Asymmetric Darzens reaction utilizing chloromethyl phenyl sulfone under phase-transfer catalyzed conditions

Article abstract of DOI:10.1016/S0040-4020(01)01244-3

The development of the catalytic asymmetric Darzens reaction utilizing chloromethyl phenyl sulfone is described. The reaction smoothly proceeded to give α,β-epoxysulfones with satisfactory enantioselectivity (up to 83% ee) using chiral quaternary ammonium

Full text of DOI:10.1016/S0040-4020(01)01244-3

TETRAHEDRON
Pergamon
Tetrahedron 58 (2002) 1407±1413
Asymmetric Darzens reaction utilizing chloromethyl phenyl
sulfone under phase-transfer catalyzed conditions
Shigeru Araip and Takayuki Shioiri
Graduate School of Pharmaceutical Sciences, Nagoya City University, Tanabe-dori, Mizuho-ku, Nagoya 467-8603, Japan
Received 25 September 2001; revised 20 November 2001; accepted 13 December 2001
AbstractÐThe development of the catalytic asymmetric Darzens reaction utilizing chloromethyl phenyl sulfone is described. The reaction
smoothly proceeded to give a,b-epoxysulfones with satisfactory enantioselectivity (up to 83% ee) using chiral quaternary ammonium salts as
the phase transfer catalyst. q 2002 Elsevier Science Ltd. All rights reserved.
The Darzens reaction1 has been recognized as one of the
most important carbon±carbon bond forming reactions by
controlling the two stereogenic centers to afford an epoxide
so that its application to asymmetric synthesis is one of the
major challenging goals in modern organic chemistry.
Although one hundred years have passed since the dis-
covery of this reaction, few successful examples of the
catalytic asymmetric Darzens reaction are known.2 Since
the Darzens reaction includes an aldol (C±C bond forma-
tion) and the following intramolecular cyclization (C±O
bond formation) steps, stoichiometric amounts of base
should be required to achieve higher chemical yields
(Scheme 1). For a strong base, proton abstraction quickly
occurs to give the carbanion followed by C±C bond forma-
tion. Therefore, past examples of asymmetric synthesis are
required to use a stoichiometric amount of a chiral source
such as chiral auxiliaries3a,b or an external ligand.3c In order
to obtain optically active epoxides via the Darzens reaction,
many trials have been examined such as chiral reagents or
substrates. On the other hand, phase transfer catalysts
(PTC)4 present one of the most ef®cient methodologies for
this reaction because PTC, such as quaternary ammonium
salts, can be converted into the corresponding base in situ in
the presence of inorganic bases such as metal carbonates or
hydroxides.4 These species allow exchange of the counter
ion to generate both a chiral nucleophile and metal halide as
side products. Moreover, this methodology gives us prac-
tical, economic and operational advantages which lead to
green chemistry. We have already reported2a±d the asym-
metric Darzens reaction using chiral PTCs. In this paper,
we report the asymmetric Darzens reaction utilizing phenyl
sulfone with carbonyl compounds under PTC conditions.2b
The advantages of using sulfones are not only their cap-
ability for further chemical transformation5 but also the
stabilization effect of the a-anion. Thus, they act as good
nucleophiles which are generated under quite mild basic
conditions. Moreover, this type of anion does exist as a
carbanion and not the enolate form so that chiral external
molecules such as the chiral quaternary ammonium cation
Scheme 1. PTC-catalyzed Darzens reaction.
Keywords: asymmetric reaction; Darzens reaction; diastereoselection; epoxides; phase-transfer.
Corresponding author. Tel./fax: 181-52-834-4172; e-mail: shioiri@phar.nagoya-cu.ac.jp
p
0040±4020/02/$ - see front matter q 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020(01)01244-3

1408
S. Arai, T. Shioiri / Tetrahedron 58 (2002) 1407±1413
Table 1. PTC effect of Darzens reaction using chioromethyl phenyl sulfone 2
Entry
PTC
R
Yield of 3a (%)
ee of 3a (%)
1
2
3
4
5
6
7
None
A: Arˆ4-CF3±C6H4
±
H
H
H
H
60
85
68
58
41
76
44
±
69
54
51
7
B: ArˆPh
C: Arˆ4-OMe±C6H4
D: Arˆ2,4-(CF3)2±C6H3
E: Arˆ9-anthraceny1a
F: Arˆ4-CF3±C6H4
H
Allyl
46
15b
a
Ammonium chloride was used.
The reaction was carried out for 5 h.
b
can affect the reaction carbon center more strongly during
the enantioselective C±C bond formation step, shown in
Scheme 1.
the desired product 3a in 85% yield with 69% ee (Table 1,
entry 1 vs 2). The diastereoselectivity of 3a was determined
by the coupling constant between Ha and Hb observed in the
NMR analysis to be the trans form only and the absolute
con®guration was determined by an X-ray crystallo-
graphical analysis to be (1R,2R)-4a.2b The other type of
PTC, which has electron donating or withdrawing groups
on the benzene ring such as B, C or D, resulted in moderate
to lower enantioselectivities so that the tri¯uoromethyl
group on the C-4 position was found to be superior (Table
1, entries 3±5). Recently, the 9-anthracenylmethyl function
was found to be quite useful for asymmetric phase transfer
reactions.6 However, it was not effective in this Darzens
Initially, we focused on using chloromethyl phenyl sulfone
2 as a nucleophile for the Darzens reaction. This substrate
was found to possess acidic protons that allowed the reac-
tion to proceed smoothly with aromatic aldehydes in toluene
under PTC conditions. Although the reaction between
benzaldehyde (1a) and the sulfone 2 quickly proceeded
even in the absence of PTC at room temperature, a catalytic
amount of the chiral quaternary ammonium salt (PTC A)
derived from the quinine did act as a good catalyst to afford
Table 2. Catalytic asymmetric Darzens reaction using aromatic aldehydes
Entry
Ar
1b: a-Np
1c: b-Np
Time (h)
Yield of 3 (%)
ee of 3 (%)
1
2
3
4
5
6
7
8
1
1
2
1
1.5
2
1.5
1
1
1.5
1.5
1.5
1
3b: 42
3c: 82
3d: 84
3e: 82
3f: 71
3g: 70
3h: 83
3i: 72
3j: 80
3k: 69
3m: 78
3n: 83
3p: 27
3q: 90
65
65
78
74
72
81
65
64
64
71
65
64
47
33
1d: 4-Me±C6H4
1e: 3-Me±C6H4
1f: 4-Ph±C6H4
1g: 4-t-Bu±C6H4
1h: 3-PhO±C6H4
1i: 4-Cl±C6H4
1j: 4-Br±C6H4
1k: 3-Br±C6H4
1m: 4-CF3±C6H4
1n: 3-CF3±C6H4
1p: 2-Br±C6H4
1q: 2-CF3±C6H4
9
10
11
12
13
14
2

S. Arai, T. Shioiri / Tetrahedron 58 (2002) 1407±1413
1409
Table 3. Phase-transfer catalyzed Darzens reaction using aliphatic alde-
hyde
to give the desired product 5a with 32% ee (entry 2). The
interaction between heteroatoms such as N or O in PTC and
the metal center would be expected to form some kind of
complex though the active species are still unclear.
Although other aldehydes such as 4b±d also gave unsatis-
factory enantiomeric excesses, the addition of Sn(OTf)2 was
more effective, achieving up to a 31% ee than in the absence
of Sn(OTf)2 (entries 3±5, Table 3). This system also
affected the aromatic system as shown in entry 6. We
were pleased that the reaction of 1a also proceeded to
give 3a in 66% yield with 83% ee in the presence of
10 mol% of Sn(OTf)2, even though the reaction rate drama-
tically decreased.
Entry
R
Additive
Time (h)
Yield (%)
ee (%)
1
2
3
4
5
6
4a: i-Pr
4a: i-Pr
4b: Et
4c: t-Bu
4d: Et2CH
1a: Ph
None
3
20
1
26
24
20
5a: 100
5a: 81
5b: 71
5c: 77
5d: 75
3a: 66
±
Sn(OTf)2
Sn(OTf)2
Sn(OTf)2
Sn(OTf)2
Sn(OTf)2
32
12
17
31
83
Finally, we tried to use methyl ketone derivatives as the
electrophilic agents. Still now, the enantiocontrol of the
chiral quaternary carbons via direct C±C bond forming
process is a challenging goal in organic synthesis. In the
beginning, we investigated the use of acetophenone 6a as
a substrate. Although the reaction smoothly proceeded using
tetrahexylammonium bromide (THAB, 10 mol%) as the
PTC, the desired epoxides 7a and 8b were obtained as a
diastereomixture (cis/transˆ1.4: 1) in 94% yield (Table 4,
entry 1). On the other hand, the reaction utilizing PTC A
was found to be quite slow to give 7a and 8b with moderate
yields under similar conditions. Their enantioselectivities
were revealed to be 60% ee for 7a and 22% ee for 8a
(entry 2). The diastereoselectivity is strongly dependent
on the substituents in 6 and the catalyst structure. For
example, an a-naphthyl group increased the ratio of trans
in the THAB system though PTC A exclusively gave 7b
with a much lower ee and yield (entry 3 vs 4). Moreover,
other sterically hindered substrates such as the tert-butyl
ketone 6c afforded the trans isomer 7c only using THAB.
Aliphatic ketones such as 6d exhibited a higher reactivity in
the presence of PTC A (10 mol%) and the reaction smoothly
occurred even at 08C though its diastereoselectivity was
revealed to be 2.4:1 and the enantiomeric ef®ciency was
around 30% ee (entry 7). The reaction of other types of
sterically hindered ketones 6e were quite ineffective, pro-
ducing 8e as a racemate in lower yield (entry 8).
reaction (see entry 6 in Table 1). Furthermore, the presence
of the free hydroxy group at the C-9 position in the catalyst
will be essential. These results are summarized in Table 1.
Encouraged by these results, we next examined other
aromatic aldehydes. As shown in Table 2, this reaction
system is quite general for aromatic aldehydes. For
example, both the a and b-naphthaldehydes 1b and 1c
gave the corresponding a,b-epoxysulfones 3b and 3c in
moderate to good yields with 65% ee, respectively (entries
1 and 2 in Table 2). Other derivatives which possess alkyl or
aryl-substituents on the para position such as 1d±1f also
gave moderate to good ee in higher chemical yields (entries
3±5). Especially, 1g afforded 3g with 81% ee in 70% yield
(entry 6). An electron donating group was also effective to
afford the desired product 3h from 1h with good yield and
ee (entry 7). This reaction has also been found to be effective
for the halogenated derivatives such as 1i, 1j, and 1k or the
tri¯uoromethyl derivatives 1m and 1n, as shown in entries
8±13 in Table 2. On the other hand, 2-substituted aldehydes
gave a lower ee relative to the 3 or 4-substituted derivatives
(entries 13 and 14). The reason is still unclear but we assume
that it would depend on the steric repulsion between the
catalyst and the functional group on the 2 position.
We next focused on the use of aliphatic aldehydes 4. Despite
the good enantioef®ciency of aromatic aldehydes, isobutyr-
aldehyde 4a gave the Darzens product 5a in quantitative
yield as the racemate under similar reaction conditions
(Table 3, entry 1). On the other hand, the addition of a
catalytic amount of metal salts such as Sn(OTf)2 was
found to act as an effective additive in the aliphatic system
In conclusion, we have found that chiral quaternary ammo-
nium salts derived from cinchona alkaloids act as an
ef®cient phase transfer catalyst in the asymmetric Darzens
reaction. Especially, aromatic aldehydes 1 and the sulfone 2
with PTC A gave the desired product with moderate to high
Table 4. Reaction with ketone 6
Entry
Ketone
PTC
Time (h)
Yield of 7 (ee)
Yield of 8 (ee)
1
2
3
4
5
6
7
8
6a: R1ˆPh, R2ˆMe
THAB
A
THAB
A
THAB
A
A
A
13
18
23
60
45
60
27
48
7a: 54 (2)
7a: 29 (60)
7b: 61 (2)
7b: 30 (6)
7c: 47 (2)
7c: 11 (0)
7d: 69 (29)
7e: 0
8a: 40 (2)
8a: 14 (22)
8b: 34 (2)
8b: 0 (2)
8c: 0 (2)
8c: 0 (2)
8d: 29 (28)
8e: 19 (0)
6a: R1ˆPh, R2ˆMe
6b: R1ˆa-Np, R2ˆMe
6b: R1ˆa-Np, R2ˆMe
6c: R1ˆt-Bu, R2ˆMe
6c: R1ˆt-Bu, R2ˆMe
6d: R1ˆPh(CH2)2, R2ˆMe
6e: R1ˆPh, R2ˆi-Pr

1410
S. Arai, T. Shioiri / Tetrahedron 58 (2002) 1407±1413
enantioselectivities (up to 83% ee). To the best of our
knowledge, this is the highest value for the catalytic asym-
metric Darzens reaction in the sulfone system. Furthermore,
the addition of Sn(OTf)2 was found to be more effective in
these PTC catalyzed reactions. The development of more
general system for a variety of substrates and the creation of
novel catalysts are now under investigation.
1.0, CH2Cl2). (65% ee); IR (nujol): 2924, 1321, 1152 cm21
;
1H NMR (CDCl3, 270 MHz) d: 4.29 (d, Jˆ1.3 Hz, 1H), 4.77
(d, Jˆ1.3 Hz, 1H), 7.23±7.29 (m, 1H), 7.48±7.55 (m, 3H),
7.56±7.61 (m, 2H), 7.78±7.87 (m, 4H), 8.03 (dd, Jˆ6.9,
1.7 Hz, 2H); 13C NMR (CDCl3, 67.8 MHz) d: 57.7, 71.0,
122.3, 126.5, 126.8, 126.9, 127.8, 127.9, 128.8 (X2), 129.5,
130.0, 132.8, 133.7, 134.6, 136.9; MS m/z 310 (M1), 169
(base peak), 141; Anal. calcd for C18H14O3S: C, 69.66; H,
4.55. Found: C, 69.65; H, 4.53; HPLC: DAICEL CHIRAL-
PAK AD, ¯ow rate 1.0 mL/min, hexane/i-PrOHˆ4:1, reten-
tion time 18.1, 25.2 min.
1. Experimental
1H and 13C NMR were measured at 270 and 67.8 MHz,
respectively, with Me4Si as the internal reference and
CDCl3 as the solvent. Flash column chromatography was
performed on Cica-MERCK Silica Gel 60 (230±400 mesh
ASTM). Analytical thin layer chromatography (TLC) was
carried out on precoated (0.25 mm) Merck silica gel F-254
plates. All the solvents were dried prior to use.
1.1.4. (1R,2S)-1,2-Epoxy-2-(4-methylphenyl)ethyl phenyl
20
sulfone (3d). A colorless solid; mp 1098C; [a]D ˆ229.6 (c
1.0, CH2Cl2). (77% ee); IR (nujol): 1458, 1377, 1154 cm21
;
1H NMR (CDCl3, 270 MHz) d: 2.35 (s, 3H), 4.18 (d,
Jˆ1.3 Hz, 1H), 4.55 (d, Jˆ1.3 Hz, 1H), 7.10±7.23 (m,
5H), 7.59±7.82 (m, 3H), 7.99 (d, Jˆ6.9 Hz, 2H); 13C
NMR (CDCl3, 67.8 MHz) d: 21.1, 57.4, 70.9, 126.0,
128.7, 129.4, 129.5, 134.4, 136.8, 139.6; MS m/z 274
(M1), 250, 141 (SO2Ph), 133 (M12SO2Ph), 77 (Ph, base
peak); HRMS calcd for C15H14O3S 274.0664, found
274.0675; Anal. calcd for C15H14O3S: C, 65.67; H, 5.14.
Found: C, 65.36; H, 5.16; HPLC: DAICEL CHIRALCEL
OD, ¯ow rate 1.0 mL/min, hexane/i-PrOHˆ4:1, retention
time 14.3, 19.4 min.
1.1. General procedure for asymmetric Darzens reaction
of sulfone with aromatic aldehydes under phase-transfer
catalyzed conditions
1.1.1. (1R,2S)-1,2-Epoxy-2-phenylethyl phenyl sulfone
(3a). To a solution of chloromethyl phenyl sulfone 2
(95 mg, 0.5 mmol), benzaldehyde 1a (61 mL, 0.6 mmol)
and N-(4-tri¯uoromethylbenzyl)quininium bromide (PTC
A) (28 mg, 0.05 mmol) in toluene (3.0 mL) was added a
portion of KOH (113 mg, 2.0 mmol) at room temperature.
After the reaction mixture was stirred for 1 h at room
temperature, the reaction was quenched with 1N HCl
(3.0 mL), and the mixture was extracted with ethyl acetate
(15 mL£3), washed with brine, and dried over Na2SO4.
Removal of the solvent followed by ¯ash column chroma-
tography (silica gel, hexane/diethyl etherˆ15:1) gave the
desired product 3a (110.8 mg, 85%, 69% ee). A colorless
1.1.5. (1R,2S)-1,2-Epoxy-2-(3-methylphenyl)ethyl phenyl
20
sulfone (3e). A colorless solid; mp 121±1238C; [a]D
243.1 (c 1.0, CH2Cl2). (74% ee); IR (nujol): 1458, 1377,
ˆ
1154 cm21; H NMR (CDCl3, 270 MHz) d: 2.33 (s, 3H),
1
4.18 (d, Jˆ1.3 Hz, 1H), 4.55 (d, Jˆ1.3 Hz, 1H), 7.06 (br s,
2H), 7.15±7.27 (m, 2H), 7.56±7.67 (m, 2H), 7.68±7.78 (m,
1H), 7.99 (dd, Jˆ6.9, 1.3 Hz, 2H); 13C NMR (CDCl3,
67.8 MHz) d: 21.1, 57.3, 70.8, 123.1, 126.5, 128.5, 128.6,
129.3, 130.2, 132.4, 134.4, 136.7, 138.5; MS m/z 274 (M1),
133 (M12SO2Ph), 105 (base peak), 141; HRMS calcd for
C15H14O3S 274.0664, found 274.0664; HPLC: DAICEL
CHIRALCEL OD, ¯ow rate 1.0 mL/min, hexane/i-PrOHˆ
4:1, retention time 7.7, 10.5 min.
20
solid; mp 134±1358C; [a]D ˆ236.0 (c 1.0, CH2Cl2) (69%
ee); IR (nujol): 1315, 1153 cm21 1H NMR (CDCl3,
;
270 MHz) d: 4.18 (d, Jˆ1.3 Hz, 1H), 4.59 (d, Jˆ1.3 Hz,
1H), 7.19±7.28 (m, 2H), 7.34±7.41 (m, 3H), 7.65 (d,
Jˆ7.6 Hz, 2H), 7.71±7.80 (m, 1H), 8.00 (d, Jˆ7.3 Hz,
2H); 13C NMR (CDCl3, 67.8 MHz) d: 57.2, 70.8, 128.6,
129.3, 129.4, 132.5, 134.4, 136.5; MS m/z 260 (M1), 103
(M12SO2Ph), 77 (base peak); HPLC: DAICEL CHIRAL-
PAK AD, ¯ow rate 1.0 mL/min, hexane/i-PrOHˆ9:1,
retention time 22.4, 25.0 min.
1.1.6. (1R,2S)-1,2-Epoxy-2-(4-phenylphenyl)ethyl phenyl
23
sulfone (3f). A colorless solid; mp 105±1078C; [a]D
28.5 (c 1.0, CH2Cl2). (72% ee); IR (nujol): 1323,
ˆ
1146 cm21; H NMR (CDCl3, 270 MHz) d: 4.23 (d, Jˆ
1
1.3 Hz, 1H), 4.64 (d, Jˆ1.3 Hz, 1H), 7.20±7.48 (m, 5H),
7.54±7.68 (m, 6H), 7.71±7.79 (m, 1H), 8.01 (dd, Jˆ8.9,
1.7 Hz, 2H); 13C NMR (CDCl3, 67.8 MHz) d: 57.2, 70.9,
126.5, 127.0, 127.4, 127.7, 128.8, 129.3, 129.4, 131.5, 134.5,
136.7, 140.0, 142.4; MS m/z 336 (M1), 195 (base peak);
HRMS calcd for C20H16O3S 336.0820, found 336.0823;
HPLC: DAICEL CHIRALPAK AD, ¯ow rate 1.0 mL/min,
hexane/i-PrOHˆ4:1, retention time 19.7, 39.2 min.
1.1.2. (1R,2S)-1,2-Epoxy-2-(1-naphthyl)ethyl phenyl sul-
20
fone (3b). A colorless solid; mp 978C; [a]D ˆ169.0 (c 1.0,
1
CH2Cl2). (65% ee); IR (nujol): 2932, 1321, 1151 cm21; H
NMR (CDCl3, 270 MHz) d: 4.19 (d, Jˆ1.6 Hz, 1H), 5.18 (d,
Jˆ1.6 Hz, 1H), 7.36±7.46 (m, 2H), 7.52±7.70 (m, 4H),
7.72±7.79 (m, 1H), 7.82±7.93 (m, 2H), 8.05 (dd, Jˆ7.3,
1.7 Hz, 2H), 8.11 (d, Jˆ8.3 Hz, 1H); 13C NMR (CDCl3,
67.8 MHz) d: 55.8, 70.4, 122.5, 122.7, 125.0, 126.3,
127.0, 128.6, 128.7, 129.38, 129.43, 130.7, 133.1, 134.5,
136.8; MS m/z 310 (M1), 169 (base peak), 141; HRMS
calcd for C18H14O3S 310.0664, found 310.0628; HPLC:
DAICEL CHIRALCEL OD, ¯ow rate 1.0 mL/min, hex-
ane/i-PrOHˆ9:1, retention time 17.8, 23.1 min.
1.1.7. (1R,2S)-1,2-Epoxy-2-(4-tert-butylphenyl)ethyl
phenyl sulfone (3g). A colorless solid; mp 93±948C;
24
[a]D ˆ232.4 (c 1.0, CH2Cl2). (81% ee); IR (nujol):
1
1325, 1154 cm21; H NMR (CDCl3, 270 MHz) d: 1.30 (s,
9H), 4.18 (d, Jˆ1.7 Hz, 1H), 4.57 (d, Jˆ1.7 Hz, 1H), 7.20
(d, Jˆ8.6 Hz, 2H), 7.34 (d, Jˆ8.6 Hz, 2H), 7.56±7.68 (m,
2H), 7.70±7.77 (m, 1H), 7.99 (dd, Jˆ7.3, 1.7 Hz, 2H); 13C
NMR (CDCl3, 67.8 MHz) d: 31.1, 34.6, 57.3, 70.8, 125.6,
125.8, 128.7, 129.3, 129.5, 134.4, 136.8, 152.7; MS m/z 316
1.1.3. (1R,2S)-1,2-Epoxy-2-(2-naphthyl)ethyl phenyl sul-
20
fone (3c). A colorless solid; mp 1258C; [a]D ˆ213.1 (c

S. Arai, T. Shioiri / Tetrahedron 58 (2002) 1407±1413
1411
(M1), 301 (M12Me), 287 (M12Me2), 177 (base peak);
HRMS calcd for C14H1135ClO3S 294.0117, found
294.0117; Anal. calcd for C18H20O3S: C, 68.33; H, 6.37.
Found: C, 68.18; H, 6.34; HPLC: DAICEL CHIRALPAK
AD, ¯ow rate 1.0 mL/min, hexane/i-PrOHˆ4:1, retention
time 10.2, 25.4 min.
1.1.12. (1R,2S)-1,2-Epoxy-2-(4-tri¯uoromethylphenyl)-
ethyl phenyl sulfone (3m). A colorless solid; mp 102±
22
1038C; [a]D ˆ223.1 (c 1.0, CH2Cl2). (65% ee); IR
(nujol): 1325, 1156, 1127 cm21
;
1H NMR (CDCl3,
270 MHz) d: 4.16 (d, Jˆ1.7 Hz, 1H), 4.66 (d, Jˆ1.7 Hz,
1H), 7.40 (d, Jˆ8.3 Hz, 2H), 7.64 (d, Jˆ8.3 Hz, 2H), 7.61±
7.69 (m, 2H), 7.72±7.80 (m, 1H), 8.00 (d, Jˆ7.6 Hz, 2H);
13C NMR (CDCl3, 67.8 MHz) d: 56.5, 70.8, 121.6, 125.7 (q,
Jˆ3.7 Hz), 126.4, 128.8, 129.5, 131.5 (q, Jˆ33 Hz), 134.7,
136.5, 136.7; MS m/z 328 (M1), 309 (M12F), 187, 159
(base peak); Anal. calcd for C15H11F3O3S: C, 54.88; H,
3.38. Found: C, 54.58; H, 3.39; HPLC: DAICEL CHIRAL-
PAK AD, ¯ow rate 1.0 mL/min, hexane/i-PrOHˆ4:1,
retention time 12.5, 19.9 min.
1.1.8. (1R,2S)-1,2-Epoxy-2-(3-phenoxyphenyl)ethyl phenyl
22
sulfone (3h). A colorless solid; mp 588C; [a]D ˆ227.7 (c
1.0, CH2Cl2). (65% ee); IR (nujol): 1584, 1489, 1327 cm21; 1H
NMR (CDCl3, 270 MHz) d: 4.14 (d, Jˆ1.3 Hz, 1H), 4.55 (d,
Jˆ1.3 Hz, 1H), 6.87 (d, Jˆ2.0 Hz, 1H), 7.94±7.05 (m, 4H),
7.10±7.17 (m, 1H), 7.28±7.40 (m, 3H), 7.58±7.67 (m, 2H),
7.70±7.77 (m, 1H), 7.88 (dd, Jˆ7.3, 1.7 Hz, 2H); 13C NMR
(CDCl3, 67.8 MHz) d: 56.9. 70.7, 115.8, 119.0, 119.5, 120.6,
123.6, 128.6, 129.3, 129.7, 130.1, 134.4, 134.6, 136.6, 156.3,
157.8; MS m/z 352 (M1), 211 (M12SO2Ph, base peak), 183,
118; HRMS calcd for C20H16O4S 352.0769, found 352.0764;
HPLC: DAICEL CHIRALPAL AD, ¯ow rate 1.0 mL/min,
hexane/i-PrOHˆ4:1, retention time 12.2, 14.8 min.
1.1.13. (1R,2S)-1,2-Epoxy-2-(3-tri¯uoromethylphenyl)-
ethyl phenyl sulfone (3n). A colorless solid; mp 102±
22
1038C; [a]D ˆ222.5 (c 1.0, CH2Cl2). (64% ee); IR
(nujol): 1464, 1377, 1327 cm21
;
1H NMR (CDCl3,
270 MHz) d: 4.18 (d, Jˆ1.7 Hz, 1H), 4.67 (d, Jˆ1.7 Hz,
1H), 7.45±7.55 (m, 3H), 7.60±7.70 (m, 2H), 7.71±7.82 (m,
1H), 8.00 (dd, Jˆ6.9, 1.7 Hz, 2H); 13C NMR (CDCl3,
67.8 MHz) d: 56.6, 70.9, 122.6, 126.3, 128.8, 129.4,
129.5, 129.6, 1331.6, 134.0, 134.7, 136.6; MS m/z 328
(M1), 309 (M12F), 187, 159 (base peak); Anal. calcd for
C15H11F3O3S: C, 54.88; H, 3.38. Found: C, 54.78; H, 3.38;
HPLC: DAICEL CHIRALCEL OD, ¯ow rate 1.0 mL/min,
hexane/i-PrOHˆ9:1, retention time 10.4, 12.6 min.
1.1.9. (1R,2S)-1,2-Epoxy-2-(4-chlorophenyl)ethyl phenyl
25
sulfone (3i). A colorless solid; mp 938C; [a]D ˆ212.9 (c
1.0, CH2Cl2). (64% ee); IR (nujol): 1449, 1327, 1154 cm21
;
1H NMR (CDCl3, 270 MHz) d: 4.14 (d, Jˆ1.7 Hz, 1H), 4.57
(d, Jˆ1.7 Hz, 1H), 7.20 (d, Jˆ8.6 Hz, 2H), 7.35 (d, Jˆ
8.6 Hz, 2H), 7.62±7.69 (m, 2H), 7.70±7.79 (m, 1H), 7.99
(dd, Jˆ6.9, 2.0 Hz, 2H); 13C NMR (CDCl3, 67.8 MHz) d:
56.7, 70.8, 127.4, 128.8, 129.0, 129.5, 131.2, 134.6, 135.5,
136.6; MS m/z 296, 294 (M1), 155, 153 (M12SO2Ph), 125
(base peak), 127; HRMS calcd for C14H1135ClO3S 294.0117,
found 294.0117; Anal. calcd for C14H11ClO3S: C, 57.05; H,
3.76. Found: C, 57.03; H, 3.88; HPLC: DAICEL CHIRAL-
CEL OD, ¯ow rate 1.0 mL/min, hexane/i-PrOHˆ4:1, reten-
tion time 15.7, 20.0 min.
1.1.14. (1R,2S)-1,2-Epoxy-2-(2-bromophenyl)ethyl phenyl
20
sulfone (3p). A colorless solid; mp 1108C; [a]D ˆ112.5 (c
1.0, CH2Cl2). (47% ee); IR (nujol): 1445, 1325, 1154 cm21
;
1H NMR (CDCl3, 270 MHz) d: 4.05 (d, Jˆ1.7 Hz, 1H), 4.75
(d, Jˆ1.7 Hz, 1H), 7.13 (dd, Jˆ7.3, 2.0 Hz, 1H), 7.18±7.33
(m, 2H), 7.53±7.66 (m, 2H), 7.71±7.78 (m, 1H), 8.02 (dd,
Jˆ7.3, 1.3 Hz, 2H); 13C NMR (CDCl3, 67.8 MHz) d: 57.3,
70.3, 122.4, 126.1, 127.6, 128.8, 129.3, 130.4, 132.4, 132.5,
134.6, 136.3; MS m/z 340, 338 (M1), 199, 197 (M12
SO2Ph), 171, 169, 118 (base peak); Anal. calcd for
C14H11BrO3S: C, 49.57; H, 3.27. Found: C, 49.40; H,
3.30; HPLC: DAICEL CHIRALPAK AD, ¯ow rate
1.0 mL/min, hexane/i-PrOHˆ4:1, retention time 10.6,
14.2 min.
1.1.10. (1R,2S)-1,2-Epoxy-2-(4-bromophenyl)ethyl phenyl
20
sulfone (3j). A colorless solid; mp 1238C; [a]D ˆ216.9 (c
1.0, CH2Cl2). (64% ee); IR (nujol): 1449, 1331, 1156 cm21; 1H
NMR (CDCl3, 270 MHz) d: 4.14 (d, Jˆ1.3 Hz, 1H), 4.57 (d,
Jˆ1.3 Hz, 1H), 7.51 (d, Jˆ7.9 Hz, 2H), 7.58 (d, Jˆ7.9 Hz,
2H), 7.60±7.68 (m, 2H), 7.71±7.79 (m, 1H), 7.99 (dd, Jˆ7.3,
1.7 Hz, 2H); 13C NMR (CDCl3, 67.8 MHz) d: 56.8, 70.7,
123.6, 127.6, 128.7, 129.5, 131.7, 131.9, 134.6, 136.5; MS
m/z 211, 209, 183 (M12SO2Ph, base peak), 157, 155; Anal.
calcd for C14H11BrO3S: C, 49.57; H, 3.27. Found: C, 49.37; H,
3.35; HPLC: DAICEL CHIRALPAK AD, ¯ow rate 1.0 mL/
min, hexane/i-PrOHˆ4:1, retention time 17.1, 23.3 min.
1.1.15. (1R,2S)-1,2-Epoxy-2-(2-tri¯uoromethylphenyl)-
ethyl phenyl sulfone (3q). A colorless solid; mp 718C;
20
[a]D ˆ13.4 (c 1.0, CH2Cl2). (33% ee); IR (nujol): 1586,
1
1451, 1327, 1177 cm21; H NMR (CDCl3, 270 MHz) d:
4.04 (d, Jˆ1.7 Hz, 1H), 4.77 (d, Jˆ1.7 Hz, 1H), 7.36 (d,
Jˆ7.6 Hz, 1H), 7.42±7.80 (m, 5H), 7.92±8.09 (m, 3H); 13C
NMR (CDCl3, 67.8 MHz) d: 54.4, 70.4, 121.7, 125.5, 125.8,
128.8, 129.1, 129.3, 131.2, 132.4, 134.6, 135.5, 136.1; MS
m/z 328 (M1), 187, 159 (base peak); Anal. calcd for
C15H11F3O3S: C, 54.88; H, 3.38. Found: C, 54.92; H, 3.44;
HPLC: DAICEL CHIRALPAK AD, ¯ow rate 1.0 mL/min,
hexane/i-PrOHˆ4:1, retention time 7.7, 8.8 min.
1.1.11. (1R,2S)-1,2-Epoxy-2-(3-bromophenyl)ethyl phenyl
20
sulfone (3k). A colorless solid; mp 102±1038C; [a]D
224.2 (c 1.0, CH2Cl2). (71% ee); IR (nujol): 1464, 1377,
ˆ
1152 cm21 1H NMR (CDCl3, 270 MHz) d: 4.15 (d,
;
Jˆ1.7 Hz, 1H), 4.56 (d, Jˆ1.7 Hz, 1H), 7.39 (br s, 1H),
7.46±7.53 (m, 1H), 7.53±7.60 (m, 1H), 7.60±7.68 (m,
2H), 7.70±7.79 (m, 1H), 7.99 (dd, Jˆ7.3, 1.3 Hz, 2H); 13C
NMR (CDCl3, 67.8 MHz) d: 56.4, 70.7, 122.8, 124.9, 128.7,
129.2, 129.4, 130.3, 132.5, 134.6, 134.9, 136.5; MS m/z 340,
338 (M1), 199, 197 (M12SO2Ph), 171, 169, 118 (base
peak); Anal. calcd for C14H11BrO3S: C, 49.57; H, 3.27.
Found: C, 49.37; H, 3.39; HPLC: DAICEL CHIRALCEL
OD-H, ¯ow rate 0.8 mL/min, hexane/i-PrOHˆ4:1, reten-
tion time 10.0, 11.3 min.
1.2. A general procedure for asymmetric Darzens
reaction of sulfone with aliphatic aldehydes under phase-
transfer catalyzed conditions
1.2.1. (1R,2S)-1,2-Epoxy-3-methylbutyl phenyl sulfone
(5a). To a suspension of chloromethyl phenyl sulfone 2

1412
S. Arai, T. Shioiri / Tetrahedron 58 (2002) 1407±1413
(190 mg, 1.0 mmol), isobutyraldehyde 4a (0.11 mL,
1.2 mmol), N-(4-tri¯uoromethylbenzyl)quininium bromide
(PTC A) (56 mg, 0.10 mmol) and tin(II) tri¯ate (42 mg,
0.10 mmol) in toluene (3.0 mL) was added a portion of
KOH (113 mg, 2.0 mmol) at room temperature. After the
reaction mixture was stirred for 20 h at room temperature,
the reaction mixture was poured into silica gel, and follow-
ing ¯ash column chromatography (hexane/diethyl etherˆ
5:1) gave the desired product 5a (183.2 mg, 81%, 32%
1.3. A general procedure for asymmetric Darzens
reaction of sulfone with ketones under phase-transfer
catalyzed conditions
1.3.1. (1R,2S)-1,2-Epoxy-2-phenylpropyl phenyl sulfone
(7a) and (1S,2S)-1,2-epoxy-2-phenylpropyl phenyl sul-
fone (8a). To a suspension of chloromethyl phenyl sulfone
2
(190 mg, 1.0 mmol), acetophenone 6a (0.14 mL,
1.2 mmol) and N-(4-tri¯uoromethylbenzyl)quininium
bromide (PTC A) (56 mg, 0.1 mmol) in diethyl ether
20
ee). A colorless oil; [a]D ˆ229.1 (c 2.0, CH2Cl2). (32%
1
ee); IR (neat): 2968, 1470, 1327, 1156 cm21; H NMR
(3.0 mL) was added
a portion of KOH (220 mg,
(CDCl3, 270 MHz) d: 1.01 (d, Jˆ6.6 Hz, 3H), 1.03 (d, Jˆ
6.6 Hz, 3H), 1.68±1.82 (m, 1H), 3.51 (d, Jˆ6.6, 1.7 Hz,
1H), 3.93 (d, Jˆ1.7 Hz, 1H), 7.55±7.64 (m, 2H), 7.66±
7.75 (m, 1H), 7.94 (dd, Jˆ6.9, 1.3 Hz, 2H); 13C NMR
(CDCl3, 67.8 MHz) d: 17.7, 18.1, 28.7, 62.3, 67.2, 128.4,
129.1, 134.2, 136.9; MS m/z 211 (M12Me), 143, 78 (base
peak); Anal. calcd for C11H14O3S: C, 58.28; H, 6.24. Found:
C, 58.38; H, 6.38; HPLC: DAICEL CHIRALCEL OD, ¯ow
rate 1.0 mL/min, hexane/i-PrOHˆ9:1, retention time 7.4,
8.2 min.
3.9 mmol) at room temperature. After the reaction mixture
was stirred for 18 h at room temperature, the mixture was
poured into silicagel, and following ¯ash column chroma-
tography (hexane/AcOEtˆ6:1) gave the desired products 7a
(79.8 mg, 29, 60% ee) and 8a (14 and 22% ee, respectively;
1
chemical yield of 8a was determined by H NMR due to
puri®cation dif®culty).
25
Compound 7a. A colorless oil; [a]D ˆ22.0 (c 2.0, CHCl3).
1
(37% ee); IR (neat): 1447, 1327, 1156 cm21; H NMR
(CDCl3, 270 MHz) d: 2.12 (s, 3H), 3.80 (s, 1H), 7.20±
7.30 (m, 8H), 7.91 (d, Jˆ7.3 Hz, 2H); 13C NMR (CDCl3,
67.8 MHz) d: 17.1, 65.5, 75.5, 124.9, 128.1, 128.4, 128.5,
134.2, 138.6, 139.1; MS m/z 274 (M1), 133 (M12SO2Ph,
base peak), 105, 77; HRMS calcd for C15H14O3S 274.0664,
found 274.0666; HPLC: DAICEL CHIRALPAK AD, ¯ow
rate 1.0 mL/min, hexane/i-PrOHˆ9:1, retention time 12.4,
16.1 min.
1.2.2. (1R,2S)-1,2-Epoxybutyl phenyl sulfone (5b). A
20
colorless oil; [a]D ˆ210.7 (c 1.0, CH2Cl2). (10% ee); IR
(neat): 2972, 1325, 1156 cm21; 1H NMR (CDCl3, 270 MHz)
d: 1.02 (t, Jˆ7.3 Hz, 3H), 1.64±1.84 (m, 2H), 3.66 (dt,
Jˆ5.0, 2.0 Hz, 1H), 3.92 (d, Jˆ2.0 Hz, 1H), 7.55±7.64
(m, 2H), 7.66±7.75 (m, 1H), 7.94 (dd, Jˆ6.9, 1.7 Hz,
2H); 13C NMR (CDCl3, 67.8 MHz) d: 9.1, 23.2, 58.6,
67.8, 128.5, 129.2, 134.2, 136.9; MS m/z 183 (M12Et),
125, 78 (base peak); HRMS calcd for C8H7O3S 183.0116,
found 183.0116; Anal. calcd for C10H12O3S: C, 56.87; H,
5.70. Found: C, 56.89; H, 5.79; HPLC: DAICEL CHIRAL-
CEL OD, ¯ow rate 1.0 mL/min, hexane/i-PrOHˆ9:1, reten-
tion time 9.0, 10.8 min.
Compound 8a. A colorless oil; IR (neat): 1147, 1333, 1306,
1
1156 cm21; H NMR (CDCl3, 270 MHz) d: 1.68 (s, 3H),
4.23 (s, 1H), 7.21±7.47 (m, 7H), 7.50±7.80 (m, 3H); 13C
NMR (CDCl3, 67.8 MHz) d: 25.7, 66.3, 75.3, 126.3, 128.0,
128.4, 128.6, 128.8, 133.8, 135.0, 137.4; MS m/z 274 (M1),
133 (M12SO2Ph, base peak), 105, 77; HRMS calcd for
C17H18O3S 274.0664, found 274.0683; HPLC: DAICEL
CHIRALPAK AD, ¯ow rate 1.0 mL/min, hexane/
i-PrOHˆ9:1, retention time 10.5, 13.1 min.
1.2.3. (1R,2S)-3,3-Dimethyl-1,2-epoxybutyl phenyl sul-
23
fone (5c). A colorless oil; [a]D ˆ217.7 (c 1.0, CH2Cl2).
1
(17% ee); IR (neat): 2963, 1325, 1156 cm21; H NMR
(CDCl3, 270 MHz) d: 0.97 (s, 9H), 3.51 (d, Jˆ1.7 Hz,
1H), 3.96 (d, Jˆ1.7 Hz, 1H), 7.48±7.59 (m, 2H), 7.60±
7.68 (m, 1H), 7.93 (dd, Jˆ8.6, 1.7 Hz, 2H); 13C NMR
(CDCl3, 67.8 MHz) d: 25.4, 30.5, 64.9, 66.1, 128.5, 129.2,
134.3, 137.0; MS m/z 225 (M12Me), 143, 125, 77 (base
peak); HRMS calcd for C12H16O3S 240.0820, found 240.08;
Anal. calcd for C12H16O3S: C, 59.97; H, 6.71. Found: C,
59.74; H, 6.79; HPLC: DAICEL CHIRALPAK AS, ¯ow
rate 0.5 mL/min, hexane/i-PrOHˆ9:1, retention time 13.7,
15.0 min.
1.3.2. (1R,2S)-1,2-Epoxy-2-(1-naphthyl)propyl phenyl
25
sulfone (7b). A white amorphous solid; [a]D ˆ15.4 (c
1.0, CH2Cl2). (6% ee); IR (CHCl3): 1449, 1327, 1312,
1
1156 cm21; H NMR (CDCl3, 270 MHz) d: 2.25 (s, 3H),
4.09 (s, 1H), 7.27±7.78 (m, 9H), 8.00±8.25 (m, 3H); 13C
NMR (CDCl3, 67.8 MHz) d: 19.4, 66.4, 74.0, 123.3, 125.0,
126.0, 126.9, 128.1, 128.6, 128.9, 129.2, 134.2, 136.2,
138.6; MS m/z 324 (M1), 183 (M12SO2Ph, base peak),
155, 77; HRMS calcd for C19H16O3S 324.0819, found
324.0816; HPLC: DAICEL CHIRALCEL OD, ¯ow rate
1.0 mL/min, hexane/i-PrOHˆ9:1, retention time 9.5,
11.6 min.
1.2.4. (1R,2S)-1,2-Epoxy-3-ethylpentyl phenyl sulfone
26
(5d). A colorless oil; [a]D ˆ225.6 (c 2.0, CH2Cl2). (31%
1
ee); IR (neat): 2967, 1325, 1156 cm21; H NMR (CDCl3,
270 MHz) d: 0.95 (t, Jˆ7.3 Hz, 3H), 0.97 (t, Jˆ7.3 Hz, 3H),
1.08±1.20 (m, 1H), 1.33±1.53 (m, 2H), 3.47 (dd, Jˆ8.3,
1.7 Hz, 1H), 3.91 (d, Jˆ1.7 Hz, 1H), 7.54±7.64 (m, 2H),
7.66±7.74 (m, 1H), 7.89 (dd, Jˆ7.3, 1.3 Hz, 2H); 13C NMR
(CDCl3, 67.8 MHz) d: 10.8, 11.4, 23.3, 24.8, 42.6, 61.0,
67.8, 128.5, 129.2, 134.2, 137.1; MS m/z 225 (M12Me2),
143, 77 (base peak); Anal. calcd for C13H18O3S: C, 61.39; H,
7.13. Found: C, 61.30; H, 7.24; HPLC: DAICEL CHIRAL-
PAK AD, ¯ow rate 1.0 mL/min, hexane/i-PrOHˆ9:1, reten-
tion time 8.3, 10.0 min.
1.3.3. cis-1,2-Epoxy-2-(1-naphthyl)propyl phenyl sulfone
(8b). A colorless oil; IR (neat): 1449, 1327, 1312,
1
1157 cm21; H NMR (CDCl3, 270 MHz) d: 1.81, 1.82 (s,
3H), 4.33 (s, 0.22£1H), 4.48 (s, 0.68£1H), 7.10±8.18 (m,
12H); 13C NMR (CDCl3, 67.8 MHz) d: 25.7, 26.5, 66.1,
67.0, 73.9, 75.9, 124.1, 124.2, 124.5, 124.6, 125.3, 125.7,
125.9, 126.2, 126.3, 128.3, 128.4, 128.50, 128.53, 128.6,
128.8, 129.0, 129.7, 130.0, 132.0, 133.1, 133.8, 136.3; MS
m/z 324 (M1), 183 (M12SO2Ph, base peak), 155, 77;
HRMS calcd for C19H16O3S 324.0820, found 324.0816.

S. Arai, T. Shioiri / Tetrahedron 58 (2002) 1407±1413
1413
1.3.4. trans-1,2-Epoxy-2,3,3-trimethylbutyl phenyl sul-
fone (7c). A colorless oil; IR (neat): 1449, 1325,
Pharmaceutical Sciences) for his kind help in determining
the absolute con®guration by X-ray crystallographic analy-
sis. One of the authors (S. A.) is grateful to the Takeda
Science Foundation and Ciba-Geigy Foundation for their
®nancial support.
1
1156 cm21; H NMR (CDCl3, 270 MHz) d: 0.95 (s, 9H),
1.78 (s, 3H), 3.97 (s, 1H), 7.55±7.75 (m, 3H), 7.96 (d,
Jˆ7.6 Hz, 2H); 13C NMR (CDCl3, 67.8 MHz) d: 13.0,
25.4, 35.2, 71.1, 72.1, 128.0, 129.3, 134.1, 139.1; MS m/z
239 (M12Me), 197 (M12tert-Bu), 77 (base peak); HRMS
calcd for C12H15O3S 239.0742, found 239.0741; Anal. calcd
for C13H18O3S: C, 61.39; H, 7.13. Found: C, 61.16; H, 7.08;
HPLC: DAICEL CHIRALPAK AD, ¯ow rate 1.0 mL/min,
hexane/i-PrOHˆ9:1, retention time 6.5, 7.0 min.
References
1. Newman, M. S.; Magerlein, B. J. Organic Reactions 1949,
Chapter 10, pp 413±441.
2. (a) Arai, S.; Shioiri, T. Tetrahedron Lett. 1998, 39, 2145±2148.
(b) Arai, S.; Ishida, T.; Shioiri, T. Tetrahedron Lett. 1998, 39,
8229±8302. (c) Arai, S.; Shirai, Y.; Ishida, T.; Shioiri, T. Chem.
Commun. 1999, 49±50. (d) Arai, S.; Shirai, Y.; Ishida, T.;
1.3.5. (1R,2S)-1,2-Epoxy-2-methyl-4-phenylbutyl phenyl
25
sulfone (7d). A colorless oil; [a]D ˆ216.6 (c 4.0, CHCl3).
1
(27% ee); IR (neat): 1455, 1327, 1156 cm21; H NMR
Â
Shioiri, T. Tetrahedron 1999, 55, 6375±6386. (e) Bako, P.;
(CDCl3, 270 MHz) d: 1.72±2.05 (m, 2H), 1.85 (s, 3H),
2.69 (d, Jˆ8.2 Hz, 2H), 3.74 (s, 1H), 7.05±7.32 (m, 5H),
7.53±7.74 (m, 3H), 7.91 (d, Jˆ7.3 Hz, 2H); 13C NMR
(CDCl3, 67.8 MHz) d: 16.2, 30.7, 40.0, 66.1, 73.5, 126.1,
128.0, 128.3, 128.4, 129.3, 134.1, 138.6, 140.0; MS m/z 302
(M1), 161 (M12SO2Ph), 91 (base peak), 77; Anal. calcd for
C17H18O3S: C, 67.52; H, 6.00. Found: C, 67.24; H, 6.20;
HPLC: DAICEL CHIRALCEL OD, ¯ow rate 1.0 mL/min,
hexane/i-PrOHˆ9:1, retention time 13.4, 15.8 min.
È Ä
Szolloy, A.; Bombicz, P.; Toke, L. Synlett 1997, 291±292.
(f) Bako, P.; Võzvardi, K.; Toppet, S.; der Eycken, E. V.;
Ä
Â
 Â
Hoonaert, G. J.; ToÄke, L. Tetrahedron 1998, 54, 14975±
Â
 Â
14988. (g) Bako, P.; Novak, T.; Ludanyi, K.; Pete, B.; ToÄke,
L.; Keglevich, G. Tetrahedron: Asymmetry 1999, 10, 2373±
Â
Â
2380. (h) Bako, P.; Czinege, E.; Bako, T.; Czugler, M.; ToÄke,
L. Tetrahedron: Asymmetry 1999, 10, 4439±4451 and
references cited therein.
3. (a) Takagi, R.; Kimura, J.; Shinohara, Y.; Ohba, Y.; Takezono,
K.; Hiraga, Y.; Kojima, S.; Ohkata, K. J. Chem. Soc., Perkin
Trans. 1 1998, 689±698. (b) Baldoli, C.; Buttero, P. D.;
Licandoro, E.; Maiorana, S.; Papagni, A. J. Chem. Soc.,
Chem. Commun. 1987, 762±763. (c) Takahashi, T.; Muraoka,
M.; Capo, M.; Koga, K. Chem. Pharm. Bull. 1995, 43, 1821±
1823.
1.3.6. (1S,2S)-1,2-Epoxy-2-methyl-4-phenylbutyl phenyl
25
sulfone (8d). A colorless oil; [a]D ˆ224.4 (c 2.0, CHCl3).
1
(28% ee); IR (CHCl3): 1449, 1327, 1156 cm21; H NMR
(CDCl3, 270 MHz) d: 1.34 (s, 3H), 2.30±2.55 (m, 2H),
2.72±3.04 (m, 2H), 3.78 (s, 1H), 7.20±7.40 (m, 5H),
7.50±7.72 (m, 3H), 7.93 (d, Jˆ7.6 Hz, 2H); 13C NMR
(CDCl3, 67.8 MHz) d: 22.6, 32.2, 34.0. 67.4, 74.5, 126.1,
128.1, 128.2, 128.4, 129.4, 134.2, 138.8, 140.9; MS m/z 301
(M12H), 189, 161 (M12SO2Ph), 91 (base peak); Anal.
calcd for C17H18O3S: C, 67.52; H, 6.00. Found: C, 67.27;
H, 6.21; HPLC: DAICEL CHIRALPAK AS, ¯ow rate
1.0 mL/min, hexane/i-PrOHˆ9:1, retention time 8.6,
9.8 min.
4. (a) Nelson, A. Angew. Chem., Int. Ed. Engl. 1999, 38, 1583±
1585. For recent books on PTC, see: (b) Phase-Transfer
Catalysis. Mechanism and Synthesis; Halpern, M. E., Ed.;
American Chemical Society: Washington, DC, 1997.
(c) Handbook of Phase Transfer Catalysis; Sasson, Y.,
Neumann, R., Eds.; Blackie: London, 1997. (d) Shioiri, T.;
Arai, S. In Stimulating Concepts in Chemistry; Vogtle, F.,
Stoddart, J. F., Shibasaki, M., Eds.; Wiley±VCH: Germany,
2000; pp 123±143. (e) O'Donnell, M. J. Catalytic Asymmetric
Synthesis. In Asymmetric Phase Transfer Reactions; Ojima, I.,
Ed.; 2nd ed, Wiley±VCH: New York, 2000 Chapter 10.
5. Sulphones in Organic Synthesis; Simpkins, N. S., Ed.;
Tetrahedron Organic Chemistry Series, Pergamon: Oxford,
1993; Vol. 10.
1.3.7. cis-1,2-Epoxy-3-methyl-2-phenylbutyl phenyl sul-
fone (8e). A colorless oil; IR (neat): 2971, 1449, 1331,
1
1156 cm21; H NMR (CDCl3, 270 MHz) d: 0.88 (d, Jˆ
6.8 Hz, 3H), 0.98 (d, Jˆ7.1 Hz, 3H), 1.80±1.92 (m, 1H),
4.22 (s, 1H), 7.20±7.30 (m, 5H), 7.35±7.45 (m, 3H), 7.50±
7.67 (m, 3H); 13C NMR (CDCl3, 67.8 MHz) d: 16.9, 18.1,
35.7, 71.9, 74.1, 127.3, 127.7, 127.9, 128.3, 128.4, 130.0,
133.5, 137.3; MS m/z 302 (M1), 161 (M12SO2Ph), 91
(base peak); Anal. calcd for C17H18O3S: C, 67.52; H, 6.00.
Found: C, 67.29; H, 6.12; HPLC: DAICEL CHIRALPAK
AD, ¯ow rate 1.0 mL/min, hexane/i-PrOHˆ9:1, retention
time 8.7, 10.3 min.
6. See reviews, Ref. 4d,e and O'Donnell, M. J.; Delgado, F.;
Dominguez, E.; Blas, deJ.; Scott, W. L. Tetrahedron:
Asymmetry 2001, 12, 821±828. See also Okino, T.; Takemoto,
Y. Org. Lett. 2001, 3, 1515±1517.
Acknowledgements
We thank Professor Toshimasa Ishida (Osaka University of