Remote stereocontrol by sulfinyl groups: Asymmetric alkylation of chiral 2-p-tolylsulfinyl benzyl carbanions

Article abstract of DOI:10.1016/j.tet.2005.08.014

Alkylation reactions of the benzyllithiums derived from enantiomerically pure 2-p-tolylsulfinyl alkylbenzenes have been carried out with excellent yields and high de. A lithiation-substitution sequence, stereochemically controlled by a remote sulfoxide, accounts for the experimental results.

Full text of DOI:10.1016/j.tet.2005.08.014

Tetrahedron 61 (2005) 10099–10104
Remote stereocontrol by sulfinyl groups: asymmetric alkylation of
chiral 2-p-tolylsulfinyl benzyl carbanions
*
´
Jose L. Garcıa Ruano, M. Teresa Aranda and Margarita Puente
´
´ ´ ´
Departamento de Quımica Organica, Facultad de Ciencias, Universidad Autonoma de Madrid, Cantoblanco, 28049-Madrid, Spain
Received 18 May 2005; revised 29 July 2005; accepted 2 August 2005
Available online 24 August 2005
Abstract—Alkylation reactions of the benzyllithiums derived from enantiomerically pure 2-p-tolylsulfinyl alkylbenzenes have been carried
out with excellent yields and high de. A lithiation-substitution sequence, stereochemically controlled by a remote sulfoxide, accounts for the
experimental results.
q 2005 Elsevier Ltd. All rights reserved.
1. Introduction
previous step to the nucleophilic attack. The importance of
these reactions for the asymmetric synthesis of benzylic
centers prompted us to investigate the behavior of these
prochiral benzyl carbanions in other type of reactions, such
as those of nucleophilic substitution, where the electrophiles
are not coordinating. Moreover, these reactions would
provide compounds lacking of any other functionality. In
this paper, we describe the results obtained in reactions
of 2-p-tolylsulfinyl alkylbenzenes with different alkylating
agents in the presence of LDA.
Many important classes of natural products with biological
significance have benzylic carbon stereocenters that lack
heteroatoms and bear an alkyl group, which is usually
methyl.1 The absence of any functionality at a such position
reduces the number of possibilities for synthesizing them
and converts the creation of these benzylic chiral centers in
a significant challenge in asymmetric synthesis.2 Enantio-
selective deprotonation/substitution processes of benzylic
positions have been widely investigated in the last years.3
The alkylation of benzylcarbanions with heteroatom-
containing substituents at a position (O, N, Si, S) has been
intensively explored employing several chiral auxiliaries
such as formamidines,4 oxazolines,5 (S)-methoxymethyl
pyrrolidine derivatives6 or carbamates.7 Tricarbonylchro-
mium arene complexes8 or chiral ligands, such as bis
(oxazolines)9 and (K)-sparteine,10 have been also applied.
The observed ee were variable and dependent on the
alkylating agent.
2. Results and discussion
Sulfoxides 1 and 2 were prepared in high ee (O98%)
according to the procedure previously reported12a start-
ing from ortho-bromo derivatives of ethylbenzene and
n-propylbenzene, respectively. The last one is not commer-
cially available and was prepared by reductive deoxygena-
tion of benzylic alcohol 3 employing the combination of
14
chlorodimethylsilane and a catalytic amount of InCl3
(Scheme 1).15
In our continuing search for new applications of sulfoxides
in asymmetric synthesis,11 we found that ortho-p-tolylsulfinyl
group can stabilize benzyllithium carbanions and promote
highly diastereoselective reactions, according to asym-
metric 1,4-induction processes. Their nucleophilic addition
to carbonyl compounds12 and N-sulfinyl imines13 evolved
with a complete control at the configuration of the benzylic
center. The success of these reactions was attributed to the
coordination of the electrophile to the benzyllithium as a
We first studied the alkylation reactions on sulfoxide 1
(Table 1). The addition of LDA (1.2 equiv) to a solution of 1
in THF at K78 8C, immediately produces a colored solution
indicative of formation of the anion. We further added the
alkylating reagents and maintained the same temperature
during 3 h. The alkylation with benzyl or allyl bromide
proceeded with high yields and stereoselectivities to afford
5a or 6a as the major products, respectively (entries 1 and
4). Diastereoselectivity was not improved by decreasing the
temperature till K90 8C (entries 2 and 5). Remarkable
decreases in the de are observed when alkyl chlorides are
Keywords: Benzylic stereocenter; Chiral benzyllithium; Sulfoxide; Remote
stereocontrol; Asymmetric alkylation; 1,4-Induction process.
Corresponding author. Tel.: C34 914974701; fax: C34 4973966;
e-mail: joseluis.garcia.ruano@uam.es
*
0040–4020/$ - see front matter q 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2005.08.014

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J. L. Garcıa Ruano et al. / Tetrahedron 61 (2005) 10099–10104
10100
Scheme 1. Synthesis of the starting sulfoxides 1 and 2.
Table 1. Alkylation of (S)-1-p-tolylsulfinyl-2-ethylbenzene (1)
Entry
RX
Temperature (8C)
Compound
a:b
Overall yield
1
2
3
4
5
6
7
8
BnBr
BnBr
BnCl
AllylBr
AllylBr
AllylCl
EtI
K78
K90
K78
K78
K90
K78
K78
K78
5
5
5
6
6
6
92:8
92:8
87 (78)a
b
70:30
87:13
86:14
52:48
—
78
86 (55)a
b
74
—
86
EtOTf
7
86:14
a Isolated yield of the major epimer.
b Yield not determined.
used as electrophiles instead of bromides (entries 3 and 6).
This influence of the leaving group on the stereoselectivity
had been also observed by Beak.10e,f These results show that
the stereoselectivity is dependent on the leaving group of the
alkyl halide. Less reactive alkylating agents are not efficient
enough and thus ethyl triflate had to be used (entry 8)
instead ethyl iodide, which afforded a complex mixture
(entry 7).
enlarged until 28 h. As it was expected, the 1H NMR spectra
for diastereoisomers 10a and 7b are identical, as well as
those for 10b and 7a.
The separation of the obtained diastereoisomers was not an
easy task. Compound 5a was achieved diastereomerically
pure by flash chromatography, whereas 6a was separated
from 6b by crystallization. Diastereoisomers 7–10 had to be
separated by chiral HPLC (see Section 4).
Sulfoxide 2 was treated under the same conditions as 1.
Reactivity of 2 is clearly lower than that of 1 as it can be
deduced from the presence of a significant amount of
Table 2. Alkylation of (S)-1-p-tolylsulfinyl-2-propylbenzene (2)
1
unreacted 2, detected by H NMR, in the crudes of all the
performed experiences. After several modifications of the
experimental conditions (temperature, solvent and reaction
time) we determined that the best results were obtained by
adding the electrophile in two batches with 2 h between the
additions. However, even in these conditions, a variable
residue of 2 remains unreacted. The results are collected in
Table 2.
Entry
RX
Product
a:b
Overall
yield
The previously commented lower reactivity of 2 is
compensated by its higher stereoselectivity. Benzylation
and allylation proceeded with around 90% de (entries 1 and
2) whereas methylation with MeOTf took place with 78%
de (entry 3). Both, yield and diastereoselectivity slightly
decreased with MeI (70% de, entry 4). The conversion was
not complete in any case even when the reaction time is
1
2
3
4
BnBr
8
9
10
10
95:5
94:6
89:11
85:15
75a
80b
74b
65b
AllylBr
MeOTf
MeI
a Starting material (4%) was recovered.
b Starting material (10%) was recovered.

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J. L. Garcıa Ruano et al. / Tetrahedron 61 (2005) 10099–10104
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Table 3. Desulfinylation of ortho-sulfinyl alkylbenzenes 5–10
R, R0 (sulfoxide)
Entry
Method
Product
Yield
Configuration
1
2
3
4
5
6
Me, Bn (5a)
Ra-Ni
Ra-Ni
n-BuLi
n-BuLi
n-BuLi
n-BuLi
11
12
13
14
15
16
60
59
43
22
38
52
R
R
R
S
R
R
Et, Bn (8a:8b, 95:5)
Me, Et (7a:7b, 65:35)
Et, Me (10a:10b, 93:7)
Me, Allyl (6a)
Et, Allyl (9a:9b, 91:9)
2.1. Desulfinylation reactions: configurational
assignment
The configuration of the predominant diastereoisomers was
established by conversion of compounds 5–10 into optically
active alkylbenzenes. The structure determination had been
established by comparison with authentic samples (ee), see
Section 4. Desulfinylation of benzylic derivatives 5 and 8
with Raney nickel gave (R)-11 and (R)-12, respectively
(Table 3, entries 1 and 2). The reactions of dialkyl
derivatives 7 and 10 with Ra-Ni only progress till sulfenyl
derivatives even enlarging the reaction times. Therefore, it
was necessary to perform the hydrogenolysis with n-BuLi16
(entries 3 and 4) to afford (R)-13 and (S)-14.† The low yields
obtained with n-BuLi are not surprising on the basis of the
large similarity of the aryl groups joined to the sulfinyl
group. Treatment of allylic derivatives 6 and 9 with Ra-Ni
afforded complex mixtures, being the sulfenyl derivatives
with reduced double bound the major products. By
enlarging the reaction times desulfurated products with no
double bond could be isolated in low yields. The reactions
of 6 and 9 with n-Bu–Li afforded better yields of 15 and 16,
respectively (entries 5 and 6).
Figure 1. Stereochemical course of the reaction.
incomplete stereoselectivity observed for alkylations (de
ranged between 70–90%) may be explained by assuming the
lower reactivity of these electrophiles. This fact determines
that they partially require to be attacked by the less stable
but more reactive species B, without defined configuration
(Fig. 1).
3. Conclusion
We have described the asymmetric alkylation of 2-p-
tolylsulfinyl alkylbenzenes controlled by the remote sulfinyl
group. Reactions are highly stereoselective and their de is
higher by increasing the reactivity of the electrophiles and
the length of the chain of the starting material. Desulfuration
with Ra-Ni or n-BuLi yields compounds with chiral
benzylic centers in high but not complete optical purity,
which is probably due to some problems in the purification
of the intermediates.
2.2. Stereochemical discussion
The stereochemical outcome of the alkylations is in accord-
ance with that previously proposed for reaction of ortho-p-
tolylsulfinyl benzyllithium carbanions with aldehydes.12
Taking into account steric effects, benzyllithium derivative
A must be the most stable among all diastereomers and
conformers since the most sized groups at sulfur (p-Tol) and
benzyl carbon (R) lack of allylic strain with the ortho
protons (Fig. 1). In the reactions of these species with
aldehydes, the carbonyl oxygen becomes associated with
the lithium as a previous step to the nucleophilic addition.
As this association is not possible with alkyl halides or
triflates, their reactivity is clearly lower (longer reaction
times). However, the fact that the configuration at the
benzylic carbon for the major diastereoisomer for alky-
lations was the same than that obtained in nuclephilic
additions to aldehydes, suggests that both reactions proceed
with retention in the configuration of the carbanions. The
4. Experimental
4.1. General experimental methods
Solvents were purified according to standard procedures.
Reactions were monitored by TLC on commercially
available precoated plates (Merck silica gel 60 F254).
Flash chromatography was performed with Merck silica
gel 60 (230–400 mesh ASTM). Melting points were
measured using a Gallemkamp apparatus in open capillary
tubes. Specific rotations were measured at room temperature
on a Perkin-Elmer 241 MC polarimeter and concentrations
† Compounds 13 and 14 are enantiomers of the same product. They are
achieved from the use of enriched mixtures of diastereoisomers 7a or 10a,
respectively.

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J. L. Garcıa Ruano et al. / Tetrahedron 61 (2005) 10099–10104
10102
are expressed in g/100 mL. H and 13C NMR spectra were
recorded in CDCl3 on a Bruker AC-300 spectrometer (300
and 75 MHz, respectively). Chemical shifts are reported in
ppm and J values are given in Hz. The attributions are
supported by double resonance experiments. IR spectra
were obtained in film with a Bruker Vector 22 spectrometer
(4000–400 cmK1). Mass spectra were measured by electron
impact (EI, 70 eV) or FAB with a VG AutoSpec spectro-
meter. Elemental analyses were obtained with a Perkin-
Elmer 2400 CHNS/O series II. Daicel Chiralcel OD or
Chiralpack AD columns and hexane/isopropanol as eluant
by using an Agilent 1100 HPLC equipment.
CH2). 13C NMR: d 142.7, 142.1, 141.9, 141.5, 130.9, 129.9,
129.5, 127.1, 125.9, 124.8, 33.8, 24.0, 21.3, 13.9. Anal.
Calcd for C16H18OS: C, 74.38; H, 7.02; S, 12.41. Found: C,
74.38; H, 7.09; S, 12.26. m/z (EIC): 258 (MC, 6), 241 (100),
211 (44), 166 (41), 149 (74), 91 (51), 77 (18). HRMS calcd
for C16H18OS: 258.1078. Found: 258.1070.
1
4.3. General procedure for alkylations
A solution of n-BuLi 2.5 M in hexane (0.60 mmol,
1.2 equiv) was added over i-Pr2NH (0.90 mmol, 1.8 equiv)
in THF (3 mL) at 0 8C. After 45 min stirring, the mixture
was cooled at K78 8C and a solution of the sulfoxide 1 or 2
(0.50 mmol, 1.0 equiv) in THF (2 mL) was added and
purple anion formed. After 1 h stirring, the electrophile
(1.5 mmol, 3.0 equiv) was added. 3 h later, the mixture was
hydrolyzed at that temperature (5 mL of saturated NH4Cl),
extracted (3!5 mL of CH2Cl2), dried (Na2SO4), washed
with brine and the solvent evaporated. The residue was
purified by flash column chromatography. For sulfoxide 2
two further equivalents were added after 2 h of reaction and
3 h later the mixture was hydrolyzed. Conditions of
separation by HPLC are indicated in any case.
4.2. Synthesis of 2-p-tolylsulfinyl alkylbenzenes
4.2.1. 1-(2-Bromophenyl)-1-propanol (3). A solution of
ethylmagnesium bromide, previously formed by addition of
bromoethane (6.5 mL, 88.0 mmol) over Mg (1.9 g,
80.0 mmol) in anhydrous ether (20 mL), was added slowly
over a solution of 2-bromobenzaldehyde (9.8 mL,
84.0 mmol) in anhydrous ether (10 mL) at 0 8C. After 5 h
stirring at room temperature, the mixture was hydrolyzed
(30 mL of saturated NH4Cl), extracted (3!30 mL of ether),
dried (MgSO4), washed with brine and the solvent
evaporated. The residue was purified by flash column
chromatography (eluant, hexane/AcOEt 9:1). Yield: 53% as
4.3.1. [2R,(S)S]-2-[2-(p-Tolylsulfinyl)phenyl]-1-phenyl-
propane (5a). This compound was obtained starting from
sulfoxide 1. Eluant for chromatography: hexane/AcOEt 1:3.
Yield 5aC5b (92:8): 87%. The mixture of 5a and 5b
resulting from the chromathography of the crude reaction
was newly chromatographied (eluant:hexane/EtOAc 3:2) to
give 5a with deO98% (yield 78%). Daicel Chiralpack AD
(hexane/i-PrOH 90:10, flow rate 1 mL/min): tSZ23.4 min
and tRZ24.9 min. (a(D20 K174.7 (c 2, CHCl3). IR: 3026,
2963, 2925, 1595, 1493, 1083, 1030 cmK1. 1H NMR: d 7.79
(d, 1H, JZ7.4 Hz, Ar), 7.50–7.35 (m, 3H, Ar), 7.25–7.16
(m, 7H, Ar), 6.91 (m, 2H, Ar), 3.60 (sx, 1H, JZ6.9 Hz,
CH3–CH–), 2.72 (d, 2H, JZ7.5 Hz, Ph-CH2–), 2.36 (s, 3H,
CH3–Ar), 1.26 (d, 3H, JZ6.9 Hz, CH3–CH–). 13C NMR: d
145.5, 142.2, 141.7, 141.3, 139.7, 131.3, 129.8, 129.0,
128.1, 127.3, 126.5, 125.9, 125.7, 43.1, 36.3, 21.9, 21.3.
Anal. Calcd for C22H22OS: C, 79.00; H, 6.63; S, 9.59.
Found: C, 78.89; H, 6.68; S, 9.99. m/z (EIC): 334 (MC, !1),
317 (100), 243 (24), 225 (95), 211 (31), 135 (24), 91 (79), 77
(15). HRMS calcd for C22H22OS: 334.1391. Found:
334.1379.
colorless oil. IR: 3385, 2967, 1466, 1020, 741 cmK1. H
1
NMR: d 7.52 (m, 2H, Ar), 7.33 (t, 1H, JZ7.5 Hz, Ar), 7.11
(dt, 1H, JZ1.6, 7.5 Hz, Ar), 5.00 (dd, 1H, JZ4.8, 7.5 Hz,
–CH–OH), 2.09 (broad s, 1H, –OH), 1.94–1.59 (m, 2H,
CH3–CH2—), 1.00 (t, 3H, JZ7.5 Hz, CH3–CH2–). 13C
NMR: d 143.5, 132.6, 128.7, 127.6, 127.3, 122.1, 74.2, 30.5,
10.1. Anal. Calcd for C9H11BrO: C, 50.26; H, 5.15. Found:
C, 50.36; H, 5.12. m/z (EIC): 214 (MC, 12), 185 (100), 157
(22), 105 (14), 84 (42), 77 (88). HRMS calcd for C9H11BrO:
213.9993. Found: 213.9986.
4.2.2. 1-Bromo-2-propylbenzene (4). A solution of alcohol
3 (4.3 g, 20.1 mmol) in freshly distilled CH2Cl2 (30 mL)
was added to a solution of InCl3 (5–10 mol%) and
Me2SiClH (6.0 mL, 54.2 mmol) in CH2Cl2 (50 mL) at
room temperature under Ar atmosphere. After 45 min
stirring, the mixture was hydrolyzed (50 mL of H2O),
extracted (3!50 mL of ether), dried (MgSO4), washed with
brine and the solvent evaporated. The residue was purified
by flash column chromatography (eluant, hexane). Yield:
75% as colorless oil. IR: 2960, 2871, 1469, 1439, 1021,
4.3.2. [4R,(S)S]-4-[2-(p-Tolylsulfinyl)phenyl]-1-pentene
(6a). This compound was obtained starting from sulfoxide
1. Eluant for chromatography: hexane/AcOEt 4:1. Yield
6aC6b (87:13): 86%. The mixture of 6a and 6b resulting
from the chromathography of the crude reaction was
crystallized to give 6a with deO98% (yield 55%). Mp:
67–68 8C (Et2O/hexane, white solid). Daicel Chiralpack AD
(hexane/i-PrOH 87:13, flow rate 1 mL/min): tSZ11.4 min
and tRZ12.4 min. (a(D20 K120.0 (c 1, CHCl3). IR: 2961,
748 cmK1. H NMR: d 7.52 (d, JZ7.5 Hz, 1H, Ar), 7.21
1
(m, 2H, Ar), 7.04 (m, 1H, Ar), 2.71 (m, 2H, –CH2–Ar), 1.65
(sx, 2H, JZ7.3 Hz, CH3–CH2–), 0.98 (t, 3H, JZ7.3 Hz,
CH3–CH2–). 13C NMR: d 141.8, 132.6, 130.3, 127.3, 127.2,
124.4, 38.2, 23.0, 13.8. Anal. Calcd for C9H11Br: C, 54.30;
H, 5.57. Found: C, 54.49; H, 5.15.
4.2.3. (S)-1-p-Tolylsulfinyl-2-propylbenzene (2). The
synthesis of this compound was performed starting from 4
according to the procedure previously reported for 1.12a
Yield: 51% as white solid. Mp: 29–30 8C (Et2O/hexane).
(a(2D0 K128.2 (c 1, CHCl3). IR: 2961, 1642, 1467, 1085,
1
2931, 1593, 1472, 1081, 1027 cmK1. H NMR: d 7.96 (m,
1H, Ar), 7.48 and 7.23 (AA0BB0 system, 4H, Tol), 7.47–
7.38 (m, 2H, Ar), 7.28 (m, 1H, Ar), 5.49–5.35 (m, 1H,
–CH]CH2), 4.86–4.81 (m, 2H, CH2]CH–), 3.26 (sx, 1H,
JZ6.7 Hz, CH3–CH–), 2.36 (s, 3H, CH3–Ar), 2.15–1.92 (m,
2H, –CH2–CH–), 1.25 (d, 3H, JZ6.9 Hz, CH3–CH–). 13C
NMR: d 145.1, 142.0, 141.6, 135.8, 131.1, 129.9, 127.2,
126.4, 126.3, 124.7, 116.5, 41.2, 34.2, 21.6, 21.3. Anal.
1033 cm0K1. H NMR: d 7.92 (m, 1H, Ar), 7.47 and 7.23
1
(AA0BB system, 4H, Tol), 7.39 (m, 2H, Ar), 7.19 (m, 1H,
Ar), 2.82–2.55 (m, 2H, –CH2–Ar), 2.35 (s, 3H, CH3–Ar),
1.57 (m, 2H, –CH2–CH3), 1.14 (t, 3H, JZ7.5 Hz, CH3–

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J. L. Garcıa Ruano et al. / Tetrahedron 61 (2005) 10099–10104
10103
Calcd for C18H20OS: C, 76.01; H, 7.09; S, 11.27. Found: C,
76.38; H, 7.22; S, 11.12. m/z (EIC): 284 (MC, 2), 267 (91),
243 (30), 225 (100), 211 (24), 143 (55), 135 (32), 91 (47), 77
(20). HRMS calcd for C18H20OS: 284.1235. Found:
284.1233.
149 (46), 91 (52), 77 (27). HRMS calcd for C19H22OS:
298.1391. Found: 298.1389.
4.3.6. [2S,(S)S]-2-[2-(p-Tolylsulfinyl)phenil]-butane
(10a). This compound was obtained from the reaction of
sulfoxide 2 with methyl triflate. Eluant for chromatography:
hexane/AcOEt 4:1. Yield 10aC10b (89:11): 86%. Only the
NMR parameters of major diastereoisomer 10a are
4.3.3. [2R,(S)S]-2-[2-(p-Tolylsulfinyl)phenil]-butane (7a).
This compound was obtained from the reaction of sulfoxide
1 with ethyl triflate. Eluant for chromatography: hexane/
AcOEt 4:1. Yield 7aC7b (86:14): 86%. Daicel Chiralcel
OD (hexane/i-PrOH 98:2, flow rate 1 mL/min): tSZ
27.9 min and tRZ30.3 min. Only the NMR parameters of
major diastereoisomer 7a are indicated. IR: 2957, 1463,
1082, 1057, 10280cmK1. 1H NMR: d 7.97 (m, 1H, Ar), 7.49
and 7.24 (AA0BB system, 4H, Tol), 7.45–7.36 (m, 2H, Ar),
7.28 (m, 1H, Ar), 3.10 (sx, 1H, JZ6.9 Hz, CH3–CH–), 2.36
(s, 3H, CH3-Ar), 1.52–1.26 (m, 2H, CH3–CH2–), 1.24 (d,
3H, JZ6.9 Hz, CH3–CH–), 0.60 (t, 3H, JZ7.3 Hz, CH3–
CH2–). 13C NMR: d 145.6, 141.9, 141.2, 130.9, 129.5,
126.6, 125.9, 124.4, 123.9, 35.5, 29.4, 21.5, 20.9, 11.5.
Anal. Calcd for C17H20OS: C, 75.50; H, 7.24; S, 11.52.
Found: C, 75.21; H, 7.46; S, 11.76.
1
indicated. H NMR: d 7.99 (m, 1H, Ar), 7.46 and 7.22
(AA0BB0 system, 4H, Tol), 7.41 (m, 2H, Ar), 7.25 (m, 1H,
Ar), 3.06 (sx, 1H, JZ6.9 Hz, CH3–CH–), 2.35 (s, 3H, CH3–
Ar), 1.63 (quint, 2H, JZ7.3 Hz, CH3–CH2–), 0.88 (d, 3H,
JZ6.9 Hz, CH3–CH–), 0.84 (t, 3H, JZ7.3 Hz, CH3–CH2–).
13C NMR: d 145.3, 142.7, 142.4, 141.5, 131.1, 129.9, 127.0,
126.1, 126.0, 124.1, 35.9, 31.3, 21.3, 20.9, 12.0.
4.4. General procedure for desulfynilations summarized
in Table 3
Method A The sulfoxide was dissolved in a minimal amount
of ethanol and excess of Raney nickel was added. The
reaction mixture was vigorously stirred at room temperature
and was monitored by TLC. When no starting material
remained, stirring was stopped and the solvent was carefully
decanted and filtered on Celite. The solvent was evaporated
and the product was obtained from the residue in high purity
(Table 3).
4.3.4. [2R,(S)S]-2-[2-(p-Tolylsulfinyl)phenyl]-1-phenyl-
butane (8). This compound was obtained starting from
sulfoxide 2. Eluant for chromatography: hexane/AcOEt 3:1.
Yield 8aC8b (95:5): 75%. Daicel Chiralpack AD (hexane/
i-PrOH 87:13, flow rate 1 mL/min): t2Z18.5 min, tSZ
1
19.6 min and tRZ23.2 min. The H NMR parameters of
minor diastereoisomer are indicated in italics. These values
Method B A solution of n-BuLi in hexane (10 equiv) was
added over a solution of sulfoxide in THF at K78 8C under
Ar atmosphere. After 3 min stirring, the mixture was
hydrolyzed at that temperature (saturated NH4Cl), extracted
(CH2Cl2), dried (Na2SO4), washed with brine and the
solvent evaporated. The residue was purified by flash
column chromatography with hexane as eluant.
are required to establish the de. (a(2D0 K190.6 (c 1, CHCl3).
1
IR: 2961, 1644, 1454, 1083, 1032 cmK1. H NMR: d 7.96
(m, 1H, Ar, minor diastereoisomer), 7.75 (m, 1H, Ar), 7.51–
7.34 (m, 3H, Ar), 7.17–7.10 (m, 7H, Ar), 6.87 (m, 2H, Ar),
3.44 (m, 1H, –CH2–CH–CH2–), 2.80 and 2.69 (d AB
system, 2H, JZ7.5, 13.5 Hz, Ph-CH2–), 2.35 (s, 3H, CH3-Ar),
1.83–1.15 (m, 2H, CH3–CH2–), 0.81 (t, 3H, JZ7.5 Hz,
CH3–CH2–), 0.39 (t, 3H, JZ7.3 Hz, CH3–CH2, minor
diastereoisomer). 13C NMR: d 143.9, 143.7, 141.7, 141.1,
139.8, 131.2, 129.8, 129.1, 128.1, 127.4, 126.7, 125.9,
125.7, 43.5, 42.0, 29.2, 21.3, 11.7. m/z (EIC): 348 (MC, !1),
331 (100), 241 (36), 211 (37), 91 (62), 77 (9). HRMS calcd
for C23H24OS: 348.1548. Found: 348.1521.
4.4.1. (R)-1,2-Diphenylpropane (11).17 This compound
was obtained according to method A starting from sulfoxide
5a. Yield: 60%. (a(2D0 K73.7 (c 1, CHCl3). Lit.17b (a(2D0
K78.6 (c 2.02, CHCl3) to eeO99%. 1H NMR: d 7.34–7.08
(m, 10H, Ar), 3.11–2.91 (m, 2H, Ph–CH2–), 2.84–2.71 (m,
1H, CH3–CH–), 1.25 (d, 3H, JZ7.0 Hz, CH3–CH–). 13C
NMR: d 146.9, 140.8, 129.1, 128.2, 128.1, 127.0, 126.0,
125.8, 45.0, 41.8, 21.1.
4.3.5. [4R,(S)S]-4-[2-(p-Tolylsulfinyl)phenil]-1-hexene
(9). This compound was obtained starting from sulfoxide
2. Eluant for chromatography: hexane/AcOEt 3:1. Yield
9aC9b (94:6): 80%. Daicel Chiralpack AD (hexane/i-PrOH
90:10, flow rate 1 mL/min): tSZ13.1 min, tRZ14.0 min and
t2Z15.9 min. The 1H NMR parameters of minor diastereo-
isomer are indicated in italics. These values are required to
establish the de. (a(2D0 K94.2 (c 1, CHCl3). IR: 2962, 2929,
1640, 1469, 1084, 1033 cmK1. 1H NMR: d 7.98 (m, 1H, Ar),
7.910 (m, 1H, Ar, minor diastereoisomer), 7.47 and 7.22
(AA BB0 system, 4H, Tol), 7.45–7.39 (m, 2H, Ar), 7.25–
7.20 (m, 1H, Ar), 5.37–5.24 (m, 1H, –CH]CH2), 4.79–4.75
(m, 2H, CH2]CH–), 3.05 (m, 1H, CH2–CH–), 2.35 (s, 3H,
CH3-Ar), 2.19–1.90 (m, 2H, –CH2–CH–), 1.87–1.45 (m,
2H, CH3–CH2–), 0.82 (t, 3H, JZ7.3 Hz, CH3–CH2–), 0.47
(t, 3H, JZ7.3 Hz, CH3–CH2, minor diastereoisomer). 13C
NMR: d 143.4, 142.1, 141.7, 135.9, 131.1, 129.9, 127.2,
126.6, 126.5, 124.5, 116.4, 41.3, 39.8, 29.1, 21.4, 11.7. m/z
(EIC): 298 (MC, 1), 281 (100), 257 (10), 241 (70), 239 (53),
4.4.2. (R)-1,2-Diphenylbutane (12).18 This compound was
obtained according to method A starting from a mixture of
sulfoxides 8a:8b (95:5). Yield: 59%. (a(2D0 K101.9 (c 1,
CHCl3). Lit.18 (a(D20 C12.5 (c 0.3, CHCl3) to S configura-
tion. The ee was not determined by the authors in that report.
1H NMR: d 7.43–7.18 (m, 10H, Ar), 3.04 (m, 2H, Ph–CH2–),
2.92–2.83 (m, 1H, CH2–CH–CH2–), 1.96–1.69 (m, 2H,
CH3–CH2–), 0.92 (t, 3H, JZ7.3 Hz, CH3–CH2). 13C NMR:
d 145.0, 140.8, 129.1, 128.1, 128.0, 127.8, 125.9, 125.7,
49.8, 43.5, 28.3, 12.1.
4.4.3. (R)-2-Rhenylbutane (13).19 This compound was
obtained according to method B starting from a mixture of
sulfoxides 7a:7b (65:35). Yield: 43%. (a(2D0 K6.2 (c 0.5,
CHCl3). Lit.19a (a(D20 C28.4 (neat) to S configuration. The
1
ee was not determined by the authors in that report. H
NMR: d 7.35–7.14 (m, 5H, Ar), 2.60 (sx, 1H, JZ7.0 Hz,

´
J. L. Garcıa Ruano et al. / Tetrahedron 61 (2005) 10099–10104
10104
6. (a) Chan, T. H.; Pellon, P. J. Am. Chem. Soc. 1989, 111,
8737–8738. (b) Chan, T. H.; New, K. T. J. Org. Chem. 1992,
57, 6107–6111.
CH3–CH–), 1.61 (quint, 2H, –CH2–CH–), 1.25 (d, 3H, JZ
7.0 Hz, CH3–CH–), 0.84 (t, 3H, JZ7.5 Hz CH3–CH2–).
4.4.4. (S)-2-Phenylbutane (14).19 This compound was
obtained according to method B starting from a mixture of
sulfoxides 10a:10b (3:97). Yield: 22%. (a(2D0 C10.4 (c 0.5,
CHCl3). Lit.19a (a(D20 C28.4 (neat). The ee was not
determined by the authors in that report.
7. (a) Carstens, A.; Hoppe, D. Tetrahedron 1994, 50, 6097–6108.
(b) Derwing, C.; Hoppe, D. Synthesis 1996, 149–154.
8. Brisander, M.; Caldirola, P.; Johansson, A. M.; Hacksell, U.
J. Org. Chem. 1998, 63, 5362–5367 and references cited
therein.
9. Nakamura, S.; Nakagawa, R.; Watanabe, Y.; Toru, T. J. Am.
Chem. Soc. 2000, 122, 11340–11347.
4.4.5. (R)-4-Phenylpentene (15).20 This compound was
obtained according to method B starting from sulfoxide 6a.
Yield: 38%. (a(D20 K21.4 (c 1, CHCl3). Lit.20a (a(2D0 K19.3
10. (a) Wilkinson, J. A.; Rossington, S. B.; Ducki, S.; Leonard, J.;
Hussain, N. Tetrahedron: Asymmetry 2004, 15, 3011–3013.
(b) Johson, T. A.; Jang, D. O.; Slafer, B. W.; Curtius, M. D.;
Beak, P. J. Am. Chem. Soc. 2002, 124, 11689–11698. (c) Lutz,
G. P.; Du, H.; Gallagher, D. J.; Beak, P. J. Org. Chem. 1996,
61, 4542–4554. (d) Laumer, J. M.; Kim, D. D.; Beak, P. J. Org.
Chem. 2002, 67, 6797–6804. (e) Thayumanavan, S.; Basu, A.
J. Am. Chem. Soc. 1997, 119, 8209–8217. (f) Basu, A.; Beak,
P. J. Org. Chem. 1996, 118, 1575–1576.
1
(neat) to eeZ97.4%. H NMR: d 7.32–7.14 (m, 5H, Ar),
5.75–5.61 (m, 1H, –CH]CH2), 5.00–4.89 (m, 2H,
CH2]CH–), 2.57–2.34 (m, 3H, –CH2–CH–), 1.81–1.49
(m, 2H, CH3–CH2–), 0.79 (t, 3H, JZ7.3 Hz, CH3–CH2–).
13C NMR: d 145.2, 137.2, 128.2, 127.8, 125.9, 115.7, 47.6,
40.9, 28.8, 12.0.
4.4.6. (R)-4-Fenilhexeno (16).19a,21 This compound was
obtained according to method B starting from a mixture of
sulfoxides 9a:9b (95:5). Yield: 52%. (a(2D0 K8.0 (c 1,
CHCl3). Lit.19a (a(D20 K8.99 (neat), eew86–89%. 1H NMR:
d 7.32–7.14 (m, 5H, Ar), 5.75–5.61 (m, 1H, –CH]CH2),
5.00–4.89 (m, 2H, CH2]CH–), 2.57–2.34 (m, 3H, –CH2–
CH–), 1.81–1.49 (m, 2H, CH3–CH2–), 0.79 (t, 3H, JZ
7.3 Hz, CH3–CH2–). 13C NMR: d 145.2, 137.2, 128.2,
127.8, 125.9, 115.7, 47.6, 40.9, 28.8, 12.0.
´ ´
11. (a) Garcıa Ruano, J. L.; Fajardo, C.; Martın, M. R.
´
Tetrahedron 2005, 61, 4363–4371. (b) Garcıa Ruano, J. L.;
´ ´
Alonso de Diego, S. A.; Martın, M. R.; Torrente, E.; Martın
´
Castro, A. M. Org. Lett. 2004, 6, 4945–4948. (c) Garcıa
´
Ruano, J. L.; Fajardo, C.; Martın, M. R.; Midura, W.;
Mikolajczyk, M. Tetrahedron: Asymmetry 2004, 15,
´ ´
2475–2482. (d) Garcıa Ruano, J. L.; Aleman, J.; del Prado,
´
M.; Fernandez, I. J. Org. Chem. 2004, 69, 4454–4463. (e)
´
Garcıa Ruano, J. L.; Alemparte, C. J. Org. Chem. 2004, 69,
´
1405–1408. (f) Garcıa Ruano, J. L.; Tito, A.; Peromingo, M. T.
J. Org. Chem. 2003, 68, 10013–10019.
´
12. (a) Garcıa Ruano, J. L.; Carren˜o, M. C.; Toledo, M. A.;
Acknowledgements
Aguirre, J. M.; Aranda, M. T.; Fisher, J. J. Angew. Chem., Int.
´
Ed. 2000, 39, 2736–2737. (b) Garcıa Ruano, J. L.; Aranda,
We thank CAICYT (Grant BQU2003-04012) for financial
support.
M. T.; Aguirre, J. M. Tetrahedron 2004, 60, 5383–5392.
´ ´
13. (a) Garcıa Ruano, J. L.; Aleman, J.; Soriano, J. F. Org. Lett.
´ ´
2003, 5, 677–680. (b) Garcıa Ruano, J. L.; Aleman, J. Org.
Lett. 2003, 5, 4513–4516.
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