Highly stereoselective route to dialkyl sulfoxides based upon the sequential displacement of oxygen and carbon leaving groups by grignard reagents on sulfinyl compounds

Full text of DOI:10.1021/jo010334m

J . Org. Chem. 2001, 66, 5933-5936
5933
Sch em e 1
High ly Ster eoselective Rou te to Dia lk yl
Su lfoxid es Ba sed u p on th e Sequ en tia l
Disp la cem en t of Oxygen a n d Ca r bon
Lea vin g Gr ou p s by Gr ign a r d Rea gen ts on
Su lfin yl Com p ou n d s
Maria Annunziata M. Capozzi, Cosimo Cardellicchio,
Francesco Naso,* Giulia Spina, and Paolo Tortorella
Sch em e 2
Sch em e 3
Consiglio Nazionale delle Ricerche, Centro di Studio sulle
Metodologie Innovative di Sintesi Organiche,
Dipartimento di Chimica, Universita` di Bari,
via Amendola 173, 70126 Bari, Italy
naso@area.ba.cnr.it
Received March 30, 2001
In recent work,1-3 we have shown that the stereo-
specific displacement of a carbanionic leaving group4 from
suitable sulfinyl compounds by means of Grignard re-
agents represents a novel and versatile route to chiral
nonracemic sulfoxides, a class of compounds which has
always enjoyed a deserved popularity.5,6
Basically, we have set up a two-step procedure by
subjecting sulfinyl derivatives, obtained by enantioselec-
tive oxidation of the corresponding sulfides, to the action
of organometallic reagents.1,2 In particular, as shown in
Scheme 1, the oxidation of arylthio- or alkylthiometh-
ylphosphonates in high enantiomeric purity (91 to >98%),
followed by reaction with Grignard reagents, led to a
variety of sulfoxides.1
Taking into account the yields, the stereochemical
course of the reactions, and the availability of the
substrates in high enantiomeric purity, it appeared that
the best substrate was the p-bromophenyl methyl sul-
foxide.2 In this substrate, the whole p-bromophenyl
moiety was displaced by Grignard reagents as a carban-
ionic leaving group with full inversion of configuration.
Alkyl methyl sulfoxides were then obtained in good
isolated yields (74-90%) and with high enantiomeric
purity (ee > 98%).2
Our two-step strategy (enantioselective oxidation/
enantiospecific displacement of a carbanionic leaving
group, as depicted in Schemes 1 and 2) has allowed an
easy access to dialkyl sulfoxides, a type of sulfoxide which
has attracted considerable interest.7-10 However, a struc-
tural limitation resulting from the application of our
protocol to the synthesis of dialkyl sulfoxides was the fact
that, in the first step, that is, the oxidation of the sulfides,
good ee values were obtained only when either the
methyl1,2 or ethyl1 group was present.
We reasoned that, in principle, this limitation could
be circumvented by combining our carbanionic leaving
group approach with the classical displacement5 of the
OMenthyl group from a suitable menthyl sulfinate ac-
cording to Scheme 3, where (LG) is a carbanionic leaving
group.
We report now our successful experimental efforts to
transform Scheme 3 in a general procedure for the
synthesis of dialkyl sulfoxides.
Particularly high ee values (>98%) were obtained in
the synthesis of methyl alkyl sulfoxides, whereas ethyl
or phenyl sulfoxides were prepared with lower ee values
(91-94%).
An important improvement2 in the synthesis of methyl
sulfoxides with ee values >98% was brought about by
reacting the Grignard reagent with aryl methyl sulfox-
ides, easily obtained by enantioselective cumene hydro-
peroxide oxidation of the corresponding sulfide, a process
mediated by a diethyl (R,R)-tartrate/titanium complex
(Scheme 2).
(1) Capozzi, M. A. M.; Cardellicchio, C.; Fracchiolla, G.; Naso, F.;
Tortorella, P. J . Am. Chem. Soc. 1999, 121, 4708.
(2) Capozzi, M. A. M.; Cardellicchio, C.; Naso, F.; Tortorella, P. J .
Org. Chem. 2000, 65, 2843-2846.
(3) (a) Cardellicchio, C.; Fiandanese, V.; Naso, F. J . Org. Chem.
1992, 57, 1718-1722. (b) Cardellicchio, C.; Fiandanese, V.; Naso, F.;
Scilimati, A. Tetrahedron Lett. 1992, 33, 5121-5124. (c) Cardellicchio,
C.; Iacuone, A.; Naso, F.; Tortorella, P. Tetrahedron Lett. 1996, 37,
6017-6020. (d) Cardellicchio, C.; Fracchiolla, G.; Naso, F.; Tortorella,
P. Tetrahedron 1999, 55, 525-532.
(4) For earlier work on the use of carbanionic leaving groups in
sulfoxide chemistry see: (a) Durst, T.; LeBelle, M. J .; Van Der Elzen,
R.; Tin, K.-C. Can. J . Chem. 1974, 52, 761-766. (b) Lockard, J . P.;
Schroeck, C. W.; J ohnson, C. R. Synthesis 1973, 485-486. For work
on the fate of carbanionic leaving groups see: (c) Hoffmann, R. W.;
Nell, P. G.; Leo, R.; Harms, K. Chem. Eur. J . 2000, 6, 3359-3365.
(5) Drabowicz, J .; Kiełbasinski, P.; Mikołajczyk, M. Synthesis of
Sulphoxides. In The Chemistry of Sulphones and Sulphoxides; Patai,
S., Rappoport, Z., Stirling, C., Eds.; J ohn Wiley and Sons: New York,
1988; pp 233-378.
Resu lts a n d Discu ssion
According to our experience in the field of carbanionic
leaving groups, a good candidate for a two-step synthesis
of chiral sulfoxides was represented by the menthyl
(7) Alayrac, C.; Nowaczyk, S.; Lemarie´, M.; Metzner, P. Synthesis
1999, 669-675.
(8) Fernandez, I.; Khiar, N.; Llera, J . M.; Alcudia, F. J . Org. Chem.
1992, 57, 6789-6796.
(9) Colonna, S.; Gaggero, N.; Pasta, P.; Ottolina, G. Chem. Commun.
1997, 439-440.
(6) (a) Solladie´, G. Optically active â-ketosulfoxides in asymmetric
synthesis. In Advanced Asymmetric Synthesis; Stephenson, G. R., Ed.;
Chapman and Hall: London, 1996; pp 60-92. (b) Carren˜o, M. C. Chem.
Rev. 1995, 95, 1717-1760. (c) Walker, A. J . Tetrahedron: Asymmetry
1992, 3, 961-998. (d) Solladie´, G. Synthesis 1981, 185-196.
(10) (a) Rebiere, F.; Samuel, O.; Ricard, L.; Kagan, H. B. J . Org.
Chem. 1991, 56, 5991-5999. (b) Benson, S. C.; Snyder, J . K. Tetrahe-
dron Lett. 1991, 32, 5885-5888. (c) Wudl, F.; Lee, T. B. K. J . Am.
Chem. Soc. 1973, 95, 6349-6358.
10.1021/jo010334m CCC: $20.00 © 2001 American Chemical Society
Published on Web 08/02/2001

5934 J . Org. Chem., Vol. 66, No. 17, 2001
Notes
Ta ble 1. Ster eosp ecific Su bstitu tion of Lea vin g Gr ou p s by Gr ign a r d Rea gen ts on Su lfin yl Com p ou n d s
substrate
entry (configuration)
product
solventa temp (°C) RMgX/substrate ratio (configuration) yieldb (%) ee (%)
R1
ethyl
n-decyl
i-propyl
cyclohexyl
ethyl
R2
1
2
3
4
5
6
7
8
9
1 (S)
1 (S)
1 (S)
1 (S)
2 (R)
2 (R)
3 (R)
3 (R)
3 (R)
4 (R)
5 (R)
benzene
benzene
benzene
benzene
THF
5
5
5
1.1:1
1.1:1
1.1:1
1.1:1
1.5:1
1.5:1
1.5:1
1.5:1
1.5:1
1.5:1
1.5:1
2 (R)c
3 (R)c
4 (R)c
5 (R)c
6 (S)e
7 (S)e
6 (R)e
8 (S)e
9 (S)e
88
91
83
97
76
89
95
97
96
42
60
>98d
>98d
>98d
>98d
>98d
>98d
>98d
>98d
5
n-decyl
-30
-30
-30
-30
-30
-30
-30
ethyl
cyclohexyl THF
n-decyl
n-decyl
n-decyl
i-propyl
ethyl
i-propyl
THF
THF
cyclohexyl THF
cyclohexyl THF
f
>98
10
11
10g
7 (R)e
>98d
>98d
cyclohexyl ethyl
THF
Solvent for the substrate. Grignard reagents were prepared in THF. Isolated yield. c Configuration expected on the basis of a
a
b
stereochemical course occurring with inversion. Determined by HPLC (see text). e Configuration expected on the basis of a stereochemical
d
course occurring with inversion and confirmed by NMR upon addition of (R)-(methoxy)phenylacetic acid (see text). f Determined by NMR
g
upon addition of (R)-(methoxy)phenylacetic acid. The product should be (S), provided that also this reaction occurred with inversion of
configuration.
Sch em e 4
formation of alkyl p-bromophenyl sulfoxides 2-5 was
found to take place in high yield (83-97%). Under these
reaction conditions, only the substitution of the men-
thoxide ion occurred. The enantiomeric purity of the
obtained sulfoxides was determined by HPLC and was
found to be >98%. Taking into account that the nucleo-
philic displacement of a menthoxide ion at a sulfur atom
occurs with inversion, the configuration of the products
2-5 should be (R).
The second step of the procedure, that is, the carbon
for carbon substitution on the alkyl p-bromophenyl
sulfoxides 2-5, was performed with alkyl Grignard
reagents, yielding the target dialkyl sulfoxide in good
yields and with the same enantiomeric purity of the
starting material (ee > 98%). In particular, when an
n-alkyl p-bromophenyl sulfoxide (Table 1, entries 5-9)
was the substrate for the second step, dialkyl sulfoxides
were obtained in high yields (76-97%). On the other
hand, when a sec-alkyl p-bromophenyl sulfoxide was
used, the yields were lower (Table 1, entries 10-11). As
a consequence, an n-alkyl sec-alkyl sulfoxide could be
obtained in better yields by reacting the secondary alkyl
Grignard reagents with an n-alkyl p-bromophenyl sul-
foxide.
p-bromobenzenesulfinate (1). In preliminary experi-
ments, we checked that this substrate actually reacted
with Grignard reagents, undergoing a carbon for oxygen
substitution, followed by a carbon for carbon substitution
(Scheme 4).
First of all, the possibility of transforming this double
displacement sequence into a convenient route to dialkyl
sulfoxides was strictly dependent upon the availability
of the starting material. Menthyl p-bromobenzenesulfi-
nate (1) with the (S) configuration at the sulfur stereo-
genic center had been prepared starting from a sulfinic
acid derivative.11 However, this procedure did not seem
to be adequate for the preparation of the substrate on a
large scale. On the other hand, different menthyl sulfi-
nates had been prepared by the reaction between (-)-
menthol and sulfonyl chlorides, with the addition of
trimethyl phosphite as a reducing agent.12 By modifying
this procedure, we were able to obtain substrate (S)-1
on a scale of several grams. According to our protocol,
menthyl p-bromobenzenesulfinate was prepared as a
mixture of diastereomers, the predominant one being the
stereoisomer with the (S) configuration at the sulfur
stereogenic center (see Experimental Section). This di-
astereomer was separated by crystallization, and itera-
tion of the procedure, after subjecting the mother liquors
enriched in the (R)-stereoisomer to epimer equilibration
by adding HCl, led to a 57% overall yield of (S)-1.
Menthyl (S)-p-bromobenzenesulfinate (1) in benzene
was subjected to reactions with 1.1 equiv of alkyl Grig-
nard reagents in THF at 5 °C (Table 1, entries 1-4). The
A stereochemical course of inversion of configuration
should be expected also in the carbon for carbon
substitution.1,2,3b-d This type of stereochemical outcome
has been observed in similar cases.5
The configuration of the sulfoxides 6-9 could be
inferred also by using an NMR technique, according to a
work of Buist et al.13 Indeed, (methoxy)phenylacetic acid
was reported to yield a complex with alkyl sulfoxides, and
a distinction between the two possible diastereomeric
complexes resulting from the interaction with (R)-(meth-
oxy)phenylacetic acid could be made on the basis of the
signals attributed to the methylene group bound to the
sulfur atom. When this analysis was performed, the
results were consistent with the configuration expected
from a sequence requiring inversion in both steps. The
determination of the configuration of 10 was not possible
(11) (a) Cooke, R. S.; Hammond, G. S. J . Am. Chem. Soc. 1970, 92,
2739-2745. (b) Nishide, K.; Nakayama, A.; Kusumoto, T.; Hiyama,
T.; Takehara, S.; Shoji, T.; Osawa, M.; Kuriyama, T.; Nakamura, K.;
Fujisawa, T. Chem. Lett. 1990, 623-626.
(12) Klunder, J . M.; Sharpless, K. B. J . Org. Chem. 1987, 52, 2598-
2602.
(13) Buist, P. H.; Marecak, D.; Holland, H. L.; Brown, F. M.
Tetrahedron: Asymmetry 1995, 6, 7-11.

Notes
J . Org. Chem., Vol. 66, No. 17, 2001 5935
by NMR, because of the absence of methylene groups
bound to the sulfur atom.
Exp er im en ta l Section
1
The purified reaction products were characterized by their H
In conclusion, the present work extends the applica-
tions of carbanionic leaving groups to a simple and viable
route to various types of dialkyl sulfoxides in high
enantiomeric purity. A common precursor is prepared
first, and the target sulfoxides are obtained in two
consecutive displacements with the organometallic re-
agent. The simple control of the sequence of these
displacements leads to the required configuration.
Our method compares favorably with other procedures,
which are less general, each one being restricted to
limited types of dialkyl sulfoxides or presenting other
disadvantages.7-10 For instance, the method of Kagan et
al.10a requires in the first step a reaction of an organo-
metallic reagent on a cyclic sulfite. This reaction is not
always regioselective, and the ratio between the two
resulting sulfinates depends on the organometallic re-
agent used. On the other hand, the work of Alcudia et
al.8 hinges on the availability of alkanesulfinates of
diacetone-D-glucose (DAG), obtained by the crystalliza-
tion or the chromatographic separation of mixtures of
diastereomers. Depending on the type of sulfoxides
needed, the appropriate type of DAG sulfinate has to be
prepared.
At this point, it seems also appropriate to make a
comparison between the use of Grignard reagents and
the use of lithium alkyls in the second step of our
procedure. In this respect, it is worth noting that a
displacement of the aryl group has been reported by
J ohnson et al.4b in the reactions of phenyl or p-tolyl
methyl sulfoxide with n-butyllithium, leading to n-butyl
methyl sulfoxide with 87 or 93% optical purity, respec-
tively.14 However, the reaction appears to be of limited
scope. Indeed, only unreacted material was recovered in
the reaction between p-tolyl butyl sulfoxide and meth-
yllithium. Therefore, if we take into account also the
tendency of lithium alkyls to abstract a proton from alkyl
sulfoxides,6d and the serious lack of reproducibility of
results in terms of ee values and stereochemical course
evidenced in a recent work of Drabowicz et al.15 for the
reaction between tert-butyllithium and n-butyl p-tolyl
sulfoxide, one is led to the conclusion that the use of
Grignard reagents associated with an appropriate sub-
strate is by far to be preferred in the synthesis of dialkyl
sulfoxides.
and 13C NMR spectra, recorded in CDCl3 at 500 and 125 MHz,
respectively, and their mass spectra, determined by GC/MS
analysis (SE30, 30 m, capillary columns and mass selective
detector, 70 eV).
The de values of the diastereomeric mixture of menthyl
p-bromobenzenesulfinate were determined by GC analysis (SE30,
30 m, capillary columns). The ee values of the sulfoxides 2-8
and 10 were determined by HPLC (Chiralcel OB-H or OD-H).
The ee values of 9 were determined by NMR, after the addition
of (R)-(methoxy)phenylacetic acid.
Racemic 2-10, used as references in HPLC or NMR methods,
were prepared starting from a mixture of (R)-1 and (S)-1 of low
de, which resulted from the purification of (S)-1. The same
compounds could also be obtained by treating acetone solutions
containing small amounts of chiral nonracemic material with a
drop of HCl. After the usual workup, a complete racemization
of the starting sulfoxide was revealed.
Syn th esis of Men th yl (S)-p-Br om oben zen esu lfin a te (1).
Triethylamine (8.2 mL) was added under a nitrogen atmosphere
to a solution of (1R,2S,5R)-(-)-menthol (6.1 g, 39 mmol) and
p-bromobenzenesulfonyl chloride (15 g, 58.7 mmol) in 140 mL
of methylene chloride. Trimethyl phosphite (9.3 mL) was then
added, and the mixture was refluxed for 3 h. After this time,
the mixture was cooled and quenched with a 1.2 N solution of
HCl. The separated organic layer was washed twice with a 2 M
solution of Na2CO3 and twice with brine, and the solvent was
evaporated at a reduced pressure. The crude residue was heated
in a Kugelrohr oven at 40 °C and at 10-3 mbar to remove some
impurities (phosphorus compounds and traces of unreacted
menthol). After this treatment, menthyl (S)-p-bromobenzene-
sulfinate (1) was found to be the predominant stereoisomer (de
) 13%). The residue was treated with 60 mL of hexane, and 6.3
g of a white solid and a solution were obtained. The white
crystalline solid was found to be highly enriched in menthyl (S)-
p-bromobenzenesulfinate (1, de 89%). A simple recrystallization
from acetone yielded 4.1 g of pure (S)-1. The hexane and acetone
solutions were combined and evaporated to give a residue which
was crystallized three times (acetone), yielding an additional 1.5
g of pure (S)-1. The mother liquors of these crystallizations were
collected and evaporated. The residue, highly enriched in (R)-1,
was dissolved in 60 mL of acetone and treated with 0.1 mL of
12 N HCl at room temperature for 2 h. After the usual workup,
(S)-1 and (R)-1 were present in almost equal amounts. The crude
mixture was heated in a Kugelrohr oven to evaporate a small
amount of formed menthol. The diastereomeric couple was
recrystallized twice (acetone), yielding an additional 2.1 g of pure
(S)-1. From the combination of the two processes (production of
menthyl (S)-p-bromobenzenesulfinate and separations of the
diastereomers), a 57% overall yield of pure (S)-1 was obtained.
Men th yl (S)-p-br om oben zen esu lfin a te (1) mp 120-121 °C
(acetone) (lit.11a 108-113.5 °C; lit.11b 117-118 °C). [R]D -156.5
(c 1, CHCl3) (lit.11a [R]D -159.8 (c 2.7, CHCl3); lit.11b [R]D -158
(c 1.11, MeOH)).
The ready availability of a variety of chiral nonracemic
sulfoxides with primary and/or secondary alkyl groups
should now promote their use in the important field of
asymmetric synthesis or for novel applications.16
Finally, it is worth noting that in the present work our
attention was focused on the synthesis of dialkyl sulfox-
ides because these represented a type of compounds for
which there was much more need of a general route.
However, in principle, by adopting the carbanionic leav-
ing group strategy, it should be possible to prepare any
type of sulfoxide, provided that appropriate substrates
with suitable leaving groups are uncovered.
Rea ction of Alk yl Gr ign a r d Rea gen ts w ith Men th yl (S)-
p-Br om oben zen esu lfin a te (1). A solution of 4.6 mmol of
Grignard reagent in THF was added to a solution of 4.2 mmol
of 1 in 25 mL of benzene at 5 °C and under N2. After 1.5 h, the
reaction mixture was quenched with a saturated solution of NH4-
Cl. The usual workup yielded a residue which was purified by
column chromatography and crystallization (hexane).
(R)-p-Br om op h en yl eth yl su lfoxid e (2)17 mp 53-55 °C
(hexane). [R]D +162.0 (c 1, CHCl3). The ee value, measured by
HPLC (Chiralcel OB-H, hexane-i-propanol 70:30), was >98%.
(R)-p-Br om op h en yl n -d ecyl su lfoxid e (3) mp 51-52 °C
1
(hexane). [R]D +122.8 (c 1, CHCl3). H NMR (500 MHz, CDCl3):
δ 7.65-7.62 (m, 2H), 7.48-7.45 (m, 2H), 2.74 (t-like, J ) 7.7
Hz, 2H), 1.74-1.67 (m, 1H), 1.59-1.54 (m, 1H), 1.42-1.31 (m,
2H), 1.30-1.22 (m, 12H), 0.85 (t, J ) 7.1 Hz, 3H). 13C NMR (125
MHz, CDCl3): δ 143.28, 132.39, 125.64, 125.29, 57.33, 31.83,
29.44, 29.31, 29.22, 29.13, 28.63, 22.64, 21.99, 14.08. MS (70
eV): 330 (10), 328 (10), 190 (33), 188 (24), 55 (39), 43 (100). Anal.
(14) Values calculated on the basis of optical rotations taken in
acetone: J ohnson, C. R.; Kirchhoff, R. A.; Corkins, H. G. J . Org. Chem.
1974, 39, 2458-2459.
(15) Drabowicz, J .; Dudzin´ski, B.; Mikołajczyk, M.; Wang, F.;
Dehlavi, A.; Goring, J .; Park, M.; Rizzo, C. J .; Polavarapu, P. L.;
Biscarini, P.; Wieczorek, M. W.; Majzner, W. R. J . Org. Chem. 2001,
66, 1122-1129.
(16) Fanizzi, F. P.; Alicino, V.; Cardellicchio, C.; Tortorella, P.;
Rourke, J . P. Chem. Commun. 2000, 673-674.
(17) Racemic 2: Kim, Y. H.; Lee, H. K. Chem. Lett. 1987, 1499-
1502.

5936 J . Org. Chem., Vol. 66, No. 17, 2001
Notes
Calcd for C16H25BrOS: C, 55.65; H, 7.30. Found: C, 55.37; H,
7.20. The ee value, measured by HPLC (Chiralcel OD-H,
hexane-i-propanol 90:10), was >98%.
was >98%. A further NMR control of the enantiomeric purity
was performed by adding (R)-(methoxy)phenylacetic acid.
(S)-n -Decyl i-p r op yl su lfoxid e (8) mp ) 38-40 °C (pen-
tane). [R]D -42.8 (c 1, CHCl3). 1H NMR (500 MHz, CDCl3): δ
2.76 (heptet, J ) 7.0 Hz, 1H), 2.61 (ddd, J ) 12.8, J ) 9.2, J )
5.6 Hz, 1H), 2.56 (ddd, J ) 12.8, J ) 9.1, J ) 7.2 Hz, 1H), 1.85-
1.71 (m, 2H), 1.51-1.12 (m, 20H), 0.88 (t, J ) 7.1 Hz, 3H). 13C
NMR (125 MHz, CDCl3): δ 50.09, 48.73, 31.84, 29.48, 29.36,
29.25, 29.21, 28.96, 22.86, 22.64, 16.06, 14.62, 14.08. Anal. Calcd
for C13H28OS: C, 67.18; H, 12.14. Found: C, 67.06; H, 11.95.
The ee value, measured by HPLC (Chiralcel OD-H, hexane-i-
propanol 97:3), was >98%. A further NMR control of the
enantiomeric purity was performed by adding (R)-(methoxy)-
phenylacetic acid.
(R)-p-Br om op h en yl i-p r op yl su lfoxid e (4) mp 68-70 °C
1
(hexane). [R]D +160.8 (c 1, CHCl3). H NMR (500 MHz, CDCl3):
δ 7.66-7.63 (m, 2H), 7.47-7.44 (m, 2H), 2.80 (heptet, J ) 6.9
Hz, 1H), 1.22 (d, J ) 6.9 Hz, 3H), 1.11 (d, J ) 6.9 Hz, 3H). 13C
NMR (125 MHz, CDCl3): δ 140.93, 132.06, 126.53, 125.39, 54.57,
15.73, 13.73. Anal. Calcd for C9H11BrOS: C, 43.74; H, 4.49.
Found: C, 43.42; H, 4.57. The ee value, measured by HPLC
(Chiralcel OB-H, hexane-i-propanol 70:30), was >98%.
(R)-p-Br om op h en yl cycloh exyl su lfoxid e (5) mp 119-120
°C (hexane). [R]D +156.3 (c 1, CHCl3). 1H NMR (500 MHz,
CDCl3): δ 7.64-7.62 (m, 2H), 7.45-7.42 (m, 2H), 2.55-2.49 (m,
1H), 1.85-1.62 (m, 5H), 1.43-1.31 (m, 2H), 1.28-1.14 (m, 3H).
13C NMR (125 MHz, CDCl3): δ 141.01, 132.12, 126.57, 125.36,
(S)-Cycloh exyl n -d ecyl su lfoxid e (9) mp 69-70 °C (hex-
ane). [R]D -22.1 (c 1, CHCl3). 1H NMR (500 MHz, CDCl3): δ
2.63 (ddd, J ) 12.9, J ) 8.9, J ) 6.2 Hz, 1H), 2.60 (ddd, J )
12.9, J ) 8.8, J ) 7.4 Hz, 1H), 2.52 (tt, J ) 11.6, J ) 3.6 Hz,
1H), 2.12-2.08 (m, 1H), 1.93-1.62 (m, 7H), 1.51-1.21 (m, 18H),
0.86 (t, J ) 7.0 Hz, 3H). 13C NMR (125 MHz, CDCl3): δ 58.84,
48.95, 31.87, 29.50, 29.39, 29.27, 29.23, 28.98, 26.48, 25.58, 25.50,
25.23, 24.83, 22.75, 22.67, 14.11. Anal. Calcd for C16H32OS: C,
70.52; H, 11.84. Found: C, 70.59; H, 11.92. The ee value,
measured by NMR by addition of (R)-(methoxy)phenylacetic acid,
was found to be >98%.
63.25, 26.20, 25.58, 25.37, 25.28, 23.85. Anal. Calcd for C12H15
-
BrOS: C, 50.18; H, 5.26. Found: C, 50.32; H, 5.34. The ee value,
measured by HPLC (Chiralcel OB-H, hexane-i-propanol 80:20),
was >98%.
R ea ct ion of Alk yl Gr ign a r d R ea gen t s w it h p -Br om o-
p h en yl Su lfoxid es (2-5). A solution of 1.5 mmol of Grignard
reagent in THF was added to a solution of 1 mmol of alkyl
p-bromophenyl sulfoxide in 15 mL of THF at -30 °C and under
N2. After 1.5 h, the reaction mixture was quenched with a
saturated solution of NH4Cl. The usual workup yielded a residue,
which was purified by column chromatography and crystalliza-
tion (hexane) or distillation.
(S)-Cycloh exyl i-p r op yl su lfoxid e (10)20 bp 60-65 °C, p
) 4 × 10-4 Torr, Kugelrohr. [R]D +20.5 (c 1, CHCl3). The ee
value, measured by HPLC (Chiralcel OD-H, hexane-i-propanol
95:5), was >98%.
n -Decyl eth yl su lfoxid e (6)18 mp 51-52 °C (hexane). [R]D
+26.0 (c 1, CHCl3) for the (S) configuration; [R]D -25.5 (c 1,
CHCl3) for the (R) configuration. The ee value, measured by
HPLC (Chiralcel OB-H, hexane-i-propanol 95:5), was >98%. A
further NMR control of the enantiomeric purity was performed
by adding (R)-(methoxy)phenylacetic acid.
Ack n ow led gm en t. This work was financially sup-
ported in part by the Ministero dell’Universita` e della
Ricerca Scientifica e Tecnologica, Rome (National Project
“Stereoselezione in Sintesi Organica. Metodologie e
Applicazioni”), and by the University of Bari.
Cycloh exyl eth yl su lfoxid e (7)9,19 bp 60-65 °C, p ) 3 ×
10-4 Torr, Kugelrohr. [R]D +2.9 (c 1, CHCl3) for the (R) config-
uration; [R]D -2.5 (c 1, CHCl3) for the (S) configuration (lit.19
[R]D -27.2 (c 1, EtOH) for a 72% ee mixture). The ee value,
measured by HPLC (Chiralcel OD-H, hexane-i-propanol 95:5),
Su p p or tin g In for m a tion Ava ila ble: Relevant spectral
data for compounds 1-10. This material is available free of
charge via the Internet at http://pubs.acs.org.
J O010334M
(18) Racemic 6: Novitskaya, N. N.; Chernikova, S. I. Neftekhimiya
1970, 10, 429-436; Chem. Abstr. 1970, 73, 76486r.
(19) Holland, H. L.; Brown, F. M.; Lakshmaiah, G.; Larsen, B. G.;
Patel, M. Tetrahedron: Asymmetry 1997, 8, 683-698.
(20) Racemic 10: Firouzabadi, H.; Iranpoor, N.; Zolfigol, M. A. Synth.
Commun. 1998, 28, 1179-1187.