Ring-Closure Reactions through Intramolecular Displacement of the Phenylselenonyl Group by Nitrogen Nucleophiles: A New Stereospecific Synthesis of N-Tosyl and N-Benzoyl-1,3-oxazolidin-2-ones from β-Hydroxyalkyl Phenyl Selenides

Article abstract of DOI:10.1002/chem.200305497

A new and convenient method for the stereospecific synthesis of variously substituted 1,3-oxazolidin-2-ones from the easily available β-hydroxyalkyl phenyl selenides is presented. After transformation into the N-tosyl or N-benzoyl carbamates, the selenide

Full text of DOI:10.1002/chem.200305497

FULL PAPER
Ring-Closure Reactions through Intramolecular Displacement of the
Phenylselenonyl Group by Nitrogen Nucleophiles: A New Stereospecific
Synthesis of N-Tosyl and N-Benzoyl-1,3-oxazolidin-2-ones from b-
Hydroxyalkyl Phenyl Selenides
Marcello Tiecco,* Lorenzo Testaferri, Andrea Temperini, Luana Bagnoli,
[a]
Francesca Marini, andClaudio Santi
Abstract: A new and convenient method for the stereospecific synthesis of vari-
ously substituted 1,3-oxazolidin-2-ones from the easily available b-hydroxyalkyl
phenyl selenides is presented. After transformation into the N-tosyl or N-benzoyl
carbamates, the selenides were oxidized to the corresponding selenones. The key
step of the process is the ring-closure reaction, which occurs by stereospecific in-
tramolecular nucleophilic substitution of the selenone group by the nitrogen atom
of the carbamate. Enantiomerically pure 1,3-oxazolidin-2-one derivatives can be
easily prepared by using enantiomerically pure b-hydroxyalkyl phenyl selenides as
starting materials.
Keywords: carbamates ¥ cyclization ¥
heterocycles stereoselectivity
substitution reactions
¥
¥
Introduction
actions. In, turn, these have been used to effect the stereose-
lective synthesis of several natural and pharmaceutical prod-
ucts.[16]
1,3-Oxazolidin-2-ones are important heterocyclic com-
pounds[1] that display good antibacterial properties[2] and are
used prolifically in pharmaceutical chemistry.[3] The synthe-
sis of these cyclic carbamates is generally performed by con-
densation of 1,2-amino alcohols[4] with carbonyl derivatives
such as phosgene,[5] triphosgene,[6] isocyanates,[4] chlorofor-
mates,[7] ureas,[8] or diethyl carbonate.[9] The catalyzed addi-
tion of CO2,[10] and the palladium-catalyzed oxidative car-
bonylation[11] of b-amino alcohols have also been employed.
Other methods include the reaction of epoxides with isocya-
nates,[12] and the reaction of alkenes with N-bromosuccini-
mide and isocyanates.[13] An alternative strategy for the
preparation of 1,3-oxazolidin-2-ones involves the cyclization
of aryl and benzoylcarbamate derivatives of epoxy alcohols
or bromohydrins.[14] Chiral, non-racemic 1,3-oxazolidin-2-
ones, known as Evans× chiral auxiliaries,[15] have been suc-
cessfully employed in a wide range of asymmetric reactions
such as aldol condensations, alkylations, and Diels Alder re-
Herein we report a new and convenient stereospecific
synthesis (Scheme 1) of substituted N-tosyl or N-benzoyl-
1,3-oxazolidin-2-ones 4 starting from b-hydroxyalkyl phenyl
selenides 1. We also describe the further transformation of 4
into the N-substituted 1,2-amino alcohols 5.
Results andDiscussion
The reaction sequence employed in the present work is
schematically illustrated in Scheme 1. The b-hydroxyalkyl
phenyl selenides 1 used as starting materials are easily avail-
able intermediates that have been used for several interest-
ing synthetic applications.[17] By reaction with tosyl or ben-
zoyl isocyanate in CH2Cl2 or CCl4 at room temperature,
these compounds are rapidly converted into their N-tosyl or
N-benzoyl carbamate derivatives 2, respectively. Treatment
of these b-carbamoyloxyalkyl phenyl selenides with an
excess of m-chloroperoxybenzoic acid (m-CPBA) in THF or
CH2Cl2, in the presence of potassium hydrogenphosphate,[18]
afforded the corresponding selenones 3. The N-tosyl or N-
benzoyl-1,3-oxazolidin-2-ones 4 were then obtained as a
result of the displacement of the selenonyl group by the ni-
trogen atom of the carbamic group. This cyclization reac-
tion, which represents the crucial step of the entire process,
[a] Prof. M. Tiecco, Prof. L. Testaferri, Dr. A. Temperini, Dr. L. Bagnoli,
Dr. F. Marini, Dr. C. Santi
Dipartimento di Chimica e Tecnologia del Farmaco
Sezione di Chimica Organica, Universit‡ di Perugia
06123 Perugia (Italy)
Fax : (+39)07-5585-5116
E-mail: tiecco@unipg.it
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¹ 2004Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
DOI: 10.1002/chem.200305497
Chem. Eur. J. 2004, 10, 1752 1764

1752 1764
The yields obtained for the N-tosyl-1,3-oxazolidin-2-ones
9 and N-benzoyl-1,3-oxazolidin-2-ones 10 are reported in
Table 1. For the sake of simplicity, only the structures of the
starting hydroxyalkyl phenyl selenides 6 are indicated in the
Table. From the data reported in Table 1, it can be seen that
compounds 9 and 10 were obtained in good to excellent
yields. This indicates that the procedure has general applica-
tion and that a number of functional groups in the carba-
mate molecule are tolerated under the mild reaction condi-
tions employed.
Different procedures were required for cyclization of the
N-tosyl 12 or N-benzoyl carbamates 13, which were pre-
pared from the hydroxyalkyl phenyl selenides 11, as the
phenylseleno group is linked to a secondary carbon atom
(Scheme 3).
Scheme 1. Synthesis of 1,3-oxazolidin-2-ones
phenyl selenides 1. R=Ts or Bz.
4 from b-hydroxyalkyl
is a stereospecific intramolecular nucleophilic substitution,
and occurs easily because of the great leaving ability of the
selenonyl group. The leaving ability of the selenonyl group
has already been observed in intermolecular[19] and intramo-
lecular[20] substitution reactions that involve carbon or
oxygen nucleophiles. However, little is known about cycliza-
tion reactions promoted by nitrogen atoms[21] in which het-
erocycles that contain nitrogen are formed.
Scheme 3. Synthesis of N-tosyl and N-benzoyl 4,5-disubstituted 1,3-oxa-
zolidin-2-ones. R=Ts: 12 and 14; R=Bz: 13 and 15.
Preliminary experiments were carried out using hydrox-
yalkyl phenyl selenides 6, in which the selenium atom is at-
tached to a primary carbon atom (Scheme 2). As a result,
The b-(N-tosylcarbamoyloxy)alkyl phenyl selenides 12a
and 12b were oxidized to the corresponding selenones in
CH2Cl2 at 188C in the presence of K2HPO4 (Method B).
Unfortunately, subsequent cyclization of the selenones gave
rise to inseparable mixtures of 1,3-oxazolidin-2-ones 14a or
14b, and tosyl iminocarbonates 16a or 16b, respectively, the
latter being derived from competitive O-cyclization
(Scheme 4).
Scheme 2. Synthesis of N-tosyl and N-benzoyl 5-substituted 1,3-oxazoli-
din-2-ones. R=Ts: 7 and 9; R=Bz: 8 and 10.
slightly different conditions were required to effect the cycli-
zation reactions of the N-tosyl or the N-benzoyl carbamates.
Oxidation of the N-tosyl carbamates 7 to the correspond-
ing selenones was effected with m-CPBA in THF at 08C in
the presence of potassium hydrogenphosphate (Scheme 2,
Method A). These selenones then spontaneously underwent
cyclization. The N-benzoyl carbamates 8 were oxidized
under the same conditions employed for 7, but to undergo
clean cyclization it was necessary to use acetone rather than
THF as the solvent. Moreover, the reaction was conducted
at room temperature and in the presence of powdered po-
tassium carbonate. The selenones obtained from the N-tosyl
carbamates 7 could not be isolated, but their formation
could be inferred by thin-layer chromatography (TLC). On
the other hand, formation of the corresponding selenones
from the N-benzoyl carbamates 8 was clearly demonstrated
both by TLC and 13C NMR spectroscopy of the crude reac-
tion mixtures. In particular, a signal characteristic of a meth-
ylene linked to a selenonyl group[20c] was observed at dꢀ
66 ppm.
Scheme 4. Cyclization and subsequent hydrolysis of compound 12.
Hydrolysis of the reaction mixtures with cesium carbonate
in methanol afforded the N-tosyl-1,2-amino alcohols 17a
and 17b, and these could easily be separated from the corre-
sponding 1,2-diols 18a and 18b. Attempts to exclusively
obtain the oxazolidin-2-ones by changing solvents and/or the
base used, were unsuccessful. However, it should be noted
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M. Tiecco et al.
FULL PAPER
Table 1. Synthesis of 5-substituted-N-tosyl 9 and N-benzoyl-1,3-oxazolidin-2-ones 10 from hydroxyalkyl phenyl selenides 6.[a]
Hydroxyselenides 6
Oxazolidinones 9
Yield [%][b,c]
Oxazolidinones 10
Yield [%][b]
89
a
96
b
81
c
d
e
f
75
69
92
75
93
69
g
79
h
i
62
86
l
77
80
m
[a] Method A was employed. [b] Yields are based on the amount of the carbamate employed. [c] The N-tosyl-1,3-oxazolidin-2-ones were not purified by
chromatography.
that the selenone from carbamate 12c was easily trans-
formed into the corresponding N-tosyl-1,3-oxazolidin-2-one
14c under the conditions employed for compounds 8. The
results of these experiments are reported in Table 2.
Oxidation of the N-benzoyl carbamates 13 occurred
smoothly in CH2Cl2 at 188C in the presence of K2HPO4
(Method B). However, cyclization of the resultant selenones
to give the 4,5-disubstituted N-benzoyl oxazolidin-2-ones 15
occurred only after powdered potassium hydroxide (carba-
mates 13a, 13d, and 13 f) or potassium carbonate (carba-
mates 13b and 13e) were added to the reaction mixtures.
These bases are probably necessary to partially deprotonate
the carbamate nitrogen, and thus, afford a stronger nucleo-
philic reagent. To prevent b-elimination of the selenoxide
intermediate, cyclization of carbamate 13g was effected with
K2HPO4 in 2-propanol. The results of these experiments are
collected in Table 3. The data indicates that formation of the
4,5-disubstituted oxazolidin-2-ones by cyclization of the sele-
nones derived from the N-ben-
zoyl carbamates proceeds more
Table 2. Oxidation of N-tosyl carbamates 12 with m-CPBA in the presence of K2HPO4.[a]
N-Tosyl carbamates 12 Reaction products
cleanly than cyclization of the
selenones derived from the N-
tosyl carbamates. Moreover, re-
moval of the tosyl group is gen-
erally more difficult than re-
moval of the benzoyl group.[22]
The structures of the 1,3-oxa-
zolidin-2-ones obtained from
the experiments reported in
Table 3 clearly indicate that in-
tramolecular substitution of the
phenylselenonyl group by the
nitrogen atom is a stereospecif-
ic reaction that occurs with in-
Yield [%]
40
12a
17a[b]
12b
12c
17b[b]
14c
48
73[c]
[a] The oxidation cyclization reaction was effected with Method B. [b] After hydrolysis of the reaction mix-
tures with cesium carbonate in methanol. [c] Under the reaction conditions employed for compounds 8.
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Intramolecular Displacement of the Phenylselenonyl Group by Nitrogen Nucleophiles
1752 1764
Table 3. Synthesis of 4,5-disubstituted-N-benzoyl-1,3-oxazolidin-2-ones 15.[a]
20 by treatment with benzoyl
isocyanate (Table 4). The oxida-
tion cyclization procedure was
then effected as described
N-Benzoyl carbamates 13
Oxazolidinones 15
Yield [%]
73[b]
13a
13b
15a
15b
above for compounds
8 to
afford the optically active (eeꢁ
98%) 5-substituted N-benzoyl-
1,3-oxazolidin-2-ones 21. The
results of these experiments,
which are collected in Table 4,
confirm the great versatility of
the procedure described in this
paper. In particular, the mild
conditions employed are com-
patible with various kinds of
substituents. For example, the
b-hydroxyalkyl phenyl selenide
19a reacted with tosyl isocya-
nate to afford the correspond-
ing N-tosyl carbamate 22a,
which after oxidation and cycli-
zation according to Method A
formed the enantiomerically
pure N-tosyl-1,3-oxazolidin-2-
one 23a in good yield.
74[c]
13d
15d
69[b]
13e
13 f
13g
15e
15 f
15g
80[c]
44[b]
81[d]
The substituted 1,3-oxazoli-
din-2-ones prepared in this
paper can easily be converted
[a] The reaction was effected with Method B. [b] Powdered potassium hydroxide was added. [c] Powdered
potassium carbonate was added. [d] The reaction was carried out with potassium hydrogenphosphate in
2-propanol.
version of configuration at the
carbon atom a to the selenonyl
group (Scheme 3).[21b]
Table 4. Preparation of enantiomerically pure N-benzoyl-5-substituted-1,3-oxazolidin-2-ones 21 from enantio-
merically pure b-hydroxyalkyl phenyl selenides 19.[a]
b-Hydroxyalkyl phenyl selenides
N-Benzoyl carbamates Yield
Oxazolidinones 21 Yield
19
20
[%]
[%]
Interestingly, enantiomerical-
ly pure 1,3-oxazolidin-2-ones, as
well as the corresponding 1,2-
amino alcohols, are formed
when enantiomerically pure b-
hydroxyalkyl phenyl selenides,
are used. More importantly, the
b-hydroxyalkyl phenyl selenides
required can themselves be
easily obtained in several ways.
They can be prepared by the
ring opening of commercially
a
97
88
77
b
92
67
c
67
d
e
f
75[b]
82
available epoxides with sodium
[23]
98
89
phenyl selenolate.
Alterna-
tively, halohydrins or lactones
can be employed as starting
materials. Several examples of
these syntheses are described in
the experimental section.
Thus, the enantiomerically
pure b-hydroxyalkyl phenyl se-
lenides 19, in which the seleni-
um atom is attached to a pri-
mary carbon atom, and there-
fore, have structures similar to
6, were converted into the cor-
74
g
58[c]
79
h
56[b][d]
[a] The reaction was effected under the conditions employed for compounds 8. [b] The yield was calculated
from the starting hydroxyselenide. The corresponding carbamate was not isolated. [c] The yield was calculated
responding benzoyl carbamates from the starting epoxide. [d] Major diastereoisomer.
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M. Tiecco et al.
FULL PAPER
Jasco DIP-1000 digital polarimeter. Elemental analyses were carried out
on a Carlo Erba 1106 elemental analyzer. Commercial grade Et2O,
CH2Cl2, CCl4, and THF were used without purification. Column chroma-
tography was performed with Merck silica gel 60 (70 230 mesh).
into other useful compounds in both a regio- and stereospe-
cific manner. Among these, is an important class of deriva-
tives, namely the 1,2-amino alcohols.[24] As indicated in
Scheme 5, upon treatment with catalytic amounts of cesium
The starting b-hydroxyalkyl phenyl selenides 6a,[25] 6c,[26] 6d,[27] 6 f,[27]
6m,[28] 11a,[29] 11c,[27] 11d,[27] 11g,[27] and 19a[26] were prepared as descri-
bed in the literature. Compounds 11b and 11 f were obtained by regio-
and stereospecific hydroxyselenation of the corresponding allylic
ethers[30] using phenylselenyl chloride.[31] Compound 6l was prepared by
acidic hydrolysis of the corresponding oxazoline,[32] while 6g was ob-
tained by alkaline hydrolysis and subsequent esterification of the corre-
sponding lactone with diazomethane [32]. The b-hydroxyalkyl phenyl sele-
nides 6b, 6e, 6h, 6i, 11e, 19g, and 19h were prepared as reported in the
literature by regiospecific ring opening of the corresponding racemic or
chiral, non-racemic epoxides using sodium phenyl selenolate in etha-
nol.[33] Compound 19e was obtained by cleavage of the corresponding hy-
droxy g-lactone with sodium phenyl selenolate in DMF[34] upon heating
at reflux. Compounds 19d and 19 f were obtained by SN2 displacement of
the corresponding chlorohydrins with sodium phenyl selenolate in
HMPA.[35] Yields, as well as physical and spectral data are reported
below.
Most of the optically active epoxides, chlorohydrins, and the hydroxy g-
lactone were commercially available and had an enantiomeric excess (ee)
equal or greater than 98%.
The epoxides required for the preparation of compounds 19g[36a] and
19h[36b] were obtained according to the procedures reported in the litera-
ture. Compound 19g, which was not isolated, was directly transformed
into the corresponding carbamate.
Scheme 5. Examples of the hydrolysis of optically active 5-substituted
1,3-oxazolidin-2-ones
carbonate at room temperature, N-tosyl-1,3-oxazolidin-2-
one 23a was smoothly cleaved to give the N-tosyl-1,2-amino
alcohol 24a. Treatment of 21a and 21b with lithium hydrox-
ide monohydrate resulted in selective removal of the benzo-
yl group to give the simple 1,3-oxazolidinones 25a and 25b,
respectively. Reductive cleavage of 25a was then affected
with lithium aluminum hydride to afford the optically active
N-methyl-1,2-amino alcohol 26. Alternatively, hydrolysis of
25a with sodium hydroxide in a mixture of ethanol and
water at 1008C afforded the enantiomerically pure 1,2-
amino alcohol 27.
1-(Phenylseleno)but-3-en-2-ol (6b):[37] Yield: 38%, oil; 13C NMR
(50 MHz, CDCl3, 258C, TMS): d=138.8, 133.1 (2C), 129.3, 129.2 (2C),
127.3, 116.0, 70.9, 36.2 ppm.
1-Butoxy-3-(phenylseleno)propan-2-ol (6e): Yield: 55%, oil; 1H NMR
(200 MHz, CDCl3, 258C, TMS): d=7.60 7.47 (m, 2H; CH), 7.30 7.20 (m,
3H; CH), 3.90 3.70 (m, 1H; CH), 3.57 3.35 (m, 4H; CH2), 3.10 (dd,
2J(H,H)=12.7 and 3J(H,H)=6.0 Hz, 1H; CH2), 3.01 (dd, 2J(H,H)=12.7
and 3J(H,H)=6.8 Hz, 1H; CH2), 2.69 (d, 3J(H,H)=4.5 Hz, 1H; OH),
1.63 1.15 (m, 4H; CH2), 0.91 ppm (t, 3J(H,H)=7.2 Hz, 3H; CH3);
13C NMR (50 MHz, CDCl3, 258C, TMS): d=132.5 (2C), 128.9 (2C),
127.9, 126.9, 73.1, 71.1, 69.2, 31.6, 31.4, 19.0, 13.7 ppm; GC-MS: m/z (%):
288 (47) [M]+, 183 (38), 157 (38), 113 (23), 77 (18), 57 (100), 41 (30); ele-
mental analysis calcd (%) for C13H20O2Se (287.3): C 54.36, H 7.02; found:
C 54.53, H 7.15.
In conclusion, we have described a new and convenient
method for the stereospecific synthesis of variously substi-
tuted 1,3-oxazolidin-2-ones starting from the easily available
b-hydroxyalkyl phenyl selenides. The key step of this proc-
ess is the ring-closure reaction in which stereospecific intra-
molecular nucleophilic substitution of the selenonyl group is
effected by the nitrogen atom of the carbamate. The results
obtained also confirm that the selenonyl group is an ex-
tremely good leaving group. We have also demonstrated
that enantiomerically pure 5-substituted N-benzoyl-1,3-oxa-
zolidin-2-ones can be easily prepared from enantiomerically
pure b-hydroxyalkyl phenyl selenides. This newly developed
methodology has general application, and may represent a
valid alternative to the procedures previously reported in
Methyl 4-hydroxy-5-(phenylseleno)pentanoate (6g): Yield: 78%, oil;
1H NMR (200 MHz, CDCl3, 258C, TMS): d=7.50 7.40 (m, 2H; CH),
7.25 7.15 (m, 3H; CH), 3.70 3.55 (m, 1H; CH), 3.58 (s, 3H; OCH3), 3.05
(dd, 2J(H,H)=12.7 and 3J(H,H)=4.0 Hz, 1H; CH2), 2.83 (dd, 2J(H,H)=
12.7 and 3J(H,H)=8.3 Hz, 1H; CH2), 2.50 (brs, 1H; OH), 2.43 (dt,
3
2
2J(H,H)=9.1 and J(H,H)=3.1 Hz, 1H; CH2), 2.36 (dt, J(H,H)=9.1 and
3J(H,H)=2.6 Hz, 1H; CH2), 1.96 1.60 ppm (m, 2H; CH2); 13C NMR
(50 MHz, CDCl3, 258C, TMS): d=174.1, 132.9 (2C), 129.2 (2C), 128.7,
127.3, 69.1, 51.6, 36.7, 31.3, 30.4ppm; GC-MS: m/z (%): 256 (16)
[MÀ32]+, 171 (32), 157 (36), 91 (64), 85 (100), 77 (33); elemental analysis
calcd (%) for C12H16O3Se (287.2): C 50.18, H 5.61; found: C 50.16, H
5.60.
10-(1,3-Dioxolan-2-yl)-1-(phenylseleno)decan-2-ol (6h): Yield: 80%, oil;
1H NMR (200 MHz, CDCl3, 258C, TMS): d=7.58 7.46 (m, 2H; CH),
3
7.30 7.20 (m, 3H; CH), 4.84 (t, J(H,H)=4.7 Hz, 1H; CH), 4.02 3.75 (m,
14]
the literature.[4
4H; CH2), 3.74 3.56 (m, 1H; CH), 3.12 (dd, 2J(H,H)=12.6 and
3J(H,H)=3.7 Hz, 1H; CH2), 2.88 (dd, 2J(H,H)=12.6 and 3J(H,H)=
8.4Hz, 1H; CH 2), 2.50 (brs, 1H; OH), 1.72 1.19 ppm (m, 16H; CH2);
13C NMR (50 MHz, CDCl3, 258C, TMS): d=132.9 (2C), 129.5, 129.1
(2C), 127.1, 104.6, 69.8, 64.7 (2C), 37.1, 36.6, 33.8, 29.4 (4C), 25.7,
24.0 ppm; GC-MS: m/z (%): 386 (7), 172 (15), 157 (8), 73 (100); elemen-
tal analysis calcd (%) for C19H30O3Se (385.4): C 59.21, H 7.85; found: C
59.13, H 7.67.
Experimental Section
General: 1H NMR and 13C NMR spectra were recorded on a Bruker
Avance DR 200 spectrometer at 200 and 50.3 MHz, respectively (J values
are given in Hz). FT-IR spectra were recorded with a Jasco model 410
spectrometer. GC-MS analyses were effected with an HP-6890 gas chro-
matograph (dimethyl silicone column; 12.5 m) equipped with an HP-5973
mass-selective detector at an ionizing voltage of 70 eV. Melting points
are uncorrected. Optical rotations were measured in a 50 mm cell with a
2-[2-Hydroxy-3-(phenylseleno)propyl]-1H-isoindol-1,3-(2H)-dione (6i):
Yield: 98%; m.p. 848C; 1H NMR (200 MHz, CDCl3, 258C, TMS): d=
7.90 7.79 (m, 2H; CH), 7.78 7.70 (m, 2H; CH), 7.60 7.50 (m, 2H; CH),
7.30 7.15 (m, 3H; CH), 4.15 3.95 (m,1H; CH), 3.88 (m, 2H; CH2), 3.77
2
3
(brs, 1H; OH), 3.12 (dd, J(H,H)=13.0 and J(H,H)=5.3 Hz, 1H; CH2),
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Intramolecular Displacement of the Phenylselenonyl Group by Nitrogen Nucleophiles
1752 1764
3.00 ppm (dd, 2J(H,H)=13.0 and 3J(H,H)=7.0 Hz, 1H; CH2); 13C NMR
(50 MHz, CDCl3, 258C, TMS): d=168.6 (2C), 134.1 (2C), 133.2 (2C),
131.8 (2C), 129.9 (2C), 129.2, 127.4, 123.4 (2C), 69.0, 43.2, 33.6 ppm; ele-
mental analysis calcd (%) for C17H15NO3Se (360.3): C 56.68, H 4.20, N
3.89; found: C 56.69, H 4.23, N 3.87.
tert-Butyl (1S,2R)- and(1 S,2S)-1-(cyclohexylmethyl)-2-hydroxy-3-(phe-
nylseleno)propylcarbamate (19h): Yield: 67%, oil; mixture of diaster-
eoisomers (82:18); 1H NMR (200 MHz, CDCl3, 258C, TMS): d=7.57
3
7.45 (m, 4H; CH), 7.30 7.20 (m, 6H; CH), 4.71 (d, J(H,H)=9.6 Hz, 1H;
NH), 4.62 (d, 3J(H,H)=6.9 Hz, 1H; NH), 3.85 3.65 (m, 2H; CH), 3.61
3.49 (m, 2H; CH), 3.22 2.85 (m, 4H; CH2), 3.00 (brs, 2H; OH), 1.88
0.66 (m, 26H; CH and CH2), 1.45 ppm (s, 18H; CH3); 13C NMR
(50 MHz, CDCl3, 258C, TMS): d=156.1 (2C), 138.1 (2C), 133.0 (2C),
129.2 (4C), 128.9 (2C), 127.3 (2C), 79.2 (2C), 73.3, 71.3, 52.3, 51.0, 40.6,
37.4, 34.3 (2C), 34.2 (2C), 33.6 (2C), 32.8, 32.3, 28.3 (6C), 26.5 (2C),
26.3 (2C), 26.1 ppm (2C); elemental analysis calcd (%) for C21H33NO3Se
(426.5): C 59.14, H 7.80, N 3.28; found: C 59.22, H 7.78, N 3.17.
N-[2-Hydroxy-3-(phenylseleno)propyl]benzamide (6l): Yield: 67%; m.p.
137 1418C; 1H NMR (200 MHz, CDCl3, 258C, TMS): d=7.78 7.68 (m,
2H; CH), 7.61 7.37 (m, 4H; CH), 7.32 7.22 (m, 4H; CH), 6.46 (brs, 1H;
NH), 3.96 3.74(m, 2H; CH), 3.55 30.4 (m, 1H; CH), 3.11 (dd,
2J(H,H)=12.9 and 3J(H,H)=5.1 Hz, 1H; CH2), 2.97 (dd, 2J(H,H)=12.9
and 3J(H,H)=7.8 Hz, 1H; CH2), 1.60 ppm (brs, 1H; OH); 13C NMR
(50 MHz, CDCl3, 258C, TMS): d=167.8, 134.4, 132.0 (2C), 131.1, 128.9
(2C), 128.1 (3C), 127.2 (2C), 126.6, 69.7, 45.5, 32.6 ppm; GC-MS: m/z
(%): 317 (47) [MÀ18]+, 159 (60), 130 (100), 105 (93), 77 (75); elemental
analysis calcd (%) for C16H17NO2Se (334.3): C 57.49, H 4.87, N 4.19;
found: C 57.50, H 4.57, N 4.17.
Preparation of 19b and19c : Sodium hydride (0.106 g, 4.4 mmol) was
added to a solution of diphenyl diselenide (0.628 g, 2 mmol) in dry THF
(30 mL). The suspension was refluxed for 2 h, allowed to cool to room
temperature, and then HMPA (1 mL) was added. (S)-(+)-Glycidyl buty-
rate (0.691 g, 4.8 mmol) was added to the resultant orange solution and
after 1 h the reaction was quenched with HCl (5 mL, 10%). The reaction
mixture was extracted with diethyl ether and the combined organic
layers were dried over sodium sulfate and evaporated. The reaction prod-
uct was purified by chromatography on a silica-gel column using a mix-
ture of diethyl ether and light petroleum (2:8) as eluent. Compound 19c
was obtained in 25% yield. The corresponding diol derivative (30%
yield) was also isolated and was selectively silylated at the primary hy-
droxy group under standard conditions[38] to afford 19b. The crude hy-
droxy selenide was then immediately transformed into the corresponding
benzoyl carbamate. Yields, as well as physical and spectral data are re-
ported below.
(2SR,3RS)-1-(Benzyloxy)-2-(phenylseleno)hexan-3-ol (11b): Yield: 91%,
1
oil; H NMR (200 MHz, CDCl3, 258C, TMS): d=7.60 7.50 (m, 2H; CH),
7.40 7.15 (m, 8H; CH), 4.50 (s, 2H; CH2), 3.90 (dd, 2J(H,H)=10.2 and
2
3J(H,H)=4.8 Hz, 1H; CH2), 3.85 (brs, 1H; OH), 3.78 (dd, J(H,H)=10.2
and 3J(H,H)=7.0 Hz, 1H; CH2), 3.42 (dt, 3J(H,H)=7.0 and 4.8 Hz, 1H;
CH), 2.95 2.88 (m, 1H; CH), 1.70 1.25 (m, 4H; CH2), 0.90 ppm (t,
3J(H,H)=6.9 Hz, 3H; CH3); 13C NMR (50 MHz, CDCl3, 258C, TMS):
d=137.5, 134.6 (2C), 129.1 (2C), 128.4 (2C), 127.7 (5C), 73.3, 72.8, 71.4,
51.2, 37.2, 19.0, 14.0 ppm; elemental analysis calcd (%) for C19H24O2Se
(363.4): C 62.80, H 6.66; found: C 62.82, H 6.64.
(2SR,3SR)-1,4-Bis(benzyloxy)-3-(phenylseleno)butan-2-ol (11e): Yield:
79%, oil; 1H NMR (200 MHz, CDCl3, 258C, TMS): d=7.60 7.50 (m,
2H; CH), 7.38 7.14 (m, 13H; CH), 4.49 (m, 2H; CH2), 4.48 (m, 2H;
CH2), 4.30 4.17 (m, 1H; CH), 3.89 (dd, 2J(H,H)=9.9 and 3J(H,H)=
7.4Hz, 1H; CH 2), 3.80 (dd, 2J(H,H)=9.9 and 3J(H,H)=4.4 Hz, 1H;
CH2), 3.71 (dd, 2J(H,H)=9.4and 3J(H,H)=6.4Hz, 1H; CH 2), 3.65 (dd,
2J(H,H)=9.4and 3J(H,H)=5.8 Hz, 1H; CH2), 3.55 3.44 (m, 1H; CH),
2.95 ppm (d, 3J(H,H)=3.6 Hz, 1H; OH); 13C NMR (50 MHz, CDCl3,
258C, TMS): d=137.9, 137.7, 134.0 (2C), 129.4, 129.0 (2C), 128.4 (3C),
127.7 (4C), 127.3 (2C), 126.9 (2C), 73.3, 73.2, 72.6, 72.0, 70.8, 48.7 ppm;
elemental analysis calcd (%) for C24H26O3Se (441.4): C 65.30, H 5.94;
found: C 65.22, H 5.96.
(2R)-2-Hydroxy-3-(phenylseleno)propylbutyrate (19c): Yield: 25%, oil;
[a]2D4 =À42.57 (c=2.81 in CHCl3); 1H NMR (200 MHz, CDCl3, 258C,
TMS): d=7.63 7.50 (m, 2H; CH), 7.40 7.20 (m, 3H; CH), 4.21 (dd,
2J(H,H)=11.4and 3J(H,H)=4.3 Hz, 1H; CH2), 4.12 (dd, 2J(H,H)=11.4
and 3J(H,H)=5.6 Hz, 1H; CH2), 3.95 (dddt, 3J(H,H)=7.5, 5.6, 5.2, and
4.3 Hz, 1H; CH), 3.09 (dd, 2J(H,H)=12.9 and 3J(H,H)=5.2 Hz, 1H;
CH2), 2.98 (dd, 2J(H,H)=12.9 and 3J(H,H)=7.5 Hz, 1H; CH2), 2.74(d,
3J(H,H)=4.3 Hz, 1H; OH), 2.30 (t, 3J(H,H)=7.3 Hz, 2H; CH2), 1.63
(sext, 3J(H,H)=7.3 Hz, 2H; CH2), 0.95 ppm (t, 3J(H,H)=7.3 Hz, 3H;
CH3); 13C NMR (50 MHz, CDCl3, 258C, TMS): d=173.6, 133.1 (2C),
129.3, 129.2 (2C), 127.5, 68.5, 66.7, 35.9, 32.2, 18.3, 13.6 ppm; GC-MS m/z
(%): 302 (75) [M]+, 214(26), 183 (32), 157 (57), 145 (90), 77 (25), 71
(100); elemental analysis calcd (%) for C13H18O3Se (301.2): C 51.83, H
6.02, N 15.93; found: C 51.82, H 6.00, N 15.95.
4-(Benzyloxy)-2-methyl-3-(phenylseleno)butan-2-ol (11 f): Yield: 94%,
1
oil; H NMR (200 MHz, CDCl3, 258C, TMS): d=7.65 7.50 (m, 2H; CH),
7.38 7.12 (m, 8H; CH), 4.51 (m, 2H; CH2), 3.90 (m, 2H; CH2), 3.73 (s,
1H; OH), 3.34(dd, 3J(H,H)=6.7 and 5.2 Hz, 1H; CH), 1.38 (s, 3H;
CH3), 1.35 ppm (s, 3H; CH3); 13C NMR (50 MHz, CDCl3, 258C, TMS):
d=137.3, 134.2 (2C), 129.9, 129.2 (2C), 128.5 (2C), 127.9, 127.8 (2C),
127.6, 73.4, 73.3, 72.1, 59.7, 29.2, 27.0 ppm; elemental analysis calcd (%)
for C18H22O2Se (349.3): C 61.89, H 6.35; found: C 61.90, H 6.33.
Synthesis of the N-tosyl- and N-benzoyl carbamates
General procedure: Under an inert atmosphere, tosyl or benzoyl isocya-
nate (1.1 mmol) was added to a solution of the b-hydroxyalkyl phenyl
selenide (1 mmol) in CH2Cl2 (5 mL) (CCl4 for compounds 11d, 11 f, 19d,
19g, and 19h). The reaction was stirred at room temperature until TLC
analysis did not show any more starting alcohol to be present (1 24h),
and the solvent was then evaporated. The crude tosyl carbamate deriva-
tives were sufficiently pure to be employed directly without further puri-
fication. On the other hand, the crude benzoyl carbamates were purified
by column chromatography on silica gel using a mixture of diethyl ether
and light petroleum (4:6) as eluent. Yields, as well as physical and spec-
tral data are reported below. Compounds 20d and 20h were used without
purification.
(1S)-1-Phenyl-2-(phenylseleno)ethanol (19d):[23,27] Yield: 72%, oil;
[a]2D1 =+14.4 (c=1.54in CHCl ).
3
Methyl (3S)-3-hydroxy-4-(phenylseleno)butanoate (19e): Yield: 55%,
1
oil; H NMR (200 MHz, CDCl3, 258C, TMS): d=7.58 7.46 (m, 2H; CH),
7.30 7.20 (m, 3H; CH), 4.22 4.08 (m, 1H; CH), 3.67 (s, 3H; OCH3),
3.22 2.92 (m, 2H; CH2), 3.10 (brs, 1H; OH), 2.67 (dd, 2J(H,H)=16.0
and 3J(H,H)=4.3 Hz, 1H; CH2), 2.55 ppm (dd, 2J(H,H)=16.0 and
3J(H,H)=7.7 Hz, 1H; CH2); 13C NMR (50 MHz, CDCl3, 258C, TMS):
d=172.3, 132.7 (2C), 129.3, 129.1 (2C), 127.1, 67.1, 51.7, 40.2, 34.6 ppm;
GC-MS: m/z (%): 274(50) [ M]+, 172 (32), 157 (54), 117 (100), 91 (55),
77 (30); elemental analysis calcd (%) for C11H14O3Se (273.2): C 48.36, H
5.17; found: C 48.53, H 5.14.
1-[(Phenylseleno)methyl]undecyl-(4-methylphenyl)sulfonylcarbamate
1
(7a): Yield: 98%, oil; H NMR (200 MHz, CDCl3, 258C, TMS): d=7.95
7.82 (m, 2H; CH), 7.50 (brs, 1H; NH), 7.45 7.36 (m, 2H; CH), 7.35 7.18
3
(m, 5H; CH), 4.87 (dq, J(H,H)=6.9 and 6.0 Hz, 1H; CH), 2.95 (m, 2H;
(3S)-3-Hydroxy-4-(phenylseleno)butanenitrile (19 f): Yield: 77%, oil;
[a]2D4 =À22.71 (c=4.82 in CHCl3); 1H NMR (200 MHz, CDCl3, 258C,
TMS): d=7.60 7.50 (m, 2H; CH), 7.35 7.25 (m, 3H; CH), 3.96 (ddtd,
CH2), 2.42 (s, 3H; CH3), 1.68 1.45 (m, 2H; CH2), 1.38 1.04(m, 16H;
CH2), 0.90 ppm (t, 3J(H,H)=6.3 Hz, 3H; CH3); 13C NMR (50 MHz,
CDCl3, 258C, TMS): d=150.0, 144.9, 135.6, 133.1 (2C), 129.9 (2C), 129.5
(2C), 129.1, 128.3 (2C), 127.3, 76.9, 33.5, 31.9, 31.3, 29.5 (2C), 29.3 (3C),
24.9, 22.6, 21.6, 14.1 ppm; IR: n˜ =3239, 2925, 2854, 1749, 1438, 1348,
1163, 1090 cmÀ1; elemental analysis calcd (%) for C26H37NO4SSe (538.6):
C 57.98, H 6.92, N 2.60; found: C 57.89, H 86.95, N 2.52.
2
3J(H,H)=7.5, 6.0, 5.2, and 4.2 Hz, 1H; CH), 3.12 (dd, J(H,H)=13.0 and
3J(H,H)=5.2 Hz, 1H; CH2), 3.02 (d, 3J(H,H)=4.2 Hz, 1H; OH), 3.00
(dd, 2J(H,H)=13.0 and 3J(H,H)=7.5 Hz, 1H; CH2), 2.69 (dd, 2J(H,H)=
16.7 and 3J(H,H)=5.2 Hz, 1H; CH2), 2.59 ppm (dd, 2J(H,H)=16.7 and
3J(H,H)=6.0 Hz, 1H; CH2); 13C NMR (50 MHz, CDCl3, 258C, TMS):
d=133.3 (2C), 129.4 (2C), 128.0, 127.8, 117.1, 66.2, 34.5, 24.9 ppm; GC-
MS: m/z (%): 241 (100) [M]+, 171 (61), 157 (61), 91 (64), 77 (32), 51
(15); elemental analysis calcd (%) for C10H11NOSe (240.2): C 50.01, H
5.13, N 4.19; found: C 50.03, H 5.15, N 4.20.
1-[(Phenylseleno)methyl]prop-2-enyl-(4-methylphenyl)sulfonylcarbamate
(7b): Yield: 98%, oil; 1H NMR (200 MHz, CDCl3, 258C, TMS): d=7.80
(d, 3J(H,H)=8.3 Hz, 2H; CH), 7.40 7.05 (m, 7H; CH), 5.63 (ddd,
3J(H,H)=17.4, 10.4, and 6.3 Hz, 1H; CH), 5.28 4.94 (m, 3H; CH), 5.00
1757
Chem. Eur. J. 2004, 10, 1752 1764
www.chemeurj.org
¹ 2004Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

M. Tiecco et al.
FULL PAPER
(brs, 1H; NH), 2.95 (dd, 2J(H,H)=12.8 and 3J(H,H)=6.6 Hz, 1H; CH2),
2.87 (dd, 2J(H,H)=12.8 and 3J(H,H)=6.5 Hz, 1H; CH2), 2.34ppm (s,
3H; CH3); 13C NMR (50 MHz, CDCl3, 258C, TMS): d=149.5, 145.1,
135.5, 134.7, 133.9 (2C), 129.6 (2C), 129.2 (2C), 128.4 (2C), 127.5 (2C),
119.1, 76.8, 31.1, 21.7 ppm; elemental analysis calcd (%) for C18H19NO4Se
(424.4): C 50.94, H 4.51, N 3.30; found: C 50.92, H 4.52, N 3.33.
7.82 7.72 (m, 2H; CH), 7.64 7.40 (m, 5H; CH), 7.30 7.11 (m, 3H; CH),
5.09 (quintet, 3J(H,H)=6.2 Hz, 1H; CH), 3.15 (d, 3J(H,H)=6.2 Hz, 2H;
CH2), 1.88 1.68 (m, 2H; CH2), 1.41 1.11 (m, 16H; CH2), 0.90 ppm (t,
3J(H,H)=6.8 Hz, 3H; CH3); 13C NMR (50 MHz, CDCl3, 258C, TMS):
d=164.9, 150.4, 133.2, 132.9, 132.8 (2C), 129.7, 129.0, 128.6 (2C), 128.0,
127.6, 127.4, 127.1, 75.8, 33.5, 31.8, 31.2, 29.4 (2C), 29.3 (2C), 29.2, 25.0,
22.6, 14.0 ppm; elemental analysis calcd (%) for C26H35NO3Se (488.5): C
63.92, H 7.22, N 2.87; found: C 63.94, H 7.40, N 2.75.
1-[(Phenylseleno)methyl]pent-4-ethyl-(4-methylphenyl)sulfonylcarba-
1
mate (7c): Yield: 98%, oil; H NMR (200 MHz, CDCl3, 258C, TMS): d=
7.88 7.68 (m, 2H; CH), 7.65 (brs, 1H; NH), 7.40 7.10 (m, 7H; CH),
5.75 5.45 (m, 1H; CH), 5.05 4.65 (m, 3H; CH), 2.88 (m, 2H; CH2), 2.32
(s, 3H; CH3), 1.90 1.50 ppm (m, 4H; CH2); 13C NMR (50 MHz, CDCl3,
258C, TMS): d=150.0, 145.0, 136.9, 135.6, 133.1 (2C), 129.6 (2C), 129.2
(2C), 128.3, 127.4(2C), 126.4, 115.0, 76.3, 32.6, 31.2, 29.1, 21.7 ppm; ele-
mental analysis calcd (%) for C20H23NO4SSe (452.4): C 53.09, H 5.12, N
3.10; found: C 53.10, H 5.13, N 3.11.
1-[(Phenylseleno)methyl]pent-4-enylbenzoylcarbamate (8c): Yield: 88%,
oil; H NMR (200 MHz, CDCl3, 258C, TMS): d=8.10 (s, 1H; NH), 7.82
1
7.72 (m, 2H; CH), 7.60 7.40 (m, 6H; CH), 7.30 7.10 (m, 2H; CH), 5.74
(ddt, 3J(H,H)=17.1, 10.2, and 6.5 Hz, 1H; CH), 5.10 (quintet, 3J(H,H)=
6 Hz, 1H; CH), 5.08 4.91 (m, 2H; CH2), 3.12 (m, 2H; CH2), 2.20 2.01
(m, 2H; CH2), 1.91 1.72 ppm (m, 2H; CH2); 13C NMR (50 MHz, CDCl3,
258C, TMS): d=164.7, 150.2, 136.9, 132.8 (3C), 129.6, 129.0 (2C), 128.6
(2C), 127.5 (2C),127.1 (2C), 115.3, 75.3, 32.6, 31.1, 29.2 ppm; elemental
analysis calcd (%) for C20H21NO3Se (402.3): C 59.70, H 5.26, N 3.48;
found: C 59.71, H 5.28, N 3.50.
1-Phenyl-2-(phenylseleno)ethyl-(4-methylphenyl)sulfonylcarbamate (7d):
Yield: 80%, oil; 1H NMR (200 MHz, CDCl3, 258C, TMS): d=8.00 7.90
(m, 2H; CH), 7.75 (brs, 1H; NH), 7.46 7.14 (m, 12H; CH), 5.79 (dd,
3J(H,H)=7.7 and 6.2 Hz, 1H; CH), 3.30 (dd, 2J(H,H)=12.9 and
3J(H,H)=7.7 Hz, 1H; CH2), 3.20 (dd, 2J(H,H)=12.9 and 3J(H,H)=
6.2 Hz, 1H; CH2), 2.46 ppm (s, 3H; CH3); 13C NMR (50 MHz, CDCl3,
258C, TMS): d=149.5, 145.0, 137.9, 133.3 (2C), 129.6 (2C), 129.1 (2C),
128.7 (3C), 128.5 (2C), 128.3 (2C), 127.4, 126.5 (2C), 78.2, 33.0,
21.6 ppm; elemental analysis calcd (%) for C22H21NO4SSe (474.4): C
55.75, H 4.46, N 2.95; found: C 55.64, H 4.48, N 2.82.
2-Butoxy-1-[(phenylseleno)methyl]ethylbenzoylcarbamate (8e): Yield:
1
99%, oil; H NMR (200 MHz, CDCl3, 258C, TMS): d=8.30 (s, 1H; NH),
7.82 7.77 (m, 2H; CH), 7.60 7.40 (m, 5H; CH), 7.30 7.12 (m, 3H; CH),
5.20 5.12 (m, 1H; CH), 3.71 (dd, 2J(H,H)=10.8 and 3J(H,H)=4.6 Hz,
1H; CH2), 3.66 (dd, 2J(H,H)=10.8 and 3J(H,H)=4.0 Hz, 1H; CH2),
3.48 3.31 (m, 2H; CH2), 3.20 (d, 3J(H,H)=6.6 Hz, 2H; CH2); 1.60 1.47
(m, 2H; CH2), 1.40 1.28 (m, 2H; CH2), 0.90 ppm (t, 3J(H,H)=7.0 Hz,
3H; CH3); 13C NMR (50 MHz, CDCl3, 258C, TMS): d=164.8, 149.9,
132.9, 132.8, 132.6, 129.4, 129.2, 129.1 (2C), 127.8 (2C), 127.6, 127.0 (2C),
74.3, 71.2, 70.1, 31.4, 27.1, 19.1, 13.8 ppm; elemental analysis calcd (%)
for C21H25NO4Se (434.4): C 58.06, H 5.80, N 3.22; found: C 58.40, H 5.78,
N 3.24.
2-Butoxy-1-[(phenylseleno)methyl]ethyl-(4-methylphenyl)sulfonylcarba-
mate (7e): Yield: 86%, oil; 1H NMR (200 MHz, CDCl3, 258C, TMS):
d=8.00 7.90 (m, 2H; CH), 7.50 7.40 (m, 2H; CH), 7.38 7.16 (m, 5H;
CH), 5.45 (brs, 1H; NH), 4.96 (ddt, 3J(H,H)=6.8, 6.4, and 4.4 Hz, 1H;
2
CH), 3.54(m, 2H; CH ), 3.32 (m, 2H; CH2), 3.11 (dd, J(H,H)=13.0 and
2
3J(H,H)=6.8 Hz, 1H; CH2), 3.01 (dd, 2J(H,H)=13.0 and 3J(H,H)=
6.4Hz, 1H; CH 2), 2.44 (s, 3H; CH3), 1.51 1.18 (m, 4H; CH2), 0.88 ppm
(t, 3J(H,H)=7.0 Hz, 3H; CH3); 13C NMR (50 MHz, CDCl3, 258C, TMS):
d=149.7, 145.0, 135.5, 132.7 (2C), 129.5 (2C), 129.2 (2C), 129.1, 128.4
(2C), 127.3, 75.3, 71.3, 70.0, 31.5, 27.3, 31.6, 19.1, 13.8 ppm; elemental
analysis calcd (%) for C21H27NO5SSe (484.5): C 52.06, H 5.62, N 2.89;
found: C 52.08, H 5.64, N 2.88.
9-(1,3-Dioxolan-2-yl)-1-[(phenylseleno)methyl]nonylbenzoylcarbamate
(8h): Yield: 98%, oil; 1H NMR (200 MHz, CDCl3, 258C, TMS): d=8.10
(s, 1H; NH), 7.84 7.74 (m, 2H; CH), 7.63 7.40 (m, 5H; CH), 7.30 7.22
(m, 3H; CH), 5.08 (quintet, 3J(H,H)=6.1 Hz, 1H; CH); 4.82 (t,
3J(H,H)=4.8 Hz, 1H; CH), 4.00 3.76 (m, 4H; CH2), 3.13 (m, 2H; CH2),
1.81 1.56 (m, 6H; CH2), 1.47 1.09 ppm (m, 10H; CH2); 13C NMR
(50 MHz, CDCl3, 258C, TMS): d=164.8, 150.3, 132.9, 132.8 (3C), 129.7,
129.0 (2C), 128.6 (2C), 127.6 (2C), 127.1, 104.5, 75.8, 64.7 (2C), 37.7,
33.5, 31.1, 29.3, 29.2 (2C), 29.1, 25.0, 23.9 ppm; elemental analysis calcd
(%) for C27H35NO5Se (532.5): C 60.90, H 6.62, N 2.63; found: C 60.81, H
6.63, N 2.38.
4-Oxo-1-[(phenylseleno)methyl]pentyl-(4-methylphenyl)sulfonylcarba-
1
mate (7 f): Yield: 98%, oil; H NMR (200 MHz, CDCl3, 258C, TMS): d=
7.91 7.80 (m, 2H; CH), 7.40 7.10 (m, 7H; CH), 5.30 (s, 1H; NH), 4.90
4.70 (m, 1H; CH), 2.90 (m, 2H; CH2), 2.46 2.22 (m, 2H; CH2), 2.38 (s,
3H; CH3), 2.10 1.70 (m, 2H; CH2), 2.00 ppm (s, 3H; CH3); 13C NMR
(50 MHz, CDCl3, 258C, TMS): d=207.8, 150.2, 144.9, 135.5, 133.1, 132.9
(2C), 129.6 (2C), 129.5, 129.1, 128.2, 127.3, 126.2, 75.8, 38.7, 31.1, 29.8,
27.3, 21.4ppm; elemental analysis calcd (%) for C 20H23NO5SSe (468.4): C
51.28, H 4.95, N 2.98; found: C 51.26, H 4.97, N 2.95.
2-(Benzoylamino)-1-[(phenylseleno)methyl]ethylbenzoylcarbamate (8l):
1
Yield: 96%; m.p. 60 628C; H NMR (200 MHz, CDCl3, 258C, TMS): d=
8.75 (s, 1H; NH), 7.87 7.72 (m, 2H; CH), 7.70 7.12 (m, 13H; CH), 6.25
(brs, 1H; NH), 5.18 (ddt, 3J(H,H)=6.9, 6.3, and 5.6 Hz, 1H; CH), 3.84
(t, 3J(H,H)=5.6 Hz, 2H; CH2), 3.20 (dd, 2J(H,H)=13.3 and 3J(H,H)=
6.3 Hz, 1H; CH2), 3.09 ppm (dd, 2J(H,H)=13.3 and 3J(H,H)=6.9 Hz,
1H; CH2); 13C NMR (50 MHz, CDCl3, 258C, TMS): d=167.8, 165.3,
151.2, 133.8, 133.1, 132.9 (2C), 132.5, 131.5, 129.2 (2C), 128.7 (2C), 128.5,
128.4(2C), 127.8 (2C), 127.3, 127.1 (2C), 75.2, 39.1, 28.4ppm; elemental
analysis calcd (%) for C24H22N2O4Se (481.4): C 59.88, H 4.61, N 5.82;
found: C 59.86, H 4.63, N 5.84.
Methyl 4-({[(4-methylphenyl)sulfonyl]aminocarbonyl}oxy)-5-(phenylsele-
no)pentenoate (7g): Yield: 78%, oil; 1H NMR (200 MHz, CDCl3, 258C,
TMS): d=7.93 7.83 (m, 2H; CH), 7.45 7.35 (m, 2H; CH), 7.34 7.14 (m,
5H; CH), 5.10 (brs, 1H; NH), 4.86 (dtd, 3J(H,H)=8.3, 6.2, and 4.0 Hz,
1H; CH), 3.61 (s, 3H; OCH3), 2.96 (dd, 2J(H,H)=13.0 and 3J(H,H)=
6.2 Hz, 1H; CH2), 2.88 (dd, 2J(H,H)=13.0 and 3J(H,H)=6.2 Hz, 1H;
CH2), 2.39 (s, 3H; CH3), 2.20 (m, 2H; CH2), 2.05 1.80 ppm (m, 2H;
CH2); 13C NMR (50 MHz, CDCl3, 258C, TMS): d=173.8, 150.0, 145.0,
135.4, 133.0 (2C), 129.8, 129.6 (2C), 129.2, 128.2 (2C), 127.9, 127.4, 75.8,
51.8, 30.9, 29.5, 28.6, 21.6 ppm; elemental analysis calcd (%) for
C20H23NO6SSe (484.4): C 49.59, H 4.79, N 2.89; found: C 49.67, H 4.78, N
2.78.
4-tert-Butyl-1-(phenylseleno)cyclohexylbenzoylcarbamate (8m): Yield:
99%; m.p. 147 1508C; 1H NMR (200 MHz, CDCl3, 258C, TMS): d=
7.90 7.73 (m, 1H; CH), 7.80 (brs, 1H; NH), 7.65 7.39 (m, 6H; CH),
7.30 7.11 (m, 3H; CH), 5.10 (s, 2H; CH2), 2.65 2.48 (m, 2H; CH2), 1.73
1.56 (m, 2H; CH2), 1.54 1.12 (m, 4H; CH2), 1.12 0.90 (m, 1H; CH),
0.87 ppm (s, 9H; CH3); 13C NMR (50 MHz, CDCl3, 258C, TMS): d=
166.2, 149.9, 133.0, 132.6 (2C), 132.5, 129.8, 128.8 (2C), 128.3 (2C), 127.6
(2C), 126.8, 94.3, 46.8, 36.7, 34.7 (2C), 32.0, 27.1 (3C), 22.1 ppm (2C); el-
emental analysis calcd (%) for C25H31NO3Se (472.5): C 63.55, H 6.61, N
2.96; found: C 63.57, H 6.63, N 2.98.
2-(1,3-Dioxo-1,3-dihydro-2H-isoindol-2-yl)-1-[(phenylseleno)methyl]eth-
yl-(4-methylphenyl)sulfonylcarbamate (7i): Yield: 98%, wax; 1H NMR
(200 MHz, CDCl3, 258C, TMS): d=8.20 (brs, 1H; NH), 7.94 7.65 (m,
6H; CH), 7.55 7.42 (m, 2H; CH), 7.32 7.14(m, 5H; CH), 5.20 5.04(m,
1H; CH), 3.94(m, 2H; CH ), 3.00 (m, 2H; CH2), 2.38 ppm (s, 3H; CH3);
2
(1SR,2RS)-2-(Phenylseleno)-1-propylpentyl-(4-methylphenyl)sulfonylcar-
13C NMR (50 MHz, CDCl3, 258C, TMS): d=168.0 (2C), 149.7, 144.6,
135.3, 134.0 (2C), 133.5 (2C), 131.6, 129.6, 129.4 (2C), 129.2, 129.1, 128.8,
127.8, 127.6, 126.3, 123.4, 123.2, 74.2, 40.1, 28.7, 21.4 ppm; elemental anal-
ysis calcd (%) for C25H22N2O6Se (557.5): C 53.86, H 3.98, N 5.03; found:
C 53.89, H 3.96, N 5.05.
1
bamate (12a): Yield: 98%, oil; H NMR (200 MHz, CDCl3, 258C, TMS):
3
d=7.91 (d, J(H,H)=8.3 Hz, 2H; CH), 7.53 7.45 (m, 2H; CH), 7.40 7.20
(m, 5H; CH), 5.00 (s, 1H; NH), 4.90 (dt, 3J(H,H)=8.8 and 4.1 Hz, 1H;
CH), 3.20 (dt, 3J(H,H)=8.8 and 4.5 Hz, 1H; CH), 2.42 (s, 3H; CH3),
1.80 1.30 (m, 6H; CH2), 1.30 1.05 (m, 2H; CH2), 0.90 (t, 3J(H,H)=
6.6 Hz; 3H; CH3), 0.82 ppm (t, 3J(H,H)=7.4Hz, 3H; CH 3); 13C NMR
(50 MHz, CDCl3, 258C, TMS): d=150.1, 144.9, 135.6, 134.9 (2C), 129.5
1-[(Phenylseleno)methyl]undecylbenzoylcarbamate (8a): Yield: 99%,
oil; 1H NMR (200 MHz, CDCl3, 258C, TMS): d=7.88 (brs, 1H; NH),
1758
¹ 2004Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
Chem. Eur. J. 2004, 10, 1752 1764

Intramolecular Displacement of the Phenylselenonyl Group by Nitrogen Nucleophiles
1752 1764
(3C), 129.0 (2C), 128.3 (2C), 127.7, 79.8, 50.2, 33.3, 33.2, 21.6, 21.2, 18.6,
13.6 ppm (2C); elemental analysis calcd (%) for C22H29NO4SSe (482.5):
C 54.76, H 6.06, N 2.90; found: C 54.69, H 6.98, N 2.93.
3-(Benzyloxy)-1,1-dimethyl-2-(phenylseleno)propylbenzoylcarbamate
1
(13 f): Yield: 85%, oil; H NMR (200 MHz, CDCl3, 258C, TMS): d=8.09
(s, 1H; NH), 7.74 7.43 (m, 5H; CH), 7.42 7.11 (m, 10H; CH), 4.43 (m,
2H; CH2), 4.19 (dd, 3J(H,H)=6.2 and 4.6 Hz, 1H; CH), 3.93 (dd,
2J(H,H)=10.8 and 3J(H,H)=6.2 Hz, 1H; CH2), 3.82 (dd, 2J(H,H)=10.8
and 3J(H,H)=4.6 Hz, 1H; CH2), 1.72 (s, 3H; CH3), 1.68 ppm (s, 3H;
CH3); 13C NMR (50 MHz, CDCl3, 258C, TMS): d=164.9, 149.3, 137.7,
133.9 (2C), 133.0, 132.5, 129.8, 128.9 (2C), 128.4(2C), 128.1 (2C), 127.4
(4C), 127.3 (2C), 86.3, 72.7, 70.7, 52.9, 25.6, 25.1 ppm; elemental analysis
calcd (%) for C26H27NO4Se (496.5): C 62.90, H 5.48, N 2.82; found: C
62.72, H 5.50, N 2.70.
(1RS)-1-[(1SR)-2-(Benzyloxy)-1-(phenylseleno)ethyl]butyl-(4-methylphe-
nyl)sulfonylcarbamate (12b): Yield: 98%, oil; 1H NMR (200 MHz,
CDCl3, 258C, TMS): d=7.90 (d, 3J(H,H)=8.3 Hz, 2H; CH), 7.55 7.42
(m, 2H; CH), 7.40 7.20 (m, 10H; CH), 7.25 (s, 1H; NH), 5.14 (dt,
3J(H,H)=6.2 and 5.0 Hz, 1H; CH), 4.42 (m, 2H; CH2), 3.75 3.60 (m,
2H; CH2), 3.59 3.44 (m, 1H; CH), 2.43 (s, 3H; CH3), 1.70 1.54(m, 2H;
CH2), 1.22 1.04(m, 2H; CH 2), 0.80 ppm (t, 3J(H,H)=7.3 Hz, 3H; CH3);
13C NMR (50 MHz, CDCl3, 258C, TMS): d=150.0, 144.8, 137.7, 135.6,
134.6 (2C), 129.6 (3C), 129.5 (3C), 129.1, 128.2 (2C), 127.8 (3C), 126.3,
77.7, 72.8, 69.9, 48.1, 33.6, 21.5, 18.4, 13.6 ppm; elemental analysis calcd
(%) for C27H31NO5SSe (560.6): C 57.85, H 5.57, N 2.50; found: C 57.88,
H 5.58, N 2.50.
(1SR,2RS)-3-Cyano-1-methyl-2-(phenylseleno)propylbenzoylcarbamate
1
(13g): Yield: 79%, oil; H NMR (200 MHz, CDCl3, 258C, TMS): d=8.60
(s, 1H; NH), 7.90 7.73 (m, 2H; CH) 7.70 7.20 (m, 8H; CH), 5.10 (quin-
tet, 3J(H,H)=6.5 Hz, 1H; CH), 3.34(q, 3J(H,H)=6.5 Hz, 1H; CH), 2.85
(m, 2H; CH2), 1.52 ppm (d, 3J(H,H)=6.5 Hz, 3H; CH3); 13C NMR
(50 MHz, CDCl3, 258C, TMS): d=165.0, 150.3, 136.1 (2C), 133.0, 132.6,
129.5 (2C), 129.1, 128.8 (2C), 127.7 (2C), 126.1, 118.2, 74.5, 43.3, 21.1,
18.8 ppm; elemental analysis calcd (%) for C19H18N2O3Se (401.3): C
56.86, H 4.52 N, 6.98; found: C 58.88, H 4.54, N 7.00.
(1RS,2RS)-2-(Phenylseleno)cyclohexyl-(4-methylphenyl)sulfonylcarba-
mate (12c): Yield: 98%, oil; 1H NMR (200 MHz, CDCl3, 258C, TMS):
d=7.93 (d, 3J(H,H)=8.3 Hz, 2H; CH), 7.70 (brs, 1H; NH), 7.50 7.40
3
(m, 2H; CH), 7.38 7.15 (m, 5H; CH), 4.66 (td, J(H,H)=9.1 and 3.8 Hz,
3
1H; CH), 3.08 (ddd, J(H,H)=9.8, 9.1, and 3.9 Hz, 1H; CH), 2.40 (s, 3H;
CH3), 2.15 1.97 (m, 2H; CH2), 1.74 1.50 (m, 2H; CH2), 1.48 1.15 ppm
(m, 4H; CH2); 13C NMR (50 MHz, CDCl3, 258C, TMS): d=149.9, 144.6,
135.4, 135.1 (2C), 129.0 (2C), 128.6 (2C), 128.0 (2C), 127.4 (2C), 77.8,
45.1, 31.5, 30.7, 24.9, 22.9, 21.3 ppm; elemental analysis calcd (%) for
C20H23NO4SSe (452.4): C 53.09, H 5.12, N 3.10; found: C 53.07, H 5.15, N
3.80.
(1S)-2-(Benzyloxy)-1-[(phenylseleno)methyl]ethylbenzoylcarbamate
(20a): Yield: 97%, oil; H NMR (200 MHz, CDCl3, 258C, TMS): d=8.02
1
(s, 1H; NH); 7.80 7.70 (m, 2H; CH), 7.60 7.40 (m, 5H; CH), 7.38 7.14
(m, 8H; CH), 5.24 5.11 (m, 1H; CH), 4.45 (m, 2H; CH2), 3.76 (dd,
2J(H,H)=10.7 and 3J(H,H)=4.6 Hz, 1H; CH2), 3.69 (dd, 2J(H,H)=10.7
and 3J(H,H)=4.0 Hz, 1H; CH2), 3.18 ppm (m, 2H; CH2); 13C NMR
(50 MHz, CDCl3, 258C, TMS): d=164.8, 150.0, 137.4, 132.8, 132.7, 132.6
(2C), 132.5, 129.3, 129.1 (2C), 128.6 (2C), 128.3 (2C), 127.7 (2C), 127.6
(2C), 127.1, 74.2, 73.2, 69.5, 27.0 ppm; elemental analysis calcd (%) for
C24H23NO4Se (468.4): C 61.54, H 4.95, N 2.99; found: C 61.52, H 4.97, N
3.00.
(1SR,2RS)-2-(Phenylseleno)-1-propylpentylbenzoylcarbamate
(13a):
Yield: 91%, oil; 1H NMR (200 MHz, CDCl3, 258C, TMS): d=7.85 7.35
(m, 8H; CH), 7.28 7.00 (m, 2H; CH), 6.04(brs, 1H; NH), 5.07 (dt,
3J(H,H)=9.4and 3.7 Hz, 1H; CH), 3.84 (ddd,
3J(H,H)=8.3, 4.5, and
3.7 Hz, 1H; CH), 2.00 1.20 (m, 8H; CH2), 0.95 (t, 3J(H,H)=6.9 Hz, 3H;
CH3), 0.90 ppm (t, 3J(H,H)=6.9 Hz, 3H; CH3); 13C NMR (50 MHz,
CDCl3, 258C, TMS): d=164.8, 150.5, 134.6, 134.5, 132.6, 131.7, 130.1,
129.2 (2C), 128.8, 128.5, 127.9, 127.5, 127.3, 78.4, 50.2, 32.8, 32.2, 21.2,
18.6, 13.6, 13.2 ppm; elemental analysis calcd (%) for C22H27NO3Se
(432.4): C 61.11, H 6.29, N 3.24; found: C 61.23, H 6.20, N 3.22.
(1R)-2-[(tert-Butyl(diphenyl)silyl)oxy]-1-[(phenylseleno)methyl]ethyl-
benzoylcarbamate (20b): Yield: 92%, oil; 1H NMR (200 MHz, CDCl3,
258C, TMS): d=7.75 7.21 (m, 18H; CH), 7.50 (s, 1H; NH), 7.20 7.14
(m, 2H; CH), 5.14(dddd, 3J(H,H)=6.4, 6.1, 5.2, and 4.8 Hz, 1H; CH),
3.96 (dd, 2J(H,H)=11.1 and 3J(H,H)=4.8 Hz, 1H; CH2), 3.88 (dd,
2J(H,H)=11.1 and 3J(H,H)=5.2 Hz, 1H; CH2), 3.29 (dd, 2J(H,H)=13.2
and 3J(H,H)=6.1 Hz, 1H; CH2), 3.20 (dd, 2J(H,H)=13.2 and 3J(H,H)=
6.4Hz, 1H; CH 2), 1.07 ppm (s, 9H; CH3); 13C NMR (50 MHz, CDCl3,
258C, TMS): d=164.6, 149.7, 145.5, 135.6 (2C), 135.5, 133.1, 132.9. 132.8,
129.8 (2C), 129.6, 129.1 (2C), 128.8 (2C), 128.7 (2C), 127.7 (4C), 127.5
(3C), 127.2, 75.7, 63.9, 27.3, 26.8 (3C), 19.2 ppm; elemental analysis calcd
(%) for C33H35NO4SeSi (616.7): C 64.27, H 5.72, N 2.27; found: C 64.36,
H 5.81, N 2.26.
(1RS)-1-[(1SR)-2-(Benzyloxy)-1-(phenylseleno)ethyl]butylbenzoylcarba-
mate (13b): Yield: 93.4%, oil; 1H NMR (200 MHz, CDCl3, 258C, TMS):
d=8.05 (s, 1H; NH), 7.80 7.70 (m, 2H; CH), 7.65 7.50 (m, 2H; CH),
7.48 7.38 (m, 3H; CH), 7.35 7.12 (m, 8H; CH), 5.35 5.23 (m, 1H; CH),
4.50 (m, 2H; CH2), 3.81 3.66 (m, 3H; CH and CH2), 1.84 1.64 (m, 2H;
CH2), 1.48 1.25 (m, 2H; CH2), 0.87 ppm (t, 3J(H,H)=7.2 Hz, 3H; CH3);
13C NMR (50 MHz, CDCl3, 258C, TMS): d=164.7, 150.4, 137.7, 134.5
(2C), 132.9, 132.7, 129.0 (2C), 128.6 (3C), 128.2 (2C), 127.6 (3C), 127.5
(3C), 76.7, 72.7, 70.2, 48.0, 33.4, 18.6, 13.6 ppm; elemental analysis calcd
(%) for C27H29NO4Se (510.5): C 63.53, H 5.73, N 2.74; found: C 63.55, H
5.74, N 2.75.
(2R)-2-{[(Benzoylamino)carbonyl]oxy}-3-(phenylseleno)propylbutyrate
1
(20c): Yield: 67%, oil; H NMR (200 MHz, CDCl3, 258C, TMS): d=8.55
(s, 1H; NH), 7.90 7.77 (m, 2H; CH), 7.62 7.38 (m, 5H; CH), 7.31 7.11
(m, 3H; CH), 5.29 5.16 (m, 1H; CH), 4.37 (dd, 2J(H,H)=12.0 and
3J(H,H)=3.7 Hz, 1H; CH2) 4.27 (dd, 2J(H,H)=12.0 and 3J(H,H)=
5.8 Hz, 1H; CH2), 3.17 (dd, 2J(H,H)=13.1 and 3J(H,H)=6.3 Hz, 1H;
CH2), 3.08 (dd, 2J(H,H)=13.1 and 3J(H,H)=6.5 Hz, 1H; CH2), 2.23 (t,
3J(H,H)=7.3 Hz, 2H; CH2), 1.58 (sextet, 3J(H,H)=7.3 Hz, 2H; CH2),
0.90 ppm (t, 3J(H,H)=7.3 Hz, 3H; CH3); 13C NMR (50 MHz, CDCl3,
258C, TMS): d=172.8, 164.7, 149.8, 132.7 (3C), 132.5, 129.0 (2C), 128.7,
128.4(2C), 127.5 (2C), 127.2, 72.8, 63.4, 35.5, 26.9, 17.9, 13.3 ppm; ele-
mental analysis calcd (%) for C21H23NO5Se (448.4): C 56.25, H 5.17, N
3.12; found: C 56.23, H 5.19, N 3.11.
(1R,2S)-1-Methyl-2-(phenylseleno)cyclohexylbenzoylcarbamate
(13d):
Yield: 98%, oil; 1H NMR (200 MHz, CDCl3, 258C, TMS): d=7.80 7.65
(m, 2H; CH), 7.70 (s, 1H; NH), 7.64 7.41 (m, 5H; CH), 7.31 7.12 (m,
3H; CH), 4.05 (dd, 3J(H,H)=9.0 and 4.0 Hz, 1H; CH), 2.38 1.92 (m,
4H; CH2), 1.88 1.33 (m, 4H; CH2), 1.72 ppm (s, 3H; CH3); 13C NMR
(50 MHz, CDCl3, 258C, TMS): d=165.1, 149.0, 134.2 (2C), 133.2, 132.7,
130.3, 129.0 (2C), 128.6 (2C), 127.6 (2C), 127.3, 87.6, 51.3, 35.7, 30.5,
24.6, 22.3, 22.1 ppm; elemental analysis calcd (%) for C21H23NO3Se
(416.4): C 60.58, H 5.57, N 3.36; found: C 60.60, H 5.59, N 3.37.
(1RS,2RS)-3-(Benzyloxy)-1-[(benzyloxy)methyl]-2-(phenylseleno)propyl-
benzoylcarbamate (13e): Yield: 90%, oil; 1H NMR (200 MHz, CDCl3,
258C, TMS): d=7.85 (s, 1H; NH), 7.77 7.68 (m, 2H; CH), 7.60 7.50 (m,
3H; CH), 7.50 7.42 (m, 2H; CH), 7.32 7.16 (m, 13H; CH), 5.56 (td,
3J(H,H)=5.8 and 3.6 Hz, 1H; CH), 4.50 (m, 2H; CH2), 4.48 (m, 2H;
CH2), 3.88 (dd, 2J(H,H)=10.3 and 3J(H,H)=5.6 Hz, 1H; CH2), 3.82 (dd,
2J(H,H)=10.3 and 3J(H,H)=5.6 Hz, 1H; CH2), 3.80 (dd, 2J(H,H)=9.2
and 3J(H,H)=5.8 Hz, 1H; CH2), 3.76 (dd, 2J(H,H)=9.2 and 3J(H,H)=
5.8 Hz, 1H; CH2), 3.68 ppm (td, 3J(H,H)=5.6 and 3.6 Hz, 1H; CH);
13C NMR (50 MHz, CDCl3, 258C, TMS): d=163.3, 149.8, 137.8, 134.0
(2C), 133.0, 132.9, 129.1 (2C), 128.8 (3C), 128.4(6C), 127.8 (5C), 127.6
(3C), 74.4, 73.2, 73.1, 70.4, 69.4, 45.5 ppm; elemental analysis calcd (%)
for C32H31NO5Se (588.6): C 65.30, H 5.31, N 2.38; found: C 65.32, H 5.32,
N 2.40.
Methyl (3S)-3-{[(benzoylamino)carbonyl]oxy}-4-(phenylseleno)butanoate
(20e): Yield: 98%; m.p. 44 468C; 1H NMR (200 MHz, CDCl3, 258C,
TMS): d=8.40 (s, 1H; NH), 7.85 7.74 (m, 2H; CH), 7.61 7.35 (m, 5H;
CH), 7.30 7.10 (m, 3H; CH), 5.39 (dddd, 3J(H,H)=7.2, 6.3, 5.6, and
5.4Hz, 1H; CH), 3.55 (s, 3H; OCH 3), 3.27 (dd, 2J(H,H)=13.3 and
3J(H,H)=5.6 Hz, 1H; CH2), 3.18 (dd, 2J(H,H)=13.3 and 3J(H,H)=
6.3 Hz, 1H; CH2), 2.88 (dd, 2J(H,H)=16.2 and 3J(H,H)=5.4Hz, 1H;
CH2), 2.75 ppm (dd, 2J(H,H)=16.2 and 3J(H,H)=7.2 Hz, 1H; CH2);
13C NMR (50 MHz, CDCl3, 258C, TMS): d=170.0, 164.7, 149.8, 132.8,
132.6, 132.5 (2C), 129.1 (2C), 128.8 (2C), 128.5 (2C), 127.6, 127.1, 71.8,
51.7, 37.7, 30.0 ppm; elemental analysis calcd (%) for C19H19NO5Se
(420.4): C 54.29, H 4.56, N 3.33; found: C 54.27, H 4.54, N 3.35.
1759
Chem. Eur. J. 2004, 10, 1752 1764
www.chemeurj.org
¹ 2004Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

M. Tiecco et al.
FULL PAPER
(1S)-2-Cyano-1-[(phenylseleno)methyl]ethylbenzoylcarbamate
(20 f):
n˜ =2920, 2851, 1759, 1369, 1177 cmÀ1
;
GC-MS: m/z (%): 381 (2)
Yield: 89%, oil; [a]2D3 =+58.74( c=3.01 in CHCl3); 1H NMR (200 MHz,
CDCl3, 258C, TMS): d=8.75 (s, 1H; NH), 7.90 7.75 (m, 2H; CH), 7.62
7.35 (m, 5H; CH), 7.31 7.15 (m, 3H; CH), 5.10 (ddt, 3J(H,H)=7.6, 5.6,
and 5.0 Hz, 1H; CH), 3.28 (dd, 2J(H,H)=13.4and 3J(H,H)=5.6 Hz, 1H;
[MÀ64]+, 155 (15), 108 (100), 91 (38); elemental analysis calcd (%) for
C20H31NO4S (381.5): C 62.96, H 8.19, N 3.67; found: C 62.99, H 8.31, N
3.68.
3-[(4-Methylphenyl)sulfonyl]-5-vinyl-1,3-oxazolidin-2-one (9b): Yield:
81%, oil; 1H NMR (200 MHz, CDCl3, 258C, TMS): d=7.92 (d,
3J(H,H)=8.2 Hz, 2H; CH), 7.38 (d, 3J(H,H)=8.2 Hz, 2H; CH), 5.81
2
CH2), 3.05 (dd, J(H,H)=13.4and 3J(H,H)=7.6 Hz, 1H; CH2), 2.89 ppm
3
(d, J(H,H)=5.0 Hz, 2H; CH2); 13C NMR (50 MHz, CDCl3, 258C, TMS):
3
d=164.9, 149.4, 133.0, 132.8 (2C), 132.3, 129.2 (2C), 128.5 (2C), 127.9,
127.7 (2C), 127.6, 115.8, 70.0, 28.6, 22.1 ppm; elemental analysis calcd
(%) for C18H16N2O3Se (387.3): C 55.82, H 4.16, N 7.23; found: C 55.80, H
4.14, N 7.25.
(ddd, J(H,H)=17.1, 10.3, and 6.5 Hz, 1H; CH), 5.50 5.30 (m, 2H; CH2),
4.98 (ddd, 3J(H,H)=8.1, 7.3, and 6.5 Hz, 1H; CH), 4.18 (dd, 2J(H,H)=
9.2 and 3J(H,H)=8.1 Hz, 1H; CH2), 3.70 (dd, 2J(H,H)=9.2 and
3J(H,H)=7.3 Hz, 1H; CH2), 2.45 ppm (s, 3H; CH3); 13C NMR (50 MHz,
CDCl3, 258C, TMS): d=151.4, 145.8, 133.7, 132.3, 129.9 (2C), 128.1 (2C),
120.6, 74.6, 49.5, 21.6 ppm; GC-MS: m/z (%): 203 (28) [MÀ64]+, 155
(21), 118 (34), 91 (100), 56 (25); elemental analysis calcd (%) for
C12H13NO4S (267.3): C 53.92, H 4.90, N 5.24; found: C 53.95, H 4.93, N
5.27.
(1S,2S)-2-(Dibenzylamino)-3-phenyl-1-[(phenylseleno)methyl]propylben-
zoylcarbamate (20g): Yield: 58%; m.p. 46 488C; 1H NMR (200 MHz,
CDCl3, 258C, TMS): d=7.64 7.50 (m, 2H; CH), 7.50 7.00 (m, 24H;
CH), 5.43 (ddd, 3J(H,H)=7.2, 6.8, and 4.6 Hz, 1H; CH), 3.65 (m, 4H;
CH2), 3.43 (ddd, 3J(H,H)=7.8, 7.2, and 5.8 Hz, 1H; CH), 3.30 (dd,
2J(H,H)=13.5 and 3J(H,H)=6.8 Hz, 1H; CH2), 3.20 (dd, 2J(H,H)=14.5
and 3J(H,H)=5.8 Hz, 1H; CH2), 3.03 (dd, 2J(H,H)=13.5 and 3J(H,H)=
6.8 Hz, 1H; CH2), 2.76 ppm (dd, 2J(H,H)=14.5 and 3J(H,H)=7.8 Hz,
1H; CH2); 13C NMR (50 MHz, CDCl3, 258C, TMS): d=164.3, 150.1,
140.4, 139.2 (2C), 133.5 (2C), 132.9, 132.8, 129.9, 129.0 (2C), 128.9 (4C),
128.7 (4C), 128.4 (3C), 128.3 (2C), 127.6 (2C), 127.2 (2C), 125.8 (2C),
123.6, 75.8, 60.6, 54.2 (2C), 32.1, 30.9 ppm; elemental analysis calcd (%)
for C38H36N2O3Se (647.7): C 70.47, H 5.60, N 4.33; found: C 70.55, H
5.58, N 4.15.
5-But-3-enyl-3-[(4-methylphenyl)sulfonyl]-1,3-oxazolidin-2-one
(9c):
Yield: 75%, oil; 1H NMR (200 MHz, CDCl3, 258C, TMS): d=7.92 (d,
3J(H,H)=8.3 Hz, 2H; CH), 7.38 (d, 3J(H,H)=8.3 Hz, 2H; CH), 5.75
3
(ddt, J(H,H)=16.9, 10.2, and 6.6 Hz, 1H; CH), 5.12 4.98 (m, 2H; CH2),
4.55 (dtd, 3J(H,H)=8.2, 7.2, and 5.5 Hz, 1H; CH2), 4.12 (dd, 2J(H,H)=
9.0 and 3J(H,H)=8.2 Hz, 1H; CH2), 3.63 (dd, 2J(H,H)=9.0 and
3J(H,H)=7.2 Hz, 1H; CH2), 2.45 (s, 3H; CH3), 2.27 2.08 (m, 2H; CH2),
1.98 1.58 ppm (m, 2H; CH2); 13C NMR (50 MHz, CDCl3, 258C, TMS):
d=151.5, 145.7, 136.0, 133.9, 129.8 (2C), 128.1 (2C), 116.3, 73.8, 49.5,
32.2, 28.4, 21.6 ppm; elemental analysis calcd (%) for C14H17NO4S
(295.4): C 56.90, H 5.80, N 4.74; found: C 56.68, H 5.82, N 4.56.
(1S)-2-(Benzyloxy)-1-[(phenylseleno)methyl]ethyl-(4-methylphenyl)sulfo-
nylcarbamate (22a): Yield: 98%, oil; 1H NMR (200 MHz, CDCl3, 258C,
TMS): d=8.38 (s, 1H; NH), 7.90 (d, 3J(H,H)=8.3 Hz, 2H; CH), 7.50
7.10 (m, 12H; CH), 5.10 (dddd, 3J(H,H)=6.9, 6.3, 4.0, and 2.0 Hz, 1H;
CH), 4.39 (m, 2H; CH2), 3.66 (dd, 2J(H,H)=10.4and 3J(H,H)=2.0 Hz,
1H; CH2), 3.60 (dd, 2J(H,H)=10.4and 3J(H,H)=4.0 Hz, 1H; CH2), 3.10
(dd, 2J(H,H)=13.0 and 3J(H,H)=6.9 Hz, 1H; CH2), 3.01 (dd, 2J(H,H)=
13.0 and 3J(H,H)=6.3 Hz, 1H; CH2), 2.40 ppm (s, 3H; CH3); 13C NMR
(50 MHz, CDCl3, 258C, TMS): d=149.9, 144.8, 137.3, 135.4, 132.7 (2C),
129.5, 129.4, 129.0 (2C), 128.2 (3C), 127.6 (2C), 127.5 (2C), 127.2, 126.2,
75.1, 73.0, 69.3, 27.0, 21.5 ppm; elemental analysis calcd (%) for
C24H25NO5SSe (518.5): C 55.60, H 4.86, N 2.70; found: C 55.57, H 4.99, N
2.62.
3-[(4-Methylphenyl)sulfonyl]-5-phenyl-1,3-oxazolidin-2-one (9d): Yield:
1
69%; m.p. 100 1038C; H NMR (200 MHz, [D6]DMSO, 258C, TMS): d=
3
8.02 7.90 (m, 2H; CH), 7.60 7.30 (m, 7H; CH), 5.83 (t, J(H,H)=7.8 Hz,
1H; CH), 4.61 (m, 1H; CH2), 4.00 (m, 1H; CH2), 2.50 ppm (s, 3H; CH3);
13C NMR (50 MHz, [D6]DMSO, 258C, TMS): d=151.3, 145.7, 136.7,
133.7, 130.0 (2C), 129.2, 128.9 (2C), 127.9 (2C), 126.1 (2C), 75.3, 51.1,
21.1 ppm; GC-MS: m/z (%): 253 (17) [MÀ64]+, 149 (83), 105 (28), 91
(100), 65 (23), 56 (37); elemental analysis calcd (%) for C16H15NO4S
(317.4): C 60.55, H 4.76, N 4.41; found: C 60.53, H 4.78, N 4.44.
5-(Butoxymethyl)-3-[(4-methylphenyl)sulfonyl]-1,3-oxazolidin-2-one
1
(9e): Yield: 79%, oil; H NMR (200 MHz, CDCl3, 258C, TMS): d=7.99
Conversion of b-carbamoyloxy selenides into 5-substituted N-tosyl or N-
benzoyl-1,3-oxazolidin-2-ones
7.89 (m, 2H; CH), 7.43 7.30 (m, 2H; CH), 4.61 (ddt, 3J(H,H)=8.95, 6.1,
and 3.9 Hz, 1H; CH), 4.08 (dd, 2J(H,H)=9.0 and J(H,H)=8.95 Hz, 1H;
3
MethodA : Powdered potassium hydrogenphosphate (0.870 g, 5 mmol)
and meta-chloroperoxybenzoic acid (0.688 g, 4mmol) were added to a
solution of the crude N-tosyl carbamate 7 (1 mmol) in THF (15 mL) at
08C. The progress of the reaction (1 9 h) was monitored by TLC and the
mixture was allowed to slowly reach room temperature. When the sele-
none was completely consumed the reaction was quenched with saturated
aqueous Na2CO3 (10 mL) and extracted with diethyl ether. The combined
organic layers were washed with a solution of NaOH (10%) to eliminate
the tosylamide impurity, dried over sodium sulfate, and evaporated to
give the 1,3-oxazolidin-2-one 9 in pure form. For compounds 8 the reac-
tion mixture was stirred until the starting selenide had been completely
transformed (2 h) into the corresponding selenone, as indicated by TLC
and 13C NMR analysis, and the reaction mixture was then concentrated
in vacuo. The residue was suspended in reagent-grade acetone (20 mL)
and powdered potassium carbonate was added at room temperature. The
disappearance of the selenone was monitored by TLC (2 24h), and the
mixture was then concentrated in vacuo, poured into water, and extract-
ed with diethyl ether. The organic layer was dried over sodium sulfate
and evaporated. The reaction product was purified by column chroma-
tography on silica gel using a mixture of diethyl ether and light petrole-
um (2:8) as eluent. Yields, as well as physical and spectral data are re-
ported below.
CH2), 3.95 (dd, 2J(H,H)=9.0 and 3J(H,H)=6.1 Hz, 1H; CH2), 3.55 (m,
2H; CH2), 3.40 (m, 2H; CH2), 2.45 (s, 3H; CH3), 1.50 1.12 (m, 4H;
CH2), 0.88 ppm (t, 3J(H,H)=6.6 Hz, 3H; CH3); 13C NMR (50 MHz,
CDCl3, 258C, TMS): d=151.6, 145.5, 134.2, 129.8 (2C), 128.1 (2C), 72.7,
71.7, 69.8, 46.1, 31.4, 21.6, 19.0, 13.0 ppm; IR: n˜ =2960, 1788, 1372,
1173 cmÀ1; elemental analysis calcd (%) for C15H21NO5S (327.4): C 55.03,
H 6.49, N 4.28; found: C 55.01, H 6.50, N 4.30.
3-[(4-methylphenyl)sulfonyl]-5-(3-oxobutyl)-1,3-oxazolidin-2-one
(9 f):
Yield: 75%, oil; 1H NMR (200 MHz, CDCl3, 258C, TMS): d=7.85 7.75
(m, 2H; CH), 7.32 7.22 (m, 2H; CH), 4.56 4.40 (m, 1H; CH), 4.03 (dd,
2J(H,H)=9.2 and 3J(H,H)=8.1 Hz, 1H; CH2), 3.52 (dd, 2J(H,H)=9.2
and 3J(H,H)=6.9 Hz, 1H; CH2), 2.50 (t, 3J(H,H)=7.0 Hz, 2H; CH2),
2.34(s, 3H; CH 3), 2.04(s, 3H; CH 3), 2.00 1.60 ppm (m, 2H; CH2);
13C NMR (50 MHz, CDCl3, 258C, TMS): d=206.9, 151.5, 145.8, 133.7,
129.9 (2C), 128.1 (2C), 73.6, 49.6, 37.8, 29.9, 28.0, 21.6 ppm; IR: n˜ =3259,
1763, 1714, 1363, 1177 cmÀ1; GC-MS: m/z (%): 254()4 [ MÀ77]+, 156
(65), 112 (48), 91 (100), 65 (26), 43 (40); elemental analysis calcd (%) for
C14H17NO5S (311.4): C 54.01, H 5.50, N 4.50; found: C 54.12, H 5.53, N
4.33.
Methyl 3-(3-[(4-methylphenyl)sulfonyl]-2-oxo-1,3-oxazolidin-5-yl)propa-
noate (9g): Yield: 92%, oil; 1H NMR (200 MHz, CDCl3, 258C, TMS):
d=7.87 (d, 3J(H,H)=8.3 Hz, 2H; CH), 7.31 (d, 3J(H,H)=8.3 Hz, 2H;
CH), 4.66 4.45 (m, 1H; CH), 4.10 (dd, 2J(H,H)=9.1 and 3J(H,H)=
8.1 Hz, 1H; CH2), 3.62 (s, 3H; OCH3), 3.59 (dd, 2J(H,H)=9.1 and
3J(H,H)=6.9 Hz, 1H; CH2), 2.40 (m, 2H; CH2), 2.39 (s, 3H; CH3), 2.02
1.85 ppm (m, 2H; CH2); 13C NMR (50 MHz, CDCl3, 258C, TMS): d=
172.4, 151.3, 145.8, 133.7, 129.9 (2C), 128.1 (2C), 73.4, 51.8, 49.4, 29.3,
28.8, 21.6 ppm; IR: n˜ =2954, 1784, 1736, 1369, 1172 cmÀ1; GC-MS: m/z
(%): 297 (1) [MÀ32]+, 172 (57), 140 (100), 108 (39), 91 (93), 65 (23); ele-
5-Decyl-3-[(4-methylphenyl)sulfonyl]-1,3-oxazolidin-2-one (9a): Yield:
96%, oil; 1H NMR (200 MHz, CDCl3, 258C, TMS): d=7.90 7.80 (m,
2H; CH), 7.40 7.30 (m, 2H; CH), 4.60 4.40 (m, 1H; CH), 4.09 (dd,
2J(H,H)=9.0 and 3J(H,H)=7.9 Hz, 1H; CH2), 3.57 (dd, 2J(H,H)=9.0
and 3J(H,H)=7.2 Hz, 1H; CH2), 2.40 (s, 3H; CH3), 1.80 1.10 (m, 18H;
CH2), 0.95 ppm (t, 3J(H,H)=6.6 Hz, 3H; CH3); 13C NMR (50 MHz,
CDCl3, 258C, TMS): d=151.6, 145.5, 133.8, 129.7 (2C), 128.0 (2C), 74.6,
49.5, 34.0, 31.7, 29.3, 29.2, 29.1 (2C), 28.9, 24.2, 22.5, 21.5, 13.9 ppm; IR:
1760
¹ 2004Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
Chem. Eur. J. 2004, 10, 1752 1764

Intramolecular Displacement of the Phenylselenonyl Group by Nitrogen Nucleophiles
1752 1764
mental analysis calcd (%) for C14H17NO6S (327.4): C 51.30, H 4.23, N
4.28; found: C 51.50, H 4.25, N 4.29.
elemental analysis calcd (%) for C15H19NO4 (277.3): C 64.97, H 6.91, N
5.05; found: C 64.99, H 6.90, N 5.04.
3-Benzoyl-5-(8-(1,3-dioxolan-2-yl)octyl)-1,3-oxazolidin-2-one
(10h):
2-(3-[(4-Methylphenyl)sulfonyl]-2-oxo-1,3-oxazolidin-5-yl)methyl-1H-iso-
indol-1,3-(2H)-dione (9i): Yield: 86%, oil; 1H NMR (200 MHz, CDCl3,
258C, TMS): d=7.90 (d, 3J(H,H)=8.3 Hz, 2H; CH), 7.86 7.68 (m, 4H;
CH), 7.30 (d, 3J(H,H)=8.3 Hz, 2H; CH), 4.88 (dddd, 3J(H,H)=8.2, 6.6,
6.2, and 5.6 Hz, 1H; CH), 4.16 (dd, 2J(H,H)=9.6 and 3J(H,H)=8.2 Hz,
1H; CH2), 4.02 (dd, 2J(H,H)=14.3 and 3J(H,H)=6.6 Hz, 1H; CH2), 3.91
(dd, 2J(H,H)=9.6 and 3J(H,H)=6.2 Hz, 1H; CH2), 3.85 (dd, 2J(H,H)=
14.3 and 3J(H,H)=5.6 Hz, 1H; CH2), 2.40 ppm (s, 3H; CH3); 13C NMR
(50 MHz, CDCl3, 258C, TMS): d=167.6 (2C), 150.8, 145.7, 134.3 (2C),
133.6, 131.4 (2C), 129.8 (2C), 128.1 (2C), 123.5 (2C), 71.0, 47.4, 39.9,
21.5 ppm; elemental analysis calcd (%) for C19H16N2O6S (400.4): C 56.99,
H 4.03, N 7.00; found: C 56.97, H 4.00, N 7.03.
1
Yield: 62%; m.p. 89 918C; H NMR (200 MHz, CDCl3, 258C, TMS): d=
7.71 7.36 (m, 5H; CH), 4.84 (t, 3J(H,H)=4.7 Hz, 1H; CH), 4.64 (tdd,
3J(H,H)=7.9, 7.6, and 5.7 Hz, 1H; CH), 4.18 (dd, 2J(H,H)=10.9 and
3J(H,H)=7.9 Hz, 1H; CH2), 4.01 3.78 (m, 4H; CH2), 3.77 (dd, J(H,H)=
2
10.9 and 3J(H,H)=7.6 Hz, 1H; CH2), 1.95 1.18 ppm (m, 16H; CH2);
13C NMR (50 MHz, CDCl3, 258C, TMS): d=169.7, 152.8, 132.7, 122.1,
128.9 (2C), 127.7 (2C), 104.5, 74.3, 64.7 (2C), 48.7, 34.3, 33.7, 29.3, 29.2,
29.1, 29.0, 24.3, 23.9 ppm; elemental analysis calcd (%) for C21H29NO5
(375.5): C 67.18, H 7.79, N 3.73; found: C 67.20, H 7.80, N 3.71.
N-[(3-Benzoyl-2-oxo-1,3-oxazolidin-5-yl)methyl]benzamide (10l): Yield:
77%; m.p. 110 1138C; 1H NMR (200 MHz, CDCl3, 258C, TMS): d=
3
7.85 7.75 (m, 2H; CH), 7.63 7.22 (m, 8H; CH), 6.79 (t, J(H,H)=6.4Hz,
(3aRS,7aSR)-3-[(4-Methylphenyl)sulfonyl]hexahydro-1,2-benzoxazol-
2(3H)-one (14c): Yield: 73%, oil; 1H NMR (200 MHz, CDCl3, 258C,
TMS): d=7.87 (d, 3J(H,H)=8.2 Hz, 2H; CH), 7.25 (d, 3J(H,H)=8.2 Hz,
1H; NH), 4.90 (dddd, 3J(H,H)=8.3, 7.2, 6.4, and 3.5 Hz, 1H; CH), 4.24
(dd, 2J(H,H)=11.3 and 3J(H,H)=8.3 Hz, 1H; CH2), 3.98 (dd, 2J(H,H)=
11.3 and 3J(H,H)=7.2 Hz, 1H; CH2), 3.96 (ddd, 2J(H,H)=14.7 and
3J(H,H)=6.4and 3.5 Hz, 1H; CH 2), 3.75 ppm (dt, 2J(H,H)=14.7 and
3J(H,H)=6.4Hz, 1H; CH 2); 13C NMR (50 MHz, CDCl3, 258C, TMS):
d=169.4, 168.3, 152.8, 133.5, 132.5, 132.3, 131.8, 128.8 (2C), 128.4 (2C),
127.9, 127.7, 127.3, 127.1, 73.1, 66.2, 42.1 ppm; IR: n˜ =3364, 3067, 1805,
1777, 1678, 1528, 1360, 1197 cmÀ1; elemental analysis calcd (%) for
C18H16N2O4 (324.3): C 66.66, H 4.97, N 8.64; found: C 66.54, H 4.99, N
8.52.
3
2H; CH), 4.53 4.43 (m, 1H; CH), 4.27 (dt, J(H,H)=9.4and 6.0 Hz, 1H;
CH), 2.35 (s, 3H; CH3), 2.25 1.98 (m, 2H; CH2), 1.84 1.70 (m, 1H; CH),
1.69 1.10 ppm (m, 5H; CH and CH2); 13C NMR (50 MHz, CDCl3, 258C,
TMS): d=152.1, 145.3, 135.4, 129.6 (2C), 128.4 (2C), 75.0, 57.4, 28.0,
26.3, 21.6, 20.5, 18.7 ppm; elemental analysis calcd (%) for C14H17NO4S
(295.4): C 56.93, H 5.80, N 4.74; found: C 56.75, H 5.92, N 4.76.
(5R)-5-[(Benzyloxy)methyl]-3-(4-methylphenyl)sulfonyl-1,3-oxazolidin-2-
1
one (23a): Yield: 88%, oil; H NMR (200 MHz, CDCl3, 258C, TMS): d=
3-Benzoyl-8-(tert-butyl)-1-oxa-3-azaspiro[4,5]decan-2-one (10m): Yield
80%; m.p. 142 1458C; 1H NMR (200 MHz, CDCl3, 258C, TMS): d=
7.70 7.60 (m, 2H; CH), 7.60 7.35 (m, 3H; CH), 3.80 (s, 2H; CH2), 2.20
2.00 (m, 2H; CH2), 1.82 1.42 (m, 6H; CH2), 1.20 1.00 (m, 1H; CH),
0.90 ppm (s, 9H; CH3); 13C NMR (50 MHz, CDCl3, 258C, TMS): d=
170.1, 152.4, 133.0, 132.2, 129.0 (2C), 127.8 (2C), 79.6, 54.7, 46.8, 36.7
(2C), 32.4, 27.5 (3C), 22.6 ppm (2C); elemental analysis calcd (%) for
C19H25NO3 (315.4): C 72.35, H 7.99, N 4.44; found: C 72.37, H 7.97, N
4.43.
7.86 (d, 3J(H,H)=8.2 Hz, 2H; CH), 7.35 7.12 (m, 7H; CH), 4.61 (dddd,
3J(H,H)=9.0, 6.1, 3.8, and 3.7 Hz, 1H; CH), 4.44 (s, 2H; CH2), 4.06 (dd,
2J(H,H)=9.1 and 3J(H,H)=9.0 Hz, 1H; CH2), 3.93 (dd, 2J(H,H)=9.0
and 3J(H,H)=6.1 Hz, 1H; CH2), 3.59 (dd, 2J(H,H)=11.0 and 3J(H,H)=
3.7 Hz, 1H; CH2), 3.52 (dd, 2J(H,H)=11.0 and 3J(H,H)=3.8 Hz, 1H;
CH2), 2.38 ppm (s, 3H; CH3); 13C NMR (50 MHz, CDCl3, 258C, TMS):
d=151.1, 145.5, 137.0, 134.0, 130.2 (2C), 128.4 (2C), 128.0, 127.9 (2C),
127.5 (2C), 73.4, 72.5, 69.1, 46.1, 21.5 ppm; GC-MS: m/z (%): 361 (1)
[M]+, 255 (15), 155 (23), 91 (100), 65 (12), 107 (13); elemental analysis
calcd (%) for C18H19NO5S (361.4): C 59.82, H 5.30, N 3.88; found: C
59.85, H 5.32, N 3.86.
(5R)-3-Benzoyl-5-[(benzyloxy)methyl]-1,3-oxazolidin-2-one (21a): Yield:
90%; m.p. 93 948C; [a]D26 =À17.76 (c=3.63 in CHCl3); 1H NMR
(200 MHz, CDCl3, 258C, TMS): d=7.60 7.43 (m, 3H; CH), 7.42 7.28 (m,
7H; CH), 4.75 (ddt, 3J(H,H)=8.5, 5.8, and 3.5 Hz, 1H; CH), 4.59 (m,
2H; CH2), 4.16 (dd, 2J(H,H)=10.8 and 3J(H,H)=8.5 Hz, 1H; CH2), 4.04
(dd, 2J(H,H)=10.8 and 3J(H,H)=5.8 Hz, 1H; CH2), 3.77 (dd, 2J(H,H)=
10.8 and 3J(H,H)=3.5 Hz, 1H; CH2), 3.65 ppm (dd, 2J(H,H)=10.8 and
3J(H,H)=3.5 Hz, 1H; CH2); 13C NMR (50 MHz, CDCl3, 258C, TMS):
d=169.4, 152.6, 137.1, 132.7, 131.9 (2C), 128.6 (3C), 128.5 (2C), 127.8,
127.6 (2C), 73.5, 72.4, 69.7, 45.3 ppm; IR: n˜ =2894, 1764, 1682,
1367 cmÀ1; elemental analysis calcd (%) for C18H17NO4 (311.3): C 69.44,
H 5.50, N 4.50; found: C 69.53, H 5.39, N 4.51.
3-Benzoyl-5-decyl-1,3-oxazolidin-2-one (10a): Yield: 89%; m.p. 83 858C;
1H NMR (200 MHz, CDCl3, 258C, TMS): d=7.70 7.60 (m, 2H; CH),
7.60 7.34(m, 3H; CH), .465 (dtd,
3J(H,H)=7.9, 7.6, and 5.7 Hz, 1H;
CH), 4.19 (dd, 2J(H,H)=10.9 and 3J(H,H)=7.9 Hz, 1H; CH2), 3.78 (dd,
2J(H,H)=10.9 and 3J(H,H)=7.6 Hz, 1H; CH2), 1.95 1.15 (m, 18H;
CH2), 0.89 ppm (t, 3J(H,H)=6.7 Hz, 3H; CH3); 13C NMR (50 MHz,
CDCl3, 258C, TMS): d=169.7, 152.8, 132.7, 132.2, 128.9 (2C), 127.7 (2C),
74.4, 48.7, 34.4, 31.8, 29.4 (2C), 29.3, 29.2, 29.1, 24.4, 22.6, 14.0 ppm; IR:
n˜ =2921, 1790, 1772, 1681, 1354, 1195 cmÀ1; GC-MS: m/z (%): 331 (2)
[M]+, 105 (100), 77 (16); elemental analysis calcd (%) for C20H29NO3
(332.4): C 72.47, H 8.82, N 4.23; found: C 72.48, H 8.83, N 4.25.
(5S)-3-Benzoyl-5-{[(tert-butyl(diphenyl)silyl)oxy]methyl}-1,3-oxazolidin-
2-one (21b): Yield: 77%; m.p. 100 1028C; [a]2D4 =+32.75 (c=4.60 in
CHCl3); 1H NMR (200 MHz, CDCl3, 258C, TMS): d=7.72 7.56 (m, 6H;
CH), 7.54 7.33 (m, 9H; CH), 4.77 4.65 (m, 1H; CH), 4.19 (m, 2H; CH2),
3.98 (dd, 2J(H,H)=11.6 and 3J(H,H)=3.4Hz, 1H; CH 2), 3.77 (dd,
2J(H,H)=11.6 and 3J(H,H)=3.1 Hz, 1H; CH2), 1.08 ppm (s, 9H; CH3);
13C NMR (50 MHz, CDCl3, 258C, TMS): d=169.5, 152.7, 135.5 (4C),
132.8, 132.4, 132.2, 132.0, 130.0 (2C), 128.9 (2C), 127.9 (4C), 127.6 (2C),
3-Benzoyl-5-but-3-enyl-1,3-oxazolidin-2-one (10c): Yield: 93%; m.p. 72
748C; 1H NMR (200 MHz, CDCl3, 258C, TMS): d=7.70 7.60 (m, 2H;
CH), 7.60 7.30 (m, 3H; CH), 5.80 (ddd, 3J(H,H)=17.0, 10.3, and 6.6 Hz,
1H; CH), 5.16 5.00 (m, 2H; CH2), 4.64 (dtd, 3J(H,H)=7.8, 7.6, and
5.5 Hz, 1H; CH), 4.16 (dd, 2J(H,H)=10.9 and 3J(H,H)=7.8 Hz, 1H;
2
3
CH2), 3.96 (dd, J(H,H)=10.9 and J(H,H)=7.6 Hz, 1H; CH2), 2.35 2.08
(m, 2H; CH2), 2.05 1.70 ppm (m, 2H; CH2); 13C NMR (50 MHz, CDCl3,
258C, TMS): d=169.9, 152.7, 136.2, 132.7, 132.2, 128.9 (2C), 127.7 (2C),
116.2, 73.6, 48.6, 32.5, 28.6 ppm; GC-MS: m/z (%): 245 (3) [M]+, 105
(100), 77 (24); elemental analysis calcd (%) for C14H15NO3 (245.3): C
68.56, H 6.16, N 5.71; found: C 68.68, H 6.18, N 5.60.
73.3, 63.9, 44.8, 26.7 (3C), 19.2 ppm; IR: n˜ =2930, 1790, 1682, 1113 cmÀ1
;
elemental analysis calcd (%) for C27H29NO4Si (459.6): C 70.56, H 6.36, N
3.05; found: C 70.54, H 6.35, N 3.03.
[(5S)-3-Benzoyl-2-oxo-1,3-oxazolidin-5-yl]methylbutyrate (21c): Yield:
67%; m.p. 77 798C; [a]D24 =+4.15 (c=3.44 in CHCl3); 1H NMR
(200 MHz, CDCl3, 258C, TMS): d=7.70 7.50 (m, 3H; CH), 7.50 7.38 (m,
2H; CH), 4.86 (dddd, 3J(H,H)=8.6, 6.3, 4.7, and 3.5 Hz, 1H; CH), 4.38
(dd, 2J(H,H)=12.4and 3J(H,H)=3.5 Hz, 1H; CH2), 4.27 (dd, 2J(H,H)=
12.4and 3J(H,H)=4.7 Hz, 1H; CH2), 4.24 (dd, 2J(H,H)=11.1 and
3J(H,H)=8.6 Hz, 1H; CH2), 3.95 (dd, 2J(H,H)=11.1 and 3J(H,H)=
6.3 Hz, 1H; CH2), 2.36 (t, 3J(H,H)=7.3 Hz, 2H; CH2), 1.68 (sextet,
3J(H,H)=7.3 Hz, 2H; CH2), 0.95 ppm (t, 3J(H,H)=7.3 Hz, 3H; CH3);
13C NMR (50 MHz, CDCl3, 258C, TMS): d=172.9, 169.4, 152.2, 144.5,
132.4, 128.9 (2C), 127.8 (2C), 71.0, 63.4, 45.2, 35.7, 18.2, 13.5 ppm; GC-
MS: m/z (%): 291 (1) [M]+, 247 (6), 177 (20), 105 (100), 77 (32); IR: n˜ =
2965, 1793, 1776, 1736, 1674, 1343, 1162 cmÀ1; elemental analysis calcd
3-Benzoyl-5-(butoxymethyl)-1,3-oxazolidin-2-one (10e): Yield: 69%;
m.p. 61 628C; 1H NMR (200 MHz, CDCl3, 258C, TMS): d= 7.70 7.60
(m, 2H; CH), 7.58 7.34(m, 3H; CH), 4.73 (ddt, 3J(H,H)=8.5, 5.8, and
3.6 Hz, 1H; CH), 4.16 (dd, 2J(H,H)=10.8 and 3J(H,H)=8.5 Hz, 1H;
CH2), 4.04 (dd, 2J(H,H)=10.8 and 3J(H,H)=5.8 Hz, 1H; CH2), 3.71 (dd,
2J(H,H)=10.9 and 3J(H,H)=3.6 Hz, 1H; CH2), 3.60 (dd, 2J(H,H)=10.9
and 3J(H,H)=3.6 Hz, 1H; CH2), 3.52 (t, 3J(H,H)=6.5 Hz, 2H; CH2),
1.68 1.48 (m, 2H; CH2), 1.48 1.18 (m, 2H; CH2), 0.91 ppm (t, 3J(H,H)=
7.2 Hz, 3H; CH3); 13C NMR (50 MHz, CDCl3, 258C, TMS): d=169.6,
152.8, 132.8, 132.1, 128.8, 128.7, 127.7, 127.6, 72.6, 71.7, 70.5, 45.5, 31.5,
19.1, 13.8 ppm; GC-MS: m/z (%): 205 (10) [MÀ72]+, 105 (100), 77 (25);
1761
Chem. Eur. J. 2004, 10, 1752 1764
www.chemeurj.org
¹ 2004Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

M. Tiecco et al.
FULL PAPER
(%) for C15H17NO5 (201.3): C 61.85, H 5.88, N 4.81; found: C 61.83, H
5.86, N 4.80.
organic layers were dried over sodium sulfate and concentrated in vacuo.
The residue was dissolved in methanol (10 mL) and a catalytic amount of
cesium carbonate (0.04g) was added. The mixture was stirred overnight
and the solvent was removed under reduced pressure. The residue was
purified by column chromatography using a mixture of diethyl ether and
ethyl acetate (8:2) as eluent to afford 17a or 17b, respectively. Reaction
yields are reported in Table 2, while physical and spectral data are report-
ed below.
(5S)-3-Benzoyl-5-phenyl-1,3-oxazolidin-2-one (21d): Yield: 75%; m.p.
134 1378C; [a]2D0 =+78.35 (c=1.52 in CHCl3); 1H NMR (200 MHz,
CDCl3, 258C, TMS): d=7.74 7.64 (m, 2H; CH), 7.62 7.32 (m, 8H; CH),
2
5.64(dd, 3J(H,H)=8.1 and 8.0 Hz, 1H; CH), 4.47 (dd, J(H,H)=11.1 and
3J(H,H)=8.1 Hz, 1H; CH2), 4.08 ppm (dd, 2J(H,H)=11.1 and 3J(H,H)=
8.0 Hz, 1H; CH2); 13C NMR (50 MHz, CDCl3, 258C, TMS): d=169.6,
152.7, 136.6, 132.5, 132.4, 129.4, 129.1 (2C), 129.0, 127.8 (3C), 125.7 (2C),
75.1, 50.8 ppm; elemental analysis calcd (%) for C16H13NO3 (267.3): C
71.9, H 4.90, N 5.24; found: C 72.04, H 4.99, N 5.14.
N-[(1SR,2SR)-2-Hydroxy-1-propylpentyl]-(4-methylphenyl)sulfonamide
1
(17a): Yield: 40%, oil; H NMR (200 MHz, CDCl3, 258C, TMS): d=7.72
(d, 3J(H,H)=8.3 Hz, 2H; CH), 7.25 (d, 3J(H,H)=8.3 Hz, 2H; CH), 5.19
(d, 3J(H,H)=8.8 Hz, 1H; NH), 3.60 3.40 (m, 1H; CH), 3.13 (dtd,
3J(H,H)=8.8, 6.6, and 2.9 Hz, 1H; CH), 2.37 (s, 3H; CH3), 2.25 (brs,
1H; OH), 1.60 1.00 (m, 8H; CH2), 0.77 (t, 3J(H,H)=6.9 Hz, 3H; CH3),
0.71 ppm (t, 3J(H,H)=7.3 Hz, 3H; CH3); 13C NMR (50 MHz, CDCl3,
258C, TMS): d=143.0, 138.3, 129.4 (2C), 126.8 (2C), 72.0, 57.3, 36.0,
34.5, 21.3, 18.7 (2C), 13.8, 13.7 ppm; GC-MS: m/z (%): 256 (2) [MÀ43]+,
226 (100), 155 (55), 91 (61), 72 (24); elemental analysis calcd (%) for
C15H25NO3S (299.4): C 60.17, H 8.42, N 4.68; found: C 60.25, H 8.53, N
4.56.
Methyl [(5S)-3-benzoyl-2-oxo-1,3-oxazolidin-5-yl]acetate (21e): Yield:
82%; m.p. 79 828C; [a]D23 =+44.42 (c=5.15 in CHCl3); 1H NMR
(200 MHz, CDCl3, 258C, TMS): d=7.70 7.60 (m, 2H; CH), 7.60 7.50 (m,
3
1H; CH), 7.48 7.35 (m, 2H; CH), 5.00 (dddd, J(H,H)=8.2, 7.2, 6.7, and
6.1 Hz, 1H; CH), 4.29 (dd, 2J(H,H)=11.2 and 3J(H,H)=8.2 Hz, 1H;
CH2), 3.89 (dd, 2J(H,H)=11.2 and 3J(H,H)=7.2 Hz, 1H; CH2), 3.72 (s,
3H; OCH3), 2.92 (dd, 2J(H,H)=16.8 and 3J(H,H)=6.1 Hz, 1H; CH2),
2.78 ppm (dd, 2J(H,H)=16.8 and 3J(H,H)=6.7 Hz, 1H; CH2); 13C NMR
(50 MHz, CDCl3, 258C, TMS): d=169.4, 169.1, 152.2, 132.5, 132.2, 128.9
(2C), 127.7 (2C), 69.8, 52.1, 48.3, 38.3 ppm; IR: n˜ =2955, 1786, 1740,
N-{[(1RS,2RS)-1-(Benzyloxy)methyl]-2-hydroxypentyl}-(4-methylphenyl-
sulfonamide (17b): Yield: 48%, oil; 1H NMR (200 MHz, CDCl3, 258C,
TMS): d=7.75 (d, 3J(H,H)=8.3 Hz, 2H; CH), 7.40 7.18 (m, 7H; CH),
5.55 (d, 3J(H,H)=7.4 Hz, 1H; NH), 4.40 (m, 2H; CH2), 3.87 3.77 (m,
1H; CH), 3.51 (m, 2H; CH2), 3.37 3.24(m, 1H; CH), 2.96 (brs, 1H;
OH), 2.42 (s, 3H; CH3), 1.40 1.05 (m, 4H; CH2), 0.76 ppm (t, 3J(H,H)=
6.7 Hz, 3H; CH3); 13C NMR (50 MHz, CDCl3, 258C, TMS): d=143.1,
138.1, 137.3, 129.5 (2C), 128.4(2C), 127.8, 127.6 (2C), 126.9 (2C), 73.2,
71.8, 71.7, 55.7, 35.5, 21.4, 18.6, 13.8 ppm; elemental analysis calcd (%)
for C20H27NO4S (377.5): C 63.63, H 7.21, N 3.71; found: C 63.69, H 7.24,
N 3.73.
1680, 1329, 1209 cmÀ1
; elemental analysis calcd (%) for C13H13NO5
(263.3): C 59.31, H 4.98, N 5.32; found: C 59.30, H 4.96, N 5.30.
[(5R)-3-Benzoyl-2-oxo-1,3-oxazolidin-5-yl]acetonitrile (21 f): Yield: 74%;
m.p. 119 1228C; [a]2D3 =À24.68 (c=2.79 in MeOH); 1H NMR (200 MHz,
CDCl3, 258C, TMS): d=7.72 7.61 (m, 2H; CH), 7.60 7.50 (m, 1H; CH),
7.50 7.37 (m, 2H; CH), 5.05 4.88 (m, 1H; CH), 4.32 (dd, 2J(H,H)=11.3
and 3J(H,H)=8.4Hz, 1H; CH 2), 3.96 (dd, 2J(H,H)=11.3 and 3J(H,H)=
5.8 Hz, 1H; CH2), 3.05 ppm (m, 2H; CH2); 13C NMR (50 MHz, CDCl3,
258C, TMS): d=168.1, 150.9, 131.9, 131.3, 128.0 (2C), 126.9 (2C), 114.8,
68.0, 46.6, 22.3 ppm; IR: n˜ =2979, 2260, 1784, 1685, 1375, 1207,
1054cm À1; elemental analysis calcd (%) for C12H10N2O3 (230.2): C 62.60,
H 4.38, N 12.17; found: C 62.71, H 4.40, N 12.25.
Synthesis of the 4,5-disubstituted N-benzoyl-1,3-oxazolidin-2-ones 15:
The N-benzoyl carbamates 13 were treated with m-chloroperoxybenzoic
acid as described above in Method B. The nature of the substrates (see
Table 3) determined whether powdered potassium hydroxide (0.392 g,
7 mmol) or potassium carbonate (0. 692 g, 5 mmol) was then added to
the reaction mixture and stirring was continued until the selenone was
consumed (3 24h). The reaction mixture was then concentrated, poured
into water, and extracted with diethyl ether. The combined organic layers
were washed with brine, dried over sodium sulfate, filtered, and evapo-
rated. The reaction products were separated by column chromatography
on silica gel using a mixture of diethyl ether and light petroleum (8:2) as
eluent. The physical and spectral data for compound 15d have already
been reported in the literature.[14c] The physical and spectral data for the
new compounds are reported below.
(5R)-3-Benzoyl-5-[(1S)-1-(dibenzylamino)-2-phenylethyl]-1,3-oxazolidin-
2-one (21g): Yield: 79%; m.p. 45 488C; [a]2D2 =+10.27 (c=1.90 in
1
CHCl3); H NMR (200 MHz, CDCl3, 258C, TMS): d=7.54 7.00 (m, 20H;
CH), 4.67 4.52 (m, 1H; CH), 4.02 (dd, 2J(H,H)=11.2 and 3J(H,H)=
8.2 Hz, 1H; CH2), 3.68 (dd, 2J(H,H)=11.2 and 3J(H,H)=7.4Hz, 1H;
CH2), 3.60 (m, 4H; CH2), 3.17 2.93 ppm (m, 3H; CH and CH2);
13C NMR (50 MHz, CDCl3, 258C, TMS): d=169.3, 152.5, 139.4, 138.6
(2C), 132.7, 132.1, 129.5 (2C), 128.8 (3C), 128.7 (3C), 128.5 (3C), 128.4
(3C), 127.7 (2C), 127.3 (2C), 126.4, 74.6, 61.8, 54.7 (2C), 47.5, 32.5 ppm;
elemental analysis calcd (%) for C32H30N2O3 (490.6): C 78.34, H 6.16, N
5.71; found: C 78.36, H 6.14, N 5.70.
tert-Butyl (1S)-1-[(5S)-3-benzoyl-2-oxo-1,3-oxazolidin-5-yl]-2-cyclohexyl-
ethylcarbamate (21h): Major diastereoisomer; yield: 49%; m.p. 170
1738C; 1H NMR (200 MHz, CDCl3, 258C, TMS): d=7.70 7.32 (m, 5H;
CH), 4.70 4.50 (m, 2H; CH and CH2), 4.22 4.00 (m, 2H, CH), 3.95 (brs,
1H; NH), 1.90 0.70 (m, 13H; CH and CH2), 1.40 ppm (s, 9H, CH3);
13C NMR (50 MHz, CDCl3, 258C, TMS): d=169.3, 155.9, 152.0, 132.8,
132.3, 128.9 (2C), 127.8 (2C), 80.2, 76.0, 49.6, 46.0, 39.6, 34.1, 33.6, 32.5,
28.2 (3C), 26.3, 26.2, 26.0 ppm.
(4RS,5RS)-3-Benzoyl-4,5-dipropyl-1,3-oxazolidin-2-one (15a): Yield:
73%, oil; 1H NMR (200 MHz, CDCl3, 258C, TMS): d=7.72 7.39 (m,
5H; CH), 4.32 (dt, 3J(H,H)=7.3 and 4.8 Hz, 1H; CH), 4.29 (ddd,
3J(H,H)=8.6, 4.8, and 3.5 Hz, 1H; CH), 1.95 1.35 (m, 8H; CH2), 1.00 (t,
3J(H,H)=7.2 Hz, 3H; CH3), 0.99 ppm (t, 3J(H,H)=7.1 Hz, 3H; CH3);
13C NMR (50 MHz, CDCl3, 258C, TMS): d=169.9, 153.0, 133.4, 132.2,
128.9 (2C), 127.8 (2C), 79.1, 59.4, 37.0, 34.1, 18.0, 17.5, 13.8, 13.6 ppm;
GC-MS: m/z (%): 275 (16) [M]+, 105 (100), 77 (31); elemental analysis
calcd (%) for C16H21NO3 (275.3): C 69.79, H 7.69, N 5.09; found: C 69.81,
H 7.70, N 5.07.
tert-Butyl (1S)-1-[(5R)-3-benzoyl-2-oxo-1,3-oxazolidin-5-yl]-2-cyclohexyl-
ethylcarbamate (21h): Minor diastereoisomer; Yield: 7%; m.p. 152
1558C; 1H NMR (200 MHz, CDCl3, 258C, TMS): d=7.70 7.30 (m, 5H,
CH), 4.72 4.52 (m, 1H; CH), 4.50 (brs, 1H; NH), 4.27 3.81 (m, 3H; CH
and CH2), 1.92 0.70 (m, 13H; CH and CH2), 1.43 ppm (s, 9H; CH3);
13C NMR (50 MHz, CDCl3, 258C, TMS): d=169.6, 155.5, 152.6, 133.2,
132.4, 129.0 (2C), 127.9 (2C), 80.3, 76.0, 50.5, 45.7, 39.6, 34.1, 33.6, 32.1,
29.7, 28.3 (3C), 26.3, 26.2 ppm; elemental analysis of the mixture calcd
(%) for C23H32N2O5 (416.5): C 66.32, H 7.74, N 6.73; found: C 66.20, H
7.78, N 6.65.
(4RS,5RS)-3-Benzoyl-4-[(benzyloxy)methyl]-5-propyl-1,3-oxazolidin-2-
one (15b): Yield: 74%, oil; 1H NMR (200 MHz, CDCl3, 258C, TMS):
d=7.70 7.60 (m, 2H; CH), 7.60 7.48 (m, 1H; CH), 7.45 7.20 (m, 7H;
CH), 4.64 (dt, 3J(H,H)=7.7 and 4.9 Hz, 1H; CH), 4.58 (m, 2H; CH2),
4.40 (td, 3J(H,H)=4.9 and 2.6 Hz, 1H; CH), 3.91 (dd, 2J(H,H)=9.9 and
2
3
3J(H,H)=4.9 Hz, 1H; CH2), 3.69 (dd, J(H,H)=9.9 and J(H,H)=2.6 Hz,
1H; CH2), 1.80 1.38 (m, 4H; CH2), 0.97 ppm (t, 3J(H,H)=7.1 Hz, 3H;
CH3); 13C NMR (50 MHz, CDCl3, 258C, TMS): d=170.0, 152.9, 137.3,
133.2, 132.2, 128.9 (2C), 128.4(2C), 127.9 (2C), 127.7 (2C), 127.6, 76.9,
73.4, 67.1, 59.3, 36.6, 17.7, 13.6 ppm; GC-MS: m/z (%): 353 (1) [M]+, 24 6
(29), 105 (100), 77 (25); elemental analysis calcd (%) for C21H23NO4
(353.4): C 71.37, H 6.56, N 3.96; found: C 71.49, H 6.64, N 3.88.
Conversion of N-tosyl carbamate 12a and12b into
N-tosylamido
alcohols 17a and17b
MethodB : Solid m-chloroperoxybenzoic acid (0.688 g, 4mmol) was
added to a mixture of N-tosyl carbamate 12a or 12b (1 mmol) and pow-
dered potassium hydrogenphosphate (0.870 g, 5 mmol) in CH2Cl2
(15 mL) at 188C. The resultant mixture was stirred for 3 4h and was
then concentrated in vacuo. Aqueous sodium carbonate (10%) was
added and the mixture was extracted with diethyl ether. The combined
(4SR,5SR)-3-Benzoyl-4,5-bis[(benzyloxy)methyl]-1,3-oxazolidin-2-one
(15e): Yield: 80%, oil; 1H NMR (200 MHz, CDCl3, 258C, TMS): d=
7.60 7.16 (m, 15H; CH), 4.84 4.65 (m, 2H; CH), 4.55 4.31 (m, 4H;
1762
¹ 2004Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
Chem. Eur. J. 2004, 10, 1752 1764

Intramolecular Displacement of the Phenylselenonyl Group by Nitrogen Nucleophiles
1752 1764
CH2), 3.98 3.74ppm (m, 4H; CH 2); 13C NMR (50 MHz, CDCl3, 258C,
TMS): d=169.6, 152.9, 137.2, 137.1, 133.1, 132.1 (2C), 128.9 (2C), 128.6
(3C), 128.4 (3C), 127.9 (2C), 127.8, 127.7, 127.6, 75.3, 73.6, 73.4, 67.4,
65.1, 56.3 ppm; elemental analysis calcd (%) for C26H25NO5 (431.5): C
72.37, H 5.84, N 3.25; found: C 72.39, H 5.82, N 3.27.
Reductive hydrolysis of 25a: LiAlH4 (1m solution, 2 mL) was added
dropwise to a solution of 25a (0.207 g, 1 mmol) in dry THF (10 mL) at
08C. The mixture was stirred at room temperature for about 1 h and was
then refluxed for 1 h. Methanol was added to the cooled reaction mix-
ture, and this was then dried over sodium sulfate and concentrated at re-
duced pressure. The residue was purified by chromatography on silica gel
using a mixture of CH2Cl2 and methanol (6:4) as eluent to afford pure
26.
3-Benzoyl-4-[(benzyloxy)methyl]-5,5-dimethyl-1,3-oxazolidin-2-one
(15 f): Yield: 44%, oil; 1H NMR (200 MHz, CDCl3, 258C, TMS): d=
7.67 7.46 (m, 2H; CH), 7.45 7.21 (m, 8H; CH), 4.52 (s, 2H; CH2), 4.33
(dd, 3J(H,H)=5.6 and 2.7 Hz, 1H; CH), 3.89 (dd, 2J(H,H)=10.1 and
3J(H,H)=5.6 Hz, 1H; CH2), 3.80 (dd, 2J(H,H)=10.1 and 3J(H,H)=
2.7 Hz, 1H; CH2), 1.56 (s, 3H; CH3), 1.54ppm (s, 3H; CH 3); 13C NMR
(50 MHz, CDCl3, 258C, TMS): d=170.1, 152.5, 137.3, 133.3, 132.3 (2C),
128.8 (2C), 128.4, 127.8 (2C), 127.6 (2C), 126.8, 81.4, 73.4, 65.7, 62.5,
28.5, 21.3 ppm; elemental analysis calcd (%) for C20H21NO4 (339.4): C
70.78, H 6.24, N 4.13; found: C 70.80, H 6.22, N 4.12.
(2R)-1-(Benzyloxy)-3-(methylamino)propan-2-ol (26): Yield: 84%, oil;
[a]2D5 =+0.45 (c=8.00 in CHCl3); 1H NMR (200 MHz, CDCl3, 258C,
TMS): d=7.37 7.24(m, 5H; CH), .543 (s, 2H; CH
2), 3.92 (ddt,
3J(H,H)=7.2, 5.8, and 4.7 Hz, 1H; CH), 3.47 (m, 2H; CH2), 3.33 (s, 1H;
OH), 3.30 (s, 1H; NH), 2.64(m, 2H; CH 2), 2.40 ppm (s, 3H; CH3);
13C NMR (50 MHz, CDCl3, 258C, TMS): d=137.9, 128.3 (2C), 127.6
(3C), 73.3, 72.9, 68.3, 54.1, 36.0 ppm; elemental analysis calcd (%) for
C11H17NO2 (195.3): C 67.66, H 8.78, N 7.17; found: C 67.78, H 8.90, N
7.19.
Synthesis of the 1,3-oxazolidinone 15g: Potassium hydrogenphosphate
(0.870 g, 5 mmol) and m-chloroperoxybenzoic acid (0.688 g, 4mmol)
were added to a solution of N-benzoyl carbamate 13g (1 mmol) in iso-
propyl alcohol (20 mL) at room temperature. After about 2 h the mixture
was concentrated in vacuo, diluted with water, and extracted with diethyl
ether. The combined organic layers were washed with brine, dried over
sodium sulfate, filtered, and evaporated. Product 15g was obtained in
pure form after column chromatography on silica gel using a mixture of
diethyl ether and light petroleum (2:8) as eluent,.
Hydrolysis of 25a: Oxazolidin-2-one 25a (0.207 g, 1 mmol) was refluxed
with a 10% sodium hydroxide solution (10 mL), and was then allowed to
cool to room temperature. The solution was extracted with diethyl ether,
the organic phase was washed with brine, and pure compound 27[41] was
obtained after evaporation of the solvent.
(2R)-1-Amino-3-(benzyloxy)propan-2-ol (27): Yield: 94%, oil; [a]2D7 =+
6.25 (c=2.76 in CHCl3); 1H NMR (200 MHz, CDCl3, 258C, TMS): d=
7.35 7.20 (m, 5H; CH), 4.50 (m, 2H; CH2), 3.79 3.65 (m, 1H; CH), 3.44
(m, 2H; CH2), 2.80 (brs, 3H; NH2 and OH), 2.80 2.60 ppm (m, 2H;
CH2); 13C NMR (50 MHz, CDCl3, 258C, TMS): d=137.9, 128.3 (2C),
127.6 (3C), 73.2, 72.5, 70.8, 44.3 ppm; elemental analysis calcd (%) for
C10H15NO2 (181.2): C 66.27, H 8.34, N 7.73; found: C 66.29, H 8.35, N
7.75.
[(4RS,5RS)-3-Benzoyl-5-methyl-2-oxo-1,3-oxazolidin-4-yl]acetonitrile
(15g): Yield: 81%; m.p. 128 1318C; 1H NMR (200 MHz, CDCl3, 258C,
TMS): d=7.75 7.35 (m, 5H; CH), 4.60 (dq, 3J(H,H)=6.5 and 6.3 Hz,
1H; CH), 6.32 (td, 3J(H,H)=6.5 and 3.0 Hz, 1H; CH), 3.08 (dd,
2J(H,H)=17.3 and 3J(H,H)=6.5 Hz, 1H; CH2), 2.87 (dd, 2J(H,H)=17.3
and 3J(H,H)=3.0 Hz, 1H; CH2), 1.51 ppm (d, 3J(H,H)=6.3 Hz, 3H;
CH3); 13C NMR (50 MHz, CDCl3, 258C, TMS): d=170.0, 151.7, 133.0,
132.3, 129.2 (2C), 127.9 (2C), 115.1, 74.7, 57.3, 19.9, 19.4 ppm; GC-MS:
m/z (%): 244 (13) [MÀ1]+, 105 (100), 77 (26); elemental analysis calcd
(%) for C13H12N2O3 (244.2): C 63.93, H 5.30, N 11.47; found: C 63.85, H
5.42, N 11.49.
Acknowledgements
Financial support from MIUR, the National Project ™Stereoselezione in
Sintesi Organica Metodologie ed Applicazioni∫, the FIRB Project ™Pro-
gettazione, Preparazione e Valutazione Biologica e Farmacologica di
Nuove Molecole Organiche Quali Potenziali Farmaci Innovativi∫, Con-
sorzio CINMPIS, and the University of Perugia, Progetti di Ateneo, is
gratefully acknowledged.
Ring cleavage of the N-tosyl-1,3-oxazolidin-2-one 23a:
A catalytic
amount of cesium carbonate (0.03 g) was added to a solution of N-tosyl-
1,3-oxazolidin-2-one 23a (1 mmol) in methanol (10 mL). The reaction
was stirred at room temperature for 12 h and was then concentrated in
vacuo. The residue was purified by chromatography on
a silica-gel
column using a mixture of light petroleum and ethyl acetate (6:4) as
eluent. The physical and spectral data for compound 24a are reported
below.
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N-[(2R)-3-(Benzyloxy)-2-hydroxypropyl]-(4-methylphenyl)sulfonamide
(24a): Yield: 72%; m.p. 68 708C; [a]2D8 =+8.35 (c=2.00 in CH2Cl2);
1H NMR (200 MHz, CDCl3, 258C, TMS): d=7.70 (d, 3J(H,H)=8.3 Hz,
2H; CH), 7.40 7.14 (m, 5H; CH), 7.25 (d, 3J(H,H)=8.3 Hz, 2H; CH),
5.42 (dd, 3J(H,H)=7.1 and 5.6 Hz, 1H; NH), 4.46 (s, 2H; CH2), 3.86
(dddd, 3J(H,H)=6.8, 5.9, 4.7, and 3.9 Hz, 1H; CH), 3.45 (dd, 2J(H,H)=
9.9 and 3J(H,H)=4.7 Hz, 1H; CH2), 3.39 (dd, 2J(H,H)=9.9 and
2
3J(H,H)=5.9 Hz, 1H; CH2), 3.10 (brs, 1H; OH), 3.08 (dd, J(H,H)=13.0
and 3J(H,H)=3.9 Hz, 1H; CH2), 2.91 (dd, 2J(H,H)=13.0 and 3J(H,H)=
6.8 Hz, 1H; CH2), 2.40 ppm (s, 3H; CH3); 13C NMR (50 MHz, CDCl3,
258C, TMS): d=143.4, 137.5, 136.6, 129.7 (2C), 128.4 (2C), 127.8 (2C),
127.7, 127.0 (2C), 73.4, 71.6, 68.9, 45.7, 21.4 ppm; GC-MS: m/z (%): 274
(1) [MÀ61]+, 184(23), 155 (42), 91 (100), 74(16); elemental analysis
calcd (%) for C17H21NO4S (335.4): C 60.87, H 6.31, N 4.18; found: C
60.85, H 6.33, N 4.15.
Removal of the benzoyl group from N-benzoyl-1,3-oxazolidin-2-ones 21a
and21b : N-benzoyl-1,3-oxazolidin-2-one 21a or 21b (1 mmol) and lithi-
um hydroxide monohydrate (0.084g, 2 mmol) were stirred at room tem-
perature in a mixture of THF and water (10 mL, 3:1) for 4h. The reac-
tion mixture was then concentrated and CH2Cl2 (20 mL) was added. The
solution was dried over sodium sulfate and evaporated, and the residue
was purified by chromatography using diethyl ether as eluent. The physi-
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1763
Chem. Eur. J. 2004, 10, 1752 1764
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¹ 2004Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

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Received: September 1, 2003
Revised: December 1, 2003 [F5497]
1764
¹ 2004Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
Chem. Eur. J. 2004, 10, 1752 1764