Efficient asymmetric synthesis of α-alkylated benzylic methyl sulfonates

Article abstract of DOI:10.1016/j.tet.2005.01.046

The first highly efficient auxiliary-controlled synthesis of various α-substituted sulfonic acid derivatives is described. Alkyl or aryl halides were reacted with lithiated benzylic sulfonic esters bearing 1,2:5,6-di-O-isopropylidene-α-d-allofuranose as a

Full text of DOI:10.1016/j.tet.2005.01.046

Tetrahedron 61 (2005) 3231–3243
Efficient asymmetric synthesis of a-alkylated benzylic
methyl sulfonates
†
Dieter Enders, Nicola Vignola, Otto M. Berner and Wacharee Harnying
‡
*
¨
¨
Institut fur Organische Chemie, Rheinisch-Westfalische Technische Hochschule, Professor-Pirlet-Str. 1, 52074 Aachen, Germany
Received 5 October 2004; revised 8 November 2004; accepted 6 January 2005
Available online 29 January 2005
Abstract—The first highly efficient auxiliary-controlled synthesis of various a-substituted sulfonic acid derivatives is described. Alkyl or
aryl halides were reacted with lithiated benzylic sulfonic esters bearing 1,2:5,6-di-O-isopropylidene-a-D-allofuranose as a removable
enantiopure alcohol auxiliary to give the alkylated products in excellent diastereomeric excesses. The racemization-free cleavage conditions
provided highly enantioenriched sulfonic acid derivatives (eeR98%).
q 2005 Elsevier Ltd. All rights reserved.
1. Introduction
Australian marine sponge Echinodictyum and have anti-
bacterial activity.2 The semisynthetic penicillin 3, namely
a-sulfobenzylpenicillin, has been reported to show potent
antibacterial activity against Pseudomonas aeruginosa.3,4
Cefsulodin, a representative compound of the semisynthetic
cephalosporins, exhibits in vivo antipseudomonal activity.5
Moreover, the synthetic a-phosphono sulfonates 4 are
potent squalene synthase inhibitors (Fig. 1).6,7
Enantiopure a-substituted sulfonic acids as well as their
various derivatives are important building blocks and
precursors of biologically interesting compounds. A number
of these compounds has been isolated, synthesized, and
tested for their biological activity. 6-Gingesulfonic acid 1,
for example, which has been isolated from Zingiberis
rhizoma, shows potent anti-ulcer activity.1 The natural
products echinosulfonic acid A, B, and C (2, RZEt, Me,
H, respectively) have been isolated from the southern
In general, enantiopure a-substituted sulfonic acids are
obtained from the corresponding racemates by resolution
Figure 1. Biologically active a-substituted sulfonic acid derivatives.
Keywords: Asymmetric synthesis; Alkylation; Sulfonates; Sugar auxiliary.
* Corresponding author. Fax: C49 241 8092127; e-mail: enders@rwth-aachen.de
† Present address: Max-Planck-Institut fu¨r Kohlenforschung, Kaiser-Wilhelm-Platz 1, 45470 Mu¨lheim an der Ruhr, Germany.
‡ Present address: Kemira Fine Chemicals Oy, PO Box 44, 02271 Espoo, Finland.
0040–4020/$ - see front matter q 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2005.01.046

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D. Enders et al. / Tetrahedron 61 (2005) 3231–3243
techniques with chiral amines.8 To the best of our knowl-
edge, only two stereoselective methods for the asymmetric
synthesis of a-substituted sulfonic acids have been reported
so far. Enantiopure (R)-1-phenylethanol, obtained by
catalytic asymmetric reduction of methyl phenyl ketone,
could be transformed into (S)-(K)-1-phenylethane sulfonic
acid [(K)-PES] in a two step sequence.9 In the synthesis of
the squalene synthase inhibitor 4, asymmetric a-alkylation
of an a-phosphono sulfonate bearing the chirality infor-
mation within the phosphono moiety was employed.10
the intermediate ester by b-elimination to form the N-tosyl
enamine 7 (Scheme 1).
This led us to employ a cyclic auxiliary alcohol where
b-elimination is less favourable. Thus, menthol 8 could be
easily converted into the corresponding sulfonate 9 in 88%
yield under standard conditions. In addition, the deproto-
nation with n-butyllithium and subsequent alkylation with
benzyl bromide to form the sulfonate 10 worked well but
without any diastereoselectivity (Scheme 2).
In contrast, no efficient method has been reported for
asymmetric a-alkylations of metalated sulfonic acid esters
derived from enantiopure alcohols as auxiliaries.11 As a
potential drawback we considered b-elimination or substi-
tution reactions during metalation of the sulfonates.
However, by choosing a suitable auxiliary system these
obstacles should be overcome. In preceding communi-
cations,12–16 we have described the asymmetric synthesis of
several a-substituted sulfonic acid derivatives by reacting
electrophiles with metalated sulfonic esters which possess a
chiral alcohol as auxiliary. Herein, we present in detail the
development of this methodology.
2. Results and discussion
The aim of our project was to develop a practical
methodology for an auxiliary controlled asymmetric
synthesis of a-alkylated sulfonic acids. The initial concept
was to use chiral amines as auxiliaries in order to perform
alkylations of the corresponding sulfonamides. Due to the
stability of the sulfur–nitrogen-bond, acidic hydrolysis of
the sulfonamides did not give the desired sulfonic acids but
instead enantioenriched sulfonamides.17,18 To circumvent
this dilemma we had to find a suitable alcohol as chiral
auxiliary to provide sulfonic acid esters which are more
readily cleaved and would be stable during a-lithiation to be
trapped in a stereocontrolled fashion with electrophiles.
Scheme 2. Menthol as the chiral auxiliary.
The synthetically encouraging results with menthol led us to
a screening of different cyclic alcohols (Scheme 3, Table 1).
First, two racemic auxiliary alcohols rac-11a, b were
synthesized according to a literature procedure20 by reaction
of different aryl Grignard reagents with cyclohexene oxide.
These were converted into the corresponding benzyl
sulfonates rac-12a, b, lithiated with n-butyllithium and
trapped with n-propyl iodide at K78 8C to afford the
alkylated esters 13a, b (entries 1 and 2). Remarkably, the
sterically less demanding methoxyphenyl side chain in rac-
12b resulted in a similar diastereomeric excess as the
alkylation of the sterically hindered sulfonate rac-12a.
The first alcohol we tested was the tosylated norephedrine
derivative 5.19 Unfortunately, the reaction did not proceed
to the desired benzyl sulfonate 6 due to decomposition of
Thus, we envisioned the methoxy group as a chelating
moiety in the lithiated system supporting the asymmetric
induction. This led us to use oxygen-rich alcohols like
diacetone-D-glucose 14. The corresponding sulfonate 15
was lithiated and alkylated with n-propyl iodide in the
presence of hexamethylphosphoric acid triamide (HMPA)
to give the alkylated sulfonate 16. This sugar-auxiliary
provided similar inductions as compared to the reactions
with the esters rac-12a, b (deZ59%, entry 3).
Although the induction was the same, we continued our
investigations on the sugar system as a potential auxiliary
group. We assumed that inversion of the hydroxy group
would provide a species where the reaction center is
exposed to better coordination by the rigid dioxolane
moiety. We, therefore, inverted the hydroxy group by a
simple epimerization procedure to get the new auxiliary.21
Allowing this 1,2:5,6-di-O-isopropylidene-a-D-allofuranose
Scheme 1. Attempted synthesis of the sulfonate 6 from the norephedrine
derivative 5.

D. Enders et al. / Tetrahedron 61 (2005) 3231–3243
3233
Scheme 3. Screening of different alcohols rac-11a, rac-11b, 14, 17.
Table 1. Screening of different alcohols rac-11a, rac-11b, 14, 17
Entry
Alcohol
Substrate/yield (%)
Product/yield (%)
de (%)a
1
2
3
4
rac-11a
rac-11b
14
rac-12a/78
rac-12b/62
15/81
rac-13a/55
rac-13b/71
16b/73
60
59
59
78
17
18a/91
19b/69
a Determined by 13C NMR.
b The reaction was performed in the presence of HMPA.
(17) to react with benzylsulfonyl chloride provided the
epimeric sulfonate 18a. Following the already known
procedure, sulfonate 18a could be easily alkylated with
n-propyl iodide under BuLi/HMPA-conditions to afford the
alkylated product 19 with an improved diastereomeric
excess of deZ78% (entry 4).
scope of the reaction different sulfonates 18b–d were
prepared by treatment of the allofuranose derivative 17 with
sulfonyl chlorides, which were commercially available or
could be easily obtained from the corresponding sodium
sulfonates (Scheme 4).22–24
The enantiopure sulfonates 18a,b were lithiated with
1 equiv of n-butyllithium in THF at K(90–95) 8C and
then reacted with different reactive electrophiles at K(90–
95) 8C for 1 h and at K78 8C for 24 h. After work up and
purification, the a-substituted sulfonates 20a–g were
obtained in excellent yields (90–98%) and high diastereo-
selectivities (Scheme 5, Table 2). In all cases, the
The co-solvent HMPA, which was essential for the
alkylation, could be avoided by using electrophiles that
have a higher reactivity than n-propyl iodide. Gratifyingly,
when using methyl iodide as an electrophile the methylated
product (R)-20a was obtained in high yield and a
diastereomeric excess of deZ91%. To further explore the
Scheme 4. Different sulfonates possessing 1,2:5,6-di-O-isopropylidene-a-D-allofuranose moiety.

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D. Enders et al. / Tetrahedron 61 (2005) 3231–3243
The configuration of the newly formed stereogenic centre
¨
was determined to be R by single crystal Rontgen structure
analysis in the case of product (R)-20f.12 Since we
can postulate a uniform reaction mechanism, all
described a-alkylated sulfonates should possess the same
configuration.
Finally, various procedures were screened for an efficient
racemization-free cleavage of the auxiliary, which turned
out to be more difficult than expected. Several procedures
under basic conditions were unsuccessful. The analysis
of the recovered starting material showed a decrease of
diastereomeric excess. In addition, the cleavage was
attempted by refluxing the sulfonate in aqueous ethanol in
order to eliminate the sulfonic acid by nucleophilic
substitution or to reach a transesterification or saponification
with removal of the sugar alcohol auxiliary. Unfortunately,
the protocol was unsuccesfull and obviously the high steric
demand blocked the planned cleavage processes.
Scheme 5. a-Alkylation of the sulfonates 18.
diastereomerically pure sulfonates could be obtained by
recrystallization from 2-propanol (deR98%).
In order to explore further the scope of the reaction a series
of experiments with different sulfonate residues were
conducted. Whereas benzylic carbanions lead to very high
asymmetric inductions, the allylic lithiosulfonate gave 20 h
with only a de-value of 50% and aliphatic group showed
virtually no diastereoselectivity of product 20i. Thus, at
present the methodology seems to be limited to benzylic
type of sulfonates.
We assumed that a preceding mild acetonide deprotection
would decrease the steric strain and thus allow substitution
with a protic solvent, such as water or ethanol, to provide the
desired sulfonic acid. Furthermore, this could give rise to an
intramolecular substitution reaction with one of the hydroxy
groups formed to give a stable bicyclic system. Thus, a mild
cleavage method for the removal of the acetal protection
Table 2. a-Alkylation of the sulfonates 18a–d affording the sulfonates (R)-20a–i
(R)-20
R1
R2
Yield (%)
de (%)a,b
(R)-20a
(R)-20b
(R)-20c
(R)-20d
(R)-20e
(R)-20f
(R)-20g
(R)-20h
(R)-20i
Phenyl
Phenyl
Phenyl
Phenyl
Phenyl
4-t-Butylphenyl
4-t-Butylphenyl
Vinyl
Methyl
Allyl
Benzyl
4-Bromophenyl
(2-Naphthyl)methyl
Benzyl
(2-Naphthyl)methyl
Methyl
Methyl
95
93
94
90
96
95
98
55
87
91 (R98)
90 (R98)
89 (R98)
90 (R98)
91 (R98)
91 (R98)
93 (R98)
50
Ethyl
0
a In brackets after recrystallization from 2-propanol.
b Determined by 13C NMR.
Scheme 6. Removal of the auxiliary to give the a-alkylated methyl sulfonates (R)-21.
Table 3. Removal of the sugar auxiliary to give the a-alkylated methyl sulfonates (R)-21
(R)-21
R1
R2
Yield (%)
ee [%]a
[a]rDtb
(R)-21a
(R)-21b
(R)-21c
(R)-21d
(R)-21e
(R)-21f
(R)-21g
H
H
H
H
H
t-Bu
t-Bu
Methyl
Allyl
Benzyl
4-Bromophenyl
(2-Naphthyl)methyl
Benzyl
98
90
94
77
96
90
87
R98
R98
R98
R98
R98
R98
R98
C25.6
K6.3
K77.4
K93.4
K89.5
K92.8
K108.2
(2-Naphthyl)methyl
a Determined by HPLC using a chiral stationary phase.
b All optical rotations were measured in Uvasol grade CHCl3 with concentrations of 1.0 at rt.

D. Enders et al. / Tetrahedron 61 (2005) 3231–3243
3235
groups based on a protocol reported by Lipshutz et al.25 was
utilized by refluxing the sulfonates 20 in an EtOH/H2O
solution containing a catalytic amount of Pd(OAc)2. To
isolate the final products in a more accessible form, the
intermediate sulfonic acids were directly converted with
diazomethane to the corresponding methyl sulfonates (R)-
21 in very good yields and as pure stereoisomers (Scheme 6,
Table 3).
shown in Figure 2. On the other hand, compound 22a is a
viscous oil, whose structure could be determined as the
corresponding a-anomer by NOE-measurements.
¨
Based on the Rontgen-structure of the residual sugar
fragment, the following cleavage mechanism can be
proposed as depicted in Scheme 7. First, the acetal groups
are cleaved to provide the tetraol 23. This sets the stage for
an intramolecular substitution reaction to afford the desired
enantioenriched sulfonic acid derivatives and the inter-
mediate 24. The bicyclic compound 24 reacts further in
the acidic media with the solvent (ethanol) to give the
glycosides 22 roughly as a 1:1 mixture of the anomers 22a
and 22b as witnessed via NMR spectroscopy.
In order to provide evidence for the assumptions made
concerning the mechanism of the sulfonate cleavage we
investigated more closely the by-products of the reaction.
The TLC of the reaction mixture indicated besides the
desired sulfonic acids two less polar products, which were
anticipated to be residues of the sugar moiety. Thus, the
reaction was repeated on larger scale in order to isolate and
analyse these interesting fragments. The products were
identified as intramolecularly cyclized derivatives 22a and
22b with yields of 25 and 37%, respectively. A single
Thus, the removal of the auxiliary depends on the
deprotection of the sugar moiety, which allows the
intramolecular nucleophilic substitution of the sulfonyl-
moiety to provide the desired a-alkylated sulfonic acids
without racemization. As the deprotection of the acetals is
sufficient for the sulfonic acid formation, the cleavage
should also be possible by using trifluoroacetic acid (TFA).
This seemed to be more convenient than to use the
expensive Pd(OAc)2. The allyl substituted sulfonate
(R)-20b was cleaved with TFA (2 mol%) in ethanol. By
trapping the resulting sulfonic acid (R)-25 with diazo-
methane, the sulfonate (R)-21b could be obtained with
excellent enantiomeric excess. Furthermore, it was found
that the intermediate allylic sulfonic acid (R)-25 can also be
cyclized to afford enantiopure sultones.14,15 Refluxing in
dichloromethane in the presence of 20% TFA provided
the enantioenriched sultone (R,R)-26 in good yield and
excellent enantiomeric excess with satisfactory diastereo-
selectivity (Scheme 8).
¨
crystal Rontgen-structure analysis was carried out with
compound 22b proving the structure unambiguously as
Moreover, we have expanded this methodology to provide
a great variety of different sulfonic acid derivatives as
illustrated in Scheme 9. The asymmetric Michael addition
of the sulfonate 18a with nitroalkenes leads to either the
Figure 2. Ro¨ntgen crystal structure of compound 22b.
Scheme 7. Proposed reaction sequence of the cleavage reaction.

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D. Enders et al. / Tetrahedron 61 (2005) 3231–3243
Scheme 8. TFA cleavage of the sulfonate 20b to give either the methyl sulfonate (R)-21b or the g-sultone (R,R)-26.
g-nitro sulfonates (R,R)-27 or b-alkoxycarbonyl sulfonates
(R,R)-28 depending on the conditions used for the cleavage
of the chiral auxiliary.12,13 Further functional groups could
be easily introduced by performing diastereoselective ring
opening reactions on a,g-substituted g-sultones to give
enantiopure a,g-substituted g-alkoxy,26 g-hydroxy27 (R,S)-
29 and g-amino sulfonates (R,S)-30.28
3. Experimental
3.1. General
Starting materials and reagents were purchased from
commercial suppliers without further purification. Asym-
metric alkylations were carried out under Ar in dry solvents.
Solvents were dried and purified by conventional methods
prior to use. THF was freshly distilled from sodium-lead
alloy under Ar. n-Butyllithium (1.6 M in hexane) was
purchased from Merck, Darmstadt. Preparative column
chromatography: Merck silica gel 60, particle size 0.040–
0.063 mm (230–240 mesh, flash). Analytical TLC: silica gel
60 F254 plates from Merck, Darmstadt. Optical rotation
values were measured on a Perkin–Elmer P241 polarimeter.
In summary, the proper choice of a sugar auxiliary led to
the breakthrough in the first asymmetric synthesis of
a-substituted sulfonic acid esters. High asymmetric induc-
tions were obtained with the inexpensive and readily
available 1,2:5,6-di-O-isopropyliden-a-D-allofuranose as
auxiliary group which can be cleaved off racemization-
free under mild conditions.
Scheme 9. Asymmetric synthesis of enantioenriched sulfonic acid derivatives.

D. Enders et al. / Tetrahedron 61 (2005) 3231–3243
3237
Microanalyses were obtained with a Vario EL element
analyzer. Mass spectra were acquired on a Finnigan
SSQ7000 (EI 70 eV) spectrometer. High-resolution mass
spectra were recorded on a Finnigan MAT95 spectrometer.
3.2. General procedure for the synthesis of the substrate
sulfonates (GP 1)
A solution of the alcohol (1.0 equiv) and NEt3 or pyridine
(3.0 equiv) in CH2Cl2 (10 mL/mmol) was cooled to 0 8C.
After adding the sulfonyl chloride (1.1 equiv), the solution
was stirred at rt for 24 h. The mixture was then washed with
brine and the aqueous layer extracted three times with
CH2Cl2. The combined organic layers were dried over
MgSO4, filtered and concentrated under reduced pressure.
The crude product was purified by flash column chroma-
tography (SiO2, pentane/diethyl ether).
1
IR spectra were taken on a Perkin–Elmer FT-IR 1760. H
and 13C spectra were recorded on Varian Gemini 300 or
Inova 400 spectrometers with tetramethylsilane as internal
standard. d of the minor diastereomers are indicated in
brackets. Melting points were determined on a Tottoli
melting point apparatus and are uncorrected.
3.1.1. rac-trans-2-(3,5-Di-tert-butyl-4-methoxyphenyl)-
cyclohexanol (rac-11a). To magnesium (1.7 g,
69.0 mmol) in THF (50 mL) was added a solution of
5-bromo-3,5-di-tert-butyl-4-methoxybenzene (21.2 g,
71.0 mmol) in THF (50 mL) over 1 h. The resulting mixture
was stirred for 0.5 h and then CuI (1.3 g, 7.0 mmol) was
added and the mixture was cooled to K30 8C. Cyclohexene
oxide (4.6 g, 47.6 mmol) was then added dropwise. After
the addition was complete, the mixture was stirred for 3 h
and then quenched by pouring into cold saturated NH4Cl
(30 mL). The mixture was partitioned between CH2Cl2 and
the aqueous layer further extracted three times with CH2Cl2.
The combined organic layers were dried over MgSO4,
filtered and concentrated under reduced pressure. The crude
product was purified by flash column chromatography
(SiO2, pentane/diethyl ether 6:1) to give rac-11a (12.0 g,
80%) as a colorless solid; mpZ101 8C. IR (KBr): 3381,
2953, 2920, 2852, 1597, 1449, 1415, 1393, 1361, 1305,
3.2.1. Compound 9. According to GP 1 (K)-menthol (8)
(0.8 g, 5.0 mmol) was reacted with 1.1 g phenyl-methane-
sulfonyl chloride (5.5 mmol) in the presence of 1.5 g triethyl
amine (15.0 mmol) to give 9 (1.4 g, 88%) as a colorless
solid; mpZ72 8C; [a]2D9ZC53.4 (cZ1.0, CHCl3). IR
(KBr): 2961, 2943, 2866, 1499, 1456, 1350, 1330, 1275,
1203, 1171, 1160, 1142, 942, 919, 891, 826, 701, 615 cmK1
.
1H NMR (400 MHz, CDCl3): d 0.70 (d, JZ7.1 Hz, 3H),
0.86 (d, JZ4.9 Hz, 3H), 0.88 (d, JZ4.9 Hz, 3H), 0.90–2.00
(m, 9H), 4.32 (s, 2H), 4.53 (dt, JZ4.7, 11.0 Hz, 1H), 7.3–
7.50 (m, 5H). 13C NMR (100 MHz, CDCl3): d 15.4, 20.8,
21.8, 23.0, 25.5, 31.6, 33.7, 42.0, 47.5, 57.8, 83.2, 128.7,
128.8, 130.8, 134.5. MS (EI, 70 eV): m/z (%) 310 (2) [MC],
138 (100) [MCKC7H7SO2OH], 97 (12), 95 (22), 91 (73),
83 (57). Anal. Calcd for C17H26O3S (310.45): C, 65.77; H,
8.44, found: C, 65.82; H, 8.64.
1
1262, 1224, 1118, 1065, 1015, 993, 857 cmK1. H NMR
(400 MHz, CDCl3): d 1.20–2.20 (m, 8H), 1.43 (s, 18H), 2.35
(m, 1H), 3.59 (m, 1H), 3.69 (s, 3H), 7.09 (s, 2H). 13C NMR
(100 MHz, CDCl3): d 25.0, 26.1, 32.1, 34.1, 35.7, 35.8,
53.0, 63.9, 74.4, 125.6, 136.3, 143.4, 157.9. MS (EI, 70 eV):
m/z (%) 318 (100) [MC], 303 (85) [MCKCH3], 247 (8),
187 (15), 57 (40). HRMS: m/z calcd for C21H34O2 (MC)
318.2559; found 318.2557.
3.2.2. Compound rac-12a. According to GP 1 the alcohol
rac-11a (0.8 g, 2.5 mmol) was reacted with phenyl-
methanesulfonyl chloride (0.52 g, 2.8 mmol) in the pre-
sence of triethyl amine (0.8 g, 7.5 mmol) to give rac-12a
(0.9 g, 78%) as a colorless solid; mpZ147 8C. IR (KBr):
2952, 2863, 1600, 1455, 1414, 1359, 1332, 1267, 1226,
1171, 1145, 1016, 953, 916, 900, 886, 829, 813, 769, 699,
1
620, 540 cmK1. H NMR (400 MHz, CDCl3): d 1.30–2.30
3.1.2. rac-trans-2-(3-Methoxyphenyl)-cyclohexanol (rac-
11b). To magnesium (1.7 g, 69.0 mmol) in THF (30 mL)
was added a solution of 3-bromo anisole (13.3 g,
71.0 mmol) in THF (30 mL) over 1 h. The resulting mixture
was stirred for 0.5 h and then CuI (1.3 g, 7.0 mmol) was
added and the mixture was cooled to K30 8C. Cyclohexene
oxide (4.6 g, 47.6 mmol) was then added dropwise. After
the addition was complete, the mixture was stirred for 3 h
and then quenched by pouring into cold saturated NH4Cl
(30 mL). The mixture was partitioned between CH2Cl2 and
the aqueous layer further extracted three times with CH2Cl2.
The combined organic layers were dried over MgSO4,
filtered and concentrated under reduced pressure. The crude
product was purified by flash column chromatography
(SiO2, pentane/diethyl ether 4:1) to afford rac-11b (6.9 g,
71%) as a colorless oil. IR (film): 3419, 2929, 2856, 1602,
1584, 1487, 1464, 1449, 1345, 1323, 1285, 1260, 1228,
(m, 8H), 1.43 (s, 18H), 2.71 (m, 1H), 3.13 (d, JZ13.7 Hz,
1H), 3.26 (d, JZ13.7 Hz, 1H), 3.49 (s, 3H), 4.73 (m, 1H),
7.00–7.30 (m, 9H); 13C NMR (100 MHz, CDCl3): d 24.8,
25.3, 32.1, 33.6, 34.5, 35.8, 49.8, 56.0, 64.2, 87.3, 125.9,
128.5, 130.2, 127.6, 136.3, 143.7, 158.4. MS (EI, 70 eV):
m/z (%) 472 (10) [MC], 300 (100) [MCKC7H7SO3H], 217
(2), 285 (26), 243 (17), 91 (12) [C7HC7 ]. Anal. Calcd for
C28H40O4S (472.68): C, 71.15; H, 8.53, found: C, 71.01; H,
8.42.
3.2.3. Compound rac-12b. According to GP 1 the alcohol
rac-11b (5.7 g, 36.0 mmol) was reacted with phenyl-
methanesulfonyl chloride (7.5 g, 39.6 mmol) in the
presence of triethyl amine (10.0 g, 100.0 mmol) to give
rac-12b (8.0 g, 62%) as a colorless solid; mpZ150 8C. IR
(KBr): 2952, 2863, 1600, 1455, 1414, 1359, 1332, 1267,
1226, 1171, 1145, 1016, 953, 916, 900, 886, 829, 813, 769,
699, 620, 540 cmK1. 1H NMR (400 MHz, CDCl3): d 1.20–
2.35 (m, 8H), 2.73 (m, 1H), 3.39 (d, JZ13.7 Hz, 1H), 3.55
(d, JZ13.7 Hz, 1H), 3.81 (s, 3H), 4.79 (m, 1H), 6.78–7.35
(m, 9H). 13C NMR (100 MHz, CDCl3): d 25.2, 25.7, 34.3,
34.8, 50.5, 55.6, 56.9, 86.7, 112.7, 114.1, 120.4, 128.8,
129.9, 130.7, 128.1, 144.5, 160.1. MS (EI, 70 eV): m/z (%)
360 (16) [MC], 188 (100) [MCKC7H7SO2OH], 217 (2),
1
1200, 1157, 1122, 1049, 854, 780, 700 cmK1. H NMR
(400 MHz, CDCl3): d 1.30–2.10 (m, 8H), 2.39 (m, 1H), 3.62
(m, 1H), 3.78 (s, 3H), 6.70–7.30 (m, 4H). 13C NMR
(100 MHz, CDCl3): d 25.0, 26.0, 33.2, 34.3, 53.2, 55.1,
74.2, 111.8, 113.5, 120.0, 129.5, 144.8, 159.6. MS (EI,
70 eV): m/z (%) 206 (74) [MC], 178 (12) [MCKC2H4], 135
(43), 122 (100), 91 (19) [C7HC7 ]. HRMS: m/z calcd for
C13H18O2 (MC) 206.1307; found 206.1308.

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D. Enders et al. / Tetrahedron 61 (2005) 3231–3243
159 (9), 134 (14), 91 (12) [C7HC7 ]. HRMS: m/z calcd for
3.2.7. Compound 18c. According to GP 1 the alcohol 17
(0.5 g, 2.0 mmol) was reacted with prop-2-ene-1-sulfonyl
chloride (0.3 g, 2.2 mmol) in the presence of pyridine (0.5 g,
6.0 mmol) to give 18c (0.8 g, 55%) as a colorless solid;
mpZ64 8C; [a]2D5ZC75.15 (cZ1.0; CHCl3). IR (KBr):
2979, 2933, 1384, 1372, 1344, 1216, 1261, 1217, 1171,
1118, 1082, 1051, 1017, 999, 942, 928, 910, 882, 861, 849,
C20H24O4S (MC) 360.1395, found 360.1399.
3.2.4. Compound 15. According to GP 1 the alcohol 14
(2.0 g, 8.0 mmol) was reacted with phenyl-methanesulfonyl
chloride (1.8 g, 8.8 mmol) in the presence of triethyl amine
(2.4 g, 24.0 mmol) to give 15 (2.7 g, 81%) as a colorless oil;
[a]2D7ZK42.2 (cZ1.0; CHCl3). IR (CHCl3): 2979, 1496,
1456, 1368, 1317, 1265, 1225, 1167, 1162, 1123, 1084,
1
835, 792, 647, 612, 574, 547 cmK1. H NMR (400 MHz,
CDCl3): d 1.37 (s, 6H), 1.49 (s, 3H), 1.58 (s, 3H), 3.93 (dd,
JZ6.0, 8.8 Hz, 1H), 3.96 (m, 2H), 4.09 (dd, JZ4.1, 8.2 Hz,
1H), 4.33 (m, 1H), 4.76–4.85 (m, 2H), 5.82 (d, JZ3.6 Hz,
1H), 5.47–5.54 (m, 2H). 13C NMR (100 MHz, CDCl3): d
25.0, 26.2, 26.7, 26.7, 55.9, 65.4, 74.6, 76.9, 77.0, 77.9,
103.8, 110.0, 113.6, 123.9, 124.7. MS (EI, 70 eV): m/z (%)
349 (100) [MCKCH3], 167 (11), 127 (16), 113 (57), 101
(71). Anal. Calcd for C15H24O8S (364.41): C, 49.44; H,
6.64, found: C, 49.45; H, 49.45.
1
1043, 1010, 873, 854, 829, 699, 644, 622, 562 cmK1. H
NMR (400 MHz, CDCl3): d 1.26 (s, 3H), 1.35 (s, 3H), 1.46
(s, 3H), 1.49 (s, 3H), 4.01 (dd, JZ4.4, 8.8 Hz, 1H), 4.12 (dd,
JZ5.8, 8.8 Hz, 1H), 4.16 (dd, JZ3.0, 8.5 Hz, 1H), 4.23
(ddd, JZ8.5, 6.0, 4.4 Hz), 4.40 (d, JZ14.0 Hz, 1H), 4.49 (d,
JZ14.0 Hz, 1H), 4.56 (d, JZ3.6 Hz, 1H), 5.04 (d, JZ
3.0 Hz, 1H), 5.84 (d, JZ3.6 Hz), 7.30–7.50 (m, 5H). 13C
NMR (100 MHz, CDCl3): d 25.2, 26.1, 26.5, 26.9, 57.2,
67.2, 71.9, 79.7, 82.4, 83.3, 104.9, 109.5, 112.4, 128.8,
129.0, 130.6, 127.2. MS (EI, 70 eV): m/z (%) 414 (9) [MC],
399 (100) [MCKCH3], 385 (11), 113 (23), 91 (44) [C7HC7 ].
Anal. Calcd for C19H26O8S (414.47): C, 55.06; H, 6.32,
found: C, 55.11; H, 6.35.
3.2.8. Compound 18d. According to GP 1 the alcohol 17
(2.0 g, 8.0 mmol) was reacted with propane-1-sulfonyl
chloride (1.2 g, 8.8 mmol) in the presence of pyridine
(1.8 g, 24.0 mmol) to give 18d (2.7 g, 93%) as a colorless
oil; [a]2D7ZC81.0 (cZ1.0; CHCl3). IR (CHCl3): 2986,
2938, 2885, 1458, 1372, 1257, 1218, 1168, 1121, 1045,
3.2.5. Compound 18a. According to GP 1 the alcohol 17
(2.6 g, 10.0 mmol) was reacted with phenyl-methanesulfo-
nyl chloride (2.0 g, 11.0 mmol) in the presence of triethyl
amine (3.0 g, 30.0 mmol) to give 18a (3.8 g, 91%) as a
colorless solid; mpZ130 8C; [a]2D7ZC59.1 (cZ1.0;
CHCl3). IR (KBr): 2982, 1496, 1458, 1368, 1317, 1266,
1222, 1177, 1162, 1123, 1084, 1043, 1016, 873, 854, 829,
1021, 932, 873, 839, 522 cmK1 1H NMR (400 MHz,
.
CDCl3): d 1.09 (t, JZ7.4 Hz, 3H), 1.37 (s, 3H), 1.48 (s, 3H),
1.58 (s, 3H), 1.96 (m, 2H), 3.20 (m, 2H), 3.93 (dd, JZ6.0,
8.5 Hz, 1H), 4.09 (dd, JZ6.9, 8.5 Hz, 1H), 4.15 (dd, JZ4.1,
7.7 Hz, 1H), 4.33 (m, 1H), 4.80 (m, 2H), 5.82 (d, JZ3.6 Hz,
1H). 13C NMR (100 MHz, CDCl3): d 12.8, 17.1, 25.1, 26.2,
26.6, 26.7, 53.3, 65.5, 74.7, 76.3, 77.3, 77.9, 103.8, 110.0,
113.5. MS (EI, 70 eV): m/z (%) 351 (57) [MCKCH3], 127
(17), 113 (75), 101 (100). Anal. Calcd for C15H26O8S
(366.43): C, 49.17; H, 7.15, found: C, 49.07; H, 7.08.
1
700, 646, 619, 559 cmK1. H NMR (400 MHz, CDCl3): d
1.36 (s, 3H), 1.37 (s, 3H), 1.46 (s, 3H), 1.60 (s, 3H, 3.84 (dd,
JZ6.3, 8.5 Hz, 1H), 4.01 (dd, JZ6.9, 8.5 Hz, 1H), 4.15 (dd,
JZ4.1, 8.5 Hz, 1H), 4.26 (ddd, JZ6.6, 6.3, 4.1 Hz, 1H),
4.44 (d, JZ14.0 Hz, 1H), 4.53 (d, JZ14.0 Hz, 1H), 4.56
(dd, JZ4.1, 4.6 Hz, 1H), 4.76 (dd, JZ4.7, 8.5 Hz, 1H), 5.77
(d, JZ3.9 Hz), 7.37–7.50 (m, 5H). 13C NMR (100 MHz,
CDCl3): d 25.1, 26.18, 3.7, 26.7, 57.6, 65.2, 74.6, 76.8, 77.0,
77.8, 103.6, 110.0, 113.6, 128.9, 129.2, 130.9, 127.41. MS
(EI, 70 eV): m/z (%) 399 (36) [MCKCH3], 113 (47), 101
(60), 91 (100) [C7HC7 ]. Anal. Calcd for C19H26O8S
(414.47): C, 55.06; H, 6.32, found: C, 54.81; H, 6.47.
3.3. General procedure for the a-alkylation of chiral
sulfonates (GP 2)
The enantiopure sulfonate (1.0 mmol) was dissolved in dry
THF (20 mL) and the solution cooled to K(90–95) 8C. After
30 min n-BuLi (1.0 equiv) was added dropwise. The
solution was stirred for an additional hour after which the
electrophile (1.5 equiv) was added dropwise. The mixture
was stirred for 1 h at K(90–95) 8C, then at K78 8C. After
24 h the reaction was quenched by adding pH 7 buffer
(2 mL). The mixture was partitioned between CH2Cl2 and
the aqueous layer further extracted three times with CH2Cl2.
The combined organic layers were dried over MgSO4,
filtered and concentrated under reduced pressure. The crude
product was purified by flash column chromatography
(SiO2, pentane/diethyl ether).
3.2.6. Compound 18b. According to GP 1 the alcohol 17
(0.5 g, 2.0 mmol) was reacted with (4-tert-butylphenyl)-
methanesulfonyl chloride (0.6 g, 2.2 mmol) in the presence
of pyridine (0.4 g, 6.0 mmol) to give 18b (0.9 g, 97%) as a
colorless solid; mpZ97 8C; [a]2D8ZC49.5 (cZ1.0;
CHCl3). IR (KBr): 2980, 2881, 1515, 1497, 1373, 1316,
1265, 1241, 1213, 1179, 1121, 1078, 1042, 1016, 975, 873,
839, 609, 585, 545, 527 cmK1 1H NMR (400 MHz,
.
CDCl3): d 1.32 (s, 9H), 1.36 (s, 3H), 1.40 (s, 3H), 1.46 (s,
3H), 1.60 (s, 3H), 3.85 (dd, JZ6.3, 8.5 Hz, 1H), 4.01 (dd,
JZ6.9, 8.5 Hz, 1H), 4.16 (dd, JZ4.1, 8.5 Hz, 1H), 4.28 (m,
1H), 4.41 (d, JZ14.0 Hz, 1H), 4.51 (d, JZ14.0 Hz, 1H),
4.62 (dd, JZ3.9, 4.7 Hz, 1H), 4.77 (dd, JZ4.7, 8.5 Hz, 1H),
5.77 (d, JZ3.8 Hz, 1H), 7.30–7.40 (m, 4H). 13C NMR
(100 MHz, CDCl3): d 25.2, 26.2, 26.7, 26.7, 31.2, 34.7,
57.3, 65.3, 74.7, 76.9, 77.1, 77.9, 103.8, 110.1, 113.7, 125.9,
130.5, 124.3, 152.3. MS (EI, 70 eV): m/z (%) 470 (1) [MC],
455 (40) [MCKCH3], 147 (100) [C11H1C5], 113 (35), 101
(48). Anal. Calcd for C23H34O8S (470.58): C, 58.71; H,
7.28, found: C, 58.71; H, 7.18.
3.3.1. Compound 10. According to GP 2 the sulfonate 9
(310 mg, 1.0 mmol) was reacted with benzylbromide
(190 mg, 1.1 mmol) to give 10 (300 mg, 75%) as a colorless
solid; deZ75% (13C NMR); mpZ122 8C. IR (KBr): 2960,
2936, 2870, 1496, 1454, 1353, 1326, 1165, 1073, 940, 913,
870, 845, 823, 696, 643, 632, 596, 566, 552, 478 cmK1. 1H
NMR (400 MHz, CDCl3): d 0.87–2.10 (m, 17H), 3.40 (m,
1H), 3.77 (dd, JZ3.6, 13.7 Hz, 1H), 4.35 (m, 1H), 4.52 (m,
1H), 6.98–7.40 (m, 10H). 13C NMR (100 MHz, CDCl3): d
15.5 [15.3], 20.9, 21.8 [20.8, 21.8], 23.0 [22.8], 25.6 [25.2],
31.6, 33.7, 36.5 [36.4], 41.3 [42.3], 47.6 [47.5], 69.7 [69.3],

D. Enders et al. / Tetrahedron 61 (2005) 3231–3243
3239
83.5 [82.6], 126.6, 128.2, 128.3, 128.6, 128.8, 129.7, 132.0,
136.5. MS (EI, 70 eV): m/z (%) 181 (100) [CH(Ph)CH2-
PhC], 138 (2) [MCKC14H13SO2OH]). Anal. Calcd for
C24H32O3S (400.575): C, 71.96; H, 8.05, found: C, 71.79;
H, 7.91.
132.3 [131.5]. MS (EI, 70 eV): m/z (%) 441 (12) [MCK
CH3], 133 (100) [C10HC13], 113 (66), 101 (40), 91 (96)
[C7H7]. Anal. Calcd for C22H32O8S (456.55): C, 57.88; H,
7.06, found: C, 57.74; H, 7.20.
3.3.5. Compound 19. According to GP 2 the sulfonate 18a
(410 mg, 1.0 mmol) was reacted with n-propyl iodide
(180 mg, 1.1 mmol) in the presence of 1.1 equiv of
HMPA (0.19 mL, 1.1 mmol) to give 19 (310 mg, 69%) as
a colorless solid; deZ78% (13C NMR); mpZ124 8C. IR
(KBr): 2976, 2955, 2934, 2890, 1638, 1498, 1471, 1457,
1372, 1353, 1312, 1296, 1259, 1233, 1216, 1173, 1116,
1053, 1041, 1018, 999, 932, 880, 867, 837, 804, 734, 697,
659, 630 cmK1. 1H NMR (400 MHz, CDCl3): d 0.91 (t, JZ
7.4 Hz, 3H), 1.33 (s, 3H), 1.38 [1.36] (s, 3H), 1.48 [1.43] (s,
3H), 1.56 (s, 3H), 1.25 (m, 2H), 2.20 (m, 1H), 2.41 (m, 1H),
3.89 [3.6] (dd, JZ6.6. 8.5 Hz, 1H), 4.04 (dd, JZ6.6. 8.5 Hz,
1H), 4.14 (dd, JZ3.8, 8.5 Hz, 1H), 4.22 (dd, JZ4.1, 4.7 Hz,
1H), 4.33 (m, 2H), 4.66 [4.69] (dd, JZ4.7, 8.5 Hz, 1H), 5.71
[5.8] (d, JZ3.6 Hz, 1H), 7.36–7.55 (m, 5H). 13C NMR
(100 MHz, CDCl3): d 13.4 [13.5], 19.8, 25.3, 26.2 [26.3],
26.6, 26.7, 31.9 [31.5], 65.2 [64.9], 68.2 [67.8], 74.6, 76.8,
77.0, 77.5, 103.7 [103.8], 110.1, 113.5, 128.8, 129.1, 129.9
[129.7], 131.9. MS (EI, 70 eV): m/z (%) 441 (10) [MCK
CH3], 133 (97) [C10HC13], 113 (43), 101 (48), 91 (100)
[C7HC7 ]. Anal. Calcd for C22H32O8S (456.55): C, 57.88; H,
7.06, found: C, 58.08; H, 7.07.
3.3.2. Compound 13a. According to GP 2 the sulfonate rac-
12a (470 mg, 1.0 mmol) was reacted with n-propyl iodide
(180 mg, 1.1 mmol) to give 13a (280 mg, 55%) as a
colorless solid; deZ60% (13C NMR); mpZ72 8C. IR
(KBr): 2960, 2869, 1601, 1496, 1455, 1415, 1394, 1359,
1337, 1264, 1223, 1168, 1117, 1070, 1053, 1013, 960, 922,
1
899, 870, 829, 806, 698, 634 cmK1. H NMR (400 MHz,
CDCl3): d 0.71 [0.66] (t, JZ7.4 Hz, 3H), 1.20–2.40 (m,
12H), 1.47 [1.46] (s, 18H), 2.60 [2.68] (m, 1H), 3.61 [3.55]
(dd, JZ3.9, 11.3 Hz, 1H), 3.69 (s, 3H), 4.97 [4.89] (m, 1H),
7.140–7.30 (m, 7H). 13C NMR (100 MHz, CDCl3): d 13.4,
19.6 [19.5], 24.7, 25.4, 31.0 [31.2], 32.2, 34.0 [34.4], 35.2
[35.7], 35.8, 49.9 [50.0], 64.1 [64.0], 67.4 [67.6], 83.7
[84.7], 125.3, 128.3, 128.4, 129.4 [129.5], 132.3 [132.1],
136.4 [136.5], 143.2 [143.3], 157.9 [158.0]; MS (EI, 70 eV):
m/z (%) 514 (13) [MC], 300 (100) [MCKC10H13SO2OH],
217 (2), 285 (16), 91 (20) [C7HC7 ]. HRMS: m/z calcd for
C31H46O4S (MC) 514.3117, found 514.3114.
3.3.3. Compound 13b. According to GP 2 the sulfonate
rac-12b (310 mg, 1.0 mmol) was reacted with n-propyl
iodide (180 mg, 1.1 mmol) to give 13b (250 mg, 71%) as a
colorless solid; deZ59% (13C NMR); mpZ74 8C. IR
(KBr): 2936, 2866, 1607, 1585, 1493, 1454, 1344, 1290,
1265, 1214, 1168, 1101, 1048, 998, 939, 905, 884, 863, 828,
3.3.6. (R)-1-Phenyl-ethanesulfonate (R)-20a. According
to GP 2 the sulfonate 18a (410 mg, 1.0 mmol) was reacted
with methyl iodide (200 mg, 1.5 mmol) to give (R)-20a
(410 mg, 95%) as a colorless solid; deZ91% (13C NMR);
deR98 (after recrystallization from 2-propanol); mpZ
103.4 8C; [a]2D5ZC91.3 (cZ1.0, CHCl3). IR (KBr): 2980,
2934, 2908, 1496, 1456, 1383, 1366, 1351, 1314, 1267,
1237, 1216, 1173, 1117, 1096, 1078, 1048, 1015, 1000, 931,
1
803, 785, 698, 577 cmK1. H NMR (400 MHz, CDCl3): d
0.71 [0.70] (t, JZ7.2 Hz, 3H), 1.20–2.50 (m, 12H), 2.74
[2.63] (m, 1H), 3.39 (dd, JZ7.4, 1H), 3.81 [3.82] (s, 3H),
4.86 [4.84] (m, 1H), 6.70–7.35 (m, 9H). 13C NMR
(100 MHz, CDCl3): d 13.53 [13.19], 19.63 [19.60], 24.74
[24.66], 25.31 [25.34], 31.56 [31.25], 34.41 [34.35], 34.58
[34.50], 55.01 [55.08], 50.28 [50.08], 67.73 [67.51], 85.73
[84.32], 112.05 [112.09], 113.51 [113.44], 119.70 [119.76],
128.23, 128.34 [128.40], 129.21 [129.27], 129.50 [129.33],
132.06 [132.25], 144.46 [144.12], 159.60 [159.55]. MS
(EI, 70 eV): m/z (%): 402 (8) [MC], 188 (100) [MCK
C10H13SO2OH], 133 (18), 121 (23), 91 (76) [C7HC7 ]. Anal.
Calcd for C23H30O4S (402.55): C, 68.63; H, 7.51, found: C,
68.67; H, 7.40.
1
890, 873, 831, 695, 628, 614, 563, 506 cmK1. H NMR
(400 MHz, CDCl3): d 1.33 (s, 3H), 1.37 (s, 3H), 1.46 (s, 3H),
1.56 (s, 3H), 1.87 (d, JZ7.2 Hz, 3H), 3.86 (dd, JZ6.6,
8.5 Hz, 1H), 4.01 (dd, JZ6.6, 8.5 Hz, 1H), 4.14 (dd, JZ4.1,
8.5 Hz, 1H), 4.27 (ddd, JZ3.9, 4.1, 6.6 Hz, 1H), 4.35 (dd,
JZ3.8, 4.7 Hz, 1H), 4.49 (q, JZ7.2 Hz, 1H), 4.64 (dd, JZ
4.7, 8.5 Hz, 1H), 5.72 (d, JZ3.9 Hz, 1H), 7.30–7.40 (m,
5H). 13C NMR (100 MHz, CDCl3): d 16.2, 25.1, 25.2, 26.2,
26.6, 63.1, 65.2, 74.6, 76.8, 77.5, 77.8, 103.6, 109.9, 113.3,
128.5, 129.0, 128.2, 129.2, 130.7, 133.2. MS (EI, 70 eV):
m/z (%) 413 (62) [MCKCH3], 113 (29), 105 (100)
[(CH3)(C6H5)CHC], 101 (33). Anal. Calcd for C20H28O8S
(428.50): C, 56.06; H, 6.59, found: C, 55.92; H, 6.76.
3.3.4. Compound 16. According to GP 2 the sulfonate 15
(410 mg, 1.0 mmol) was reacted with n-propyl iodide
(180 mg, 1.1 mmol) in the presence of 1.1 equiv of
HMPA (0.19 mL, 1.1 mmol) to give 16 (330 mg, 73%) as
a colorless solid; deZ59% (13C NMR); mpZ93 8C. IR
(KBr): 2981, 2960, 2937, 2876, 1456, 1373, 1255, 1210,
1169, 1076, 1047, 1026, 979, 955, 897, 882, 858, 843, 752,
3.3.7. (R)-1-Phenyl-but-3-ene-1-sulfonate (R)-20b.
According to GP 2 the sulfonate 18a (410 mg, 1.0 mmol)
was reacted with allyl bromide (180 mg, 1.5 mmol) to give
(R)-20b (420 mg, 93%) as a colorless solid; deZ90% (13C
NMR); deR98 (after recryst. from 2-propanol); mpZ
149.2 8C; [a]2D4ZC77.0 (cZ1.0, CHCl3). IR (KBr): 2978,
2934, 1497, 1457, 1370, 1355, 1313, 1255, 1220, 1172,
1115, 1054, 1038, 1015, 1001, 933, 880, 864, 840, 810, 698,
627, 571, 503 cmK1. 1H NMR (400 MHz, CDCl3): d 1.33 (s,
3H), 1.37 (s, 3H), 1.47 (s, 3H), 1.56 (s, 3H), 2.98 (m, 1H),
3.21 (m, 1H), 3.89 (dd, JZ6.6, 8.5 Hz, 1H), 4.04 (dd, JZ
6.9, 8.5 Hz, 1H), 4.14 (dd, JZ3.9, 8.5 Hz, 1H), 4.26–4.32
(m, 2H), 4.37 (dd, JZ4.1, 11.3 Hz, 1H), 4.68 (dd, JZ4.7,
1
698, 620, 615, 566 cmK1. H NMR (400 MHz, CDCl3): d
0.91 [0.90] (t, JZ7.4 Hz, 3H), 1.19 [1.28] (s, 3H), 1.38
[1.35] (s, 3H), 1.44 [1.45] (s, 3H), 1.49 [1.48] (s, 3H), 1.25
[1.22] (m, 2H), 2.17 [2.23] (m, 1H), 2.38 [2.32] (m, 1H),
33.90–4.20 (m, 5H), 4.27 [4.30] (dd, JZ3.9, 11.5 Hz, 1H),
4.96 [4.97] (d, JZ2.3 Hz, 1H), 5.62 [5.88] (d, JZ3.6 Hz,
1H), 7.38–7.50 (m, 5H). 13C NMR (100 MHz, CDCl3): d
13.4 [13.6], 19.9 [19.8], 25.2, 25.9, 26.5 [26.6], 26.9, 31.6,
67.0 [67.1], 68.2 [67.8], 71.9 [72.0], 79.8, 81.9 [82.1], 82.6
[83.4], 104.7, 109.4, 112.1 [112.3], 128.7, 129.0, 129.4,

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D. Enders et al. / Tetrahedron 61 (2005) 3231–3243
8.8 Hz, 1H), 5.01 (d, JZ9.9 Hz, 1H), 5.08 (d, JZ17.0 Hz,
1H), 5.54 (m, 1H), 5.72 (d, JZ3.9 Hz, 1H), 7.30–7.50 (m,
5H). 13C NMR (100 MHz, CDCl3): d 25.2, 26.2, 26.6, 26.6,
34.3, 65.2, 67.8, 74.6, 76.8, 77.19, 103.6, 110.0, 113.4,
118.5, 128.6, 129.1, 129.8, 131.1, 132.4. MS (EI, 70 eV): m/z
(%) 439 (78) [MCKCH3], 131 (100) [(C3H5)(C6H5)CHC],
113 (30), 101 (32). Anal. Calcd for C22H30O8S (454.53): C,
58.13; H, 6.65, found: C, 57.78; H, 6.61.
1457, 1373, 1218, 1168, 1121, 1019, 930, 872, 843, 822,
752, 699, 570 cmK1. 1H NMR (300 MHz, CDCl3): d 1.36 (s,
3H), 1.37 (s, 3H), 1.48 (s, 3H), 1.59 (s, 3H), 3.57 (dd, JZ
11.5, 13.7 Hz, 1H), 3.89 (dd, JZ6.6, 8.5 Hz, 1H), 3.97–4.05
(m, 2H), 4.16 (dd, JZ3.8, 8.8 Hz, 1H), 4.32 (ddd, JZ3.8,
6.6, 6.6 Hz, 1H), 4.68 (dd, JZ3.6, 4.7 Hz, 1H), 4.68 (dd,
JZ3.6, 11.5 Hz, 1H), 4.73 (dd, JZ4.7, 8.5 Hz, 1H), 5.74 (d,
JZ3.6 Hz, 1H), 7.10–7.90 (m, 12H). 13C NMR (75 MHz,
CDCl3): d 25.2, 26.2, 26.7, 26.7, 36.7, 65.1, 69.7, 74.5, 76.9,
77.2, 77.4, 103.6, 110.0, 113.5, 125.6, 126.0, 126.8, 127.3,
127.4, 127.7, 127.9, 131.0, 132.0, 133.1, 133.6. MS (EI,
70 eV): m/z (%) 554 (14) [MC], 539 (23) [MCKCH3], 312
(21), 231 (100) [(C11H9)(C6H5)CHC], 215 (8), 153 (35),
141 (39), 101 (17). Anal. Calcd for C30H34O8S (554.65): C,
64.96; H, 6.18, found: C, 64.83; H, 6.34.
3.3.8. (R)-1,2-Diphenyl-ethanesulfonate (R)-20c. Accord-
ing to GP 2 the sulfonate 18a (410 mg, 1.0 mmol) was
reacted with benzyl bromide (260 mg, 1.5 mmol) to give
(R)-20c (470 mg, 94%) as a colorless solid; deZ89% (13C
NMR); deR98 (after recryst. from 2-propanol); mpZ
143 8C; [a]2D4ZC34.4 (cZ1.1, CHCl3). IR (KBr): 2979,
2932, 1498, 1456, 1369, 1315, 1259, 1246, 1218, 1167,
1118, 1049, 1015, 998, 876, 857, 824, 697 cmK1. 1H NMR
(300 MHz, CDCl3): d 1.35 (s, 3H), 1.38 (s, 3H), 1.48 (s, 3H),
1.58 (s, 3H), 3.41 (dd, JZ11.5, 13.7 Hz, 1H), 3.81 (dd, JZ
3.6, 13.7 Hz, 1H), 3.92 (dd, JZ6.6, 8.5 Hz, 1H), 4.06 (dd,
JZ6.9, 8.5 Hz, 1H), 4.16 (dd, JZ3.9, 8.8 Hz, 1H), 4.30–
4.37 (m, 2H), 4.57 (dd, JZ3.6, 11.5 Hz, 1H), 4.77 (dd, JZ
4.7, 8.8 Hz, 1H), 5.74 (d, JZ3.6 Hz, 1H), 6.9–7.5 (m, 10H).
13C NMR (75 MHz, CDCl3): d 25.2, 26.2, 26.6, 26.7, 36.5,
65.2, 69.8, 74.5, 76.7, 77.2, 77.4, 103.6, 110.0, 113.5, 128.2,
128.5, 128.7, 128.8, 129.0, 129.8, 131.0, 136.1. MS (EI,
70 eV): m/z (%) 489 (48, MCKCH3), 245 (2), 181 (100)
[(C7H7)(C6H5)CHC], 113 (25), 101 (30). Anal. Calcd for
C26H32O8S (504.59): C, 61.89; H, 6.39, found: C, 61.60; H,
6.33.
3.3.11. (R)-1-(4-tert-Butylphenyl)-2-phenyl-ethanesulfo-
nate (R)-20f. According to GP 2 the sulfonate 18b
(470 mg, 1.0 mmol) was reacted with benzyl bromide
(260 mg, 1.5 mmol) to give (R)-20f (530 mg, 95%) as a
colorless solid; deZ91% (13C NMR); deR98 (after recryst.
from 2-propanol); mpZ143 8C; [a]2D6ZC22.6 (cZ1.0,
CHCl3). IR (KBr): 2903, 1606, 1455, 1370, 1313, 1246,
1215, 1177, 1165, 1117, 1083, 1057, 1043, 1019, 877, 859,
1
834, 745, 699, 672, 615, 576, 557, 521 cmK1. H NMR
(300 MHz, CDCl3): d 1.28 (s, 9H), 1.34 (s, 3H), 1.37 (s, 3H),
1.47 (s, 3H), 1.57 (s, 3H), 3.41 (dd, JZ11.3, 14.0 Hz, 1H),
3.81 (dd, JZ3.6, 14.0 Hz, 1H), 3.90 (dd, JZ6.6, 8.5 Hz,
1H), 4.04 (dd, JZ6.6, 8.5 Hz, 1H), 4.14 (dd, JZ3.9, 8.8 Hz,
1H), 4.27 (dd, JZ3.8, 4.7 Hz, 1H), 4.32 (ddd, JZ3.9, 6.6,
6.6 Hz, 1H), 4.55 (dd, JZ3.6, 11.3 Hz, 1H), 4.73 (dd, JZ
4.7, 8.8 Hz, 1H), 5.72 (d, JZ3.9 Hz, 1H), 6.90–7.40 (m,
9H). 13C NMR (75 MHz, CDCl3): d 25.3, 26.2, 26.7, 26.7,
31.2, 34.6, 36.4, 65.1, 69.4, 74.6), 76.7, 77.4, 77.6, 103.5,
110.0, 113.4, 125.5, 126.6, 128.2, 128.8, 129.4, 127.8,
136.4, 152.1. MS (EI, 70 eV): m/z (%) 545 (15) [MCK
CH3], 237 (100), 113 (4), 101 (7), 91 (20) [C7HC7 ]. Anal.
Calcd for C30H40O8S (560.70): C, 64.26; H, 7.19, found: C,
64.29; H, 7.20.
3.3.9. (R)-2-(4-Bromophenyl)-1-phenyl-ethanesulfonate
(R)-20d. According to GP 2 the sulfonate 18a (410 mg,
1.0 mmol) was reacted with 1-bromo-4-bromomethyl-
benzene (380 mg, 1.5 mmol) to give the (R)-20d (520 mg,
90%) as a colorless solid; deZ90% (13C NMR); deR98
(after recryst. from 2-propanol); mpZ143 8C; [a]2D5Z
C17.8 (cZ0.8, CHCl3). IR (KBr): 2985, 2939, 2900,
1491, 1457, 1372, 1312, 1260, 1217, 1177, 1164, 1115,
1073, 1053, 1040, 1015, 929, 876, 835, 810, 698, 642, 569,
1
528, 514 cmK1. H NMR (300 MHz, CDCl3): d 1.35 (s,
3H), 1.37 (s, 3H), 1.47 (s, 3H), 1.57 (s, 3H), 3.36 (dd, JZ
11.5, 13.7 Hz, 1H), 3.78 (dd, JZ3.6, 13.7 Hz, 1H), 3.90 (dd,
JZ6.6, 8.8 Hz, 1H), 4.05 (dd, JZ6.6, 8.8 Hz, 1H), 4.15 (dd,
JZ4.1, 8.8 Hz, 1H), 4.30–4.40 (m, 2H), 4.50 (dd, JZ3.6,
11.5 Hz, 1H), 4.76 (dd, JZ4.7, 8.8 Hz, 1H), 5.74 (d, JZ
3.6 Hz, 1H), 6.90–7.40 (m, 9H). 13C NMR (75 MHz,
CDCl3): d 25.2, 26.2, 26.7, 26.7, 36.0, 65.2, 69.5, 74.5,
76.6, 76.9, 77.4, 103.6, 110.1, 113.5, 120.7, 130.7, 135.1,
128.6, 129.2, 129.7, 130.5, 131.3. MS (EI, 70 eV): m/z (%)
569 (77) [MC(Br81)KCH3], 567 (65) [MC(Br79)KCH3],
261 (89) [(Br81C7H6)(C6H5)CHC], 259 (100) [(Br79C7H6)
(C6H5)CHC], 180 (73), 165 (14), 113 (69), 101 (9). Anal.
Calcd for C26H31O8SBr (583.50): C, 53.52; H, 5.35, found:
C, 53.64; H, 5.38.
3.3.12. (R)-1-(4-tert-Butylphenyl)-2-naphtalen-2-yl-ethane-
sulfonate (R)-20g. According to GP 2 the sulfonate 18b
(470 mg, 1.0 mmol) was reacted with 2-bromomethyl-
naphthalene (330 mg, 1.5 mmol) to give (R)-20g (600 mg,
98%) as a colorless solid; deZ93% (13C NMR); deR98
(after recryst. from 2-propanol); mpZ139 8C; [a]2D6ZC3.8
(cZ1.0., CHCl3). IR (KBr): 2978, 2903, 1602, 1510, 1454,
1370, 1318, 1258, 1217, 1166, 1122, 1018, 933, 893, 878,
1
839, 819, 795, 746, 625, 607 cmK1. H NMR (300 MHz,
CDCl3): d 11.26 (s, 9H), 1.36 (s, 3H), 1.37 (s, 3H), 1.48 (s,
3H), 1.59 (s, 3H), 3.57 (dd, JZ11.3, 14.0 Hz, 2H), 3.88 (dd,
JZ6.6, 8.5 Hz, 1H), 3.95–4.03 (m, 2H), 4.15 (dd, JZ3.6,
8.5 Hz, 1H), 4.29–4.36 (m, 2H), 4.67 (dd, JZ3.6, 11.3 Hz,
1H), 4.76 (dd, JZ4.7, 8.5 Hz, 1H), 5.73 (d, JZ3.9 Hz, 1H),
7.10–7.80 (m, 12H). 13C NMR (75 MHz, CDCl3): d 25.3,
26.2, 26.7, 26.7, 31.2, 34.6, 36.6, 65.1, 69.3, 74.5, 76.7,
77.2, 77.2, 77.4, 103.6, 110.0, 113.5, 125.5, 125.9, 126.8,
127.3, 127.4, 127.7, 127.8, 127.8, 129.4, 132.0, 133.1,
133.8, 152.1. MS (EI, 70 eV): m/z (%) 595 (4) [MCKCH3],
287 (100), 141 (16) [C11HC9 ], 101 (7). Anal. Calcd for
C34H42O8S (610.76): C, 66.86; H, 6.93, found: C, 67.12; H,
6.86.
3.3.10. (R)-2-Naphtalen-2-yl-1-phenyl-ethanesulfonate
(R)-20e. According to GP 2 the sulfonate 18a (410 mg,
1.0 mmol) was reacted with 2-bromomethyl-naphthalene
(330 mg, 1.5 mmol) to give (R)-20e (530 mg, 96%) as a
colorless solid; deZ91% (13C NMR); deR98 (after recryst.
from 2-propanol); mpZ136 8C; [a]2D6ZC17.3 (cZ1.0,
CHCl3). IR (KBr): 2987, 2937, 2899, 2185, 1637, 1602,

D. Enders et al. / Tetrahedron 61 (2005) 3231–3243
3241
3.3.13. Compound 20h. According to GP 2 the sulfonate
18c (360 mg, 1.0 mmol) was reacted with methyl iodide
(200 mg, 1.5 mmol) to give 20h (210 mg, 55%) as a
colorless oil; deZ50% (13C NMR). IR (film): 2987, 2939,
2900, 1640, 1457, 1373, 1360, 1217, 1167, 1121, 1020, 934,
The sulfonate (R)-20b (270 mg, 0.6 mmol) was reacted
according to GP 3 to give (R)-21b (130 mg, 90%) as a
colorless solid; mpZ58 8C; eeR98% (HPLC, (S,S)-Whelk-
O1); [a]2D8ZK6.3 (cZ1.0; CHCl3). IR (KBr): 2959, 2944,
2922, 1643, 1456, 1350, 1320, 1228, 1163, 993, 939, 835,
1
1
873, 832, 751, 657 cmK1. H NMR (300 MHz, CDCl3): d
767, 734, 700, 654 cmK1. H NMR (400 MHz, CDCl3): d
1.38 (s, 3H), 1.49 (s, 3H), 1.60 (s, 3H), 1.62 (s, 3H), 1.62
[1.61] (d, JZ6.9 Hz, 3H), 3.80–4.35 (m, 4H), 4.77–4.83 (m,
2H), 5.47–5.54 (m, 2H), 5.82 (d, JZ3.6 Hz, 1H), 6.00 (m,
1H). 13C NMR (75 MHz, CDCl3): d 14.3 [14.4], 25.1, 26.2,
26.6, 26.7, 55.9, 65.4 [65.5], 74.65, 76.6, 76.9, 77.9 [77.8],
103.7 [103.7], 110.0, 113.5, 121.9 [121.7], 130.0 [130.3].
MS (EI, 70 eV): m/z (%) 363 (100) [MCKCH3], 167 (7),
127 (14), 113 (49), 101 (70). Anal. Calcd for C16H26O8S
(378.44): C, 50.78; H, 6.92, found: C, 50.41; H, 7.12.
2.95 (m, 1H), 3.13 (m, 1H), 3.64 (s, 3H), 4.26 (dd, JZ4.7,
11.0 Hz, 1H), 5.02 (d, JZ10.2 Hz, 1H), 5.10 (d, JZ
17.0 Hz, 1H), 5.57 (m, 1H), 7.36–7.44 (m, 5H). 13C NMR
(100 MHz, CDCl3): d 34.0, 56.8, 66.7, 118.6, 128.7, 129.0,
129.5, 132.3, 132.7. MS (EI, 70 eV): m/z (%) 181 (100)
[MCKSO3CH3], 103 (5), 91 (28) [C7HC7 ]. Anal. Calcd for
C11H14O3S (226.29): C, 58.39; H, 6.24, found: C, 58.30; H,
6.32.
3.4.3. Methyl (R)-1,2-diphenylethane sulfonate (R)-21c.
The sulfonate (R)-20c (300 mg, 0.6 mmol) was reacted
according to GP 3 to give (R)-21c (160 mg, 94%) as a
colorless solid; mpZ67 8C; eeR98% (HPLC, Daicel OD);
[a]2D7ZK77.4 (cZ1.0; CHCl3). IR (KBr): 3032, 2964,
2935, 1497, 1454, 1347, 1329, 1158, 984, 848, 818, 767,
3.3.14. Compound 20i. According to GP 2 the sulfonate
18d (370 mg, 1.0 mmol) was reacted with methyl iodide
(200 mg, 1.5 mmol) to give 20i (330 mg, 87%) as a
colorless oil; deZ0% (13C NMR). IR (film): 2987, 2940,
2884, 1458, 1373, 1218, 1175, 1121, 1021, 931, 872, 829,
1
1
793, 757, 599, 524 cmK1. H NMR (300 MHz, CDCl3): d
755, 724, 697, 628, 582, 556 cmK1. H NMR (300 MHz,
1.05 [1.06] (t, JZ7.4 Hz, 3H), 1.37 (s, 3H), 1.45 (s, 3H),
1.48 (s, 3H), 1.57 (s, 3H), 1.46 (d, JZ7.4 Hz, 3H), 1.65
[2.17] (m, 2H), 3.19 (m, 1H), 3.92 (dd, JZ6.9, 8.5 Hz, 1H),
4.09 (dd, JZ6.9, 8.5 Hz, 1H), 4.14–4.19 (m, 1H), 4.32 (m,
1H), 4.78 (m, 2H), 5.82 (d, JZ3.0 Hz, 1H). 13C NMR
(75 MHz, CDCl3): d 10.9 [11.0], 13.3 [13.4], 23.4 [23.5],
25.2, 26.2, 26.7, 26.7, 58.9 [59.0], 65.4 [65.5], 74.7 [74.8],
76.1, 78.0, 78.0, 103.8, 110.0, 113.4. MS (EI, 70 eV): m/z
(%) 363 (100) [MCKCH3], 167 (7), 127 (14), 113 (49), 101
(70). Anal. Calcd for C16H28O8S (380.45): C, 50.51; H,
7.42, found: C, 50.36; H, 7.67.
CDCl3): d 3.41 (dd, JZ11.0, 13.7 Hz, 1H), 3.63 (s, 3H),
3.73 (dd, JZ3.6, 13.7 Hz, 1H), 4.44 (dd, JZ3.6, 11.0 Hz,
1H), 6.98–7.37 (m, 10H). 13C NMR (75 MHz, CDCl3): d
36.3, 56.9, 68.6, 126.9, 128.5, 128.8, 129.0, 129.2, 129.7,
131.7, 136.4. MS (EI, 70 eV): m/z (%) 276 (3) [MC], 181
(100) [MCKSO3CH3], 166 (18), 115 (1), 103 (14), 91 (19)
[C7HC7 ]. Anal. Calcd for C15H16O3S (276.35): C, 65.19; H,
5.84, found: C, 65.00; H, 5.83.
3.4.4. Methyl (R)-2-(4-bromophenyl)-1-phenylethane
sulfonate (R)-21d. The sulfonate (R)-20d (350 mg,
0.6 mmol) was reacted according to GP 3 to give (R)-21d
(160 mg, 77%) as a colorless solid; mpZ82 8C; eeR98%
(HPLC, (S,S)-Whelk-O1); [a]3D2ZK93.4 (cZ1.0; CHCl3).
IR (KBr): 3037, 2967, 1490, 1454, 1439, 1489, 1455, 1439,
1347, 1164, 1075, 1048, 1017, 981, 921, 856, 820, 809, 775,
731, 701, 638, 608, 569, 545, 509, 482, 462 cmK1. 1H NMR
(400 MHz, CDCl3): d 3.37 (dd, JZ11.3, 14.0 Hz, 1H), 3.63
(s, 3H), 3.68 (dd, JZ3.9, 14.0 Hz, 1H), 4.38 (dd, JZ3.9,
11.3 Hz, 1H), 6.87 (d, JZ8.5 Hz, 2H), 7.29 (d, JZ8.2 Hz,
2H), 7.33–7.36 (m, 5H). 13C NMR (100 MHz, CDCl3): d
35.7, 56.9, 68.6, 128.7, 129.1, 129.4, 130.5, 131.4, 120.7,
131.2, 135.1 (Aryl-C). MS (EI, 70 eV): m/z (%) 356 (10)
[MC(Br81)], 354 (11) [MC(Br79)], 261 (47) [MC(Br81)K
SO3CH3)], 259 (73) [MC(Br79)KSO3CH3], 180 (100), 169
(4), 89 (36). Anal. Calcd for C15H15O3SBr (355.25): C,
50.72; H, 4.26, found: C, 50.40; H, 4.51.
3.4. General procedure for the removal of the chiral
auxiliary to form the a-alkylated methyl sulfonates
(R)-21a–g (GP 3)
The sulfonate (R)-20 (0.6 mmol) was dissolved in an EtOH/
H2O-solution (19:1 mL). To the solution was added
Pd(OAc)2 (15 mol%, 20 mg) and the mixture was refluxed
for 4 d (TLC control). The palladium residues were removed
by filtration and washed twice with EtOH. The filtrate was
treated with an ethereal solution of diazomethane until the
yellow color persisted. The solvent was evaporated under
reduced pressure and the crude product purified by flash
column chromatography (SiO2, pentane/diethyl ether, 1:6)
to afford the methyl sulfonate (R)-21.
3.4.1. Methyl (R)-1-phenylethane sulfonate (R)-21a. The
sulfonate (R)-20a (260 mg, 0.6 mmol) was reacted accord-
ing to GP 3 to give (R)-21a (120 mg, 98%) as a colorless oil;
eeR98% (HPLC, Daicel OJ); [a]2D6ZC25.6 (cZ1.0;
CHCl3). IR (CHCl3): 2992, 2960, 1496, 1455, 1353, 1304,
3.4.5. Methyl (R)-2-naphtalen-2-yl-1-phenylethane sul-
fonate (R)-21e. The sulfonate (R)-20e (330 mg, 0.6 mmol)
was reacted according to GP 3 to give (R)-21e (190 mg,
96%) as a colorless solid; mpZ67 8C, eeR98% (HPLC,
Daicel OD); [a]3D1ZK89.5 (cZ1.0; CHCl3). IR (KBr):
3056, 2959, 1602, 1455, 1356, 1327, 1180, 1167, 1081, 990,
1168, 1056, 1030, 991, 802, 781, 767, 699, 624, 566 cmK1
.
1H NMR (400 MHz, CDCl3): d 1.84 (d, JZ7.1 Hz, 3H),
3.66 (s, 3H), 4.40 (q, JZ7.1 Hz, 1H), 7.37–7.47 (m, 5H).
13C NMR (100 MHz, CDCl3): dZ15.9, 56.7, 61.8, 128.6,
128.9, 128.9, 133.5. MS (EI, 70 eV): m/z (%) 200 (5) [MC],
105 (100) [MCKSO3CH3), 103 (8), 79 (9). HRMS: m/z
calcd for C9H12O3S (MC) 200.0507, found 200.0507.
1
863, 821, 784, 767, 696, 610, 577, 483 cmK1. H NMR
(400 MHz, CDCl3): d 3.58 (dd, JZ11.3, 14.0 Hz, 1H), 3.65
(s, 3H), 3.90 (dd, JZ3.8, 14.0 Hz, 1H), 4.38 (dd, JZ3.9,
11.3 Hz, 1H), 7.20–7.80 (m, 12H). 13C NMR (100 MHz,
CDCl3): d 36.5, 56.8, 68.5, 125.6, 125.9, 126.7, 127.4,
127.4, 127.7, 128.0, 128.6, 129.0, 129.5, 131.5, 132.0,
133.1, 133.7. MS (EI, 70 eV): m/z (%) 326 (27) [MC], 230
3.4.2. Methyl (R)-1-phenyl-3-butene sulfonate (R)-21b.

3242
D. Enders et al. / Tetrahedron 61 (2005) 3231–3243
(40), 215 (18), 153 (58), 141 (42) [C11HC9 ], 172 (9)
[C10HC7 ], 115 (31). Anal. Calcd for C19H18O3S (326.41): C,
69.91; H, 5.56, found: C, 69.75; H, 5.77.
64.0, 71.4, 72.3, 78.6, 79.9, 88.8, 105.0. MS (EI, 70 eV): m/z
(%)Z192 (9) [MCC2], 191 (100) [MCC1], 173 (10)
[(MCC1)KH2O], 145 (61, [(MCC1)KC2H5O], 130 (4),
103 (2), 85 (4), 73 (1). Anal. Calcd for C8H14O5 (190.20): C,
50.52; H, 7.42, found: C, 50.50; H, 7.31.
3.4.6. Methyl (R)-1-(4-tert-butylphenyl)-2-phenylethane
sulfonate (R)-21f. The sulfonate (R)-20f (340 mg,
0.6 mmol) was reacted according to GP 3 to give (R)-21f
(180 mg, 90%) as a colorless oil; eeR98% (HPLC, Daicel
AD); [a]2D6ZK92.8 (cZ1.0; CHCl3). IR (film) 3031, 3005,
2961, 2906, 2870, 1604, 1512, 1497, 1456, 1416, 1357,
3.5.2. Compound 22b. 37% yield (280 mg); colorless solid;
mpZ79 8C; [a]2D4ZK46.3 (cZ1.0; CHCl3). IR (KBr):
3414, 2975, 2899, 1725, 1640, 1445, 1404, 1376, 1360,
1111, 1085, 1054, 1001, 972, 947, 889, 839, 756, 700, 660,
648, 590 cmK1. 1H NMR (400 MHz, C5D5N): d 1.10 (t, JZ
7.1 Hz, 3H), 3.47 (dq, JZ7.1, 9.3 Hz, 1H), 4.02 (dq, JZ7.1,
9.3 Hz, 1H), 4.08 (t, JZ7.1 Hz, 1H), 4.17 (t, JZ8.5 Hz,
1H), 4.47 (m, 1H), 4.66 (s, 1H), 4.81 (d, JZ4.7 Hz), 5.04
(dd, JZ4.7, 5.0 Hz, 1H), 5.50 (s, 1H). 13C NMR (100 MHz,
C5D5N): dZ15.3, 63.79, 71.8, 72.9, 81.4, 84.6, 88.7, 111.5.
MS (EI, 70 eV): m/z (%)Z192 (9) [MCC2], 191 (100)
[MCC1], 173 (12) [(MCC1)KH2O], 145 (61, [(MCC
1)KC2H5O], 130 (4), 103 (2), 85 (6), 73 (2). Anal. Calcd
for C8H14O5 (190.20): C, 50.52; H, 7.42, found: C, 50.49;
H, 7.35.
1166, 989, 861, 829, 794, 756, 727, 699, 673, 611, 576 cmK1
.
1H NMR (400 MHz, CDCl3): d 1.29 (s, 9H), 3.41 (dd, JZ
10.7, 14.0 Hz, 1H), 3.62 (s, 3H), 3.71 (dd, JZ4.1, 14.0 Hz,
1H), 4.42 (dd, JZ4.1, 10.7 Hz, 1H), 7.00–7.40 (m, 12H).
13C NMR (100 MHz, CDCl3): d 30.9, 34.7, 36.5, 56.8,
68.5, 125.6, 125.9, 126.7, 127.4, 127.4, 127.7, 128.0,
128.6, 129.0, 129.5, 131.5, 132.1, 133.1, 133.7. MS (EI,
70 eV): m/z (%) 332 (2) [MC], 237 (2) [MCKSO3CH3],
172 (9) [C10HC7 ], 115 (2), 91 (22) [C7HC7 ], 57 (74).
HRMS: m/z calcd for C19H24O3S (MC) 332.1446, found
332.1446.
3.4.7. Methyl (R)-1-(4-tert-butylphenyl)-2-naphtalen-2-
yl-ethane sulfonate (R)-21g. The sulfonate (R)-20g
(340 mg, 0.6 mmol) was reacted according to GP 3 to
give (R)-21g (200 mg, 87%) as a colorless solid; mpZ
94 8C; eeR98% (HPLC, Daicel AD); [a]2D8ZK108.2 (cZ
1.0; CHCl3). IR (KBr) 2962, 1599, 1560, 1508, 1351, 1162,
994, 960, 859, 827, 809, 777, 765, 749, 673, 623, 603, 518,
¨
Rontgen crystal structure determination of 22b. Single
crystals were obtained by recrystallization from a n-hep-
tane/CH2Cl2 mixture (10:1). A single crystal (colorless,
transparent parallelepiped with dimensions 0.18!0.35!
0.70 mm3) was measured on a SIEMENS SMART diffract-
ometer at a temperature of about K130 8C. The substance
(C8H14O5 MrZ190.19) crystallized in the orthorhombic
1
484, 474 cmK1. H NMR (400 MHz, CDCl3): d 1.27 (s,
9H), 3.58 (dd, JZ11.0, 14.0 Hz, 1H), 3.63 (s, 3H), 3.88 (dd,
JZ3.9, 14.0 Hz, 1H), 4.53 (dd, JZ3.9, 10.7 Hz, 1H), 7.10–
8.00 (m, 11H). 13C NMR (100 MHz, CDCl3): dZ31.2, 34.6,
36.5, 56.8, 68.1, 125.8, 126.0, 126.1, 127.0, 127.6, 127.6,
127.9, 128.1, 129.4, 128.5, 132.3, 133.3, 134.1, 152.3. MS
(EI, 70 eV): m/z (%) 382 (39) [MC], 287 (100) [MCK
SO3CH3], 231 (12), 153 (16), 141 (22) [C11HC9 ], 122 (26),
57 (88). Anal. Calcd for C23H26O3S (382.52): C, 72.22; H,
6.85, found: C, 71.84; H, 6.71.
˚
space group P21P21P21, aZ5.3014 (6) A, bZ7.0086
(11) A, cZ24.599 (3) A, VZ914.0 (2) A , ZZ4, rcalcd
3
˚
˚
˚
Z
1.382 g/cm3. Repeatedly measured reflections remained
stable. A numerical absorption correction using six indexed
crystal faces gave a transmission factor between 0.943 and
0.980. Equivalent reflections were averaged. Friedel
opposites were not averaged. R(I)intZ0.025. The structure
was determined by direct methods using program SHELXS.
The H atoms were taken from a difference Fourier synthesis
and were refined with isotropic thermal parameters. The
structure was refined on F2 values using program SHELXL-
97. The final difference density was between K0.17 and
3.5. Investigations on the cleavage mechanism
The sulfonate (R)-20c (1.7 g, 4.0 mmol) was dissolved in an
EtOH/H2O solution (80:5 mL). To the solution was added
Pd(OAc)2 (15 mol%, 150 mg) and the mixture was refluxed
for 4 d (TLC control). The palladium residues were removed
by filtration and washed twice with EtOH. The filtrate was
treated with an ethereal solution of diazomethane until the
yellow color persisted. The solvent was evaporated under
reduced pressure and the compounds 22a and 22b were
isolated by flash column chromatography (SiO2, CH2Cl2/
MeOH, 30:1).
C0.31 e/AK3. Crystallographic data (excluding structure
˚
factors) have been deposited with the Cambridge Crystal-
lographic Data Centre as supplementary publication no.
CCDC-248428. Copies of the data can be obtained free of
charge on application to CCDC, 12 Union Road, Cambridge
CB21EZ, UK (fax: C44 1223 336 033; e-mail: deposit@
ccdc.cam.ac.uk).
Acknowledgements
3.5.1. Compound 22a. 25% yield (190 mg); colorless oil;
[a]2D5ZC137.8 (cZ1.15; CHCl3). IR (CHCl3): 3414, 2975,
2898, 1725, 1642, 1445, 1404, 1376, 1355, 1111, 1085,
1054, 1006, 976, 947, 889, 839, 756, 700, 667, 648,
This work was supported by the Deutsche Forschungsge-
meinschaft (SFB 380, Graduiertenkolleg 440) and the
Fonds der Chemischen Industrie. We thank Degussa
AG, BASF AG and Bayer AG for the donation of
1
592 cmK1. H NMR (400 MHz, C5D5N): d 1.09 (t, JZ
7.1 Hz, 3H), 3.49 (dq, JZ7.1, 9.6 Hz, 1H), 3.81 (dt, JZ7.1,
9.6 Hz, 1H), 3.86 (dd, JZ8.2, 8.5 Hz, 1H), 4.05 (dd, JZ6.1,
8.5 Hz, 1H), 4.38 (m, 1H), 4.53 (t, JZ3.9 Hz, 1H), 4.76 (dd,
JZ5.4, 5.5 Hz, 1H), 4.86 (dd, JZ3.6, 5.5 Hz, 1H), 5.29 (d,
JZ4.1 Hz, 1H). 13C NMR (100 MHz, C5D5N): dZ15.5,
¨
chemicals. The Rontgen structure determination by
Dr. J. W. Bats, University of Frankfurt, and the
NOE-measurements by Dr. J. Runsink are gratefully
acknowledged.

D. Enders et al. / Tetrahedron 61 (2005) 3231–3243
3243
12. Enders, D.; Vignola, N.; Berner, O. M.; Bats, J. W. Angew.
Chem. 2002, 114, 116–119. Enders, D.; Vignola, N.; Berner,
O. M.; Bats, J. W. Angew. Chem. Int. Ed. 2002, 41, 109–111.
13. Enders, D.; Berner, O. M.; Vignola, N.; Bats, J. W. Chem.
Commun. 2001, 2498–2499.
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