Cis- and trans-N-(Benzylsulfinyl)hexahydrobenzoxazolidin-2-ones as novel chiral sulfinyl transfer reagents

Article abstract of DOI:10.1016/j.tet.2004.10.018

The synthesis of N-benzylsulfinyl derivatives 5a-d from both pairs of enantiomeric hexahydrobenzoxazolidin-2-ones 4a-d is reported. The use of 5a-d as effective chiral sulfinylating reagents in the preparation of enantiopure sulfoxides (e.e.>98%) is also reported. Graphical Abstract

Full text of DOI:10.1016/j.tet.2004.10.018

Tetrahedron 60 (2004) 12147–12152
cis- and trans-N-(Benzylsulfinyl)hexahydrobenzoxazolidin-2-ones
as novel chiral sulfinyl transfer reagents
a,b
a
c
Angel Clara-Sosa,a,b Lydia Perez, Mario Sanchez, Roberto Melgar-Fernandez,
´
´
´
*
Eusebio Juaristi,c, Leticia Quintero and Cecilia Anaya de Parrodi
b,
a,
*
*
a
´ ´ ´
Depto. de Quımica y Biologıa, Universidad de las Americas-Puebla, Santa Catarina Martir, 72820 Cholula, Mexico
´
´ ´ ´
Centro de Investigacion de la Fac. de Ciencias Quımicas, Universidad Autonoma de Puebla, 72570 Puebla, Mexico
b
c
´ ´ ´ ´
Depto. de Quımica, Centro de Investigacion y de Estudios Avanzados del Instituto Politecnico Nacional, 07000 Mexico, D. F., Mexico
Received 31 August 2004; revised 6 October 2004; accepted 7 October 2004
Available online 19 October 2004
Abstract—The synthesis of N-benzylsulfinyl derivatives 5a–d from both pairs of enantiomeric hexahydrobenzoxazolidin-2-ones 4a–d is
reported. The use of 5a–d as effective chiral sulfinylating reagents in the preparation of enantiopure sulfoxides (e.e.O98%) is also reported.
q 2004 Elsevier Ltd. All rights reserved.
1. Introduction
The interest in tricoordinated sulfur compounds in general,
and sulfoxides in particular, has increased exponentially in
the past two decades as consequence of the enormous
potential of the chiral sulfinyl group as auxiliary in
asymmetric synthesis.1 Accordingly, the search for efficient
and general methods in the preparation of chiral enantiopure
sulfoxides continues to be a matter of great importance.
(1)
While the Andersen method (Eq. 1) is restricted to the
synthesis of aryl-alkyl or diaryl sulfoxides, Evans et al.6
reported in 1992 a new class of chiral sulfinyl transfer
reagents, N-sulfinyloxazolidinones 2 and 3 (RZalkyl, aryl;
Scheme 1). These sulfinylating agents were shown to react
with Grignard reagents with inversion of configuration at
the sulfur center to afford the derived chiral sulfoxides in
high yields and enantioselectivities6 (Scheme 1).
Salient methods for the preparation of non-racemic chiral
sulfoxides can be divided into three classes: (1) kinetic
resolution (either chemical2a or enzymatic2b,c) of racemic
sulfoxides, (2) asymmetric oxidation of prochiral sulfides;
especiallywithSharpless reagent,3a with chiral oxaziridines,3b
or in the presence of Noyori’s BINOL ligand,3c and (3)
stereospecific sufinylation of organometallic nucleophiles
with chiral sulfinyl transfer reagents.4–6
Special mention deserves the early (and still frequently
used) Andersen method,4a,bwhich utilizes (S)-menthyl
p-toluensulfinate (1) in the transfer of a chiral p-toluensulfinyl
moiety to various types of nucleophilic organometallics
with very high enantioselectivity (Eq. 1).
Keywords: Oxazolidinones; Sulfoxides; Sulfinyl transfer; Diastereoselec-
tive reactions; Enantioselective synthesis.
* Corresponding authors. Tel.: C52 55 50613722; fax: C52 55 57477113;
e-mail addresses: juaristi@relaq.mx; lquinter@siu.buap.mx;
anaya@mail.udlap.mx
Scheme 1.
0040–4020/$ - see front matter q 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2004.10.018

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A. Clara-Sosa et al. / Tetrahedron 60 (2004) 12147–12152
Table 2. Oxidation of N-(thiobenzyl)oxazolidinones 6a and 6b with m-
CPBA and NaIO4
Recently, we reported a convenient procedure for the
preparation of both pairs of enantiomeric hexahydroben-
zoxazolidin-2-ones 4a–d from inexpensive cyclohexene
oxide and (S)-a-phenylethylamine.7,8 We now report the use
of N-benzylsulfinyl derivatives 5a–d as effective chiral
sulfinylating reagents in the preparation of enantiopure
sulfoxides (Scheme 2).
Entry
[Ox] (equiv)
Time
(h)
Temperature
(8C)
Yield
(%)
Product
ratioa 5:7
1
2
3
4
5
m-CPBA (1.5)
m-CPBA (1.0)
m-CPBA (1.0)
NalO4 (2.0)
24
3
1.5
48
42
K20
K25
10
25
25
66
40
73
70
92
50:50
75:25
92:8
98:2
98:2
NalO4 (3.0)
a Determined by 1H NMR spectroscopy in the crude product.
1.0 equiv of m-CPBA (instead of 1.5 equiv; entries 2 and 3
in Table 2). Clearly, the use of a single equivalent of
m-CPBA oxidant minimizes formation of the N-sulfonyl
derivative 7. Furthermore, faster reaction at 10 8C instead of
K25 8C provided a better 5:7 ratio. Nevertheless, best
results were observed with NaIO4 as oxidant10 (3.0 equiv,
entry 5 in Table 2).
Scheme 2. Conditions: i, n-BuLi, THF, 0 8C, 30 min. ii, BnSSO2Bn, THF,
K78 8C. iii, NaIO4, MeOH/H2O, 30–42 h, 0 8C. iv, Fractional recrystalli-
zation or preparative TLC.
Once the optimum condition for the oxidation of N-sulfides
6 had been established, we proceeded to determine the
diastereomeric ratios in the mixtures of sulfoxides 5. The
reaction of N-(thiobenzyl)hexahydrobenzoxazolidinone
trans-(4S,5S)-6a in methanol with an aqueous solution of
NaIO4 at 0 8C afforded a 6:1 mixture of the expected
diastereoisomeric N-sulfoxides. The major product was
purified by fractional crystallization from methylene
chloride–petroleum ether (5:95) (entry 1 in Table 3).
2. Results and discussion
2.1. Synthesis of N-(benzylsulfinyl)oxazolidinones 5a–d
The reaction of the lithiated oxazolidinones 4-Li (obtained
by treatment of 4a–d with n-butyllithium at 0 8C)9 with
benzylthiosulfonate ester PhCH2SSO2CH2Ph proceeded in
excellent yields to give crystalline products 6a–d (Table 1).
As expected, oxidation of N-sulfide trans-(4R,5R)-6b under
the same conditions gave the enantiomeric sulfoxides in a
similar 6:1 ratio (entry 2 in Table 3).
Oxidation of N-sulfides 6a–b to the desired N-sulfoxides
5a–b was first attempted with m-chloroperoxybenzoic acid
(m-CPBA), according to the conditions reported by Evans et
al.6 for the preparation of N-sulfinyloxazolidinones 3.
However, a ca. 1:1 mixture of diastereoisomeric sulfoxides
5 and N-sulfonyloxazolidinone 7 was produced under this
condition (entry 1 in Table 2). Improved ratios of the
N-sulfinyloxazolidinones 5 were obtained by the use of
In contrast with the high diastereoselectivity observed in the
oxidation of trans-N-(thiobenzyl)oxazolidinones 6a and 6b,
the oxidation of cis congeners 6c and 6d proceeded with
low, 1.6:1, diastereoselectivity (entries 3 and 4 in Table 3).
Nevertheless, the major products 5c and 5d were easily
purified by preparative TLC (petroleum ether–ethyl acetate,
2:1, eluent).
Table 1. N-Thiobenzylation of hexahydrobenzoxazolidin-2-ones 4a–d with
benzylthiosulfonate ester
The absolute configuration at sulfur in sulfoxide (4S,5S,RS)-
5a was assigned by X-ray diffraction analysis from a
suitable crystal of the major product from oxidation of
sulfide (4S,5S)-6a (Fig. 1). Since the major diastereo-
isomeric sulfoxide product derived from enantiomeric
(4R,5R)-6b presented same physical and spectroscopic
properties but opposite sign of the optical rotation, its
absolute configuration was assigned as (4R,5R,SS)-5b.
Oxazolidinone
Product
Yielda (%)
Mp (8C)
[a]2D0b
(4S,5S)-4a
(4R,5R)-4b
(4S,5R)-4c
(4R,5S)-4d
6a
6b
6c
6d
91
92
90
90
102–103
104–105
50–51
K100.1
C98.1
K128.1
C131.1
The absolute configuration at the stereogenic sulfur in
sulfoxide (4R,5S,RS)-5d was similarly obtained by X-ray
diffraction analysis from a suitable crystal (Fig. 2). Again,
the major product from oxidation of (4S,5R)-6c was safely
assigned as (4S,5R,SS)-5c since it exhibited identical
50–51
a After purification by column chromatography.
b In CHCl3, concentrations in Section 3.

A. Clara-Sosa et al. / Tetrahedron 60 (2004) 12147–12152
12149
Table 3. Diastereoselectivity of the oxidation of N-(thiobenzyl)hexahydrobenzoxazolidinones 6 with NaIO4
Major producta
d.r. (RS:SS)
Yieldb (%)
Mpc (8C)
[a]D
d
Entry
Substrate
1
2
3
4
(4S,5S)-6a
(4R,5R)-6b
(4S,5R)-6c
(4R,5S)-6d
(4S,5S,RS)-5a
(4R,5R,SS)-5b
(4S,5R,SS)-5c
(4R,5S,RS)-5d
6:1
1:6
1:1.6
1.6:1
90(50)
90(55)
80(46)
80(43)
105–106
102–103
98–99
K30.6
C32.0
C185.3
K184.1
96–97
a The configuration at sulfur was assigned by X-ray diffraction crystallography.
b Of the diastereoisomeric mixture (of the purified major isomer).
c Of the major product.
d In CHCl3 concentrations in Section 3.
Figure 1. Structure and solid-state conformation of (4S,5S,RS)-N-(benzylsulfinyl)hexahydrobenzoxazolidin-2-one 5a.11
Figure 2. Structure and solid state conformation of (4R,5S,RS)-N-(benzylsulfinyl)hexahydrobenzoxazolidin-2-one 5d.11

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A. Clara-Sosa et al. / Tetrahedron 60 (2004) 12147–12152
melting points and NMR spectra, but an opposite sign in its
optical rotation, upon comparison with (4R,5S,RS)-5d.
This observation is in line with the low selectivity found in
the oxidation reaction (entries 3 and 4 in Table 3).
Finally, the calculated electrostatic potential for the lowest-
energy conformation of (4R,5S)-6d [DFT calculations12,13
at the B3LYP/6-31G(d,p) level] show similar electron
density at both diastereotopic14 sulfur lone pairs, which is in
line with the observed comparable ratios of diastereo-
isomeric ratios of N-sulfoxide derivatives (entries 3 and 4 in
Table 3).
2.2. Molecular modeling of the preferred conformations
adopted by N-sulfides 6
The contrasting behavior of cis- and trans-N-(thiobenzyl)-
hexahydrobenzoxazolidin-2-ones 6 can be understood with
consideration of their most likely reactive conformations
during oxidation, as predicted by HF/6-31G(d,p) ab initio
calculations.
2.3. Enantioselective chiral sulfinyl transfer reactions
Indeed, the structure of lowest energy for N-sulfide 6b
(Fig. 3) clearly shows that steric hindrance should inhibit
approach by the oxidant agent on the pro-(R) sulfur lone
pair. As a consequence, the preferred pathway for oxidation
involves the pro-(S) lone pair at sulfur, leading to formation
of S-configurated N-sulfoxide (4R,5R,SS)-5b as experimen-
tally observed (entry 2 in Table 3).
To determine the ability of the N-benzylsulfinyl derivatives
5a–d as effective chiral sulfinylating reagents in the
preparation of enantiopure sulfoxides, the reaction with
the Grignard reagent methylmagnesium bromide was
carried out. It is known6 that transfer of the sulfinyl group
proceeds with inversion of configuration at sulfur.
To a solution of N-benzylsulfinyl derivatives 5a–d in THF at
K78 8C was added MeMgBr affording the chiral benzyl
methyl sulfoxides 8a,b. These sulfoxides and the recovered
chiral auxiliary were purified by preparative TLC.
Sulfoxides 8a,b were obtained as white solids in 70–75%
yield (Table 4). The assignment of configuration of the
known benzyl methyl sulfoxides was achieved by chiral
HPLC and optical rotation, respectively. The enantioselec-
tivity measured was higher than 98% (Table 4) confirming
the potential of N-sulfinyl derivatives 5 as effective
sulfinylating agents in the preparation of enantiopure
sulfoxides.
Table 4. N-Benzylsulfinyl derivatives 5a–d as effective chiral sulfinylating
reagents in the preparation of enantiopure sulfoxides 8a,b
Figure 3. Lowest-energy structure calculated at HF/6-31G(d,p) ab initio
level for (4R,5R)-6b.
Furthermore, the calculated electrostatic potential for
the lowest-energy conformation of (4R,5R)-6b [DFT
calculations12,13 at the B3LYP/6-31G(d,p) level] shows
increased electron density at the sulfur pro-(S) lone pair,
which is in line with the experimentally observed SS major
sulfoxide product.
a
Entry
Substrate
Yield
(%)
[a]D
Config.b
e.e.
(%)c
Along similar lines of thought, the optimized [HF/6-31G(d,p)
level] structure for cis-N-(thiobenzyl)hexahydrobenzoxa-
zolidin-2-one (4R,5S)-6d (Fig. 4) shows that both lone pairs
at sulfur are accessible for approach by the oxidizing agent.
1
2
3
4
(4S,5S,RS)-5a
(4R,5R,SS)-5b
(4S,5R,SS)-5c
(4R,5S,RS)-5d
70
70
75
75
C51.1 (c 1.1)
K49.1 (c 0.9)
K49.3 (c 1.0)
C50.1 (c 0.9)
(RS)-8a
(SS)-8b
(SS)-8b
(RS)-8a
O98
O98
O98
O99
a In CHCl3.
b Assigned by comparison with the literature [a]DZK55.0 (c 0.9, CHCl3)
for (SS)-benzyl methyl sulfoxide.6,15
c Determined by HPLC.
3. Experimental
3.1. General methods
All manipulations of organometallic compounds were
carried out under an inert argon atmosphere. NMR spectra
were obtained on a Jeol 400 MHz Fourier transform
spectrometer. H and 13C NMR spectra were referenced to
tetramethylsilane.
1
Figure 4. Lowest-energy structure calculated at the HF/6-31G(d,p) ab initio
level for (4R,5S)-6d.

A. Clara-Sosa et al. / Tetrahedron 60 (2004) 12147–12152
12151
3.2. General procedure for the preparation of trans- and
cis-N-(thiobenzyl)hexahydrobenzoxazolidin-2-one, 6a–d
pressure. The aqueous phase was extracted with 3!25 mL
portions of dichloromethane, and the combined organic
phase was dried with sodium sulfate. The solvent was
removed under reduced pressure. The solid obtained from
6a,b (0.30 g) was purified by fractional recrystallization
from dichloromethane–petroleum ether (95:5) to yield the
major diastereoisomers 5a,b as white crystals. The solid
obtained from 6c,d (0.27 g) was purified by preparative
TLC on silica gel (hexanes–EtOAc, 67:33, as eluent) to
yield the major diastereoisomer 5c,d as white crystals.
To a solution of hexahydrobenzoxazolidin-2-ones 4a–d7
(0.2 g, 1.42 mmol) in THF (10 mL) was slowly added at
0 8C n-BuLi (0.98 mL, 1.56 mmol, 1.6 M in hexanes). The
resulting mixture was stirred for 30 min at 0 8C, after which
was cooled at K78 8C. The lithiated oxazolidinones 4-Li
were treated with commercially available (S)-benzyl
phenyl-methanethiosulfonate (0.48 g, 1.70 mmol) in THF
(2 mL). The resulting solution was stirred for 3 h, allowed to
warm to rt, quenched with saturated aqueous NH4Cl,
extracted with 3!25 mL portions of dichloromethane,
and the combined organic phases dried with sodium sulfate.
The solvent was then removed under reduced pressure. The
pale yellow solid obtained (0.36 g) was purified by column
chromatography on silica gel (petroleum ether–EtOAc,
50:50, as eluent) to yield 6a–d.
3.3.1. (4S,5S,RS)-trans-N-(Benzylsulfinyl)hexahydroben-
zoxazolidin-2-one, 5a. Mp 105–106 8C; 0.17 g (50% yield),
[a]2D0ZK30.6 (c 1.0, CHCl3); 1H NMR (CDCl3, 400 MHz)
dZ1.3–1.6 (m, 8H), 1.8–2.0 (m, 4H), 2.23 (m, 1H), 2.43 (m,
1H), 3.55 (dt, 1H, 3JZ3.6, 11.6 Hz), 3.96 (dt, 1H, 3JZ3.6,
11.2 Hz), 4.28 (dd, 2H, 2JZ13.0 Hz), 7.2–7.4 (m, 5H);
13C{1H} NMR (CDCl3, 100 MHz) dZ23.3, 23.7, 28.7,
29.4, 61.0, 62.0, 81.8, 128.9, 129.9, 130.2, 158.0; IR (film)
3061, 2962, 2922, 2858, 1755, 1732, 1454, 1392, 1302,
1217, 1163, 1136, 1099, 1032, 762, 698 cmK1; HRMS-
ESCm/z found 302.0828 [(MCNa)C; calcd 302.0827 for
C14H17NO3SCNaC].
3.2.1. trans-(4S,5S)-N-(Thiobenzyl)hexahydrobenzoxa-
zolidinone 6a. Mp 102–103 8C; 0.34 g (91% yield),
[a]2D0ZK100.1 (c 1.0, CHCl3); 1H NMR (CDCl3,
400 MHz) dZ0.90 (m, 2H), 1.30 (m, 2H), 1.75 (m, 3H),
2.09 (m, 1H), 2.48 (td, 3JZ3.8, 11.2 Hz, 1H), 3.61 (td, 3JZ
3
3
3.8, 11.2 Hz, 1H), 3.81 (d, JZ12.8 Hz, 1H), 4.19 (d, JZ
12.8 Hz, 1H), 7.32 (m, 5H); 13C{1H} NMR (CDCl3,
100 MHz) dZ23.3, 23.8, 27.5, 28.5, 41.5, 66.2, 82.4,
127.6, 128.6, 129.5, 136.3, 159.5; IR (film) 3865, 3741,
3618, 3564, 2993, 2361, 1767, 1651, 1512, 1458, 1381,
1242, 1057 cmK1; C14H17NO2S (263.36) calcd: 63.79% C,
6.45% H, 5.31% N; found: 63.63% C, 6.51% H, 5.34% N.
3.3.2. (4R,5R,SS)-trans-N-(Benzylsulfinyl)hexahydroben-
zoxazolidin-2-one, 5b. Mp 102–103 8C; 0.18 g (55% yield),
[a]D20ZC32.0 (c 0.9, CHCl3). H and 13C NMR spectra
1
identical with those for 5a.
3.3.3. (4S,5R,SS)-cis-N-(Benzylsulfinyl)hexahydroben-
zoxazolidin-2-one, 5c. Mp 98–99 8C; 0.15 g (46% yield),
[a]2D0ZC185.3 (c 1.0, CHCl3); 1H NMR (CDCl3,
400 MHz) dZ0.92 (m, 1H), 1.10 (m, 1H), 1.34 (m, 2H),
1.55 (m, 2H), 1.75 (m, 2H), 4.14 (c, 1H, 3JZ12.0, 6.4 Hz),
3.2.2. trans-(4R,5R)-N-(Thiobenzyl)hexahydrobenzoxa-
zolidinone 6b. Mp 104–105 8C; 0.35 g (92% yield),
1
[a]D20ZC98.1 (c 0.9, CHCl3). H and 13C NMR spectra
identical with those for 6a.
2
3
4.34 (d, 1H, JZ12.8 Hz), 4.44 (c, 1H, JZ11.6, 5.6 Hz),
2
4.90 (d, 1H, JZ12.8 Hz), 7.38 (m, 5H); 13C{1H} NMR
3.2.3. cis-(4R,5S)-N-(Thiobenzyl)hexahydrobenzoxazoli-
dinone 6d. Mp 50–51 8C; 0.34 g (90% yield),
[a]2D0ZC131.1 (c 1.0, CHCl3); 1H NMR (CDCl3,
400 MHz) dZ1.29 (m, 2H), 1.45 (m, 2H), 1.65 (m, 4H),
(CDCl3, 100 MHz) dZ19.1, 19.3, 26.9, 27.5, 55.5, 59.0,
75.0, 128.4, 128.7, 128.8, 129.8, 154.8; IR (film) 1755,
1217 cmK1; HRMS-ESCm/z found 302.0841 [(MCNa)C;
calcd 302.0827 for C14H17NO3SCNaC].
3
3
3.10 (c, JZ5.6, 12.1 Hz, 1H), 3.80 (d, JZ12.8 Hz, 1H),
3
3
4.15 (d, JZ12.4 Hz, 1H), 4.32 (c, JZ5.8, 12.1 Hz, 1H),
7.30 (m, 5H); 13C{1H} NMR (CDCl3, 100 MHz) dZ19.1,
19.6, 25.7, 26.8, 41.8, 58.2, 74.4, 127.6, 128.6, 129.4, 135.6,
159.1; IR (film) 3865, 3741, 3618, 2993, 1759, 1512, 1381,
1242, 1057 cmK1; HRMS-ESCm/z found 264.1068
[(MCH)C; calcd 264.1058 for C14H17NO2SCHC].
3.3.4. (4R,5S,RS)-cis-N-(Benzylsulfinyl)hexahydroben-
zoxazolidin-2-one, 5d. Mp 96–97 8C; 0.14 g (43% yield),
1
[a]D20ZK184.1 (c 1.0, CHCl3). H and 13C NMR spectra
identical with those for 5c.
3.4. Preparation of (SS) and (RS)-benzyl methyl
sulfoxides 8a,b
3.2.4. cis-(4S,5R)-N-(Thiobenzyl)hexahydrobenzoxazoli-
dinone 6c. Mp 50–51 8C; 0.34 g (90% yield),
1
[a]D20ZK128.1 (c 1.1, CHCl3). H and 13C NMR spectra
identical with those for 6d.
To a previously cooled solution at K78 8C of N-(benzyl-
sulfinyl) hexahydrobenzoxazolidin-2-one 5a–d (0.04 g,
0.143 mmol) in THF (10 mL) was added dropwise MeMgBr
(1.4 M, in toluene–THF 75:25, 0.20 mL, 0.28 mmol). The
reaction was quenched with saturated aqueous NH4Cl
(1 mL). The solvent was removed under reduced pressure,
extracted with 3!25 mL portions of ethyl acetate, and
the combined organic phase was dried with sodium sulfate.
The solvent was then removed under reduced pressure. The
product and the chiral auxiliary were purified by preparative
TLC (petroleum ether–EtOAc, 33:67, as eluent). The
recovered chiral auxiliary afforded 18 mg (90%).
3.3. General procedure for the preparation of trans- and
cis-N-(benzylsulfinyl)hexahydrobenzoxazolidin-2-one,
5a–d
To a solution of N-(thiobenzyl)hexahydrobenzoxazolidin-2-
one 6a–d (0.31 g, 1.2 mmol) in MeOH (12 mL) was added
NaIO4 (0.77 g, 3.7 mmol) in H2O (6 mL). The reaction
mixture was stirred for 42 h at rt. The white solid formed
was filtered, and the MeOH was removed under reduced

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A. Clara-Sosa et al. / Tetrahedron 60 (2004) 12147–12152
5. (a) Hiroi, K.; Sato, S.; Kitayama, R. Chem. Pharm. Bull. 1983,
10, 3471. (b) Rebiere, F.; Samuel, O.; Ricard, L.; Kagan, H. B.
J. Org. Chem. 1991, 56, 5991. (c) Benson, S. C.; Snyder, J. K.
Tetrahedron Lett. 1991, 32, 5885. (d) Wills, M.; Butlin, R. J.;
Linneya, I. D.; Gibson, R. W. J. Chem. Soc., Perkin Trans. 1
3.5. Conditions for the analysis and assignment of
configuration of the chiral sulfoxides 8a,b
Chiral HPLC: Chiralcel OD column 254 nm UV detector,
diameter 0.46 cm, length 25 cm, 1.0 mL/min. Hexanes–i-
PrOH, 90:10.
´
1991, 3383. (e) Garcıa-Ruano, J. L.; Alonso, R.; Zarzuelo,
M. M.; Noheda, P. Tetrahedron: Asymmetry 1995, 6, 1133.
(f) Oppolzer, W.; Froelich, O.; Wiaux-Zamar, C.; Bernardi-
nelli, G. Tetrahedron Lett. 1997, 38, 2825. (g) Liu, G.; Cogan,
D. A.; Ellman, J. A. J. Am. Chem. Soc. 1997, 119, 9913.
Specific rotations of the chiral sulfoxides were measured
and compared with those reported on the literature to assign
the configuration.6,15
´
(h) Garcıa-Ruano, J. L.; Alemparte, C.; Aranda, M. T.;
3.5.1. (RS)-Benzyl methyl sulfoxide 8a. The sulfoxide was
obtained as a white solid (0.016 g, 75.0% yield); e.e.O98%;
tRZ35.4 min, [a]2D0ZC50.1 (c 1.0, CHCl3).
Zarzuelo, M. M. Org. Lett. 2003, 5, 75.
6. Evans, D. A.; Faul, M. M.; Colombo, L.; Bisaha, J. J.; Clardy,
J.; Cherry, D. J. Am. Chem. Soc. 1992, 114, 5977.
7. (a) Anaya de Parrodi, C.; Juaristi, E.; Quintero, L.; Clara-Sosa,
A. Tetrahedron: Asymmetry 1997, 8, 1075. (b) Anaya de
3.5.2. (SS)-Benzyl methyl sulfoxide 8b. The sulfoxide was
obtained as a white solid (0.016 g, 75.0% yield); e.e.O98%;
tRZ38.4 min, [a]D20ZK49.3 (c 1.1, CHCl3). [Lit.15
[a]2D0ZK55.0 (c 0.9, CHCl3)].
´
´
Parrodi, C.; Clara-Sosa, A.; Perez, L.; Quintero, L.; Maran˜on,
V.; Toscano, R. A.; Avin˜a, J. A.; Rojas-Lima, S.; Juaristi, E.
Tetrahedron: Asymmetry 2001, 12, 69.
8. For recent reviews on the use of (R)- and (S)-a-phenylethy-
lamine in the preparation of enantiopure compounds, see:
(a) Juaristi, E.; Escalante, J.; Leon-Romo, J. L.; Reyes, A.
Tetrahedron: Asymmetry 1998, 9, 715. (b) Juaristi, E.;
Leon-Romo, J. L.; Reyes, A.; Escalante, J. Tetrahedron:
Asymmetry 1999, 10, 2441.
References and notes
´
1. Reviews: (a) Solladie, G. Synthesis 1981, 185. (b) Mikołajczyk,
M.; Drabowicz, J. In Topics in Stereochemistry; Allinger, N. L.,
Eliel, E. L., Wilen, S., Eds.; Wiley: New York, 1982; Vol. 13,
pp 333–468. (c) Posner, G. H. In Asymmetric Synthesis;
Morrison, J. D., Ed.; Academic Press: New York, 1983; Vol. 2,
Chapter 8, pp 225–241. (d) Barbachyn, M. R.; Johnson, C. R.
In Asymmetric Synthesis; Morrison, J. D., Ed.; Academic Press:
New York, 1984; Vol. 4, Chapter 2, pp 227–261. (e) Cinquini,
M.; Cozzi, F.; Montanari, F. In Organic Sulfur Chemistry,
Theoretical and Experimental Advances; Bernardi, F.,
Csizmadia, I. G., Mangini, A., Eds.; Elsevier: Amsterdam,
1985; pp 355–407. (f) Andersen K. K. In The Chemistry of
Sulphones and Sulphoxides; Patai, S., Rappoport, Z., Stirling,
C. J. M., Eds.; Wiley: Chichester, 1988; Chapter 3, pp 55–94.
9. Gage, J. R.; Evans, D. A. Org. Synth. 1990, 68, 83.
10. For a review on the oxidation of sulfides, see: Madesclaire, M.
Tetrahedron 1986, 42, 5459.
11. Crystal data for (4S,5S,RS)-5a: C14H17N1O3S1, molecular
˚
weightZ279.35, monoclinic P 21, aZ9.5214(7) A, bZ
˚
˚
5.6279(5) A, cZ12.8734(11) A, aZ90.08, bZ104.386(3)8,
3
˚
gZ90.08, VZ668.20(10) A , crystal size: 0.32!0.20!
0.15 mm, R1Z0.0444 (wR2Z0.0980); for (4R,5S,RS)-5d:
C14H17N1O3S1, molecular weightZ279.35, orthorhombic P
˚
˚
˚
21 21 21, aZ6.9022(2) A, bZ9.3434(3) A, cZ22.0288(8) A,
3
˚
aZ90.08, bZ90.08, gZ90.0, VZ668.20(10) A , crystal size:
0.20!0.15!0.12 mm, R1Z0.0469 (wR2Z0.0840). Atomic
coordinates for the structures reported in this paper have been
deposited with the Cambridge Crystallographic Data Centre.
The coordinates can be obtained, on request from the Director,
Cambridge Crystallographic Data Centre, 12 Union Road,
Cambridge CB2 IEZ, UK. (Fax: C44 1223 336 036; e-mail:
deposit@ccdc.cam.ac.uk; deposition number: CCDC 248001,
CCDC 248002).
´
(g) Carren˜o, M. C. Chem. Rev. 1995, 95, 1717. (h) Fernandez, I.;
Khiar, N. Chem. Rev. 2003, 103, 3651.
2. (a) Cope, A. C.; Caress, E. A. J. Am. Chem. Soc. 1966, 88,
1711. (b) Ohta, H.; Kato, Y.; Tsuchihashi, G. Chem. Lett.
1986, 217. (c) Burgess, K.; Henderson, I. Tetrahedron Lett.
1989, 30, 3633.
3. (a) Pitchen, P.; Dunach, E.; Deshmukh, M. N.; Kagan, H. B.
J. Am. Chem. Soc. 1984, 106, 8188. (b) Davis, F. A.;
ThimmaReddy, R.; Weismiller, M. C. J. Am. Chem. Soc.
1989, 111, 5964. (c) Komatsu, N.; Nishibayashi, Y.; Sugita, T.;
Uemura, S. Tetrahedron Lett. 1992, 33, 5391.
12. (a) Becke, A. D. J. Chem. Phys. 1993, 98, 5648. (b) Lee, C.;
Yang, W.; Parr, R. G. Phys. Rev. B 1988, 37, 785.
13. (a) The figures of molecular structures, molecular orbital and
electron density were generated with the programs: (a)
Cambridge Crystallographic Data Center, Mercury, version
1.2.1; 2004. (b) Planaria Software LLC, ArgusLab, version
4.0.0; 2004.
4. Andersen, K. K. Tetrahedron Lett. 1962, 3, 93. (b) Andersen,
K. K.; Gaffield, W.; Papanikolaou, N. E.; Foley, J. W.; Perkins,
´
R. I. J. Am. Chem. Soc. 1964, 88, 5637. (c) Solladie, G.; Hutt,
J.; Girardin, A. Synthesis 1987, 173. (d) Whitesell, J. K.;
´
Wong, M. S. J. Org. Chem. 1991, 56, 4552. (e) Fernandez, I.;
14. Juaristi, E. Introduction to Stereochemistry and Conformation-
al Analysis; Wiley: New York, 1991; Chapter 6, pp 91–105.
15. Trost, B. M.; Massiot, G. S. J. Am. Chem. Soc. 1977, 99, 4405.
Khiar, N.; Llera, J. M.; Alcudia, F. J. Org. Chem. 1992, 57,
6789.