1,2-epimino-3,4-epoxybutane: A versatile chiral building block

Article abstract of DOI:10.1055/s-2001-12359

The synthesis of enantiomerically pure 1,2-epimino-3,4-epoxy-(N-toluenesulfonyl)butane (6) in the S,R-(erythro) and R,R-(threo) configurations is described. This building block offers a new route to targets with an 1,2-aminohydroxy functionality. As an example, the new 1,4-biselectrophile is employed in a cyclopentane synthesis.

Full text of DOI:10.1055/s-2001-12359

PAPER
577
1,2-Epimino-3,4-epoxybutane: A Versatile Chiral Building Block
Guido Harms,a Ernst Schaumann,*a Gunadi Adiwidjajab
a Institut für Organische Chemie, Technische Universität Clausthal, Leibnizstraße 6, 38678 Clausthal-Zellerfeld, Germany
b Mineralogisch-Petrographisches Institut, Universität Hamburg, Grindelallee 48, 20146 Hamburg, Germany
Fax +49(5323)722858; E-mail: ernst.schaumann@tu-clausthal.de
Received 17 November 2000; revised 27 December 2000
lating agent and as a base in the deprotonation of the sul-
fonamide.
Abstract: The synthesis of enantiomerically pure 1,2-epimino-3,4-
epoxy-(N-toluenesulfonyl)butane (6) in the S,R-(erythro) and R,R-
(threo) configurations is described. This building block offers a new
route to targets with an 1,2-aminohydroxy functionality. As an ex-
ample, the new 1,4-biselectrophile is employed in a cyclopentane
synthesis.
COOMe
MeOOC
a)
MeOOC
TBSO
b)
NHTs
NHTs
HO
60%
92%
Key words: amino alcohols, domino reactions, epoxides, ring
COOMe
MeOOC
COOMe
opening, cyclopentanes
1
2a
3a
OH
OTs
NHTs
NTs
c)
d)
e)
NHTs
A vicinal aminohydroxy unit is a frequently encountered
feature in many natural products and in biologically active
synthetic molecules. Therefore, the asymmetric Sharpless
aminohydroxylation represents an important synthetic
tool.1 However, this approach gives access only to cis
configured -amino alcohols and yields vary depending
on the type of C=C bond which is aminohydroxylated. For
TBSO
TBSO
TsO
threo-5
99%
95%
65%
O
HO
threo-4
threo-6
Reagents and conditions: a) Chloramine T, K2OsO4•2H2O
(DHQ)2PHAL, H2O/MeCN (Ref. 6); b) TBSCl, imidazole; c)
Ca(BH4)2, EtOH/THF; d) TsCl, Me3N•HCl, Et3N; e) TBAF•3H2O
the synthesis of the corresponding trans compounds, ring Scheme 1
opening reactions of an aziridine with an oxygen
nucleophile2 or of an epoxide with a suitable nitrogen nu-
cleophile are recommended as methods of choice.3 We
now present an alternative where the vicinal arrangement
of oxygen and nitrogen functionalities in an activated
form is already present in the precursor as in 6. Thus, re-
actions with a wide range of carbon nucleophiles are pos-
sible, and, because of the different reactivities of
epoxides4 and aziridines,5 proceed with complete control
of chemoselectivity. Moreover, the stereoisomers of 6 can
be looked upon as 1,4-biselectrophiles and so invite to be
submitted to our silicon-based domino cyclisation.4
The synthesis of erythro-6 starts from diethyl threo-2,3-
epoxysuccinate (7), which is obtained from diethyl tar-
trate employing the method of Mori et al.9 This function-
alized epoxide is opened by chloramine T to give the
N-protected amino alcohol 2b in one step from epoxide 7
and not as usual in two steps.10 The following steps pro-
ceed in equally good yields as for the threo-compound to
give erythro-6 in 32% overall yield (Scheme 2). Of
course, use of the enantiomers of 2a or 7, respectively,
would give the mirror image molecules making all four
stereoisomers of 6 readily accessible.
We aimed at a method which would allow access to both
diastereomers of 6 in enantiomerically pure form and, for
convenience, to use the diastereomers of the same precur-
sor molecule. Actually, dialkyl 3-hydroxy-2-(tosyl)ami-
nosuccinates 2 turned out to open a route to the
diastereomers of 6. Thus, threo-6 is readily available in
five steps from dimethyl fumarate (Scheme 1). Asymmet-
ric aminohydroxylation of dimethyl fumarate 1 leads to
aminohydroxylated succinate 2a.6 Silylation of 2a with
tert-butylchlorodimethylsilane under standard conditions
provides 3a, which is reduced in high yield with calcium
borohydride to give threo-4.7 For the tosylation of 4 the
method of Sakakura et al.8 turned out to be the only effi-
cient way to give the precursor threo-5 of the title com-
pound. Subsequent treatment with tetrabutylammonium
fluoride (TBAF) yields enantiomerically pure threo-6
(Scheme 1). Thus, TBAF acts simultaneousely as desily-
EtOOC
EtOOC
HO
EtOOC
TBSO
a)
b)
NHTs
COOEt
2b
NHTs
COOEt
3b
O
60%
92%
EtOOC
7
OH
NHTs
OTs
NHTs
NTs
c)
d)
97%
e)
65%
TBSO
TsO
erythro-5
TBSO
99%
HO
erythro-4
O
erythro-6
Reagents and conditions: a) Chloramine T; H2O/t-BuOH; b) TBSCl,
imidazole; c) Ca(BH4)2, EtOH/THF; d) TsCl, Me3N•HCl, Et3N; e)
TBAF•3H2O
Scheme 2
Synthesis 2001, No. 4, 577–580 ISSN 0039-7881 © Thieme Stuttgart · New York

578
G. Harms et al.
PAPER
CH correlated spectra. Melting points are uncorrected. Specific ro-
tations were recorded on a Perkin-Elmer 43B polarimeter. IR spec-
tra were recorded on a Bruker Vektor 22 FTIR spectrometer.
Elemental analyses were performed by the Institut für Phar-
mazeutische Chemie, Braunschweig. TLC was performed on Merck
60 F254 precoated silica plates and spots were detected by spraying
with a solution of 10% KMnO4 and 0.5 M Na2CO3 in H2O or 3% p-
methoxybenzaldehyde and 1% H2SO4 in MeOH and heating. Flash
chromatography was performed with silica gel 60 (Merck, 40 63
µm). Concentrations were performed on a rotary evaporator at
40 °C. Petroleum ether (PE) with the boiling range 60 70 °C was
used in the seperations. All solvents were distilled before use.
Building block erythro-6 was successfully employed in a
cyclopentane synthesis (Scheme 3). As expected based on
the pronounced difference in the reactivity of the epoxide
versus the aziridine ring, the formaldehyde equivalent 8
chemoselectively attacks the oxirane ring to give interme-
diate 9. Alkoxide 9 is obviously in equilibrium with silyl
ether 10 via a homo-Brook rearrangement. Contrary to
our earlier experience,4 intramolecular ring opening of the
aziridine unit by the carbanion in 10 does not occur spon-
taneously, but requires Lewis-acid assistance to give the
functionalized cyclopentane 11.
Diethyl (2R,3S)-2-Hydroxy-3-[(4-methylphenyl)sulfonylami-
no]succinate (2b)
Diethyl (2R,3R)-threo-2,3-epoxysuccinate (7;9 1.09 g, 5.8 mmol)
was dissolved in t-BuOH/H2O (40 mL) and chloramine T trihydrate
(8 g, 5 equiv) added. The solution was stirred for 7 d. When there
was no more starting material left (detected by TLC), the t-BuOH
was distilled from the reaction mixture under reduced pressure. The
aqueous residue was extracted with CH2Cl2 (4 î 40 mL) and the
combined organic layers washed with brine (2 î 20 mL) and dried
(MgSO4). The crude product was purified by flash chromatography
(PE/EtOAc, 5:1) to give colorless crystals (970 mg, 47%); mp 96
98 °C; [ ]D20 +30.3 (c = 1.03, CH2Cl2).
O
O
SMe
THF, -80°C
DMPU
TsN
SMe
SMe
+
TsN
SMe
TMS
6
TMS
8
9
MeS
SMe
OH
TMSO
SMe
SMe
.
~TMS
BF3 Et2O
TsN
42 %
TsHN
10
11
IR (KBr) : = 3475, 3279, 2957, 1746, 1438, 1341, 1162, 1092
cm .
1
Scheme 3
1H NMR (200 MHz): = 1.13 and 1.31 (t, 3 H, J = 7 Hz, CH2CH3),
2.42 (s, 3 H, ArCH3), 3.31 (d, 1 H, J = 6 Hz, OH), 4.01 and 4.07 (dq,
1 H, J = 11, 7 Hz, CH2CH3), 4.27 (q, 2 H, J = 7 Hz, CH2CH3), 4.40
(dd, 1 H, J = 3, 8 Hz, CHNHTos), 4.49 (dd, 1 H, J = 3, 6 Hz,
CHOH), 5.70 (d, 1 H, J = 8 Hz, NH), 7.31 (d, 2 H, J = 8 Hz, ArH),
7.77 (d, 2 H, J = 8 Hz, ArH).
The constitution and expected configuration of 11 were
confirmed by an X-ray structural investigation (Fig-
ure).11,12
13C NMR (50 MHz): = 13.79 and 14.03 (+, CH2CH3), 21.52 (+,
ArCH3), 58.86 (+, CNHTos), 62.46 ( , CH2CH3), 72.41 (+, COH),
127.21 and 129.71 (+, Carom), 136.58 and 143.87 (o, Carom), 167.52
and 170.77 (o, CO2Et).
Anal. calcd: C, 50.08; H, 5.84; N, 3.90; S, 8.93; found, C, 50.09; H,
5.82; N, 3.92; S, 8.90.
Dimethyl (2R,3R)-2-(tert-Butyldimethylsiloxy)-3-[(4-methyl-
phenyl)sulfonylamino]succinate (3a); Typical Procedure
Compound 2a6 (950 mg, 2.6 mmol) was dissolved in DMF (5 mL)
and imidazole (500 mg, 1.2 equiv) and TBDMSCl (471 mg,
1.2 equiv) were added. The mixture was stirred for 16 h at 35 °C.
H2O was added and the cloudy solution extracted with CH2Cl2
(5 î 20 mL), the combined CH2Cl2 layers were washed with H2O
(30 mL) and brine (30 mL), and dried (MgSO4). Filtration and con-
centration gave a crude oil that was purified by column chromatog-
raphy (PE/EtOAc, 3:1) to give the product as colorless crystals
(1.13 g, 85%); mp 103 106 °C; [ ]D24 +12.9 (c = 0.96, CH2Cl2).
1
IR (film): = 3285, 2954, 2858, 761, 1742, 1163, 839, 664 cm .
1H NMR (200 MHz):
= 0.07 and 0.07 [s, 3 H, Si(CH3)2], 0.82 (s,
Figure Crystal structure of 11
9 H, SiC4H9-t), 2.34 (s, 3 H, ArCH3), 3.54 and 3.56 (s, 3 H, OCH3),
4.44 (dd, 1 H, J = 2, 11 Hz, CHNHTs), 4.64 (d, 1 H, J = 2 Hz,
CHOTBS), 5.32 (d, 1 H, J = 11 Hz, NH), 7.26 (d, 2 H, J = 8 Hz,
ArH), 7.69 (d, 2 H, J = 8 Hz, ArH).
1H NMR and 13C NMR spectra were recorded on Bruker DPX-200
and AMX-400 instruments in CDCl3 as the solvent. Chemical shifts
were measured in (ppm) and coupling constants J in Hz. TMS was
used as reference for 1H NMR spectra ( = 0.00 ppm). The solvent
peak was used as reference for 13C spectra ( = 77.00 ppm). For as-
signment of the number of substituents attached to the specified car-
bon, each carbon is described as +(secondary carbon), - (primary or
tertiary carbon) or o (quarterny carbon), as determined by DEPT
method. When necessary, NMR data were assigned using HH and
13C NMR (50 MHz):
= 6.01 and 4.88 [+, Si(CH3)2], 18.11 (o,
SiC4H9-t), 21.47 (+, ArCH3), 25.39 (+, SiC4H9-t), 52.22 and 52.68
(+, OCH3), 59.12 (+, CNHTos), 73.03 (+, COTBS), 127.18 and
129.45 (+, Carom), 137.20 and 143.50 (o, Carom), 169.01 and 169.86
(o, CO2Me).
Anal. calcd: C, 51.21; H, 7.01; N, 3.14; S, 7.20; found, C, 51.33; H,
7.45; N, 2.82; S, 7.18.
Synthesis 2001, No. 4, 577–580 ISSN 0039-7881 © Thieme Stuttgart · New York

PAPER
1,2-Epimino-3,4-epoxybutane: A Versatile Chiral Building Block
579
Diethyl (2R,3S)-2-(tert-Butyldimethylsiloxy)-3-[(4-methylphe-
nyl)sulfonylamino]succinate (3b)
(2R,3S)-2-(tert-Butyldimethylsiloxy)-1,4-bis[(4-methylphenyl)-
sulfonyloxy]-3-[(4-methylphenyl)sulfonylamino)butane (threo-
5); Typical Procedure
Compound 3b was prepared from 2b in an analogous manner; yield:
1.03 g (89%); oil [ ]D24 +66.4 (c = 1.12, CH2Cl2).
Compound threo-4 (3.17 g, 8.1 mmol) was stirred in anhyd CH2Cl2
(130 mL) with Et3N (5.6 mL, 5 equiv) at r.t. until a clear solution
had formed. Then Me3N•HCl (744 mg, 1 equiv) was added and the
mixture stirred for a further 10 min before the solution was cooled
to 10 °C. A solution of TsCl (6.17 g, 4 equiv) in anhyd CH2Cl2 (40
mL) was added dropwise over 30 45 min and the mixture was
stirred at r.t. After no more starting material could be detected by
TLC (ca 30 min), H2O was added (50 mL) and the mixture stirred
for 15 min. The aqueous layer was then extracted with CH2Cl2
(2 î 50 mL). The combined organic layers were washed with brine
(30 mL) and dried (MgSO4). Filtration and concentration gave the
crude product as colorless solid. Purification by flash chromatogra-
phy yielded the pure product (PE/EtOAc, 4:1); yield: 5.22 g (97%);
mp 38 45 °C; [ ]D20 +12.5 (c = 1.04, CH2Cl2).
1
IR (film): = 3281, 2931, 2858, 1761, 1165, 840, 663 cm .
1H NMR (200 MHz): = 0.08 [s, 6 H, Si(CH3)2], 0.88 (s, 9 H,
SiC4H9-t), 1.13 and 1.29 (t, 3 H, J = 7 Hz, CH2CH3), 2.42 (s, 3 H,
ArCH3), 4.01 (m, 4 H, CH2CH3), 4.41 (dd, 1 H, J = 3, 7 Hz,
CHNHTs), 4.49 (d, 1 H, J = 3, 6 Hz, CHOTBS), 5.43 (d, 1 H, J = 7
Hz, NH), 7.30 (d, 2 H, J = 8 Hz, ArH), 7.76 (d, 2 H, J = 8 Hz, ArH)
13C NMR (50 MHz):
= 5.30 and 5.05 [+, Si(CH3)2], 13.82 and
14.08 (+, CH2CH3), 18.12 (o, CMe3), 21.50 (+, ArCH3), 25.53 [+,
SiC(CH3)3], 59.24 (+, CNHTos), 61.30 and 62.24 ( , CH2CH3),
74.59 (+, COTBS), 127.24 and 129.73 (+, Carom), 136.38 and 143.79
(o, Carom), 167.88 and 170.04 (o, CO2Et).
Anal. calcd.: C, 53.25; H, 7.45; N, 2.96; S, 6.77; found, C, 53.26; H,
7.64; N, 2.95 S, 6.77.
1
IR (film): = 3289, 2930, 2858, 1598, 1366, 1178 cm .
1H NMR (200 MHz):
= 0.04 [s, 6 H, Si(CH3)2], 0.77 (s, 9 H, t-
(2R,3S)-2-(tert-Butyldimethylsiloxy)-3-[(4-methylphenyl)sulfo-
nylamino]butane-1,4-diol (threo-4); Typical Procedure
C4H9), 2.46, 2.47, 2.47 (s, 9 H, ArCH3), 3.67 (dd, 1 H, J = 10, 6 Hz,
TsNHCH), 3.80 (dd, 1 H, J = 9, 9 Hz, CHOTBS), 3.39 3.49 and
3.89 3.99 (m, CH2OTs), 4.78 (d, 1 H, J = 9 Hz, NH), 7.80 7.60
and 7.40 7.20 (m, 12 H, ArH).
To a solution of 3a (1.0 g, 2.24 mmol) in EtOH (20 mL) in a
100 mL flask was added a suspension of CaCl2 (1.24 g, 5 equiv) in
THF (30 mL) and the mixture was stirred virgorously. After 15 min,
NaBH4 (873 mg, 10 equiv) was added cautiously at r.t. After further
2 h, the mixture was hydrolyzed with aq citric acid (1 M, 20 mL)
and ice. The mixture was then concentrated and the resulting aque-
ous suspension was diluted with H2O (50 mL) and extracted with
CH2Cl2 (5 î 40 mL). The combined organic layers were washed
with aq sat. NaHCO3 solution (3 î 30 mL) and brine (30 mL), and
13C NMR (50 MHz):
= 5.32 and 4.69 (+, SiCH3), 17.86 (o,
CMe3), 21.60 and 21.69 (+, ArCH3), 25.66 [+, C(CH3)3], 52.75 (+,
CHNHTos), 66.84 and 67.81 ( , CH2OTs), 68.91 (+, COTBS),
126.93, 127.91, 128.03 and 129.98 (+, Carom), 130.05, 132.34,
136.67, 144.15, 145.23 and 145.37 (o, Carom).
Anal. calcd.: C, 53.35; H, 6.21; N, 2.01; S, 13.78; found, C, 53.41;
H, 6.52; N, 1.76; S, 13.46.
dried (MgSO4). Filtration and concentration gave the product as
20
colorless crystals (845 mg, 99%); mp 143 °C; [ ]D
(c = 1.03, CH2Cl2).
41.0
(2R,3R)-2-(tert-Butyldimethylsiloxy)-1,4-bis[(4-methylphenyl)-
sulfonyloxy)-3-[(4-methylphenyl)sulfonylamino]butane (eryth-
ro-5)
IR (film): = 3281, 2933, 2856, 1438, 1338, 1257, 1162, 1037, 833,
1
781, 673 cm .
This compound was prepared from erythro-4 in an analogous man-
1H NMR (200 MHz): = 0.09 and 0.10 [s, 3 H, Si(CH3)2], 0.88 (s,
9 H, t-C4H9), 2.44 (s, 3 H, ArCH3), 3.19 (m, 2 H, CH2OH), 3.59 (m,
1 H, TsNHCH), 3.69 (m, 2 H, CH2OH), 3.91 (ddd, 1 H, J = 6, 3, 3
Hz, CHOTBS), 5.35 (d, 1 H, J = 8 Hz, NH), 7.32 (d, 2 H, J = 8 Hz,
ArH), 7.77 (d, 2 H, J = 8 Hz, ArH).
25
ner as described above; oil; yield: 493 mg (98%); [ ]D +1.6
(c = 5.93, CH2Cl2).
1
IR (film): = 3287, 3066, 2930, 2858, 1737, 1599 cm .
1H NMR (200 MHz):
= 0.04 and 0.01 [s, 3 H, Si(CH3)2)], 0.76
(s, 9 H, t-C4H9), 2.44 2.46 (s, 9 H, ArCH3), 3.32 3.46 (m, 1 H,
TsNHCH), 3.73 (dd, 1 H, J = 11, 4 Hz, CHOTBS), 3.81 3.94 and
3.98 4.05 (m, 2 H, CH2OH), 4.84 (d, 1 H, J = 9 Hz, NH), 7.80
7.60 and 7.40 7.20 (m, 12 H, ArH).
13C NMR (50 MHz):
CMe3), 21.52 (+, ArCH3), 25.68 [+, C(CH3)3], 55.37 (+,
CHNHTos), 59.83 and 61.42 ( , CH2OH) 71.80 (+, COTBS),
126.99 and 129.81 (+, Carom), 137.25 and 143.73 (o, Carom).
= 5.00 and 4.75 (+, SiCH3), 17.89 (o,
13C NMR (50 MHz):
= 5.26 and 4.56 (+, SiCH3), 17.87 [o,
C(CH3)3], 21.58 and 21.68 (+, ArCH3), 25.63 (+,CMe3), 53.94 (+,
CHNHTos), 66.95 and 70.24 ( , CH2OTs), 70.20 (+, COTBS),
127.19, 127.99, 128.08, 129.94 and 130.02 (+, Carom), 131.89,
132.34, 136.58, 144.00, 145.25 and 145.71 (o, Carom).
(2R,3R)-2-(tert-Butyldimethylsiloxy)-3-[(4-methylphenyl)sulfo-
nylamino]butan-1,4-diol (erythro-4)
Compound erythro-4 was prepared analogously from 3b; yield:
5.6 g (99%); [ ]D20 +10.9 (c = 1.0, CH2Cl2); mp 135 °C.
Anal. calcd.: C, 53.35; H, 6.21; N, 2.01; S, 13.78; found, C, 53.41;
H, 6.52; N, 1.76; S, 13.46.
IR (film): = 3501, 3301, 2930, 2858, 1598, 1327, 1255, 1160,
1092, 838, 780, 668, 553 cm .
1
1H NMR (200 MHz): = 0.06 and 0.07 [s, 3 H, Si(CH3)2], 0.86 (s,
9 H, t-C4H9), 2.43 (s, 3 H, ArCH3), 2.68 (s, 2 H, OH), 3.31 3.48 (m,
2 H, CHCH), 3.49 3.90 (m, 4 H, CH2OH), 5.40 (d, 1 H, J = 8 Hz,
NH), 7.31 (d, 2 H, J = 8 Hz, ArH), 7.77 (d, 2 H, J = 8 Hz, ArH).
(2S)-1-[(4-Methylphenyl)sulfonyl]-2-[(2R)-oxiran-2-yl]aziri-
dine (threo-6); Typical Procedure
Compound threo-5 (4.696 g, 6.73 mmol) was dissolved in anhyd
THF (100 mL) and at 15 °C TBAF•3 H2O (10.6 g, 5 mmol) in an-
hyd THF (40 mL) was added slowly. The solution was allowed to
warm to r.t. overnight. After 16 h, the mixture was quenched by ad-
dition of Et2O (60 mL)/aq sat. NH4Cl solution (60 mL) and stirred
for 15 min. H2O was added until the precipitate dissolved. The or-
ganic layer was concentrated, diluted with Et2O (200 mL), washed
with brine (30 mL) and dried (MgSO4). Purification by flash chro-
13C NMR (50 MHz):
= 5.44 and 4.70 (+, SiCH3), 17.91 (o,
CMe3), 21.48 (+, ArCH3), 25.69 [+, C(CH3)3], 56.05 (+,
CHNHTos), 60.84 ( , CH2OH), 63.22 ( , CH2OH) 73.49 (+, COT-
BS), 127.06 and 129.80 (+, Carom), 137.05 and 143.71 (o, Carom).
Anal. calcd.: C, 52.41; H, 8.02; N, 3.60; S, 8.23; found, C, 52.50; H,
8.28; N, 3.51; S, 7.93.
matography gave the poduct as colorless crystals (1.05 g, 65%); mp
25
108 °C; [ ]D
9.1 (c = 1.05, CH2Cl2).
Synthesis 2001, No. 4, 577–580 ISSN 0039-7881 © Thieme Stuttgart · New York

580
G. Harms et al.
PAPER
IR (film): = 3000, 2925, 1598, 1324, 1162, 1094, 937, 817, 721
cm .
13C NMR (50 MHz): = 13.11 (+, SCH3), 21.54 (+, ArCH3), 44.40
( , NCHCH2), 46.17 ( , COHCH2), 59.63 [o, C(Sme)2], 60.88 (+,
NCH), 77.20 (+, COH), 127.14 and 129.85 (+, Carom), 136.81,
143.83 (o, Carom).
1
1H NMR (200 MHz): = 2.30 (d, 1 H, J = 4 Hz, CH2N), 2.45 (s, 3
H, ArCH3), 2.60 (dd, 1 H, J = 5, 2 Hz, CH2O), 2.67 (d, 1 H, J = 7
Hz, CH2N), 2.75 (dd, 1 H, J = 5, 4 Hz, CH2O), 2.90 (dt, 1 H, J = 7,
4 Hz, CHN), 3.00 (dt, 1 H, J = 4, 2 Hz, CHO), 7.34 and 7.82 (d, 2
H, ArH).
13C NMR (50 MHz): = 21.66 (+, ArCH3), 30.69 ( , CH2N), 38.58
(+, CHN), 45.51 ( , CH2O), 49.16 (+, CHO), 127.97 and 129.74 (+,
Crystal Data of 11
C14H21NO3S3 (347.50). Crystal size 0.54 î 0.23 î 0.21 mm.
Orthorhombic. Space group P212121. Unit cell dimensions
a = 6.450(1) Å, b = 12.929(1) Å, c = 20.778(1) Å. Cell volume
Z = 1732.7(3) Å3. Method of collection: ‘Collect Nonius’, ‘SIR-
97,11 ‘SHELXL-97’, Extinction coefficient = 0.084(7). Reflections
collected = 3945.
Carom), 134.57 and 144.82 (o, Carom).
(2R)-1-[4-Methylphenyl)sulfonyl]-2-[(2R)-oxiran-2-yl]aziri-
dine (erythro-6)
Compound erythro-6 was prepared from erythro-5 in a similar man-
ner as described above; yield: 66 mg (58%); mp 106 °C; [ ]D
+44.8 (c = 1.03, CH2Cl2).
Acknowledgement
25
Support of this work by Fonds der Chemischen Industrie, Frankfurt,
is gratefully acknowledged.
IR (Film): = 3072, 3020, 2924, 1595, 1310, 1166, 953, 874, 822,
1
719, 703 cm .
References
1H NMR (200 MHz): = 2.25 (d, 1 H, J = 4 Hz, CH2N), 2.45 (s, 3
H, ArCH3), 2.56 (dd, 1 H, J = 5, 2 Hz, CH2O), 2.62 (d, 1 H, J = 7
Hz, CH2N), 2.76 (dd, 1 H, J = 5, 2 Hz, CH2O), 2.91 (ddd, 1 H, J = 7,
4, 4 Hz, CHN), 2.99 (ddd, 1 H, J = 4, 4, 2 Hz, CHO), 7.82 and 7.35
(d, 2 H, ArH).
(1) Recent review: O'Brien, P. Angew. Chem., Int. Ed. 1999, 38,
326.
Liu, H.; Sharpless, K. B.; Gontcharov, A. V. Org. Lett. 1999,
1, 783, and references cited therein.
(2) e.g.: Papa, C.; Tomasini, C. Eur. J. Org. Chem. 2000, 1569.
(3) e.g.: Michel, P.; Rassat, A. J. Org. Chem. 2000, 65, 2572.
(4) e.g.: Schaumann, E.; Kirschning A. and Narjes F. J. Org.
Chem.,1991, 56, 717.
13C NMR (50MHz): = 21.68 (+, ArCH3), 30.64 ( , CH2N), 38.89
(+, CHN), 45.19 ( , CH2O), 49.35 (+, CHO), 127.87 and 129.68 (+,
Carom), 134.43 and 144.78 (o, Carom).
Anal. calcd.: C, 55.21; H, 5.48; N, 5.85; S, 13.40; found C, 55.23;
H, 5.49; N, 5.50; S, 13.36.
Bräuer, N.; Kirschning, A.; Schaumann, E. Eur. J. Org. Chem.
1998, 2729.
Nowak, A.; Bolte, O.; Schaumann, E. Tetrahedron Lett. 1998,
529.
(5) e.g: Breternitz, H.-J.; Schaumann, E.; Adiwidjaja, G.
Tetrahedron Lett. 1991, 32, 1299.
Wu, J.; Hou, X.-L.; Dai, L.-X. J. Org. Chem. 2000, 65, 1344.
(6) Li, G.;. Chang, H.-T.; Sharpless K. B. Angew. Chem., Int. Ed.
Engl. 1996, 35, 451.
(7) For reductions with metalborohydrides, see: Brown, H. C.;
Narasimhan, S.; Choi, Y. M. J. Org. Chem. 1982, 47, 4702.
(8) Yoshida, Y.; Sakakura, Y.; Aso, N.; Okada S.; Tanabe, Y.
Tetrahedron 1999, 55, 2183.
(9) Mori, K.; Iwasawa, H. Tetrahedron 1980, 36, 87.
Kaneko, T.; Katsura, H. Bull. Chem. Soc. Jpn. 1963, 36, 899.
Seito, S.; Bunya, N.; Inaba, M.; Moriwake, T.; Torii, S.
Tetrahedron Lett. 1985, 26, 5309.
(11) The crystallographic data have been deposited at the
Cambridge Crystallographic Data Centre (no. CCDC
152022).
(12) Giacovazzo, C.; Monaco, H.L.; Viterbo, D.; Scordari, F.;
Gilli, G.; Zanotti, G.; Catti, M. Fundamentals of
Crystallography. IUCr Texts on Crystallography – 2; Oxford
University Press: New York, 1992.
N-[2-Hydroxy-4,4-bis(methylsulfanyl)cyclopentyl]-4-methyl-
benzenesulfonamide (11)
Freshly distilled bis(methylthio)trimethylsilylmethane (90 mg,
1.1 equiv, 0.48 mmol) was dissolved in anhyd THF (2 mL). BuLi
(0.34 mL, 1.2 equiv, 1.6 M in hexane) and DMPU (0.06 mL) were
added slowly at 78 °C. The mixture was allowed to warm to 0 °C
during 1 h and stirred for another hour at this temperature. The pale
yellow solution was added via canula to a solution of erythro-6 (100
mg, 1 equiv) in anhyd THF (4 mL) at 78 °C. After stirring for 1 h
at 50 °C, freshly distilled BF3•OEt2 (0.18 mL, 10 equiv) was add-
ed slowly. After 10 min, aq sat. NaHCO3 solution (1 mL) was add-
ed. The layers were separated and the aqueous layer was extracted
with Et2O (4 î 20 mL). The combined organic layers were washed
with brine (2 mL). Purification by flash chromatography gave the
25
product as colorless crystals (69 mg 42%); mp 135 °C; [ ]D 15.1
(c = 1.00, CHCl3).
1
IR (KBr): = 3373, 3277, 2923, 1655, 1330, 1160, 816, 666 cm .
1H NMR (200 MHz): = 1.76 (dd, 1 H, J = 14, 7 Hz, CNHTsCH2),
1.96 (dd, 1 H, J = 14, 7 Hz, CHOHCH2), 2.01 (s, 3 H, SCH3), 2.00
(s, 3 H, SCH3), 2.32 [dd, 1 H, J = 14, 7 Hz, C(NHTs)CH2], 2.42 (dd,
1 H, J = 14, 7 Hz, CHOHCH2), 2.44 (s, 3 H, ArCH3), 3.56 3.70 (m,
1 H, CHNHTs), 4.29 (ddd, 1 H, J = 7, 7, 6 Hz, CHOH), 5.42 (d, 1
H, J = 8 Hz, NH), 7.33 and 7.79 (d, 2 H, J = 7 Hz, ArH).
Article Identifier:
1437-210X,E;2001,0,04,0577,0580,ftx,en;T04100SS.pdf
Synthesis 2001, No. 4, 577–580 ISSN 0039-7881 © Thieme Stuttgart · New York