Asymmetric Synthesis of α,γ-Substituted γ-Sultones via Allylation of Chiral Lithiated Sulfonates

Article abstract of DOI:10.1002/ejoc.200300342

The first auxiliary controlled asymmetric synthesis of enantiopure α,γ-substituted γ-sultones via α-allylation of lithiated sulfonates by using 1,2:5,6-di-O-isopropylidene-α -D-allofuranose as chiral auxiliary is described. The high asymmetric inductions

Full text of DOI:10.1002/ejoc.200300342

FULL PAPER
Asymmetric Synthesis of α,γ-Substituted γ-Sultones via Allylation of Chiral
Lithiated Sulfonates
Dieter Enders,*[a] Wacharee Harnying,[a] and Nicola Vignola[a]
Dedicated to Professor Helmut Schwarz on the occasion of his 60th birthday
Keywords: Sultones / Asymmetric synthesis / Chiral auxiliaries / Sulfonates / One-pot reaction / Cyclization
The first auxiliary controlled asymmetric synthesis of enanti-
opure α,γ-substituted γ-sultones via α-allylation of lithiated
auxiliary and diastereoselective ring closure of the sulfonic
acid intermediates in a one-pot procedure led to the title
compounds in good to excellent yields and diastereo- and
enantiomeric excesses (de, ee Ն 98%).
sulfonates by using 1,2:5,6-di-O-isopropylidene-α-
D-allofur-
anose as chiral auxiliary is described. The high asymmetric
inductions of the α-allylations were reached in good to excel- ( Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
lent yields. Successive epimerization-free cleavage of the
Germany, 2003)
Introduction
ates possessing a diene moiety, followed by flexible elabor-
ation with cleavage of the resultant sultones.[8] Moreover,
they have shown a powerful application of the sultone route
in the synthesis of methyl nonactate, the monomeric subu-
nit of the mactrotetrolides,[9] and the total synthesis of the
macrodiolide antibiotic pamamycin-607.[10] A further appli-
cation in an enantioselective synthesis of the sesqiterpenoid
alcohol (Ϫ)-myltaylenol employing a sultone as a key inter-
mediate has been reported by Winterfeldt et al.[11] Cam-
phenesultone as a starting material for the total synthesis
of β-santalol has been described by Wolinsky et al.[12] Cam-
arasa et al. have discovered a novel class of potent and
specific anti-HIV-1 agents, called TSAO derivatives contain-
ing a sultone moiety and their projects focused on the
modification and synthesis of the analogues of 3Ј-spiro sul-
tone nucleosides and adamantane spiro sultones.[13]
Sultones are synthetically useful heterocycles which can
react with a variety of compounds to introduce the alkylsul-
fonic acid function and offer novel possibilities for stereose-
lective transformations.[1] There have been several new de-
velopments for the synthesis of sultones which have also
been applied in total syntheses of natural products. A novel
synthetic route for the synthesis of α,β-unsaturated γ-sul-
tones and their application in DielsϪAlder reactions have
been reported.[2] Moreover, unsaturated sultones with nor-
mal, medium and large ring sizes can be prepared easily by
ring-closing metathesis of sulfonates.[3] Only a few dia-
stereoselective syntheses of γ-sultones have been reported.
For example, palladium-catalyzed rearrangement of cyclic
allylic sulfites selectively provided trans-α,β-disubstituted γ-
sultones.[4] An intramolecular Michael reaction of γ-alkyl-
sulfonyloxy-α,β-unsaturated esters using higher order cyano
copper or silver amides as a base gave γ-sultones stereose-
lectively.[5] Considering the reported methods, only a few
synthetic routes to enantiopure sultones and their appli-
cations in synthesis have been reported. Various mixed dis-
ulfonate ester derivatives of carbohydrates led to chiral
products in which a sultone is fused to a sugar ring via
intramolecular displacement reactions.[6] In the same man-
ner nucleoside sultones have been prepared as building
blocks for the preparation of novel nucleotide analogues.[7]
Metz et al. have developed an efficient and highly stereose-
lective intramolecular DielsϪAlder reaction of vinylsulfon-
To the best of our knowledge, no chiral auxiliary con-
trolled methodology for the asymmetric synthesis of sul-
tones has been reported so far. Based on the results of our
communication,[14] we now wish to describe in detail the
efficient asymmetric synthesis of α,γ-substituted γ-sultones
via α-allylation of chiral lithiated sulfonates.
Results and Discussion
In previous communications and a full paper we have
described highly efficient asymmetric electrophilic α-substi-
tutions of sulfonates bearing 1,2:5,6-di-O-isopropylidene-α-
-allofuranose as a chiral auxiliary with various alkyl hal-
ides and nitroolefins.[15] We have now extended our method-
ology to the enantioselective synthesis of α,γ-substituted γ-
sultones by using allylic halides as electrophiles. The chiral
substrate 1a (Figure 1) was prepared by the reaction of the
[a]
Institut für Organische Chemie, Rheinisch-Westfälische
Technische Hochschule,
Professor-Pirlet-Str. 1, 52074 Aachen, Germany
Fax: (internat.) ϩ49-(0)241-8092127
E-mail: Enders@rwth-aachen. de
Eur. J. Org. Chem. 2003, 3939Ϫ3947
DOI: 10.1002/ejoc.200300342
 2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
3939

D. Enders, W. Harnying, N. Vignola
FULL PAPER
The absolute configuration of the newly formed stereog-
enic center was assigned to be (R) in analogy to the results
shown in the previous report on the synthesis of α-alkylated
analogues[15a] and also confirmed by X-ray crystallography
of a corresponding sultone (vide infra).
In analogy to the procedure reported in the previous
communication,[15a] removal of the chiral auxiliary to form
the corresponding sulfonic acids 3 was achieved by re-
fluxing the sulfonates 2 in an EtOH/H2O solution contain-
ing 15 mol % Pd(OAc)2 for 4 days (method A). As an
alternative method for cleaving the chiral auxiliary without
epimerization at the α-position of the sulfonyl group, re-
fluxing the diastereomerically pure sulfonates in ethanol
containing 2% TFA for 24 h led to the corresponding sul-
fonic acids 3 (method B). In order to facilitate the purifi-
cation of the sulfonic acids, they were directly converted
into the corresponding methyl sulfonates (R)-4 with diazo-
methane (Scheme 2). The methyl sulfonates 4aϪe were ob-
tained in very good yields and enantiomerically pure
(Table 2). A comparison of the two methods concluded that
in the case of alkylation product 4a the cleavage method
using TFA results in only slightly lower yields. In contrast,
cleavage of the allylated sulfonates 4b,c using TFA gave sig-
nificantly lower yields of the corresponding acids. This
could be attributed to the cyclization to the corresponding
sultones which could be detected in a small amount in the
crude reaction mixture. Care must be taken when the reac-
tion is performed in ethanol, which can cause the ring open-
ing of sultones. To reduce this side reaction, the reaction
time had to be limited to 24 h reflux.
Figure 1. The enantiopure sulfonates 1aϪc
chiral auxiliary with benzylsulfonyl chloride which is com-
mercially available, while the syntheses of 1b and 1c were
started from the corresponding sodium sulfonates, which
were prepared according to known procedures.[16]
The enantiopure sulfonates 1 were lithiated with one
equivalent of n-butyllithium in tetrahydrofuran at Ϫ90 to
Ϫ95 °C and reacted with different allylic halides at this tem-
perature for 2 h and then at Ϫ78 °C for 15 h. Decreasing
the amount of THF to 10 mL per mmol of substrates led
to the highest yield and diastereoselectivity. The α-allylated
sulfonates 2aϪg were obtained in good to excellent yields
(72Ϫ98%) with high diastereomeric excesses (de ϭ
82Ϫ95%) (Scheme 1, Table 1). In all cases diastereomer-
ically pure α-allylated sulfonates could be obtained by
recrystallization (de Ն 98%). For 2f and 2g, recrystallization
produced a 1:13 and 1:4 mixture of the enantiopure (Z)-
and (E)-sulfonates, respectively. The isomeric mixture could
be used for the next step without separation.
Scheme 2. Removal of the chiral auxiliary to form the methyl sul-
fonates (R)-4: Method A: Pd(OAc)2, EtOH/H2O, reflux, 4 days.
Method B: 2% TFA/EtOH, reflux, 24 h
Scheme 1. Asymmetric α-allylation of chiral sulfonates 1 to afford
the product (R)-2
Cleavage of the chiral auxiliary using TFA liberated the
sulfonic acids 3 whose cyclization to the desired sultones 5
had to be optimized (Scheme 3, Table 3). The most reactive
substrate in the cyclization reaction was the α-allylsulfonic
acid 3a obtained from (R)-2a after cleavage of the chiral
auxiliary. Refluxing in a 2% TFA/CH2Cl2 solution for 22 h
gave the geminal disubstituted 5a in very good yield and
excellent enantiomeric excess. Under the same conditions,
sultone 5b was obtained in excellent yield (90%). In con-
trast, (R)-2c yielded 5c in a lower yield of only 29%, which
could be significantly improved by increasing the concen-
tration of the TFA solution. Sultones 5cϪe could be synthe-
sized in good yields (64Ϫ72%) and high diastereoselectivit-
ies (ds ϭ 89Ϫ90%) by refluxing the corresponding crude
Table 1. Asymmetric α-allylation of chiral sulfonates 1 to afford
the product (R)-2aϪg
(R)-2 R1
R2
R3
Yield [%] de [%][a]
a
b
c
d
e
f
4-tert-Butylphenyl CH3
H
H
H
H
H
80
72
98
98
98
90 (98)
88 (98)
94 (98)
95 (98)
90 (98)
90 (98[b]
82 (98[b]
Phenyl
Phenyl
CH3
H
4-tert-Butylphenyl
2-Naphthyl
4-tert-Butylphenyl
Phenyl
H
H
H
H
CH3 93
CH3 78
)
)
g
[a] Determined by 13C NMR; in parentheses: after recrystallization.
[b]
Obtained as a 1:13 and 1:4 mixture of the enantiopure cis and
trans sulfonates 2f and 2g, respectively.
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Eur. J. Org. Chem. 2003, 3939Ϫ3947

Asymmetric Synthesis of α,γ-Substituted γ-Sultones
FULL PAPER
Table 2. Removal of the chiral auxiliary to form the methyl sulfonates 4
(R)-4
R1
R2
Yield [%]
ee [%][a]
Method A
Method B
a
b
c
d
e
4-tert-Butylphenyl
Phenyl
4-tert-Butylphenyl
Phenyl
(2-Naphthyl)methyl
Allyl
Allyl
Crotyl
Crotyl
86
85
80
Ϫ
83
Ն98
Ն98
Ն98
Ն98
Ն98
73[b]
65[b]
80
4-tert-Butylphenyl
Ϫ
81
[a]
[b]
Determined by HPLC using a chiral stationary phase (see Exp. Sect.).
sponding sultone.
The crude product contained a small amount of the corre-
Table 3. Removal of the auxiliary and cyclization of the sulfonic acid 3 to afford the γ-sultones 5
5
R1
R2
R3
Cyclization conditions
% TFA/CH2Cl2 Temp., time
Yield [%]
ds [%][a]
ee [%][b]
a
4-tert-Butylphenyl
CH3
H
10
2
2
r.t., 3 d
29
82
90
29
33
45
72
64
77
51
64
71
69
Ϫ
Ϫ
Ϫ
Ն98
Ն98
Ն98
Ն98
Ն98
Ն98
Ն98
Ն98
Ն98
Ն98
Ն98
Ն98
Ն98
reflux, 22 h
reflux, 20 h
reflux, 3 d
reflux, 30 h
reflux, 3 d
reflux, 24 h
reflux, 24 h
reflux, 24 h
reflux, 24 h
reflux, 16 h
reflux, 16 h
reflux, 16 h
b
c
Phenyl
Phenyl
CH3
H
H
H
2
89 (99)
89 (99)
90 (99)
90 (99)
89 (99)
89 (99)
73[c] (99)
78[c] (99)
73[c] (99)
73[c] (99)
10
10
20
20
20
20
30
30
40
d
e
f
4-tert-Butylphenyl
2-Naphthyl
4-tert-Butylphenyl
H
H
H
H
H
CH3
g
Phenyl
H
CH3
[a]
[b]
Determined by 13C NMR, in parentheses: after column chromatography or HPLC. Determined by HPLC using a chiral stationary
[c]
phase (see Exp. Sect.).
The product mixture consisted of two diastereomeric γ-sultones and small amounts of two diastereomeric
δ-sultones.
diastereomeric γ-sultones and small amounts of two dia-
stereomeric δ-sultones. In all cases the diastereomerically
and enantiomerically pure sultones 5aϪg could be obtained
by flash column chromatography or HPLC (de, ee Ն 98%).
NOE investigations of the products revealed that the pro-
tons at the α- and γ-position are cis to each other. The abso-
lute configuration of the newly formed stereogenic center
was established unambiguously as (R) by X-ray crystal-
lography in the case of product 5c and again shows that
the protons at the α- and γ-position are cis to each other
(Figure 2). The stereochemistry of the major diastereomer
of other sultones is also expected to be (R,R) based on the
assumption of a uniform reaction mechanism operating
during the allylation and cyclization reactions.
Scheme 3. Removal of chiral auxiliary and cyclization of the sul-
fonic acid 3 to afford the γ-sultones 5
sulfonic acids 3 in a CH2Cl2 solution containing 20% TFA
for 24 h. Under these conditions, however, 5f could only
be obtained in 51% yield. A further increase of the TFA
concentration in solution and a small decrease of reaction
time overcame this problem and led to higher yields of 5f
and 5g of 64% and 71%, respectively. The yield of 5g could
not be increased by using an even higher concentration of
TFA. Removal of the chiral auxiliary and cyclization of the
sulfonates 2f,g led to a product mixture consisting of two Figure 2. X-ray crystal structure of 5c
Eur. J. Org. Chem. 2003, 3939Ϫ3947
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3941

D. Enders, W. Harnying, N. Vignola
FULL PAPER
was continued at Ϫ78 °C overnight. The mixture was quenched
with water. After separation of the organic layer the aqueous phase
was extracted with CH2Cl2. The combined organic layers were
washed with water, brine and dried with MgSO4. The solvent was
evaporated under reduced pressure and the crude product was puri-
fied by flash column chromatography (SiO2, n-pentane/diethyl
ether) to give the product 2.
Figure 3. Proposed transition state of the cyclization of sulfonic
acids
Removal of the Chiral Auxiliary to Give the α-Allylated Methyl Sul-
fonates (R)-4aϪe. Method B: General Procedure 2 (GP 2): The mix-
ture of the sulfonate (R)-2 (0.5 mmol) and a 2% TFA/EtOH solu-
tion (20 mL) was refluxed for 24 h. The resulting colorless solution
was treated with an ethereal solution of diazomethane until the
yellow color persisted. The solvent was evaporated under reduced
pressure and the crude product was purified by flash column chro-
matography (SiO2, diethyl ether/n-pentane).
To explain the stereochemical outcome of the sultone for-
mation we assume a Markownikov protonation of the olef-
inic double bond under the acidic reaction conditions. The
cyclization can proceed via two possible transition states
as depicted in Figure 3. Transition state A should be more
favored than B owing to its lower 1,3-steric interaction be-
tween the alkyl group and the benzylic H-atom. This tran-
sition state model can account for the preferred cis-configu-
ration of the α,γ-substituted γ-sultones.
Removal of the Chiral Auxiliary and Cyclization to Give the γ-Sul-
tones (R,R)-5aϪg. General Procedure 3 (GP 3): The mixture of the
sulfonate (R)-2 (1.0 mmol) and a 2% TFA/EtOH solution (40 mL)
was refluxed for 24 h, the solvent was removed under reduced
pressure and the crude sulfonic acid was used in the next reaction
step without further purification. The crude product 3 was dis-
solved in a TFA/CH2Cl2 solution (20 mL) and the reaction mixture
was refluxed. The mixture was quenched with water. After separ-
ation of the organic layer the aqueous phase was extracted with
CH2Cl2. The combined organic layers were washed with saturated
aqueous NaHCO3 solution. After drying over MgSO4 the solvent
was evaporated and the crude product was purified by flash column
chromatography (SiO2, diethyl ether/ n-pentane).
Conclusion
In summary, a highly efficient diastereo- and enantiose-
lective route to α,γ-substituted γ-sultones via α-allylation of
lithiated chiral sulfonates has been developed. Acid-cata-
lyzed cleavage of the chiral auxiliary and diastereoselective
ring closure of the sulfonic acid intermediates were carried
out following a one-pot procedure. Applications of these
enantiopure compounds as enantiopure synthetic inter-
mediates will be the subject of further investigations in
our laboratories.
(R)-1-(4-tert-Butylphenyl)-3-methyl-3-butene-1-sulfonate (2a): Ac-
cording to GP 1, sulfonate 1b (2.35 g, 5 mmol) was deprotonated
with nBuLi (3.13 mL, 1.6 ) and reacted with 3-bromo-2-methyl-
propene (0.76 mL, 7.5 mmol). Workup and flash column chroma-
tography (Et2O/pentane, 1:4) gave (R)-2a (2.10 g, 80%); de ϭ 90%
(NMR). The major diastereomer was obtained as a colorless solid
after recrystallization from 2-propanol; de Ն 98% (NMR); m.p. 109
°C; [α]2D4 ϭ ϩ79.13 (c ϭ 1.0; CHCl3). IR (KBr): ν˜ ϭ 2980 (vs), 2938
(s), 2904 (s), 1655 (m), 1614 (w), 1516 (m), 1458 (m), 1416 (w),
1373 (vs), 1315 (w), 1234 (s), 1217 (s), 1168 (vs), 1119 (s), 1049 (vs),
1018 (vs), 931 (m), 875 (vs), 828 (vs), 789 (m), 743 (w), 606 (vs),
Experimental Section
General Remarks: All moisture-sensitive reactions were carried out
using standard Schlenk techniques unless stated otherwise. Solvents
were dried and purified by conventional methods prior to use. THF
was freshly distilled from sodiumϪlead alloy under argon. Re-
agents of commercial quality were used from freshly opened con-
tainers or purified by common methods. nBuLi (1.6  in hexane)
was purchased from Merck, Darmstadt. Preparative column chro-
matography used Merck silica gel 60, particle size 0.040Ϫ0.063 mm
(230Ϫ240 mesh, flash). Analytical TLC used silica-gel 60 F254
plates from Merck, Darmstadt. Optical rotation values were meas-
ured with a PerkinϪElmer P241 polarimeter. Microanalyses were
obtained with a Vario EL element analyzer. Mass spectra were ac-
quired with a Finnigan SSQ7000 (CI, 100 eV, EI 70 eV) spec-
trometer. High-resolution mass spectra were recorded with a Finni-
1
548 (m), 522 (m) cmϪ1. H NMR (400 MHz, CDCl3): δ ϭ 1.30 [s,
9 H, C(CH3)3], 1.33, 1.36, 1.46, 1.56 [each s, 3 H, (O)2C(CH3)2],
1.62 (s, 3 H, CH3CϭCH2), 2.93 [dd, J ϭ 11.5, 14.3 Hz, 1 H,
CHHC(CH3)ϭCH2], 3.16 [dd,
J
ϭ
3.3, 14.3 Hz,
1
H,
CHHC(CH3)ϭCH2], 3.90 (dd, J ϭ 6.6, 8.3 Hz, 1 H, CHHOC),
4.04 (dd, J ϭ 6.9, 8.3 Hz, 1 H, CHHOC), 4.15 [dd, J ϭ 4.1, 8.5 Hz,
1 H, CH(OC)CH(OC)CH2O], 4.23 [app. t, J ϭ 4.4 Hz, 1 H,
CH(OC)CH(OC)2], 4.30 (dt, J ϭ 4.1, 6.6 Hz, 1 H, CH(OC)CH2O],
4.52 (dd, J ϭ 3.6, 11.5, 1 H, CHSO3), 4.64 (br. s, 1 H, CHHϭ
CCH3), 4.66 (dd, J ϭ 4.7, 8.5 Hz, 1 H, CHOSO2), 4.71 (br. s, 1 H,
CHHϭCCH3), 5.69 [d, J ϭ 3.6 Hz, 1 H, CH(OC)2], 7.35 (s, 4 H,
ArH) ppm. 13C NMR (100 MHz, CDCl3): δ ϭ 22.1 (CH3CϭCH2),
25.3, 26.2, 26.6, 26.6 [(O)2C(CH3)2], 31.2 [C(CH3)3], 34.6
[C(CH3)3], 37.6 [CH2C(CH3)ϭCH2], 65.1 (CH2OC), 66.5 (CHSO3),
74.5, 76.6, 76.7, 77.4 (CHO), 103.5 [CH(OC)2], 109.9, 113.3
[(O)2C(CH3)2], 114.2 [CH2ϭC(CH3)], 125.4, 127.9 (ArC), 129.4
(ArCH), 139.5 [C(CH3)ϭCH2], 151.9 (ArC) ppm. MS (CI, 100 eV,
isobutane): m/z (%) ϭ 525 (43) [Mϩ ϩ 1], 471 (3), 243 (41), 201
(100). C27H40O8S (524.67): calcd. C 61.81, H 7.68; found C 61.72,
H 7.99.
gan MAT95 spectrometer. IR spectra were taken with
a
PerkinϪElmer FT/IR 1760 instrument. H and 13C NMR spectra
were recorded with Gemini 300 or Varian Inova 400 instruments
and all measurements were performed with tetramethylsilane as in-
ternal standard. Melting points were determined with a Tottoli
melting point apparatus and are uncorrected.
1
α-Allylated Chiral Sulfonates (R)-2aϪg. General Procedure 1 (GP
1): The enantiopure sulfonate 1 (1.0 equiv.) was dissolved in dry
THF (10 mL per mmol) and cooled to between Ϫ90 and Ϫ95 °C
under argon. nBuLi (1.0 equiv.) was added dropwise. After stirring
for 1 h, the allylic halide (1.5 equiv.) was added dropwise. The reac-
tion mixture was stirred at Ϫ90 to Ϫ95 °C for 2 h, then stirring
(R)-3-Methyl-1-phenyl-3-butene-1-sulfonate (2b): According to GP
1, sulfonate 1a (2.07 g, 5 mmol) was deprotonated with nBuLi
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Eur. J. Org. Chem. 2003, 3939Ϫ3947

Asymmetric Synthesis of α,γ-Substituted γ-Sultones
FULL PAPER
(3.13 mL, 1.6 ) and reacted with 3-bromo-2-methylpropene
(0.76 mL, 7.5 mmol). Workup and flash column chromatography
from 2-propanol; de Ն 98% (NMR); m.p. 92 °C; [α]2D4 ϭ ϩ70.00
(c ϭ 1.0; CHCl3). IR (KBr): ν˜ ϭ 2965 (vs), 2906 (s), 1642 (m), 1616
(Et2O/pentane, 1:4) gave (R)-2b (1.68 g, 72%); de ϭ 88% (NMR). (m), 1513 (m), 1459 (m), 1416 (w), 1372 (vs), 1317 (w), 1219 (vs),
The major diastereomer was obtained as a colorless solid after 1169 (vs), 1119 (m), 1020 (vs), 925 (s), 874 (vs), 829 (vs), 738 (w),
recrystallization from 2-propanol; de Ն 98% (NMR); m.p. 132 °C; 608 (s), 537 (m), 517 (m) cmϪ1. H NMR (400 MHz, CDCl3): δ ϭ
[α]2D4 ϭ ϩ90.69 (c ϭ 1.0; CHCl3). IR (KBr): (ν˜ ϭ 2984 (vs), 2936
1.31 [s, 9 H, C(CH3)3], 1.33, 1.37, 1.46, 1.57 [each s, 3 H,
(s), 2902 (m), 1653 (m), 1497 (w), 1456 (m), 1370 (vs), 1314 (w), (O)2C(CH3)2], 2.95 (m, 1 H, CHHCHϭCH2), 3.20 (m, 1 H,
1
1218 (s), 1167 (vs), 1116 (s), 1082 (m), 1047 (vs), 1015 (vs), 931
CHHCHϭCH2), 3.89 (dd, J ϭ 6.6, 8.5 Hz, 1 H, CHHOC), 4.03
1
(m), 876 (vs), 828 (vs), 798 (m), 734 (w), 697 (s), 628 (s) cmϪ1. H (dd, J ϭ 6.8, 8.5 Hz, 1 H, CHHOC), 4.15 [dd, J ϭ 3.9, 8.5 Hz, 1
NMR (400 MHz, CDCl3): δ ϭ 1.33, 1.36, 1.46, 1.56 [each s, 3 H, H, CH(OC)CH(OC)CH2O], 4.22 [app. t, J ϭ 4.3, 1 H, CH(OC)-
(O)2C(CH3)2], 1.62 (s, 3 H, CH3CϭCH2), 2.95 [ddd, J ϭ 0.6, 11.8, CH(OC)2], 4.32 [dt, J ϭ 3.9, 6.6, 1 H, CH(OC)CH2O], 4.36 (dd,
14.3 Hz, 1 H, CHHC(CH3)ϭCH2], 3.17 [dd, J ϭ 3.3, 14.3 Hz, 1
H, CHHC(CH3)ϭCH2], 3.89 (dd, J ϭ 6.6, 8.5 Hz, 1 H, CHHOC),
J ϭ 3.9, 11.3, 1 H, CHSO3), 4.66 (dd, J ϭ 4.7, 8.5 Hz, 1 H,
CHOSO2), 5.00 (dd, J ϭ 1.4, 10.2 Hz, 1 H, CHHϭCH), 5.09 (dd,
4.04 (dd, J ϭ 6.6, 8.5 Hz, 1 H, CHHOC), 4.14 [dd, J ϭ 3.9, 8.5 Hz, J ϭ 1.4, 17.0 Hz, 1 H, CHHϭCH), 5.55 [ddt (ABX2 system), J ϭ
1 H, CH(OC)CH(OC)CH2O], 4.29 [m, 2 H, CH(OC)CH(OC)2 and 6.9, 10.2, 17.0 Hz, 1 H, CH2CHϭCH2], 5.71 [d, J ϭ 3.9 Hz, 1 H,
CH(OC)CH2O], 4.53 (dd, J ϭ 3.6, 11.8 Hz, 1 H, CHSO3), 4.62 CH(OC)2], 7.35Ϫ7.42 (m, 4 H, ArH) ppm. 13C NMR (100 MHz,
(br. s, 1 H, CHHϭCCH3), 4.68 (dd, J ϭ 4.7, 8.8 Hz, 1 H,
CDCl3): δ ϭ 25.3, 26.2, 26.6 [2 ϫ (O)2C(CH3)2], 31.2 [C(CH3)3]
CHOSO2), 4.71 (m, 1 H, CHHϭCCH3), 5.70 [d, J ϭ 3.6 Hz, 1 H, 34.2 (CH2CHϭCH2), 34.6 [C(CH3)3], 65.1 (CH2OC), 67.6
CH(OC)2], 7.35Ϫ7.39 (m, 3 H, ArH), 7.43Ϫ7.47 (m, 2 H, ArH) (CHSO3), 74.6, 76.7, 77.2, 77.4 (CHO), 103.6 [CH(OC)2], 109.9,
ppm. 13C NMR (100 MHz, CDCl3): δ ϭ 22.1 (CH3CϭCH2), 25.2,
113.3 [(O)2C(CH3)2], 118.3 (CH2ϭCH), 125.5 (ArCH), 127.9
26.2, 26.6, 26.7 [2 ϫ (O)2C(CH3)2], 37.7 [CH2C(CH3)ϭCH2], 65.2 (ArC), 129.4 (ArCH),), 132.6 (CHϭCH2), 152.1 (ArC) ppm. MS
(CH2OC), 66.8 (CHSO3), 74.6, 76.6, 76.7, 77.4 (CHO), 103.5 (CI, 100 eV, isobutane): m/z (%) ϭ 511 (93) [Mϩ ϩ 1], 495 (6), 261
[CH(OC)2], 109.9, 113.4 [(O)2C(CH3)2], 114.4 (CH2ϭC(CH3), (9), 203 (23), 187 (100). C26H38O8S (510.65): calcd. C 61.15, H 7.50;
128.5, 129.0, 129.8 (ArCH), 131.1 (ArC), 139.4 [C(CH3)ϭCH2]
ppm. MS (CI, 100 eV, isobutane): m/z (%) ϭ 469 (100) [Mϩ ϩ 1],
243 (44), 203 (15). 145 (12). C23H32O8S (468.57): calcd. C 58.96,
H 6.88; found C 58.78, H 6.94.
found C 61.14, H 7.89.
(R)-1-(Naphth-2-yl)-3-butene-1-sulfonate (2e): According to GP 1,
sulfonate 1c (0.83 g, 1.8 mmol) was deprotonated with nBuLi
(1.13 mL, 1.6 ) and reacted with allyl iodide (0.25 mL, 2.7 mmol).
Workup and flash column chromatography (Et2O/pentane, 1:4)
(R)-1-Phenyl-3-butene-1-sulfonate (2c): According to GP 1, sulfon-
ate 1a (2.07 g, 5 mmol) was deprotonated with nBuLi (3.13 mL, gave (R)-2e (0.88 g, 98%); de ϭ 90% (NMR). The major dia-
1.6 ) and reacted with allyl iodide (0.75 mL, 7.5 mmol). Workup
and flash column chromatography (Et2O/pentane, 1:4) gave (R)-
2c (2.22 g, 98%); de ϭ 95% (NMR). The major diastereomer was
obtained as a colorless solid after recrystallization from 2-propa-
stereomer was obtained as a colorless solid after recrystallization
from 2-propanol; de Ն 98% (NMR); m.p. 102 °C; [α]2D4 ϭ ϩ70.50
(c ϭ 0.9; CHCl3). IR (KBr): ν˜ ϭ 3062 (w), 2985 (s), 2937 (m), 2904
(m), 1642 (w), 1600 (w), 1510 (w), 1458 (w), 1370 (vs), 1316 (m),
nol; de Ն 98% (NMR); m.p. 149 °C; [α]2D4 ϭ ϩ77.00 (c ϭ 1.0; 1218 (s), 1171 (vs), 1116 (s), 1047 (vs), 1014 (vs), 928 (m), 875 (s),
CHCl3). IR (KBr): ν˜ ϭ 2978 (w), 2934 (w), 1497 (w), 1457 (m), 838 (s), 746 (m), 655 (m), 601 (m), 480 (m) cmϪ1 1H NMR
.
1370 (vs), 1355 (s), 1313 (m), 1255 (s), 1220 (s), 1172 (vs), 1115 (s), (400 MHz, CDCl3): δ ϭ 1.19, 1.37, 1.46, 1.50 [each s, 3 H,
1054 (s), 1038 (s), 1015 (vs), 1001 (s), 933 (m), 880 (s), 864 (m), 840 (O)2C(CH3)2], 3.09 (m, 1 H, CHHCHϭCH2), 3.28 (m, 1 H,
1
(s), 810 (m), 698 (m), 627 (m), 571 (m), 503 (m) cmϪ1. H NMR CHHCHϭCH2), 3.89 (dd, J ϭ 6.6, 8.5 Hz, 1 H, CHHOC), 4.03
(400 MHz, CDCl3): δ ϭ 1.33, 1.37, 1.46, 1.57 [each s, 3 H,
(O)2C(CH3)2], 2.96 (m, 1 H, CHHCHϭCH2), 3.21 (m, 1 H,
(dd, J ϭ 6.9, 8.5 Hz, 1 H, CHHOC), 4.13 [dd, J ϭ 4.1, 8.5 Hz, 1
H, CH(OC)CH(OC)CH2O], 4.21 [app. t, J ϭ 4.3 Hz, 1 H, CH(OC-
CHHCHϭCH2), 3.89 (dd, J ϭ 6.6, 8.5 Hz, 1 H, CHHOC), 4.04 )CH(OC)2], 4.28 [dt, J ϭ 4.1, 6.6 Hz, 1 H, CH(OC)CH2O], 4.55
(dd, J ϭ 6.9, 8.5 Hz, 1 H, CHHOC), 4.14 [dd, J ϭ 3.9, 8.5 Hz, 1 (dd, J ϭ 4.1, 11.3 Hz, 1 H, CHSO3), 4.66 (dd, J ϭ 4.9, 8.5 Hz, 1
H, CH(OC)CH(OC)CH2O], 4.26Ϫ4.32 [m, 2 H, CH(OC)CH(OC)2 H, CHOSO2), 4.88 (dd, J ϭ 1.4, 10.2 Hz, 1 H, CHHϭCH), 5.09
and CH(OC)CH2O], 4.37 (dd, J ϭ 4.1, 11.3, 1 H, CHSO3), 4.68
(dd, J ϭ 4.7, 8.8 Hz, 1 H, CHOSO2), 5.01 (dd, J ϭ 1.4, 10.2 Hz, 1
(dd, J ϭ 1.4, 17.0 Hz, 1 H, CHHϭCH), 5.55 [ddt (ABX2 system),
J ϭ 6.9, 10.2, 17.0 Hz, 1 H, CH2CHϭCH2], 5.72 [d, J ϭ 3.8 Hz, 1
H, CHHϭCH), 5.08 (dd, J ϭ 1.4, 17.0 Hz, 1 H, CHHϭCH), 5.54 H, CH(OC)2], 7.48Ϫ7.55 (m, 2 H, ArH), 7.59 (dd, J ϭ 1.7, 8.5 Hz,
[ddt (ABX2 system), J ϭ 6.9, 10.2, 17.0 Hz, 1 H, CH2CHϭCH2],
5.72 [d, J ϭ 3.9 Hz, 1 H, CH(OC)2], 7.36Ϫ7.41 (m, 3 H, ArH),
1 H, ArH), 7.82Ϫ7.89 (m, 3 H, ArH), 7.92 (br. s, 1 H, ArH) ppm.
13C NMR (100 MHz, CDCl3): δ ϭ 25.2, 26.2, 26.5, 26.6 [2 ϫ
7.43Ϫ7.48 (m, 2 H, ArH) ppm. 13C NMR (100 MHz, CDCl3): δ ϭ (O)2C(CH3)2], 34.2 (CH2CHϭCH2), 65.2 (CH2OC), 68.1 (CHSO3),
25.2, 26.2, 26.6, 26.6 [2 ϫ (O)2C(CH3)2], 34.2 (CH2CHϭCH2), 74.6, 76.8, 77.2, 77.4 (CHO), 103.5 [CH(OC)2], 110.0, 113.4
65.2 (CH2OC), 67.8 (CHSO3), 74.6, 76.8, 77.2, 77.4 (CHO), 103.6 [(O)2C(CH3)2], 118.6 (CH2ϭCH), 126.2, 126.3, 126.7, 127.5, 128.0,
[CH(OC)2], 110.0, 113.4 [(O)2C(CH3)2], 118.5 (CH2ϭCH), 128.6,
129.0, 129.8 (ArCH), 131.1 (ArC), 132.4 (CHϭCH2) ppm. MS (CI, 132.9, 133.3 (ArC) ppm. MS (EI, 70 eV): m/z (%) ϭ 504 (4) [Mϩ],
100 eV, isobutane): m/z (%) ϭ 455 (100) [Mϩ ϩ 1], 439 (4), 415
489 (14), 282 (10), 267 (10), 217 (7), 203 (8), 181 (100), 161 (41),
(30), 397 (12), 357 (4), 203 (5), 131 (12), 101 (2). C22H30O8S 58 (36). C26H32O8S (504.59): calcd. C 61.89, H 6.39; found
128.4 (ArCH), 128.5 (ArC), 130.0 (ArCH), 132.3 (CHϭCH2),
(454.53): calcd. C 58.13, H 6.65; found C 57.78, H 6.61.
C 61.80, H 6.48.
(R)-1-(4-tert-Butylphenyl)-3-butene-1-sulfonate (2d): According to
(R)-1-(4-tert-Butylphenyl)-3-pentene-1-sulfonate (2f): According to
GP 1, sulfonate 1b (2.35 g, 5 mmol) was deprotonated with nBuLi GP 1, sulfonate 1b (2.35 g, 5 mmol) was deprotonated with nBuLi
(3.13 mL, 1.6 ) and reacted with allyl iodide (0.75 mL, 7.5 mmol).
Workup and flash column chromatography (Et2O/pentane, 1:4)
gave (R)-2d (2.50 g, 98%); de ϭ 95% (NMR). The major dia-
stereomer was obtained as a colorless solid after recrystallization
(3.13 mL, 1.6 ) and reacted with 85% (E)-crotyl bromide (0.8 mL,
7.5 mmol). Workup and flash column chromatography (Et2O/pen-
tane, 5:1) gave (R)-2f (2.44 g, 93%); de ϭ 90% (NMR). A 1:13 mix-
ture of the enantiopure (Z)- and (E)-sulfonate (R)-2f was obtained
Eur. J. Org. Chem. 2003, 3939Ϫ3947
www.eurjoc.org
 2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
3943

D. Enders, W. Harnying, N. Vignola
FULL PAPER
as
a
colorless solid after recrystallization from 2-propanol;
1H NMR (400 MHz, CDCl3): δ ϭ 1.27 [s, 9 H, C(CH3)3], 3.58 (dd,
de Ն 98% (NMR); m.p. 103 °C. IR (KBr): ν˜ ϭ 2980 (vs), 2902 (s), J ϭ 11.0, 14.0 Hz, 1 H, CHHAr), 3.63 (s, 3 H, CH3O), 3.88 (dd,
1614 (w), 1517 (w), 1457 (m), 1370 (vs), 1313 (w), 1218 (s), 1168
J ϭ 3.9, 14.0 Hz, 1 H, CHHAr), 4.53 (dd, J ϭ 3.9, 10.7 Hz, 1 H,
(vs), 1118 (s), 1052 (vs), 1018 (vs), 969 (m), 877 (vs), 834 (vs), 612 CHSO3), 7.10Ϫ8.00 (m, 11 H, ArH) ppm. 13C NMR (100 MHz,
1
(s), 550 (m), 505 (m) cmϪ1. H NMR [400 MHz, CDCl3, (E)-iso-
CDCl3): δ ϭ 31.2 [C(CH3)3], 34.6 [C(CH3)3], 36.5 (CH2Ar), 56.8
(CH3O), 68.1 (CHSO3), 125.8, 126.0, 126.1, 127.0, 127.6, 127.6,
mer]: δ ϭ 1.32 [s, 9 H, C(CH3)3], 1.33, 1.36, 1.45, 1.56 [each s, 3 H,
(O)2C(CH3)2], 1.56 [s, 6 H, (O)2C(CH3)2 and CH3CHϭCH], 2.88 127.9, 128.1, (ArCH), 128.5 (ArC), 129.4 (ArCH), 132.3, 133.3,
(m, 1 H, CHHCHϭCHCH3), 3.11 (m, 1 H, CHHCHϭCHCH3), 134.1, 152.3 (ArC) ppm. MS (EI, 70 eV): m/z (%) ϭ 382 (39) [Mϩ],
3.88 (dd, J ϭ 6.6, 8.5 Hz, 1 H, CHHOC), 4.03 (dd, J ϭ 6.8, 8.5 Hz, 287 (100), 231 (12), 153 (16), 141 (22), 122 (26), 57 (88). C23H26O3S
1 H, CHHOC), 4.15 [dd, J ϭ 3.9, 8.5 Hz, 1 H, CH(OC)CH(OC)-
CH2O], 4.21 [app. t, J ϭ 4.3, 1 H, CH(OC)CH(OC)2], 4.29 [m, 2
H, CH(OC)CH2O) and CHSO3), 4.64 (dd, J ϭ 4.7, 8.5 Hz, 1 H,
CHOSO2), 5.16 (m, 1 H, CH2CHϭCHCH3), 5.51 (m, 1 H,
CH2CHϭCHCH3), 5.69 [d, J ϭ 3.9 Hz, 1 H, CH(OC)2], 7.35Ϫ7.41
(m, 4 H, ArH) ppm. 13C NMR [100 MHz, CDCl3, (E)-isomer]:
δ ϭ 17.9 (CH3CHϭCH), 25.3, 26.2, 26.7,[2 ϫ (O)2C(CH3)2], 31.2
(CH2CHϭCH), 34.6 [C(CH3)3], 65.1 (CH2OC), 68.1 (CHSO3),
74.5, 76.6, 78.0, 77.3 (CHO), 103.5 [CH(OC)2], 110.0, 113.3
[(O)2C(CH3)2], 125.0 (CH2CHϭCHCH3), 125.5 (ArCH), 128.1
(ArC), 129.0 (CH2CHϭCHCH3), 129.4 (ArCH), 152.0 (ArC) ppm.
MS (CI, 100 eV, isobutane): m/z (%) ϭ 525 (74) [Mϩ ϩ 1], 509 (5),
403 (7), 261 (23), 243 (7), 201 (100), 143 (21). C27H40O8S (524.67):
calcd. C 61.81, H 7.68; found C 61.73, H 8.00.
(382.52): calcd. C 72.22, H 6.85; found C 71.84, H 6.71.
Methyl (R)-1-Phenyl-3-butene-1-sulfonate (4b): According to GP 2,
sulfonate (R)-2c (0.22 g, 0.5 mmol) was refluxed in a 2% TFA/
EtOH solution (20 mL) for 24 h. Workup and flash column chro-
matography (n-pentane/diethyl ether, 9:1) gave (R)-4b as a colorless
solid (0.08 g, 73%); ee Ն 98% (HPLC); m.p. 58 °C; [α]2D8 ϭ Ϫ6.30
(c ϭ 1.0; CHCl3). IR (KBr): ν˜ ϭ 2959 (w), 2944 (w), 2922 (w), 1643
(m), 1456 (m), 1350 (vs), 1320 (s), 1228 (m), 1163 (vs), 993 (vs),
939 (s), 835 (s), 767 (s), 734 (s), 700 (s), 654 (m) cmϪ1. H NMR
1
(400 MHz, CDCl3): δ ϭ 2.95 (m, 1 H, CHHCHϭCH2), 3.13 (m, 1
H, CHHCHϭCH2), 3.64 (s, 3 H, CH3O), 4.26 (dd, J ϭ 4.7,
11.0 Hz, 1 H, CHSO3), 5.02 (d, J ϭ 10.2 Hz, 1 H, CHHϭCH),
5.10 (d, J ϭ 17.0 Hz, 1 H, CHHϭCH), 5.57 (m, 1 H, CHϭCH2),
7.36Ϫ7.44 (m, 5 H, ArH) ppm. 13C NMR (100 MHz, CDCl3): δ ϭ
34.1 (CH2CHϭCH2), 56.8 (CH3O), 66.7 (CHSO3), 118.6 (CH2ϭ
CH), 128.7, 129.0 (ArCH), 129.5 (ArC), 132.3 (CHϭCH2) ppm.
MS (EI, 70 eV): m/z (%) ϭ 181 (100) [Mϩ Ϫ SO2OCH3], 103 (5),
91 (28) [C7H7ϩ]. C11H14O3S (226.29): calcd. C 58.39, H 6.24; found
C 58.30, H 6.32.
(R)-1-Phenyl-3-pentene-1-sulfonate 2g: According to GP 1, sulfon-
ate 1a (2.06 g, 5 mmol) was deprotonated with nBuLi (3.13 mL, 1.6
) and reacted with 85% (E)-crotyl bromide (0.8 mL, 7.5 mmol).
Workup and flash column chromatography (Et2O/pentane, 1:4)
gave (R)-2g (1.81 g, 78%); de ϭ 82% (NMR). A 1:4 mixture of the
enantiopure (Z)- and (E)-sulfonate (R)-2g was obtained as a color-
less solid after recrystallization from ethanol; de Ն 98% (NMR);
m.p. 143 °C. IR (KBr): ν˜ ϭ 3068 (w), 2987 (s), 2937 (m), 2902 (m),
1498 (w), 1457 (m), 1370 8vs), 1314 (w), 1255 (s), 1219 (s), 1169
(vs), 1117 (s), 1047 (vs), 1015 (vs), 879 (s), 840 (s), 697 (m), 629
Methyl (R)-1-(4-tert-Butylphenyl)-3-butene-1-sulfonate (4c): Ac-
cording to GP 2, sulfonate (R)-2d (0.25 g, 0.5 mmol) was refluxed
in a 2% TFA/EtOH solution (20 mL) for 24 h. Workup and flash
column chromatography (n-pentane/diethyl ether, 9:1) gave (R)-4c
as a colorless liquid (0.09 g, 65%); ee Ն 98% (HPLC, Daicel OD);
[α]2D5 ϭ Ϫ10.69 (c ϭ 1.0; CHCl3). IR (KBr): ν˜ ϭ 3080 (w), 2964
(vs), 2906 (m), 2870 (m), 1643 (w), 1612 (w), 1514 (m), 1464 (m),
1416 (w), 1356 (vs), 1270 (m), 1168 (vs), 1111 (m), 991 (vs), 856
1
(m), 577 (m), 505 (m) cmϪ1. H NMR [400 MHz, CDCl3, (E)-iso-
mer]: δ ϭ 1.32, 1.36, 1.46, 1.56 [each s, 3 H, (O)2C(CH3)2], 1.55 [m,
6 H, (O)2C(CH3)2 and CH3CHϭCH], 2.88 (m, 1 H, CHHCHϭ
CHCH3), 3.14 (m, 1 H, CHHCHϭCHCH3), 3.88 (dd, J ϭ 6.6,
8.5 Hz, 1 H, CHHOC), 4.03 (dd, J ϭ 6.6, 8.5 Hz, 1 H, CHHOC),
4.14 [dd, J ϭ 3.9, 8.5 Hz, 1 H, CH(OC)CH(OC)CH2O], 4.29 [m, 3
H, CH(OC)CH2O) and CH(OC)CH(OC)2 and CHSO3], 4.66 (dd,
J ϭ 4.7, 8.5 Hz, 1 H, CHOSO2), 5.14 (m, 1 H, CH2CHϭCHCH3),
5.49 (m, 1 H, CH2CHϭCHCH3), 5.70 [d, J ϭ 3.9 Hz, 1 H,
CH(OC)2], 7.35Ϫ7.40 (m, 3 H, ArH), 7.42Ϫ7.48 (m, 2 H, ArH)
ppm. 13C NMR (100 MHz, CDCl3): δ ϭ 12.9 [(Z)] and 17.8 [(E),
(CH3CHϭCH)], 25.2, 26.2, 26.6, 26.6 [2 ϫ (O)2C(CH3)2], 27.8 [(Z)]
and 33.2 [(E), (CH2CHϭCH)], 65.1 (CH2OC), 67.9 [(Z)] and 68.3
[(E), (CHSO3)], 74.6, 76.8, 77.1, 77.4 (CHO), 103.6 [CH(OC)2],
109.9, 113.4 [(O)2C(CH3)2], 124.0 [(Z)] and 124.8 [(E), (CH2CHϭ
CHCH3)], 127.4 [(Z)], 128.5, 128.9 (ArCH), 129.2 (CH2CHϭ
CHCH3), 129.8 (ArCH), 131.3 [(E)] and 131.5 [(Z), (ArC)] ppm.
MS (EI, 70 eV): m/z (%) ϭ 468 (2) [Mϩ], 453 (87), 251 (2), 145
(100), 129 (12), 113 (26), 101 (33), 91 (9), 55 (7). C23H32O8S
(468.57): calcd. C 58.96, H 6.88; found C 59.14, H 7.09.
1
(m), 761 (s), 601 (s) cmϪ1. H NMR (400 MHz, CDCl3): δ ϭ 1.32
[s, 9 H, C(CH3)3], 2.95 (m, 1 H, CHHCHϭCH2), 3.10 (m, 1 H,
CHHCHϭCH2), 3.63 (s, 3 H, CH3O), 4.26 (dd, J ϭ 4.4, 10.7 Hz,
1 H, CHSO3), 5.01 (dd, J ϭ 1.4, 10.2 Hz, 1 H, CHHϭCH), 5.11
(dd, J ϭ 1.6, 17.0 Hz, 1 H, CHHϭCH), 5.59 [ddt (ABX2 system),
J ϭ 6.9, 10.2, 17.0 Hz 1 H, CH2CHϭCH2], 7.34 and 7.41 [each d
(AB system), J ϭ 8.5 Hz, 2 H, ArH] ppm. 13C NMR (100 MHz,
CDCl3): δ ϭ 31.2 [C(CH3)3], 34.0 (CH2CHϭCH2), 34.5 [C(CH3)3],
56.7 (CH3O), 66.1 (CHSO3), 118.4 (CH2ϭCH), 125.5 (ArCH),
128.3 (ArC), 129.0 (ArCH), 132.3 (CHϭCH2), 151.9 (ArC) ppm.
MS (EI, 70 eV): m/z (%) ϭ 282 (1) [Mϩ], 267 (2), 187 (31), 157 (5),
129 (16), 115 (6), 91 (5), 57 (100).C15H22O3S (282.40): calcd. C
63.80, H 7.85; found C 63.69, H 8.08.
Methyl (R)-1-Phenyl-3-pentene-1-sulfonate (4d): According to GP
2, sulfonate (R)-2g (a 1:4 mixture of the enantiopure (Z) and (E),
0.22 g, 0.5 mmol) was refluxed in a 2% TFA/EtOH solution
(20 mL) for 24 h. Workup and flash column chromatography (n-
Methyl
(R)-1-(4-tert-Butylphenyl)-2-(naphth-2-yl)ethanesulfonate pentane/diethyl ether, 9:1) gave (R)-4d as a colorless liquid (0.09 g,
(4a): According to GP 2, the corresponding (R)-sulfonate (0.35 g,
0.6 mmol) was refluxed in a 2% TFA/EtOH solution (25 mL) for
80%); ee Ն 98% (HPLC). IR (CHCl3): ν˜ ϭ 3065 (w), 3030 (m),
2960 (m), 2920 (m), 2856 (w), 1497 (m), 1455 (m), 1356 (vs), 1218
24 h. Workup and flash column chromatography (n-pentane/diethyl (m), 1166 (vs), 990 (vs), 832 (m), 760 (vs), 699 (s), 626 (m), 614
ether, 9:1) gave (R)-4a as a colorless solid (0.18 g, 83%); ee Ն 98%
(m), 579 (m) cmϪ1. 1H NMR (400 MHz, CDCl3): δ ϭ 1.55 [dd, J ϭ
1.4, 6.6 Hz, 3 H, (E) CH3CHϭCH], 1.59 [m, 3 H, (Z) CH3CHϭ
(HPLC, Daicel OD); m.p. 94 °C; [α]2D4 ϭ Ϫ108.2 (c ϭ 1.0; CHCl3).
IR (KBr): ν˜ ϭ 2962 (m), 1599 (w), 1560 (w), 1508 (w), 1351 (vs), CH], 2.88 [(E)] and 2.95 [each m, 1 H, (Z) CHHCHϭCHCH3],
1162 (vs), 994 (vs), 960 (m), 859 (m), 827 (s), 809 (w), 777 (s), 765 3.05 [(E)] and 3.13 [each m, 1 H, (Z) CHHCHϭCHCH3], 3.62 [(E)]
(vs), 749 (m), 673 (m), 603 (vs), 518 (m), 484 (m), 474 (m) cmϪ1
.
and 3.64 [each s, 3 H, (Z) SO3CH3], 4.21 (dd, J ϭ 4.4, 10.7 Hz, 1 H,
3944
 2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org Eur. J. Org. Chem. 2003, 3939Ϫ3947

Asymmetric Synthesis of α,γ-Substituted γ-Sultones
FULL PAPER
CHSO3), 5.16 (m, 1 H, CH2CHϭCHCH3), 5.51 (m, 1 H, CH2CHϭ (m), 1389 (m), 1379 (m), 1336 (vs), 1304 (m), 1278 (m), 1237 (m),
CHCH3), 7.36Ϫ7.43 (m, 5 H, ArH) ppm. 13C NMR (100 MHz, 1219 (m), 1200 (m), 1185 (vs), 1148 (vs), 1106 (s), 1076 (m), 978
CDCl3): δ ϭ 12.9 [(Z)] and 17.8 [(E) CH3CHϭCH], 27.5 (Z) and (m), 933 (m), 881 (m), 830 (vs), 773 (s), 699 (s) cmϪ1 1H NMR
.
33.0 [(E), CH2CHϭCH], 56.7 (SO3CH3), 66.7 [(Z)] and 67.1 [(E),
CHSO3)], 124.0 [(Z)] and 124.7 [(E), CH2CHϭCHCH3], 127.5 [(Z), J ϭ 7.1, 13.2 Hz, 1 H, CHH), 2.80 (t, J ϭ 13.6 Hz, 1 H, CHH),
128.6, 128.9, 128.9 [(Z)], 129.4, 129.4, 129.5 (CH2CHϭCHCH3 and 4.58 (dd, J ϭ 7.1, 13.7 Hz, 1 H, CHAr), 7.38Ϫ7.41 (m, 3 H, ArH),
(400 MHz, CDCl3): δ ϭ 1.58, 1.63 (each s, 3 H, CH3), 2.58 (dd,
ArCH), 131.8 (ArC) ppm. MS (EI, 70 eV): m/z (%) ϭ 240 (0.2) 7.43Ϫ7.48 (m, 2 H, ArH) ppm. 13C NMR (100 MHz, CDCl3): δ ϭ
[Mϩ], 186 (7), 145 (100), 129 (18), 117 (23), 105 (7), 91 (24), 77 (6),
65 (5), 55 (6). C12H16O3S (240.32): calcd. C 59.97, H 6.71; found
C 59.91, H 6.74.
28.0, 29.1 (CH3), 41.4 (CH2), 61.7 (CHAr), 86.0 (COSO2), 128.6
(ArCH), 128.6 (ArC), 128.8, 129.3 (ArC) ppm. MS (EI, 70 eV):
m/z (%) ϭ 226 (6) [Mϩ], 161 (10), 145 (7), 131 (34), 104 (100), 91
(13). C11H14O3S (226.29): calcd. C 58.39, H 6.24; found C 58.31,
H 6.21.
Methyl (R)-1-(4-tert-Butylphenyl)-3-pentene-1-sulfonate (4e): Ac-
cording to GP 2, sulfonate (R)-2f (a 1:13 mixture of the enantiop-
ure (Z) and (E), 0.22 g, 0.4 mmol) was refluxed in a 2% TFA/EtOH (3R,5R)-5-Methyl-3-phenyl-1,2-oxathiolane 2,2-Dioxide [(R,R)-5c]:
solution (20 mL) for 24 h. Workup and flash column chromatogra- According to GP 3, sulfonate (R)-2c (0.45 g, 1 mmol) was refluxed
phy (n-pentane/diethyl ether, 9:1) gave (R)-4e as a colorless liquid in a 2% TFA/EtOH solution (40 mL) for 24 h. After removal of
(0.10 g, 81%); ee Ն 98% (HPLC, Daicel OD). IR (CHCl3): ν˜ ϭ solvent under reduced pressure, the crude sulfonic acid 3 was re-
3031 (m), 2962 (vs), 2869 (m), 1612 (w), 1512 (m), 1450 (m), 1416 fluxed in a 20% TFA/CH2Cl2 solution (20 mL) for 24 h. The crude
(w), 1356 (vs), 1295 (m), 1167 (vs), 1111 (m), 990 (vs), 856 (m), 762 product, which consisted of a 90:10 mixture of cis:trans dia-
(s), 605 (s) cmϪ1
1.32 [s, 9 H, C(CH3)3], 1.56 (dd, J ϭ 1.4, 6.6 Hz, 3 H, CH3CHϭ
CH), 2.87 (m, 1 H, CHHCHϭCHCH3), 3.02 (m, 1 H, CHHCHϭ
.
1H NMR [400 MHz, CDCl3, (E)-isomer]: δ ϭ
stereomers, was purified by flash column chromatography (n-pen-
tane/diethyl ether, 4:1) and gave (R,R)-5c as a colorless solid
(0.15 g, 72%); ds Ն 99% (NMR); ee Ն 98% (GC, Chirasil-Dex);
CHCH3), 3.63 (s, 3 H, SO3CH3), 4.18 (dd, J ϭ 4.4, 10.7 Hz, 1 H, m.p. 134 °C; [α]2D4 ϭ Ϫ11.29 (c ϭ 1.0; CHCl3). IR (KBr): ν˜ ϭ 3035
CHSO3), 5.19 (m, 1 H, CH2CHϭCHCH3), 5.53 (m, 1 H, CH2CHϭ (w), 2995 (w), 2973 (w), 1498 (m), 1459 (m), 1387 (m), 1331 (vs),
CHCH3), 7.32, 7.40 [each d (AB system), J ϭ 8.5 Hz, 2 H, ArH] 1252 (m), 1194 (m), 1165 (vs), 1130 (w), 1113 (w), 1026 (s), 942
ppm. 13C NMR [100 MHz, CDCl3, (E)-isomer]: δ ϭ 17.8
(w), 910 (w), 858 (m), 820 (vs), 795 (vs), 770 (m), 698 (s), 598 (m)
(CH3CHϭCH), 31.2 [C(CH3)3], 33.0 (CH2CHϭCH), 34.6 cmϪ1. 1H NMR (400 MHz, CDCl3): δ ϭ 1.56 (d, J ϭ 6.0 Hz, 3 H,
[C(CH3)3], 56.6 (SO3CH3), 66.7 (CHSO3), 125.0 (CH2CHϭ CH3CHO), 2.56 (dt, J ϭ 10.4, 13.2 Hz, 1 H, CHH), 2.79 (ddd, J ϭ
CHCH3), 125.5, 129.1 (ArCH), 129.1 (CH2CHϭCHCH3), 151.9 5.5, 6.9, 13.2 Hz, 1 H, CHH), 4.54 (dd, J ϭ 6.9, 13.2 Hz, 1 H,
(ArC) ppm. MS (EI, 70 eV): m/z (%) ϭ 296 (7) [Mϩ], 281 (3), 227 CHAr), 4.78 (m, 1 H, CH3CHO), 7.36Ϫ7.45 (m, 5 H, ArH) ppm.
(1), 201 (22), 186 (2), 171 (2), 143 (27), 129 (5), 117 (3), 91 (3), 79
13C NMR (100 MHz, CDCl3): δ ϭ 20.8 (CH3), 37.6 (CH2), 63.3
(4), 57 (100). C16H24O3S (296.37): calcd. C 64.84, H 8.16; found (CHAr), 77.4 (CHO), 128.6, 128.8, 129.3 (ArCH), 129.3 (ArC)
C 64.60, H 8.49.
ppm. MS (EI, 70 eV): m/z ϭ 212 (10) [Mϩ], 148 (14), 104 (100),
91 (5), 78 (10). C10H12O3S (212.27): calcd. C 56.59, H 5.70; found
C 56.48, H 5.65.
(3R)-3-(4-tert-Butylphenyl)-5,5-dimethyl-1,2-oxathiolane 2,2-Diox-
ide [(R)-5a]: According to GP 3, sulfonate (R)-2a (0.25 g, 0.5 mmol)
was refluxed in a 2% TFA/EtOH solution (20 mL) for 24 h. After
removal of solvent under reduced pressure, the crude sulfonic acid
(3R,5R)-3-(4-tert-Butylphenyl)-5-methyl-1,2-oxathiolane 2,2-Diox-
ide [(R,R)-5d]: According to GP 3, sulfonate (R)-2d (0.52 g,
3 was refluxed in a 2% TFA/CH2Cl2 solution (20 mL) for 22 h. 1 mmol) was refluxed in a 2% TFA/EtOH solution (40 mL) for
Workup and flash column chromatography (n-pentane/diethyl
ether, 4:1) gave (R)-5a as a colorless solid (0.11 g, 82%); ee Ն 98%
(HPLC, Daicel OD); m.p. 186 °C; [α]2D4 ϭ Ϫ37.9 (c ϭ 1.0; CHCl3).
24 h. After removal of solvent under reduced pressure, the crude
sulfonic acid 3 was refluxed in a 20% TFA/CH2Cl2 solution
(20 mL) for 24 h. The crude product, which consisted of an 89:11
IR (KBr): ν˜ ϭ 2966 (s), 2875 (m), 1513 (m), 1464 (m), 1340 (vs), mixture of cis:trans diastereomers, was purified by flash column
1303 (m), 1276 (m), 1184 (vs), 1148 (s), 1125 (m), 1105 (m), 1022
chromatography (n-pentane/diethyl ether, 4:1) and gave (R,R)-5d as
a colorless solid (0.17 g, 64%); ds Ն 99% (NMR); ee Ն 98%
(w), 977 (w), 931 (m), 886 (m), 839 (vs), 770 (m), 588 (m) cmϪ1
.
1H NMR (400 MHz, CDCl3): δ ϭ 1.32 [s, 9 H, C(CH3)3], 1.60, 1.65 (HPLC, Daicel AD); m.p. 153 °C; [α]2D4 ϭ Ϫ8.6 (c ϭ 1.2; CHCl3).
(each s, 3 H, CH3), 2.58 (dd, J ϭ 7.1, 13.2 Hz, 1 H, CHH), 2.81 IR (KBr): ν˜ ϭ 2963 (s), 2870 (m), 1614 (w), 1514 (m), 1475 (m),
(t, J ϭ 13.6 Hz, 1 H, CHH), 4.58 (dd, J ϭ 7.1, 13.7 Hz, 1 H,
CHAr), 7.38Ϫ7.41 (m, 3 H, ArH), 7.39Ϫ7.45 (m, 4 H, ArH) ppm.
1454 (m), 1387 (m), 1334 (vs), 1251 (m), 1193 (s), 1164 (vs), 1129
(m), 1099 (m), 1031 (s), 940 (m), 916 (m), 865 (m), 825 (vs), 794
13C NMR (100 MHz, CDCl3): δ ϭ 28.0, 29.1 (CH3), 31.2 (vs), 706 (m), 677 (w), 603 (s), 568 (m) cmϪ1. 1H NMR (400 MHz,
[C(CH3)3], 41.5 (CH2), 61.5 (CHAr), 85.7 (COSO2), 128.5 (ArC),
CDCl3): δ ϭ 1.32 [s, 9 H, C(CH3)3], 1.59 (d, J ϭ 6.3 Hz, 3 H,
125.8, 128.3 (ArCH), 152.4 (ArC) ppm. MS (EI, 70 eV): m/z (%) ϭ CH3CHO), 2.59 (dt, J ϭ 10.4, 13.2 Hz, 1 H, CHH), 2.81 (ddd, J ϭ
282 (27) [Mϩ], 267 (41)], 160 (53), 145 (100), 117 (11), 91 (5), 57
(7). C15H22O3S (282.40): calcd. C 63.80, H 7.85; found C 63.83,
H 7.72.
5.5, 6.9, 13.2 Hz, 1 H, CHH), 4.54 (dd, J ϭ 7.2, 13.2 Hz, 1 H,
CHAr), 4.82 (m, 1 H, CH3CHO), 7.38 and 7.44 [each d (AB sys-
tem), J ϭ 8.5 Hz, 2 H, ArH] ppm. 13C NMR (100 MHz, CDCl3):
δ ϭ 20.9 (CH3), 31.2 [C(CH3)3], 34.6 [C(CH3)3], 37.7(CH2), 63.0
(CHAr), 77.2 (CHO), 125.9 (ArCH), 126.2 (ArC), 128.3 (ArCH),
152.5 (ArC) ppm. MS (EI, 70 eV): m/z (%) ϭ 268 (22) [Mϩ], 253
(30), 160 (51), 145 (100), 117 (13), 91 (5). C14H20O3S (268.38):
calcd. C 62.66, H 7.51; found C 62.43, H 7.05.
(3R)-5,5-Dimethyl-3-phenyl-1,2-oxathiolane 2,2-Dioxide [(R)-5b]:
According to GP 3, sulfonate (R)-2b (0.23 g, 0.5 mmol) was re-
fluxed in a 2% TFA/EtOH solution (20 mL) for 24 h. After removal
of solvent under reduced pressure, the crude sulfonic acid 3 was
refluxed in a 2% TFA/CH2Cl2 solution (20 mL) for 20 h. Workup
and flash column chromatography (n-pentane/diethyl ether, 4:1)
gave (R)-5b as a colorless solid (0.10 g, 90%); ee Ն 98% (HPLC,
Daicel OJ); m.p. 119 °C; [α]2D5 ϭ Ϫ44.22 (c ϭ 1.0; CHCl3). IR
(KBr): ν˜ ϭ 2985 (m), 2935 (m), 1602 (w), 1585 (w), 1498 (m), 1456
(3R,5R)-5-Methyl-3-(naphth-2-yl)-1,2-oxathiolane
2,2-Dioxide
[(R,R)-5e]: According to GP 3, sulfonate (R)-2e (0.50 g, 1 mmol)
was refluxed in a 2% TFA/EtOH solution (40 mL) for 24 h. After
removal of solvent under reduced pressure, the crude sulfonic acid
Eur. J. Org. Chem. 2003, 3939Ϫ3947
www.eurjoc.org
 2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
3945

D. Enders, W. Harnying, N. Vignola
3 was refluxed in a 20% TFA/CH2Cl2 solution (20 mL) for 24 h. 9.5 (CH2CH3), 28.5 (CH2CH3), 35.8 (CH2), 63.0 (CHAr), 82.0
FULL PAPER
The crude product, which consisted of an 89:11 mixture of cis:trans
diastereomers, was purified by HPLC (n-pentane/EtOAc, 1:1) and
(CHO), 128.8, 129.1, 129.5 (ArCH) ppm. MS (EI, 70 eV): m/z
(%) ϭ 226 (6) [Mϩ], 161 (13), 145 (3), 133 (3), 117 (7), 104 (100),
gave (R,R)-5e as a colorless solid (0.20 g, 77%); ds Ն 99% (NMR); 91 (5), 77 (8). C11H14O3S (226.29): calcd. C 58.39, H 6.24; found
ee Ն 98% (HPLC, Daicel OD); m.p. 166 °C; [α]2D4 ϭ Ϫ17.27 (c ϭ
1.0; CHCl3). IR (KBr): ν˜ ϭ 3055 (w), 2989 (w), 2932 (w), 1600 (w),
1508 (w), 1448 (w), 1388 (m), 1371 (m), 1338 (vs), 1252 (m), 1196
(m), 1168 (vs), 1132 (m), 1109 (m), 1034 (s), 862 (m), 814 (vs), 746
(s), 606 (m), 479 (m) cmϪ1. 1H NMR (400 MHz, CDCl3): δ ϭ 1.56
(d, J ϭ 6.2 Hz, 3 H, CH3CHO), 2.72 (dt, J ϭ 10.4, 12.9 Hz, 1 H,
CHH), 2.89 (ddd, J ϭ 5.8, 7.1, 12.9 Hz, 1 H, CHH), 4.72 (dd, J ϭ
7.2, 12.9 Hz, 1 H, CHAr), 4.85 (m, 1 H, CH3CHO), 7.48Ϫ7.58 (m,
3 H, ArH), 7.80Ϫ7.91 (m, 4 H, ArH) ppm. 13C NMR (100 MHz,
CDCl3): δ ϭ 20.6 (CH3), 37.9 (CH2), 63.7 (CHAr), 77.4 (CHO),
125.4, 126.8 (ArCH), 126.9 (ArC), 127.0, 127.7, 128.1, 128.7, 129.0
(ArCH), 133.1, 133.6 (ArC) ppm. MS (EI, 70 eV): m/z ϭ 262 (31)
[Mϩ], 154 (100). HRMS (EI, Mϩ): m/z calcd. for C14H14O3S:
262.0664; found 262.0663.
C 58.22, H 6.63.
X-ray Crystallographic Study of 5c: The compound (C10H12O3S;
Mr ϭ 212.27) crystallizes in orthorhombic space group P212121
(No.19) with cell dimensions a ϭ 5.9209(7), b ϭ 11.219(3), and c ϭ
3
˚
˚
15.264(2) A. A cell volume of V ϭ 1013.9(3) A and Z ϭ 4 results
in a calculated density of dcalcd. ϭ 1.391 g·cmϪ3. 4090 reflections
have been collected at T ϭ 150 K on an ENRAF-NONIUS CAD4
diffractometer employing graphite-monochromated Cu-Kα-radi-
˚
ation (λ ϭ 1.54179 A) in the ω/2Θ mode. Data collection covered
the range Ϫ7 Յ h Յ 7, Ϫ13 Յ k Յ 13, and Ϫ14Յ l Յ 14 up to
Θmax. ϭ 72.8°. Lorentz and polarization corrections have been ap-
plied to the diffraction data but no absorption correction (µ ϭ
2.678 mmϪ1) The structure has been solved by direct methods as
implemented in the Xtal3.7 suite of crystallographic routines[17]
where GENSIN has been used to generate the structure-invariant
relationships and GENTAN for the general tangent phasing pro-
cedure. 1848 observed reflections [I Ͼ 2σ(I)] have been included in
the final full-matrix least-squares refinement on F involving 127
parameters and converging at R(Rw) ϭ 0.067(0.077, w ϭ σ2), a final
shift/error Ͻ 0.0003, S ϭ 3.544, and a residual electron density of
(3R,5R)-3-(4-tert-Butylphenyl)-5-ethyl-1,2-oxathiolane 2,2-Dioxide
[(R,R)-5f]: According to GP 3, sulfonate (R)-2f (0.26 g, 0.5 mmol)
was refluxed in a 2% TFA/EtOH solution (20 mL) for 24 h. After
removal of solvent under reduced pressure, the crude sulfonic acid
3 was refluxed in a 30% TFA/CH2Cl2 solution (10 mL) for 16 h.
The crude product, which consisted of a 78:4:4:14 mixture of
cis:trans diastereomers of the corresponding γ-sultone and δ-sul-
tone respectively, was purified by preparative HPLC and gave
(R,R)-5f as a colorless solid (0.09 g, 64%); ds Ն 99% (NMR);
ee Ն 98% (HPLC, Chiralpak AD); m.p. 111 °C; [α]2D4 ϭ Ϫ0.70 (c ϭ
1.0; CHCl3). IR (KBr): ν˜ ϭ 2964 (s), 2871 (m), 1657 (w), 1515 (m),
1464 (m), 1420 (w), 1384 (s), 1341 (vs), 1169 (vs), 983 (m), 926 (m),
Ϫ1.37/0.95 e·AϪ3. Xabs. ϭ Ϫ0.05(5)[18] for the structure shown in
˚
Figure 2. Most of the hydrogen positions have been calculated.
Their isotropic displacement parameters have been fixed at 1.5
times the value of the relevant heavy atom. All hydrogen param-
eters have been kept fixed in the refinement.
CCDC-205259 contains the supplementary crystallographic data
for this paper. These data can be obtained free of charge at
www.ccdc.cam.ac.uk/conts/retrieving.html [or from the Cambridge
Crystallographic Data Centre, 12, Union Road, Cambridge
CB2 1EZ, UK; fax: (internat.) ϩ44-1223/336-033; E-mail:
deposit@ccdc.cam.ac.uk].
870 (m), 838 (vs), 818 (vs), 621 (m) cmϪ1 1H NMR (400 MHz,
.
CDCl3): δ ϭ 1.09 (t, J ϭ 7.4 Hz, 3 H, CH2CH3), 1.32 [s, 9 H,
C(CH3)3], 1.83 (m, 1 H, CHHCH3), 1.98 (m, 1 H, CHHCH3), 2.62
(dt, J ϭ 10.4, 13.2 Hz, 1 H, CHHCHO), 2.78 (ddd, J ϭ 5.8, 7.1,
13.2 Hz, 1 H, CHHCHO), 4.53 (dd, J ϭ 7.1, 13.2 Hz, 1 H, CHAr),
4.82 (m, 1 H, CH2CHO), 7.38, 7.44 [each d (AB system), J ϭ
8.5 Hz, 2 H, ArH] ppm. 13C NMR (100 MHz, CDCl3): δ ϭ 9.4
(CH2CH3), 28.4 (CH2CH3), 31.2 [C(CH3)3], 34.7 [C(CH3)3], 35.8
(CH2CH), 62.7 (CHAr), 81.9 (CHO), 125.9 (ArCH), 126.2 (ArC),
128.3 (ArCH), 152.5 (ArC) ppm. MS (EI, 70 eV): m/z (%) ϭ 282
(24) [Mϩ], 267 (27), 189 (6), 160 (62), 145 (100), 117 (13), 91 (7),
57 (34). C15H22O3S (282.40): calcd. C 63.80, H 7.85; found
C 63.57, H 8.04.
Acknowledgments
This work was supported by the Deutsche Forschungsgemeinschaft
(SFB 380, Graduiertenkolleg 440) and the Fonds der Chemischen
Industrie. We thank Degussa AG, BASF AG and Bayer AG for the
donation of chemicals. The X-ray structure determination by Dr.
G. Raabe and the NOE-measurements by Dr. J. Runsink are grate-
fully acknowledged.
(3R,5R)-5-Ethyl-3-phenyl-1,2-oxathiolane 2,2-Dioxide [(R,R)-5g]:
According to GP 3, sulfonate (R)-2g (0.32 g, 0.7 mmol) was re-
fluxed in a 2% TFA/EtOH solution (30 mL) for 24 h. After removal
of solvent under reduced pressure, the crude sulfonic acid 3 was
refluxed in a 30% TFA/CH2Cl2 solution (10 mL) for 16 h. The
crude product, which consisted of a 73:4:7:16 mixture of cis:trans
diastereomers of the corresponding γ-sultone and δ-sultone respec-
tively, was purified by preparative HPLC and gave (R,R)-5g as a
colorless solid (0.11 g, 71%); ds Ն 99% (NMR); ee Ն 98% (HPLC,
Daicel OD); m.p. 106 °C; [α]2D3 ϭ Ϫ3.41 (c ϭ 0.8; CHCl3). IR
(KBr): ν˜ ϭ 3068 (w), 3040 (w), 2978 (m), 2943 (m), 2884 (w), 1500
(m), 1454 (m), 1383 (m), 1337 (vs), 1244 (m), 1160 (vs), 1053 (m),
963 (m), 926 (m), 860 (m), 822 (vs), 778 (m), 759 (m), 702 (m), 602
(m), 555 (m), 532 (m), 491 (m) cmϪ1. 1H NMR (300 MHz, CDCl3):
δ ϭ 1.09 (t, J ϭ 7.4 Hz, 3 H, CH2CH3), 1.84 (m, 1 H, CHHCH3),
1.97 (m, 1 H, CHHCH3), 2.62 (dt, J ϭ 10.4, 13.1 Hz, 1 H,
CHHCHO), 2.80 (ddd, J ϭ 5.4, 6.9, 13.1 Hz, 1 H, CHHCHO),
4.54 (dd, J ϭ 6.9, 13.1 Hz, 1 H, CHAr), 4.63 (m, 1 H, CH2CHO),
7.39Ϫ7.48 (m, 5 H, ArH) ppm. 13C NMR (75 MHz, CDCl3): δ ϭ
[1]
[1a]
For reviews on sultone chemistry see:
A. J. Buglass, J. G.
Tillet, in The Chemistry of Sulfonic Acids, Esters and their De-
rivatives, (Eds.: S. Patai, Z. Rappoport), John Wiley & Sons,
New York, 1991, 789Ϫ878. [1b]D. W. Roberts, D. L. Williams,
[1c]
Tetrahedron 1987, 43, 1027.
340, 1.
P. Metz, J. Prakt. Chem. 1998,
[2] [2a]
D. Takada, H. Suemune, K. Sakai, Chem. Pharm. Bull.
[2b]
1990, 38, 234Ϫ235.
B. F. Bonini, G. Kemperman, S. T. H.
Willems, M. Fochi, G. Mazzanti, B. Zwanenburg, Synlett 1998,
[2c]
1411Ϫ1413.
L. S. Jiang, W. H. Chan, A. W. M. Lee, Tetra-
[2d]
hedron 1999, 55, 2245Ϫ2262.
W. H. Chan, A. W. M. Lee,
L. S. Jiang, T. C. W. Mak, Tetrahedron: Asymmetry 1997, 8,
2501Ϫ2504.
[3]
[4]
[5]
[6]
S. Karsch, P. Schwab, P. Metz, Synlett 2002, 2015Ϫ2018.
Y. Tamaru, K. Nagao, J. Org. Chem. 1990, 55, 1823Ϫ1829.
N. Asao, M. Meguro, Y. Yamamoto, Synlett 1994, 185Ϫ186.
B. Fraser-Reid, K. M. Sun, R. Y-K. Tsang, Can. J. Chem. 1981,
59, 260Ϫ263.
[7]
P. A. Crooks, R. C. Reynolds, J. A. Maddry, A. Rathore, M.
3946
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Eur. J. Org. Chem. 2003, 3939Ϫ3947

Asymmetric Synthesis of α,γ-Substituted γ-Sultones
FULL PAPER
´
´
S. Akhtar, J. A. Montgomery, J. A. Secrist, III, J. Org. Chem.
1992, 52, 2830Ϫ2835.
J. Perez-Perez, J. Balzarini, M. Hosoya, E. D. Clercq, M. J.
Camarasa, Bioorg. Med. Chem. Lett. 1992, 2, 647Ϫ648. [13c] E.
[8] [8a]
[8b]
´
Lobaton, M.-J. Camarasa, S. Velazquez, Synlett 2000,
1312Ϫ1314.
P. Metz, M. Fleischer, Synlett 1993, 399Ϫ400.
P. Metz,
[8c]
M. Fleischer, R. Fröhlich, Tetrahedron 1995, 51, 711Ϫ732.
B. Plietker, P. Metz, Tetrahedron Lett. 1998, 39, 7827Ϫ7830. [8d]
B. Plietker, D. Seng, R. Fröhlich, P. Metz, Eur. J. Org. Chem.
2001, 3669Ϫ3676.
[14]
D. Enders, W. Harnying, N. Vignola, Synlett 2002, 1727Ϫ1729.
[15] [15a]
D. Enders, N. Vignola, O. M. Berner, Angew. Chem. 2002,
[15b]
114, 116; Angew. Chem. Int. Ed. 2002, 41, 109.
O. M. Berner, Chem. Commun. 2001, 2498Ϫ2499.
D. Enders,
[15c]
D. En-
[9]
U. Meiners, E. Cramer, R. Fröhlich, B. Wibbeling, P. Metz,
Eur. J. Org. Chem. 1998, 2073Ϫ2078.
ders, O. M. Berner, N. Vignola, W. Harnying, Synthesis 2002,
1945Ϫ1952.
D. Brundish, A. Bull, V. Donovan, J. D. Fullerton, S. M.
Garman, J. F. Hayler, D. Janus, P. D. Kane, M. McDonnell, G.
P. Smith, R. Wakeford, C. V. Walker, G. Howarth, W. Hoyle,
M. C. Allen, J. Ambler, K. Butler, M. D. Talbot, J. Med. Chem.
1999, 42, 4584Ϫ4603.
T. Kwak, J. Am. Chem. Soc. 1998, 120, 9517Ϫ9525.
Abdellaoui, P. Depreux, D. Lesieur, B. Pfeiffer, P. Bontempelli,
Synth. Commun. 1995, 25, 1303Ϫ1311.
(Eds.: S. R. Hall, D. J. du Boulay, R. Olthof-Hazekamp), 2000,
Xtal3.7 System, University of Western Australia.
H. D. Flack, Acta Crystallogr., Sect. A 1983, 39, 876.
Received June 3, 2003
[10] [10a] H. Bernsmann, B. Hungerhoff, R. Fechner, R. Fröhlich, P.
[16] [16a]
[10b]
Metz, Tetrahedron Lett. 2000, 41, 1721Ϫ1724.
H. Bern-
smann, R. Fröhlich, P. Metz, Tetrahedron Lett. 2000, 41,
[10c]
4347Ϫ4351.
H. Bernsmann, M. Gruner, P. Metz, Tetra-
[10d]
hedron Lett. 2000, 41, 7629Ϫ7633.
Y. Wang, H. Bern-
smann, M. Gruner, P. Metz, Tetrahedron Lett. 2001, 42,
[16b]
S. Otto, J. B. F. N. Engberts, J. C.
[16c]
H.
7801Ϫ7804.
[11]
[12]
S. Doye, T. Hotopp, E. Winterfeldt, Chem. Commun. 1997,
1491Ϫ1492.
[17]
[18]
D. Solas, J. Wolinsky, J. Org. Chem. 1983, 48, 1988Ϫ1991.
[13] [13a]
´
´
´
M. J. Perez-Perez, A. San-Felix, J. Balzarini, E. D. Clercq,
M. J. Camarasa, J. Med. Chem. 1992, 35, 2988Ϫ2995. [13b] M.-
Eur. J. Org. Chem. 2003, 3939Ϫ3947
www.eurjoc.org
 2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
3947