Ring-opening reaction of Bus- and SES-protected aziridines using lithiated dithianes

Article abstract of DOI:10.1039/b814413c

The scope and limitation of the ring-opening reaction of sulfonyl-activated aziridines using lithiated dithianes was investigated. Nucleophilic attack of lithiated dithianes on aziridines containing tert-butylsulfonyl (Bus) and 2-(trimethylsilyl)ethylsulf

Full text of DOI:10.1039/b814413c

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PAPER
www.rsc.org/obc | Organic & Biomolecular Chemistry
Ring-opening reaction of Bus- and SES-protected aziridines using
lithiated dithianes†
Ken Sakakibara and Kyoko Nozaki*
Received 19th August 2008, Accepted 14th October 2008
First published as an Advance Article on the web 25th November 2008
DOI: 10.1039/b814413c
The scope and limitation of the ring-opening reaction of sulfonyl-activated aziridines using lithiated
dithianes was investigated. Nucleophilic attack of lithiated dithianes on aziridines containing
tert-butylsulfonyl (Bus) and 2-(trimethylsilyl)ethylsulfonyl (SES) demonstrated efficient ring cleavage to
yield b-amino carbonyl equivalents, g-lactam and syn- and anti-1,5-aminoalcohols. The first example of
a ring-opening reaction of di-substituted aziridine using dithiane is also reported. Finally, the Bus and
SES-possessing dithianes obtained were deprotected to demonstrate their synthetic usefulness.
Introduction
Optically active b-amino carbonyl compounds are common inter-
mediates for various kinds of biologically active compounds. One
of the common synthetic approaches to this type of compound
is the asymmetric Mannich reaction.1–3 As an alternative method,
nucleophilic ring opening of N-p-toluenesufonyl (=Ts) aziridine
using lithiated dithianes has been reported.4–12
The latter methodology is advantageous for several reasons:
(1) because the carbonyl group is masked in the product,
undesirable side reactions such as self-aldol condensation are
suppressed. (2) The amino group in the product is protected
by a p-tosyl group. (3) The reaction is not reversible, therefore,
the products are obtained in high yields. (4) Enantiomerically
pure aziridines13–17 are easily available and the configuration is
maintained throughout the reaction. However, the substrates for
the ring-opening reaction using lithiated dithianes were limited to
N-tosylaziridines. Although N-tosylaziridines are commonly em-
ployed because of their easy preparation, a major drawback is the
difficulty in their deprotection.9 Other sulfonyl-protecting groups
such as tert-butylsulfonyl (Bus),18–21 2-trimethylsilylethylsulfonyl
(SES),22,23 and p-nitrophenylsulfonyl (Ns),24,25 are known to
undergo deprotection under much milder reaction conditions
(Fig. 1).
Fig. 1 Possible sulfonyl protecting groups for aziridines.
Results and discussion
Bus-activated aziridines 1 and various dithiane anions 2–5 were
chosen as substrates (Table 1). Aziridine rac-1 was allowed to
react with lithiated 1,3-dithiane 2 to yield rac-6 (Table 1, run 1).
Enantiopure aziridine (S)-1 was converted to (S)-6 by 2 without
any racemization (Table 1, run 2). Lithiated carboxyl-1,3-dithiane
3 opened rac-1 in the presence of TMEDA (Table 1, run 3).
The crude product could not be purified because of its high
Table 1 Ring-opening reaction of Bus-activated aziridine
lithiated dithianes
1 using
In this paper, we report the scope and limitation of N-
sulfonylaziridines employable as electrophiles in the reaction with
lithiated dithianes. Depending on the kind of dithianes, b-amino
carbonyl equivalents, a g-lactam and 1,5-aminoalcohols were
obtained in good yields with a Bus- and SES-protecting group
on the nitrogen. We also report the first example of a ring-opening
reaction of di-substituted aziridine by dithiane. Deprotection of
Bus and SES is also described.
Run
Aziridine
Dithiane anion
Product
Yield (%)
1a
2a
3b
4b
5c
6a
rac-1
(S)-1
rac-1
(S)-1
rac-1
rac-1
2
2
3
3
4
5
rac-6
(S)-6
rac-7
(S)-7
rac-8
rac-9
90
91
76
78
90
92
Department of Chemistry and Biotechnology, Graduate School of Engi-
neering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, 113-8656,
Tokyo, Japan. E-mail: nozaki@chembio.t.u-tokyo.ac.jp; Fax: +81-3-5841-
7263; Tel: +81-3-5841-7261
† Electronic supplementary information (ESI) available: Full identification
data, 1H NMR spectra and 13C NMR spectra of newly synthesized
compounds. See DOI: 10.1039/b814413c
a Experimental procedure A. b Experimental procedure B. c Experimental
procedure C.
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Table 2 Ring-opening reaction of various Bus-activated aziridines
Furthermore, di-substituted aziridine meso-20 yielded the trans-
substituted product rac-21 (Scheme 2). Although several examples
of ring opening using dithiane have been reported for 2,3-di-
substituted oxiranes,27–30 this is the first example of a ring-opening
reaction of di-substituted aziridine using dithiane.
Scheme 2 Ring-opening reaction of 2,3-di-substituted-aziridine.
Run
Aziridine
Dithiane anion
Product
Yield (%)
1a
2a
3a
4a
5a
6a
rac-10
rac-11
rac-12
(R)-13
rac-14
rac-14
5
5
5
5
5
2
rac-15
rac-16
rac-17
(R)-18
rac-19b
83
94
90
85
95b
SES- and Ns-activated aziridines 22 and 23 were reacted with
lithiated dithianes (Table 3, runs 1–5). Treatment of azridine (S)-
22 with anion 2 resulted in quantitative recovery of dithiane, and
a complex mixture derived from aziridine was obtained (Table 3,
run 1). (S)-22 was treated with 3 to yield (S)-24 via cyclization
(Table 3, run 2). In contrast, reaction of (S)-22 with 4 resulted in
quantitative recovery of dithiane and a complex mixture derived
from aziridine (Table 3, run 3). Lithiated dithiane 5 smoothly
opened aziridine (S)-22 to (S)-25 (Table 3, run 4). The following
may be an explanation for the quantitative recovery of dithiane and
the complex mixture derived from aziridine (Table 3, runs 1 and 3).
In the case of lithiated dithianes 2 and 4, equilibrium between an a-
carbanion on the sulfonyl group of SES and the anion of dithiane
would lie to the right because of the higher pKa of dithianes 2·H+
and 4·H+ (Scheme 3). Deprotonated aziridines would lead to a
complex mixture and recovery of protonated dithiane. In contrast,
lithiated dithanes 3 and 5 would retain the carbanion character to
open the aziridines because of the lower pKa of dithianes 3·H+
and 5·H+ (Scheme 3). The order of pKa can roughly be estimated
to rationalize our hypothesis: 3·H+, 5·H+ (pKa 30.7) < a-proton
neighboring SES sulfonyl group < 2·H+ (pKa 39), 4·H+.26,31 Given
that 2-CO2Me-1,3-dithiane (pKa 20.9) and MeSO2Me (pKa 31.1)
have similar pKa values of dithiane 3·H+ and a-proton neighboring
SES sulfonyl group, our roughly estimated order of pKa would
c
c
—
–
a Experimental procedure A. b Regioisomer rac-19¢ was obtained in
addition to 19. c Complex mixture was obtained.
polarity. After neutralization by HCl–MeOH, the crude material
was treated with DCC–DMAP and g-lactam 7 was isolated. Ring
opening of enantiopure aziridine (S)-1 by 3 yielded (S)-7 without
racemization (Table 1, run 4). Aziridine rac-1 yielded rac-8 and
rac-9 by the reactions with lithiated dithianes 4 and 5 (Table 1,
runs 5–6).
We next examined the scope of Bus-aziridines bearing various
substituents 10–13 by lithiated dithiane 5 (Table 2, runs 1–4). All
of them easily provided the ring-opening products 15–18. The
product rac-19 was obtained from rac-14 as a mixture with its
regio-isomer 19¢ (19 : 19¢ = ~3 : 1 or ~1 : 3) (Table 2, run 5). On the
other hand, ring-opening product was not obtained from rac-14
and 2 to detect a complex mixture (Table 2, run 6).10
The different reactivity between dithiane anions 2 and 5 may be
explained as follows. Considering the big difference of pKa values
between dithiane 2·H+ (pKa 39) and 5·H+ (pKa 30.7),26 dithiane
anion 2 would cause deprotonation of aziridine rac-14 to give a
complex mixture, while lithiated dithiane 5 triggers smooth ring-
opening due to the low pKa value of 5·H+ (Scheme 1). The order of
pKa can roughly be estimated to rationalize our hypothesis: 5·H+
(pKa 30.7) < a-proton to N atom and Ph group < 2·H+ (pKa 39).
Table 3 Ring-opening reaction of SES/Ns-activated aziridines
Run
Aziridine
Dithiane anion
Product
Yield (%)
d
1a
2b
3c
4a
5a
(S)-22
(S)-22
(S)-22
(S)-22
(S)-23
2
3
4
5
5
—
(S)-24
—
(S)-25
—
—
45
d
—
86
e
—
a Experimental procedure A. b Experimental procedure B. c Experimental
procedure C. d Recovery of dithiane and a complex mixture from aziridine
were detected. e A complex mixture was given.
Scheme 1 Ring-opening reaction of Bus-activated Ph-aziridine.
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Scheme 4 Deprotection of Bus and SES.
Scheme 3 Equilibrium between lithiated dithiane and a-sulfonyl proton.
Conclusions
be supported. Finally, Ns-aziridine (S)-23 provided an insoluble
complex mixture due to competing deprotection (Table 3, run 5).32
We have further extended the ring opening of Bus-activated
aziridines to the syntheses of 1,5-amino alcohols via 1,4-Brook
rearrangement (Table 4, runs 1–4). Lithiated carbinol 26 induced
the 1,4-Brook rearrangement in the presence of HMPA, yielding
1,5-amino alcohols via the ring-opening reaction of aziridines.4
1,5-Amino alcohol syn-27 can be obtained from aziridine (S)-1 and
lithiated dithiane (R)-26 (Table 4, run 1). Anti-27 can be exclusively
obtained using the opposite enantiomer of 26 (Table 4, run 2). In
addition, syn and anti-28 were obtained by using aziridine (R)-13
and both enantiomers of lithiated dithiane 26 (Table 4, runs 3
and 4).
Bus- and SES-activated aziridines undergo an efficient ring-
opening reaction with various lithiated dithiane anions to yield
various b-amino carbonyl equivalents, g-lactam and syn- and
anti-1,5-aminoalcohols. The successful employment of aziridines
containing Bus and SES will enhance the synthetic value of the
ring-opening reaction between aziridines and dithianes. The scope
of substrates was elucidated from a pKa viewpoint. Furthermore,
we report the first example of a ring-opening reaction of di-
substituted aziridine using dithiane. The Bus and SES groups
of the dithianes obtained were deprotected to demonstrate their
synthetic usefulness.
Finally, the Bus and SES groups of the dithianes obtained were
removed to demonstrate their synthetic usefulness (Scheme 4).
First of all, Bus-bearing dithiane rac-6 was chosen as a substrate.
Unfortunately, use of the normal conditions (TfOH–anisole21) or
use of the Ts-removing conditions (Na–naphtalenide–DME9) led
to decomposition of the dithiane ring. Thus, after the dithiane
moiety was removed by Raney Ni, the deprotected compound
rac-29 was obatined using TfOH and anisole (Scheme 4). Next,
SES-possessing dithiane (S)-25 was efficiently deprotected via Boc-
introduction to yield (S)-30. It is well known that N-acyl-SES is
much more easily deprotected than monoprotected SES-amine.23
Experimental procedures and analytical data
General information
All manipulations involving air- and/or moisture-sensitive com-
pounds were carried out in a glove box under an argon atmosphere
or with the standard Schlenk technique under argon purified by
passing through a hot column packed with BASF catalyst R3–11.
All the solvents used for the reactions were distilled under argon
after drying over an appropriate drying reagent or passed through
solvent purification columns. Most reagents were used without
further purification, unless otherwise specified. Analytical thin-
layer chromatography was performed on glass plates coated with
0.25 mm 230–400 mesh silica gel containing a fluorescent indicator
(Merck, #1.05715.0009). For silica gel column chromatography,
Silica gel 60 N (spherical, neutral, particle size 63–210 mm,
Kanto Kagaku Co., Ltd.) was used. NMR spectra were recorded
in CDCl3 using a 500 MHz spectrometer (1H 500 MHz; 13C
125 MHz). Chemical shifts are reported in ppm relative to the
residual protiated solvent peak (7.26 ppm for CHCl3) for 1H and
CDCl3 (77.16 ppm) for 13C. Otherwise, TMS (0.00 ppm) was used
as an internal standard for 1H. Data are presented below: chemical
shift, multiplicity (s = singlet, d = doublet, t = triplet, q = quartet,
m = multiplet and/or multiplet resonances, br = broad), coupling
constants in hertz (Hz), and signal area integration in natural
numbers. Melting points of general organic compounds were
determined using a Yanaco MP-500D melting point apparatus.
Optical rotations were measured on a JASCO P-1010 spectrometer
Table 4 Syntheses of 1,5-aminoalcohols
Run
Aziridine
Dithiane
Product
Yield (%)
1a
2a
3a
4a
(S)-1
(R)-26
(S)-26
(R)-26
(S)-26
syn-27
anti-27
syn-28
anti-28
69
61
58
78
(S)-1
(R)-13
(R)-13
a Experimental procedure E.
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using a 10 cm cell. The recycling preparative GPC was performed
with JAI GEL-1H and JAI GEL-2H columns (CHCl3 as an
eluent). Confirmation of enantiopurity was obtained by chiral
HPLC. HPLC analyses were carried out using a JASCO LC-
2000Plus system (HPLC pump: PU-2080; gradient unit: LG-2080-
02; degasser: DG-2080-53, column oven: CO-2060; UV detector:
MD-2010) equipped with a DAICEL CHIRALPAK IA or IB
column (4.6 mm ¥ 250 mm). Elemental analyses were performed
at the University of Tokyo. High resolution mass spectra were
recorded by the FAB method using a JEOL JMS-700 mass
spectrometer.
Literature methods were used for known compounds
tBuSO2NH2,20 2-CO2H-1,3-dithiane (precursor of 3),33 carbinol
(precursor of 26),34 (R)-(2,3-epoxypropyl)benzene,35 SESNHBoc36
and most of aziridines.20,25,37,38 Other aziridines rac-12 and (S)-22
were synthesized as follows.
d 24.33, 30.28, 38.14, 59.75, 69.48, 73.28, 127.81, 127.96, 128.58,
137.81; IR (KBr disc): 1113, 1130, 1229, 1306, 1366, 1454, 1481,
2870, 2986 cm-1. HRMS-FAB+ (m/z + H+) calcd for C14H22NO3S1
284.1320, found 284.1329.
Synthetic procedure for aziridine (S)-22
(2S)-2-Benzyl-1-[2-(trimethylsilyl)ethanesulfonyl]aziridine. Azi-
ridine (S)-22 was synthesized via the literature method with a
slight modification (Scheme 6).13 A 20 mL Schlenk flask equipped
with a magnetic stirring bar was charged with (S,S)-Co-salen
complex 31 (202 mg, 0.334 mmol). The catalyst was dissolved in
toluene (1.00 mL) and treated with acetic acid (0.200 mL, 210 mg,
3.50 mmol). The solution was stirred at room temperature open to
air for 30 min; over this time the colour changed from orange–red
to dark brown. The solution was concentrated in vacuo to yield
a crude dark brown solid. The resulting catalyst residue was
dissolved in (R)-(2,3-epoxypropyl)benzene (2.24 g, 16.7 mmol)
and THF (1.00 mL). BocNHSES 32 was added to the mixture.
The reaction mixture was stirred overnight at room temperature.
The resulting mixture was dried to obtain the crude material.
This material was filtered by flash column chromatography
(hexane–AcOEt = 1 : 1, v/v) to obtain a pale brown white solid.
Synthetic procedure for aziridine rac-12
rac-1-(tert-Butylsulfonyl)-2-(benzyloxymethyl)aziridine
Aziridine rac-12 was synthesized via the literature method
with a slight modification (Scheme 5).37 BnNEt3 Cl- (91.2 mg,
+
0.400 mmol) was added to a stirred suspension of benzyl glycidyl
t
ether (657 mg, 4.00 mmol), BuSO2NH2 (823 mg, 6.00 mmol)
and K2CO3 (55.3 mg, 0.400 mmol) in 1,4-dioxane (1.80 mL).
The suspension was heated at 90 ◦C for 48 h, then cooled, and
subsequently, the solvent was removed by rotary evaporation.
Purification of the residue by column chromatography (hexane–
Et2O = 1 : 2, v/v) yielded b-hydroxysulfonamide, which was used
directly in the next step.
Scheme 5 Synthetic procedure for aziridine rac-12.
The b-hydroxysulfonamide obtained was dissolved in CH2Cl2
(20.0 mL) and pyridine (0.650 mL, 8.00 mmol). DMAP (49.0 mg,
0.400 mmol) and Ms2O (1.04 g, 6.00 mmol) were added to the
resulting solution and stirred for 2 h. Saturated aqueous K2CO3
solution was added to the suspension until bubbles were no longer
produced, and then reduced pressure was applied. The material
obtained was dissolved in CH2Cl2, dried over MgSO4, filtered and
the solvent was removed by rotary evaporation. The crude material
was used directly in the next step.
The crude mesylate was dissolved in THF (30.0 mL) and H2O
(15.0 mL), and K2CO3 (2.20 g, 16.0 mmol) was added. Following
stirring at 70 ◦C for 17 h, the reaction mixture was cooled and the
solvents were removed under reduced pressure. Purification of the
residue by column chromatography (hexane–AcOEt = 5 : 1, v/v)
yielded a brown liquid. Complete purification was achieved by the
recycling preparative SEC to obtain a colourless liquid (650 mg,
2.50 mmol, 63% yield). The characteristics of the colourless liquid
were as follows: Rf = 0.25 (hexane–EtOAc = 5 : 1, v/v); 1H
NMR (CDCl3): d 1.51 (s, 9H), 2.18 (d, J = 4.4 Hz, 1H), 2.62
(d, J = 7.1 Hz, 1H), 2.94–3.04 (m, 1H), 3.54 (dd, J = 6.1, 11.1 Hz,
1H), 4.53–4.62 (m, 2H), 7.27–7.39 (m, 5H); 13C NMR (CDCl3):
Scheme 6 Synthetic procedure for aziridine (S)-22.
This residue was dissolved in CH2Cl2 (14.0 mL) and cooled
to 0 ◦C. TFA (14.0 mL) was added dropwise, and the reaction
mixture was allowed to warm to room temperature with stirring.
After 1.5 h the solution was cooled to 0 ◦C and diluted with Et2O
(350 mL) and saturated aqueous NaHCO3 (150 mL). The organic
layer was washed with brine twice, dried over Na2SO4, filtered and
concentrated.
The b-hydroxysulfonamide obtained was dissolved in CH2Cl2
(120 mL) and pyridine (2.82 mL, 35.0 mmol); DMAP (208 mg,
1.70 mmol) and Ms2O (4.36 g, 25.0 mmol) were added, and the
resultant suspension was stirred for 2 h. Saturated aqueous K2CO3
solution was added to the suspension until bubbles were no longer
produced, and put under reduced pressure. The obtained material
was dissolved in CH2Cl2, dried over MgSO4, filtered and the
solvent was removed by rotary evaporation. The crude material
was used directly in the next step.
The crude mesylate was dissolved in THF and H2O (80.0 mL,
9.00 mL), and K2CO3 (20.0 g, 145 mmol) was added. Following
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stirring at 85 ◦C for 6 h, the reaction was cooled and the solvents
were removed under reduced atmosphere. Purification of the
residue by column chromatography (hexane–AcOEt = 5 : 1, v/v)
yielded a colourless liquid (2.80 g, 9.40 mmol, 56% yield). Spectral
data coincided with the previous data.13
Scheme 7 Preparation of lithiated dithiane 26.
General procedure
chromatography on silica gel, using AcOEt–hexane as eluant,
yielded the ring-opening product.
Typical procedure A. A solution of 1,3-dithiane or 2-Ph-1,3-
dithiane (0.550 mmol, 1.10 equiv.) in THF (3.00 mL) was cooled
◦
n
to -78 C and treated with a ~1.6 M hexane solution of BuLi
(0.550 mmol, 1.10 equiv.) dropwise via syringe. After 2 h, a solution
of the selected aziridine (0.500 mmol) in THF (2.00 mL) was
added dropwise to the reaction mixture at -78 ◦C via syringe.
The resultant solution was warmed to 0 ◦C and stirred for 3 h,
and then poured into excess HCl in MeOH and concentrated in
vacuo. Flash chromatography on silica gel, using AcOEt–hexane
as eluant, provided the ring-opening product.
Deprotection procedure
Deprotection of rac-6 to rac-29 2-amino-1-phenylbutane.
A
suspension of Raney Ni in water (from TCI, ~3 mL) was added
to a solution of dithiane rac-6 (187 mg, 0.500 mmol) in EtOH
(10◦.0 mL). The mixture was stirred under H2 (1 atm) for 20 h at
80 C. The resulting mixture was diluted with CH2Cl2 (~50 mL)
and H2O (~100 mL). The aqueous layer was extracted with CH2Cl2
(~50 mL ¥ 2) twice, dried over Na2SO4, filtered and concentrated.
The crude product was purified by flash chromatography (AcOEt–
hexane = 5 : 1, v/v, ref 0.25) to isolate dithiane-free material
(126 mg, 0.468 mmol, 93.7% yield.
Next, the tert-butylsulfamide moiety was deprotected by us-
ing the conditions and the isolation procedures developed by
Weinreb.21 Sulfoamide (60.0 mg, 0.227 mmol) in CH2Cl2 (10.0mL),
anisole (491 mg, 4.54 mmol) and TfOH (2.27 mmol in CH2Cl2
10.0 mL) were used. The crude product was purified by flash
chromatography (AcOEt–MeOH–NEt3 = 9 : 1 : 0.05, v/v, ref 0.2)
to afford the amine rac-29 (16.8 mg, 0.113 mmol, 49.8% yield).
Spectral data coincided with the previous data.39
Typical procedure B. A solution of 2-CO2H-1,3-dithiane
(90.4 mg, 0.550 mmol, 1.10 equiv.) in THF (3.50 mL) was cooled
to 0 ◦C and treated with a ~1.6 M hexane solution of nBuLi
(1.10 mmol, 2.20 equiv.) dropwise via syringe. After 10 min, a
solution of assigned aziridine (0.500 mmol) in THF (2.00 mL)
and TMEDA (0.195 mL, 1.30 mmol, 2.60 equiv.) was added
dropwise to the reaction mixture at 0 ◦C via syringe. The resultant
solution was warmed to 65 ◦C and stirred for 13 h. The resultant
mixture was poured into excess HCl in MeOH and concentrated
in vacuo. The residue was dissolved in CH2Cl2 (~50 mL), filtered
and concentrated in vacuo. The resulting oil was dissolved in
CH2Cl2 (5.00 mL), DMAP (7.33 mg, 0.0600 mmol) and DCC
(124 mg, 0.600 mmol). The suspension was stirred for 1 h at room
temperature. Flash chromatography (AcOEt–hexane = 3 : 1, v/v)
provided the g-lactam.
Deprotection of (S)-25 to (S)-30
(S)-1-(2-Phenyl-1,3-dithian-2-yl)-2-(tert-butoxycarbonyl)-3-phe-
nylpropane. A 80 mL Schlenk flask equipped with a magnetic
stirring bar was charged with (S)-25 (1.30 g, 2.15 mmol)
and DMAP (26.3 mg, 0.263 mmol). They were dissolved in
CH2Cl2 (10.0 mL) and NEt3 (435 mg, 4.30 mmol). Boc2O (1.10 g,
5.00 mmol) was dropped in one portion into the resultant solution.
The reaction mixtur◦e was stirred for 2 h at room temperature
and overnight at 40 C. The solution was concentrated in vacuo
and the residue was treated with EtOAc and excess 1M HCl.
The EtOAc was washed with brine twice, dreid (NaSO4) and
concentrated to leave a viscous solid. The material obtained was
used without further purification.
Typical procedure C. A solution of 2-Me3Si-1,3-dithiane
(106 mg, 0.550 mmol, 1.10 equiv.) in Et2O (3.00 mL) was cooled
◦
t
to -78 C and treated with a ~1.5 M pentane solution of BuLi
(0.550 mmol, 1.10 equiv.) dropwise via syringe. The resulting
solution was warmed to -45 ◦C over 1 h and then cooled to
-78 ◦C. A solution of assigned aziridine (0.500 mmol) in Et2O
(2.00 mL) was added dropwise to the reaction mixture at -78 ◦C
via syringe. The resultant solution was warmed to -20 ◦C over
15 min, and stirred for an additional 3 h at 0 ◦C. The isolation
procedure was the same as described in typical procedure A.
The crude material in THF (20 mL) was treated with TBAF in
1M THF solution (10 mL). Following stirring at room temperature
for 2 h, the solvents were removed under reduced pressure.
Purification of the residue by column chromatography (hexane–
AcOEt = 5 : 1, v/v) yielded a colorless liquid (S)-30 (1.01 g,
2.35 mmol, 90% yield). The characteristics of (S)-30 were as
follows: Rf = 0.50 (hexane–EtOAc = 5 : 1, v/v); 1H NMR (CDCl3):
d 1.35 (s, 9H), 2.08–2.30 (m, 2H), 2.45–2.83 (m, 6H), 3.55–4.18
(m, 2H) 6.91–7.07 (m, 2H), 7.13–7.30 (m, 4H), 7.35 (t, J = 8.0 Hz,
2H), 7.85 (d, J = 8.5 Hz, 2H); 13C NMR (CDCl3): d 24.93, 27.53,
28.42, 42.28, 48.29, 48.70, 57.51, 78.69, 126.19, 127.10, 128.22,
128.62, 128.68, 129.45, 137.98, 141.08, 154.44; IR (KBr disc): 1028,
1051, 1171, 1246, 1275, 1364, 1389, 1499, 1508, 1701, 2907, 2974,
3368 cm-1. Calcd for C24H31NO2S2: C, 67.09; H, 7.27; N, 3.26.
Typical procedure D. The molar ratio was the same as de-
scribed in typical procedure A. The resultant solution was warmed
to 30 ◦C and stirred for 12 h. The isolation procedure was the same
as described in typical procedure A.
Typical procedure E. A solution of carbinol (precursor of 26,
250 mg, 0.627 mmol, 1.25 equiv.) in Et2O (4.00 mL) was cooled
to 0 ◦C and treated with a ~1.6 M hexane solution of nBuLi
(0.627 mmol, 1.25 equiv.) dropwise via syringe (Scheme 7). The
◦
resulting solution was cooled to -78 C. A solution of assigned
aziridne (0.500 mmol) and HMPA (0.41 mmol, 0.820 equiv.) in
Et2O (2.00 mL) was added dropwise to the reaction mixture at
◦
◦
-78 C via syringe. The resultant solution was warmed to 0 C,
◦
and stirred for an additional 3 h at 0 C. The resultant mixture
was poured into aqueus NH4Cl and concentrated in vacuo. Flash
Found: C, 67.01; H, 7.40; N, 3.21. [a]21 = 0.342 (c 9.11 in Et2O).
D
506 | Org. Biomol. Chem., 2009, 7, 502–507
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Acknowledgements
We thank Professor Yoshiaki Nishibayashi and Dr Yoshihiro
Miyake (Tokyo University) for HRMS analyses. We also thank
Professor Makoto Fujita for measurement of optical rotation.
K. S. is grateful for financial support from the Research Fellow-
ships of the Japan Society for the Promotion of Science (JSPS) for
Young Scientists.
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