Determination of the absolute configurations of isotopically chiral molecules using vibrational circular dichroism (VCD) spectroscopy: the isotopically chiral sulfoxide, perdeuteriophenyl-phenyl-sulfoxide

Article abstract of DOI:10.1016/j.tetasy.2007.12.014

The (+) and (-) enantiomers of the isotopically chiral sulfoxide, perdeuteriophenyl-phenyl-sulfoxide, 1, have been synthesized by the reaction of the diastereomers of O-menthyl benzenesulfinate with C₆D₅MgBr. Their absolute configurations have been determined by comparison of the vibrational circular dichroism (VCD) spectra of (R)-1 and (S)-1, predicted using ab initio DFT, to the experimental VCD spectrum of 1. The absolute configuration of 1 is shown to be (S)(+)/(R)(-). This is the first application of VCD to the determination of the absolute configuration of an isotopically chiral sulfoxide.

Full text of DOI:10.1016/j.tetasy.2007.12.014

Available online at www.sciencedirect.com
Tetrahedron: Asymmetry 19 (2008) 288–294
Determination of the absolute configurations of isotopically chiral
molecules using vibrational circular dichroism (VCD) spectroscopy:
the isotopically chiral sulfoxide, perdeuteriophenyl-phenyl-sulfoxide
a
a
a
b,
*
´
Jozef Drabowicz, Adrian Zajac, Piotr Lyzwa, Philip J. Stephens,
Jian-Jung Panb and Frank J. Devlinb
aCentre of Molecular and Macromolecular Studies, Department of Heteroorganic Chemistry, Polish Academy of Sciences,
Sienkiewicza 112, 90-363 Ło´dz´, Poland
bDepartment of Chemistry, University of Southern California, Los Angeles, CA 90089-0482, United States
Received 8 October 2007; accepted 19 December 2007
Abstract—The (+) and (ꢀ) enantiomers of the isotopically chiral sulfoxide, perdeuteriophenyl-phenyl-sulfoxide, 1, have been synthesized
by the reaction of the diastereomers of O-menthyl benzenesulfinate with C6D5MgBr. Their absolute configurations have been determined
by comparison of the vibrational circular dichroism (VCD) spectra of (R)-1 and (S)-1, predicted using ab initio DFT, to the experimental
VCD spectrum of 1. The absolute configuration of 1 is shown to be (S)(+)/(R)(ꢀ). This is the first application of VCD to the determi-
nation of the absolute configuration of an isotopically chiral sulfoxide.
Ó 2008 Elsevier Ltd. All rights reserved.
1. Introduction
resulting optically active molecules under very mild reaction
conditions into an achiral sulfenyl group,4 thus allowing
efficient syntheses of enantiomeric structures, which in turn
can be very easily converted into enantiomeric, sulfur-free
end products. Moreover, the sulfinyl moiety is frequently
found in bioactive natural products. Due to a wide range
of biological activity (from flavor and aroma precursors
to antimicrobial activity) chiral sulfoxides are often consid-
ered and tested as good candidates for synthetic drugs.5
Considering the use of optically active sulfoxides as chiral
auxiliaries in asymmetric synthesis and their bioactivity, it
would be interesting to evaluate the efficiency and activity
of derivatives, which are chiral by virtue of isotopic substi-
tution (H–D or 12C–13C, respectively). Such derivatives
have already been prepared as optically active species by
the reaction of the appropriate unlabeled optically active
sulfinates with fully deuterated methylmagnesium iodide,6
n-butyl-d9-magnesium bromide,7 and benzylmagnesium
chloride prepared from benzyl-13C chloride.8 Despite the
extensive literature describing the use of optically active
sulfoxides as models in mechanistic studies and as chiral
auxiliaries in asymmetric synthesis and bioactive structures,
a limited number of methods have been used to determine
their absolute configurations. In particular, only a few
examples of correlation between the electronic circular
Over the last three decades enantiopure sulfoxides have
been widely recognized as valuable optically active starting
materials and as important chiral auxiliaries in organic syn-
thesis that are able to bring about many asymmetric trans-
formations. Their use as chiral synthons has now become
well-established and is developing rapidly into an exciting
area.1 This results from at least two reasons. First, a variety
of optically active sulfoxides are relatively easily available
via the Andersen route1a,2,3 or by asymmetric oxidation of
the parent, prochiral sulfides.2 Second, the chiral sulfinyl
group is able to exert high asymmetric induction in a num-
ber of reactions, due to the steric and stereoelectronic differ-
ences that exist between the substituents bonded to the
stereogenic sulfinyl sulfur atom. A lone electron pair, an
oxygen, and two carbon-derived substituents are able to dif-
ferentiate effectively the diastereotopic atoms or faces of a
proximal reaction center, or even of a more remote prochi-
ral reaction center. Additionally, the chiral sulfinyl residue,
which induces chirality transfer, can be reduced in the
*
Corresponding author. Tel.: +1 213 740 4119; fax: +1 213 740 3972;
e-mail: pstephen@usc.edu
0957-4166/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2007.12.014

J. Drabowicz et al. / Tetrahedron: Asymmetry 19 (2008) 288–294
289
dichroism (ECD) and the structure of optically active sulf-
oxides have been reported.9 These are based on an empirical
rule formulated by Mislow et al. after examining the chirop-
tical properties of several alkyl aryl sulfoxides of known
absolute configuration.10 Recently, this empirical rule has
found strong support from the non-empirical analysis of a
series of ECD spectra of optically active alkyl aryl sulfox-
ides, using the coupled-oscillator model for non-degenerate
transitions.11 More recently, the first non-empirical correla-
tion of absolute configuration and chiroptical properties of
alkyl aryl N-phthalimidosulfoximines, based on the analysis
of their exciton-split bichromophoric Cotton effects, has
been reported.12 The results of this correlation were applied
simultaneously to determine the absolute configuration of
the parent alkyl aryl sulfoxides due to the fact that N-phtha-
limidosulfoximines can be derived from sulfoxides via a
reaction whose mechanism is believed to retain the configu-
ration at the stereogenic sulfur atom.13
configurations, respectively, Scheme 1. Simultaneously,
racemic phenyl perdeuteriophenyl sulfoxide [( )-1] was
prepared using racemic O-ethyl benzenesulfinate 4 and
phenyl-d5-magnesium bromide (Eq. 1).
O
S
O
S
+
C6D5MgBr
ð1Þ
Ph
C6D5
Ph
OEt
( )-1
( )-4
The mid-IR IR and VCD spectra of (+)-1 and (ꢀ)-1 were
measured using 0.1 M solutions in CCl4. Measurements of
the mid-IR IR spectrum of CCl4 solutions of diphenyl-sulf-
oxide over the concentration range 0.01–0.4 M demon-
strated that Beer’s Law is obeyed up to 0.4 M, and,
therefore, that aggregation of 1 does not occur at 0.1 M.
The IR and VCD spectra of (+)-1 in the frequency range
1150–1550 cmꢀ1 are shown in Figure 1. The two absorp-
tion bands at 1317 and 1445 cmꢀ1 exhibit large VCD of
opposite signs.
In the mid-1990s, a more reliable method for determining
absolute configurations of chiral molecules was developed,
in which ab initio density functional theory (DFT) calcula-
tions of vibrational circular dichroism (VCD) spectra are
used to analyze experimental VCD spectra.14 VCD has
been used to analyze the stereochemistries of several chiral
sulfoxides.15 Herein, we report the application of VCD to
the determination of the absolute configuration of the iso-
topically chiral sulfoxide, phenyl perdeuteriophenyl sulfox-
ide, 1.
The phenyl rings in 1 can rotate about the S–C bonds con-
necting them to the sulfoxide group. To establish the num-
ber of stable conformations of 1 that exist, a 2D potential
energy surface (PES) scan with respect to the dihedral
angles OSC1C2 and OSC3C4 was carried out using DFT,
at the B3LYP/6-31G* level. Variation of the two dihedral
angles from +60° to ꢀ60° led to the results shown in Figure
2. A single valley in the PES is present, demonstrating that
over this range of dihedral angles, only one stable confor-
mation exists. A 2D PES scan in which the two dihedral
angles are varied from +180° to ꢀ180° found no addi-
tional, inequivalent, conformations. It is clear, therefore,
that 1 is a conformationally-rigid molecule. To obtain the
equilibrium geometry of 1, the lowest-energy geometry in
the 2D PES scan in Figure 2 was optimized. The values
of the OSC1C2 and OSC3C4 dihedral angles of the opti-
mized geometry are ꢀ8.8° and +8.8°, respectively. These
values are in good agreement with the dihedral angles of
the structure of diphenyl-sulfoxide determined using
X-ray crystallography,19 ꢀ11.7° and +11.4°, respectively.
D
O
S
D
D
D
D
1
2. Results and discussion
Samples of racemic and optically active perdeuteriophenyl-
phenyl-sulfoxide 1 were synthesized via the Andersen ap-
proach.3 The dextro- and levorotatory enantiomers of 1
were prepared using the diastereomeric benzenesulfinates
2, synthesized from (ꢀ)-(1R,2S,5R)- and (+)-(1S,2R,5S)-
menthol, respectively, and benzenesulfinyl chloride using
the procedure of Herbrandson and Dickerson16 (modified
by the use of Et3N instead of pyridine and by crystalliza-
tion from petroleum ether instead of methanol), Scheme
1. The (S) and (R) absolute configurations of (ꢀ)-2 and
(+)-2 at the sulfur atom were established by their
conversion to optically active methyl phenyl sulfoxide 3,
of known absolute configuration17 and enantiomeric ex-
cess,18 by reaction with methylmagnesium iodide, which
is assumed to cause full inversion of configuration at the
sulfinyl sulfur atom,1a,2a,10 Scheme 1. Then, the (ꢀ) and
(+) enantiomers of the O-menthyl benzenesulfinates 2 were
treated with perdeuteriophenyl-magnesium bromide giving
the (+) and (ꢀ) isomers of perdeuteriophenyl-phenyl-sulf-
oxide 1; assuming the inversion of configuration of the S
atom, these isomers are expected to have the (S) and (R)
As in previous work,14,15a,c–f,20 the IR and VCD spectra of
1 have been predicted using DFT, with the functionals
B3LYP and B3PW91 and the basis set TZ2P; use of the lat-
ter instead of 6-31G* reduces basis-set error in the pre-
dicted spectra. The B3LYP/TZ2P equilibrium geometry
has OSC1C2 and OSC3C4 dihedral angles of ꢀ10.2° and
+10.2°, respectively, closer to the X-ray values than those
of the B3LYP/6-31G* geometry. The predicted IR spec-
trum of 1 and the VCD spectra of (R)-1 and (S)-1 are com-
pared to the experimental spectra of (+)-1 in Figures 3 and
4. Figure 4 shows that the predicted VCD spectra of (S)-1
are qualitatively identical to the experimental VCD spec-
trum of (+)-1; the absolute configuration of (+)-1 is clearly
(S). The B3LYP/TZ2P and B3PW91/TZ2P spectra of (S)-1
are similar, but not identical, especially for the VCD of the
transitions of the normal modes 46–50. The B3LYP/TZ2P
VCD spectrum of (S)-1 is in better agreement with the
experimental VCD spectrum of (+)-1 than the B3PW91/
TZ2P spectrum. Assignment of the IR and VCD spectra
of 1 is, therefore, based on the B3LYP/TZ2P spectra. As

290
J. Drabowicz et al. / Tetrahedron: Asymmetry 19 (2008) 288–294
O
S
Ph
Me
(+)-(R)-3
[α]589 = +152.0 (CHCl3)
ee = 98.4%
MeMgI
O
O
S
S
C6D5MgBr
Ph
OMenthyl
Ph
C6D5
(-)-(1R, 2S, 5R)-
(-)-(S)-2
[α]589 = -209.3 (acetone)
menthol
(+)-(
S
)-1
[α]400 = +3.08 (CH2Cl2)
O
S
Ph
Cl
O
O
S
S
(+)-(1
S, 2R, 5S)-
C6D5MgBr
Ph
C6D5
menthol
OMenthyl
Ph
(+)-(R)-2
(-)-(R)-1
[α]589 = +174.9 (acetone)
[α]400 = -2.46 (CH2Cl2)
MeMgI
O
S
Me
Ph
(-)-(S)-3
[α]589 = -120.0 (CHCl3)
ee = 77.7%
Scheme 1.
shown in Figures 3 and 4, the bands observed in the 1150–
1550 cmꢀ1 range are due to the fundamental transitions of
normal modes 44–52. The dominant VCD bands at 1317
and 1445 cmꢀ1 are assigned to modes 48 and 51, respec-
tively. The predicted e and De values of modes 44–52 are
in excellent quantitative agreement with the experimental
values, further supporting the accuracy of the B3LYP/
TZ2P spectra and the assignment of the absolute configu-
ration of (+)-1 as (S).
nique for determining the absolute configurations of
isotopically chiral sulfoxides.
4. Experimental
4.1. General
1H NMR spectra were recorded at 200 MHz on a Brucker
spectrometer. All optical rotation measurements were done
on a Perkin–Elmer 241 MC polarimeter. Mass spectra were
obtained by direct probe using a Finigan MAT 20 mass
spectrometer. Silica gel (230–400 mesh) chromatography
was used to purify the prepared sulfoxides. Analytical
TLC was performed on Merck aluminum plates coated
with silica gel. A UV lamp (254 nm) was used to locate
compounds containing aromatic rings. All air and moisture
sensitive reactions were carried out under N2. Bromoben-
zene-d5 (99.5 atom % D) was purchased from Armar AG,
Dottingen (Switzerland). Separate procedures for the prep-
aration of (+)-1 ([a]400 = +3.08, c 2.11, CH2Cl2, ee =
98.4%), (ꢀ)-1 ([a]400 = ꢀ2.46, c 1.42, CH2Cl2, ee = 77.7%)
and racemic 1 are given below. The ee values of (+)-1
and (ꢀ)-1 were assumed to be the same as those of the sam-
ples of (ꢀ)-2 and (+)-2 from which they were obtained,
derived from the known ee’s of (+)-3 and (ꢀ)-3 obtained
by Grignard reaction of (ꢀ)-2 and (+)-2 with MeMgI,
3. Conclusion
Comparison of the VCD spectra of (R)-1 and (S)-1, pre-
dicted using DFT, to the experimental VCD spectrum of
(+)-1 proves unambiguously that the absolute configura-
tion of 1 is (S)(+)/(R)(ꢀ). This configuration is the same
as that deduced from the syntheses of (+)-1 and (ꢀ)-1 from
(ꢀ)-2 and (+)-2 (Scheme 1), assuming inversion of the con-
figuration of the S atom, proving that this mechanism is in-
deed correct.
The efficiency of VCD in assigning the absolute configura-
tion of an isotopically chiral sulfoxide has been demon-
strated. At the present time, the ECD and ORD spectra
of isotopically chiral sulfoxides cannot be reliably ana-
lyzed. VCD is, therefore, the optimum chiroptical tech-

J. Drabowicz et al. / Tetrahedron: Asymmetry 19 (2008) 288–294
291
acetone)15b]; 1H NMR (200 MHz, CDCl3) d = 0.71 (d,
2
2
5
3H, JH–H = 6.9 Hz, CH3); 0.86 [d, 3H, JH–H = 6.9 Hz,
b
2
(CH3)2CH]; 0.96 [d, 3H, JH–H = 6.9 Hz, (CH3)2CH];
Δ ε ∗ 103
1.00–2.30 [m, 8H, cyclohexane ring protons]; 4.13 and
2
4.15 [2t, 1H, JH–H = 6.9 Hz, (–CH–OH)]; 7.45–7.52 (m,
3H-aromatic), 7.67–7.85 (m, 2H-aromatic); 13C NMR
(50.34 MHz, CDCl3) d = 124.36 (t, J13C–D = 25.2 Hz);
124.74 (s); 128.77 (t, J13C–D = 24.6 Hz); 15.44; 20.82;
22.03; 23.14; 25.22; 31.72; 33.99; 42.94; 47.86; 80.36;
125.02; 128.94; 145.39 (s); 131.82.
-5
Other crops of the levorotatory diastereomer with [a]589
from ꢀ199 to ꢀ209 (c 1.3, acetone) were obtained after
repeated crystallization.
4.2.2. (+)-Phenyl perdeuteriophenyl sulfoxide (+)-1. To a
solution of perdeuteriophenyl-magnesium bromide in
diethyl ether (15 mL) prepared from bromobenzene-d5
[0.942 g, 6 mmol and magnesium (0.144 g, 6 mmol)] was
added dropwise at room temperature a solution of the levo-
rotatory sulfinate obtained above (1.184 g, 4 mmol) in
diethyl ether (10 mL). After the reaction mixture was stir-
red for 3 h at room temperature, it was quenched with
5% H2SO4 solution and diluted with water (200 mL). The
organic solution was separated from the aqueous phase,
and the aqueous phase was extracted with methylene chlo-
ride (3 ꢁ 50 mL). The organic extracts were dried over
MgSO4. Evaporation of the solvent gave the crude phenyl
perdeuteriophenyl sulfoxide (1.21 g), which was purified by
column chromatography on silica gel (30 g). The column
was washed subsequently with petroleum ether (24 ꢁ
10 mL), petroleum ether/diethyl ether [7:3 v/v
(64 ꢁ 10 mL)], and methylene chloride (150 mL). Evapora-
tion of petroleum ether/diethyl ether (7:3) fractions 57–64
and the methylene chloride solution gave the pure sulfoxide
(0.234 g) with [a]400 = +3.08 (c 2.11, CH2Cl2), mp 67–
68 °C, 1H NMR (200 MHz, CDCl3) d = 7.38–7.52 (m,
3Haromatic), 7.59–7.68 (m, 2Haromatic); 13C NMR
(50.34 MHz, CDCl3) d = 124.36 (t, J13C–D = 25.2 Hz);
124.74 (s); 128.77 (t, J13C–D = 24.6 Hz); 129.28(s); 130.99
(t, J13C–D = 24.7 Hz); 132.33 (s); 145.39 (s);145.57 (s); MS
(EI) (m/z) = 207.1; HRMS m/z: calcd for C12H5D5OS,
207.07660; found, 207.07691.
100
a
ε
1500
1400
1300
1200
wavenumbers (cm-1)
Figure 1. (a) The IR spectrum of a 0.10 M CCl4 solution of (+)-1.
Pathlength 597 l. (b) The VCD ‘half-difference’ spectrum of (+)-1, 1/2
[De(+) ꢀ De(ꢀ)], obtained from the VCD spectra of 0.10 M CCl4 solutions
of (+)-1 and (ꢀ)-1. Given the 27% higher ee of (+)-1, compared to (ꢀ)-1,
the VCD of (ꢀ)-1 was multiplied by 1.27.
which is assumed to occur with full inversion of configura-
tion of the sulfinyl S atom. Unfortunately, all attempts to
support our ee determinations by HPLC on chiral columns
have so far been unsuccessful.
4.2. The dextrorotatory enantiomer (+)-1
4.3. The levorotatory enantiomer (ꢀ)-1
4.2.1. O-(1R,2S,5R)-(ꢀ)-Menthyl-(S)-benzenesulfinate (ꢀ)-
(S)-2. A solution of (1R,2S,5R)-(ꢀ) menthol (22.4 g,
143 mmol) and triethylamine (16.2 g, 160 mmol) in Et2O
(100 mL) was added dropwise with vigorous stirring to a
solution of benzenesulfinyl chloride (23.0 g, 143 mmol) in
Et2O (150 mL) at ꢀ70 °C. After the reaction mixture was
stirred for 6 h at ꢀ70 °C and a few hours at room temper-
ature, the solution was diluted with diethyl ether (100 mL)
and quenched with water. The organic phase was separated
and washed with 5% H2SO4 solution, 5% K2CO3 solu-
tion and water and dried over MgSO4. After the solvent
was removed in vacuo, the crude sulfinate (38 g) with
[a]D = ꢀ127.8 (c 2.01, acetone) was purified by crystalliza-
tion from petroleum ether at ꢀ18 °C giving the levorota-
tory diastereomer (5.3 g) with [a]589 = ꢀ209.3 (c 1.45,
acetone), mp 42–44 °C [lit.: 49–51 °C; [a]D = ꢀ205.5 (c
2.0, acetone)15a and 37–40 °C and [a]D = ꢀ195.5 (c 2.0,
4.3.1. O-(1S,2R,5S)-(+)-Menthyl-(R)-benzenesulfinate (+)-
(R)-2. A solution of (1S,2R,5S)-(+) menthol (7.8 g,
50 mmol) and triethylamine (5.6 g, 55 mmol) in Et2O
(30 mL) was added dropwise with vigorous stirring to a
solution of benzenesulfinyl chloride (8.0 g, 50 mmol) in
Et2O (100 mL) at ꢀ70 °C. After the reaction mixture
was stirred for 6 h at ꢀ70 °C and a few hours at room tem-
perature, the solution was diluted with diethyl ether
(100 mL) and quenched with water. The organic phase
was separated and washed with 5% H2SO4 solution, 5%
K2CO3 solution and water and dried over MgSO4. After
the solvent was removed in vacuo, the crude sulfinate
(13.73 g) with [a]D = +94.6 (c 1.4, acetone) was purified
by crystallization from petroleum ether at ꢀ18 °C giving
the dextrorotatory diastereomer (2.4 g) with [a]589
+174.9 (c 1.06, acetone), mp 39–41 °C. The spectral and
=

292
J. Drabowicz et al. / Tetrahedron: Asymmetry 19 (2008) 288–294
O
4
2
S
1
3
60
40
7.0
6.5
6.0
5.5
5.0
4.5
4.0
3.5
3.0
2.5
2.0
5.0
4.5
4.0
2.5
3.5
3.0
1.5
1.0
0.5
1.5
20
2.0
1.0
1.5
1.0
0
4.0
2.5
3.0
3.5
0.5
1.0
4.5
5.0
-20
-40
-60
5.5
6.0
6.5
7.0
7.5
8.0
8.5
9.0
9.5
10.0
1.5
9.0
2.5
2.0
5.5
6.5
7.0
8.0
4.0
4.5
6.0
8.5
9.5
7.5
10.0
9.0
3.0
3.5
4.0
4.5
5.0
-60
-40
-20
0
20
40
60
OSC1C2 (deg)
Figure 2. The B3LYP/6-31G* PES of diphenyl-sulfoxide, as a function of the dihedral angles OSC1C2 and OSC3C4. The two dihedral angles were varied
in 5° steps over a range from ꢀ60° to +60°. Contours are shown at 0.5 kcal/mol intervals. d is the B3LYP/6-31G* optimized geometry.
analytical data were in full agreement with those presented
above for the levorotatory diastereomer.
ylene chloride (30 ꢁ 10 mL). Evaporation of the methylene
chloride fractions from 6 to 30 gave the pure sulfoxide
(0.263 g) with [a]400 = ꢀ2.46 (c 1.42, CH2Cl2), mp 66–
68 °C. The spectral and analytical data were in full agree-
ment with those presented above for the dextrorotatory
enantiomer.
Other crops of the dextrorotatory diastereomer with [a]589
close to +179 (c 1.1, acetone) were obtained after repeated
crystallization.
4.3.2. (ꢀ)-Phenyl perdeuteriophenyl sulfoxide (ꢀ)-1. To a
solution of perdeuteriophenyl-magnesium bromide in
diethyl ether (15 mL) prepared from bromobenzene-d5
[0.942 g, 6 mmol and magnesium (0.144 g, 6 mmol)] was
added dropwise at room temperature a solution of the
above obtained dextrorotatory sulfinate (1.184 g, 4 mmol)
in diethyl ether (10 mL). After the reaction mixture was
stirred for 3 h at room temperature, it was quenched with
5% H2SO4 solution and diluted with water (200 mL). The
organic solution was separated from the aqueous phase,
and the aqueous phase was extracted with methylene chlo-
ride (3 ꢁ 50 mL). The organic extracts were dried over
MgSO4. Evaporation of the solvent gave the crude phenyl
perdeuteriophenyl sulfoxide (1.21 g), which was purified by
column chromatography on silica gel (30 g). The column
was washed subsequently with petroleum ether (250 mL),
petroleum ether/diethyl ether 7:3 (30 ꢁ 10 mL), and meth-
4.4. ( )-Phenyl perdeuteriophenyl sulfoxide ( )-(1)
To a solution of perdeuteriophenyl-magnesium bromide in
diethyl ether (15 mL) prepared from bromobenzene-d5
[0.942 g, 6 mmol and magnesium (0.144 g, 6 mmol)] was
added dropwise at room temperature a solution of O-ethyl
benzenesulfinate (0.85 g, 5 mmol) in diethyl ether (10 mL).
After the reaction mixture was stirred for 3 h at room tem-
perature, it was quenched with 5% H2SO4 solution and di-
luted with water (200 mL). The organic solution was
separated from the aqueous phase, and the aqueous phase
was extracted with methylene chloride (3 ꢁ 50 mL). The
organic extracts were dried over MgSO4. Evaporation of
the solvent gave the crude phenyl perdeuteriophenyl sulf-
oxide (0.751 g), which was purified by column chromatog-
raphy on silica gel (30 g). The column was washed
subsequently with petroleum ether (50 mL), petroleum

J. Drabowicz et al. / Tetrahedron: Asymmetry 19 (2008) 288–294
293
Δε x 103
ε
B3PW91/TZ2P : (S)-1
B3PW91/TZ2P
48
B3LYP/TZ2P : (
S
)-1
45
52
46
47
44
49
50
51
B3LYP/TZ2P
52
49/48
51
5
48
Expt : (+)-1
50
45
45
47
47
46
44
46
52
44
49
50
51
51
51
-5
B3LYP/TZ2P : (
R
)-1
50
49
47
46
44
Expt
52
45
48
52
48
50
B3PW91/TZ2P : (R)-1
49
47
46
50
45
44
1500
1400
1300
1200
1500
1400
1300
1200
wavenumbers (cm-1)
wavenumbers (cm-1)
Figure 3. Comparison of the B3LYP/TZ2P and B3PW91/TZ2P IR
spectra of 1 to the experimental IR spectrum. The assignment of the
experimental spectrum is based on the B3LYP/TZ2P spectrum. The
calculated IR spectra have Lorentzian bandshapes (c = 4.0 cmꢀ1).
Figure 4. Comparison of the B3LYP/TZ2P and B3PW91/TZ2P VCD
spectra of (R)-1 and (S)-1 to the experimental VCD spectrum of (+)-1. The
assignment of the experimental spectrum is based on the B3LYP/TZ2P
spectrum of (S)-1. The calculated VCD spectra have Lorentzian band-
shapes (c = 4.0 cmꢀ1).
Acknowledgments
ether/diethyl ether 7:3 (50 mL), and methylene chloride
(100 mL). Evaporation of the methylene chloride fractions
gave the pure sulfoxide (0.363 g), mp 65–66 °C. The spec-
tral and analytical data were in full agreement with those
presented above for the dextrorotatory enantiomer.
We are grateful for financial support from the US National
Science Foundation (to P.J.S., Grants CHE-0209957 and
CHE-0614577). We also thank the USC High Performance
Computing and Communication (HPCC) facility for com-
puter time and Hewlett–Packard Inc. for the use of an Al-
pha Server SC (ES45) HP computer.
4.5. IR and VCD spectra
The studies in Lodz were in part financially supported by
Grant PBZ-KBN- 126/T09/02 (to J.D.) within a scientific
project by the government fund in the period 2006–2009.
The IR and VCD spectra of (+)-1, (ꢀ)-1 and ( )-1 were
measured using CCl4 solutions of 0.1 M concentration,
Thermo-Nicolet Nexus 670 IR and Bomem/BioTools
VCD instruments. Scan times and resolution of the VCD
spectra were 1 h and 4 cmꢀ1, respectively. The mid-IR IR
spectra of (+)-1, (ꢀ)-1 and ( )-1 were identical, demon-
strating that the samples were of equal chemical purity;
contributions to the IR and VCD spectra of impurities
are, therefore, unlikely. The VCD spectra of ( )-1
provided the baseline for the VCD spectra of (+)-1 and
(ꢀ)-1, minimizing the contributions of artifacts to the
spectra.
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