Preparation of a new chiral non-racemic sulfur-containing diselenide and applications in asymmetric synthesis

Article abstract of DOI:10.1002/1521-3765(20020301)8:5<1118::AID-CHEM1118>3.0.CO;2-2

The synthesis of the new chiral non-racemic sulfur-containing diselenide, di-2-methoxy-6-[(1S)-1-(methylthio)ethyl]phenyl diselenide, is described. When treated with ammonium persulfate this diselenide is transformed into the corresponding selenenyl sulfate, which acts as a strong electrophilic reagent and adds to alkenes, in the presence of methanol or water, to afford the products of selenomethoxylation or selenohydroxylation, respectively, with excellent diastereoselectivities. Starting from alkenes containing internal nucleophiles, asymmetric cyclofunctionalization reactions also resulted in good chemical yields, complete regioselectivities, and high diastereoselectivities. This sulfur-containing diselenide can also be used in catalytic amounts to promote one-pot selenenylation-deselenenylation processes, from which several types of products can be obtained in high yield and with good enantiomeric excess.

Full text of DOI:10.1002/1521-3765(20020301)8:5<1118::AID-CHEM1118>3.0.CO;2-2

FULL PAPER
Preparation of a New Chiral Non-Racemic Sulfur-Containing Diselenide and
Applications in Asymmetric Synthesis
Marcello Tiecco,* Lorenzo Testaferri, Claudio Santi, Cristina Tomassini,
Francesca Marini, Luana Bagnoli, and Andrea Temperini[a]
Abstract: The synthesis of the new
chiral non-racemic sulfur-containing dis-
elenide, di-2-methoxy-6-[(1S)-1-(meth-
ylthio)ethyl]phenyl diselenide, is de-
scribed.When treated with ammonium
persulfate this diselenide is transformed
into the corresponding selenenyl sulfate,
which acts as a strong electrophilic
reagent and adds to alkenes, in the
presence of methanol or water, to afford
the products of selenomethoxylation or
selenohydroxylation, respectively, with
excellent diastereoselectivities.Starting
from alkenes containing internal nucle-
ophiles, asymmetric cyclofunctionaliza-
tion reactions also resulted in good
chemical yields, complete regioselectiv-
ities, and high diastereoselectivities.This
sulfur-containing diselenide can also be
used in catalytic amounts to promote
one-pot selenenylation deselenenyla-
tion processes, from which several types
of products can be obtained in high yield
and with good enantiomeric excess.
Keywords: asymmetric synthesis
¥
cyclization ¥ selenium ¥ selenohy-
droxylation ¥ selenomethoxylation
Introduction
Organoselenium reagents are largely used in organic synthesis
to introduce new functional groups into organic substrates
under mild experimental conditions.[1] Several research
groups have described the synthesis of a number of chiral
non-racemic diselenides, which can be transformed in situ into
electrophilic selenenylating reagents and can induce, in the
presence of a suitable nucleophile, more or less efficient
Scheme 1.Optically active diselenides 1 and the interaction with neigh-
boring oxygen or nitrogen atoms in 2.
6]
asymmetric addition reactions to alkenes.[1 Recently a new
polymer-bound chiral electrophilic selenium reagent has also
been developed, leading to improvements in stereoselective
selenium-based solid-phase chemistry.[7]
action, which is depicted by structure 2 in Scheme 1, and
which is suggested to be the result of an orbital interaction
between the heteroatom lone pair and the low-lying anti-
bonding orbital of the SeY group (n-s*SeY), would force the
chiral center to approach the reaction center during the
addition of the selenenylating agent to the alkene.This would
result in asymmetric induction.Moreover, the same inter-
action should also dictate the structure of the active selenium
reagent, thus playing a fundamental role in the formation of
the preferred diastereomer of the addition products.We have
recently prepared and investigated the sulfur-containing
chiral diselenide 1 (X ˆ SMe, R ˆ Me).[9] The good results
obtained in the asymmetric selenomethoxylations and sele-
nohydroxylations of alkenes suggest that the interaction of
selenium with sulfur is probably more important than those
with oxygen or with nitrogen.
A common characteristic of all the optically active di-
selenides described in the literature is the close proximity of
an oxygen or a nitrogen atom to the selenium atom.This is
exemplified in Scheme 1 by the diselenides 1 (X ˆ OR', NR'2),
which are some of the products investigated by Wirth.[1] On
the basis of theoretical calculations, crystal structure deter-
minations, and NMR data[8] it has been suggested that
selenium can interact with nearby heteroatoms.This inter-
[a] Prof.M.Tiecco, Prof.L.Testaferri, Dr.C.Santi, Dr.C.Tomassini,
Dr.F.Marini, Dr.L.Bagnoli, Dr.A.Temperini
Dipartimento di Chimica e Tecnologia del Farmaco
Sezione di Chimica Organica
It has recently been observed by Wirth and co-workers that
in the case of the oxygen-containing diselenide 1 (X ˆ OH,
R ˆ Me, Et), better diastereoselectivities could be obtained
by introducing an appropriate substituent in the 6 position of
¡
Universita di Perugia
06123 Perugia (Italy)
Fax : (‡39)075-585-5116
E-mail: tiecco@unipg.it
1118
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Chem. Eur. J. 2002, 8, No. 5

1118 1124
the aromatic ring.[10] The presence of a further substituent in
the position ortho to the selenium atom can induce a greater
conformational rigidity to the chiral electrophilic reagent and
a more efficient transfer of chirality should be observed.On
the basis of these considerations we have undertaken the
synthesis of the methoxy-substituted sulfur-containing disele-
nide 3 in the hope that the corresponding electrophilic reagent
should give rise to addition reactions to alkenes with a
diastereoselectivity higher than those previously observed.
However, when the reactions were repeated at À308C the
facial selectivities and the reaction yields were considerably
increased.
In a typical experiment (Scheme 3) a solution of diselenide
3 (0.5 mmol) in CH2Cl2 (or CH3CN in the cases of the
selenohydroxylations) was treated with ammonium persulfate
Scheme 3.Synthesis of 8 and 9.
(0.5 mmol) and trifluoromethanesulfonic acid (1.0 mmol) at
room temperature for 15 min.The alkenes 7 (1.5 equiv),
dissolved in the nucleophilic solvents (MeOH or MeCN/
H2O), were added at À308C and the solution was stirred for
24 h.The progress of the reaction was monitored by GC-MS
and/or TLC.After the usual workup compounds 8 and 9 were
obtained as mixtures of the two enantiomerically pure
diastereomers by column chromatography on silica gel.In
no case could the two diastereomers be separated.Reaction
yields and diasteromeric ratios (d.r.) are reported in Table 1.
The diastereomeric ratios were determined by 1H NMR
analysis of the crude reaction mixtures.In the cases of trans-5-
decene (7e) and cyclohexene (7 f), good results could only be
obtained by using selenenyl triflate instead of the sulfate, and
by working at À788C.
Results and Discussion
The synthesis of the diselenide 3 was very easy and was similar
to that used by Wirth for the preparation of methoxy-
substituted 1 (X ˆ OH, R ˆ Me).The commercially available
ketone 4 was reduced to the corresponding optically active
alcohol 5 with (‡)-b-chlorodiisopinocampheylborane (DIP-
Cl).[11] This alcohol (98% ee) was transformed into the
tosylate and then treated with sodium methanethiolate to
afford the sulfide 6.The reaction of 6 with a 1.7m solution of
tBuLi in pentane gave the lithiated intermediate, which was
dissolved in anhydrous THF and treated with selenium metal
(Scheme 2).The diselenide 3 was obtained by oxidative
As indicated in Table 1 reaction yields are good and, most
interestingly, the diastereomeric ratios are excellent in every
case, with the exception of the selenohydroxylation products
deriving from cyclohexene.In Table 1 also gives the diaster-
eomeric ratios obtained with the di-2-[(1S)-1-(methylthio)-
ethyl]phenyl diselenide 1 (X ˆ SMe, R ˆ Me).In every case
the results obtained with the diselenide 3 are better than those
obtained with 1, indicating that the presence of the methoxy
group in the proximity of the selenium atom is greatly
beneficial for better chirality tranfer.As a matter of fact the
diastereoselectivities obtained with 3 compare favorably with
those observed with the most efficient chiral non-racemic
diselenides described in the literature.Moreover, a further
important property of the diselenide 3 is that the addition
reactions can be carried out at relatively high temperatures,
whereas with all of the other optically active selenenylating
reagents efficient asymmetric inductions are obtained only by
working at very low temperatures.
The absolute configurations of the major isomers were
estabilished in some cases by deselenenylation and compar-
ison of the resulting enantiomers with commercial products or
with compounds described in the literature.[9] As indicated in
Scheme 4, the reductive deselenenylation of 8a and 9a with
triphenyltin hydride and 2,2'-azobisisobutyronitrile (AIBN)
in refluxing benzene afforded (À)-(S)-10 and (À)-(S)-11,
whereas the oxidative elimination of 8b and 9b with hydrogen
peroxide in methanol afforded (‡)-(S)-12 and (À)-(S)-13,
respectively.
Scheme 2.Synthesis of diselenide 3.
workup of the reaction mixture.The proton NMR spectrum,
in the presence of (S)-(‡)-2,2,2-trifluoro-1-(9-anthryl)etha-
nol, demonstrated that this compound was enantiomerically
pure.
The efficiency of the diselenide 3 was first tested in the
stereoselective selenomethoxylation and selenohydroxylation
of several alkenes 7.For this purpose the diselenide 3 was
transformed in situ into the electrophilic selenenyl sulfate by
treatment with ammonium persulfate according to the
procedure described by us for the preparation of the phenyl-
selenenyl sulfate from diphenyl diselenide.[12] Some prelimi-
nary experiments carried out with styrene indicated that at
room temperature the diastereoselectivities were very poor.
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M.Tiecco et al.
FULL PAPER
Table 1.Selenomethoxylation, in methanol, and selenohydroxylation, in acetonitrile and water (2:1), of alkene 7 with the diselenide 3 and ammonium
persulfate at À308C.[a]
Starting
alkenes 7
Selenomethoxylation
products 8[b]
Yield
[%][c]
d.r.[d]
Selenohydroxylation
products 9[b]
Yield
[%][c]
d.r[d]
98:2
95:5
styrene 7a
8a
8b
8c
72
75
58
98:2
96:4
9a
9b
9c
65
70
73
98:2
96:4
b-methylstyrene 7b
a-methylstyrene 7c
98:2
96:4
98:2
90:10
95:5
90:10
2,4,6-trimethylstyrene 7d
8d
60
99:1
9d
75
99:1
96:4
88:12
trans-5-decene 7e
cyclohexene 7 f
8e
8 f
70
77
96:4
90:10
9e
9 f
79
60
91:9
72:28
82:18
1-phenyl-1-cyclohexene 7g
8g
60
98:2
[a] In the cases of 7e and 7 f the reactions were carried out at À788C with the selenenyl triflate derived from 3.[b] The two diastereoisomers could not be
separated.In no case could the presence of regioisomers be detected.[c] Based on the amounts of the diselenide employed.[d] The diastereomeric rati os
were determined from the proton NMR spectra of the crude reaction mixtures and confirmed after purification by column chromatography.The values
reported in italics refer to the reactions carried out with the diselenide 1 (X ˆ SMe, R ˆ Me).[14]
assumption that the facial selectivity of selenomethoxylation
and selenohydroxylation does not change on passing from
styrene and b-methylstyrene to a-methylstyrene and 2,4,6-
trimethylstyrene, it can be suggested that the chiral centers in
8c, 9c and 8d, 9d have the same absolute configurations as
those of 8a, 9a and 8b, 9b.
The efficiency of the diselenide 3 in promoting selenocy-
clization reactions was then explored by using some selected
examples.These reactions were carried out, as in the case of
the intermolecular processes described above, at À308C and
with the selenenyl sulfate generated by the oxidation of 3.The
ring-closure reactions investigated were those of the alkenol
14, the alkenoic acids 16 and 18, and of the O-allyl oxime 20,
which afforded the cyclic ether 15, the lactones 17 and 19, and
the isoxazolidine 21,[13] respectively.The results are collected
in Table 2.We also observed that in these cases the reactions
promoted by the electrophilic reagent deriving from 3
proceed with diastereoselectivities higher than those observed
with the diselenide 1 (X ˆ SMe, R ˆ Me).[14] The absolute
configuration of compound 19 was established after conver-
sion into the corresponding butenolide,[15] (À)-(R)-29, by
oxidation with ammonium persulfate.
Scheme 4.Reductive deselenenylation reactions of 8a and 9a and
oxidative elimination reactions of 8b and 9b.
One of the most interesting and recent developments in
organoselenium chemistry is represented by the one-pot
selenenylation deselenenylation sequences, which can be
performed with only catalytic amounts of the organoselenium
reagents.[16]
The enantiomeric excesses of 10, 11, 12, and 13 were
determined by recording their proton NMR spectra in the
presence of (S)-(‡)-2,2,2-trifluoro-1-(9-anthryl)ethanol.As
expected, the values obtained corresponded to the diastereo-
meric ratios of 8a, 9a, 8b, and 9b.Under the reasonable
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Sulfur-Containing Diselenides in Asymmetric Synthesis
1118 1124
Table 2.Selenocyclization reactions of alkenes containing internal nucle-
meric excesses, determined by recording the proton NMR
spectra in the presence of (S)-(‡)-2,2,2-trifluoro-1-(9-anthryl)-
ethanol, are reported in Table 3.The use of a larger amount of
the diselenide did not produce substantial increases in the
enantioselectivity.In the case of 18 the cyclization reaction
was performed at À308C to obtain a better enantiomeric
excess.Absolute configurations of the reaction products were
established by comparison with compounds already described
in the literature.[15, 18]
The results collected in Table 3 indicate that reaction yields
are very good in every case.The enantioselectivities of these
ring-closure reactions are not as good as those obtained in the
stoichiometric experiments described above.However, apart
from the case of the butenolide 29, the enantiomeric excesses
obtained in the other conversions can be considered satisfac-
tory and are better than those obtained in the most efficient
catalytic processes promoted by other diselenides reported in
the literature.In our opinion the enantiomeric excesses
observed in these reactions are high enough to justify the
further use of the diselenide 3 for the synthesis of enantio-
merically enriched compounds using the selenenylation de-
selenenylation sequence.
ophiles with the diselenide 3 and ammonium persulfate at À308C.
Starting alkenes
Cyclization products[a]
Yield[%][b]
d.r.[c]
14
16
18
15
69
96:4
93:7
17
19
72
60
98:2
92:8
89:11
20
21
70
96:4
[a] The two diastereoisomers could not be separated.In no case the
presence of regioisomers could be detected.[b] Based on the amounts of
the diselenide employed.[c] The diastereomeric ratios were determined
from the proton NMR spectra of the crude reaction mixtures and
confirmed after purification by column chromatography.The values
reported in italics refer to the reactions carried out with the diselenide 1
(X ˆ SMe, R ˆ Me).[14]
In conclusion, the experimental data described above
demonstrate that the easily available diselenide 3 represents
one of the most convenient reagents for very efficient
selenium-promoted asymmetric syntheses under very simple
experimental conditions.The diastereoselectivities obtained
with 3 compare favorably with those observed with the most
efficient chiral non-racemic di-
As exemplified in Scheme 5 this sequence is carried out
with the selenenyl sulfate, generated from diselenide and
persulfate, as the electrophilic reagent for the initial addition
to an alkene, as for instance 22.The resulting selenide 23 is
then oxidized by the excess of persulfate, affording the
selenides described in the liter-
ature which, moreover, afford
good results only at very low
temperatures.The efficient cat-
alytic one-pot selenenylation
deselenenylation
sequences,
which produce several types of
products in high yield and with
good enantiomeric excesses,
represent a further advantage
Scheme 5.Selenenylation deselenenylation sequence used to generate 24.
of this new diselenide.
deselenenylated compound 24 and, at the same time, regen-
erating the selenenyl sulfate.Several optically active disele-
nides have been employed in this reaction.Enantioselectiv-
ities of up to 70 80% were achieved, but turnover numbers
were still small.[4c, 5a, 17, 18]
The efficiency of the diselenide 3 confirms that the
conformational restriction imposed by the interaction of the
selenium atom with the close sulfur atom is very likely the
most important factor responsible for the high facial selectiv-
ities observed in the addition of the electrophilic selenium
We have tested the efficiency
of the diselenide 3 as a catalyst
for the promotion of the one-
pot conversion of b,g-unsatu-
rated esters 22 and 26 into the
allyl ethers 25 and 27, the ester
26 into the allylic alcohol 28,
and the g-alkenoic acid 18 into
the butenolide 29.The reac-
tions were carried out at room
temperature using 5% of the
diselenide 3 and an excess of
ammonium persulfate.Reac-
tion times, yields, and enantio-
Table 3.Selenenylation deselenenylation sequences promoted by catalytic amounts of the diselenide 3.
Starting alkenes
Solvent
T [8C] Time [h] Reaction product
Yield[%] ee[a] [%]
22 MeOH
20 68
(‡)-(R)-25 98
68
78
82
55
26 MeOH
20 48
20 96
(À)-(S)-27 98
(À)-(S)-28 98
(À)-(R)-29 85
26 MeCN/H20
18 CH2Cl2
À 30 48
[a] The enantiomeric excesses were determined by recording the proton NMR spectra in the presence of (S)-(‡)-
2,2,2-trifluoro-1-(9-anthryl)ethanol.
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M.Tiecco et al.
FULL PAPER
reagent to alkenes.[9] In this respect, as already observed by
Wirth and co-workers with the diselenide 1 (X ˆ OH, R ˆ Me,
Et),[10] the results now described confirm that the presence of
the methoxy group in the proximity of the selenium atom is
greatly beneficial for better chirality tranfer.
products thus obtained are reported in Table 1.Physical and spectral data
are reported below.
1-Methoxy-2-{[(2R)-2-methoxy-2-phenylethyl]seleno}-3-[(1S)-1-(methyl-
thio)ethyl]benzene (8a): Oil; [a]2D2 ˆ À103.2 (c ˆ 0.31 in CHCl3); 1H NMR
(400 MHz, CDCl3, 258C, TMS): d ˆ 7.4 7.3 (m, 6H; CH), 7.18 (dd,
3J(H,H) ˆ 7.7 Hz, 4J(H,H) ˆ 0.9 Hz, 1H; CH), 6.8 (dd, 3J(H,H) ˆ 8.2 Hz,
3
4J(H,H) ˆ 0.9 Hz, 1H; CH), 4.92 (q, J(H,H) ˆ 7.0 Hz, 1H; CH), 4.29 (dd,
3J(H,H) ˆ 8.7, 4.9 Hz,1H; CH), 3.8 (s, 3H; OCH3), 3.27 (s, 3H; OCH3), 3.19
(dd, 2J(H,H) ˆ 12.1 Hz, 3J(H,H) ˆ 8.7 Hz, 1H; CH2), 3.09 (dd, 2J(H,H) ˆ
12.1 Hz, 3J(H,H) ˆ 4.9 Hz, 1H; CH2), 1.96 (s, 3H; SCH3), 1.57 (d,
3J(H,H) ˆ 7.0 Hz, 3 H ; CH 3); 13C NMR (100 MHz, CDCl3, 258C, TMS):
d ˆ 159.4, 148.1, 141.1, 129.1, 128.3, 127.8, 126.4, 125,7, 119.1, 108.9, 83.3,
56.8, 55.9, 44.2, 34.7, 21.6, 13.9; 77Se NMR (76.27 MHz, CDCl3, 258C): d ˆ
Experimental Section
General: All new compounds were fully characterized by 1H NMR,
13C NMR, mass spectra, and elemental analyses. 1H, 13C, and 77Se NMR
spectra were recorded at 400, 100.62, and 76.27 MHz, respectively, on a
Bruker Avance-DRX 400 instrument.GC-MS analyses were carried out
with an HP-6890 gas chromatograph (dimethyl silicone column, 12.5 m)
equipped with an HP-5973 mass-selective detector.Optical rotations were
measured with a JASCO DIP-1000 digital polarimeter.FT-IR spectra were
recorded on a JASCO FT-IR-410 spectrophotometer.Elemental analyses
were carried out on a Carlo Erba 1106 elemental analyzer.All the alkenes
employed for the present investigation were commercially available.
‡
146.8; GC-MS: m/z (%): 396 (41) [M ], 381 (5), 361 (100), 345 (17), 213
(94), 198 (43), 135 (40), 121 (38), 103 (27), 91 (29), 77 (20), 61 (7); elemental
analysis calcd (%) for C19H24O2SSe (395.4): C 57.72, H 6.12; found: C 58.10,
H 6.15.
1-Methoxy-2-[(1S,2R)-2-methoxy-1-methyl-2-phenylethyl]seleno-3-
[(1S)-1-(methylthio)ethyl]benzene (8b): Oil; [a]2D3:5 ˆ À103.2 (c ˆ 0.34 in
CHCl3); 1H NMR (400 MHz, CDCl3, 258C, TMS): d ˆ 7.3 7.2 (m, 7H;
CH), 6.8 (dd, 3J(H,H) ˆ 8.1 Hz, 4J(H,H) ˆ 1.0 Hz, 1H; CH), 4.79 (q,
3J(H,H) ˆ 7.0 Hz, 1H; CH), 4.17 (d, 3J(H,H) ˆ 4.6 Hz, 1H; CH), 3.84 (s,
3H; OCH3), 3.63 (dq, 3J(H,H) ˆ 4.6, 7.0 Hz, 1H; CH), 3.15 (s, 3H; OCH3),
Synthesis of 1-methoxy-3-[(1S)-1-(methylthio)ethyl]benzene (6): TsCl
(1 mmol) and KOH (2 mmol) were added to a solution of the optically
pure (1R)-1-(3-methoxyphenyl)ethanol (5)[19] (1 mmol) in diethyl ether at
À208C.After 24 h MeSNa (4 mmol) was added and the reaction mixture
was warmed to room temperature and stirred for 12 h.After the usual
workup the reaction mixture was purified by flash chromatography on a
silica gel column with a mixture of diethyl ether and light petroleum (1:9) as
eluant.Pure 6 was obtained as an oil in 75% yield.[ a]2D3:9 ˆ À128 (c ˆ 9.0 in
3
3
1.86 (s, 3H; SCH3), 1.43 (d, J(H,H) ˆ 7.0 Hz, 3H; CH3), 1.2 (d, J(H,H) ˆ
7.0 Hz, 3H; CH3); 13C NMR (100 MHz, CDCl3, 258C, TMS): d ˆ 160.2,
149.0, 140.4, 129.7, 128.5, 127.9, 127.3, 126.2, 119.7, 109.3, 86.6, 57.9, 56.7, 44.7,
‡
44.5, 30.1, 16.1, 14.5; GC-MS: m/z (%): 410 (9) [M ], 261 (100), 213 (71),
198 (19), 181 (4), 149 (19), 17 (24), 115 (17), 105 (7), 91 (21), 75 (18);
elemental analysis calcd (%) for C20H26O2SSe (409.4): C 58.68, H 6.40;
found: C 58.47, H 6.52.
1
3
CHCl3); H NMR (400 MHz, CDCl3, 258C, TMS): d ˆ 7.26 (dt, J(H,H) ˆ
8.1 Hz, 5J(H,H) ˆ 1.0 Hz, 1H; CH), 6.9 (m, 2H; CH), 6.81 (ddd, 3J(H,H) ˆ
8.1 Hz, 4J(H,H) ˆ 2.6 Hz, 4J(H,H) ˆ 1.0 Hz, 1H; CH); 3.84 (q, 3J(H,H) ˆ
7.0 Hz, 1H; CH), 3.83 (s, 3H; OCH3), 1.95 (s, 3H; SCH3), 1.6 (d, 3J(H,H) ˆ
7.0 Hz, 3H; CH3); 13C NMR (100 MHz, CDCl3, 258C, TMS): d ˆ 160.1,
145.8, 129.8, 120.1, 113.3, 112.7, 55.6, 46.1, 22.5, 15.0; GC-MS: m/z (%): 182
1-Methoxy-2-[(2R)-2-methoxy-2-phenylpropyl]seleno-3-[(1S)-1-(methyl-
thio)ethyl]benzene (8c): Oil; [a]2D9:6 ˆ À3.5 (c ˆ 1.5 in CHCl3); 1H NMR
(400 MHz, CDCl3, 258C, TMS): d ˆ 7.4 7.5 (m, 6H; CH), 7.2 (dd,
3J(H,H) ˆ 7.7 Hz, 4J(H,H) ˆ 0.9 Hz, 1H; CH), 6.6 (dd, 3J(H,H) ˆ 8.2 Hz,
4J(H,H) ˆ 0.9 Hz, 1H; CH), 4.85 (q, 3J(H,H) ˆ 7.0 Hz, 1H; CH), 3.8 (s, 3H;
OCH3), 3.28 (d, 3J(H,H) ˆ 11.5 Hz, 1H; CH), 3.17 (d, 3J(H,H) ˆ 11.5 Hz,
1H; CH2), 3.08 (s, 3H; OCH3), 1.85 (s, 3H; SCH3), 1.5 (s, 3H, CH3), 1.3 (d,
3J(H,H) ˆ 7.0 Hz, 3 H ; CH 3); 13C NMR (100 MHz, CDCl3, 258C, TMS):
d ˆ 160.0, 148.4, 130.3, 129.2, 128.1, 128.0, 127.1, 126.2, 119.1, 109.3, 96.1,
‡
(44) [M ], 135 (100), 120 (9), 105 (23), 103 (13), 91 (14), 79 (8), 77 (8), 65
(5), 51 (2); elemental analysis calcd (%) for C10H14OS (182.3): C 65.89, H
7.74; found: C 66.05, H 7.64.
Synthesis of the di-2-methoxy-6-[(1S)-1-(methylthio)ethyl]phenyl disele-
nide (3): The sulfide 6 (1 mmol) was treated with a 1.7m solution of tBuLi
(1.5 mmol) in pentane at À788C.After 15 min the temperature was raised
to 258C and the mixture was stirred for 30 min.The resulting red
precipitate was dissolved in freshly distilled THF at À788C, and elemental
selenium (2 mmol) was added at the same temperature.The solution was
stirred for 12 h at room temperature and then poured into a 7% solution of
hydrochloric acid.The mixture was worked up in the usual way and the
crude product was purified by flash chromatography on a silica gel column
with a mixture of diethyl ether and light petroleum (2:8) as eluant.The
diselenide 3 was obtained as a yellow oil in 70% yield.[ a]1D9 ˆ À336.1 (c ˆ
0.5 in CHCl3); 1H NMR (400 MHz, CDCl3, 258C, TMS): d ˆ 7.3 (dd,
3J(H,H) ˆ 8.2, 7.8 Hz, 2H; CH), 7.09 (dd, 3J(H,H) ˆ 7.8 Hz, 4J(H,H) ˆ
1.2 Hz, 2H; CH), 6.8 (dd, 3J(H,H) ˆ 8.2 Hz, 4J(H,H) ˆ 1.2 Hz, 2H; CH);
4.5 (q, 3J(H,H) ˆ 7.0 Hz, 2H; CH), 3.78 (s, 6H; OCH3), 1.89 (s, 6H; SCH3),
1.35 (d, 3J(H,H) ˆ 7.0 Hz, 6H; CH3); 13C NMR (100 MHz, CDCl3, 258C,
TMS): d ˆ 160.1, 148.4, 130.1, 122.0, 118.8, 109.3, 56.1, 44.5, 21.1, 14.0; 77Se
NMR (76.27 MHz, CDCl3, 258C): d ˆ 365.7; GC-MS: m/z (%): 392 (7)
‡
55.9, 50.9, 44.4, 41.4, 23.5, 21.1, 14.0; GC-MS: m/z (%): 410 (13) [M ], 261
(39), 245 (11), 213 (31), 198 (14), 149 (20), 135 (100), 117 (13), 105 (8), 91
(12), 77 (6); elemental analysis calcd (%) for C20H26O2SSe (409.4): C 58.68,
H 6.40; found: C 58.02, H 6.54.
2-[(1R)-1-Methoxy-2-({2-methoxy-6-[(1S)-1-(methylthio)ethyl]phenyl}se-
leno)ethyl]-1,3,5-trimethylbenzene (8d): Oil; [a]2D0:9 ˆ À47.9 (c ˆ 1 in
CHCl3); 1H NMR (400 MHz, CDCl3, 258C, TMS): d ˆ 7.23 (dd,
3J(H,H) ˆ 7.8, 7.2 Hz, 1H; CH), 7.07 (dd, 3J(H,H) ˆ 7.8 Hz, 4J(H,H) ˆ
3
4
1.2 Hz, 1H; CH), 6.69 (s, 2H; CH), 6.68 (dd, J(H,H) ˆ 7.2 Hz, J(H,H) ˆ
3
3
1.2 Hz, 1H; CH), 4.91 (q, J(H,H) ˆ 7.0 Hz, 1H; CH), 4.58 (dd, J(H,H) ˆ
10.5, 3.9 Hz, 1H; CH), 4.8 (s, 3H; OCH3), 3.23 (dd, 2J(H,H) ˆ 12.4 Hz,
3J(H,H) ˆ 10.5 Hz, 1H; CH2), 3.09 (s, 3H; OCH3), 2.99 (dd, 2J(H,H) ˆ
12.4 Hz, 3J(H,H) ˆ 3.9 Hz, 1H; CH2), 2.16 (s, 9H; CH3), 1.87 (s, 3H; SCH3),
1.51 (d, 3J(H,H) ˆ 7.0 Hz, 3H; CH3); 13C NMR (100 MHz, CDCl3, 258C,
TMS): d ˆ 160.0, 149.2, 137.2, 137.1, 133.4, 129.8, 128.9, 119.7, 119.5, 109.4,
80.2, 56.8, 56.4, 45.1, 31.7, 21.9, 21.2, 20.6, 14.4; elemental analysis calcd (%)
for C22H30O2SSe (437.5): C 60.41, H 6.91; found: C 61.01, H 5.97.
‡
[M ], 377 (100), 261 (29), 213 (47), 198 (17), 149 (94), 134 (14), 91 (7), 77
(5); elemental analysis calcd (%) for C20H26O2S2Se2 (520.5): C 46.17, H 5.04;
found: C 45.84, H 5.32.
2-[1-Butyl-2-methoxyhexyl]seleno-1-methoxy-3-[(1S)-1-(methylthio)ethyl]-
benzene (8e): Oil; [a]D29:2 ˆ À25.4 (c ˆ 0.5 in CHCl3); 1H NMR (400 MHz,
CDCl3, 258C, TMS): d ˆ 7.3 (dd, 3J(H,H) ˆ 8.0, 7.8 Hz, 1H; CH), 7.2 (dd,
3J(H,H) ˆ 8 Hz, 4J(H,H) ˆ 1.2 Hz, 1H; CH), 6.76 (dd, 3J(H,H) ˆ 7.8 Hz,
4J(H,H) ˆ 1.2 Hz, 1H; CH), 5.03 (q, 3J(H,H) ˆ 7.0 Hz, 1H; CH), 3.9 (s, 3H;
OCH3), 3.65 (dt, 3J(H,H) ˆ 7.04, 4.3 Hz, 1H; CH), 3.51 (s, 3H; OCH3), 3.5
(q, 3J(H,H) ˆ 7.04 Hz, 1H; CH), 1.95 (s, 3H; SCH3), 1.56 (d, 3J(H,H) ˆ
7.0 Hz, 3H; CH3), 1.4 1.2 (m, 12H; CH2), 1 0.8 (m, 6H; CH3); 13C NMR
(100 MHz, CDCl3, 258C, TMS): d ˆ 160.0, 149.0, 130.7, 129.5, 120.1, 109.2,
84.5, 58.0, 56.3, 48.9, 44.8, 31.5, 31.0, 30.9, 28.4, 23.1, 23.0, 22.4, 14.6, 14.5,
14.4; elemental analysis calcd (%) for C21H36O2SSe (431.5): C 58.46, H 8.40;
found: C 58.55, H 8.90.
Selenomethoxylation of alkenes, general procedure: Ammonium persul-
fate (0.5 mmol) and trifluoromethanesulfonic acid (1 mmol) were added to
a solution of the diselenide 3 (0.5 mmol) in CH2Cl2 and the resulting red
solution was stirred at room temperature for 15 min.The solution was
cooled to À308C and a solution of the alkene 7 (1.5 mmol) in methanol was
added.The mixture was stirred for 24 h at the same temperature.The
progress of the reaction was monitored by GC-MS and/or TLC.The
reaction mixture was then poured into a 10% solution of NaHCO3 and
extracted with diethyl ether.The combined organic layers were washed
with brine, dried over sodium sulfate, filtered, and evaporated.The
reaction products were separated by column chromatography on silica gel
with a mixture of diethyl ether and light petroleum (1.5:8.5) as eluant. The
reaction yields and the diastereomeric ratios of the selenomethoxylation
1-Methoxy-2-[2-methoxycyclohexyl]seleno-3-[(1S)-1-(methylthio)ethyl]-
benzene (8 f): Oil; [a]D27:3 ˆ ‡1.1 (c ˆ 1 in CHCl3); 1H NMR (400 MHz,
1122
¹ WILEY-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002
0947-6539/02/0805-1122 $ 17.50+.50/0
Chem. Eur. J. 2002, 8, No. 5

Sulfur-Containing Diselenides in Asymmetric Synthesis
1118 1124
CDCl3, 258C, TMS): d ˆ 7.32 (dd, 3J(H,H) ˆ 7.8, 7.9 Hz, 1H; CH), 7.25 (dd,
3J(H,H) ˆ 7.8 Hz, 4J(H,H) ˆ 1.3 Hz, 1H; CH), 6.77 (dd, 3J(H,H) ˆ 7.9 Hz,
4J(H,H) ˆ 1.3 Hz, 1H; CH), 5.03 (q, 3J(H,H) ˆ 7.0 Hz, 1H; CH), 3.9 (s, 3H;
OCH3), 3.5 (m, 1H; CH), 3.37 (s, 3H; OCH3), 3.3 (m, 1H; CH), 1.96 (s, 3H;
SCH3), 1.8 1.6 (m, 8H; CH2), 1.5 (d, 3J(H,H) ˆ 7.0 Hz, 3H; CH3); 13C NMR
(100 MHz, CDCl3, 258C, TMS): d ˆ 160.3, 149.5, 129.8, 129.0, 119.9, 109.2,
83.4, 56.4, 46.6, 45.0, 31.6, 30.4, 30.1, 26.0, 23.7, 23.0, 14.9; GC-MS: m/z (%):
374 (27) [M ], 261 (100), 213 (86), 198 (21), 181 (6), 134 (8), 113 (7), 81 (24),
77 (3), 71 (5), 55 (3); elemental analysis calcd (%) for C17H26O2SSe (373.4):
C 54.69, H 7.02; found: C 55.01, H 7.20.
2J(H,H) ˆ 12.3 Hz, 1H; CH2), 1.99 (s, 3H; SCH3), 1.5 (d, 3J(H,H) ˆ 7.0 Hz,
3H; CH3), 1.6 (s, 3H; CH3); 13C NMR (100 MHz, CDCl3, 258C, TMS): d ˆ
159.5, 148.9, 147.3, 137.0, 130.3, 128.6, 127.2, 125.2, 120.1, 109.8, 73.8, 56.6,
‡
45.1, 30.7, 30.3, 22.2, 14.6; GC-MS: m/z (%): 396 (25) [M ], 261 (100), 245
(11), 213 (91), 198 (32), 134 (15), 121 (9), 105 (12), 91 (16), 77 (9), 61 (7);
elemental analysis calcd (%) for C19H24O2SSe (395.4): C 57.72, H 6.12;
found: C 57.14, H 6.23.
‡
(1R)-1-Mesityl-2-(2-methoxy-6-[(1S)-1-(methylthio)ethyl]phenylseleno)-
ethanol (9d): Oil; [a]2D3:2 ˆ À22.5 (c ˆ 1.7 in CHCl3); FT-IR (neat):
3478 cmÀ1 (broad band); 1H NMR (400 MHz, CDCl3, 258C, TMS): d ˆ
7.4 (dd, 3J(H,H) ˆ 7.8, 8.2 Hz, 1H; CH), 7.2 (dd, 3J(H,H) ˆ 7.8 Hz,
4J(H,H) ˆ 1.2 Hz, 1H; CH), 6.83 (dd, 3J(H,H) ˆ 8.2 Hz, 4J(H,H) ˆ 1.2 Hz,
1-Methoxy-2-[(2-methoxy-2-phenylcyclohexyl)seleno]-3-[(1S)-1-(methyl-
thio)ethyl]benzene (8g): Oil; [a]2D4:4 ˆ À88.8 (c ˆ 0.47 in CHCl3); 1H NMR
3
(400 MHz, CDCl3, 258C, TMS):
d
7.3 7.1 (m, 6H; CH), 6.81 (dd,
1H; CH), 6.76 (s, 2H; CH), 4.94 (q, J(H,H) ˆ 7.0 Hz, 1H; CH), 4.89 (dd,
3J(H,H) ˆ 7.8 Hz, 4J(H,H) ˆ 1.2 Hz, 1H; CH), 6.5 (dd, 3J(H,H) ˆ 8.2 Hz,
4J(H,H) ˆ 1.2 Hz, 1H; CH), 3.92 (q, 3J(H,H) ˆ 6.9 Hz, 1H; CH), 3.75 (s,
3H; OCH3), 3.74 (m, 1H; CH), 2.78 (s, 3H; OCH3), 2.4 2.2 (m, 6H; CH2),
1.73 (s, 3H; SCH3), 1.8 1.7 (m, 2H; CH2), 1.2 (d, 3J(H,H) ˆ 6.9 Hz, 3H;
CH3); 13C NMR (100 MHz, CDCl3, 258C, TMS): d ˆ 160.6, 148.0, 144.2,
128.9, 128.0, 127.7, 127.1, 121.2, 119.0, 109.3, 80.0, 56.2, 53.5, 50.5, 44.1, 28.6,
26.0, 22.1, 21.9, 21.4, 13.8; elemental analysis calcd (%) for C23H30O2SSe
(449.5): C 61.46, H 6.73; found: C 61.15, H 6.54.
3J(H,H) ˆ 8.75, 5.8 Hz, 1H; CH), 3.9 (s, 3H; OCH3), 3.4 (s, 1H; OH), 3.35
(m, 2H; CH2), 1.9 (s, 3H; SCH3), 1.6 (d, 3J(H,H) ˆ 7.0 Hz, 3H; CH3);
13C NMR (100 MHz, CDCl3, 258C, TMS): d ˆ 160.3, 150.0, 137.1, 136.5,
134.8, 130.5, 130.4, 120.2, 118.0, 109.6, 70.0, 56.6, 45.2, 35.5, 22.1, 21.1, 20.8,
14.6; elemental analysis calcd (%) for C21H28O2SSe (423.5): C 59.57, H 6.67;
found: C 60.20, H 6.68.
6-({2-Methoxy-6-[(1S)-1-(methylthio)ethyl]phenyl}seleno)decan-5-ol
(9e): Oil; [a]2D9:7 ˆ À13.8 (c ˆ 0.5 in CHCl3); FT-IR (neat): 3484 cmÀ1
(broad band); 1H NMR (400 MHz, CDCl3, 258C, TMS): d ˆ 7.4 (dd
3J(H,H) ˆ 8.1, 7.8 Hz, 1H; CH), 7.24 (dd, 3J(H,H) ˆ 7.8 Hz, 4J(H,H) ˆ
Selenohydroxylation of alkenes, general procedure: Ammonium persulfate
(0.5 mmol) and trifluoromethanesulfonic acid (1 mmol) were added to a
solution of the diselenide 3 (0.5 mmol) in CH3CN and the resulting red
solution was stirred at room temperature for 15 min.The solution was then
cooled to À308C and a solution of the alkene 7 (1 mmol) in CH3CN/H2O
(2:1) was added.The mixture was stirred for 24 h at the same temperature.
The progress of the reaction was monitored by GC-MS and/or TLC.The
reaction mixture was then poured into a 10% solution of NaHCO3 and
extracted with diethyl ether.The combined organic layers were washed
with brine, dried over sodium sulfate, filtered, and evaporated.The
reaction products were separated by column chromatography on silica gel
with a mixture of diethyl ether and light petroleum (3:7) as eluant.The
reaction yields and the diastereomeric ratios of the selenohydroxylation
products thus obtained are reported in Table 1.Physical and spectral data
are reported below.
3
4
1.1 Hz, 1H; CH), 6.8 (dd, J(H,H) ˆ 8.1 Hz, J(H,H) ˆ 1.1, 1H; CH), 4.95
(q, 3J(H,H) ˆ 7.0 Hz, 1H; CH), 3.9 (s, 3H; OCH3), 3.48 (ddd, 3J(H,H) ˆ 9.4,
4.3, 2.8 Hz, 1H; CH), 3.43 (s, 1H; OH), 3.38 (ddd, 3J(H,H) ˆ 8.7, 3.8,
2.8 Hz, 1H; CH), 2.0 (s, 3H; SCH3), 1.8 1.5 (m, 6H; CH2), 1.57 (d,
3J(H,H) ˆ 7.0 Hz, 3 H ; CH 3), 1.4 1.2 (m, 6H; CH2), 0.94 (t, 3J(H,H) ˆ
7.2 Hz, 3H; CH3), 0.86 (t, 3J(H,H) ˆ 7.2 Hz, 3H; CH3); 13C NMR
(100 MHz, CDCl3, 258C, TMS): d ˆ 160.3, 149.8, 130.5, 130.2, 120.2,
109.7, 72.7, 56.6, 54.7, 45.5, 33.2, 31.2, 30.1, 29.4, 29.0, 23.1, 23.0, 22.6, 15.0,
‡
14.3; GC-MS: m/z (%): 418 (4) [M ], 261 (100), 213 (65), 198 (16), 181 (4),
134 (10), 91 (5), 77 (2), 69 (8), 55 (8); elemental analysis calcd (%) for
C20H34O2SSe (417.5): C 57.54, H 8.21; found: C 57.69, H 7.88.
Product 9 f was isolated as mixture of diasteroisomers (2.5:1), which were
characterized on the basis of proton spectra.Major isomer: 1H NMR
(400 MHz, CDCl3, 258C, TMS): d ˆ 7.38 (dd, 3J(H,H) ˆ 8.0, 7.8 Hz, 1H;
CH), 7.25 (dd, 3J(H,H) ˆ 7.8 Hz, 4J(H,H) ˆ 1.2 Hz, 1H; CH), 6.84 (dd,
3J(H,H) ˆ 8.0 Hz, 4J(H,H) ˆ 1.2, 1H; CH), 5.0 (q, 3J(H,H) ˆ 7.0 Hz, 1H;
(1R)-2-({2-Methoxy-6-[(1S)-1-(methylthio)ethyl]phenyl}seleno)-1-phenyl-
ethanol (9a): Oil; [a]2D3:4 ˆ À38.8 (c ˆ 1.03 in CHCl3); FT-IR (neat):
3381 cmÀ1 (broad band); 1H NMR (400 MHz, CDCl3, 258C, TMS): d ˆ
7.4 7.1 (m, 7H; CH), 6.8 (dd, 3J(H,H) ˆ 8.1 Hz, 4J(H,H) ˆ 1.2 Hz, 1H;
CH), 4.86 (q, 3J(H,H) ˆ 7.0 Hz, 1H; CH), 4.55 (dd, 3J(H,H) ˆ 9.9 Hz,
3.0 Hz, 1H; CH), 3.89 (s, 3H; OCH3), 3.75 (s, 1H; OH); 3.28 (dd,
2J(H,H) ˆ 12.5 Hz, 3J(H,H) ˆ 3.0 Hz, 1H; CH2), 2.88 (dd, 2J(H,H) ˆ
12.5 Hz, 3J(H,H) ˆ 9.9 Hz, 1H; CH2), 1.95 (s, 3H; SCH3), 1.55 (d,
3J(H,H) ˆ 7.0 Hz, 3 H ; CH 3); 13C NMR (100 MHz, CDCl3, 258C, TMS):
d ˆ 160.1, 149.3, 148.8, 143.1, 130.5, 128.8, 128.0, 126.1, 120.3, 109.8, 72.7,
3
CH), 3.94 (s, 3H; OCH3), 3.38 (td, J(H,H) ˆ 10.0, 4.3 Hz, 1H; CH), 2.85
(m, 1H; CH); 2.1 (s, 1H; OH), 2.0 (s, 3H; SCH3), 1.8 1.5 (m, 6H; CH2),
1.58 (d, 3J(H,H) ˆ 7.0 Hz, 3H; CH3), 1.4 1.2 (m, 2H; CH2); minor isomer:
1H NMR (400 MHz, CDCl3, 258C, TMS): d ˆ 7.36 (dd, 3J(H,H) ˆ 8.0,
7.8 Hz, 1H; CH), 7.24 (dd, 3J(H,H) ˆ 7.8 Hz, 4J(H,H) ˆ 1.2 Hz, 1H; CH),
6.83 (dd, 3J(H,H) ˆ 8.0 Hz, 4J(H,H) ˆ 1.2, 1H; CH), 4.9 (q, 3J(H,H) ˆ
7.0 Hz, 1H; CH), 3.95 (s, 3H; OCH3), 3.45 (td, 3J(H,H) ˆ 10.1, 4.5 Hz,
1H; CH), 2.84 (m, 1H; CH); 2.3 (s, 1H; OH), 2.1 (s, 3H; SCH3), 1.8 1.5
(m, 6H; CH2), 1.57 (d, 3J(H,H) ˆ 7.0 Hz, 3H; CH3), 1.4 1.2 (m, 2H; CH2).
‡
56.6, 45.2, 39.6, 22.1, 14.7; GC-MS: m/z (%): 382 (14) [M ], 261 (88), 259
(45), 245 (7), 213 (100), 211 (52), 198 (36), 181 (8), 134 (14), 103 (14), 91
(19), 77 (16), 61 (8); elemental analysis calcd (%) for C18H22O2SSe (381.4):
C 56.70, H 5.81; found: C 56.43, H 5.95.
Cyclofunctionalization reactions, general procedure: A mixture of disele-
nide (0.5 mmol), ammonium persulfate (0.5 mmol), and trifluoromethane-
sulfonic acid (1 mmol) in CH2Cl2 was stirred at room temperature for
15 min.The reaction mixture was cooled to À308C and the alkenes 14, 16,
18, and 20 (1 mmol) were added.The progress of the reaction was
monitored by GC-MS and/or TLC.After 24 h the reaction mixture was
worked up in the usual way.The cyclization products were isolated in pure
form by column chromatography on silica gel with a mixture of diethyl
ether and light petroleum (2.5:7.5) as eluant. The reaction yields and the
diasteroisomeric ratios are reported in Table 2.Physical and spectral data
are reported below.
(1R,2S)-2-({2-Methoxy-6-[(1S)-1-(methylthio)ethyl]phenyl}seleno)-1-
phenylpropan-1-ol (9b): Oil; [a]2D2:8 ˆ À10.4 (c ˆ 0.53 in CHCl3); FT-IR
(neat): 3437 cmÀ1 (broad band); 1H NMR (400 MHz, CDCl3, 258C, TMS):
d ˆ 7.3 7.2 (m, 7H; CH), 6.8 (dd, 3J(H,H) ˆ 8.1 Hz, 4J(H,H) ˆ 1.2 Hz, 1H;
CH), 4.9 (q, 3J(H,H) ˆ 6.9 Hz, 1H; CH), 4.47 (d, 3J(H,H) ˆ 2.6 Hz, 1H;
3
CH), 3.91 (s, 3H; OCH3), 3.8 (dq, J(H,H) ˆ 2.6, 7.1 Hz, 1H, CH), 3.35 (s,
1H; OH), 2.0 (s, 3H; SCH3), 1.5 (d, 3J(H,H) ˆ 6.9 Hz, 3H, CH3), 1.1 (d,
3J(H,H) ˆ 7.1 Hz, 3 H ; CH 3); 13C NMR (100 MHz, CDCl3, 258C, TMS):
d ˆ 160.0, 149.5, 139.3, 135.9, 130.3, 128.0, 127.0, 125.9, 120.0, 109.3, 96.1,
‡
73.6, 56.3, 47.2, 30.3, 22.0, 13.0; GC-MS: m/z (%): 396 (1) [M ], 281 (16),
4-({2-Methoxy-6-[(1S)-1-(methylthio)ethyl]phenyl}seleno)-2,2-dimethyl-
5-phenyltetrahydrofuran (15): Oil; [a]2D6:6 ˆ À3.2 (c ˆ 1.5 in CHCl3);
1H NMR (400 MHz, CDCl3, 258C, TMS): d ˆ 7.3 7.2 (m, 6H; CH), 7.06
(dd, 3J(H,H) ˆ 7.8 Hz, 4J(H,H) ˆ 1.2 Hz, 1H; CH), 6.5 (dd, 3J(H,H) ˆ
8.2 Hz, 4J(H,H) ˆ 1.1, 1H; CH), 4.8 (d, 3J(H,H) ˆ 9.3 Hz, 1H; CH), 4.79
(q, 3J(H,H) ˆ 7.0 Hz, 1H; CH), 3.8 (dt, 3J(H,H) ˆ 8.4, 9.3 Hz, 1H; CH), 3.7
(s, 3H; OCH3), 2.37 (dd, 2J(H,H) ˆ 12.8 Hz, 3J(H,H) ˆ 8.4, 1H; CH2), 2.06
(dd, 2J(H,H) ˆ 12.8 Hz, 3J(H,H) ˆ 9.3, 1H; CH2), 1.9 (s, 3H; SCH3), 1.5 (d,
3J(H,H) ˆ 7.0 Hz, 3 H ; CH 3), 1.44 (s, 3H; CH3), 1.41 (s, 3H; CH3); 13C NMR
(100 MHz, CDCl3, 258C, TMS): d ˆ 159.7, 148.4, 140.9, 130.1, 128.5, 128.3,
128.0, 127.1, 119.5, 109.3, 87.6, 80.9, 56.0, 47.6, 46.4, 44.7, 29.8, 29.1, 21.8, 14.3;
261 (100), 213 (85), 207 (48), 198 (24), 134 (21), 122 (11), 117 (16), 105 (31),
91 (29), 77 (32), 57 (19); elemental analysis calcd (%) for C19H24O2SSe
(395.4): C 57.72, H 6.12; found: C 57.44, H 6.34.
(2R)-2-({2-Methoxy-6-[(1S)-1-(methylthio)ethyl]phenyl}seleno)-2-phenyl-
propan-2-ol (9c): Oil; [a]D23:9 ˆ À6.7 (c ˆ 4.3 in CHCl3); FT-IR (neat):
3461 cmÀ1 (broad band); 1H NMR (400 MHz, CDCl3, 258C, TMS): d ˆ
7.5 7.45 (m, 2H; CH), 7.4 7.3 (m, 3H; CH), 7.26 (m, 1H; CH), 7.18 (dd,
3J(H,H) ˆ 7.84 Hz, 4J(H,H) ˆ 1.2 Hz, 1H; CH), 6.79 (dd, 3J(H,H) ˆ 8.2 Hz,
4J(H,H) ˆ 1.2 Hz, 1H; CH), 4.89 (q, 3J(H,H) ˆ 7.0 Hz, 1H; CH), 3.96 (s,
1H, OH), 3.95 (s, 3H; OCH3), 3.5 (d, 2J(H,H) ˆ 12.3 Hz, 1H; CH2), 3.15 (d,
Chem. Eur. J. 2002, 8, No. 5
¹ WILEY-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002
0947-6539/02/0805-1123 $ 17.50+.50/0
1123

M.Tiecco et al.
FULL PAPER
elemental analysis calcd (%) for C22H28O2SSe (435.5): C 60.69, H 6.48;
found: C 61.20, H 6.32.
Acknowledgement
4-({2-Methoxy-6-[(1S)-1-(methylthio)ethyl]phenyl}seleno)-5-phenyldihy-
drofuran-2(3H)-one (17): Oil; [a]2D0:2 ˆ ‡1.5 (c ˆ 0.53 in CHCl3); FT-IR
Financial support from MURST, National Project ™Stereoselezione in
Sintesi Organica.Metodologie ed Applicazioni∫, the University of Perugia,
Progetti di Ateneo, and CNR, Rome is gratefully acknowledged.
(neat): 1782 cmÀ1
;
1H NMR (400 MHz, CDCl3, 258C, TMS): d ˆ 7.5 7.3
(m, 7H; CH), 6.8 (m, 1H; CH), 5.34 (d, 3J(H,H) ˆ 5.8 Hz, 1H; CH), 4.7 (q,
3J(H,H) ˆ 7.0 Hz, 1H; CH), 4.05 (ddd, 3J(H,H) ˆ 5.8, 7.1, 8.4 Hz, 1H; CH),
3.79 (s, 3H; OCH3), 3.01 (dd, 3J(H,H) ˆ 8.4 Hz, 2J(H,H) ˆ 18.2 Hz, 1H;
CH2), 2.68 (dd, 3J(H,H) ˆ 7.1 Hz, 2J(H,H) ˆ 18.2 Hz, 1H; CH2), 1.97 (s, 3H;
[1] a) T.Wirth, Tetrahedron, 1999, 55, 1 28; b) M.Tiecco, Top. Curr.
Chem. 2000, 208, 7 54.
[2] T.Wirth, Angew. Chem. 2000, 112, 3890 3900; Angew. Chem. Int. Ed.
2000, 39, 3742 3751.
3
SCH3), 1.55 (d, J(H,H) ˆ 7.0 Hz, 3H; CH3); 13C NMR (100 MHz, CDCl3,
258C, TMS): d ˆ 175.6, 160.0, 149.1, 139.0, 130.8, 129.0, 128.7, 126.5, 125.9,
120.0, 109.8, 87.2, 56.3, 41.1, 36.1, 30.7, 21.4, 14.2; elemental analysis calcd
(%) for C20H22O3SSe (421.4): C 57.01, H 5.26; found: C 55.98, H 5.30.
[3] a) K.Fujita, K.Murata, M.Iwaoka, S.Tomoda, Tetrahedron 1997, 53,
2029 2048; b) K.Fujita, K.Murata, M.Iwaoka, S.Tomoda,
Tetrahedron Lett. 1995, 36, 5219 5222; c) K.Fujita, K.Murata, M.
Iwaoka, S.Tomoda, J. Chem. Soc. Chem. Commun. 1995, 1641 1642.
[4] a) T.Wirth, Liebigs Ann. 1997, 2189 2196, and references therein;
b) T.Wirth, G.Fragale, Chem. Eur. J. 1997, 3, 1894 1902; c) T.Wirth,
S.H‰uptli, M.Leuenberger, Tetrahedron Asymmetry 1998, 9, 547
550; d) T.Wirth, G.Fragale, M.Spichty, J. Am. Chem. Soc. 1998, 120,
3376 3381; e) C.Santi, G.Fragale, T.Wirth, Tetrahedron Asymmetry
1998, 9, 3625 3628
(4S,5R)-5-Ethyl-4-({2-methoxy-6-[(1S)-1-(methylthio)ethyl]phenyl}sele-
no)dihydrofuran-2(3H)-one (19): Oil; [a]2D1:6 ˆ À3.2 (c ˆ 0.75 in CHCl3);
1H NMR (400 MHz, CDCl3, 258C, TMS): d ˆ 7.3 (dd, 3J(H,H) ˆ 7.9, 8.0 Hz,
3
4
1H; CH), 7.1 (dd, J(H,H) ˆ 7.8 Hz, J(H,H) ˆ 1.1 Hz, 1H; CH), 6.74 (dd,
3J(H,H) ˆ 8.0 Hz, 4J(H,H) ˆ 1.1, 1H; CH), 4.67 (q, 3J(H,H) ˆ 7.0 Hz, 1H;
3
CH), 4.25 (ddd, J(H,H) ˆ 4.8, 6.2, 7.5 Hz, 1H; CH), 3.82 (s, 3H; OCH3),
3
3.67 (ddd, 3J(H,H) ˆ 6.2, 7.6, 8.6 Hz, 1H; CH), 2.85 (dd, J(H,H) ˆ 8.6 Hz,
2J(H,H) ˆ 18.2 Hz, 1H; CH2), 2.52 (dd, 3J(H,H) ˆ 7.6 Hz, 2J(H,H) ˆ
18.2 Hz, 1H; CH2), 1.98 (s, 3H; SCH3), 1.65 1.55 (m, 2H; CH2), 0.86 (t,
3J(H,H) ˆ 7.4 Hz, 3 H ; CH 3); 13C NMR (100 MHz, CDCl3, 258C, TMS):
d ˆ 194.0, 175.0, 160.0, 149.3, 131.0, 120.1, 109.8, 88.2, 56.4, 44.7, 38.0, 36.7,
[5] a) S.Fukuzawa, K.Takahashi, H.Kato, H.Yamazaki,
J. Org. Chem.
1997, 62, 7711 7716; b) Y.Nishibayashi, S.K.Srivastava, H.Takada,
S.Fukuzawa, S.Uemura, J. Chem. Soc. Chem. Commun. 1995, 2321
‡
27.6, 21.8, 14.4, 9.9; GC-MS: m/z (%): 374 (1) [M ], 261 (96), 230 (6), 213
2322; c) S.Fukuzawa, Y.Kasugahara, S.Uemura,
1994, 35, 9403 9406.
Tetrahedron Lett.
(100), 197 (34), 181 (7), 134 (13), 91 (12), 77 (5), 57 (7); elemental analysis
calcd (%) for C16H22O3SSe (373.4): C 51.48, H 5.94; found: C 52.20, H 5.55.
¡
[6] R.Deziel, E.Malenfant, C.Thilbault, S.Fre
chette, M.Gravel,
4-({2-Methoxy-6-[(1S)-1-(methylthio)ethyl]phenyl}seleno)-3-phenylisoxa-
zolidine (21): Oil; [a]D24:0 ˆ À20.9 (c ˆ 3.17 in CHCl3); 1H NMR (400 MHz,
C6D6, 678C, TMS): d ˆ 7.75 7.68 (m, 1H; CH), 7.4 (d, 3J(H,H) ˆ 7.3 Hz,
Tetrahedron Lett. 1997, 38, 4753 4756, and references therein.
[7] L.Uehlin, T.Wirth, Org. Lett. 2001, 3, 2931 2933, and references
therein.
[8] a) M.Iwaoka, S.Tomoda, J. Am. Chem. Soc. 1996, 118, 8077 8081;
b) H.Kamatsu, M.Iwaoka, S.Tomoda, J. Chem. Soc. Chem. Commun.
1999, 205 207.
[9] M.Tiecco, L.Testaferri, L.Bagnoli, F.Marini, A.Temperini, C.
Tomassini, C.Santi, Tetrahedron Lett. 2000, 41, 3241 3245, and
references therein.
[10] G.Fragale, M.Neuburger, T.Wirth, J. Chem. Soc. Chem. Commun.
1998, 1867 1872.
3
1H; CH), 7.3 7.1 (m, 5H; CH), 6.45 (d, J(H,H) ˆ 7.7 Hz, 1H; CH), 5.02
(q, 3J(H,H) ˆ 7.0 Hz, 1H; CH), 4.4 (d, 3J(H,H) ˆ 4.6 Hz, 1H; CH), 4.25
(ddd, 3J(H,H) ˆ 11.8, 8.0, 4.6 Hz, 1H; CH), 4.17 (dd, 3J(H,H) ˆ 11.8, 5.2 Hz,
1H; CH2), 3.95 (dd, 3J(H,H) ˆ 8.0, 5.2 Hz, 1H; CH2), 3.31 (s, 3H; OCH3),
1.9 (s, 3H; SCH3), 1.55 (d, 3J(H,H) ˆ 7.0 Hz, 3H; CH3); 13C NMR
(100 MHz, C6D6, 678C, TMS): d ˆ 159.6, 148.8, 137.4, 136.2, 128.2, 127.7,
127.3, 126.7, 119.6, 109.3, 70.6, 67.7, 55.1, 44.7, 30.5, 21.4, 14.0; elemental
analysis calcd (%) for C19H23NO2SSe (408.4): C 55.88, H 5.68; found: C
55.74, H 5.63.
[11] H.C.Brown, J.Chandrasekharan, P.V.Ramachandran, J. Am. Chem.
Soc. 1988, 110, 1539 1546.
Catalytic selenenylation deselenenylation sequences, general procedure:
Ammonium persulfate (3 mmol) was added to a solution of diselenide 3
(0.025 mmol) in MeOH (selenomethoxylation) or CH3CN (selenohydrox-
ylation and cyclofunctinalization), and the resulting mixture was stirred at
608C for 15 min.The temperature was cooled to 25 8C and the alkene
(1 mmol) in MeOH (selenomethoxylation), or in CH3CN/H2O (selenohy-
droxylation), or in CH3CN (cyclofunctionalization) was added.The
progress of the reaction was monitored by GC-MS and/or TLC and the
reaction mixture was worked up in the usual way.The selenenylation
deselenenylation products were isolated in pure form by column chroma-
tography on silica gel with CH2Cl2 as eluant.The reaction yields, the
reaction times, and the diastereomeric ratios are reported in Table 3.
Physical and spectral data for 29[15] and for the enantiomers of compounds
25,[18a] 27,[18a] and 28[18a] have previously been described.Optical rotation
data of compounds 25, 27, and 28 are reported below.
[12] a) M.Tiecco, L.Testaferri, M.Tingoli, D.Bartoli,
Tetrahedron Lett.
1989, 30, 1417 1421; b) M.Tiecco, L.Testaferri, M.Tingoli, L.
Bagnoli, F.Marini, J. Chem. Soc. Perkin Trans. 1 1993, 1989 1991.
[13] M.Tiecco, L.Testaferri, M.Tingoli, L.Bagnoli,
J. Chem. Soc. Chem.
Commun. 1995, 235 236.
[14] M.Tiecco, L.Testaferri, F.Marini, S.Sternativo, L.Bagnoli, C.Santi,
A.Temperini, Tetrahedron Asymmetry 2001, 12, 1493 1502.
[15] J.Cardellach, J.Font, M.Ortuno, J. Heterocycl. Chem. 1984, 21, 327
331.
[16] a) M.Tiecco, L.Testaferri, M.Tingoli, L.Bagnoli, C.Santi,
J. Chem.
Soc. Chem. Commun. 1993, 637 638; b) Y.Nishibayashi, S.Uemura,
Top. Curr. Chem. 2000, 208, 235 255.
[17] a) K.Fujita, M.Iwaoka, S.Tomoda, Chem. Lett. 1994, 923 926; b) M.
Tiecco, L.Testaferri, C.Santi, F.Marini, L.Bagnoli, A.Temperini,
Tetrahedron Lett. 1998, 39, 2809 2812.
[18] a) M.Tiecco, L.Testaferri, F.Marini, C.Santi, L.Bagnoli, A.
Temperini, Tetrahedron Asymmetry 1999, 10, 747 757; b) M.Tiecco,
L.Testaferri, C.Santi, C.Tomassini, F.Marini, L.Bagnoli, A.
Temperini, Tetrahedron Asymmetry 2000, 11, 5645 4650.
[19] U.H.Hirt, B.Spingler, T.Wirth, J. Org. Chem. 1998, 63, 7674 7679.
Methyl (2E,4R)-4-methoxyhex-2-enoate (25): [a]2D4:0 ˆ ‡4.1 (c ˆ 2.1 in
CHCl3).
Methyl (2E,4S)-4-methoxy-4-phenylbut-2-enoate (27): [a]3D2:0 ˆ À56.9 (c ˆ
3.0 in CHCl3).
Methyl (2E,4S)-4-hydroxy-4-phenylbut-2-enoate (28): [a]2D5:0 ˆ À29.9 (c ˆ
1.0 in CHCl3).
Received: September 17, 2001 [F3557]
1124
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