Asymmetric synthesis of heterocyclic β-aminosulfones via nucleophilic 1,2-addition of 2-lithio-benzo[b]thiophene to aldehyde-SAMP-hydrazones

Article abstract of DOI:10.3987/COM-04-S(P)3

An efficient asymmetric synthesis of α-(1,1-dioxo-2,3-dihydro-1H-1λ⁶-benzo[b]thiophen -2-yl)-substituted amines is described. Key steps of the synthesis are the nucleophilic 1,2-addition of 2-lithio-benzo[b]thiophene to aldehyde-SAMP-hydrazones, a benzo[b]thiophene oxidation using dimethyldioxirane and a highly diastereoselective conjugate reduction with L-Selectride. The heterocyclic β-aminosulfones are obtained in five steps and good overall yields (23-49%) and very high diastereo-and enantiomeric excesses (de ≥ 96%, ee = 88-99%).

Full text of DOI:10.3987/COM-04-S(P)3

HETEROCYCLES, Vol. 64, 2004
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HETEROCYCLES, Vol. 64, 2004, PP. 101 - 120
Received, 20th January, 2004, Accepted, 26th March, 2004, Published online, 30th March, 2004
ASYMMETRIC SYNTHESIS OF HETEROCYCLIC ß-AMINOSULFONES
VIA
NUCLEOPHILIC
1,2-ADDITION
OF
2-LITHIO-
BENZO[b]THIOPHENE TO ALDEHYDE-SAMP-HYDRAZONES
Dieter Enders* and Giuseppe Del Signore
Institute of Organic Chemistry, RWTH Aachen University, Professor-Pirlet-Strasse
1, 52074 Aachen, Germany; Fax: +49(241)8092127, E-mail: Enders@RWTH-
Aachen.de
Abstract – An efficient asymmetric synthesis of α−(1,1-dioxo-2,3-dihydro-1H-1λ6-
benzo[b]thiophen-2-yl)-substituted amines is described. Key steps of the synthesis
are the nucleophilic 1,2-addition of 2-lithio-benzo[b]thiophene to aldehyde-SAMP-
hydrazones, a benzo[b]thiophene oxidation using dimethyldioxirane and a highly
diastereoselective conjugate reduction with L-Selectride®. The heterocyclic ß-
aminosulfones are obtained in five steps and good overall yields (23-49%) and very
high diastereo-and enantiomeric excesses (de ≥ 96%, ee = 88-99%).
INTRODUCTION
Sulfones are a major class of organosulfur compounds1 that have been extensively used as versatile
intermediates in organic synthesis.2 The importance of the sulfone moiety has evoked interest in the
development of new methodologies to introduce the sulfone functionality into an organic molecule as
well as further synthetic transformations of the sulfone intermediates. Cyclic sulfones in particular are an
efficient source of conjugated dienes through SO2 extrusion for intramolecular Diels-Alder reactions.3
Furthermore, the well-established Ramberg-Bäcklund reaction4 has demonstrated to be an excellent
pathway to gain access to cyclic olefins. On the other hand, a number of biologically significant
molecules bear a cyclic sulfone as structural motif.5 In particular, molecules incorporating the
benzo[b]thiophene-1,1-dioxide skeleton have shown to be powerful anti-inflammatory agents6 and have
found widespread use due to their antimicrobial activities.7 Moreover, recent studies have shown that
benzene-fused five membered ring sulfones are effective bicyclic acylguanidine Na+/H+ antiporter
inhibitors8 as well as non-narcotic analgesic agents.9 Because of the interesting biological activities
associated with the benzo[b]thiophene-1,1-dioxide skeleton, it would be of great interest to develop an
efficient method to access their functionalized enantioenriched derivatives. In particular, the presence of 1
This paper is dedicated to Dr. Pierre Potier on the Occasion of his 70th birthday.

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HETEROCYCLES, Vol. 64, 2004
an amino group in ß-position to the sulfone moiety would be highly desirable, permitting for instance the
incorporation of the molecules into a peptide chain and therefore opening a new entry towards possible
pharmacological applications. Intrigued by this idea and regarding our general interest in developing new
methodologies for the asymmetric synthesis of ß-aminosulfones,10 we decided to commence our synthetic
efforts towards the first asymmetric synthesis of α−(1,1-dioxo-2,3-dihydro-1H-1λ6-benzo[b]thiophen-2-
yl)-substituted amines.
RESULTS AND DISCUSSION
Our synthetic five step strategy employing the SAMP-RAMP-hydrazone methodology11 to access the
target compounds is depicted in Scheme 1.
Cbz
H
R
N
N
H
N
O S
O
OMe
23-49%
R
(S,R)-4a-f
(S)-1a-h
ee = 88-99%
_
de > 96%
1) 2-benzothienyllithium
Et2O − 78°C to rt
30-77%
.
2) exc. BH3 THF, reflux
L-selectride,
−78°C to −20°C
58-80%
H
3) ClCbz, K2CO3,
THF/H2O
Cbz
Cbz
H
R
N
N
oxone, H2O/CH2Cl2/acetone
NaHCO3
R
O S
O
S
96-98%
(S)-3a-g
(S)-2a-h
ee = 66-99%
ee = 66-99%
Scheme 1
The enantiopure aldehyde-SAMP-hydrazones (1a-h) were synthesized by direct condensation of the
corresponding aldehydes with (S)-1-amino-2-methoxymethylpyrrolidine (SAMP). The reactions were
performed in Et2O at room temperature in the presence of magnesium sulfate. After purification the
aldehyde hydrazones were obtained in almost quantitative yields. The nucleophilic 1,2-addition of 2-
lithio-benzo[b]thiophene to the aldehyde-SAMP-hydrazones (1a-h) proceeded smoothly using Et2O as

HETEROCYCLES, Vol. 64, 2004
103
solvent. High conversions and selectivities were obtained when treating the hydrazones with three
equivalents of the heteroaryllithium species at –78°C for 30 minutes after which the reaction mixture was
allowed to warm up to room temperature. Complete conversion of the starting material was obtained in
approximately 5 hours. Interestingly, at –78°C no reaction took place and attempts to explore different
solvents failed. Since the resulting hydrazines are sensitive to oxidation and thus not very stable, the
crude products were directly used in the following steps. The N,N-bond cleavage was achieved by
refluxing the crude hydrazines with a large excess of BH3·THF12 providing the corresponding amines,
which were directly protected as benzyl carbamates (2a-h) by treatment with benzyl chloroformate. The
absolute configuration of the newly formed stereogenic center was assigned as S based on our previous
studies13 and in accordance with the relative topicity observed for all 1,2-additions to the CN double bond
of aldehyde-SAMP-hydrazones. The yields over three steps as well as enantiomeric excesses are given in
table 1.
Table 1
2
a
b
c
R
Et
Yield(%)a
ee(%)b
Confg.
76
77
93
99
S
S
S
S
S
S
S
S
i-Pr
t-Bu
60
91
93
d
e
n-Bu
62
PhCH2CH2
Ph
72
95
f
46 (30)
38
77 (88)c
66c
g
h
p-MeOC6H4
Ferrocenyl
45
≥ 95%d
a) Overall yield over three steps.
b) Determined by HPLC with a chiral stationary phase (Daicel OD or Chiralpak AD 2).
c) Determined on the corresponding sulfone (3) (HPLC).
d) Determined on the corresponding hydrazine precursor by 1H and 13C NMR spectroscopy.
As can be seen from Table 1, the procedure is quite general including primary, secondary and tertiary
alkyl as well as aromatic groups R within the aldehyde component. However, in the case of the aromatic
aldehyde-SAMP-hydrazones (1f) and (1g) lower yields and enantiomeric excesses were obtained. Further
studies showed that the nucleophilic 1,2-addition on these substrates started to take place at about –10°C

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HETEROCYCLES, Vol. 64, 2004
instead of the usual –50°C observed with alkylhydrazones. Performing the reaction directly at –10°C did
not improve the selectivity.
With the α-(benzothienyl)-substituted amines in hand, we commenced our studies on the oxidation of the
benzothiophene ring. Therefore, the carbamates (2a-g) were treated with an excess of dimethyldioxirane
(DMD). DMD was generated in situ14 in the reaction mixture already containing the carbamate to be
oxidized, by reacting acetone with oxone (2KHSO5·KHSO4·K2SO4) in the presence of sodium hydrogen
carbonate. To our delight, the reaction was extremely clean and high yielding (see Table 2).
Table 2
3
a
b
c
d
e
f
R
Et
Yield(%)
ee(%)a
93
98
98
97
98
98
96
88
i-Pr
99
t-Bu
91
n-Bu
93
PhCH2CH2
Ph
95
88b
66b
g
p-MeOC6H4
a) Based on the ee-determination of 2.
b) Determined by HPLC with a chiral stationary phase (Chiralpak AD 2).
In nearly every case the sulfones (3a-g) did not require purification via flash column chromatography as
demonstrated by the elemental analyses performed directly on the crude products (see experimental part).
Finally, reduction of the double bond of 3a-f was more challenging than expected. NaBH4 as reducing
agent resulted in a sluggish reaction affording after four days very poor conversion (ca. 20%) as shown
by NMR spectral analysis. A major improvement was achieved by employing NaBH4 in the presence of a
catalytic amount of NiCl2 in MeOH. The reduction took place smoothly and the corresponding
heterocyclic ß-aminosulfones (4a,c-f) could be isolated in excellent yields (Table 3). Especially with
compounds (3a,d and e) the reduction proceeded with excellent diastereoselectivity (de ≥ 96%) affording
the corresponding anti diastereomers (4a,d and e) as a mixture of carbamate E/Z-isomers in a ratio of
approximately 2:1. Increasing the steric hindrance of the substituents resulted in a drastic decrease of the
diastereoselectivity of the reaction.

HETEROCYCLES, Vol. 64, 2004
105
Table 3
4
a
c
d
e
f
R
Et
Time (h)
Yield (%)
dea (%)
eeb (%)
93
Confg.
S,R
3
14
3
89
70
79
87
60
≥ 96
15
t-Bu
91
S,R
n-Bu
PhCH2CH2
Ph
≥ 96
≥ 96
90
93
S,R
3
95
S,R
3
88
S,R
a) Determined by 1H and 13C NMR spectroscopy.
b) Based on the ee-values of 2-or 3.
The effect was particularly marked with the tert-butyl group. When 3c was treated with NaBH4 in the
presence of NiCl2, a longer reaction time was necessary and the reaction gave three products as shown by
NMR spectral analysis of the crude mixture. Purification by flash column chromatography provided two
fractions: the former was the desired diastereomer (4c) as a mixture of carbamate E/Z-isomers, the latter
Table 4
4
a
b
c
d
e
f
R
Et
Time (h)
Yield (%)
dea (%)
≥ 96
eeb (%)
93
Confg.
S,R
5
10
10
5
66
58
60
70
70
80
i-Pr
≥ 96
99
S,R
t-Bu
≥ 96
91
S,R
n-Bu
PhCH2CH2
Ph
≥ 96
93
S,R
5
≥ 96
95
S,R
5
≥ 96
88
S,R
a) Determined by 1H and 13C NMR spectroscopy.
b) Based on the ee-values of 2 or 3.
the syn diastereomer as a single product (no second carbamate E/Z-isomer could be detected).The
diastereomers were produced in a disappointing ratio of approximately 1.3:1. To overcome the problem, a
screening of different hydride reagents and solvents was commenced. Best results were achieved when
the reductions were performed with L-selectride® in THF at low temperature. The desired products (4a-f)

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were obtained in good yields and outstanding stereocontrol (de ≥ 96%) (Table 4). Finally, the absolute
configuration of the newly formed stereogenic centre after the double bond reduction was assigned as R
by a NOE experiment performed on the deprotected ß-aminosulfone (5c). Selected NOE interactions are
depicted in Scheme 2.
Cbz
H
NH2
N
H
H
H2, Pd/C, 4 atm
16 h, rt
Me
H
Me
Me
NH2
t-Bu
t-Bu
O S
96%
O S
S
H
O
5c
O2
O
4c
de = > 96%
−
ee = 91%
Scheme 2
CONCLUSION
In summary, we have developed a very efficient asymmetric synthesis of α−(1,1-dioxo-2,3-dihydro-1H-
1λ6-benzo[b]thiophen-2-yl)-substituted amines using as key step a nucleophilic 1,2-addition of 2-lithio-
benzo[b]thiophene to aldehyde-SAMP-hydrazones. The title compounds were obtained in good overall
yields and excellent diastereo- and enantiomeric excesses. The pharmacological properties of these
interesting heterocyclic ß-aminosulfones are currently under evaluation.
EXPERIMENTAL
General procedure (GP1) for the synthesis of (1S)-(1-benzo[b]thiophen-2-yl-substituted)-carbamic acid
benzyl esters (2a-h):
To a solution of 2-benzothienyllithium (6.4 mmol) in Et2O (20 mL) cooled to –78°C was added dropwise
the aldehyde hydrazone (1a-h) (2 mmol) in dry Et2O (2 mL). After 30 min the cooling bath was removed,
the reaction mixture allowed to warm to rt and stirred for additional 2-9 h. The mixture was quenched
with saturated aqueous NH4Cl and extracted three times with Et2O. The organic layer was then washed
twice with brine, dried over MgSO4 and evaporated in vacuo. The crude hydrazine was dissolved in dry
THF (10 mL pro mmol of hydrazine) and heated up to reflux with 10 or 20 equivalents of BH3·THF (1.0
M in THF) for 9-36 h. The reaction was cooled to rt, acidified with aqueous HCl (1N) and stirred for 1 h.
The THF was evaporated under reduced pressure and the aqueous solution was made basic with a
saturated solution of K2CO3 and extracted with methylene chloride. The organic layers were concentrated
in vacuo and the residue was dissolved in a mixture of H2O and THF (1:1). 2 Equivalents of potassium

HETEROCYCLES, Vol. 64, 2004
107
carbonate were added, followed by 1.8 equivalents of benzyl chloroformate and the heterogeneous
solution was stirred at rt overnight. Et2O (10 mL) was added to the mixture, the layers were separated and
the aqueous layer was washed with two further portions (10 mL) of Et2O. The combined organic layers
were dried (MgSO4) and evaporated. The crude product was purified by column chromatography.
General procedure (GP2) for the synthesis of (S)-[1-(1,1-Dioxo-1H-1λ6-benzo[b]thiophen-2-yl)-
substituted]-carbamic acid benzyl esters (3a-g):
To a 2 neck flask, equipped with an efficient stirrer and a condenser, charged with H2O (20 mL pro
mmol), acetone (16 mL pro mmol) and NaHCO3 (1.2 g pro mmol) was added a solution of the protected
benzothiophene amine (2a-g) in CH2Cl2 (18 mL pro mmol). To the resulting heterogeneous mixture
oxone was carefully added over 5 min (2g pro mmol). The reaction mixture was stirred at rt for 2-7 h
before water was added to dissolve most of the inorganic salts. The decanted aqueous layer, and all
remaning solids were extracted with CH2Cl2, the combined organic phases washed with water and dried
over MgSO4. The solvent was removed in vacuo and the crude product purified by column
chromatography or directly used in the next step without any purification.
General procedure (GP3) for the reduction of 3a,c-f with sodium borohydride/NiCl2 (cat.):
The ß-aminosulfone (3a,c-f) was dissolved in MeOH (10 mL pro mmol) in the presence of a catalytic
amount of NiCl2 (20 mol%) and the resulting solution was cooled to –20°C. 4 Equivalents of NaBH4 were
carefully added to the mixture under vigorous stirring. After 2-7 h the solvent was removed under
reduced pressure and the residue was dissolved in a solution of CH2Cl2 and water (10 mL, ratio 1:1,). The
layers were separated and the aqueous phase extracted three times with CH2Cl2 (5 mL). The combined
organic extracts were washed with brine and dried over MgSO4. The solvent was removed in vacuo and
the crude product purified by flash chromatography.
General procedure (GP 4) for the reduction of 3a-f with L-Selectride®:
To a solution of the ß-aminosulfone (3a-f) in THF (10 mL pro mmol) were added dropwise 2 equivalents
of L-selectride at –78°C. The solution was slowly allowed to warm to –20°C and after 2-9 h was
quenched by addition of AcOH. The solvent was removed under reduced pressure and the residue was
diluted with CH2Cl2. The organic layer was washed with brine and dried over MgSO4. The solvent was
removed in vacuo and the crude product purified on silica gel chromatography.
(1S)-(1-Benzo[b]thiophen-2-ylpropyl)carbamic acid benzyl ester (2a): To a solution of 2-lithio-
benzo[b]thiophene (6.4 mmol) in 20 mL of Et2O was added hydrazone (1a) (340 mg, 2.0 mmol) in 4 mL

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HETEROCYCLES, Vol. 64, 2004
of Et2O according to GP1. Purification by column chromatography (Et2O:pentane 1:3) afforded 495 mg,
(76%) of 2a as a colorless solid; mp = 86-87°C (Et2O:pentane 1:10). ee = 93% determined by HPLC over
1
chiral stationary phase (Daicel OD). [α] 22 = –46.80 (c = 0.25 CHCl3). H NMR (300 MHz, CDCl3) δ =
D
0.89 (t, 3H, J = 7.4 Hz, CH3), 1.82-1.87 (m, 2H, CH3CH2), 4.92-5.08 (m, 4H, CHNH, NH, CH2O), 7.08-
13
7.25 (m, 8H, arom CH), 7.58-7.66 (m, 1H, arom CH), 7.67-7.69 (m, 1H, arom CH) ppm. C NMR (75
MHz, CDCl3) δ = 10.83 (CH3), 30.01 (CH3CH2), 53.43 (CHN), 67.26 (CH2O), 121.29, 122.65, 123.74,
124.44, 124.61, 128.47, 128.82 (arom CH), 136.60, 139.39, 139.86, 147.20 (arom C), 156.04 (C=O) ppm;
IR (KBr) ῦ = 3289 (s), 1715 (m), 1690 (vs), 1541 (s), 1271 (s), 1235 (s), 1040 (m), 974 (m), 746 (s), 696
(m) cm-1; MS (EI, 70 eV): m/z (%) = 326 (7) [M+•+1], 325 [M+•], 252 (11), 235 (8), 234 (53), 191 (5), 190
(37), 147 (6), 135 (13), 92 (7), 91 (100), 65 (5), 56 (10). Anal. Calcd for C19H19NO2S: C, 70.12; H, 5.88;
N, 4.30. Found: C, 70.00, H, 5.71; N, 4.22.
(1S)-(1-Benzo[b]thiophen-2-yl-2-methylpropyl)carbamic acid benzyl ester (2b) To a solution of 2-
lithio-benzo[b]thiophene (6.4 mmol) in 20 mL of Et2O was added hydrazone (1b) (370 mg, 2.0 mmol) in
4 mL of Et2O according to GP1. Purification by column chromatography (Et2O:pentane 1:3) afforded 520
mg of 2b (77%) as a colorless solid; mp = 77-78°C (Et2O:pentane 1:10). ee = 99% determined by HPLC
over chiral stationary phase (Daicel OD). [α] 22 = –43.7 (c = 1.4, CHCl3). 1H NMR (300 MHz, CDCl3) δ =
D
0.98 (t, 6H, J = 6.5 Hz, CH3CH), 2.05-2.16 (m, 1H, CH3CH), 4.86-4.91 (m, 1H, CHN), 5.05-5.16 (m, 3H,
NH, CH2O), 7.14 (s, 1H, arom CH), 7.24-7.34 (m, 7H, arom CH), 7.68 (d, 1H, J = 7.4 Hz, arom CH),
13
7.76 (d, 1H, J = 7.4 Hz, arom CH) ppm; C NMR (75 MHz, CDCl3) δ = 18.17, 19.75 (CH3), 34.00
(CH3CH), 57.56 (CHN), 67.03 (CH2O), 121.26, 122.28, 123.38, 124.05, 124.29, 128.17, 128.53 (arom
CH), 136.29, 139.11, 139.54, 146.43 (arom C), 155.94 (C=O) ppm; IR (KBr) ῦ = 3429 (m), 3327 (s),
1685 (vs), 1537 (s), 1271 (s), 1243 (m) cm−1; MS (EI, 70 eV,) m/z (%) = 339 (6) [M+•], 296 (16), 252 (25),
248 (5), 231 (32), 190 (8), 189 (22), 188 (82), 162 (5), 161 (12), 160 (17), 149 (10), 147 (12), 135 (7),
134 (6), 133 (18), 111 (8), 109 (7), 105 (5), 99 (6), 97 (10), 95 (8), 92 (9), 91 (100), 89 (24), 85 (11), 83
(10), 82 (5), 81 (7), 79 (27), 77 (17), 71 (14), 70 (5), 69 (15), 65 (7), 63 (5), 60 (5), 57 (28), 56 (6), 55
(12), 51 (10), 45 (8). Anal. Calcd for C20H21NO2S: C, 70.77; H, 6.24; N, 4.13. Found: C, 70.90, H, 6.38;
N, 3.98.
(1S)-(1-Benzo[b]thiophen-2-yl-2,2-dimethylpropyl)carbamic acid benzyl ester (2c): To a solution of
2-lithio-benzo[b]thiophene (6.4 mmol) in 20 mL of Et2O was added hydrazone (1c) (396 mg, 2.0 mmol)
in 4 mL of Et2O according to GP1. Purification by column chromatography (Et2O:pentane 1:3) afforded
425 mg of 2c (60%) as a colorless solid; mp = 73-74°C (Et2O:pentane 1:10). ee = 91% determined by

HETEROCYCLES, Vol. 64, 2004
109
1
HPLC over chiral stationary phase (Daicel OD). [α] 22 = –12.2 (c = 1.2, CHCl3). H NMR (300 MHz,
D
CDCl3) δ = 1.04 (s, 9H, (CH3)3C), 4.90 (d, 1H, J = 9.3 Hz, CHNH), 5.03 (d, 1H, JAB = 12.1 Hz CHHO),
5.10 (d, 1H, JAB = 12.1 Hz CHHO), 5.26 (d, 1H, J = 9.3 Hz, NH), 7.15 (s, 1H, arom CH), 7.23-7.35 (m,
13
7H, arom CH), 7.68-7.71 (m, 1H, arom CH), 7.74-7.79 (m, 1H, arom CH) ppm; C NMR (75 MHz,
CDCl3) δ = 26.78 (CH3), 35.10 (CH3C), 60.93 (CHN), 67.06 (CH2O), 122.08, 122.87, 123.34, 124.07,
124.25, 128.25, 128.54 (arom CH), 136.26, 139.10, 139.24, 144.41 (arom C), 155.93 (C=O) ppm; IR
(solution in CDCl3) ῦ = 3277 (m), 2957 (m), 1706 (vs), 1402 (m), 1342 (s), 1053 (m), 741 (m), 696 (m)
cm−1; MS (EI, 70 eV,) m/z (%) = 353 (3) [M+•], 297 (5), 296 (28), 252 (27), 160 (5), 129 (10), 92 (7), 91
(100), 57 (7); Anal. Calcd for C21H23NO2S: C, 71.36; H, 6.56; N, 3.96. Found: C, 70.96, H, 6.44; N, 4.07.
(1S)-(1-Benzo[b]thiophen-2-ylpentyl)carbamic acid benzyl ester (2d): To a solution of 2-lithio-
benzo[b]thiophene (6.4 mmol) in 20 mL of Et2O was added hydrazone (1d) (396 mg, 2.0 mmol) in 4 mL
of Et2O according to GP1. Purification by column chromatography (Et2O:pentane 1:3) afforded 440 mg
of 2d (62%) as a colorless solid; mp 89-90°C (Et2O:pentane 1:10). ee = 93% determined by HPLC over
chiral stationary phase (Daicel OD). [α] 22 = –52.0 (c = 1.0, CHCl3). 1H NMR (400 MHz, CDCl3) δ = 0.76
D
(t, 3H, J = 6.8 Hz, CH3CH2), 1.22-1.30 (m, 4H, CH3CH2CH2), 1.67-1.74 (m, 2H, CH2CH), 4.93-5.08 (m,
3H, CHN, CH2O), 5.20 (d, 1H, J = 8.2 Hz, NH), 7.03 (s, 1H, arom CH), 7.12-7.20 (m, 7H, arom CH),
7.54 (d, 1H, J = 7.7 Hz, arom CH), 7.62 (d, 1H, J = 9.0 Hz, arom CH) ppm; 13C NMR (100 MHz, CDCl3)
δ = 14.25 (CH3), 22.65 (CH3CH2), 28.44 (CH3CH2CH2), 36.64 (CH2CH), 51.99 (CHN), 67.20 (CH2O),
121.18, 122.65, 123.75, 124.40, 124.59, 128.42, 128.80 (arom CH), 136.69, 139.40, 139.89, 147.68 (arom
C), 156.06 (C=O) ppm; IR (KBr) ῦ = 3310 (s), 2953 (m), 2925 (m), 2855 (m), 1684 (vs), 1537 (s), 1456
(m), 1294 (m), 1256 (s), 1046 (m), 749 (s), 725 (m), 696 (m), 663 (m) cm−1; MS (EI, 70 eV) m/z (%) =
353 (16) [M+•], 263 (6), 262 (41), 252 (11), 245 (10), 218 (30), 189 (6), 188 (46), 160 (7), 147 (12), 135
(9), 108 (6), 92 (8), 91 (100), 89 (7), 84 (5), 79 (5), 77 (5), 65 (6). Anal. Calcd for C21H23N2O2S: C, 71.36;
H, 6.56; N, 3.96. Found: C, 71.02, H, 6.26; N, 3.80.
(1S)-(1-Benzo[b]thiophen-2-yl-3-phenylpropyl)carbamic acid benzyl ester (2e): To a solution of 2-
lithio-benzo[b]thiophene (6.4 mmol) in 20 mL of Et2O was added hydrazone (1e) (492 mg, 2.0 mmol) in
4 mL of Et2O according to GP1. Purification by column chromatography (Et2O:pentane 2:5) afforded 580
mg of 2e (72%) as a colorless solid; mp = 113-114°C (Et2O:pentane 1:10). ee = 95% determined by
1
HPLC over chiral stationary phase (Daicel OD). [α] 22 = –29.0 (c = 0.9, CHCl3). H NMR (300 MHz,
D
CDCl3) δ = 2.09-2.17 (m, 2H, CH2CH2), 2.54-2.67 (m, 2H, PhCH2), 4.97-5.08 (m, 4H, NH, CHNH,
CH2O), 6.99-7.26 (m, 13H, arom CH), 7.60 (d, 1H, J = 7.2 Hz, arom CH), 7.69 (d, 1H, J = 7.2 Hz, arom

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CH) ppm; 13C NMR (75 MHz, CDCl3) δ = 32.39 (PhCH2), 38.40 (CH2CH2), 51.51 (CHN), 67.10 (CH2O),
121.33, 122.48, 123.60, 124.35, 124.48, 126.23, 128.26, 128.47, 128.60 (arom CH), 136.34, 139.20,
139.60, 140.93, 146.71 (arom C), 155.69 (C=O) ppm; IR (CHCl3) ῦ = 3313 (s), 1686 (vs), 1533 (s), 1454
(m), 1260 (s), 744 (s), 698 (m); MS (EI, 70 eV) m/z (%) = 401 (5) [M+•], 309 (30), 265 (16), 251 (10),
250 (5), 248 (25), 187 (6), 159 (6), 134 (7), 92 (7), 90 (100), 65 (6). Anal. Calcd for C25H23NO2S: C,
74.78; H, 5.77; N, 3.49. Found: C, 75.05, H, 6.10; N, 3.29.
(1S)-(1-Benzo[b]thiophen-2-ylphenylmethyl)carbamic acid benzyl ester (2f): To a solution of 2-lithio-
benzo[b]thiophene (6.4 mmol) in 20 mL of Et2O was added hydrazone (1f) (436 mg, 2.0 mmol) in 4 mL
of Et2O according to GP1. Purification by column chromatography (Et2O:pentane 1:2) afforded 345 mg
of 2f (46%) as a colorless solid; mp = 101-103°C (Et2O:pentane 1:8). ee = 77% (88% after single
recrystallization) determined on the corresponding sulfone 3f by HPLC over chiral stationary phase
1
(Chiralpak AD 2). [α] 22 = –7.27 (c = 1.1, CHCl3). H NMR (300 MHz, CDCl3) δ = 5.13 (s, 2H, CH2O),
D
5.58-5.61 (br, 1H, NH), 6.23-6.26 (br 1H, CHN), 7.03 (s, 1H, arom CH), 7.21-7.37 (m, 12H, arom CH),
13
7.61-7.67 (m, 1H, arom CH), 7.72-7.75 (m, 1H, arom CH) ppm; C NMR (75 MHz, CDCl3) δ = 55.64
(CHN), 67.22 (CH2O), 122.25, 122.30, 123.59, 124.34, 124.40, 127.08, 128.17, 128.53, 128.82 (arom
CH), 136.13, 139.39 139.74, 140.57, 146.42 (arom C), 155.38 (C=O) ppm; IR (CHCl3) ῦ = 3318 (s), 1688
(vs), 1527 (s), 1240 (s), 1041 (m), 744 (m), 700 (m) cm−1; MS (EI, 70 eV) m/z (%) = 374 (6) [M+•+1], 373
(24) [M+•], 283 (17), 282 (100), 239 (11), 238 (61), 223 (9), 221 (10), 160 (6), 135 (11), 104 (42), 91 (43),
77 (8), 65 (6). Anal. Calcd for C23H19NO2S: C, 73.97; H, 5.13; N, 3.75. Found: C, 73.72, H, 5.27; N, 3.71.
(1S)-[1-Benzo[b]thiophen-2-yl-(4-methoxyphenyl)methyl]carbamic acid benzyl ester (2g): To a
solution of 2-lithio-benzo[b]thiophene (6.4 mmol) in 20 mL of Et2O was added hydrazone (1g) (496 mg,
2.0 mmol) in 4 mL of Et2O according to GP1. Purification by column chromatography (Et2O:pentane 1:2)
afforded 375 mg of 2g (38%) as a colorless solid; mp = 142-143°C (Et2O:pentane 1:5). ee = 66%
determined on the corresponding sulfone (3g) by HPLC over chiral stationary phase (Chiralpak AD 2):
[α] 22 = +5.5 (c = 1.1, CHCl3). 1H NMR (300 MHz, CDCl3) δ = 3.77 (s, 3H, OCH3), 5.13 (d, 2H, J = 1.0
D
Hz, CH2O), 5.58-5.62 (br, 1H, NH), 6.17-6.20 (br 1H, CHN), 6.83-6.88 (m, 2H, arom CH), 7.02 (s, 1H,
arom CH), 7.21-7.32 (m, 9H, arom CH), 7.61-7.64 (m, 1H, arom CH), 7.70-7.73 (m, 1H, arom CH). ppm;
13C NMR (75 MHz, CDCl3) δ = 55.22 (CHN), 55.37 (OCH3), 67.25 (CH2O), 114.22, 122.11, 122.40,
123.63, 124.36, 124.45, 128.28, 128.45, 128.61 (arom CH), 132.90, 136.27, 139.54 139.84, 147.02 (arom
C), 155.48 (C=O), 159.48 (arom C) ppm; IR (CHCl3) ῦ = 3317 (s), 1689 (vs), 1514 (s), 1457 (s), 1294
(m), 1245 (vs), 1044 (m), 1028 (m), 833 (m), 741 (m) cm−1; MS (EI, 70 eV) m/z (%) = 404 (8) [M+•+1],

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403 (21) [M+•], 313 (19), 312 (100), 269 (11), 268 (68), 253 (13), 160 (18), 135 (7), 134 (39), 109 (6), 91
(47), 65 (5). Anal. Calcd for C24H21NO3S: C, 71.44; H, 5.25; N, 3.47. Found: C, 71.76, H, 5.16; N, 3.51.
(1S)-(1-Benzo[b]thiophen-2-ylferrocenylmethyl)carbamic acid benzyl ester (2h): To a solution of 2-
lithio-benzo[b]thiophene (3.2 mmol) in 10 mL of Et2O was added hydrazone (1h) (326 mg, 1.0 mmol) in
2 mL of Et2O according to GP1. Purification by column chromatography (Et2O:pentane 1:3) afforded 220
mg of 2h (46%) as an orange solid; mp = 128-129°C (Et2O:pentane 1:8). ee ≥ 95% determined on the
corresponding hydrazine by 1H and 13C NMR spectroscopy. [α] 22 = – 9.1 (c = 1.1, CHCl3). 1H NMR (300
D
MHz, CDCl3) δ = 4.07-4.15 (m, 9H, CH Fc), 5.03 (d, 1H, JAB = 12.2 Hz, CHHO), 5.12 (d, 1H, JAB = 12.2
Hz, CHHO), 5.51-5.53 (br, 1H, NH), 5-89-5.91 (br 1H, CHN), 7.05-7.28 (m, 8H, arom CH), 7.56-7.59 (m,
13
1H, arom CH), 7.66-7.69 (m, 1H, arom CH) ppm; C NMR (75 MHz, CDCl3) δ = 50.91 (CHN), 66.78
(CH, Fc), 67.25 (CH2O), 67.44, 68.23, 69.11 (CH, Fc), 89.68 (C, Fc), 121.75, 122.42, 123.65, 124.28,
124.36, 128.34, 128.66 (arom CH), 136.38, 139.39 139.49, 146.87 (arom C), 155.39 (C=O) ppm; IR
(CHCl3) ῦ = 3428 (s), 1696 (vs), 1509 (vs), 1307 (m), 1284 (m), 1233 (s) 1044 (m), 1024 (m), 823 (m),
751 (s), 700 (m) cm−1; MS (EI, 70 eV) m/z (%) = 483 (10) [M+•+2], 482 (33) [M+•+1], 481 (100) [M+•],
479 (7), 346 (20), 280 (10), 267 (7), 226 (8), 212 (13), 210 (6), 209 (8), 121 (7), 91 (13). Anal. Calcd for
C27H23NO2FeS: C, 67.35; H, 4.81; N, 2.91. Found: C, 67.44, H, 5.18; N, 2.73.
(S)-[1-(1,1-Dioxo-1H-1λ6-benzo[b]thiophen-2-yl)propyl]carbamic acid benzyl ester (3a): To a well
stirred solution of carbamate (2a) (325 mg, 1.0 mmol) in 54 mL of a H2O/CH2Cl2/acetone (1:0.9:0.8)
mixture, were added 1.2 g of NaHCO3 followed by 2 g of oxone according to GP2. After work-up,
removal of the solvent in vacuo afforded 350 mg of 3a (98%) as a colorless solid; mp = 68-69°C
1
(Et2O:pentane 1:5). ee = 93%. [α] 22 = –72.8 (c = 1.7, CHCl3). H NMR (300 MHz, CDCl3) δ = 1.00 (t,
D
3H, J = 7.4 Hz, CH3), 1.85-1.94 (m, 1H, CH3CHH), 2.02-213 (m, 1H, CH3CHH), 4.72-4.78 (m, 1H,
CHNH,), 5.07 (d, 1H, JAB = 12.4 Hz, CHHO), 5.13 (d, 1H, JAB = 12.4 Hz, CHHO), 5.62 (d, J =8.5 Hz,
NH), 6.96 (s, 1H, CHCSO2), 7.23-7.34 (m, 6H, arom CH), 7.38-7.49 (m, 2H, arom CH), 7.60 (d, J = 7.4
13
Hz, 1H, arom CH) ppm.; C NMR (75 MHz, CDCl3) δ = 10.38 (CH3), 26.22 (CH3CH2), 50.87 (CHN),
66.85 (CH2O), 120.91, 124.84, 127.69 127.78, 127.89, 128.26, 129.80 (arom CH, CHCSO2), 130.26
(CSO2), 133.41 (arom CH), 136.02, 137.03, 143.32 (arom C), 155.50 (C=O) ppm. IR (KBr) ῦ = 3348 (m),
2970 (m), 1710 (vs), 1524 (vs), 1456 (s), 1299 (vs), 1235 (s), 1149 (vs), 1125 (m), 756 (vs), 700 (m)
cm−1; MS (EI, 70 eV) m/z (%) = 357 [M+•], 284 (9), 222 (7), 192 (5), 181 (5), 148 (7), 137 (5), 108 (5), 92
(7), 91 (100), 65 (6). Anal. Calcd for C19H19NO4S: C, 63.85; H, 5.36; N, 3.92. Found: C, 63.50, H, 5.61;
N, 3.67.

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(S)-[1-(1,1-Dioxo-1H-1λ6-benzo[b]thiophen-2-yl)-2-methylpropyl]carbamic acid benzyl ester (3b): to
a well stirred solution of carbamate (2b) (340 mg, 1.0 mmol) in 54 mL of a H2O/CH2Cl2/acetone
(1:0.9:0.8) mixture, were added 1.2 g of NaHCO3 followed by 2 g of oxone according to GP2. After
work-up, removal of the solvent in vacuo afforded 365 mg of 3b (98%) as a colorless foam; ee = 99%.
[α] 22 = –74.3 (c = 1.6, CHCl3). 1H NMR (400 MHz, CDCl3) δ = 0.99 (d, 3H, J = 6.6 Hz, CH3CH), 1.02 (d,
D
3H, J = 6.3 Hz, CH3CH), 2.35-2.43 (m, 1H, CH3CH), 4.66 (t, 1H, J = 8.9 Hz, CHNH,), 5.07 (d, 1H, JAB =
12.3 Hz, CHHO), 5.15 (d, 1H, JAB = 12.2Hz, CHHO), 5.69 (d, J = 8.9 Hz, NH), 6.96 (s, 1H, CHCSO2),
7.21-7.31 (m, 6H, arom CH), 7.41 (dt, J = 7.4, 28.3 Hz, 2H, arom CH), 7.58 (d, 1H, J = 7.2 Hz, arom CH)
ppm; 13C NMR (100 MHz, CDCl3) δ = 18.02, 19.88 (CH3), 30.48 (CH3CH), 55.62 (CHN), 66.83 (CH2O),
120.86, 124.78, 127.71 127.85, 128.05, 128.24, 129.75 (arom CH, CHCSO2), 130.25 (CSO2), 133.41
(arom CH), 136.05, 136.98, 143.18 (arom C), 155.74 (C=O) ppm. IR (KBr) ῦ = 3351 (s), 3063 (m), 3030
(m), 2966 (s), 2934 (m), 1711 (vs), 1523 (vs), 1458 (s), 1300 (vs), 1237 (vs), 1149 (vs), 1125 (m), 1099
(m), 1021 (m), 756 (vs), 700 (m), 545 (m) cm−1; MS (EI, 70 eV) m/z (%) = 371 (1) [M+•], 328 (15), 284
(22), 238 (6), 194 (7), 92 (7), 91 (100), 65 (6). Anal. Calcd for C20H21NO4S: C, 64.67; H, 5.70; N, 3.77.
Found: C, 64.58, H, 6.09; N, 3.51.
(S)-[1-(1,1-Dioxo-1H-1λ6-benzo[b]thiophen-2-yl)-2,2-dimethylpropyl]carbamic acid benzyl ester
(3c): To a well stirred solution of carbamate (2c) (353 mg, 1.0 mmol) in 54 mL of a H2O/CH2Cl2/acetone
(1:0.9:0.8) mixture, were added 1.2 g of NaHCO3 followed by 2 g of oxone according to GP2. After
work-up, removal of the solvent in vacuo afforded 375 mg of 3c (97%) as a colorless solid; mp = 75°C
(Et2O:pentane 1:5). ee = 91%. [α] 22 = –54.3 (c = 1.3 CHCl3). 1H NMR (400 MHz, CDCl3) δ = 1.10 (s, 9H,
D
(CH3)3C), 4.72 (d, 1H, J = 9.9 Hz, CHNH,), 5.04 (d, 1H, JAB = 12.1 Hz, CHHO), 5.13 (d, 1H, JAB = 12.1
Hz, CHHO), 5.64 (d, 1H, J = 9.6 Hz, NH), 7.03 (s, 1H, CHCSO2), 7.25-7.33 (m, 6H, arom. CH), 7.39-
7.49 (m, 2H, arom CH), 7.61 (d, 1H, J = 7.5 Hz, arom CH) ppm; 13C NMR (100 MHz, CDCl3) δ = 26.84
(CH3), 35.31 (CH3C), 59.23 (CHN), 66.97 (CH2O), 120.98, 124.78, 127.79 127.85, 128.24, 129.96 (arom
CH, CHCSO2), 130.15 (CSO2), 133.37 (arom CH), 136.00, 136.64, 142.98 (arom C), 155.67 (C=O) ppm.
IR (KBr) ῦ = 3350 (s), 2964 (s), 1702 (vs), 1527 (vs), 1455 (s), 1300 (vs), 1235 (vs), 1149 (vs), 1126 (s),
1067 (m), 1009 (m), 756 (s), 548 (m) cm−1; MS (EI, 70 eV) m/z (%) = 385 (1) [M+•], 284 (6), 268 (10),
239 (11), 238 (88), 195 (6), 194 (56), 137 (5), 92 (5), 91 (100), 65 (7), 57 (12). Anal. Calcd for
C21H23NO4S: C, 65.43; H, 6.01; N, 3.63. Found: C, 65.42, H, 6.24; N, 3.55.
(S)-[1-(1,1-Dioxo-1H-1λ6-benzo[b]thiophen-2-yl)pentyl]carbamic acid benzyl ester (3d): To a well
stirred solution of carbamate (2d) (353 mg, 1.0 mmol) in 54 mL of a H2O/CH2Cl2/acetone (1:0.9:0.8)

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mixture, were added 1.2 g of NaHCO3 followed by 2 g of oxone according to GP2. After work-up,
removal of the solvent in vacuo afforded 377 mg of 3d (98%) as a colorless foam. ee = 93%. [α] 2D2 = –
1
52.7 (c = 1.4, CHCl3). H NMR (400 MHz, CDCl3) δ = 0.90 (t, 3H, J = 7.2 Hz, CH3), 1.34-1.47 (m, 4H,
CH3CH2CH2), 1.85-1.96 (m, 1H, CHHCHN), 2.01-2.09 (m, 1H, CHHCHN), 4.79-4.85 (m, 1H, CHNH,),
5.07 (d, 1H, JAB = 12.1 Hz, CHHO), 5.14 (d, 1H, JAB = 12.1 Hz, CHHO), 5.45 (d, 1H, J =8.5 Hz, NH),
6.97 (s, 1H, CHCSO2), 7.26-7.33 (m, 6H, arom. CH), 7.42-7.52 (m, 2H, arom CH), 7.64 (d, 1H, J = 7.4
Hz, arom CH) ppm; 13C NMR (100 MHz, CDCl3) δ = 14.08 (CH3), 22.34 (CH3CH2), 28.20
(CH3CH2CH2), 32.82 (CH2CHN), 49.90 (CHN), 67.13 (CH2O), 121.22, 125.05, 127.85 128.06, 128.14,
128.50, 130.07 (arom CH, CHCSO2), 130.56 (CSO2), 133.63 (arom CH), 136.24, 137.38, 143.73 (arom
C), 155.63 (C=O) ppm. IR (KBr) ῦ = 3418 (vs), 2956 (s), 2930 (s), 2856 (s), 1705 (s), 1527 (s), 1456 (m),
1384 (m), 1301 (s), 1258 (s), 1149 (s), 1123 (s), 1037 (m), 755 (s), 699 (m) cm−1; MS (CI, 100 eV,
methane) m/z (%) = 386 (6) [M+•+1], 342 (6), 238 (5), 237 (35), 236 (6), 235 (35), 217 (6), 119 (6), 108
(7), 107 (14), 93 (6), 92 (10), 91 (100), 79 (23). Anal. Calcd for C21H23NO4S: C, 65.43; H, 6.01; N, 3.63.
Found: C, 65.37, H, 6.10; N, 3.60.
(S)-[1-(1,1-Dioxo-1H-1λ6-benzo[b]thiophen-2-yl)-2-phenylpropyl]carbamic acid benzyl ester (3e):
To a well stirred solution of carbamate (2e) (401 mg, 1.0 mmol) in 54 mL of a H2O/CH2Cl2/acetone
(1:0.9:0.8) mixture, were added 1.2 g of NaHCO3 followed by 2 g of oxone according to GP2. After
work-up, removal of the solvent in vacuo afforded 425 mg of 3e (98%) as a colorless solid; mp = 43-44°C
1
(Et2O:pentane 1:5). ee = 95%. [α] 22 = –50.2 (c = 1.2, CHCl3). H NMR (300 MHz, CDCl3) δ = 2.19 (m,
D
2H, CH2CH), 2.73 (t, 2H, J = 7.4 Hz, PhCH2), 4.82-4.85 (m, 1H, CHNH,), 5.05 (d, 1H, JAB = 12.3 Hz,
CHHO), 5.13 (d, 1H, JAB = 12.3 Hz, CHHO), 5.66 (d, J = 8.4 Hz, NH), 6.93 (s, 1H, CHCSO2), 7.17-7.48
13
(m, 13H, arom CH), 7.60 (d, 1H, J = 7.4 Hz, arom CH) ppm.; C NMR (75 MHz, CDCl3) δ = 31.03
(PhCH2), 34.62 (CH2CHN), 49.74 (CHN), 67.15 (CH2O), 121.28, 125.25, 126.30 128.15, 128.26, 128.47,
128.59, 128.65, 130.25 (arom CH, CHCSO2), 130.56 (CSO2), 133.79 (arom CH), 136.32, 137.37, 140.58,
143.26 (arom C), 155.79 (C=O) ppm. IR (KBr) ῦ = 3335 (m), 3062 (m), 3027 (s), 2951 (m), 1711 (vs),
1522 (vs), 1454 (s), 1300 (vs), 1240 (vs), 1149 (vs), 1047 (s), 756 (vs), 701 (s) cm−1; MS (EI, 70 eV) m/z
(%) = 386 (6) [M+•+1], 342 (6), 238 (5), 237 (35), 236 (6), 235 (35), 217 (6), 119 (6), 108 (7), 107 (14),
93 (6), 92 (10), 91 (100), 79 (23). Anal. Calcd for C25H23NO4S: C, 69.26; H, 5.35; N, 3.23. Found: C,
69.29, H, 5.53; N, 3.09.
(S)-[1-(1,1-Dioxo-1H-1λ6-benzo[b]thiophen-2-yl)phenylmethyl]carbamic acid benzyl ester (3f): To a
well stirred solution of carbamate (2f) (375 mg, 1.0 mmol) in 54 mL of a H2O/CH2Cl2/acetone (1:0.9:0.8)

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mixture, were added 1.2 g of NaHCO3 followed by 2 g of oxone according to GP2. After work-up,
purification by column flash chromatography (Et2O:pentane = 3:1) afforded 390 mg of 3f (96%) as a
1
colorless solid; mp = 63-65°C (Et2O:pentane 1:5). ee = 88%. [α] 22 = –22.0 (c = 1.5, CHCl3). H NMR
D
(300 MHz, CDCl3) δ = 5.09 (s, 1H, CH2O), 5.99-6.03 (br, 2H, CHN, NH), 6.64 (s, 1H, CHCSO2), 7.10-
13
7.49 (m, 13H, arom CH), 7.60-7.63 (m, 1H, arom CH) ppm; C NMR (75 MHz, CDCl3) δ = 51.17
(CHN), 66.23 (CH2O), 120.36, 124.20, 126.18 127.10, 127.44, 127.61, 128.00 (arom CH, CHCSO2),
129.03 (CSO2), 129.26 132.65 (arom CH), 135.03, 136.33, 136.45, 142.86 (arom C), 154.34 (C=O) ppm.
IR (KBr) ῦ = 3430 (vs), 1718 (vs), 1523 (s), 1455 (m), 1303 (vs), 1243 (s), 1149 (vs), 1127 (m), 757 (m),
702 (s), 545 (m) cm−1; MS (EI, 70 eV) m/z (%) = 405 (1) [M+•], 271 (12), 270 (67), 256 (14), 250 (11),
240 (12), 233 (6), 210 (6), 208 (5), 207 (6), 206 (8), 205 (6), 204 (13), 196 (5), 191 (6), 189 (7), 180 (5),
179 (11), 178 (11), 165 (9), 137 (10), 108 (7), 106 (6), 104 (7), 92 (9), 91 (100), 89 (5), 79 (8), 77 (13), 65
(9), 51 (6). Anal. Calcd for C23H19NO4S: C, 68.13; H, 4.72; N, 3.45. Found: C, 68.26, H, 4.92; N, 3.38.
(S)-[1-(1,1-Dioxo-1H-1λ6-benzo[b]thiophen-2-yl)-(4-methoxyphenyl)methyl]carbamic acid benzyl
ester (3g): To a well stirred solution of carbamate (2g) (405 mg, 1.0 mmol) in 54 mL of a
H2O/CH2Cl2/acetone (1:0.9:0.8) mixture, were added 1.2 g of NaHCO3 followed by 2 g of oxone
according to GP2. After work-up, purification by column flash chromatography (Et2O:pentane = 3:1)
afforded 385 mg of 3g (88%) as a colorless solid; mp = 60-62°C (Et2O:pentane 1:5). ee = 66%. [α] 22 = –
D
1
2.5 (c = 1.0 CHCl3). H NMR (400 MHz, CDCl3) δ = 3.79 (s, 3H, OCH3), 5.11 (s, 2H, CH2O), 5.80-5.84
(br, 1H, NH), 5.96-6.00 (br, 1H, CHN), 6.67 (s, 1H, CHCSO2), 6.88-6.92 (m, 2H, arom CH), 7.18-7.36
13
(m, 13H, arom CH), 7.44 (ddt, 2H, J = 1.1, 7.4, 21.4, arom CH), 7.61-7.63 (m, 1H, arom CH) ppm; C
NMR (100 MHz, CDCl3) δ = 51.73 (CHN), 55.19 (OCH3), 67.10 (CH2O), 114.20, 121.17, 124.96 127.90,
128.25, 128.32, 128.55 (arom CH, CHCSO2), 129.29, 129.94 (CSO2, arom C), 129.99 133.41 (arom CH),
135.91, 137.27, 144.09 (arom C), 155.06 (C=O), 159.48 (arom C) ppm. IR (KBr) ῦ = 3349 (m), 1717 (vs),
1512 (vs), 1457 (m), 1303 (vs), 1248 (vs), 1148 (vs), 1125 (m), 835 (m), 757 (s), 700 (m), 546 (m) cm−1;
MS (EI, 70 eV) m/z (%) = 344 (10), 327 (14), 301 (11), 236 (6), 137 (6), 135 (5), 109 (8), 108 (9), 107 (6),
91 (37), 79 (8), 77 (8). Anal. Calcd for C24H21NO5S: C, 66.19; H, 4.86; N, 3.22. Found: C, 66.15, H, 5.18;
N, 3.05.
(1S,2R)-[1-(1,1-Dioxo-2,3-dihydro-1H-1λ6-benzo[b]thiophen-2-yl)propyl]carbamic acid benzyl ester
(4a) was prepared according to GP3 or GP4. Purification via column flash chromatography
(AcOEt:pentane = 1:2) afforded a colorless solid; mp = 101-103°C (Et2O:pentane 1:3). GP3 starting from
140 mg (0.39 mmol) of 3a yielded 125 mg (89%) of 4a; ee = 93%, de ≥ 96% (determined by 1H and 13C

HETEROCYCLES, Vol. 64, 2004
115
NMR spectroscopy). GP4 starting from 140 mg (0.39 mmol) of 3a yielded 93 mg (66%) of 4a. ee = 93%,
1
13
1
de ≥ 96% (determined by H and C NMR spectroscopy). [α] 22 = –9.4 (c = 1.0, CHCl3). H NMR (300
D
MHz, CDCl3), (signals of carbamate E/Z isomers are reported) δ = 0.98 (t, < 3H, J = 7.2 Hz, CH3), 1.06 (t,
< 3H, J = 7.2 Hz, CH3), 1.80-2.04 (m, 2H, CH3CH2), 3.24-3.37 (m, 2H, CH2CHSO2), 3.64 (q, < 1H, J =
8.2 Hz, CHSO2), 3.77 (dt, < 1H, J = 4.2, 8.5 Hz, CHSO2), 4.07-4.18 (m, 1H, CHN), 5.01-5.13 (m, 2H,
NH, CH2OC=O), 5.23 (d, 1H, J = 9.2 Hz, NH), 5.79 (d, 1H, J = 10.1 Hz, NH) 7.25-7.38 (m, 6H, arom
13
CH), 7.39-7.46 (m, 1H, arom CH), 7.51-7.58 (m, 1H, arom CH), 7.65-7.71 (m, 1H, arom CH) ppm; C
NMR (100 MHz, CDCl3) δ = 10.39, 11.13 (CH3), 25.38, 26.80 (CH3CH2), 29.82, 30.71 (CH2CHSO2),
52.65, 53.08 (CHN), 63.57, 65.01 (CHSO2), 66.95, 67.08 (CH2OC=O), 121.91, 121.63, 127.03 127.20,
127.92 128.16, 128.33, 128.54, 128.64, 128.77, 128.85, 133.60, 133.65 (arom CH), 136.34, 136.41,
139.00, 139.44 ( arom C), 156.21, 156.82 (C=O) ppm. IR (KBr) ῦ = 3346 (s), 2966 (m), 1686 (vs), 1527
(vs), 1457 (m), 1290 (vs), 1243 (s), 1151 (s), 1125 (m), 1098 (m), 757 (m), 543 (m) cm−1; MS (EI, 70 eV)
m/z (%) = 359 (7) [M+•], 108 (42), 92 (5), 91 (100), 58 (5). Anal. Calcd for C19H21NO4S: C, 63.49; H,
5.89; N, 3.90. Found: C, 63.79, H, 5.51; N, 3.88.
(1S,2R)-[1-(1,1-Dioxo-2,3-dihydro-1H-1λ6-benzo[b]thiophen-2-yl)-2-methylpropyl]carbamic acid
benzyl ester (4b): To a well stirred solution of the ß-aminosulfone (3b) (185 mg, 0.5 mmol) in 5 mL of
THF at – 78°C, was added dropwise 1.0 mL of L-selectride® (1M solution in THF) according to GP4.
After work-up, purification by flash chromatography (Et2O:pentane = 1:2) afforded 108 mg of 4b (58%)
13
as a colorless foam. ee = 99%, de ≥ 96% (determined by 1H and C NMR spectroscopy). [α] 2D2 = – 39.9
1
(c = 1.0, CHCl3). H NMR (300 MHz, CDCl3), (signals of carbamate E/Z isomers are reported) δ = 0.96
(d, < 6H, J = 6.6 Hz, CH3), 1.01 (d, < 6H, J = 6.6 Hz, CH3), 2.22-2.46 (m, 1H, CH3CH), 3.24-3.30 (m, 2H,
CH2CHSO2), 3.59 (q, < 1H, J = 8.9 Hz, CHSO2), 3.71-4.00 (m, < 2H, CHN, CHSO2), 4.33 (dt, < 1H, J =
2.7, 10.2 Hz, CHN), 5.00-5.13 (m, 2H, CH2O), 5.18 (br, 1H, NH), 5.85 (d, 1H, J = 10.2 Hz, NH), 7.22-
7.41 (m, 7H, arom CH), 7.47-7.54 (m, 1H, arom CH), 7.63 (t, 1H, J = 7.9 Hz, arom CH) ppm; 13C NMR
(75 MHz, CDCl3) δ = 15.29, 19.89, 20.25, 20.57 (CH3), 29.91 (CH3CH), 30.16, 30.97 (CH2CHSO2),
31.58 (CH3CH), 55.18, 57.27 (CHN), 61.39, 63.03 (CHSO2), 66.95, 67.17 (CH2O), 121.43, 121.66,
127.04, 127.88, 128.13, 128.21, 128.35, 128.54, 128.66, 133.46, 133.64 (arom CH), 136.18, 136.42,
136.50, 139.02, 139.64 ( arom C), 156.54, 157.02 (C=O) ppm. IR (KBr) ῦ = 3350 (m), 3023 (m), 2965
(m), 1711 (vs), 1523 (s), 1457 (m), 1296 (s), 1242 (s), 1151 (s), 1121 (m), 757 (vs), 574 (m), 533 (m)
cm−1; MS (EI, 70 eV) m/z (%) = 373 (15) [M+•], 330 (10), 287 (5), 286 (47), 266 (7), 108 (10), 92 (12), 91
(100), 65 (7). Anal. Calcd for C20H23NO4S: C, 64.32; H, 6.21; N, 3.75. Found: C, 64.34, H, 6.11; N, 3.48.

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HETEROCYCLES, Vol. 64, 2004
(1S,2R)-[1-(1,1-Dioxo-2,3-dihydro-1H-1λ6-benzo[b]thiophen-2-yl)-2,2-dimethylpropyl]carbamic
acid benzyl ester (4c) Prepared according to GP3 or GP4. Purification via flash column chromatography
(Et2O:pentane = 2:1) afforded a colorless solid; mp = 56-57°C (Et2O:pentane = 1:5). GP3 starting from
1
200 mg of ß-aminosulfone (3c) yielded 81 mg (40%) of 4c. ee = 91%, de ≥ 96% (determined by H and
13C NMR spectroscopy). GP4 starting from 200 mg of ß-aminosulfone (3c) yielded 121 mg (60%) of 4c.
ee = 91%, de ≥ 96% (determined by 1H and 13C NMR spectroscopy). [α] 22 = –8.9 (c = 1.3, CHCl3). mp =
D
1
56-57°C (Et2O:pentane = 1:5). H NMR (300 MHz, CDCl3), (signals of carbamate E/Z isomers are
reported) δ = 0.98, 1.03 (s, 9H, (CH3)3C), 3.08 (d, < 2H, J = 7.2 Hz, CH2CHSO2), 3.27 (ddd, < 2H, J =
7.9, 16.3, 37.1 Hz, CH2CHSO2)*, 3.48-3.58 (m, < 1H, CHSO2) 3.61-3.67 (m, < 1H, CHSO2), 4.37 (d, <
1H, J = 10.1 Hz, CHN), 4.42 (dd, < 1H, J = 3.2, 10.9 Hz, CHN), 4.94-5.13 (m, < 3H, CH2O, NH), 6.49 (d,
< 1H, J = 11.1 Hz, NH), 7.05 (d, < 1H, J = 7.1 Hz, arom CH), 7.24-7.55 (m, 9H, arom CH), 7.66 (d, < 1H,
13
J = 7.4 Hz, arom CH) ppm. C NMR (75 MHz, CDCl3) δ = 26.60 (CH3)3C, 28.82, 29.54 (CH2CHSO2),
35.72 (CH3C), 55.79, 55.95 (CHN), 61.56 (CHSO2), 66.87, 67.10 (CH2O), 121.13, 121.64, 126.84,
127.19, 127.86, 128.06 128.30, 128.43 128.59, 133.27 (arom CH), 136.25, 136.40, 136.78, 137.98,
138.56 (arom C), 155.89, 156.97 (C=O) ppm. IR (KBr) ῦ = 3347 (s), 3046 (m), 3026 (s), 2963 (vs), 2876
(m), 1706 (vs), 1534 (vs), 1472 (m), 1454 (m), 1298 (s), 1241 (s), 1152 (vs), 1122 (s), 1059 (s), 1012 (m),
756 (vs), 700 (s), 586 (s) cm−1; MS (EI, 70 eV) m/z (%) = 387 (12) [M+•], 330 (27), 313 (8), 288 (5), 287
(11), 286 (67), 196 (10), 130 (5), 130 (5), 92 (13), 91 (100), 65 (8). Anal. Calcd for C21H25NO4S: C,
65.09; H, 6.50; N, 3.61. Found: C, 64.80, H, 6.38; N, 3.50.
(1S,2S)-[1-(1,1-Dioxo-2,3-dihydro-1H-1λ6-benzo[b]thiophen-2-yl)-2,2-dimethylpropyl]carbamic acid
benzyl ester (4c): GP3 60 mg (30%). mp = 59-60°C (Et2O:pentane = 1:5). ee = 91%, de ≥ 96%
1
13
1
(determined by H and C NMR spectroscopy). [α] 22 = –12.3 (c = 1.0, CHCl3). H-NMR (400 MHz,
D
CDCl3): δ = 1.16 (s, 9H, (CH3)3C), 3.35 (d, 2H, J = 8.9 Hz, CH2CHSO2), 3.93 (dt, 1H, J = 2.7, 8.9 Hz,
CHSO2) 4.10 (dd, 1H, J = 2.7, 10.7 Hz, CHN), 5.05 (d, 1H, JAB = 12.3 Hz, CHHO), 5.15 (d, 1H, JAB
=
12.3 Hz, CHHO), 6.25 (d, 1H, J = 10.7 Hz, NH), 7.27-7.34 (m, 9H, arom CH), 7.44 (t, 1H, J = 7.4 Hz,
arom CH), 7.56 (dt, 1H, J = 1.1, 7.4 Hz, arom CH) 7.68 (d, 1H, J = 8.0 Hz, arom CH) ppm. 13C-NMR (75
MHz, CDCl3): δ = 27.24 (CH3), 31.64 (CH2CHSO2), 35.89 (CH3C), 60.39 (CHN), 60.50 (CHSO2), 66.90
(CH2O), 121.35, 126.70, 127.68, 127.87, 128.27, 128.62, 133.29 (arom CH), 136.07, 136.13, 139.01
(arom C), 156.97 (C=O) ppm. IR (KBr): ῦ = 3421 (vs), 2963 (vs), 1722 (vs), 1513 (vs), 14724 (s), 1456
(m), 1337 (m), 1336 (m), 1301 (m), 1253 (vs), 1149 (vs), 1120 (vs), 1061 (vs), 1019 (s), 803 (s), 753 (vs),
699 (s), 541 (s). MS (EI, 70 eV): m/z (%) = 387 (2) [M+•], 330 (12), 313 (6), 287 (5), 286 (33), 222 (5),

HETEROCYCLES, Vol. 64, 2004
117
196 (5), 92 (8), 91 (100), 57 (6). Anal. Calcd for C21H25NO4S: C, 65.09; H, 6.50; N, 3.61. Found: C,
64.98, H, 6.41; N, 3.48.
(1S,2R)-[1-(1,1-Dioxo-2,3-dihydro-1H-1λ6-benzo[b]thiophen-2-yl)pentyl]carbamic acid benzyl ester
(4d): Prepared according to GP3 or GP4. Purification via column flash chromatography (Et2O:pentane =
1:2) afforded a colorless solid; mp = 82-84°C (Et2O:pentane = 1:5). GP3 starting from 190 mg (0.49
mmol) of ß-aminosulfone (3d) yielded 150 mg (79%) of 4d. ee = 93%, de ≥ 96% (determined by 1H and
13C NMR spectroscopy). GP4 starting from 190 mg (0.49 mmol) of ß-aminosulfone (3d) yielded 134 mg
(70%) of 4d. ee = 93%, de ≥ 96% (determined by 1H and 13C NMR spectroscopy). [α] 2D2 = –14.2 (c = 1.7,
1
CHCl3). H NMR (300 MHz, CDCl3), (signals of the major carbamate E/Z isomer are reported) δ = 0.86
(t, 3H, J = 6.7 Hz, CH3), 1.21-1.43 (m, 4H, CH3CH2, CH3CH2CH2), 1.55-1.72 (m, 1H, CHHCHNH),
1.79-1.92 (m, 1H, CHHCHNH), 3.17-3.38 (m, 2H, CH2CHSO2), 3.62 (q, 1H, J = 8.2 Hz, CHSO2), 4.09-
4.20 (m, 1H, CHN), 5.12 (s, 2H, CH2O), 5.24 (d, 1H, J = 9.4 Hz, NH), 7.25-7.43 (m, 7H, arom CH),
13
7.49-7.55 (m, 1H, arom CH), 7.65-7.69 (m, 1H, arom CH) ppm; C NMR (75 MHz, CDCl3) δ = 13.93
(CH3), 22.12 (CH3CH2), 27.91 (CH3CH2CH2), 30.61 (CH2CHSO2), 32.00 (CH2CHN), 51.45 (CHN),
65.23 (CHSO2), 66.95 (CH2O), 121.52, 126.97, 128.05 128.25, 128.57 128.69, 133.52 (arom CH), 136.14,
136.34, 139.40 ( arom C), 156.10 (C=O) ppm. IR (KBr) ῦ = 3402 (s), 2958 (m), 2928 (m), 1717 (vs),
1527 (vs), 1452 (m), 1298 (vs), 1238 (s), 1152 (s), 1114 (m), 1014 (m), 756 (s), 699 (m), 586 (s), 552 (m)
cm−1; MS (EI, 70 eV) m/z (%) = 387 (8) [M+•], 286 (7), 176 (7), 130 (5), 108 (33), 91 (100), 65 (5). Anal.
Calcd for C21H25NO4S: C, 65.09; H, 6.50; N, 3.61. Found: C, 64.79, H, 6.15; N, 3.48.
(1S,2R)-[1-(1,1-Dioxo-2,3-dihydro-1H-1λ6-benzo[b]thiophen-2-yl)-3-phenylpropyl]carbamic acid
benzyl ester (4e): Prepared according to GP3 or GP4. Purification via column flash chromatography
(Et2O:pentane = 1:2) afforded a colorless solid; mp = 123-125°C (Et2O:pentane = 1:5). GP3 starting from
250 mg (0.58 mmol) of ß-aminosulfone (3e) yielded 220 mg (87%) of 4e. ee = 95%, de ≥ 96%
1
(determined by H and 13C NMR spectroscopy). GP4 starting from 250 mg (0.58 mmol) of ß-
1
13
aminosulfone (3e) yielded 175 mg (70%) of 4e. ee = 95%, de ≥ 96% (determined by H and C NMR
1
spectroscopy). [α] 22 = –8.0 (c = 1.0, CHCl3). H NMR (300 MHz, CDCl3), (signals of carbamate E/Z
D
isomers are reported) δ = 2.04-2.51 (m, 2H, CH2CHNH), 2.66-2.89 (m, 2H, PhCH2), 3.13-3.32 (m, 2H,
CH2CHSO2), 3.72-3.80 (m, 1H, CHSO2) 4.18-4.35 (m, 1H, CHN), 5.06-5.18 (m, 2H, CH2O), 5.36 (d, <
1H, J = 9.1 Hz, NH), 5.90 (d, < 1H, J = 9.9 Hz, NH), 7.16-7.72 (m, 14H, arom CH) ppm; 13C NMR (75
MHz, CDCl3) δ = 29.76, 30.59 (PhCH2), 32.24, 32.71 (CH2CHSO2), 33.50, 35.27 (CH2CHNH), 50.56,
51.45 (CHN), 64.00, 64.98 (CHSO2), 67.05, 67.15 (CH2O), 121.49, 121.64, 126.20, 126.26, 127.04,

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HETEROCYCLES, Vol. 64, 2004
127.24, 127.99, 128.23, 128.40, 128.52, 128.55, 128.60, 128.64, 128.68, 128.84, 128.89, 133.66, 133.71
(arom CH), 136.16, 136.34, 136.37, 138.91, 139.39, 140.76 (arom C), 156.06, 156.71 (C=O) ppm. IR
(KBr) ῦ = 3347 (m), 3030 (m), 1714 (vs), 1526 (vs), 1453 (s), 1296 (vs), 1244 (vs), 1151 (vs), 1123 (s),
1054 (m), 911 (s), 734 (vs), 700 (s), 590 (m), 543 (m) cm−1; MS (EI, 70 eV) m/z (%) = 435 (3) [M+•], 344
(15), 327 (10), 284 (10), 283 (47), 218 (6), 196 (40), 137 (12), 130 (6), 129 (15), 117 (8), 116 (5), 115
(11), 108 (10), 107 (5), 105 (7), 104 (8), 92 (8), 91 (100), 79 (12), 77 (13). Anal. Calcd for C25H25NO4S:
C, 68.94; H, 5.79; N, 3.22. Found: C, 69.09, H, 5.74; N, 3.16.
(1S,2R)-[1-(1,1-Dioxo-2,3-dihydro-1H-1λ6-benzo[b]thiophen-2-yl)phenylmethyl]carbamic acid
benzyl ester (4f): Prepared according to GP3 or GP4. Purification via column flash chromatography
(Et2O:pentane = 1:2) afforded a colorless solid; mp = 55-57°C (Et2O:pentane = 1:5). GP3 starting from
1
13
260 mg (0.64 mmol) of 3f yielded 155 mg (60%) of 4f. ee = 88%, de ≥ 90% (determined by H and C
NMR spectroscopy). GP4 starting from 260 mg (0.64 mmol) of 3f yielded 210 mg (80%) of 4f. ee = 88%,
de ≥ 96% (determined by 1H and 13C NMR spectroscopy). [α] 22 = –16.1 (c = 2.0, CHCl3). 1H NMR (300
D
MHz, CDCl3), (signals of carbamate E/Z isomers are reported) δ = 2.99-3.08 (m, < 2H, CH2CHSO2),
3.23-3.40 (m, 2H, CH2CHSO2), 3.13-3.32 (m, < 2H, CH2CHSO2), 3.95 (q, 1H, J = 7.9 Hz, CHSO2) 5.02-
5.08 (m, 2H, CH2O), 5.26-5.35 (m, 1H, CHN), 5.78 (d, < 1H, J = 8.9 Hz, NH), 6.33 (d, < 1H, J = 8.9 Hz,
13
NH), 7.16-7.64 (m, 14H, arom CH) ppm; C NMR (75 MHz, CDCl3) δ = 30.70, 31.00 (CH2CHSO2),
54.75, 54.96 (CHN), 64.93, 65.45 (CHSO2), 67.09, 67.25 (CH2O), 121.54, 127.03, 127.09, 127.66,
127.86, 128.00, 128.11, 128.22, 128.36, 128.44, 128.55, 128.62, 128.78, 128.84, 129.00, 133.33, 133.48
(arom CH), 135.61, 135.87, 136.29, 136.36, 138.13, 138.75, 139.52, 139.68 (arom C), 155.75 (C=O) ppm.
IR (KBr) ῦ = 3347 (m), 1717 (vs), 1522 (s), 1454 (m), 1303 (vs), 1243 (s), 1149 (vs), 1126 (m), 757 (s),
701 (s), 545 (m) cm−1; MS (EI, 70 eV) m/z (%) = 407 (1) [M+•], 271 (9), 270 (54), 256 (12), 250 (10), 240
(16), 210 (5), 208 (6), 207 (5), 206 (7), 205 (5), 204 (8), 196 (9), 180 (5), 179 (16), 178 (8), 165 (7), 137
(9), 108 (10), 107 (8), 104 (5), 92 (7), 91 (100), 79 (6), 77 (8), 65 (6). Anal. Calcd for C23H21NO4S: C,
67.79; H, 5.19; N, 3.44. Found: C, 67.32, H, 4.97; N, 3.42.
(1S,2R)-1-(1,1-Dioxo-2,3-dihydro-1H-1λ6-benzo[b]thiophen-2-yl)-2,2-dimethylpropanamine (5c):
ß-Aminosulfone (4c) (190 mg, 0.49 mmol) was dissolved in dry EtOH (30 mL) and the mixture was
hydrogenated using 10% Pd/C (60 mg) as catalyst at 4 atm. After 16 h, the solution was neutralized with
solid Na2CO3 and the catalyst was filtered off. The solvent was evaporated in vacuo to give 120 mg of 5c
1
(96%) as a colorless solid. mp = 56-57°C (Et2O:pentane = 1:1). ee = 91%, de ≥ 96% (determined by H
and 13C NMR spectroscopy). [α] 22 = – 29.6 (c = 1.4, CHCl3). 1H NMR (300 MHz, CDCl3) δ = 1.03 (s, 9H,
D

HETEROCYCLES, Vol. 64, 2004
119
CH3), 1.39-1.43 (br, 2H, NH2), 3.21 (dd, 1H, J = 8.2, 16.2 Hz, CHHCHSO2), 3.50 (d, 1H, J = 0.9 Hz,
CHNH), 3.71 (t, 1H, J = 8.2 Hz CHSO2), 3.79 (dd, 1H, J = 8.2, 16.2 Hz, CHHCHSO2), 7.32-7.47 (m, 2H,
13
arom CH), 7.56 (dt, 1H, J = 1.2, 7.4 Hz, arom CH), 7.73 (d, 1H, J = 7.4 Hz, arom CH) ppm; C NMR
(75 MHz, CDCl3) δ = 26.64 (CH2), 27.08 (CH3), 34.97 (CH3C), 55.49 (CHN), 62.41 (CHSO2), 121.53,
127.38, 128.54, 133.46 (arom CH), 137.58, 137.98 (arom C) ppm. IR (KBr) ῦ = 3390 (m), 2959 (s), 2870
(m), 1601 (m), 1472 (m), 1454 (m), 1294 (vs), 1151 (vs), 1121 (s), 756 (vs), 587 (s), 550 (s) cm−1; MS
(CI, 100 eV, isobutane): m/z (%) = 255 (16) [M+•+2], 254 (100) [M+•+1], 237 (5), 197 (6), 196 (16). Anal.
Calcd for C13H19NO2S: C, 61.63; H, 7.56; N, 5.53. Found: C, 61.64, H, 7.62; N, 5.35.
REFERENCES AND NOTES
1
The Chemistry of Sulphones and Sulphoxides, ed. by S. Patai, Z. Rappoport, and C. Stirling, John
Wiley & Sons, Chichester, 1988.
2
3
N. S. Simpkins, Sulphones in Organic Synthesis, Pergamon, Oxford, 1993.
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Topics in Current Chemistry, Springer–Verlag, Berlin, Heidelberg 1999, Vol. 205, p. 132.
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1968, 1, 209. c) Clough, J. M. in Comprehensive Organic Synthesis, ed. by B. Trost and I.
Fleming, Pergamon, Oxford, 1991, Vol. 6, Chapter 3.
4
5
a) See for example: a) J. D. Buynak, L. Vogeti, and H. Chen, Org. Lett., 2001, 3, 2953 and
references cited therein; b) T. Patonay, W. Adam, A. Levai, P. Köver, M. Nemeth, E.-M. Peters,
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Ghosh, W. J. Thompson, P. M. Munson, W. Liu, and J. R. Huff, Bioorg. Med. Chem. Lett., 1995,
5, 83 and references cited therein.
6
7
D. H. Boschelli, J. B. Kramer, D. T. Connor, M. E. Lesch, D. J. Schrier, M. A. Ferin, and C. D.
Wright, J. Med. Chem., 1994, 6, 717.
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302550); c) H.-L. Elbe, R. Tiemann, H.-W. Dehne, S. Dutzmann, and M. Kugler, Ger. Offen.
DE4411912 (Bayer AG) (Chem. Abstr., 1995, 124, 175811); d) H.-L. Elbe, and K. Schaller, Ger.
Offen. DE3832848 (Bayer AG) (Chem. Abstr., 1990, 113, 37687).
8
9
M. Baumgarth, N. Beier, and R. Gericke, J. Med. Chem., 1998, 41, 3736.
a) F. Sauter, P. Stanetty, U. Jordis, E. Hetzl, and D. Konstantinou, Arch. Pharm. (Weinheim),
1982, 315, 912; b) F. Sauter, U. Jordis, P. Stanetty, G. Hüttner, and L. Otruba, Arch. Pharm.
(Weinheim), 1981, 314, 567.
10
11
a) D. Enders, S. F. Müller, G. Raabe, and J. Runsink, Eur. J. Org. Chem., 2000, 6, 879; b) D.
Enders, S. F. Müller, and G. Raabe, Synlett, 1999, 741; c) D. Enders, S. F. Müller, and G. Raabe,
Angew. Chem., 1999, 111, 212; Angew. Chem., Int. Ed., 1999, 38, 195.
For a review see: A. Job, C. F. Janeck, W. Bettray, R. Peters, and D. Enders, Tetrahedron, 2002,
58, 2253.
12
13
14
D. Enders, R. Lochtman, M. Meiers, S. F. Müller, and R. Lazny, Synlett, 1998, 1182.
D. Enders, and G. Del Signore, Tetrahedron: Asymmetry, 2004, in press.
J. C. Swarts, E. H. G. Langner, N. Krokeide-Hove, and M. J. Cook, J. Mater. Chem., 2001, 11,
434.