Se 363.0499, found 363.0495.
2-(Hydroxymethyl)-4-phenylpent-4-enoic Acid (5): Compound 4
(600 mg, 2.73 mmol) was dissolved in MeOH (25 mL), treated at 0
°C with aqueous KOH (13 mL, 30%), and stirred overnight at room
temperature. Water (30 mL) was added, and the solution was
washed with diethyl ether (25 mL). The aqueous layer was cooled
to 0 °C and CH2Cl2 (25 mL) was added followed by 5  HCl until
pH Ͻ 5. The layers were separated, and the aqueous layer was
extracted with CH2Cl2 (3 ϫ 25 mL). The combined organic phases
were dried with MgSO4, and the solvent was evaporated. The prod-
5-{2-[(S)-1-Hydroxypropyl]phenylselanylmethyl}-5-phenyltetra-
uct was obtained as a yellow solid in 95% yield (534 mg, hydrofuran-3-carboxylic Acid (6f/7f): Synthesized from 10f (same
2.59 mmol). No further purification was necessary. M.p. 59Ϫ61 °C.
IR (thin film on NaCl): ν˜ ϭ 3436, 1704, 1495, 1444, 1207, 1028,
procedure as described for 6a/7a from 10a); colorless oil. Yield 70%
(64 mg, 0.2 mmol); d.r. (6f/7f) 48:52. [α]2D3 ϭ ϩ5.04 (c ϭ 0.68,
1
1
904, 780, 706 cmϪ1. H NMR (400 MHz, CDCl3): δ ϭ 2.60Ϫ2.72
CHCl3). H NMR (400 MHz, CDCl3): δ ϭ 0.82 (t, J ϭ 6.4 Hz, 3
(m, 2 H, CH2), 2.93Ϫ3.04 (m, 1 H, CH2), 3.64Ϫ3.81 (m, 2 H, H, 7f-CH3), 0.84 (t, J ϭ 7.6 Hz, 1 H, 6f-CH3), 1.53Ϫ1.70 (m, 2 H,
CH2OH), 5.11 (s, 1 H, ϭCH2), 5.30 (s, 1 H, ϭCH2), 7.20Ϫ7.35 (m, CH2CH3), 2.48Ϫ2.70 (m, 3 H, CH2, 6f-CH), 2.98 (quint, J ϭ
5 H, Ar) ppm. 13C NMR (100 MHz, CDCl3): δ ϭ 34.2 (CH2), 45.9 8.4 Hz, 1 H, 7f-CH), 3.26 (d, J ϭ 12.4 Hz, 1 H, 6f-CH2Se), 3.27
(CH), 62.4 (CH2OH), 115.6 (ϭCH2), 126.6 (CH-Ar), 128.3 (CH-
Ar), 128.9 (CH-Ar), 140.2 (C), 145.3 (C-Ar), 180.2 (CϭO) ppm.
(d, J ϭ 12.4 Hz, 1 H, 7f-CH2Se), 3.32 (d, J ϭ 13.2 Hz, 1 H, 6f-
CH2Se), 3.34 (d, J ϭ 12.4 Hz, 1 H, 7f-CH2Se), 3.94 (t, J ϭ 8.4 Hz,
MS (EI): m/z (%) ϭ 207 (37) [M ϩ Η]ϩ, 191 (100), 173 (65), 159 1 H, 6f-CH2O), 3.99Ϫ4.10 (m, 2 H, 7f-CH2O), 4.20 (t, J ϭ 8.4 Hz,
(58); HRMS: calcd. for C12H14O3 207.1021, found 207.1019.
1 H, 6f-CH2O), 4.85 (t, J ϭ 6.8 Hz, 1 H, 7f-CHOH-Ar), 4.88 (t,
J ϭ 6.8 Hz, 1 H, 6f-CH2O), 6.90Ϫ7.4 (m, 9 H, Ar) ppm. 7f: 13C
NMR (100 MHz, CDCl3): δ ϭ 9.3 (CH3), 30.1 (CH2CH3), 39.9
(CH2), 40.7 (CH), 43.7 (CH2Se), 68.1 (CH2O), 73.3 (CHOH-Ar),
85.8 (C), 124.2 (CH-Ar), 125.2 (CH-Ar), 126.3 (CH-Ar), 126.6
(CH-Ar), 126.9 (CH-Ar), 127.3 (CH-Ar), 128.9 (C-Ar), 133.3 (CH-
Ar), 142.9 (C-Ar), 145.0 (C-Ar), 176.6 (CϭO) ppm. IR (NaCl): ν˜ ϭ
3217, 1710, 1447, 1199, 1050, 758, 703 cmϪ1. MS (EI): m/z (%) ϭ
402 (100) [M Ϫ H2O]ϩ, 391 (38), 216 (22), 208 (99), 197 (50), 152
(6), 118 (96); HRMS: for C21H24O4Se calcd. 420.0834, found
420.0834.
5-(Iodomethyl)-5-phenyltetrahydrofuran-3-carboxylic Acid (6a/7a):
Compound 10a (125 mg, 0.36 mmol) was dissolved in MeOH
(3 mL) and treated with aqueous KOH (1.5 mL, 30%). The reaction
mixture was stirred at room temperature for 6 h and diluted with
water (10 mL). Diethyl ether (10 mL) was added, the aqueous layer
was acidified by adding 2  HCl until pH Ͻ 4 and extracted with
CH2Cl2 (3 ϫ 10 mL). The collected organic extracts were dried
over MgSO4, and the solvent was evaporated to produce a colorless
solid (112 mg, 0.34 mmol) with 94% yield. d.r. (6a/7a) 43:57; m.p.
1
108Ϫ110 °C. H NMR (400 MHz, CDCl3): δ ϭ 2.63 (dd, J ϭ 8.8,
18.8 Hz, 2 H, CH2), 3.03 (quint, J ϭ 8.0 Hz, 1 H, 7a-CH), 3.41 (d, 5-{[2-[(R)-1-(Ethylsulfanyl)ethyl]phenyl]selanylmethyl}-5-phenyl-
J ϭ 10.4 Hz, 1 H, 6a-CH2I), 3.46 (d, J ϭ 10.8 Hz, 1 H, 6a-CH2I), tetrahydrofuran-3-carboxylic Acid (6i/7i): Synthesized according to
3.50 (d, J ϭ 10.8 Hz, 1 H, 7a-CH2I), 3.54 (d, J ϭ 10.4 Hz, 1 H, 7a-
CH2I), 3.93 (t, J ϭ 8.8 Hz, 1 H, 6a-CH2O), 4.09 (t, J ϭ 8.8 Hz, 1
GP 1. Purification by flash chromatography on silica gel with di-
ethyl ether/petroleum ether, 2:1. Yield 28% (19 mg, 0.042 mmol);
H, 7a-CH2O), 4.19 (t, J ϭ 8.2 Hz, 1 H, 7a-CH2O), 4.27 (t, J ϭ colorless oil; d.r. (6i/7i) 38:62. [α]2D3 ϭ Ϫ18.1 (c ϭ 0.21, CHCl3). 7i:
8.4 Hz, 1 H, 6a-CH2O), 7.15Ϫ7.40 (m, 5 H, Ar) ppm. 7a: 13C 1H NMR (400 MHz, CDCl3): δ ϭ 1.06 (t, J ϭ 7.2 Ηz, 3 H, CH3),
NMR (100 MHz, CDCl3): δ ϭ 17.8 (CH2), 40.8 (CH2O), 44.4 1.45 (d, J ϭ 7.2 Ηz, 3 H, CH3), 2.25 (q, J ϭ 7.6 Ηz, 2 H, CH2CH3),
(CH), 69.7 (CH2I), 86.0 (C), 125.7 (CH-Ar), 128.3 (CH-Ar), 128.9 2.58 (d, J ϭ 7.6 Ηz, 1 H, CH2), 2.62 (d, J ϭ 7.6 Ηz, 1 H, CH2),
(CH-Ar), 142.5 (C-Ar), 179.4 (CϭO) ppm. IR (NaCl): ν˜ ϭ 3440,
3.00 (quint, J ϭ 8.4 Ηz, 1 H, CH), 3.28 (d, J ϭ 12.0 Ηz, 1 H,
1707, 1447, 1188, 1057, 762, 702 cmϪ1. MS (EI): m/z (%) ϭ 350 (3) CH2Se), 3.38 (d, J ϭ 11.6 Ηz, 1 H, CH2Se), 4.05 (t, J ϭ 8.8 Ηz, 1
[M ϩ NΗ4]ϩ, 224 (100), 208 (37), 191 (15), 152 (16), 134 (10), 119
(20), 106 (9), 78 (6), 52 (55); HRMS: calcd. for C12H13O3I
350.0253, found 350.0256.
H, CH2O), 4.18 (t, J ϭ 7.2 Ηz, 1 H, CH2O), 4.60 (q, J ϭ 7.2 Ηz,
1 H, CHS), 6.90Ϫ7.48 (m, 9 H, Ar) ppm. 13C NMR (100 MΗz,
CDCl3): δ ϭ 15.1 (CH3CH2), 22.8 (CH2CH3), 25.6 (CH3), 41.0
(CH-Ar), 41.8 (CH), 42.9 (CH2), 44.0 (CH2Se), 69.6 (CH2O), 87.7
(C), 125.5 (CH-Ar), 127.5 (CH-Ar), 127.8 (CH-Ar), 127.9 (CH-
Ar), 128.0 (CH-Ar), 128.8 (CH-Ar), 132.0 (C-Ar), 134.1 (CH-Ar),
144.2 (C-Ar), 146.0 (C-Ar), 178.5 (CϭO) ppm. IR (NaCl): ν˜ ϭ
3367, 3046, 2956, 2915, 1725, 1711, 1594, 1489, 1464, 1448, 1368,
1333, 1263, 1217, 1157, 1101, 1049, 1027, 761, 700, 650 cmϪ1. MS
(EI): m/z (%) ϭ 398 (2) [M ϩ NH4]ϩ, 468 (100), 451 (33), 433 (9),
422 (38); ΗRMS calcd. for C22H26O3SSe 468.1106, found 468.1109.
5-Phenyl-5-(phenylselanylmethyl)tetrahydrofuran-3-carboxylic Acid
(6b/7b): Synthesized according to GP 1: yield 75% (192 mg,
0.54 mmol). Synthesized from 10b (same procedure as described
for 6a/7a from 10a), product needed no further purification: yield
80% (205 mg, 0.58 mmol); white solid; d.r. (6b/7b) 37:63; m.p.
1
52Ϫ55 °C. 6b: H NMR (400 MHz, CDCl3): δ ϭ 2.50Ϫ2.70 (m, 2
H, CH2), 3.18 (d, J ϭ 12.4 Hz, 1 H, CH2Se), 3.30Ϫ3.38 (m, 1 H,
CH), 3.32 (d, J ϭ 11.6 Hz, 1 H, CH2Se), 3.89 (t, J ϭ 8.4 Hz, 1 H,
CH2O), 4.18 (t, J ϭ 8.4 Hz, 1 H, CH2O), 7.00Ϫ7.40 (m, 10 H, 5-{[2-[(R)-1-(Ethylsulfanyl)ethyl]-6-methoxyphenyl]selanylmethyl}-
Ar) ppm. 13C NMR (100 MHz, CDCl3): δ ϭ 39.3 (CH2), 40.7 (CH2 5-phenyltetrahydrofuran-3-carboxylic Acid (6j/7j): Synthesized ac-
Se), 43.9 (CH), 68.1 (CH2O), 85.9 (C), 124.1 (CH-Ar), 125.8 (CH-
Ar), 126.3 (CH-Ar), 127.3 (CH-Ar), 128.0 (CH-Ar), 129.9 (C-Ar), with diethyl ether/petroleum ether, 2:1. Yield 23% (17 mg,
131.6 (CH-Ar), 143.8 (C-Ar), 177.7 (CϭO) ppm. 77Se NMR 0.035 mmol), colorless oil, d.r. (6j/7j) 47:53. [α]D23 ϭ Ϫ26.96 (c ϭ
(57.3 MHz, CDCl3): δ ϭ 255.3 ppm. 7b: 1H NMR (400 MHz, 0.46, CHCl3). 1H NMR (400 MHz, CDCl3): δ ϭ 1.05 (t, J ϭ
cording to GP 1. Purification by flash chromatography on silica gel
4572
 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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Eur. J. Org. Chem. 2004, 4567Ϫ4581

Nucleophile-Selective Selenocyclizations
FULL PAPER
7.6 Ηz, 3 H, 6j-CH3), 1.08 (t, J ϭ 7.6 Ηz, 3 H, 7j-CH3), 1.34 (d,
(CϭO) ppm. 77Se NMR (57.3 MHz, CDCl3): δ ϭ 259.7 ppm. 9b:
J ϭ 7.2 Ηz, 3 H, 6j-CH3), 1.44 (d, J ϭ 7.2 Ηz, 3 H, 7j-CH3), 2.25 1H NMR (400 MHz, CDCl3): δ ϭ 2.33Ϫ2.41 (m, 1 H, CH2),
(q, J ϭ 7.2 Ηz, 2 H, 6j-CH2CH3), 2.29 (q, J ϭ 8.4 Ηz, 2 H, 7j-
2.71Ϫ2.80 (m, 1 H, CH), 3.17 (quint, J ϭ 5.6 Hz, 1 H, CH), 3.34
CH2CH3), 2.49Ϫ2.57 (m, 1 H, CH2), 2.70Ϫ2.90 (m, 1 H, CH2), (d, J ϭ 13.6 Hz, 1 H, CH2Se), 3.38 (d, J ϭ 13.2 Hz, 1 H, CH2Se),
2.98 (quint, J ϭ 8.4 Ηz, 1 H, 9j-CH), 3.21 (d, J ϭ 11.6 Ηz, 1 H,
6j-CH2Se), 3.23 (d, J ϭ 12.0 Ηz, 1 H, 7j-CH2Se), 3.38Ϫ3.45 (m, 1
3.62 (dd, J ϭ 6.0, 11.2 Hz, 1 H, CH2OH), 3.78 (dd, J ϭ 5.2,
11.6 Hz, 1 H, CH2OH), 7.10Ϫ7.40 (m, 10 H, Ar) ppm. 13C NMR
H, 6j-CH), 3.76 (s, 3 H, 7j-OCH3), 3.79 (s, 3 H, 6j-OCH3), 3.88 (t, (100 MHz, CDCl3): δ ϭ 34.9 (CH2), 40.3 (CH2Se); 42.5 (CH), 60.5
J ϭ 8.8 Ηz, 1 H, 6j-CH2O), 4.04 (t, J ϭ 8.4 Ηz, 1 H, 7j-CH2O), (CH2OH), 86.0 (C), 123.6 (CH-Ar), 126.5 (CH-Ar), 127.1 (CH-
4.13 (t, J ϭ 8.4 Ηz, 1 H, 7j-CH2O), 4.21 (t, J ϭ 8.4 Ηz, 1 H, 6j- Ar), 127.6 (CH-Ar), 128.3 (CH-Ar), 128.9 (C-Ar), 132.0 (C-Ar),
CH2O), 4.76 (q, J ϭ 6.8 Ηz, 1 H, 7j-CH-Ar), 4.89 (q, J ϭ 7.2 Ηz, 142.2 (CH-Ar), 176.0 (CϭO) ppm. 77Se NMR (57.3 MHz, CDCl3):
1 H, 6j-CH-Ar), 6.60Ϫ7.40 (m, 9 H, Ar) ppm. 7j: 13C NMR
δ ϭ 258.5 ppm. IR (thin film on NaCl): ν˜ ϭ 3426, 3068, 2932, 1771,
(100 MΗz, CDCl3): δ ϭ 15.1 (CH3CH2), 22.9 (CH2CH3), 25.6 1579, 1478, 1448, 1314, 1155, 1022, 969, 738, 701 cmϪ1. MS (EI):
(CH3), 40.6 (CH), 41.3 (CH2), 44.0 (CH-Ar), 45.4 (CH2Se), 56.4 m/z (%) ϭ 380 (12) [M ϩ NΗ4]ϩ, 362 (13), 224 (81), 206 (100), 194
(OCH3), 69.5 (CH2O), 87.9 (C), 109.3 (CH-Ar), 120.0 (CH-Ar), (32), 178 (37), 161 (28), 119 (35), 96 (20), 78 (20); HRMS: calcd.
127.7 (CH-Ar), 128.6 (CH-Ar), 129.7 (CH-Ar), 144.5 (C-Ar), 146.1
(C-Ar), 150.1 (C-Ar), 159.7 (C-Ar), 178.3 (CϭO) ppm. IR (NaCl):
ν˜ ϭ 3364, 2962, 2922, 2360, 1707, 1569, 1463, 1423, 1260, 1057,
771, 695 cmϪ1. MS (EI): m/z (%) ϭ 398 (2) [M ϩ NH4]ϩ, 503 (1),
275 (22), 245 (16), 213 (42), 183 (100), 145 (23), 102 (36); ΗRMS:
calcd. for C23H28O4SSe 503.0766, found 503.0763.
for C18H18O3Se 380.0765, found 380.0766.
3-(Hydroxymethyl)-5-{[2-(hydroxymethyl)phenyl]selanylmethyl}-5-
phenyldihydro-3H-furan-2-one (8c/9c): Synthesized according to GP
1. Purification by flash chromatography on silica gel with ethyl
acetate/petroleum ether, 2:1. Yield 51% (30 mg, 0.077 mmol); color-
less oil; d.r. (8c/9c) 80:20. 1H NMR (400 MHz, CDCl3): δ ϭ
2.50Ϫ2.80 (m, 2 H, CH2), 3.35 (d, J ϭ 13.2 Hz, 1 H, CH2Se), 3.50
(d, J ϭ 13.2 Hz, 1 H, CH2Se), 3.68 (dd, J ϭ 4.4, 11.2 Hz, 1 H, 8c-
CH2OH), 3.76 (dd, J ϭ 5.2, 11.2 Hz, 1 H, 9c-CH2OH), 3.92 (dd,
J ϭ 3.6, 11.2 Hz, 1 H, 8c-CH2OH), 4.05 (q, J ϭ 12.4 Hz, 2 H, 9c-
CH2OH), 4.66 (q, J ϭ 12.8 Hz, 2 H, 8c-CH2OH-Ar), 7.05Ϫ7.58
(m, 9 H, 2 ϫ Ar) ppm. 8c: 13C NMR (100 MHz, CDCl3): δ ϭ 36.6
(CH2), 41.7 (CH2Se), 43.1 (CH), 60.7 (CH2OH), 65.7 (CH2OH-
Ar), 87.2 (C), 125.0 (C-Ar), 125.2 (CH-Ar), 128.6 (CH-Ar), 128.7
(CH-Ar), 129.0 (CH-Ar), 129.2 (CH-Ar), 130.6 (C-Ar), 135.2 (CH-
Ar), 141.9 (CH-Ar), 143.1 (C-Ar), 177.5 (CϭO) ppm. IR (NaCl):
3-(Hydroxymethyl)-5-(iodomethyl)-5-phenyldihydro-3H-furan-2-one
(8a/9a): Compound 5 (50 mg, 0.24 mmol) was dissolved in CH2Cl2
(8 mL), iodine monochloride (0.39 mmol, 1  solution in CH2Cl2)
was added, and the reaction mixture was stirred at room tempera-
ture for 15 min. The reaction was quenched with saturated aqueous
Na2S2O3 and extracted with CH2Cl2. The combined organic ex-
tracts were dried over MgSO4, the solvent was evaporated, and the
crude product was purified by flash chromatography on silica gel
using tert-butyl methyl ether/petroleum ether (1:1) as eluent. Yield
74% (63 mg, 0.18 mmol); colorless white solid; m.p. 108Ϫ110 °C;
d.r. (8a/9a) 76:24. The mixture was further purified by flash chro-
matography on silica gel using tert-butyl methyl ether/petroleum
ether (1:1) as eluent to yield 56% (45 mg, 0.134 mmol) of the cis
isomer (8a) and 18% (15 mg, 0.045 mmol) of a mixture of 8a and
9a. The X-ray structure of the isomer 8a clarified the stereochem-
ν˜ ϭ 3376, 2359, 1758, 1643, 1446, 1236, 1145, 952, 766, 700 cmϪ1
.
MS (EI): m/z (%) ϭ 410 (2) [M ϩ NΗ4]ϩ, 166 (9), 128 (30), 105
(49), 91 (73), 79 (31), 42 (47); HRMS: calcd. for C19H20O4Se
410.0865, found 410.0866.
2-{[4-(Hydroxymethyl)-5-oxo-2-phenyltetrahydrofuran-2-yl]methyl-
selanyl}benzoic Acid (8d/9d): Synthesized according to GP 1. Purifi-
cation by flash chromatography on silica gel with ethyl acetate/
petroleum ether, 1:1. Yield 23% (9 mg, 0.022 mmol), colorless oil;
d.r. (8d/9d) 80:20. 1H NMR (400 MHz, CDCl3): δ ϭ 2.40Ϫ2.98 (m,
1 H, CH2), 3.27 (quint, J ϭ 4.8 Hz, 1 H, 8d-CH), 3.66 (d, J ϭ
11.2 Hz, 1 H, 8d-CH2Se), 3.73 (d, J ϭ 11.2 Hz, 1 H, 8d-CH2Se),
3.79 (dd, J ϭ 4.4, 11.6 Hz, 1 H, 8d-CH2OH), 3.86 (dd, J ϭ 4.8,
11.2 Hz, 1 H, 9d-CH2OH), 3.92 (dd, J ϭ 4.0, 11.6 Hz, 1 H, 8d-
CH2OH), 7.22Ϫ8.10 (m, 9 H, Ar) ppm. 13C NMR (100 MHz,
CDCl3): δ ϭ 35.3 (CH2), 40.4 (CH2Se), 42.9 (CH), 61.1 (CH2OH),
85.6 (C), 125.5 (CH-Ar), 128.9 (CH-Ar), 129.1 (C-Ar), 129.2 (CH-
Ar), 129.3 (CH-Ar), 129.4 (CH-Ar), 129.7 (CH-Ar), 130.6 (CH-
Ar), 134.2 (C-Ar), 140.0 (CH-Ar), 172.0 (OϭCAr), 177.1 (Cϭ
O) ppm. IR (NaCl): ν˜ ϭ 3428, 1770, 1688, 1599, 1579, 1453, 1423,
1
istry.[13] M.p. 108Ϫ110 °C; 8a: H NMR (400 MHz, CDCl3): δ ϭ
2.56Ϫ2.77 (m, 3 H, CH2C, CH), 3.58 (d, J ϭ 11.2 Hz, 1 H, CH2I),
3.63 (d, J ϭ 11.2 Hz, 1 H, CH2I), 3.77 (dd, J ϭ 4.8, 11.2 Hz, 1 H,
CH2OH), 3.92 (dd, J ϭ 4.0, 11.2 Hz, 1 H, CH2OH), 7.25Ϫ7.40 (m,
5 H, Ar) ppm. 13C NMR (100 MHz, CDCl3): δ ϭ 16.1 (CH2I), 37.1
(CH2C), 43.3 (CH); 61.1 (CH2OH), 85.1 (C), 125.4 (CH-Ar), 129.2
1
(CH-Ar), 129.3 (CH-Ar), 140.0 (C-Ar), 176.9 (CϭO) ppm. 9a: H
NMR (400 MHz, CDCl3): δ ϭ 2.48Ϫ2.55 (m,
1 H, CH2),
2.80Ϫ2.89 (m, 1 H, CH2), 3.53Ϫ3.65 (m, 2 H, CH2Se), 3.65 (dd,
J ϭ 5.6, 10.8 Hz, 1 H, CH2OH), 3.83 (dd, J ϭ 4.8, 11.2 Hz, 1 H,
CH2OH), 7.20Ϫ7.45 (m, 5 H, Ar) ppm. IR (thin film on NaCl):
ν˜ ϭ 3437, 1768, 1644, 1448, 1152, 699, 650 cmϪ1. MS (EI): m/z
(%) ϭ 350 (27) [M ϩ NΗ4]ϩ, 332 (11), 302 (3), 258 (3), 224 (75),
206 (100), 178 (26), 161 (16), 145 (13), 119 (11), 91 (5); HRMS:
calcd. for C12H13O3I 350.0253, found 350.0250.
1328, 1292, 1157, 1097, 1067, 1032, 926, 766, 706 cmϪ1
.
3-(Hydroxymethyl)-5-phenyl-5-(phenylselanylmethyl)dihydro-3H-
furan-2-one (8b/9b): Synthesized according to GP 1. Purification
by flash chromatography on silica gel with tert-butyl methyl ether/
petroleum ether, 1:1. Yield 60% (52 mg, 0.144 mmol), white solid;
Methyl 2-{[4-(Hydroxymethyl)-5-oxo-2-phenyltetrahydrofuran-2-yl]-
methylselanyl}benzoate (8e/9e): Synthesized according to GP 1.
Purification by flash chromatography on silica gel with ethyl acet-
ate/petroleum ether, 1:2. Yield 31% (22 mg, 0.052 mmol); colorless
m.p. 50Ϫ52 °C; d.r. (8b/9b) 83:17; 8b: 1H NMR (400 MHz, CDCl3): oil; d.r. (8e/9e) 84:16; m.p. 140Ϫ142 °C. 1H NMR (400 MHz,
δ ϭ 2.54Ϫ2.71 (m, 3 H, CH2, CH), 3.35 (d, J ϭ 13.2 Hz, 1 H,
CDCl3): δ ϭ 2.40Ϫ2.59 (m, 1 H, 9e-CH2), 2.59Ϫ2.76 (m, 3 H, 8e-
CH2Se), 3.48 (d, J ϭ 13.2 Hz, 1 H, CH2Se), 3.75 (dd, J ϭ 5.2, CH2, CH), 2.88Ϫ2.98 (m, 1 H, 9e-CH2), 3.22 (quint, J ϭ 8.4 Hz,
11.2 Hz, 1 H, CH2OH), 3.88 (dd, J ϭ 4.0, 11.2 Hz, 1 H, CH2OH), 1 H, 9e-CH), 3.38 (d, J ϭ 12.4 Hz, 1 H, CH2Se), 3.47 (d, J ϭ
7.10Ϫ7.40 (m, 10 H, 2 ϫ Ar) ppm. 13C NMR (100 MHz, CDCl3): 12.4 Hz, 1 H, CH2Se), 3.64 (dd, J ϭ 4.9, 11.6 Hz, 1 H, 9e-CH2OH),
δ ϭ 35.3 (CH2), 40.0 (CH2Se), 41.5 (CH), 59.8 (CH2OH), 85.9 (C),
3.75 (dd, J ϭ 5.2, 11.2 Hz, 1 H, 8e-CH2OH), 3.84 (s, 3 H, 8e-
123.8 (CH-Ar), 126.4 (CH-Ar), 127.3 (CH-Ar), 128.1 (CH-Ar), OCH3), 3.85 (s, 3 H, 9e-OCH3), 3.87 (dd, J ϭ 3.9, 11.4 Hz, 1 H, 8e-
128.3 (CH-Ar), 129.1 (C-Ar), 132.2 (CH-Ar), 140.4 (C-Ar), 176.1 CH2OH), 7.10Ϫ7.95 (m, 9 H, Ar) ppm. 8e: 13C NMR (100 MHz,
Eur. J. Org. Chem. 2004, 4567Ϫ4581
www.eurjoc.org
 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
4573

S. S. Khokhar, T. Wirth
FULL PAPER
CDCl3): δ ϭ 37.0 (CH2), 38.2 (CH2Se), 43.0 (CH), 52.8 (OCH3), 0.45, CHCl3). 1H NMR (400 MHz, CDCl3): δ ϭ 1.26 (d, J ϭ
61.2 (CH2OH), 87.2 (C), 125.3 (CH-Ar), 125.5 (CH-Ar), 128.9 6.8 Hz, 3 H, 8 h-CH3), 1.30 (d, J ϭ 6.8 Hz, 3 H, 9 h-CH3),
(CH-Ar), 129.0 (CH-Ar), 129.2 (CH-Ar), 131.8 (CH-Ar), 133.1 (C- 2.30Ϫ2.52 (m, 1 H, CH2CH3), 2.56Ϫ2.65 (m, 1 H, 9 h-CH),
Ar), 136.9 (C-Ar), 141.9 (C-Ar), 167.7 (CϭO-Ar), 177.5 (Cϭ 2.82Ϫ3.00 (m, 1 H, CH2), 3.18 (d, J ϭ 14.0 Hz, 1 H, 8 h-CH2Se),
O) ppm. IR (NaCl): ν˜ ϭ 3458, 2925, 1767, 1708, 1579, 1433, 1303,
3.35 (d, J ϭ 14.0 Hz, 1 H, 9 h-CH2Se), 3.43 (d, J ϭ 14.0 Hz, 1 H,
1273, 1256, 1147, 1097, 1032, 750, 698 cmϪ1. MS (EI): m/z (%) ϭ 9 h-CH2Se), 3.58 (d, J ϭ 14.0 Hz, 1 H, 8 h-CH2Se), 3.70 (dd, J ϭ
421 (9) [M ϩ H]ϩ, 288 (9), 215 (100), 191 (12), 159 (6), 143 (6),
100 (5); HRMS: for C20H20O5Se calcd. 421.0549, found 421.0546.
4.8, 11.6 Hz, 1 H, 8 h-CH2OH), 3.80 (s, 3 H, 8 h-OCH3), 3.82 (s, 3
H, 9 h-OCH3), 3.93 (dd, J ϭ 3.6, 11.6 Hz, 1 H, 9 h-CH2OH), 3.95
(dd, J ϭ 4.0, 11.6 Hz, 1 H, 8 h-CH2OH), 5.36 (q, J ϭ 6.4 Hz, 1 H,
3-(Hydroxymethyl)-5-{2-[(R)-(1-hydroxypropyl)phenyl]selanyl-
methyl}-5-phenyldihydro-3H-furan-2-one (8f/9f): Synthesized ac-
cording to GP 1. Purification by flash chromatography on silica gel
with tert-butyl methyl ether/petroleum ether, 2:1. Yield 40% (27 mg,
0.064 mmol); colorless oil; d.r. (8f/9f) 79:21. [α]2D2 ϭ Ϫ8.0 (c ϭ 0.40,
8 h-CHOH-Ar), 5.56 (q, J ϭ 6.4 Hz,
1 H, 9 h-CHOH-Ar),
6.70Ϫ7.40 (m, 8 H, Ar) ppm. 13C NMR (100 MHz, CDCl3): δ ϭ
25.4 (CH3), 36.5 (CH2), 39.3 (CH2Se), 43.2 (CH), 56.5 (OCH3),
60.4 (CH2OH), 69.7 (CHOH-Ar), 87.8 (C), 109.9 (CH-Ar), 116.7
(C-Ar), 118.5 (CH-Ar), 125.1 (CH-Ar), 128.6 (CH-Ar), 128.9 (CH-
Ar), 142.4 (C-Ar), 151.1 (C-Ar), 159.3 (C-Ar), 178.2 (CϭO) ppm.
IR (NaCl): ν˜ ϭ 3447, 2937, 1760, 1637, 1564, 1464, 1261, 1157,
1054, 916, 846, 786, 705 cmϪ1. MS (EI): m/z (%) ϭ 454 (12) [M ϩ
NH4]ϩ, 436 (15), 419 (23), 312 (6), 286 (12), 260 (12), 254 (27), 246
(36); HRMS: calcd. for C21H24O5Se 454.1127, found 454.1131.
1
CHCl3). H NMR (400 MHz, CDCl3): δ ϭ 0.84 (t, J ϭ 7.6 Hz, 3
H, 9f-CH3), 0.85 (t, J ϭ 7.6 Hz, 3 H, 8f-CH3), 1.49Ϫ1.76 (m, 2 H,
CH2CH3), 2.35Ϫ2.67 (m, 2 H, 9f-CH2), 2.57 (t, J ϭ 11.6 Hz, 1 H,
8f-CH2O), 2.85 (t, J ϭ 11.6 Hz, 1 H, 8f-CH2O), 2.58Ϫ2.67 (m, 1
H, CH), 3.32 (d, J ϭ 13.6 Hz, 1 H, 9f-CH2Se), 3.35 (d, J ϭ 13.6 Hz,
1 H, 8f-CH2Se), 3.45 (d, J ϭ 14.0 Hz, 1 H, 8f-CH2Se), 3.51 (d, J ϭ
13.2 Hz, 1 H, 9f-CH2Se), 3.62 (dd, J ϭ 3.6, 11.6 Hz, 1 H, 9f-
CH2OH), 3.73 (dd, J ϭ 4.8, 11.6 Hz, 1 H, 8f-CH2OH), 3.92 (dd,
J ϭ 5.2, 11.6 Hz, 1 H, 9f-CH2OH), 3.96 (dd, J ϭ 4.0, 11.6 Hz, 1
H, 8f-CH2OH), 4.98 (dd, J ϭ 6.0, 13.2 Hz, 1 H, 8f-ArCHOH), 5.18
(t, J ϭ 5.6 Hz, 1 H, 9f-ArCHOH), 7.05Ϫ7.55 (m, 9 H, Ar) ppm.
8f: 13C NMR (100 MHz, CDCl3): δ ϭ 10.7 (CH3), 32.2 (CH2CH3),
36.5 (CH2), 42.6 (CH2Se), 43.1 (CH), 60.7 (CH2OH), 74.6
(CHOH), 87.5 (C), 125.1 (CH-Ar), 126.7 (CH-Ar), 128.5 (CH-Ar),
128.7 (CH-Ar), 129.1 (CH-Ar), 129.2 (CH-Ar), 129.8 (C-Ar), 135.3
(CH-Ar), 142.1 (C-Ar), 147.5 (C-Ar), 178.0 (CϭO) ppm. IR
(NaCl): ν˜ ϭ 3390, 3055, 2928, 1770, 1448, 1315, 1260, 1159, 1029,
970, 759, 701 cmϪ1. MS (EI): m/z (%) ϭ 420 (9) [M]ϩ, 403 (2), 224
(100), 206 (26), 136 (53); HRMS: calcd. for C21H34O4Se 420.0834,
found 420.0838.
5-{[2-[(R)-1-(Ethylsulfanyl)ethyl]phenyl]selanylmethyl}-3-(hydroxy-
methyl)-5-phenyldihydro-3H-furan-2-one (8i/9i): Synthesized ac-
cording to GP 1. Purification by flash chromatography on silica gel
with diethyl ether/petroleum ether, 2:1. Yield 28% (19 mg,
0.042 mmol); colorless oil; d.r. (cis/trans) ϭ 85:15. [α]2D1 ϭ Ϫ11.7
1
(c ϭ 0.29, CHCl3). H NMR (400 MHz, CDCl3): δ ϭ 1.09 (t, J ϭ
7.2 Ηz, 3 H, 8i-CH3), 1.10 (t, J ϭ 7.2 Ηz, 3 H, 9i-CH3), 1.44 (d,
J ϭ 7.2 Ηz, 3 H, 9i-CH3), 1.48 (d, J ϭ 7.2 Ηz, 3 H, 8i-CH3), 2.31
(q, J ϭ 7.6 Ηz, 2 H, CH2CH3), 2.56Ϫ2.70 (m, 2 H, CH2), 3.38 (d,
J ϭ 12.4 Ηz, 1 H, 8i-CH2Se), 3.48 (d, J ϭ 12.8 Ηz, 1 H, 8i-CH2Se),
3.49 (d, J ϭ 13.2 Ηz, 1 H, 9i-CH2Se), 3.65 (dd, J ϭ 4.8, 12.0 Ηz, 1
H, 9i-CH2OH), 3.73 (dd, J ϭ 4.8, 11.6 Ηz, 1 H, 8i-CH2OH), 3.79
(dd, J ϭ 4.0, 12.0 Ηz, 1 H, 9i-CH2OH), 3.88 (dd, J ϭ 3.6, 11.6 Ηz,
1 H, 8i-CH2OH), 4.48 (q, J ϭ 6.8 Ηz, 1 H, 9i-CH), 4.57 (q, J ϭ
6.8 Ηz, 1 H, 8i-CH), 7.00Ϫ7.50 (m, 9 H, Ar) ppm. 8i: 13C NMR
(100 MΗz, CDCl3): δ ϭ 15.0 (CH3CH2), 22.6 (CH2CH3), 25.6
(CH3), 30.7 (CH), 41.5 (CH), 43.0 (CH2Se), 61.2 (CH2OH), 87.2
(C), 125.3 (CH-Ar), 127.7 (CH-Ar), 128.0 (CH-Ar), 128.6 (CH-
Ar), 129.0 (CH-Ar), 131.2 (C-Ar), 134.8 (C-Ar), 141.8 (C-Ar),
146.2 (C-Ar), 177.5 (CϭO) ppm. IR (NaCl): ν˜ ϭ 3453, 2961, 2915,
1776, 1464, 1442, 1261, 1157, 1025, 762, 701, 650 cmϪ1. MS (EI):
m/z (%) ϭ 468 (4) [M ϩ NH4]ϩ, 245 (64), 206 (83), 194 (32), 180
(47), 167 (100), 145 (38), 136 (42), 119 (98), 108 (39), 78 (36);
ΗRMS calcd. for C22H26O3SSe 468.1106, found 468.1104.
3-(Hydroxymethyl)-5-{[2-[(S)-1-(methoxymethoxy)propyl]phenyl]-
selanylmethyl}-5-phenyldihydrofuran-2-one (8g/9g): Synthesized ac-
cording to GP 1. Purification by flash chromatography on silica gel
with tert-butyl methyl ether/petroleum ether, 2:1. Yield 68% (47 mg,
0.101 mmol); colorless oil; d.r. (8g/9g) 85:15. [α]2D1 ϭ Ϫ49.2 (c ϭ
0.065, CHCl3). 1H NMR (400 MHz, CDCl3): δ ϭ 0.89 (t, J ϭ
7.6 Hz, 3 H, 9 g-CH3), 0.91 (t, J ϭ 7.2 Hz, 3 H, 8 g-CH3),
1.49Ϫ1.72 (m, 2 H, CH2CH3), 2.30Ϫ2.94 (m, 2 H, CH2), 3.05Ϫ3.16
(m, 1 H, 9 g-CH), 3.30 (s, 3 H, 9 g-OCH3), 3.31 (d, J ϭ 11.2 Hz, 1
H, 9 g-CH2Se), 3.36 (s, 3 H, 8 g-OCH3), 3.53 (d, J ϭ 13.2 Hz, 1 H,
9 g-CH2Se), 3.63 (dd, J ϭ 4.4, 12.8 Hz, 1 H, 8 g-CH2OH), 3.73 (dd,
J ϭ 4.8, 11.2 Hz, 1 H, 9 g-CH2OH), 4.48 (dd, J ϭ 6.8, 10.0 Hz, 2
H, 8 g-OCH2O), 4.99 (dd, J ϭ 4.8, 8.0 Hz, 1 H, 8 g-CHO), 5.07
(dd, J ϭ 4.8, 8.0 Hz, 1 H, 9 g-CH2OH), 7.05Ϫ7.42 (m, 9 H,
Ar) ppm. 8g: 13C NMR (100 MHz, CDCl3): δ ϭ 10.9 (CH3), 31.8
(CH2CH3), 35.5 (CH2), 41.1 (CH2Se), 43.3 (CH), 56.0 (OCH3),
60.3 (CH2OH), 78.3 (CHO), 86.9 (C), 94.7 (OCH2O), 125.1 (CH-
Ar), 125.2 (CH-Ar), 127.1 (CH-Ar), 128.4 (C-Ar), 128.5 (CH-Ar),
129.0 (CH-Ar), 130.2 (CH-Ar), 133.8 (CH-Ar), 142.4 (C-Ar), 144.4
(C-Ar), 177.2 (CϭO) ppm. IR (NaCl): ν˜ ϭ 3472, 2922, 1770, 1644,
1448, 1158, 1104, 1029, 916, 756, 701 cmϪ1. MS (EI): m/z (%) ϭ
482 (55) [M ϩ NH4]ϩ, 464 (21), 456(29), 433 (91), 420 (55), 403
(68), 391 (100), 377 (26), 359 (47); HRMS: calcd. for C23H28O5Se
482.1440, found 482.1438.
5-{[2-[(R)-1-(Ethylsulfanyl)ethyl]-6-methoxyphenyl]selanylmethyl}-
3-(hydroxymethyl)-5-phenyldihydro-3H-furan-2-one (8j/9j): Synthe-
sized according to GP 1. Purification by flash chromatography on
silica gel with diethyl ether/petroleum ether, 2:1. Yield 21% (15 mg,
0.031 mmol); colorless oil; d.r. (8j/9j) 82:18. [α]2D3 ϭ Ϫ49.2 (c ϭ
0.59, CHCl3). 1H NMR (400 MHz, CDCl3): δ ϭ 1.08 (t, J ϭ
7.6 Ηz, 3 H, 9j-CH3), 1.12 (t, J ϭ 7.2 Ηz, 3 H, 8j-CH3), 1.39 (d,
J ϭ 7.2 Ηz, 3 H, 8j-CH3), 1.59 (d, J ϭ 7.2 Ηz, 3 H, 9j-CH3),
2.19Ϫ2.37 (m, 2 H, CH2CH3), 2.49Ϫ2.62 (m, 2 H, CH2), 2.98
(quintet, J ϭ 8.4 Ηz, 1 H, 9j-CH), 3.10 (dd, J ϭ 3.2, 11.6 Ηz, 1 H,
9j-CH2OH), 3.23 (d, J ϭ 12.4 Ηz, 1 H, CH2Se), 3.26 (d, J ϭ
12.0 Ηz, 1 H, CH2Se), 3.30 (dd, J ϭ 4.0, 12.0 Ηz, 8j-CH2OH), 3.77
(s, 3 H, 8j-OCH3), 3.78 (dd, J ϭ 4.0, 9.2 Ηz, 1 H, 8j-CH2OH) 3.79
(s, 3 H, 9j-OCH3), 3.97 (dd, J ϭ 4.0, 9.2 Hz, 1 H, 9j-CH2OH), 4.56
(q, J ϭ 6.8 Ηz, 1 H, 9j-CH-Ar), 4.73 (q, J ϭ 8.4 Ηz, 1 H, 8j-CH-
Ar), 6.60Ϫ7.40 (m, 9 H, Ar) ppm. 8j: 13C NMR (100 MΗz,
CDCl3): δ ϭ 16.7 (CH3CH2), 22.9 (CH2S), 23.2 (CH3), 40.4 (CH-
5-{[2-[(S)-1-Hydroxyethyl]-6-methoxyphenyl]selanylmethyl}-3-
(hydroxymethyl)-5-phenyldihydro-3H-furan-2-one (8h/9h): Synthe-
sized according to GP 1. Purification by flash chromatography on
silica gel with ethyl acetate/petroleum ether, 1:1. Yield 35% (23 mg, Ar), 40.8 (CH2), 48.0 (CH), 48.4 (CH2Se), 53.7 (OCH3), 60.9
0.053 mmol); colorless oil; d.r. (8h/9h) 85:15. [α]2D2 ϭ Ϫ62.2 (c ϭ
(CH2OH), 85.2 (C), 106.7 (CH-Ar), 117.3 (CH-Ar), 124.9 (CH-
4574
 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
Eur. J. Org. Chem. 2004, 4567Ϫ4581

Nucleophile-Selective Selenocyclizations
FULL PAPER
Ar), 125.8 (CH-Ar), 126.0 (CH-Ar), 126.4 (CH-Ar), 127.1 (CH- 12.4 Hz, 1 H, trans-CH2OH-Ar), 4.66 (d, J ϭ 12.4 Hz, 1 H, trans-
Ar), 130.5 (CH-Ar), 137.6 (CH-Ar), 142.0 (C-Ar), 144.0 (C-Ar), CH2OH-Ar), 4.69 (d, J ϭ 12.4 Hz, 1 H, cis-CH2OH-Ar) ppm.
157.1 (C-Ar), 177.8 (CϭO) ppm. IR (NaCl): ν˜ ϭ 3427, 2966, 2915,
trans-10c: 13C NMR (100 MHz, CDCl3): δ ϭ 41.6 (CH2), 42.9
(CH2Se), 45.2 (CH), 52.4 (CH2O), 66.2 (CH2OH-Ar), 69.8 (OCH3),
2363, 1734, 1564, 1464, 1373, 1261, 1047, 1032, 755, 695, 650 cmϪ1
.
MS (EI): m/z (%) ϭ 398 (2) [M ϩ NH4]ϩ, 503 (23), 275 (38), 245 87.2 (C), 125.5 (CH-Ar), 127.7 (CH-Ar), 127.9 (CH-Ar), 128.3
(16), 213 (100), 159 (26); ΗRMS calcd. for C23H28O4SSe 503.0766, (CH-Ar), 128.7 (CH-Ar), 129.0 (CH-Ar), 129.2 (CH-Ar), 131.3 (C-
found 503.0767.
Ar), 135.5 (CH-Ar), 143.2 (C-Ar), 144.2 (C-Ar), 145.0 (C-Ar),
173.0 (CϭO) ppm. IR (NaCl): ν˜ ϭ 3430, 3056, 2946, 1732, 1584,
1446, 1373, 1333, 1273, 1200, 1122, 1027, 931, 755, 704 cmϪ1. MS
(EI): m/z (%) ϭ 424 (2) [M ϩ NΗ4]ϩ, 389 (5), 238 (100), 221 (74),
205 (20), 143 (11), 108 (20); HRMS: calcd. for C20H22O4Se
424.1022, found 424.1020.
Methyl
5-(Iodomethyl)-5-phenyltetrahydrofuran-3-carboxylate
(10a): Synthesized according to the procedure for the synthesis of
8a/9a using substrate 4. Purification by flash chromatography on
silica gel with tert-butyl methyl ether/petroleum ether, 1:2. Yield
93% (236 mg, 0.68 mmol); white solid; m.p. 69Ϫ71 °C; d.r. (cis/
trans) 42:58. 1H NMR (400 MHz, CDCl3): δ ϭ 2.58 (d, J ϭ 8.8 Hz, Methyl 5-[(2-Carboxyphenyl)selanylmethyl]-5-phenyltetrahydrofu-
1 H, CH2C), 2.63 (d, J ϭ 8.6 Hz, 1 H, CH2C), 3.00 (quint, J ϭ ran-3-carboxylate (10d): Synthesized according to GP 1. Purifi-
8.4 Hz, 1 H, cis-CH), 3.35 (quint, J ϭ 8.4 Hz, 1 H, trans-CH), 3.40
(d, J ϭ 10.8 Hz, 1 H, cis-CH2I), 3.45 (d, J ϭ 11.2 Hz, 1 H, cis-
CH2I), 3.47 (s, 3 H, cis-OCH3), 3.49 (d, J ϭ 10.8 Hz, 1 H, trans-
cation by flash chromatography on silica gel with ethyl acetate/
petroleum ether, 1:1. Yield 79% (30 mg, 0.072 mmol); white solid;
m.p. 146Ϫ148 °C; d.r. (cis/trans) 50:50. 1H NMR (400 MHz,
CH2I), 3.55 (d, J ϭ 10.8 Hz, 1 H, trans-CH2I), 3.64 (s, 3 H, trans- CDCl3): δ ϭ 2.62Ϫ2.78 (m, 2 H, CH2), 2.98 (quint, J ϭ 7.6 Hz, 1
OCH3), 3.93 (t, J ϭ 8.4 Hz, 1 H, cis-CH2O), 4.08 (t, J ϭ 8.4 Hz, 1 H, trans-CH), 3.21 (d, J ϭ 12.0 Hz, 1 H, cis-CH2Se), 3.31 (d, J ϭ
H, trans-CH2O), 4.16 (t, J ϭ 8.4 Hz, 1 H, trans-CH2O), 4.24 (t,
J ϭ 8.4 Hz, 1 H, cis-CH2O), 7.15Ϫ7.45 (m, 5 H, Ar) ppm. trans- 3.37 (d, J ϭ 11.6 Hz, 1 H, trans-CH2Se), 3.46 (s, 3 H, cis-OCH3),
10a: 13C NMR (100 MHz, CDCl3): δ ϭ 16.6 (CH2), 39.6 (CH2O),
3.63 (s, 3 H, trans-OCH3), 3.94 (t, J ϭ 8.4 Hz, 1 H, cis-CH2O),
12.0 Hz, 1 H, cis-CH2Se), 3.33 (d, J ϭ 12.0 Hz, 1 H, trans-CH2Se),
43.0 (OCH3), 51.2 (CH), 68.5 (CH2I), 84.4 (C), 124.2 (CH-Ar), 4.05 (t, J ϭ 8.4 Hz, 1 H, trans-CH2O), 4.17 (t, J ϭ 7.6 Hz, 1 H,
126.6 (CH-Ar), 127.4 (CH-Ar), 141.4 (C-Ar), 171.4 (CϭO) ppm. trans-CH2O), 4.22 (t, J ϭ 8.4 Hz, 1 H, cis-CH2O), 7.10Ϫ8.10 (m,
IR (NaCl): ν˜ ϭ 3449, 2952, 1735, 1447, 1200, 1027, 763, 702 cmϪ1
.
9 H, Ar) ppm. trans-10d: 13C NMR (100 MHz, CDCl3): δ ϭ 36.9
(CH2), 39.8 (CH2Se), 42.8 (CH), 50.9 (OCH3), 68.4 (CH2O), 85.9
MS (EI): MS: m/z (%) ϭ 364 (28) [M ϩ NH4]ϩ, 347 (5), 238 (100),
221 (56), 205 (29), 152 (14), 136 (10), 119 (21), 110 (10), 98 (13), (C), 123.7 (CH-Ar), 124.0 (CH-Ar), 126.3 (CH-Ar), 126.6 (CH-
90 (18), 52 (60), 44 (65); HRMS: calcd. for C13H15O3I 364.0410, Ar), 127.4 (CH-Ar), 131.4 (CH-Ar), 132.1 (CH-Ar), 137.9 (C-Ar),
found 364.0414.
143.1 (C-Ar), 144.3 (C-Ar), 170.4 (OϭCAr), 171.8 (CϭO) ppm. IR
(NaCl): ν˜ ϭ 2946, 1732, 1584, 1558, 1462, 1428, 1373, 1256, 1207,
1142, 1033, 741, 703 cmϪ1. MS (EI): m/z (%) ϭ 438 (19) [M ϩ
NΗ4]ϩ, 318 (19), 238 (100), 221 (74), 205 (18), 143 (8), 105 (6), 78
(5); HRMS: calcd. for C20H20O5Se 438.0814, found 438.0815.
Methyl
5-Phenyl-5-(phenylselanylmethyl)tetrahydrofuran-3-car-
boxylate (10b): Synthesized according to GP 1. Purification by
flash chromatography on silica gel with tert-butyl methyl ether/
petroleum ether, 1:10. Yield 68% (318 mg, 085 mmol); white solid;
m.p. 44Ϫ46 °C; d.r. (cis/trans) 39:61. 1H NMR (400 MHz, CDCl3):
Methyl
5-{[2-(Methoxycarbonyl)phenyl]selanylmethyl}-5-phenyl-
δ ϭ 2.49Ϫ2.70 (m, 3 H, CH2C, cis-CH), 2.96 (quint, J ϭ 8.4 Hz, 1 tetrahydrofuran-3-carboxylate (10e): Synthesized according to GP
H, trans-CH), 3.20 (d, J ϭ 12.4 Hz, 1 H, cis-CH2Se), 3.31 (d, J ϭ
12.0 Hz, 1 H, trans-CH2Se), 3.34 (d, J ϭ 12.4 Hz, 1 H, cis-CH2Se),
3.40 (d, J ϭ 12.0 Hz, 1 H, trans-CH2Se), 3.47 (s, 3 H, cis-OCH3),
3.62 (s, 3 H, trans-OCH3), 3.91 (t, J ϭ 8.4 Hz, 1 H, cis-CH2O),
4.04 (t, J ϭ 8.4 Hz, 1 H, trans-CH2O), 4.13 (t, J ϭ 8.4 Hz, 1 H,
1. Purification by flash chromatography on silica gel with ethyl
acetate/petroleum ether, 1:2. Yield 79% (31 mg, 0.072 mmol); white
solid; m.p. 140Ϫ142 °C; d.r. (cis/trans) 48:52. H NMR (400 MHz,
CDCl3): δ ϭ 2.60Ϫ2.80 (m, 2 H, CH2), 2.97 (quint, J ϭ 7.6 Hz, 1
H, trans-CH), 3.19 (d, J ϭ 11.6 Hz, 1 H, cis-CH2Se), 3.29 (d, J ϭ
1
trans-CH2O), 4.18 (t, J ϭ 8.4 Hz, 1 H, cis-CH2O), 7.00Ϫ7.40 (m, 12.0 Hz, 1 H, cis-CH2Se), 3.30 (d, J ϭ 11.6 Hz, 1 H, trans-CH2Se),
10 H, Ar) ppm. trans-10b: 13C NMR (100 MHz, CDCl3): δ ϭ 41.3 3.34 (d, J ϭ 11.6 Hz, 1 H, trans-CH2Se), 3.46 (s, 3 H, cis-OCH3),
(CH2), 42.3 (CH2 Se), 44.2 (CH), 52.6 (OCH3), 69.8 (CH2O), 87.5 3.62 (s, 3 H, trans-OCH3), 3.83 (s, 3 H, cis-OCH3-Ar), 3.85 (s, 3 H,
(C), 125.6 (CH-Ar), 127.1 (CH-Ar), 127.8 (CH-Ar), 128.8 (CH- trans-OCH3-Ar), 3.92 (t, J ϭ 8.4 Hz, 1 H, cis-CH2O), 4.05 (t, J ϭ
Ar), 129.3 (CH-Ar), 131.6 (C-Ar), 133.1 (CH-Ar), 144.5 (C-Ar), 8.4 Hz, 1 H, trans-CH2O), 4.15 (t, J ϭ 7.6 Hz, 1 H, trans-CH2O),
173.8 (CϭO) ppm. IR (thin film on NaCl): ν˜ ϭ 3440, 1735, 1644,
4.20 (t, J ϭ 8.4 Hz, 1 H, cis-CH2O), 7.05Ϫ7.95 (m, 9 H, Ar) ppm.
1578, 1478, 1436, 1200, 1061, 1022, 737, 703 cmϪ1. MS (EI): m/z trans-10e: 13C NMR (100 MHz, CDCl3): δ ϭ 38.2 (CH2), 39.3
(%) ϭ 377 (56) [M ϩ Η]ϩ, 238 (56), 221 (37), 205 (63), 52 (39);
HRMS: calcd. for C19H20O3Se 377.0656, found 377.0660.
(CH2Se), 41.5 (CH), 44.1 (OCH3-Ar), 52.7 (OCH3), 69.7 (CH2O),
86.9 (C), 125.0 (CH-Ar), 125.5 (CH-Ar), 127.8 (CH-Ar), 128.9
(CH-Ar), 131.8 (CH-Ar), 132.9 (CH-Ar), 138.5 (C-Ar), 144.6 (C-
Ar), 145.9 (C-Ar), 167.7 (OϭCAr), 173.2 (CϭO) ppm. IR (NaCl):
ν˜ ϭ 3428, 2946, 1735, 1710, 1579, 1458, 1434, 1273, 1253, 1202,
1052, 1027, 740 cmϪ1. MS (EI): m/z (%) ϭ 452 (100) [M ϩ NΗ4]ϩ,
435 (30), 403 (3), 391 (5); HRMS: calcd. for C21H22O5Se 452.0971,
found 452.0971.
Methyl 5-{[2-(Hydroxymethyl)phenyl]selanylmethyl}-5-phenyltetra-
hydrofuran-3-carboxylate (10c): Synthesized according to GP 1.
Purification by flash chromatography on silica gel with diethyl
ether/petroleum ether, 1:4. Yield 30% (11 mg, 0.027 mmol); color-
less oil; d.r. (cis/trans) 48:52. 1H NMR (400 MHz, CDCl3): δ ϭ 2.52
(dd, J ϭ 8.4 Hz, 2 H, cis-CH2), 2.58 (d, J ϭ 8.4 Hz, 2 H, trans-
CH2), 2.97 (q, J ϭ 8.4 Hz, 1 H, cis-CH), 3.21 (d, J ϭ 12.4 Hz, 1 Methyl 5-{[2-[(S)-1-Hydroxypropyl]phenyl]selanylmethyl}-5-phenyl-
H, trans-CH2Se), 3.31 (d, J ϭ 10.8 Hz, 1 H, cis-CH2Se), 3.36 (d, tetrahydrofuran-3-carboxylate (10f): Synthesized according to GP
J ϭ 10.8 Hz, trans-CH2Se), 3.39 (d, J ϭ 12.4 Hz, 1 H, cis-CH2Se), 1. Purification by flash chromatography on silica gel with tert-butyl
3.46 (s, 3 H, trans-OCH3), 3.62 (s, 3 H, cis-OCH3), 3.95 (t, J ϭ
methyl ether/petroleum ether, 1:2. Yield 78% (37 mg, 0.11 mmol);
8.8 Hz, 1 H, cis-CH2O), 4.06 (t, J ϭ 8.0 Hz, 1 H, trans-CH2O), colorless oil; d.r. (cis/trans) 30:70. [α]2D3 ϭ Ϫ6.71 (c ϭ 0.69, CHCl3).
4.08 (t, J ϭ 8.0 Hz, 1 H, trans-CH2O), 4.10 (t, J ϭ 8.4 Hz, 1 H, 1H NMR (400 MHz, CDCl3): δ ϭ 0.85 (t, J ϭ 7.2 Hz, 3 H, trans-
cis-CH2O), 4.58 (d, J ϭ 12.4 Hz, 1 H, cis-CH2OH-Ar), 4.59 (d, J ϭ CH3), 0.83 (t, J ϭ 7.2 Hz, 3 H, cis-CH3), 1.55Ϫ1.70 (m, 2 H,
Eur. J. Org. Chem. 2004, 4567Ϫ4581
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4575

S. S. Khokhar, T. Wirth
FULL PAPER
CH2CH3), 2.35Ϫ2.41 (m, 1 H, trans-CH2), 2.47Ϫ2.66 (m, 4 H, cis- Ar), 159.7 (C-Ar), 174.0 (CϭO) ppm. IR (NaCl): ν˜ ϭ 3440, 1730,
CH2, cis-CH, trans-CH2), 2.86Ϫ3.02 (quint, J ϭ 8.4 Hz, 1 H, trans-
1644, 1463, 1260, 1057 cmϪ1. MS (EI): m/z (%) ϭ 446 (27) [M]ϩ,
CH), 3.25 (d, J ϭ 12.4 Hz, 1 H, trans-CH2Se), 3.29 (d, J ϭ 12.4 Hz, 432 (20), 246 (74), 228 (100); HRMS: calcd. for C22H26O5Se
1 H, trans-CH2Se), 3.32 (d, J ϭ 12.4 Hz, 1 H, cis-CH2Se), 3.38 (d,
J ϭ 12.0 Hz, 1 H, cis-CH2Se), 3.46 (s, 3 H, trans-OCH3), 3.62 (s, 3
H, cis-OCH3), 3.90 (t, J ϭ 8.4 Hz, 1 H, cis-CH2O), 4.00Ϫ4.11 (m,
2 H, trans-CH2O), 4.19 (t, J ϭ 8.0 Hz, 1 H, cis-CH2O), 6.95Ϫ7.40
(m, 9 H, Ar) ppm. trans-10f: 13C NMR (100 MHz, CDCl3): δ ϭ
9.33 (CH3), 30.2 (CH2CH3), 40.1 (CH2), 42.8 (CH), 43.9 (CH2Se),
51.2 (OCH3), 68.4 (CH2O), 73.1 (CHOH-Ar), 85.7 (C), 124.2 (CH-
Ar), 125.1 (CH-Ar), 126.2 (CH-Ar), 126.8 (CH-Ar), 127.2 (CH-
Ar), 127.3 (CH-Ar), 129.0 (C-Ar), 133.1 (CH-Ar), 143.8 (C-Ar),
145.2 (C-Ar), 171.6 (CϭO) ppm. IR (NaCl): ν˜ ϭ 3478, 2958, 2876,
1736, 1585, 1446, 1200, 1052, 1027, 977, 756, 703 cmϪ1. MS (EI):
m/z (%) ϭ 433 (1) [M]ϩ, 416 (67), 391 (2), 222 (100), 198 (35);
HRMS: calcd. for C22H26O4Se 434.0991, found 434.0999.
446.0967, found 446.0956.
Methyl
5-{[2-[(R)-1-(Ethylsulfanyl)ethyl]phenyl]selanylmethyl}-5-
phenyltetrahydrofuran-3-carboxylate (10i): Synthesized according to
GP 1. Purification by flash chromatography on silica gel with di-
ethyl ether/petroleum ether, 1:2. Yield 40% (26 mg, 0.056 mmol);
colorless oil; d.r. (cis/trans) 33:67. [α]2D3 ϭ Ϫ8.08 (c ϭ 1.04, CHCl3).
1H NMR (400 MHz, CDCl3): δ ϭ 1.06 (t, J ϭ 7.2 Hz, 3 H, trans-
CH3), 1.07 (t, J ϭ 7.2 Hz, 3 H, cis-CH3), 1.40 (d, J ϭ 7.2 Hz, 3 H,
cis-CH3),1.45 (d, J ϭ 7.2 Hz, 3 H, trans-CH3), 1.47 (t, J ϭ 7.2 Hz,
3 H, trans-CH3), 1.59 (t, J ϭ 7.2 Hz, 3 H, cis-CH3), 2.27 (m, 1 H,
cis-CH), 2.50Ϫ2.71 (m, 2 H, CH2), 2.97 (m, 1 H, trans-CH), 3.20
(d, J ϭ 12.0 Hz, 1 H, cis-CH2Se), 3.31 (d, J ϭ 12.0 Hz, 1 H, trans-
CH2Se), 3.32 (d, J ϭ 12.0 Hz, 1 H, trans-CH2Se), 3.37 (d, J ϭ
12.0 Hz, 1 H, cis-CH2Se), 3.48 (s, 3 H, cis-OCH3), 3.63 (s, 3 H,
trans-OCH3), 3.92 (t, J ϭ 8.8 Hz, 1 H, cis-CH2O), 4.05 (t, J ϭ
8.8 Hz, 1 H, trans-CH2O), 4.13 (t, J ϭ 8.0 Hz, 1 H, trans-CH2O),
4.17 (t, J ϭ 8.4 Hz, 1 H, cis-CH2O), 4.52 (q, J ϭ 6.8 Hz, 1 H, cis-
ArCH), 4.59 (q, J ϭ 6.8 Hz, 1 H, trans-ArCH), 6.90Ϫ7.40 (m, 9
H, Ar) ppm. trans-10i: 13C NMR (100 MHz, CDCl3): δ ϭ 13.7
(CH3CH2), 21.4 (CH2CH3), 24.2 (CH3), 28.7 (ArCH), 40.4 (CH2),
42.8 (CH2Se), 44.0 (CH), 51.1 (OCH3), 68.4 (CH2O), 86.1 (C),
124.1 (CH-Ar), 126.0 (CH-Ar), 126.3 (CH-Ar), 126.6 (CH-Ar),
127.3 (CH-Ar), 130.6 (CH-Ar), 132.6 (C-Ar), 143.0 (C-Ar), 144.0
(CH-Ar), 144.5 (C-Ar), 172.4 (CϭO) ppm. IR (NaCl): ν˜ ϭ 3046,
2966, 2925, 2865, 1737, 1584, 1494, 1446, 1368, 1268, 1199, 1057,
1022, 761, 705 cmϪ1. MS (EI): m/z (%) ϭ 482 (18) [M ϩ NH4]ϩ,
403 (58), 238 (100), 221 (68), 205 (27), 167 (11), 122 (8); HRMS:
calcd. for C23H28O3SSe 482.1263, found 482.1270.
Methyl 5-{(2-[(S)-1-(Methoxymethoxy)propyl]phenyl)selanylmeth-
yl}-5-phenyltetrahydrofuran-3-carboxylate (10g): Synthesized ac-
cording to GP 1. Purification by flash chromatography on silica gel
with ethyl acetate/petroleum ether, 1:1. Yield 41% (18 mg,
0.038 mmol); colorless oil; d.r. (cis/trans) 44:56. [α]2D1 ϭ Ϫ81.8 (c ϭ
0.34, CHCl3). 1H NMR (400 MHz, CDCl3): δ ϭ 0.88 (t, J ϭ
7.6 Hz, 3 H, CH3), 1.55Ϫ1.70 (m, 2 H, CH2CH3), 2.53Ϫ2.73 (m,
2 H, CH2), 2.97 (quint, J ϭ 7.6 Hz, 1 H, CH), 3.18 (d, J ϭ 12.0 Hz,
1 H, cis-CH2Se), 3.29 (d, J ϭ 12.0 Hz, 1 H, trans-CH2Se), 3.32 (d,
J ϭ 12.4 Hz, 1 H, trans-CH2Se), 3.40 (d, J ϭ 12.0 Hz, 1 H, cis-
CH2Se), 3.48 (s, 3 H, cis-OCH3), 3.62 (s, 3 H, trans-OCH3), 3.92
(t, J ϭ 8.4 Hz, 1 H, cis-CH2O), 4.05 (t, J ϭ 8.4 Hz, 1 H, trans-
CH2O), 4.11 (t, J ϭ 8.0 Hz, 1 H, trans-CH2O), 4.17 (t, J ϭ 8.4 Hz,
1 H, cis-CH2O), 4.38 (dd, J ϭ 3.6, 6.4 Hz, 1 H, OCH2O), 4.45
(dd, J ϭ 3.6, 6.8 Hz, 1 H, OCH2O), 4.90 (t, J ϭ 7.6 Hz, 1 H, cis-
ArCHOH), 4.92 (t, J ϭ 7.6 Hz, 1 H, trans-ArCHOH), 7.00Ϫ7.40
(m, 9 H, Ar) ppm. trans-10g: 13C NMR (100 MHz, CDCl3): δ ϭ
10.9 (CH3), 31.0 (CH2CH3), 41.1 (CH2), 41.6 (CH2Se), 45.3 (CH),
52.3 (OCH3), 56.0 (OCH3-Ar), 69.7 (CH2O), 78.6 (ArCHOH), 87.1
(C), 95.0 (OCH2O), 125.6 (CH-Ar), 126.9 (CH-Ar), 127.6 (CH-Ar),
127.8 (CH-Ar), 127.9 (CH-Ar), 128.2(C-Ar), 128.7 (CH-Ar), 130.9
(CH-Ar), 134.1 (C-Ar), 144.5 (C-Ar), 173.2 (CϭO) ppm. IR
(NaCl): ν˜ ϭ 3377, 2948, 2360, 1737, 1567, 1501, 1439, 1404, 1346,
1240, 1201, 1175, 1102, 1032, 958, 911, 807 cmϪ1. MS (EI): m/z
(%) ϭ 496 (100) [M ϩ NH4]ϩ, 447 (55), 417 (86), 358 (91), 340
(32), 312 (26); HRMS: calcd. for C24H30O5SSe 496.1597, found
496.1599.
Methyl 5-{[2-[(R)-1-(Ethylsulfanyl)ethyl]-6-methoxyphenyl]selanyl-
methyl}-5-phenyltetrahydrofuran-3-carboxylate (10j): Synthesized
according to GP 1. Purification by flash chromatography on silica
gel with diethyl ether/petroleum ether, 1:1. Yield 38% (24 mg,
0.046 mmol); colorless oil; d.r. (cis/trans) 42:58. [α]2D3 ϭ Ϫ9.56 (c ϭ
0.126, CHCl3). 1H NMR (400 MHz, CDCl3): δ ϭ 1.06 (t, J ϭ
7.6 Hz, 3 H, cis-CH3), 1.10 (t, J ϭ 7.6 Hz, 3 H, trans-CH3), 1.36
(d, J ϭ 6.4 Hz, 3 H, CH3), 1.42 (q, J ϭ 6.8 Hz, 2 H, CH2CH3),
2.47Ϫ2.57 (m, 1 H, CH2), 2.67Ϫ2.74 (m, 1 H, CH2), 2.95 (quint,
J ϭ 8.4 Hz, 1 H, cis-CH), 3.76 (d, J ϭ 12.0 Hz, 1 H, CH2Se), 3.80
(d, J ϭ 12.8 Hz, 1 H, CH2Se), 3.77 (s, 3 H, trans-OCH3), 3.80 (s,
3 H, cis-OCH3), 3.91 (t, J ϭ 8.4 Hz, 1 H, cis-CH2O), 4.03 (t, J ϭ
8.4 Hz, 1 H, trans-CH2O), 4.11 (t, J ϭ 8.0 Hz, 1 H, trans-CH2O),
4.20 (t, J ϭ 8.0 Hz, 1 H, cis-CH2O), 4.87 (q, J ϭ 6.8 Hz, 1 H,
ArCH), 6.60Ϫ7.40 (m, 9 H, Ar) ppm. trans-10j: 13C NMR
(100 MHz, CDCl3): δ ϭ 15.1 (CH3CH2), 23.1 (CH3) 25.6 (CH2),
40.9 (ArCH), 43.4 (CH2C), 44.1 (CH), 45.6 (CH2Se), 52.5 (OCH3),
56.4 (ArOCH3), 69.7 (CH2O), 87.3 (C), 109.3 (CH-Ar), 119.9 (C-
Ar), 125.5 (CH-Ar), 127.6 (CH-Ar), 128.6 (CH-Ar), 128.7 (CH-
Ar), 129.8 (CH-Ar), 144.2 (C-Ar), 146.5 (C-Ar), 159.1 (C-Ar),
173.8 (CϭO) ppm. IR (NaCl): ν˜ ϭ 3418, 2950, 1736, 1568, 1464,
1373, 1261, 1202, 1050, 1022, 786, 761, 730, 704 cmϪ1. MS (EI):
m/z (%) ϭ 511 (15) [M ϩ NH4]ϩ, 433 (34), 275 (23), 238 (100), 221
(71), 205 (30), 152 (18); HRMS: calcd. for C24H30O4SSe 511.1030,
found 511.1053.
5-{[2-((S)-1-Hydroxyethyl)-6-methoxyphenyl]selanylmethyl}-5-
phenyltetrahydrofuran-3-carboxylic Acid (10h): Synthesized accord-
ing to GP 1. Purification by flash chromatography on silica gel with
ethyl acetate/petroleum ether, 1:1. Yield 38% (21 mg, 0.047 mmol);
colorless oil; d.r. (cis/trans) 30:70. [α]2D3 ϭ ϩ55 (c ϭ 0.04, CHCl3).
1H NMR (400 MHz, CDCl3): δ ϭ 1.28 (d, J ϭ 6.8 Hz, 3 H, cis-
CH3), 1.30 (d, J ϭ 6.8 Hz, 3 H, trans-CH3), 2.30Ϫ2.72 (m, 2 H,
CH2C), 2.94 (quint, J ϭ 6.8 Hz, 1 H, trans-CH), 3.29 (d, J ϭ
12.4 Hz, 1 H, cis-CH2Se), 3.35 (d, J ϭ 12.8 Hz, 1 H, cis-CH2Se),
3.48 (s, 3 H, cis-OCH3), 3.62 (s, 3 H, trans-OCH3), 3.80 (s, 3 H,
trans-ArOCH3), 3.81 (s, 3 H, cis-ArOCH3), 3.96 (t, J ϭ 8.4 Hz, 1
H, cis-CH2O), 3.98 (t, J ϭ 8.0 Hz, 1 H, trans-CH2O), 4.04 (t, J ϭ
8.0 Hz, 1 H, trans-CH2O), 4.21 (t, J ϭ 8.4 Hz, 1 H, cis-CH2O),
5.18 (d, J ϭ 6.4 Hz, 1 H, trans-ArCHOH), 5.22 (d, J ϭ 6.8 Hz, 1 H,
Methyl 2-[(tert-Butyldimethylsilanyl)oxymethyl]-4-phenylpent-4-en-
cis-ArCHOH), 6.60Ϫ7.30 (m, 8 H, Ar) ppm. trans-10h: 13C NMR oate: Compound 5 (250 mg, 1.14 mmol) was dissolved in DMF
(100 MHz, CDCl3): δ ϭ 24.6 (CH3), 40.0 (CH2C), 41.8 (CH2Se), (6.5 mL), treated with tert-butyldimethylsilyl chloride (196 mg,
44.1 (CH), 52.6 (OCH3), 56.4 (CHOH), 69.7 (CH2O), 88.0 1.3 mmol) and imidazole (176 mg, 2.6 mmol), and stirred at room
(CCH2Se), 109.8 (CH-Ar), 118.3 (C-Ar), 125.5 (CH-Ar), 127.4 temperature overnight. The mixture was diluted with diethyl ether
(CH-Ar), 128.5 (CH-Ar), 129.9 (CH-Ar), 145.4 (C-Ar), 150.6 (C-
(25 mL) and washed with saturated aqueous NaCl. The organic
4576
 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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Eur. J. Org. Chem. 2004, 4567Ϫ4581

Nucleophile-Selective Selenocyclizations
FULL PAPER
layer was dried with MgSO4, and after evaporation of the solvent
the crude product was purified by flash chromatography on silica
1463, 1258, 1112, 740 cmϪ1. MS (EI): m/z (%) ϭ 477 (35) [M ϩ
Η]ϩ, 419 (7), 338 (84), 321 (100), 263 (23), 222 (36), 206 (23), 164
gel using tert-butyl methyl ether/petroleum ether (1:4) as eluent. (15), 132 (44), 119 (37), 91 (22), 78 (13); HRMS: calcd. for
The product (yellow oil) was isolated in 89% yield (340 mg,
1.02 mmol). 1H NMR (400 MHz, CDCl3): δ ϭ 0.00 [s, 6 H,
Si(CH3)2], 0.85 [s, 9 H, C(CH3)3], 2.65Ϫ2.75 (m, 1 H, CH),
2.75Ϫ2.88 (m, 2 H, CH2), 3.60 (s, 3 H, OCH3), 3.64Ϫ3.78 (m, 2
H, CH2O), 5.03 (d, J ϭ 1.2 Hz, 1 H, ϭCH2), 5.22 (d, J ϭ 0.8 Hz,
1 H, ϭCH2), 7.23Ϫ7.40 (m, 5 H, Ar) ppm. 13C NMR (100 MHz,
CDCl3): δ ϭ Ϫ0.50 (SiMe2), 18.6 (CMe3), 26.1 [C(CH3)3], 34.3
(CH2), 47.4 (CH), 51.8 (OCH3), 63.7 (CH2O), 114.9 (ϭCH2), 126.6
(CH-Ar), 128.0 (CH-Ar), 128.8 (CH-Ar), 140.7 (C), 146.0 (C-Ar),
174.9 (CϭO) ppm. IR (thin film on NaCl): ν˜ ϭ 3420, 2954, 2857,
1739, 1629, 1495, 1472, 1435, 1387, 1361, 1256, 1205, 1169, 1106,
1006, 901, 837, 777, 707 cmϪ1. MS (EI): m/z (%) ϭ 335 (100) [M
ϩ Η]ϩ, 277 (11), 245 (4), 220 (3), 203 (9), 159 (2), 132 (2), 106 (3),
91 (3), 76 (2), 58 (2), 52 (19), 44 (2); HRMS: calcd. for C19H30O3Si
335.2042, found 335.2040.
C24H32O3SeSi 477.1364, found 477.1365.
5-(Iodomethyl)-3-methylene-5-phenyldihydrofuran-2-one (12): So-
dium hydride (18.6 mg, 0.15 mmol) was suspended in THF (5 mL),
and 8a (0.056 mmol, 18.6 mg) was added. This reaction mixture
was stirred at room temperature for 5 h, quenched with water, and
extracted with diethyl ether (3 ϫ 10 mL). The combined organic
extracts were dried over MgSO4, and the solvent was evaporated
to produce a pale yellow solid, which was purified by flash chroma-
tography on silica gel with ethyl acetate/ petroleum ether, 1:2 to
produce a pale yellow solid in 32% yield (16 mg, 0.018 mmol). M.p.
66Ϫ68 °C. 1H NMR (400 MHz, CDCl3): δ ϭ 3.03 (tt, J ϭ 2.8,
2.8 Hz, 1 H, CH2), 3.47 (tt, J ϭ 2.8, 2.8 Hz, 1 H, CH2), 3.66 (dd,
J ϭ 7.2, 12.0 Hz, 1 H, CH2I), 3.81 (dd, J ϭ 3.6, 12.4 Hz, 1 H,
CH2I), 5.59 (t, J ϭ 2.8 Hz, 1 H, ϭCH2), 6.18 (t, J ϭ 2.8 Hz, 1 H, ϭ
CH2), 7.22Ϫ7.38 (m, 5 H, Ar) ppm. 13C NMR (100 MHz, CDCl3):
δ ϭ 37.0 (CH2), 69.7 (CH2I), 86.5 (C), 122.9 (HCϭCH2), 125.3
(CH-Ar), 128.7 (CH-Ar), 129.2 (CH-Ar), 135.0 (CHϭCH2), 140.9
(C-Ar), 170.1 (CϭO) ppm. IR (NaCl): ν˜ ϭ 2931, 2853, 1767, 1456,
1270, 1116, 1011, 808 cmϪ1. MS (EI): m/z (%) ϭ 315 (35) [M]ϩ,
187 (34), 173 (100), 141 (21), 128 (12), 115 (19), 105 (60), 91 (25),
77 (14), 51 (17), 40 (25); HRMS: calcd. for C12H11O2I 332.0142,
found 332.0147.
2-[(tert-Butyldimethylsilanyl)oxymethyl]-4-phenylpent-4-enoic Acid:
Methyl 2-[(tert-butyldimethylsilanyl)oxymethyl]-4-phenylpent-4-en-
oate (268 mg, 0.8 mmol) was dissolved in methanol (7.5 mL),
treated at 0 °C with aqueous KOH (3.5 mL, 30%), and stirred at
room temperature overnight. Water (15 mL) was added, and the
solution was washed with diethyl ether (15 mL). The aqueous layer
was cooled to 0 °C, and CH2Cl2 (15 mL) was added followed by 5
 HCl until pH Ͻ 5. The layers were separated and the aqueous
layer was extracted with CH2Cl2 (3 ϫ 15 mL). The combined or-
ganic phases were dried with MgSO4, the solvent was evaporated,
and the crude product was purified by flash chromatography on
silica gel using tert-butyl methyl ether/petroleum ether (1:4) as elu-
ent. The product was obtained as a yellow solid in 59% yield
(150 mg, 0.47 mmol) together with 5 (30%, 49 mg, 0.24 mmol).
M.p. 46Ϫ48 °C. 1H NMR (400 MHz, CDCl3): δ ϭ 0.00 [s, 6 H,
Si(CH3)2], 0.85 [s, 9 H, C(CH3)3], 2.62Ϫ2.79 (m, 2 H, CH2), 2.91
(dd, J ϭ 7.0, 14.4 Hz, 1 H, CH), 3.75 (d, J ϭ 5.6 Hz, 2 H, CH2O),
5.13 (s, 1 H, ϭCH2), 5.32 (s, 1 H, ϭCH2), 7.22Ϫ7.42 (m, 5 H,
Ar) ppm. 13C NMR (100 MHz, CDCl3): δ ϭ 17.1 [C(CH3)3], 24.7
[C(CH3)3], 32.5 (CH2), 45.4 (CH), 61.8 (CH2O), 113.7 (CϭCH2),
125.2 (CH-Ar), 126.7 (CH-Ar), 127.4 (CH-Ar), 139.1 (CϭCH2),
144.2 (C-Ar), 178.7 (CϭO) ppm. IR (thin film on NaCl): ν˜ ϭ 3386,
2955, 1709, 1638, 1470, 1256, 1110, 835, 777 cmϪ1. MS (EI): m/z
(%) ϭ 321 (58) [M ϩ Η]ϩ, 263 (30), 245 (4), 224 (5), 189 (3), 171
(2), 143 (3), 118 (2), 91 (5), 75 (2); HRMS: calcd. for C18H28O3Si
321.1886, found 321.1882.
Electrophile 13: Synthesized from 2,2Ј-diselenobis(benzyl al-
cohol).[17a]
Electrophile 14: Synthesized from 2,2Ј-diselenobis(benzoic acid).[17b]
Electrophile 15: Synthesized from 2,2Ј-diselenobis(benzoic acid
methyl ester).[17c]
Electrophile 16: Synthesized from (S,S)-bis{[2-(1-hydroxypro-
pyl)phenyl] diselenide}.[21]
Electrophile 17: Synthesized from (S,S)-bis{[2-[1-(methoxymeth-
oxy)propyl]phenyl] diselenide}.[5]
Electrophile 18: Synthesized from (S,S)-bis{[2-(1-hydroxyethyl)-6-
methoxyphenyl] diselenide}.[5]
Electrophile 19: Synthesized from (R,R)-bis{[2-[1-(ethylsulfanyl)-
ethyl]phenyl] diselenide}.
(R)-1-Bromo-2-[1-(ethylsulfanyl)ethyl]benzene: In a dry flask at Ϫ20
°C (S)-2-(2-bromophenyl)-ethanol[22] (2.0 g, 9.95 mmol), potassium
hydroxide (1.11 g, 19.7 mmol), and p-toluenesulfonyl chloride
(2.15 g, 11 mmol) were dissolved in diethyl ether/THF (1:1)
(40 mL), and the reaction mixture was stirred at Ϫ20 °C for 24 h.
3-[(tert-Butyldimethylsilanyl)oxymethyl]-5-phenyl-5-(phenylselanyl-
methyl)dihydrofuran-2-one (11b): Synthesized according to GP1.
Purification by flash chromatography on silica gel with tert-butyl
methyl ether/petroleum ether, 1:4. Yield 24%, (18 mg, 0.04 mmol); At Ϫ20 °C sodium ethanethiolate (1.04 g, 12.4 mmol) was added,
white solid; m.p. 41Ϫ43 °C; d.r. (cis/trans) 68:32. 1H NMR and the reaction mixture was warmed up to room temperature and
(400 MHz, CDCl3): δ ϭ Ϫ0.85 [d, J ϭ 3.2 Hz, 6 H, trans-Si(CH3)2], stirred for an additional 14 h. The reaction was quenched with
0.00 [d, J ϭ 3.2 Hz, 6 H, cis-Si(CH3)2], 0.60 [s, 9 H, trans-C(CH3)3], water (25 mL) and extracted with diethyl ether (3 ϫ 25 mL). The
0.80 [s, 9 H, cis-C(CH3)3], 2.52Ϫ2.75 (m, 3 H, CH2C, cis-CH), collected organic extracts were dried over MgSO4, and the solvent
3.05Ϫ3.13 (m, 1 H, trans-CH), 3.37 (d, J ϭ 12.8 Hz, 1 H, CH2Se), was evaporated to produce a yellow oil, which was further purified
3.46 (d, J ϭ 12.8 Hz, 1H CH2Se), 3.63 (dd, J ϭ 3.2, 10.0 Hz, 1 H, by flash chromatography on silica gel with petroleum ether to ob-
trans-CH2OSi), 3.72 (dd, J ϭ 3.2, 10.4 Hz, 1 H, cis-CH2OSi), 3.80 tain a colorless oil. Yield 65% (1.59 g, 6.46 mmol). HPLC con-
(dd, J ϭ 4.8, 10.0 Hz, 1 H, trans-CH2OSi), 3.91 (dd, J ϭ 4.4, ditions: Chiracel OD-H, flow rate: 0.5 ml minϪ1, 2-propanol/n-hex-
10.0 Hz, 1 H, cis-CH2OSi), 7.10Ϫ7.50 (m, 10 H, Ar) ppm. 13C
NMR (100 MHz, CDCl3): δ ϭ 17.3 [C(CH3)3], 24.8 [C(CH3)3], 35.7 Ϫ54.7 (c ϭ 1, CHCl3). H NMR (400 MHz, CDCl3): δ ϭ 1.12 (t,
(CH2), 40.1 (CH2Se), 42.1 (CH), 59.8 (CH2OSi), 85.2 (C), 123.6 J ϭ 7.4 Hz, 3 H, CH3), 1.43 (d, J ϭ 7.2 Hz, 3 H, CH3), 2.20Ϫ2.38
(CH-Ar), 124.0 (CH-Ar), 126.2 (CH-Ar), 127.1 (CH-Ar), 127.5 (m, 2 H, SCH2), 4.49 (q, J ϭ 7.2 Hz, 1 H, CH), 6.98 (t, J ϭ 8.0 Hz,
ane, 2:98, 15 °C, Rf(R) ϭ 8.2 min, Rf(S) ϭ 9.3 min; e.r. 96:4. [α]D20
ϭ
1
(CH-Ar), 128.2 (CH-Ar), 132.2 (CH-Ar), 141.1 (C-Ar), 175.0 (Cϭ
1 H, Ar), 7.24 (t, J ϭ 8.0 Hz, 1 H, Ar), 7.42 (d, J ϭ 8.0 Hz, 1 H,
O) ppm. IR (thin film on NaCl): ν˜ ϭ 3443, 2976, 2855, 1778, 1649, Ar), 7.55 (d, J ϭ 8.0 Hz, 1 H, Ar) ppm. 13C NMR (100 MHz,
Eur. J. Org. Chem. 2004, 4567Ϫ4581
www.eurjoc.org
 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
4577

S. S. Khokhar, T. Wirth
FULL PAPER
CDCl3): δ ϭ 15.0 (CH3CH2), 22.6 (CH3), 25.7 (CH2), 42.5 (CH), Bis[1-(3-methoxyphenyl)ethyl] Ether: [α]2D3 ϭ ϩ44.63 (c ϭ 2.16,
1
124.2 (Ar), 128.3 (Ar), 128.7 (Ar), 129.1 (Ar), 132.9 (Ar), 143.6 CHCl3). H NMR (400 MHz, CDCl3): δ ϭ 1.43 (d, J ϭ 6.4 Hz, 3
(Ar) ppm. IR (NaCl): ν˜ ϭ 2970, 2924, 2360, 1467, 1438, 1372, H, CH3), 1.51 (d, J ϭ 6.4 Hz, 3 H, CH3), 3.78 (s, 3 H, OCH3), 3.86
1263, 1021, 755, 726, 658 cmϪ1. MS (EI): m/z (%) ϭ 245 (51) [M
(s, 3 H, OCH3), 4.28 (q, J ϭ 6.4 Hz, 1 H, CH), 4.56 (q, J ϭ 6.4 Hz,
ϩ NH4]ϩ, 183 (87), 165 (23), 135 (12), 104 (100), 77 (30), 59 (7); 1 H, CH), 6.78Ϫ6.93 (m, 6 H, Ar), 7.21Ϫ7.35 (m, 2 H, Ar) ppm.
HRMS: calcd. for C10H13BrS 243.9916, found 243.9912.
13C NMR (100 MHz, CDCl3): δ ϭ 23.4 (CH3), 25.1 (CH3) 55.6
(CH), 75.0 (OCH3), 111.7 (CH-Ar), 112.8 (CH-Ar), 119.0 (CH-
Ar), 129.9 (CH-Ar), 146.4 (C-Ar), 160.2 (C-Ar) ppm. IR (NaCl):
ν˜ ϭ 2972, 2925, 2825, 1723, 1601, 1579, 1486, 1455, 1433, 1368,
1317, 1282, 1257, 1158, 1093, 1047, 956, 874, 782, 700 cmϪ1. MS
(EI): m/z (%) ϭ 304 (49) [M ϩ NH4]ϩ, 286 (9), 269 (12), 168 (8),
152 (100), 136 (18), 74 (11); HRMS: calcd. for C18H22O3 304.1907,
found 304.1903.
(R,R)-Bis{2-[1-(ethylsulfanyl)ethyl]phenyl} Diselenide: TieccoЈs pro-
cedure was followed.[19e] Under Ar at Ϫ78 °C (R)-1-Bromo-2-[1-
(ethylsulfanyl)ethyl]benzene (100 mg, 0.41 mmol) in Et2O (3 mL)
was slowly treated with tBuLi (0.82 mmol, 0.54 mL, 1.5  in pen-
tane). The reaction mixture was stirred at Ϫ78 °C for 15 min,
warmed up to room temperature, and stirred for 30 min. After
cooling to Ϫ78 °C selenium powder (32 mg, 0.41 mmol) was added.
The reaction mixture was allowed to warm up to room temperature
and stirred for 4 h. The reaction was quenched with aqueous HCl
(1 ) and extracted with Et2O (3 ϫ 5 mL). The combined organic
extracts were dried over MgSO4, and after evaporation of the sol-
vent the deep red oil was purified by flash chromatography on silica
gel (diethyl ether/petroleum ether, 1:10). Yield 60 mg (0.12 mmol,
60%); red oil. [α]2D1 ϭ Ϫ18.0 (c ϭ 1.0, CHCl3). 1H NMR (400 MHz,
CDCl3): δ ϭ 1.10 (t, J ϭ 7.6 Hz, 6 H, CH3), 1.46 (d, J ϭ 6.8 Hz, 6
H, CH3), 2.31 (q, J ϭ 7.2 Hz, 2 H, SCH2), 2.32 (q, J ϭ 7.2 Hz, 2
H, SCH2), 4.37 (q, J ϭ 7.2 Hz, 2 H, CH), 7.04 (dt, J ϭ 7.6, 1.2 Hz,
2 H, Ar), 7.17 (dt, J ϭ 7.6, 1.2 Hz, 2 H, Ar), 7.35 (dd, J ϭ 8.0,
1.2 Hz, 2 H, Ar), 7.68 (dd, J ϭ 8.0, 1.2 Hz, 2 H, Ar) ppm. 13C
NMR (100 MHz, CDCl3): δ ϭ 15.0 (CH3CH2), 22.0 (CH2), 25.7
(CH3), 43.7 (CH), 127.4 (CH-Ar), 128.2 (CH-Ar), 128.6 (CH-Ar),
132.4 (C-Ar), 134.5 (CH-Ar), 145.0 (C-Ar) ppm. 77Se NMR
(57.3 MHz, CDCl3): δ ϭ 430.3 ppm. IR (NaCl): ν˜ ϭ 3056, 2965,
(R,R)-Bis{2-[1-(Ethylsulfanyl)ethyl]-6-methoxyphenyl} Diselenide:
TieccoЈs procedure was followed.[19e] Under Ar at Ϫ78 °C (R)-1-
[1-(ethylsulfanyl)ethyl]-3-methoxybenzene (130 mg, 0.66 mmol) was
slowly treated with tBuLi (1 mmol, 0.66 mL, 1.5  in pentane). The
reaction mixture was stirred at Ϫ78 °C for 15 min, warmed up to
room temperature, and stirred for 30 min. After cooling to Ϫ78 °C
and addition of THF (1 mL), selenium powder (1.32 mmol,
104 mg) was added. The reaction mixture was allowed to warm up
to room temperature and stirred for 24 h. The reaction was
quenched with aqueous HCl (1) and extracted with diethyl ether
(3 ϫ 5 mL). The combined organic extracts were dried over
MgSO4, and after evaporation of the solvent the deep red oil was
purified by flash chromatography on silica gel (diethyl ether/petro-
leum ether, 1:10). Yield 62 mg (0.112 mmol, 34%); yellow oil.
[α]2D1 ϭ Ϫ173.8 (c ϭ 0.97, CHCl3). 1H NMR (400 MHz, CDCl3):
δ ϭ 1.04 (t, J ϭ 7.6 Hz, 6 H, CH3), 1.22 (d, J ϭ 6.8 Hz, 6 H, CH3),
2.23 (q, J ϭ 7.2 Hz, 4 H, CH2), 3.65 (s, 6 H, OCH3), 4.52 (q, J ϭ
6.8 Hz, 2 H, CH), 6.67 (d, J ϭ 8.0 Hz, 2 H, Ar), 7.01 (d, J ϭ
7.6 Hz, 2 H, Ar) 7.18 (dd, J ϭ 8.0, 10.4 Hz, 2 H, Ar) ppm. 13C
NMR (100 MHz, CDCl3): δ ϭ 13.8 (CH3CH2), 20.9 (CH2), 24.1
(CH3), 42.0 (CH), 55.0 (OCH3), 108.0 (CH-Ar), 118.0 (CH-Ar),
120.6 (CH-Ar), 129.4 (C-Ar), 148.0 (C-Ar), 159.0 (C-Ar) ppm. IR
(NaCl): ν˜ ϭ 3427, 2970, 2920, 1562, 1462, 1262, 1045, 781,
650 cmϪ1. MS (EI): m/z (%) ϭ 573 (7) [M ϩ NH4]ϩ, 275 (58), 213
(100), 181 (10), 151 (20), 135 (17), 119 (8), 100 (15); HRMS: calcd.
for C22H30O2S2Se2 572.9910, found 572.9905.
2915, 1719, 1579, 1463, 1373, 1262, 1021, 755, 730 cmϪ1
.
Electrophile 20: Synthesized from (R,R)-bis{2-[1-(ethylsulfanyl)-
ethyl]-6-methoxyphenyl} diselenide.
(R)-1-[1-(Ethylsulfanyl)ethyl]-3-methoxybenzene: (S)-1-(3-Methoxy-
phenyl)ethanol[5] (1.5 g, 9.86 mmol) was dissolved in diethyl ether/
THF (1:1) (40 mL) at Ϫ20 °C, KOH (19.7 mmol, 1.104 g) and tosyl
chloride (10.8 mmol, 2.12 g) were added, and the reaction mixture
was stirred at Ϫ20 °C for 24 h. Sodium ethanethiolate (19.7 mmol,
1.66 g) was added, the mixture was allowed to warm up to room
temperature, and stirred for an additional 14 h. The reaction was
quenched with water (50 mL) and extracted with diethyl ether
(3 ϫ 25 mL). The combined organic extracts were dried over
MgSO4, and after evaporation of the solvent the yellow oil was
purified by flash chromatography on silica gel using ethyl acetate/
petroleum ether, 1:4 as eluent. A side product, bis[1-(3-methoxy-
3-(Hydroxymethyl)-5-methyl-5-phenyldihydrofuran-2-one
(21/22):
Synthesized according to GP 2. Purification by flash chromatogra-
phy on silica gel with ethyl acetate/ petroleum ether, 2:1. Yield 56%
(10 mg, 0.049 mmol); colorless oil; 21: 1H NMR (400 MHz,
CDCl3): δ ϭ 1.70 (s, 3 H, CH3), 2.29 (t, J ϭ 11.2 Hz, 1 H, CH2),
2.59 (t, J ϭ 11.2 Hz, 1 H, CH2), 2.59Ϫ2.69 (m, 1 H, CH), 3.69 (dd,
phenyl)ethyl] ether, was isolated in 16% yield as a colorless oil. J ϭ 5.2, 11.2 Hz, 1 H, CH2OH), 3.89 (dd, J ϭ 4.0, 11.2 Hz, 1 H,
Yield 28% (542 mg, 2.76 mmol); colorless oil. HPLC conditions:
CH2OH), 7.20Ϫ7.40 (m, 5 H, Ar) ppm. 13C NMR (100 MHz,
CDCl3): δ ϭ 30.6 (CH3), 39.4 (CH2), 43.1 (CH), 61.2 (CH2OH),
86.1 (C), 124.6 (CH-Ar), 128.2 (CH-Ar), 129.1 (CH-Ar), 144.1 (C-
Chiracel OD-H, flow rate: 0.5 ml minϪ1, 2-propanol/n-hexane,
1:99, 25 °C, Rf(R) ϭ 11.2 min, Rf(S) ϭ 12.9 min; e.r. 96:4. [α]D21
ϭ
1
Ϫ84.8 (c ϭ 0.125, CHCl3). H NMR (400 MHz, CDCl3): δ ϭ 1.18 Ar), 178.4 (CϭO) ppm. HPLC conditions: Chiracel OD-H, flow
(t, J ϭ 7.6 Hz, 3 H, CH3), 1.58 (d, J ϭ 7.2 Hz, 3 H, CH3), 2.37 (q, rate: 0.5 ml minϪ1, 2-propanol/n-hexane, 3:97, 10 °C, Rf(1) ϭ
1
J ϭ 5.2 Hz, 2 H, CH2), 3.84 (s, 3 H, OCH3), 3.99 (q, J ϭ 7.2 Hz,
68.0 min, Rf(2) ϭ 81.4 min. 22: H NMR (400 MHz, CDCl3): δ ϭ
1 H, CH), 6.78 (d, J ϭ 8.0 Hz, 1 H, Ar), 6.95 (d, J ϭ 10.4 Hz, 2 1.65 (s, 3 H, CH3), 2.51Ϫ2.65 (m, 2 H, CH2), 3.02Ϫ3.12 (m, 1 H,
H, Ar), 7.24(dd, J ϭ 8.0 Hz, 1 H, Ar) ppm. 13C NMR (100 MHz,
CH), 3.72 (dd, J ϭ 6.0, 10.8 Hz, 1 H, CH2OH), 3.88 (dd, J ϭ 5.2,
CDCl3): δ ϭ 14.9 (CH3CH2), 23.0 (CH3), 25.6 (CH2), 44.1 (CH), 11.2 Hz, 1 H, CH2OH), 7.10Ϫ7.30 (m, 5 H, Ar) ppm. HPLC con-
55.6 (OCH3), 112.6 (CH-Ar), 113.2 (CH-Ar), 120.1 (CH-Ar), 129.8
ditions: Chiracel OD-H, flow rate: 0.5 ml minϪ1, 2-propanol/n-hex-
ane, 3:97, 10 °C, Rf(1) ϭ 98.2 min, Rf(2) ϭ 190.9 min. IR (NaCl):
(CH-Ar), 146.3 (C-Ar), 160.1 (C-Ar) ppm. IR (NaCl): ν˜ ϭ 2967,
2917, 1600, 1485, 1454, 1369, 1318, 1259, 1203, 1154, 1044, 874, ν˜ ϭ 3394, 2359, 1758, 1643, 1446, 1236, 1145 cmϪ1. MS (EI): m/z
781, 701 cmϪ1. MS (EI): m/z (%) ϭ 197 (56) [M]ϩ, 152 (100), 135
(%) ϭ 207 (100) [M ϩ H]ϩ, 190 (46), 160 (7), 147 (22), 124 (13),
(25), 72 (12); HRMS: calcd. for C11H16OS 197.0995, found 113 (14), 91 (66); HRMS: calcd. for C12H14O3 207.1016, found
197.0994.
207.1013.
www.eurjoc.org
4578
 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2004, 4567Ϫ4581

Nucleophile-Selective Selenocyclizations
FULL PAPER
Methyl 5-Methyl-5-phenyltetrahydrofuran-3-carboxylate (23/24): 2875, 1644, 1446, 1188, 1048, 763, 702 cmϪ1. MS (EI): m/z (%) ϭ
Synthesized according to GP 2. Purification by flash chromatogra-
phy on silica gel with ethyl acetate/petroleum ether, 1:10. Yield 68%
(28.8 mg, 0.13 mmol). 23: 1H NMR (400 MHz, CDCl3): δ ϭ 1.42
(s, 3 H, CH3), 2.35 (dd, J ϭ 8.9, 12.6 Hz, 1 H, CH2), 2.50 (dd, J ϭ
8.1, 12.6 Hz, 1 H, CH2), 3.28 (quint, J ϭ 8.1 Hz, 1 H, CH), 3.50
(s, 3 H, OCH3), 4.00 (t, J ϭ 8.5 Hz, 1 H, CH2O), 4.20 (t, J ϭ
8.4 Hz, 1 H, CH2O), 7.10Ϫ7.35 (m, 5 H, Ar) ppm. 13C NMR
(100 MHz, CDCl3): δ ϭ 30.2 (CH3), 42.9 (CH2), 44.9 (CH), 52.3
(OCH3), 69.4 (CH2O), 85.3 (C), 125.0 (CH-Ar), 127.0 (CH-Ar),
128.6 (CH-Ar), 147.5 (C-Ar), 173.6 (CϭO) ppm. GC conditions:
Chirasil-Dex CB (25 m), 75Ϫ110 °C at 0.5 °C minϪ1, Rf(major) ϭ
54.9 min, Rf(minor) ϭ 56.0 min. 24: 1H NMR (400 MHz, CDCl3):
δ ϭ 1.50 (s, 3 H, CH3), 2.27 (dd, J ϭ 9.4, 12.3 Hz, 1 H, CH2), 2.53
(dd, J ϭ 8.1, 12.4 Hz, 1 H, CH2), 2.96 (quint, J ϭ 8.2 Hz, 1 H,
CH), 3.62 (s, 3 H, OCH3), 4.02 (t, J ϭ 8.7 Hz, 1 H, CH2O), 4.11 (t,
J ϭ 8.7 Hz, 1 H, CH2O), 7.12Ϫ7.32 (m, 5 H, Ar) ppm. 13C NMR
(100 MHz, CDCl3): δ ϭ 30.1 (CH3), 43.1 (CH2), 44.3 (CH), 52.5
(OCH3), 69.5 (CH2O), 85.8 (C), 124.9 (CH-Ar), 127.2 (CH-Ar),
128.7 (CH-Ar), 146.9 (C-Ar), 174.4 (CϭO) ppm. HPLC con-
ditions: Chiracel OD-H, flow rate: 0.5 ml minϪ1, 2-propanol/n-hex-
ane, 3:97, 10 °C, Rf(minor) ϭ 17.5 min, Rf(major) ϭ 19.7 min. IR
(thin film on NaCl): ν˜ ϭ 3466, 2966, 1736, 1629, 1489, 1445, 1373,
1328, 1268, 1199, 1167, 1062, 1022, 761, 702 cmϪ1. MS (EI): m/z
(%) ϭ 221 (11) [M]ϩ, 205 (100), 173 (10), 159 (4), 145 (49), 131 (6),
117 (16), 105 (36), 91 (7), 77 (11), 65 (4), 51 (8), 43 (12); HRMS:
319 (6) [M ϩ H]ϩ, 301 (100), 283 (5), 206 (14), 192 (23), 174 (4),
156 (6); ΗRMS calcd. for C12H15O2I 336.0455, found 336.0456.
[5-Phenyl-5-(phenylselanylmethyl)tetrahydrofuran-3-yl]methanol
(26b/27b): Synthesized according to GP 1. Purification by flash
chromatography on silica gel with ethyl acetate/petroleum ether,
1:2. Yield 74% (46 mg, 0.13 mmol); colorless oil; d.r. (26b/27b)
66:34. 1H NMR (400 MHz, CDCl3): δ ϭ 2.01 (dd, J ϭ 6.8, 12.8 Hz,
1 H, 27b-CH2), 2.08 (dd, J ϭ 8.4, 11.6 Hz, 1 H, 26b-CH2), 2.33
(quint, J ϭ 7.2 Hz, 1 H, 26b-CH), 2.38Ϫ2.44 (m, 1 H, 26b-CH2),
2.52 (dd, J ϭ 8.8, 12.8 Hz, 1 H, 27b-CH2), 2.67 (quint, J ϭ 7.2 Hz,
1 H, 27b-CH), 3.25 (d, J ϭ 12.0 Hz, 1 H, 27b-CH2Se), 3.26 (d, J ϭ
12.0 Hz, 1 H, 26b-CH2Se), 3.33 (d, J ϭ 12.0 Ηz, 1 H, 27b-CH2Se),
3.42 (d, J ϭ 12.4 Hz, 1 H, 26b-CH2Se), 3.60 (d, J ϭ 6.8 Hz, 2 H,
CH2O), 3.76 (dd, J ϭ 6.4, 8.8 Ηz, 1 H, 26b-CH2OH), 3.94 (t, J ϭ
8.4 Hz, 1 H, 26b-CH2OH), 4.04 (t, J ϭ 7.2 Hz, 1 H, 27b-CH2OH),
4.12 (t, J ϭ 7.2 Hz, 1 H, 27b-CH2OH), 7.01Ϫ7.40 (m, 10 H,
Ar) ppm. 26b: 13C NMR (100 MΗz, CDCl3): δ ϭ 39.3 (CH2), 40.6
(CH2Se); 41.9 (CH), 63.6 (CH2OH), 69.3 (CH2O), 85.7 (C), 124.2
(CH-Ar), 125.6 (CH-Ar), 126.1 (CH-Ar), 127.3 (CH-Ar), 127.9
(CH-Ar), 130.3 (C-Ar), 131.4 (CH-Ar), 143.9 (C-Ar) ppm. IR
(NaCl): ν˜ ϭ 3414, 3060, 2930, 2876, 1642, 1579, 1478, 1446, 1202,
1049, 1022, 764, 737, 703 cmϪ1. MS (EI): m/z (%) ϭ 349 [M]ϩ (17),
331 (29), 220 (7), 192 (100), 178 (22), 174 (7), 144 (8), 108 (20), 84
(7); ΗRMS calcd. for C18H20O2Se 366.0967, found 366.0962.
ϩ
calcd. for C13H16O3 ϩ NH4 238.1438, found 238.1438.
1-{2-[[(S)-4-(Hydroxymethyl)-2-phenyltetrahydrofuran-2-yl]methyl-
selanyl]phenyl}propan-1-ol (26f/27f): Synthesized according to GP
1. Purification by flash chromatography on silica gel with ethyl
acetate/petroleum ether, 1:2. Yield 28% (20 mg, 0.05 mmol); color-
less oil; d.r. (26f/27f) 59:41. [α]2D2 ϭ ϩ8.0 (c ϭ 0.075, CHCl3). 1H
NMR (400 MHz, CDCl3): δ ϭ 0.84 (t, J ϭ 7.2 Hz, 1 H, 27f-CH3),
0.86 (t, J ϭ 7.6 Hz, 1 H, 26f-CH3), 1.53Ϫ1.74 (m, 2 H, CH2CH3),
1.92Ϫ2.15 (m, 1 H, CH2), 2.30 (quint, J ϭ 6.8 Hz, 1 H, 26f-CH),
2.35Ϫ2.52 (m, 1 H, CH2), 2.66 (quint, J ϭ 7.2 Hz, 1 H, 27f-CH),
3.23 (d, J ϭ 12.0 Ηz, 1 H, 27f-CH2Se), 3.30 (d, J ϭ 12.0 Ηz, 1 H,
26f-CH2Se), 3.35 (d, J ϭ 12.4 Ηz, 1 H, 26f-CH2Se), 3.36 (d, J ϭ
11.2 Hz, 1 H, 27f-CH2Se), 3.60 (d, J ϭ 9.6 Ηz, 2 H, CH2O), 3.76
(dd, J ϭ 6.4 Hz, 1 H, 26f-CH2OH), 3.96 (t, J ϭ 8.0 Hz, 1 H, 26f-
CH2OH), 4.05 (t, J ϭ 7.2 Hz, 1 H, 27f-CH2OH), 4.13 (t, J ϭ
7.2 Hz, 1 H, 27f-CH2OH), 4.86 (q, J ϭ 6.8 Hz, 1 H, 26f-CH-Ar),
5.02Ϫ5.10 (m, 1 H, CH-Ar), 6.90Ϫ7.44 (m, 9 H, Ar) ppm. 26f: 13C
NMR (100 MΗz, CDCl3): δ ϭ 10.8 (CH3), 31.4 (CH2CH3), 41.2
(CH), 41.9 (CH2Se), 43.2 (CH2), 64.8 (CH2OH), 70.6 (CH2O), 74.8
(CH-Ar), 87.3 (C), 125.7 (CH-Ar), 126.5 (CH-Ar), 127.3 (CH-Ar),
127.6 (CH-Ar), 128.3 (CH-Ar), 128.4 (CH-Ar), 130.7 (C-Ar), 134.8
(CH-Ar), 146.6 (C-Ar) ppm. IR (NaCl): ν˜ ϭ 3418, 2928, 2865,
1632, 1446, 1268, 1197, 1047, 753, 703 cmϪ1. MS: m/z (%) ϭ 389
(43) [M Ϫ H2O]ϩ, 371 (22), 197 (31), 176 (36), 158 (36), 108 (100),
2-(2-Phenylallyl)propane-1,3-diol (25): Lithium aluminum hydride
(17 mg, 0.44 mmol) was dissolved in dry THF (5 mL). Compound
5 (180 mg, 0.88 mmol) was dissolved in THF (5 mL), added in and
stirred at room temperature overnight. The reaction was quenched
at 0 °C with diluted H2SO4, extracted with diethyl ether, dried over
MgSO4, and the solvent was evaporated to produce a colorless
solid which was further purified by flash chromatography on silica
gel with tert-butyl methyl ether. Yield 85% (144 mg, 0.75 mmol);
1
m.p. 55Ϫ56 °C. H NMR (400 MHz, CDCl3): δ ϭ 1.75Ϫ1.85 (m,
1 H, CH), 2.47 (d, J ϭ 7.6 Hz, 2 H, CH2), 3.58 (dd, J ϭ 7.2,
10.8 Hz, 2 H, CH2OH), 3.72 (dd, J ϭ 3.6, 10.4 Hz, 1 H, CH2OH),
5.04 (d, J ϭ 0.8 Hz, 1 H, ϭCH2), 5.26 (d, J ϭ 1.2 Hz, 1 H, ϭCH2),
7.15Ϫ7.45 (m, 5 H, Ar) ppm. 13C NMR (100 MΗz, CDCl3): δ ϭ
34.3 (CH2), 40.5 (CH), 66.2 (CH2OH), 114.8 (ϭCH2), 126.6 (CH-
Ar), 128.1 (CH-Ar), 128.9 (CH-Ar), 140.9 (Cϭ), 146.6 (C-Ar) ppm.
IR (NaCl): ν˜ ϭ 3374, 2927, 2882, 1626, 1494, 1444, 1092, 1028,
971, 898, 779, 709 cmϪ1. MS (EI): m/z (%) ϭ 192 (10), 174 (31),
157 (76), 150 (23), 143 (30), 128 (27), 117 (100), 103 (17), 91 (10);
ΗRMS calcd. for C12H16O2 193.1223, found 193.1222.
[5-(Iodomethyl)-5-phenyltetrahydrofuran-3-yl]methanol (26a/27a):
Synthesized according to the procedure for the synthesis of 8a/9a
using substrate 25. Purification by flash chromatography on silica
gel with ethyl acetate/petroleum ether, 1:1. Yield 43% (29 mg,
ϩ
100 (7); ΗRMS calcd. for C21H26O3Se ϩ NΗ4 424.1385, found
424.1389.
0.091 mmol); colorless oil; d.r. (26a/27a) 70:30. 1H NMR {5-[2-[(R)-1-(Ethylsulfanyl)ethyl]phenylselanylmethyl]-5-phenyltetra-
(400 MHz, CDCl3): δ ϭ 1.95Ϫ2.15 (m, 1 H, CH2), 2.30Ϫ2.58 (m, hydrofuran-3-yl}methanol (26i/27i): Synthesized according to GP 1.
3 H, CH2, 26a-CH), 2.70 (quint, J ϭ 7.6 Hz, 1 H, 27a-CH), 3.42 Purification by flash chromatography on silica gel with ethyl acet-
(d, J ϭ 10.4 Hz, 1 H, 27a-CH2I), 3.47 (t, J ϭ 10.4 Hz, 1 H, 27a-
CH2I), 3.49 (d, J ϭ 10.4 Hz, 1 H, 26a-CH2I), 3.50 (d, J ϭ 10.4 Hz,
1 H, 26a-CH2I), 3.63 (d, J ϭ 6.4 Ηz, 2 H, CH2O), 3.80 (t, J ϭ
ate/petroleum ether, 1:2. Yield 33% (28 mg, 0.06 mmol); colorless
1
oil; d.r. (26i/27i) 81:19. [α]2D2 ϭ Ϫ7.71 (c ϭ 1.4, CHCl3). H NMR
(400 MHz, CDCl3): δ ϭ 1.07 (t, J ϭ 7.2 Hz, 3 H, 26i-CH3), 1.10 (t,
8.0 Ηz, 1 H, 26a-CH2OH), 3.97 (t, J ϭ 8.0 Ηz, 1 H, 26a-CH2OH), J ϭ 7.6 Hz, 3 H, 27i-CH3), 1.41 (d, J ϭ 7.2 Hz, 3 H, 27i-CH3), 1.45
4.04 (t, J ϭ 7.2 Ηz, 1 H, 27a-CH2OH), 4.18 (t, J ϭ 8.4 Hz, 1 H,
(d, J ϭ 7.2 Hz, 3 H, 26i-CH3), 2.06Ϫ2.14 (m, 1 H, CH2), 2.24Ϫ2.45
27a-CH2OH), 7.10Ϫ7.45 (m, 5 H, Ar) ppm. 26a: 13C NMR (m, 4 H, CH2S, CH2, CH), 2.50Ϫ2.56 (m, 1 H, 27i-CH2), 2.68
(100 MΗz, CDCl3): δ ϭ 19.3 (CH2), 40.9 (CH2O), 42.2 (CH), 64.8 (quint, J ϭ 7.6 Hz, 1 H, 27i-CH), 3.24 (d, J ϭ 12.0 Hz, 1 H, 26i-
(CH2OH), 70.9 (CH2I), 85.5 (C), 125.8 (CH-Ar), 127.9 (CH-Ar),
CH2Se), 3.27 (d, J ϭ 12.0 Hz, 1 H, 27i-CH2Se), 3.36 (d, J ϭ
128.8 (CH-Ar), 143.3 (C-Ar) ppm. IR (NaCl): ν˜ ϭ 3438, 2931, 12.0 Hz, 1 H, 27i-CH2Se), 3.38 (d, J ϭ 12.0 Hz, 1 H, 26i-CH2Se),
Eur. J. Org. Chem. 2004, 4567Ϫ4581
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 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
4579

S. S. Khokhar, T. Wirth
FULL PAPER
3.62 (d, J ϭ 6.8 Hz, 2 H, 26i-CH2O), 3.63 (d, J ϭ 6.4 Hz, 1 H, 27i- Ar), 127.0 (CH-Ar), 127.4 (CH-Ar), 128.1 (CH-Ar), 132.8 (CH-
CH2O), 3.77 (t, J ϭ 8.4 Hz, 1 H, 26i-CH2OH), 3.78 (t, J ϭ 6.8 Hz, Ar), 134.4 (C-Ar), 138.9 (C-Ar) ppm. IR (NaCl): ν˜ ϭ 3405, 3059,
1 H, 27i-CH2OH), 3.95 (t, J ϭ 8.0 Hz, 1 H, 26i-CH2OH), 4.54 (q,
J ϭ 6.8 Hz, 1 H, 27i-CH-Ar), 4.58 (q, J ϭ 6.8 Hz, 1 H, 26i-CH-
2869, 1732, 1578, 1494, 1476, 1437, 1376, 1302, 1176, 1048, 1023,
739, 697 cmϪ1. MS (EI): m/z (%) ϭ 335 (100) [M ϩ H]ϩ, 317 (22),
Ar), 6.90Ϫ7.40 (m, 9 H, Ar) ppm. 26i: 13C NMR (100 MΗz, 178 (100), 160 (12); ΗRMS calcd. for C17H18O2Se 335.0545,
CDCl3): δ ϭ 15.1 (CH3), 23.0 (CH3CH), 25.6 (CH2S), 40.8 (CH2), found 335.0552.
42.0 (CH), 42.6 (CH2Se), 42.9 (CH-Ar), 65.1 (CH2O), 70.7
(CH2OH), 87.2 (C), 125.6 (CH-Ar), 127.5 (CH-Ar), 127.9 (CH-
Ar), 128.0 (CH-Ar), 128.7 (CH-Ar), 132.1 (C-Ar), 133.9 (CH-Ar),
(1S)-1-{2-[4-(Hydroxymethyl)-2-phenyltetrahydrofuran-3-yl]phenyl-
selanyl}propan-1-ol (29f/30f): Synthesized according to GP 1. Puri-
fication by flash chromatography on silica gel with tert-butyl
145.4 (C-Ar), 145.9 (C-Ar) ppm. IR (NaCl): ν˜ ϭ 3396, 3056, 2928,
methyl ether/petroleum ether, 2:1. Yield 64% (35 mg, 0.11 mmol);
2869, 1599, 1584, 1494, 1464, 1446, 1378, 1262, 1202, 1047, 806,
colorless oil; d.r. (29f/30f) 93:7. [α]2D2 ϭ ϩ70.6 (c ϭ 0.60, CHCl3).
763, 730, 704 cmϪ1. MS (EI): m/z (%) ϭ 436 (100) [M]ϩ, 407 (24);
1H NMR (400 MHz, CDCl3): δ ϭ 0.82 (t, J ϭ 7.6 Ηz, 3 H, CH3),
ΗRMS calcd. for C22H28O2SSe 436.0970, found 436.0975.
152Ϫ1.72 (m, 2 H, CH2), 2.48Ϫ2.62 (m, 1 H, CH), 3.17 (dd, J ϭ
2-Styrylpropane-1,3-diol (28): Lithium aluminum hydride (417 mg,
11 mmol) was dissolved in dry THF (10 mL). (E)-2-(Methoxycar-
6.8, 8.4 Ηz, 1 H, CHSe), 3.43 (dd, J ϭ 6.0, 10.8 Ηz, 1 H, CH2O),
3.58 (dd, J ϭ 6.4, 10.8 Ηz, 1 H, CH2O), 3.89 (dd, J ϭ 4.8, 9.2 Ηz,
bonyl)-4-phenylbut-3-enoic acid[23] (1.00 g, 4.55 mmol) dissolved in 1 H, CH2OH), 3.97 (dd, J ϭ 7.6, 8.8 Ηz, 1 H, CH2OH), 4.68 (d,
THF (5 mL) was added to this mixture at 0 °C and stirred at room
temperature overnight. The reaction was quenched at 0 °C with
ethanol (20 mL), and the solvents were evaporated. The solid was
dissolved in water (15 mL), extracted with diethyl ether (3 ϫ
J ϭ 8.8 Hz, 1 H, 29f-OCH), 4.87 (d, J ϭ 8.8 Ηz, OCH), 5.98 (q,
J ϭ 6.0 Ηz, 1 H, 29f-ArCHOH), 5.09 (q, J ϭ 6.0 Ηz, 1 H, 29f-
ArCHOH), 6.80Ϫ7.44 (m, 9 H, Ar) ppm. 29f: 13C NMR (100
MΗz, CDCl3): δ ϭ 10.7 (CH3), 31.7 (CH2), 51.0 (CHSe), 51.5
15 mL), the combined organic phases were dried over MgSO4, the (CH), 63.3 (CH2OH), 67.5 (CH2O), 71.0 (ArCHOH), 87.5 (OCH),
solvent was evaporated, and the residual yellow oil was further
purified by flash chromatography on silica gel with diethyl ether to
121.8 (C-Ar), 128.2 (CH-Ar), 128.3 (CH-Ar), 128.5 (CH-Ar), 128.8
(CH-Ar), 129.2 (CH-Ar), 131.8 (CH-Ar), 136.8 (CH-Ar), 140.2 (C-
Ar), 147.4 (C-Ar) ppm. IR (NaCl): ν˜ ϭ 3358, 3056, 2962, 2880,
give a pale yellow solid in 32% yield (260 mg, 1.46 mmol); m.p.
1
76Ϫ78 °C. H NMR (400 MHz, CDCl3): δ ϭ 2.51Ϫ2.54 (m, 1 H, 1615, 1456, 1378, 1263, 1192, 1048, 972, 911, 754, 699 cmϪ1. MS
CH), 3.77 (d, J ϭ 6.0 Hz, 4 H, CH2OH), 6.03 (dd, J ϭ 8.4, 16.0 Hz, (EI): m/z (%) ϭ 392 (36) [M]ϩ, 187 (11), 149 (10), 122 (12), 107
1 H, ϭCH), 6.50 (d, J ϭ 16.0 Hz, 1 H, ϭCH), 7.12Ϫ7.35 (m, 5
(100), 85 (48), 61 (15); ΗRMS calcd. for C20H24O3Se 392.0885,
H, Ar) ppm. 13C NMR (100 MΗz, CDCl3): δ ϭ 47.6 (CH), 65.5 found 392.0887.
(CH2OH), 126.6 (CH-Ar), 127.2 (ϭCH), 128.0 (CH-Ar), 129.0
{4-[2-[(R)-2-(Ethylsulfanyl)ethyl]phenylselanyl]-5-phenyltetra-
(CH-Ar), 133.6 (CHϭ), 137.2 (C-Ar) ppm. IR (NaCl): ν˜ ϭ 3408,
2925, 2885, 1647, 1494, 1449, 1031, 967, 748, 694 cmϪ1. MS (EI):
m/z (%) ϭ 196 (100) [M ϩ NΗ4]ϩ, 178 (8), 161 (16), 130 (24);
ΗRMS calcd. for C11H14O2 196.1332, found 196.1333.
hydrofuran-3-yl}methanol (29i/30i): Synthesized according to GP 1.
Purification by flash chromatography on silica gel with diethyl
ether/petroleum ether, 2:1. Yield 30% (14 mg, 0.032 mmol); color-
less oil;, d.r. (29i/30i) 86:14. [α]2D3 ϭ Ϫ30.5 (c ϭ 0.57, CHCl3). 1H
NMR (400 MHz, CDCl3): δ ϭ 1.05 (t, J ϭ 7.6 Ηz, 3 H, 30i-CH3),
(4-Iodo-5-phenyltetrahydrofuran-3-yl)methanol (29a/30a): Synthe-
sized according to the procedure for the synthesis of 8a/9a using 1.11 (t, J ϭ 7.6 Ηz, 3 H, 29i-CH3), 1.39 (d, J ϭ 6.8 Ηz, 3 H, 29i-
substrate 28. Purification by flash chromatography on silica gel CH3), 1.43 (d, J ϭ 6.8 Ηz, 3 H, 30i-CH3), 2.32 (q, J ϭ 7.6 Ηz, 2
with tert-butyl methyl ether/petroleum ether, 1:2. Yield 79% (34 mg, H, SCH2), 2.48Ϫ2.62 (m, 1 H, CH), 3.20 (dd, J ϭ 6.8, 8.4 Ηz, 1
0.11 mmol);, colorless oil; d.r. (29a/30a) 88:12. 1H NMR (400 MHz, H, 29i-CH2O), 3.29 (dd, J ϭ 6.4, 9.2 Ηz, 1 H, 30i-CH2O),
CDCl3): δ ϭ 2.73Ϫ2.83 (m, 1 H, CH), 3.69 (dd, J ϭ 6.4, 10.8 Ηz,
3.52Ϫ3.66 (m, 1 H, CH2O), 3.97 (dd, J ϭ 5.2, 8.8 Ηz, 1 H,
1 H, CH2O), 3.71 (t, J ϭ 8.8 Ηz, 1 H, CHI), 3.84 (t, J ϭ 8.4 Ηz, 1 CH2OH), 4.03 (dd, J ϭ 7.6, 8.8 Ηz, 1 H, 29i-CH2OH), 4.26 (dd,
H, 30a-CHI), 3.98 (dd, J ϭ 6.8, 8.8 Ηz, 1 H, CH2OH), 4.07 (t, J ϭ J ϭ 7.6, 8.4 Ηz, 1 H, 30i-CH2OH) 4.43 (q, J ϭ 6.8 Hz, 1 H, 30i-
8.8 Ηz, CH2OH), 4.26 (dd, J ϭ 6.8, 9.2 Ηz, 1 H, 30a-CH2OH), SCH), 4.56 (q, J ϭ 6.8 Ηz, 1 H, 29i-SCH), 4.72 (d, J ϭ 8.4 Ηz, 1
4.94 (d, J ϭ 8.8 Ηz, 1 H, 29a-OCH), 5.28 (d, J ϭ 5.2 Ηz, 1 H, 30a-
H, 29i-OCH), 4.82 (d, J ϭ 7.2 Ηz, 1 H, 30i-OCH), 6.75Ϫ7.44 (m,
OCH), 7.18Ϫ7.42 (m, 5 H, Ar) ppm. 29a: 13C NMR (100 MΗz, 9 H, Ar) ppm. 29i: 13C NMR (100 MΗz, CDCl3): δ ϭ 15.1 (CH3),
CDCl3): δ ϭ 27.8 (CH), 52.0 (CHI), 60.8 (CH2OH), 68.6 (CH2), 22.6 (CH2), 25.6 (CH3), 43.0 (CHS), 50.7 (CH), 51.1 (CH-Se), 63.6
88.6 (OCH), 124.8 (C-Ar), 125.6 (CH-Ar), 127.5 (CH-Ar), 137.1
(CH-Ar) ppm. IR (NaCl): ν˜ ϭ 3364, 3032, 2938, 1602, 1494, 1454, 128.8 (CH-Ar), 129.1 (CH-Ar), 129.6 (CH-Ar), 136.6 (C-Ar), 140.3
1377, 1312, 1216, 1150, 1052, 966, 914, 759 cmϪ1. MS (EI): m/z
(C-Ar), 146.8 (C-Ar) ppm. IR (NaCl): ν˜ ϭ 3428, 3056, 2956, 2915,
(CH2OH), 70.4 (CH2O), 87.8 (C), 126.8 (CH-Ar), 127.8 (CH-Ar),
(%) ϭ 305 (33) [M ϩ H]ϩ, 178 (13), 151 (15), 117 (100), 99 (14), 2855, 1589, 1494, 1454, 1373, 1263, 1212, 1157, 1041, 1027, 754,
85 (44), 79 (11), 60 (42); ΗRMS calcd. for C11H13O2I ϩ NH4ϩ
322.0298, found 322.0301.
699, 650 cmϪ1. MS (EI): m/z (%) ϭ 398 (2) [M ϩ NH4]ϩ, 440 (8),
391 (15), 376 (25), 363 (100), 344 (12), 335 (8); ΗRMS calcd. for
C21H26O2SSe 440.1157, found 440.1161.
[5-Phenyl-4-(phenylselanyl)tetrahydrofuran-3-yl]methanol (29b/30b):
Synthesized according to GP 1. Purification by flash chromatogra-
phy on silica gel with ethyl acetate/petroleum ether, 1:4. Yield 50%
(30 mg, 0.091 mmol); colorless oil; d.r. (29b/30b) 94:6. 1H NMR
(5-Methyl-5-phenyltetrahydrofuran-3-yl)methanol (31): Synthesized
according to GP 2. Purification by flash chromatography on silica
gel with ethyl acetate/petroleum ether, 1:2. Yield 61% (7 mg,
(400 MHz, CDCl3): δ ϭ 2.45Ϫ2.56 (m, 1 H, CH), 3.10 (t, J ϭ 0.039 mmol); colorless oil; d.r. (cis/trans) 80:20. 1H NMR
7.6 Ηz, 1 H, CHSe), 3.58Ϫ3.72 (m, 2 H, CH2), 3.93 (dd, J ϭ 2.8,
5.6 Ηz, 2 H, CH2OH), 4.24 (dd, J ϭ 4.3, 6.0 Ηz, 1 H, 30b-
(400 MHz, CDCl3): δ ϭ 1.44 (s, 3 H, trans-CH3), 1.49 (s, 3 H, cis-
CH3), 1.70 (dd, J ϭ 8.8, 12.0 Hz, 1 H, cis-CH2), 1.89 (dd, J ϭ 7.2,
CH2OH), 4.67 (d, J ϭ 8.8 Ηz, 1 H, OCH), 4.86 (d, J ϭ 6.8 Ηz, 1 12.4 Hz, 1 H, trans-CH2), 2.22 (dd, J ϭ 8.4, 12.8 Hz, 1 H, trans-
H, OCH), 7.05Ϫ7.44 (m, 10 H, Ar) ppm. 29b: 13C NMR (100
CH2), 2.30 (quint, J ϭ 8.0 Hz, 1 H, cis-CH), 2.41 (dd, J ϭ 7.6,
MΗz, CDCl3): δ ϭ 48.3 (CHSe), 48.8 (CH), 62.3 (CH2OH), 69.0 12.0 Hz, 1 H, cis-CH2), 2.63 (quint, J ϭ 7.6 Hz, 1 H, trans-CH),
(CH2OH), 85.8 (OCH), 125.4 (CH-Ar), 126.4 (CH-Ar), 126.7 (CH- 3.38 (dd, J ϭ 7.6, 10.8 Hz, 1 H, trans-CH2O), 3.44 (dd, J ϭ 6.4,
4580
 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
Eur. J. Org. Chem. 2004, 4567Ϫ4581

Nucleophile-Selective Selenocyclizations
FULL PAPER
T. G. Back, Z. Moussa, Org. Lett. 2000, 2,
M. Tiecco, L. Testaferri, C. Santi, C. Tomas-
[3h]
[3i]
3191Ϫ3208.
3007Ϫ3009.
10.4 Hz, 1 H, trans-CH2O), 3.59 (dd, J ϭ 2.4, 6.8 Hz, 2 H, cis-
CH2O), 3.73 (dd, J ϭ 6.4, 8.8 Hz, 1 H, cis-CH2OH), 3.92 (t, J ϭ
8.8 Hz, 1 H, cis-CH2OH), 4.20 (t, J ϭ 7.6 Hz, 1 H, trans-CH2OH),
7.10Ϫ7.35 (m, 5 H, Ar) ppm. cis-isomer: 13C NMR (100 MHz,
CDCl3): δ ϭ 29.4 (CH3), 40.8 (CH), 41.5 (CH2), 64.1 (CH2OH),
68.7 (CH2O), 84.0 (C), 123.6 (CH-Ar), 125.5 (CH-Ar), 127.2 (CH-
Ar), 146.4 (C-Ar) ppm. IR (NaCl): ν˜ ϭ 3397, 2976, 2925, 2875,
1489, 1446, 1373, 1263, 1127, 1097, 1037, 906, 850, 801, 761,
700 cmϪ1. MS (EI): m/z (%) ϭ 210 (100) [M ϩ NH4]ϩ, 193 (16),
177 (8), 136 (8), 115 (7), 74 (10); HRMS: calcd. for C12H16O2
210.1489, found 210.1490.
sini, F. Marini, L. Bagnoli, A. Temperini, Tetrahedron: Asym-
metry 2000, 11, 4645Ϫ4650.
Review: T. Wirth, Angew. Chem. 2000, 112, 3890Ϫ3900; Angew.
Chem. Int. Ed. 2000, 39, 3740Ϫ3749.
L. Uehlin, G. Fragale, T. Wirth, Chem. Eur. J. 2002, 8,
[4]
[5]
1125Ϫ1133.
[6]
M. Gruttadauria, C. Aprile, R. Noto, Tetrahedron Lett. 2002,
43, 1669Ϫ1672.
M. Spichty, G. Fragale, T. Wirth, J. Am. Chem. Soc. 2000,
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122, 10914Ϫ10916.
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C. Aprile, M. Gruttadauria, M. E. Amato, F. DЈAnna, P. Lo
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H. Komatsu, M. Iwaoka, S. Tomoda, Chem. Commun. 1999,
205Ϫ206.
(5-Phenyltetrahydrofuran-3-yl)methanol (32): Synthesized according
to GP 2. Purification by flash chromatography on silica gel with
ethyl acetate/petroleum ether, 1:2. Yield 73% (3 mg, 0.02 mmol);
colorless oil; d.r. (trans/cis) 92:8. 1H NMR (400 MHz, CDCl3): δ ϭ
1.42Ϫ1.51 (m, 2 H, CH2), 2.41 (dd, J ϭ 6.4, 12.4 Hz, 1 H, CH2O),
2.58 (quint, J ϭ 7.2 Hz, 1 H, CH), 3.59 (dd, J ϭ 2.4, 6.4 Hz, 1 H,
CH2O), 3.87 (dd, J ϭ 5.6, 8.8 Hz, 1 H, CH2OH), 3.95 (t, J ϭ
8.8 Hz, 1 H, CH2OH), 4.79 (dd, J ϭ 6.4, 9.6 Hz, 1 H, trans-CHO),
4.92 (t, J ϭ 7.6 Hz, 1 H, cis-CHO), 7.15Ϫ7.35 (m, 5 H, Ar) ppm.
trans-isomer: 13C NMR (100 MHz, CDCl3): δ ϭ 28.7 (CH2), 41.3
(CH), 64.3 (CH2OH), 70.0 (CH2O), 80.2 (OCH), 124.7 (CH-Ar),
126.4 (CH-Ar), 127.4 (CH-Ar), 141.3 (C-Ar) ppm. IR (NaCl): ν˜ ϭ
3428, 3016, 2918, 2845, 1652, 1453, 1373, 1265, 1217, 1053, 909,
758, 700 cmϪ1. MS (EI): m/z (%) ϭ 196 (100) [M ϩ NH4]ϩ, 179
(8); HRMS: calcd. for C11H14O2 196.1332, found 196.1331. HPLC
conditions: Chiracel OD-H, flow rate: 0.5 ml minϪ1, 2-propanol/
n-hexane, 3:97, 10 °C, Rf(cis-1) ϭ 91.4 min, Rf(cis-2) ϭ 99.0 min,
Rf(trans-1) ϭ 112.3 min, Rf(trans-2) ϭ 126.1 min.
[9]
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[11]
[12]
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M. Tanaka, K. Tomioka, K. Koga, Tetrahedron 1994, 50,
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CCDC-214760 contains the supplementary crystallographic
data for this paper. These data can be obtained free of charge
at www.ccdc.cam.ac.uk/conts/retrieving.html [or from the
Cambridge Crystallographic Data Centre, 12 Union Road,
Cambridge CB2 1EZ, UK; Fax: (internat.) ϩ44-1223-336033;
E-mail: deposit@ccdc.cam.ac.uk].
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2,2Ј-Diselenobis(benzoic acid methyl ester): T.
Funding was provided by EPSRC grant no. GR/R42832 (scholar-
ship for S. S. K.) and grant no. GR/S25456 (NMR). We thank
Dr. Matthew Cox for the synthesis of the diselenide precursor for
electrophile 19 and the EPSRC National Mass Spectrometry Ser-
vice Centre, Swansea, for high resolution mass spectrometric
data.[1]
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