Substitution effects in intramolecular aziridine-allylsilane cyclizations

Article abstract of DOI:10.1016/j.tet.2008.11.043

We report here the synthesis of an aziridine tethered to a substituted allylsilane via a substituted tether. These tether-substituted aziridine-allylsilanes cyclize differently upon treatment with BF₃·OEt₂ than tether-unsubstituted a

Full text of DOI:10.1016/j.tet.2008.11.043

Tetrahedron 65 (2009) 741–747
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Substitution effects in intramolecular aziridine–allylsilane cyclizations
y
*
David J. Lapinsky , Aravinda B. Pulipaka, Stephen C. Bergmeier
Department of Chemistry & Biochemistry, Ohio University, Athens, OH 45701, USA
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 11 August 2008
Received in revised form 11 November 2008
Accepted 14 November 2008
Available online 24 November 2008
We report here the synthesis of an aziridine tethered to a substituted allylsilane via a substituted tether.
These tether-substituted aziridine–allylsilanes cyclize differently upon treatment with BF3$OEt2 than
tether-unsubstituted aziridine–allylsilanes and provide a 6-endo-type product. We show that steric in-
teractions between the N-substituent of the aziridine and substitution on the tether can control the
product distribution.
Ó 2008 Elsevier Ltd. All rights reserved.
1. Introduction
was the amino acid derivative 11, which was prepared via an
enantioselective Claisen rearrangment.13,14 Basic hydrolysis of
The inter-1 and intramolecular2–5 cyclization reactions of azir-
idines with allylsilanes have been shown to be a general method for
the synthesis of a variety of nitrogen containing heterocycles and
optically pure amino acid derivative 11 followed by esterification
and tosylation provided diprotected amino acid 12a (82% yield,
three steps). Reduction of the methyl ester with LiAlH4 and Mit-
sunobu ring closure provided aziridine 14a in good overall yield.
The enantiomeric purity of intermediates 12a, 13a, and 14a was
determined to be >98% by chiral HPLC analysis. Compounds 12a,
13a, and 14a were compared with the corresponding enantiomers
of these intermediates, synthesized in an identical manner starting
from the known enantiomer of amino acid derivative 11. Olefin 14a
was treated with 9-BBN followed by (E)-1-iodo-2-methyl-3-tri-
methylsilylpropene (15)15 and PdCl2(dppf)$CH2Cl2 under Suzuki
carbocycles including g-amino olefins (2), the silylated azabicycles
(3), or the desilylated azabicycle (4) (Fig. 1). Compounds 2 and 3
have served as valuable precursors to the Rauwolfia alkaloid
(ꢀ)-yohimbane (5)4 and bicyclic proline analogs (6).3
With goals of studying the intramolecular cyclization of azir-
idine–allylsilanes containing a substituted tether and a substituted
allylsilane, as well as applying this methodology to natural product
synthesis, an aziridine–allylsilane (10) was envisioned via retro-
synthetic analysis of (þ)-
a
-skytanthine (7)6–12 (Scheme 1). This
alkaloid features a 3-azabicyclo[4.3.0]nonane that could be formed
upon Mitsunobu ring closure of amino alcohol 8. Alcohol 8 could be
derived from a hydroboration/oxidation sequence of olefin 9,
though an appropriate hydroboration protocol would be needed to
set the desired stereochemistry of the C-5 methyl group (sky-
SiR3
BF3•OEt2
(
)
n
( )n
NHTs
TsN
1
tanthine numbering). Finally, it was hypothesized that
g-amino
2
olefin 9 would result from an intramolecular cyclization reaction of
aziridine–allylsilane 10, featuring a methyl group on the tether
connecting the two reacting moieties.
cat. BF3•OEt2
X
H
N
( )n
NTs
H
H
H
2. Results and discussion
3, X = SiR3
4, X = H
N
The synthesis of aziridine–allylsilane 10 was achieved using
a Suzuki cross-coupling between olefinic aziridine 14 and allylsi-
lane 15 (Scheme 2). The starting point for the proposed synthesis
5
CO2H
(
)
n
NH•HBr
* Corresponding author. Tel.: þ1 740 517 8462; fax: þ1 740 593 0148.
E-mail address: bergmeis@ohio.edu (S.C. Bergmeier).
Present address: Division of Pharmaceutical Sciences, Mylan School of Phar-
6
y
Figure 1. Previous syntheses utilizing intramolecular aziridine–allylsilane cyclizations.
macy, Duquesne University, Pittsburgh, PA, United States.
0040-4020/$ – see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2008.11.043

742
D.J. Lapinsky et al. / Tetrahedron 65 (2009) 741–747
cycloaddition3 was also isolated (19% yield). While this com-
H
H
H
H
5
OH
pound appears to be a single diastereomer, we have not been
able to confirm the relative stereochemistry. Based on previous
cyclizations we would expect that the methyl group and
bridgehead hydrogen should be trans.3 It should be noted that
silylated azabicycle 19 could be converted into an additional
NMe
NHTs
9
7
8
H
SiMe3
amount of cis
g-amino olefin 18 by fluoride-induced silicon
fragmentation.1 As a result, the true diastereoselectivity for the
cyclization of aziridine–allylsilane 10c is 2.3:1 (cis/trans). It was
important to see that the cyclization of 10c was comparable to 16
in terms of diastereoselectivity and yield, and that the reaction
proceeded in an identical manner with attack of the allylsilane at
the more substituted carbon of the aziridine ring.
H
NHTs
NTs
H
9
10
Scheme 1. Retrosynthesis of (þ)-
a-skytanthine using an intramolecular aziridine–
allylsilane cyclization.
Satisfied that the modifications made to the allylsilane moiety
had no deleterious effect on the results of the cyclization reaction,
we turned our attention toward the cyclization of aziridine–allyl-
silane 10a. This aziridine–allylsilane features a methyl group on the
tether connecting the two reacting moieties and the previously
examined modifications to the allylsilane moiety (Scheme 3).
Aziridine–allylsilane 10a was cyclized under similar reaction con-
ditions as control aziridine–allylsilane 10c (i.e., 100 mol % of
BF3$OEt2, ꢀ78 to 0 ꢁC, 20 h), but the results proved dramatically
different. The major product of the reaction was the formation of
six-membered carbocycle 20a (33% yield) as a single diastereomer.
This product results from attack of the allylsilane at the less
substituted carbon of the aziridine ring and not the more
substituted carbon as we have usually seen with our aziridine–
allylsilanes.2–4 The inseparable mixture of five-membered
carbocycles 9a (12% yield, 2.2:1 (cis/trans)) results from cyclization
in the traditional mode. From this reaction, it is clearly evident that
the substitution of a methyl group on the tether has contributed to
an alternative mode of cyclization.
cross-coupling conditions.16 It was satisfying to find that the cou-
pling provided target aziridine–allylsilane 10a in 43% yield. In order
to study the effect of the C-9 methyl group on the intramolecular
cyclization of aziridine–allylsilane 10a, a control aziridine–allylsi-
lane containing the same allylsilane moiety with no substitution of
the tether was needed. Aziridine–olefin 14c5 was subsequently
cross-coupled in an identical manner to provide control aziridine–
allylsilane 10c containing no C-9 methyl group (skytanthine
numbering).
1) K2CO3, MeOH,
H2O
2) MeOH, HCl
3) RCl
TfaHN
CO2H
RHN
CO2Me
11
12a, R = Ts,
82% from 11
12b, R = Ms,
66%from 11
R1
LiAlH4
Ph3P
DIAD
OH
SiMe3
H
RHN
RN
13a, R = Ts, 92%
13b, R = Ms, 92%
14a, R = Ts, R1 = Me,
86%
BF3•OEt2
+
NTs
(300 mol%)
0 °C, 4 hrs.
84%
NHTs
NHTs
14b, R = Ms, R1 = Me,
86%
16
17b
17a
17a : 17b, 2.6 : 1
14c, R = Ts, R1 = H
H
H
SiMe3
NTs
5
5
5
SiMe3
SiMe3
1) 9-BBN
BF3•OEt2
H
+
NTs
H
NR
2) Cs2CO3
PdCl2(dppf)•CH2Cl2
NHTs
(100 mol%)
-78 ° to 0 °C,
17.5 hrs.
9
9
9
H
R1
10c
18, 59%
1.5 : 1
(cis : trans)
19, 19%
10a, R = Ts, R1 = Me, 43%
10b, R = Ms, R1 = Me, 34%
10c, R = Ts, R1 = H, 66%
I
SiMe3
15
5
H
5
4
SiMe3
BF3•OEt2
Scheme 2. Synthesis of aziridine–allylsilanes.
H
+
NTs
(100 mol%)
-78 ° to 0 °C,
20 hrs.
NHTs
9
9
With the necessary aziridine–allylsilanes in hand, their cycli-
zation reactions were examined. The cyclization of 16 has pre-
viously been shown to provide an inseparable 2.6:1 mixture of
NHTs
9a, 12%
10a
20a, 33%
2.2 : 1
(cis : trans)
cis 17a to trans 17b
g-amino olefins (84% yield) resulting from
treatment with 300 mol % of BF3$OEt2 at 0 ꢁC for 4 h.2 The azir-
idine–allylsilane 10c was examined in the cyclization reaction
first. This allylsilane differs from previously used allylsilanes by
possessing two structural variables yet encountered in these
types of cyclizations, an E-olefin geometry and methyl sub-
Scheme 3. Initial aziridine–allylsilane cyclizations.
The relative stereochemistry of products such as 9 was pre-
viously determined to be primarily cis-disubstituted cyclo-
pentanes.2–4 However, the stereochemistry at C-4 of compound 20a
could not be directly determined in a similar fashion. A chemical
proof of the stereochemistry via a cyclization of the olefin with the
amine was thus carried out. Six-membered carbocycle 20a, as
stitution of the carbon
b to the silyl group. Upon treatment of
aziridine–allylsilane 10c with 100 mol % of BF3$OEt2, the major
product of the reaction was the formation of an inseparable
a
single diastereomer, was hydroborated with 400 mol % of
mixture of cis and trans
g-amino olefins 18 (59% yield) whose
BH3$THF at room temperature for 15 h, then subsequently oxidized
to provide a mixture of amino alcohols (Scheme 4). The crude
amino alcohol mixture was subjected to Mitsunobu reaction
apparent diastereomeric ratio was 1.5:1 (cis/trans) based on the
integration values of the sulfonamide protons. A cis-fused silylated
azabicycle (19) resulting from a formal [3þ2] intramolecular

D.J. Lapinsky et al. / Tetrahedron 65 (2009) 741–747
743
conditions to provide 2-azabicyclo[3.3.1]nonane 21 in 50% yield
over two steps. The result of this hydroboration/oxidation/Mitsu-
nobu reaction sequence confirms that the 1,3-substituents of sub-
strate 20a possess a cis relationship since a trans relationship
would not result in ring closure under Mitsunobu conditions. The
relative stereochemistry of the 4-methyl group was established
based on coupling constants between the C-3 hydrogens and the
C-4 methine. The identity of H-4, H-3, and Me-4 was identified
based upon 2D spectra. The identity of H-3exo was established
through the observation of NOESY cross-peaks with H-20 and H-200
of the tosyl group as we have previously observed.3 As shown in
Scheme 4, H-3exo has coupling constants of 11.5 Hz and 6.5 Hz,
while H-3endo has coupling constants of 11.5 Hz and 11.0 Hz. Clearly
the 11.5 Hz coupling constants are the geminal coupling constants
between H-3exo and H-3endo. H-3exo has a coupling constant with H-
4exo of only 6.5 Hz, consistent with the equatorial/axial relationship
between H-3exo and H-4exo. The coupling between H-3endo and H-
4exo is 11.0 Hz consistent with a diaxial relationship.
BF3•OEt2
NHTs
NTs
22
NHTs
23, 45%
24, not observed
Me
Me
Me
BF3•OEt2
NHTs
NTs
NHTs
26, 41%
25
27, not observed
Scheme 5. Previously observed aziridine cyclizations with simple
p-nucleophiles.
methyl group and the aziridine groups in roughly axial confor-
mations. The lowest energy conformation (Conformation B)
leading to product 20 has the tether in a pseudo-boat confor-
mation with both the methyl group and aziridine in equatorial
orientations. We hypothesized that having both the aziridine and
methyl in a pseudo-axial conformation drives the reaction to-
ward Conformation B where both groups occupy an equatorial
conformation. This conformational analysis led us to hypothesize
that placing a smaller activating group (R¼Ms) on the nitrogen
could decrease strain of the unfavorable diaxial conformation in
10a and potentially generate more five-membered ring product
(9) upon cyclization.
To test this hypothesis, a mesylated analog (10b) of tether-
substituted aziridine–allylsilane 10a was synthesized and
cyclized. Mesylated analog 10b was synthesized in an identical
manner to its tosyl analog (10a) with the only difference being
the substitution of MsCl for TsCl (Scheme 2). As shown in
Scheme 6, aziridine–allylsilane 10b featuring the smaller mesyl
activating group was treated under the same cyclization condi-
tions (i.e., 100 mol % of BF3$OEt2, ꢀ78 to 0 ꢁC, 18 h) as aziridine–
allylsilane 10a containing the larger tosyl group. The major
product of the reaction was an inseparable mixture of five-
membered carbocycle 9b and six-membered carbocycle 20b in
54% yield. The ratio of the carbocycles was determined to be
1.2:1 based on integration values for the sulfonamide protons
(two distinct triplets for cis and trans 9b (ratio of 1.8:1) and one
distinct doublet for 20b). As a result of using a smaller mesyl
group, the cyclization showed a slight improvement in terms of
desired five-membered carbocycle formation when compared to
its tosyl counterpart (45% yield of 1:3 five-membered/six-mem-
bered carbocycles).
H
1) BH3•THF
4
Me
Me
2) EtOH, NaOH, H2O2
3) Ph3P, DIAD
50%
N
H
Ts
NHTs
20
21
H-4
Me-4
H-3exo
H-4exo
CH3
N
SO2
H-3endo
N
H-3exo
H-2"
H-2'
Ts
H-3endo
Me
21
Scheme 4. Hydroboration/oxidation/Mitsunobu ring closure.
A priori it is not clear why 10a provides both 9a and 20a upon
treatment with BF3$OEt2. One is tempted to use Baldwin’s rules for
ring closure to classify these cyclizations.17–19 However, the sp2
hybridization of the nucleophilic carbon precludes this application.
A second set of rules for ring closure was developed to address the
cyclization reactions of enolates.20 We have used a modification of
the enolate classification system to name these cyclizations. Thus,
the cyclization of 16 to 17 would be classified as a 5-(
p-exo)-exo-
aziridine, indicating that the -nucleophile (the allylsilane) is exo to
p
the newly formed ring and the aziridine is exo in the typical Bald-
win’s rules nomenclature. The reaction of 10a thus cyclizes via both
a 6-(p-exo)-endo-aziridine to provide 20a and the expected 5-(p-
exo)-exo-aziridine cyclization to provide 9a. endo-Aziridine
cyclizations have been previously observed in the cyclizations of
p
-nucleophiles such as olefins and arenes.21
CH3
aziridines with simple
In addition this type of 6-(
H
H
p-endo)-endo-epoxide cyclization has
H
SiMe3
R
been reported.22–25 For example, the cyclizations of 22 and 25
provide only the six-membered ring products 23 and 26, re-
N
H3C
N
R
SiMe3
H
spectively (Scheme 5), in a 6-(
None of the five-membered cyclization products (24 or 27)
resulting from a 5-( -endo)-exo-aziridine was observed. We have
thus identified a previously unobserved type of cyclization the 6-
-exo)-endo-aziridine cyclization. A related (but tether-unsub-
stituted) epoxide–allylsilane has been reported to provide very low
yields (1–9%) of this type of 6-(
-exo)-endo-epoxide cyclization.26
In an effort to understand the origins of this change in
regioselectivity of the cyclization we modeled two possible cycli-
zation conformations (Fig. 2). The lowest energy conformation
(Conformation A) leading to the expected product 9 shows the
p-endo)-endo-aziridine cyclization.
10
10
Conformation A
Conformation B
p
(p
H
p
NHR
NHR
20
9
Figure 2. Steric interactions leading to five- or six-membered carbocycles.

744
D.J. Lapinsky et al. / Tetrahedron 65 (2009) 741–747
and K2CO3 (2.44 g,17.7 mmol), then refluxed for 16.5 h. The mixture
H
was cooled to room temperature, acidified to pH 7 using concen-
trated HCl, and concentrated to provide a crude amino acid salt that
was used without further purification. A suspension of the crude
salt (assume 3.39 mmol) in dry MeOH (6.8 mL) was cooled to 0 ꢁC
and treated carefully with freshly distilled AcCl (1.2 mL,16.9 mmol).
After the addition, the reaction mixture was refluxed for 14.5 h,
cooled to room temperature, and concentrated to provide a crude
methyl ester hydrochloride salt that was used without further
NHMs
SiMe3
BF3•OEt2
H
NMs
10b
9b
(100 mol%)
-78 to 0 °C,
18 hrs, 54%
9b : 20b, 1.2 : 1
purification.
A suspension of the crude ester salt (assume
NHMs
20b
3.39 mmol) in CH2Cl2 (6.8 mL) was cooled to 0 ꢁC and treated with
Et3N (1.2 mL, 8.5 mmol) and TsCl (0.71 g, 3.7 mmol). After the ad-
dition, the ice bath was removed and the reaction mixture was
stirred for an additional 13 h. The mixture was diluted with CHCl3
and washed with 1 M HCl. The aqueous layer was extracted with
CHCl3 and the combined organic layers were washed with satd aq
NaHCO3 solution, brine, dried (MgSO4), filtered, concentrated, and
chromatographed (25% EtOAc in hexanes) to give 0.83 g of dipro-
Scheme 6. Cyclization of N-Ms aziridine–allylsilane 10b.
While attempts to prepare the alkaloid (þ)-
a-skytanthine via an
aziridine–allylsilane cyclization ultimately proved unsuccessful, an
alternative cyclization pathway for tether-substituted C-3 azir-
idine–allylsilanes has been identified. Furthermore, it is apparent
that the ratio of cyclization products is dependent upon the steric
environment of the aziridine ring nitrogen substituent. It also ap-
pears that the course of the cyclization is not affected by
tected amino acid 12a (82% from acid 11). Rf 0.23 (25% EtOAc in
25
hexanes), [
a]
ꢀ9.0 (c 5.2, CHCl3). 1H NMR (CDCl3, 250 MHz)
d 7.67
D
(d, 2H, J¼8.8 Hz), 7.24 (d, 2H, J¼8.8 Hz), 5.59 (m, 1H), 5.32 (d, 1H,
J¼10.8 Hz), 5.01 (m, 2H), 3.81 (m,1H), 3.39 (s, 3H), 2.47 (m,1H), 2.38
substitution on the allylsilane component. The 6-(p-exo)-endo-
aziridine cyclization of 10a leading to the six-membered carbocycle
appears to be more stereoselective than the corresponding reaction
pathway leading to five-membered carbocycles.
(s, 3H), 0.99 (d, 3H, J¼6.8 Hz). 13C NMR (CDCl3, 100 MHz)
d 171.0,
143.5, 137.9, 136.7, 129.5, 127.2, 116.7, 59.9, 51.9, 41.4, 21.4, 15.8. Anal.
Calcd for C14H19NO4S: C, 56.55; H, 6.44; N, 4.71. Found: C, 56.83; H,
6.37; N, 4.64. Chiral HPLC tR¼9.609 min (>98% ee).
3. Experimental
3.1. General
3.3. Methyl (2R,3S)-3-methyl N-[methylsulfonyl]-2-
aminopent-4-enoate (15)
1H NMR spectra were recorded on a Bruker AG 250 MHz spec-
trometer. 13C NMR spectra were recorded on a Varian VX 400 MHz
spectrometer. Chemical shifts are reported in parts per million
relative to CDCl3 (7.27 for 1H, 77.23 for 13C) or C6D6 (7.16 for 1H,
128.39 for 13C). Coupling constants (J) are reported in hertz. The use
The (þ)-phenethylamine salt of 1113,14 was dissolved in satd aq
KHSO4 solution and extracted with EtOAc. The combined organic
layers were dried (MgSO4), filtered, and concentrated to give the
free acid 11, which used without further purification. A solution of
free acid 11 (1.71 g, 7.61 mmol) in MeOH (289 mL) was treated with
H2O (17.4 mL) and K2CO3 (5.48 g, 39.6 mmol), then refluxed for
18 h. The mixture was cooled to room temperature, acidified to pH
7 using concentrated HCl, and concentrated to provide a crude
amino acid salt that was used without further purification. A sus-
pension of the crude salt (assume 7.61 mmol) in dry MeOH
(15.2 mL) was cooled to 0 ꢁC and treated carefully with freshly
distilled AcCl (2.7 mL, 38.0 mmol). After the addition, the reaction
mixture was refluxed for 19 h, cooled to room temperature, and
concentrated to provide a crude methyl ester hydrochloride salt
that was used without further purification. A suspension of the
crude ester salt (assume 7.61 mmol) in CH2Cl2 (15.2 mL) was cooled
to 0 ꢁC and treated with Et3N (2.7 mL, 19.0 mmol) and freshly dis-
tilled MsCl (0.7 mL, 8.4 mmol). After the addition, the ice bath was
removed and the reaction mixture was stirred for an additional
16.5 h. The mixture was diluted with CHCl3 and washed with 1 M
HCl. The aqueous layer was extracted with CHCl3 and the combined
organic layers were washed with satd aq NaHCO3 solution, brine,
dried (MgSO4), filtered, concentrated, and chromatographed (35%
of denotes a signal from minor isomer. Thin layer chromatography
*
(TLC) was performed on EM Science pre-coated silica gel 60 F254
aluminum foils. Purification of the reaction products was carried
out by flash chromatography using a glass column dry packed with
silica gel (ICN SiliTech 32-63D 60 Å) according to the method of
Still.27 Visualization was accomplished with UV light, I2, and/or
phosphomolybdic acid solution followed by heating. HRMS mea-
surements were determined at The Ohio State University Chemical
Instrument Center with a Kratos MS-30 mass spectrometer in the
electron impact (EI) mode. Optical activity was measured on an
Autopol IV automatic polarimeter. Chiral HPLC was performed us-
ing an (R,R)-WHELK-O 1 5/100 HPLC column (250 mmꢂ4.6 mm,
particle size 5 mm) purchased from Regis Technologies. HPLC runs
were performed using 10% EtOH in hexanes at a flow rate of 1.5 mL/
min. Tetrahydrofuran (THF) and diethyl ether (Et2O) were distilled
from sodium and benzophenone prior to use. Dimethylformamide
(DMF), dichloromethane (CH2Cl2), and boron trifluoride diethyl
etherate (BF3$OEt2) were distilled from CaH2 before use. Triethyl-
amine (Et3N) was distilled from CaH2 and stored over KOH pellets.
Methanol (MeOH) was distilled from Mg and I2 and stored over
molecular sieves. All reactions were carried out in flame-dried
glassware under an Ar atmosphere unless otherwise specified.
EtOAc in hexanes) to give 1.11 g of diprotected amino acid 12b (66%
34
from acid 11). Rf 0.34 (40% EtOAc in hexanes), [
CHCl3). 1H NMR (CDCl3, 250 MHz)
(m,1H), 3.76 (s, 3H), 2.93 (s, 3H), 2.66 (m,1H),1.04 (d, 3H, J¼6.9 Hz).
a
]
ꢀ5.4 (c 3.2,
D
d
5.74 (m, 1H), 5.14 (m, 3H), 4.07
13C NMR (CDCl3, 100 MHz)
d 171.7, 138.1, 116.8, 59.9, 52.4, 41.3, 40.9,
3.2. Methyl (2R,3S)-3-methyl N-[(4-methylphenyl)sulfonyl]-2-
15.1. HRMS calcd for C8H15NO4S$Naþ 244.0614, found 244.0607.
aminopent-4-enoate (12a)
3.4. (2R,3S)-3-Methyl-N-[(4-methylphenyl)sulfonyl]-2-amino-
4-pentenol (13a)
The PEA salt of 1113,14 was dissolved in satd aq KHSO4 solution
and extracted with EtOAc. The combined organic layers were dried
(MgSO4), filtered, and concentrated to give the free acid 11, which
was used without further purification. A solution of free acid 11
(0.76 g, 3.4 mmol) in MeOH (129 mL) was treated with H2O (7.7 mL)
A solution of ester 12a (1.00 g, 3.35 mmol) in THF (8.4 mL) was
cannulated into a 0 ꢁC suspension of LiAlH4 (0.64 g, 16.7 mmol) in
THF (6.7 mL). After the addition, the ice bath was removed and

D.J. Lapinsky et al. / Tetrahedron 65 (2009) 741–747
745
the reaction mixture was stirred for an additional 20 h. The re-
action was quenched by the sequential dropwise addition of H2O
(0.64 mL), 15% aq NaOH (0.64 mL), and H2O (1.91 mL), stirring for
15 min after each addition. The precipitate was filtered, washed
with EtOAc, and concentrated. Chromatography (40% EtOAc in
43.5, 39.4, 38.9, 32.3, 17.0. HRMS calcd for C7H13SO2N$Naþ
198.0559, found 198.0560.
3.8. (2R)-2-[(1S)-1-Methyl-5-methyl-5-[(trimethylsilyl)-
methyl]-4-pentenyl]-N-[(4-methylphenyl)-
sulfonyl]aziridine (10a)
hexanes) provided 0.83 g of alcohol 13a (92%). Rf 0.36 (50% EtOAc
24
in hexanes), [
d
a
]
D
ꢀ7.1 (c 5.2, CHCl3). 1H NMR (CDCl3, 250 MHz)
7.76 (d, 2H, J¼8.8 Hz), 7.28 (d, 2H, J¼8.8 Hz), 5.54 (m, 1H), 5.38
9-BBN (9.3 mL, 0.5 M in THF, 4.7 mmol) was added to a 0 ꢁC
solution of olefin 14a (1.06 g, 4.2 mmol) in THF (20 mL). After the
addition, the ice bath was removed and the reaction mixture was
stirred for an additional 4 h. H2O (4.2 mL) and a solution of iodide
1515 (1.19 g, 4.68 mmol) in THF (10 mL) were added to a flask con-
taining Cs2CO3 (4.14 g,12.70 mmol) and PdCl2(dppf)$CH2Cl2 (0.31 g,
0.38 mmol). The organoborane solution was then added via can-
nula to the iodide flask with an additional THF (3 mL) rinsing. The
reaction mixture was stirred in the dark for 17 h, then poured into
H2O and Et2O. The layers were separated and the aqueous layer was
extracted with Et2O. The combined organic layers were washed
with H2O, brine, dried (MgSO4), filtered, concentrated, and chro-
(d, 1H, J¼7.8 Hz), 4.97 (m, 2H), 3.55 (m, 2H), 3.12 (m, 1H), 2.60 (br
s, 1H), 2.41 (s, 3H), 2.28 (m, 1H), 0.89 (d, 3H, J¼6.8 Hz). 13C NMR
(CDCl3, 100 MHz)
d 143.4, 139.6, 137.8, 129.6, 127.1, 116.0, 62.4,
59.4, 39.6, 21.5, 16.4. Anal. Calcd for C13H19SO3N: C, 57.97; H, 7.11;
N, 5.20. Found: C, 58.03; H, 7.09; N, 5.12. Chiral HPLC
tR¼8.977 min (>98% ee).
3.5. (2R,3S)-3-Methyl-N-[methylsulfonyl]-2-amino-4-
pentenol (13b)
A solution of ester 12b (1.04 g, 4.69 mmol) in THF (11.7 mL) was
cannulated into a 0 ꢁC suspension of LiAlH4 (0.89 g, 23.4 mmol) in
THF (9.4 mL). After the addition, the ice bath was removed and the
reaction mixture was stirred for an additional 16 h. The reaction
was quenched by the sequential dropwise addition of H2O
(0.89 mL), 15% aq NaOH (0.89 mL), and H2O (2.67 mL), stirring for
15 min after each addition. The precipitate was filtered, washed
with EtOAc, and concentrated. Chromatography (65% EtOAc in
matographed (100% benzene) to give 0.69 g of aziridine–allylsilane
26
10a (43%). Rf 0.36 (15% EtOAc in hexanes), [
a
]
D
ꢀ11.3 (c 1.6, CHCl3).
1H NMR (CDCl3, 250 MHz)
d
7.83 (d, 2H, J¼7.8 Hz), 7.33 (d, 2H,
J¼7.8 Hz), 4.84 (t, 1H, J¼6.8 Hz), 2.66 (d, 1H, J¼6.8 Hz), 2.51 (m, 1H),
2.45 (s, 3H), 2.12 (d, 1H, J¼4.9 Hz), 1.96 (q, 2H, J¼7.8 Hz), 1.56 (s, 3H),
1.44 (s, 2H), 1.38–1.21 (m, 3H), 0.77 (d, 3H, J¼6.9 Hz), ꢀ0.01 (s, 9H).
13C NMR (CDCl3, 100 MHz)
d 144.3, 135.1, 133.3, 129.5, 128.1, 121.7,
45.6, 34.9, 34.6, 33.4, 29.8, 25.4, 21.6, 18.5, 17.5, ꢀ1.3. HRMS calcd for
hexanes) provided 0.83 g of alcohol 13b (92%). Rf 0.18 (65% EtOAc in
27
C20H33SiNSO2$Naþ 402.1893, found 402.1897.
hexanes), [
a
]
ꢀ9.7 (c 2.6, CHCl3). 1H NMR (CDCl3, 250 MHz)
d 5.73
D
(m,1H), 5.11 (m, 3H), 3.73 (dd,1H, J¼3.9, 2.9 Hz), 3.59 (dd,1H, J¼5.9,
3.9. (2R)-2-[5-Methyl-5-[(trimethylsilyl)methyl]-4-pentenyl]-
N-[(4-methylphenyl)sulfonyl]aziridine (10c)
5.9 Hz), 3.33 (m, 1H), 3.03 (s, 3H), 2.64 (br s, 1H), 2.41 (m, 1H), 1.09
(d, 3H, J¼6.8 Hz). 13C NMR (CDCl3, 100 MHz)
d 139.8, 116.2, 63.2,
59.9, 41.8, 40.2, 16.5. HRMS calcd for C7H15SO3N$Naþ 216.0665,
9-BBN (7.1 mL, 0.5 M in THF, 3.6 mmol) was added to a 0 ꢁC
solution of olefin 14c5 (0.77 g, 3.2 mmol) in THF (20 mL). After the
addition, the ice bath was removed and the reaction mixture was
stirred for an additional 3 h. H2O (3.2 mL) and a solution of iodide
1515 (0.90 g, 3.6 mmol) in THF (5.2 mL) were added to a flask con-
taining Cs2CO3 (3.16 g, 9.68 mmol) and PdCl2(dppf)$CH2Cl2 (0.24 g,
0.29 mmol). The organoborane solution was then added to the io-
dide flask via cannula. The reaction mixture was stirred in the dark
for 14.5 h, then poured into H2O and Et2O. The layers were sepa-
rated and the aqueous layer was extracted with Et2O. The combined
organic layers were washed with H2O, brine, dried (MgSO4), fil-
tered, concentrated, and chromatographed (100% benzene) to give
0.78 g of aziridine–allylsilane 10c (66%). Rf 0.35 (15% EtOAc in
found 216.0653.
3.6. (2R)-2-[(1S)-1-Methyl-2-propenyl]-N-[(4-methylphenyl)-
sulfonyl]aziridine (14a)
Diisopropyl azodicarboxylate (0.2 mL, 1.2 mmol) was added
dropwise to a 0 ꢁC solution of alcohol 13a (0.29 g, 1.1 mmol) and
PPh3 (0.31 g, 1.2 mmol) in THF (5.4 mL). After the addition, the ice
bath was removed and the reaction mixture was stirred for an
additional 16 h. The mixture was concentrated and chromato-
graphed (5–15% EtOAc in hexanes) to give 0.23 g of aziridine 14a
(86%). Rf 0.26 (15% EtOAc in hexanes), [
NMR (CDCl3, 250 MHz)
25
a
]
D
ꢀ20.5 (c 5.5, CHCl3). 1H
26
hexanes), [a]
D
ꢀ6.1 (c 0.52, CHCl3). 1H NMR (CDCl3, 250 MHz)
d
7.81 (d, 2H, J¼8.8 Hz), 7.32 (d, 2H,
J¼7.8 Hz), 5.67 (m, 1H), 5.02 (m, 2H), 2.63 (d, 1H, J¼6.9 Hz), 2.59 (m,
1H), 2.43 (s, 3H), 2.11 (d, 1H, J¼4.9 Hz), 1.91 (m, 1H), 0.89 (d, 3H,
d
7.82 (d, 2H, J¼7.8 Hz), 7.33 (d, 2H, J¼7.8 Hz), 4.82 (t, 1H, J¼7.8 Hz),
2.72 (m, 1H), 2.63 (d, 1H, J¼6.9 Hz), 2.45 (s, 3H), 2.05 (d, 1H,
J¼4.9 Hz), 1.92 (q, 2H, J¼6.8 Hz), 1.55 (s, 3H), 1.44 (s, 2H), 1.60–1.25
J¼6.8 Hz). 13C NMR (CDCl3, 100 MHz)
d 144.5, 138.6, 134.9, 129.6,
(m, 4H), ꢀ0.01 (s, 9H). 13C NMR (CDCl3, 100 MHz)
d 144.3, 135.2,
128.0,115.2, 44.3, 39.3, 32.8, 21.6,17.1. Anal. Calcd for C13H17NSO2; C,
62.12; H, 6.82; N 5.57. Found: C, 62.36; H, 6.83; N, 5.48. Chiral HPLC
tR¼6.007 min (>98% ee).
133.3, 129.6, 127.9, 121.6, 40.4, 33.7, 30.8, 29.8, 27.4, 27.1, 21.6, 18.6,
ꢀ1.3. HRMS calcd for C19H 31SiNSO2$Naþ 388.1737, found 388.1747.
3.7. (2R)-2-[(1S)-1-Methyl-2-propenyl]-N-[methylsulfonyl]-
aziridine (14b)
3.10. (2R)-2-[(1S)-1-Methyl-5-[(trimethylsilyl)methyl]-4-
hexenyl]-N-[methylsulfonyl]aziridine (10b)
Diisopropyl azodicarboxylate (0.9 mL, 4.4 mmol) was added
dropwise to a 0 ꢁC solution of alcohol 13b (0.78 g, 4.0 mmol) and
PPh3 (1.16 g, 4.4 mmol) in THF (20.1 mL). After the addition, the ice
bath was removed and the reaction mixture was stirred for an
additional 65 h. The mixture was concentrated and chromato-
9-BBN (3.3 mL, 0.5 M in THF, 1.6 mmol) was added to a 0 ꢁC
solution of olefin 14b (0.26 g, 1.49 mmol) in THF (11.6 mL). After the
addition, the ice bath was removed and the reaction mixture was
stirred for an additional 5 h. H2O (1.5 mL) and a solution of iodide
1515 (0.42 g, 1.6 mmol) in THF (5 mL) were added to a flask con-
taining Cs2CO3 (1.46 g, 4.48 mmol) and PdCl2(dppf)$CH2Cl2 (0.11 g,
0.13 mmol). The organoborane solution was then added via cannula
to the iodide flask with an additional THF (1.6 mL) rinsing. The
reaction mixture was stirred in the dark for 19 h, then poured into
H2O and Et2O. The layers were separated and the aqueous layer was
graphed (4–30% EtOAc in hexanes) to give 0.64 g of aziridine 14b
25
(86%). Rf 0.48 (40% EtOAc in hexanes), [
a
]
ꢀ74.4 (c 5.0, CHCl3). 1H
D
NMR (CDCl3, 250 MHz)
d
5.76 (m, 1H), 5.09 (m, 2H), 3.03 (s, 3H),
2.61 (m, 1H), 2.55 (d, 1H, J¼6.9 Hz), 2.14 (d, 1H, J¼3.9 Hz), 2.06 (m,
1H), 1.13 (d, 3H, J¼6.9 Hz). 13C NMR (CDCl3, 100 MHz)
d 138.5, 115.4,

746
D.J. Lapinsky et al. / Tetrahedron 65 (2009) 741–747
extracted with Et2O. The combined organic layers were washed
with H2O, brine, dried (MgSO4), filtered, concentrated, and chro-
matographed (100% benzene) to give 0.16 g of aziridine–allylsilane
10b (34%). Rf 0.41 (25% EtOAc in hexanes). 1H NMR (CDCl3,
d
7.88 (two overlapping d, 3.61H), 6.85–6.80 (two overlapping d,
3.62H), 5.29 (t, 1H, J¼6.8 Hz), 5.16 (t, 0.46H, J¼5.9 Hz), 4.74–4.68
(three overlapping app s, 2.93H), 4.62 (app s, 0.58H), 3.06–2.87 (m,
1.88H), 2.92–2.73 (m, 1.77H), 2.73–2.62 (m, 0.51H), 2.32 (q, 0.54H,
J¼6.8 Hz), 2.11 (q, 1.16H, J¼8.8 Hz), 1.91 (s, 3H), 1.88 (s, 3H), 1.83–
1.63 (m, 0.75H), 1.55 (s, 3H), 1.52 (s, 3H), 1.60–1.48 (m, 1.66H), 1.44–
1.22 (m, 2.86H),1.12–0.96 (m, 0.66H), 0.92–0.88 (two overlapping d,
*
*
250 MHz)
d
4.89 (t, 1H, J¼6.8 Hz), 3.07 (s, 3H), 2.61 (d, 1H, J¼6.8 Hz),
*
2.54 (m,1H), 2.1 (d,1H, J¼4.9 Hz), 2.04 (q, 2H, J¼6.8 Hz),1.57 (s, 3H),
*
1.46 (s, 2H), 1.45–1.27 (m, 3H), 1.06 (d, 3H, J¼5.9 Hz), 0.0 (s, 9H). 13C
NMR (CDCl3, 100 MHz)
d
133.5, 121.6, 45.0, 39.4, 34.8, 34.6, 33.0,
5.76H). 13C NMR (CDCl3, 100 MHz)
137.0 , 136.9, 129.6, 129.6 , 127.1, 127.0
48.3, 48.1 , 46.2, 44.4, 37.7, 37.2 , 33.1, 33.1
21.5 , 21.5, 19.4, 18.8
. HRMS for C17H25NSO2$Naþ calcd 330.1498,
d
148.3, 146.1
, 111.4 , 111.2, 53.0, 49.4
, 29.6, 28.6 , 23.1
*
, 143.2, 143.2
*
,
,
29.8, 25.4, 18.6, 17.7, ꢀ1.3. HRMS calcd for C14H29SiNSO2$Naþ
*
*
*
*
*
326.1586, found 326.1599.
*
*
*
*
*
, 23.1,
*
*
3.11. cis and trans-(1R)-2-(2-Propenyl)-1-[(4-
found 330.1505. Data for cyclohexane 20a: Rf 0.30 (100% benzene),
24
methylphenyl)sulfonyl]aminomethyl-cyclopentane (18) and
(3aR,6aS)-N-[(4-methylphenyl)sulfonyl]-1-methyl-1-
[(trimethylsilyl)methyl]hexahydrocyclopenta[c]pyrrole (19)
[a
]
þ81.0 (c 8.3, CHCl3). 1H NMR (C6D6, 250 MHz)
d 7.96 (d, 2H,
D
J¼7.8 Hz), 6.84 (d, 2H, J¼7.8), 5.54 (d, D2O-exchangeable, 1H,
J¼8.8 Hz), 4.66 (app s, 1H), 4.63 (app s, 1H), 2.92 (m, 1H), 2.00–1.90
(m, 1H), 1.90 (s, 3H), 1.73–1.63 (m, 1H), 1.49–1.34 (m, 2H), 1.49 (s,
3H), 1.15–0.75 (m, 4H), 0.91 (d, 3H, J¼6.8 Hz). 13C NMR (CDCl3,
A solution of aziridine–allylsilane 10c (0.30 g, 0.83 mmol) in
CH2Cl2 (8.3 mL) was cooled to ꢀ78 ꢁC and treated with freshly
distilled BF3$OEt2 (0.1 mL, 0.8 mmol). After the addition, the re-
action mixture was warmed to 0 ꢁC and maintained at this tem-
perature for 17.5 h. The mixture was quenched with satd aq
NaHCO3 and warmed to room temperature. The mixture was di-
luted with CH2Cl2 and H2O and the layers were separated. The
aqueous layer was extracted with CH2Cl2. The combined organic
layers were washed with brine, dried (MgSO4), filtered, concen-
trated, and chromatographed (100% benzene) to first give 57.3 mg
of bicycle 19 (19%) followed by an inseparable mixture of 142.7 mg
of olefins 18 (59%, ca. 1.5:1 cis/trans). Data for bicycle 19: Rf 0.40
100 MHz)
d 148.8, 143.0, 138.6, 129.5, 126.9, 108.6, 59.2, 44.3, 39.8,
38.2, 34.1, 30.7, 21.4, 20.8, 18.8. HRMS for C17H25NSO2$Naþ calcd
330.1498, found 330.1508.
3.13. (1S,5S,8S)-4,8-Dimethyl-N-[(4-methylphenyl)sulfonyl]-
2-azabicyclo[3.3.1]nonane (21)
BH3$THF (2.1 mL, 1 M in THF, 2.1 mmol) was added to a solution
of olefin 20a (0.16 g, 0.53 mmol) in THF (1.1 mL). After the addition,
the reaction mixture was stirred for 15 h, then cooled to 0 ꢁC. EtOH
(1.2 mL) was added dropwise and the mixture was stirred for 5 min
before adding 6 N NaOH (0.4 mL) and 30% H2O2 (0.8 mL). The
mixture was refluxed for 1 h, then cooled to room temperature and
diluted with H2O and EtOAc. The layers were separated and the
aqueous layer was extracted with EtOAc. The combined organic
layers were washed with brine, dried (MgSO4), filtered, and con-
centrated to give 165.7 mg of a crude mixture of amino alcohols
(96%) that was used without further purification. Diisopropyl azo-
dicarboxylate (0.1 mL, 0.6 mmol) was added dropwise to a 0 ꢁC
solution of the crude mixture of amino alcohols (0.17 g, 0.53 mmol)
and PPh3 (0.15 g, 0.58 mmol) in THF (2.6 mL). After the addition, the
ice bath was removed and the reaction mixture was stirred for an
additional 23.5 h. The mixture was concentrated and chromato-
graphed (100% benzene) to give 80.9 mg of bicycle 21 (50% from
(15% EtOAc in hexanes). 1H NMR (CDCl3, 250 MHz)
d 7.71 (d, 2H,
J¼7.8 Hz), 7.26 (d, 2H, J¼7.8 Hz), 3.62 (t, 1H, J¼9.8 Hz), 2.92 (dd, 1H,
J¼15.6, 5.9 Hz), 2.67–2.50 (m, 1H), 2.41 (s, 3H), 2.32–2.22 (m, 1H),
1.91–1.80 (m, 1H), 1.74–1.12 (m, 5H), 1.49 (s, 3H), 1.45 (s, 2H), 0.04 (s,
9H). 13C NMR (CDCl3, 100 MHz)
d
142.5, 138.6, 129.2, 127.1, 70.7,
56.8, 54.1, 38.8, 31.9, 31.3, 28.2, 26.0, 25.0, 21.4, 0.4. Data for olefins
26
18: Rf 0.27 (15% EtOAc in hexanes), [
notes signal from minor isomer) 1H NMR (C6D6, 250 MHz)
7.91 (two overlapping d, 4.15H), 6.87–6.82 (two overlapping d,
4.20H), 5.63 (t, 1H, J¼5.9 Hz), 5.55 (t, 0.68H, J¼6.8 Hz), 4.70–4.68
(two overlapping app s, 3.24H), 4.60 (app s, 0.82H), 3.08–3.06 (m,
1.26H), 2.91–2.82 (m, 0.90H), 2.78–2.65 (m, 1.04H), 2.62–2.54 (m,
0.53H), 2.13–2.08 (m, 2.14H), 1.92 (s, 3H), 1.90 (s, 3H), 1.86–1.68 (m,
2.03H), 1.57
(s, 3H), 1.50 (s, 3H), 1.57–1.14 (m, 12.79H). 13C NMR
(CDCl3, 100 MHz) 147.3, 145.5 , 143.2, 143.1 , 137.1 , 137.0, 129.6,
129.6 , 127.0, 127.0 , 111.0, 110.9 , 52.1 , 49.3, 47.5, 44.1 , 42.4, 40.8
31.7, 30.1 , 23.8, 23.3, 23.3 , 22.6 , 21.4, 19.1 . HRMS for
a
]
ꢀ8.8 (c 7.3, CHCl3). (
*
de-
D
d
7.95–
*
*
*
*
*
*
olefin 20a) as a single diastereomer. Rf 0.41 (15% EtOAc in hexanes),
23
d
*
*
*
[a
]
ꢀ15.9 (c 1.1, CHCl3). 1H NMR (C6D6, 250 MHz)
d 7.77 (d, 2H,
D
*
*
*
*
*
*
,
J¼7.8 Hz), 6.83 (d, 2H, J¼7.8 Hz), 3.67–3.60 (m, 2H), 2.49–2.41 (m,
2H), 2.09–1.92 (m, 1H), 1.92 (s, 3H), 1.67–1.61 (m, 1H), 1.39–1.22 (m,
1H), 1.19–0.78 (m, 5H), 0.86 (d, 3H, J¼7.8 Hz), 0.59 (d, 3H, J¼6.8 Hz).
*
, 29.0, 27.6
*
*
*
*
C16H23NSO2$Naþ calcd 316.1342, found 316.1344.
13C NMR (CDCl3, 100 MHz)
d 142.9, 135.3, 129.5, 127.3, 54.7, 47.5,
3.12. cis and trans-(1R,5S)-2-(2-Propenyl)-5-methyl-1-[(4-
methylphenyl)sulfonyl]aminomethyl-cyclopentane (9a) and
(1S,3S,6S)-3-(2-propenyl)-6-methyl-1-[(4-methylphenyl)-
sulfonyl]amino-cyclohexane (20a)
33.3, 32.5, 32.3, 26.5, 22.6, 21.6, 21.4, 20.3, 16.7. HRMS for
C17H25NSO2$Naþ calcd 330.1498, found 330.1497.
3.14. cis and trans-(1R,5S)-2-(2-Propenyl)-5-methyl-1-
[methylsulfonyl]aminomethyl-cyclopentane (9b) and
(1S,3S,6S)-3-(2-propenyl)-6-methyl-1-[methylsulfonyl]amino-
cyclohexane (20b)
A solution of aziridine–allylsilane 10a (0.60 g, 1.6 mmol) in
CH2Cl2 (15.9 mL) was cooled to ꢀ78 ꢁC and treated with freshly
distilled BF3$OEt2 (0.2 mL, 1.6 mmol). After the addition, the re-
action mixture was warmed to 0 ꢁC and maintained at this tem-
perature for 20 h. The mixture was quenched with satd aq NaHCO3
and warmed to room temperature. The mixture was diluted with
CH2Cl2 and H2O and the layers were separated. The aqueous layer
was extracted with CH2Cl2. The combined organic layers were
washed with brine, dried (MgSO4), filtered, concentrated, and
chromatographed (100% benzene) to first give an inseparable
mixture of 57.4 mg of cyclopentanes 9a (12%, ca. 2.2:1 cis/trans)
A solution of aziridine–allylsilane 10b (88 mg, 0.29 mmol) in
CH2Cl2 (3 mL) was cooled to ꢀ78 ꢁC and treated with freshly dis-
tilled BF3$OEt2 (0.04 mL, 0.29 mmol). After the addition, the re-
action mixture was warmed to 0 ꢁC and maintained at this
temperature for 20 h. The mixture was quenched with satd aq
NaHCO3 and warmed to room temperature. The mixture was di-
luted with CH2Cl2 and H2O and the layers were separated. The
aqueous layer was extracted with CH2Cl2. The combined organic
layers were washed with brine, dried (MgSO4), filtered, concen-
trated, and chromatographed (100% benzene) to give an inseparable
mixture of 36 mg (54%) of cyclopentane 9b (2.2:1 cis/trans) and
followed by 162.5 mg of cyclohexane 20a (33%). Data for cyclo-
24
pentanes 9a: Rf 0.42 (100% benzene), [
*
a
]
þ41.0 (c 3.1, CHCl3).
D
(
denotes signal from minor isomer) 1H NMR (C6D6, 250 MHz)

D.J. Lapinsky et al. / Tetrahedron 65 (2009) 741–747
747
cyclohexane 20b. Rf 0.18 (25% EtOAc in hexanes). 1H NMR (CDCl3,
250 MHz)
J¼7.5 Hz), 4.11 (d, 0.9H, J¼9.0 Hz), 2.95–2.68 (m, 2.0H), 2.40 (s,
1.3H), 2.30 (s, 1.0H), 2.26 (s, 0.6H), 2.10 (m, 1.4H), 1.69 (m, 0.6H), 1.58
(m, 3H), 1.56–1.20 (m, 0.6H), 1.21 (m, 2H), 0.88 (m, 3H). 13C NMR
3. Bergmeier, S. C.; Fundy, S. L.; Seth, P. P. Tetrahedron 1999, 55, 8025.
4. Bergmeier, S. C.; Seth, P. P. J. Org. Chem. 1999, 64, 3237.
5. Lapinsky, D. J.; Bergmeier, S. C. Tetrahedron 2002, 58, 7109.
6. Harris, G. S.; Fidman, E. C.; Stemitz, F. R.; Castedo, L. J. Nat. Prod. 1988, 51,
543.
7. Oppolzer, W.; Jacobsen, E. J. Tetrahedron Lett. 1986, 27, 1141.
8. Tsunoda, T.; Ozaki, F.; Shirakata, N.; Tamaoka, Y.; Yamamoto, H.; Ito, S. Tetra-
hedron Lett. 1996, 52, 2463.
d
4.73 (m, 2H), 4.42 (br t, 0.7H, J¼7.5 Hz), 4.28 (br t, 0.4H,
(CDCl3, 100 MHz)
d 149.0, 148.3, 146.2, 111.7, 111.5, 109.2, 59.5, 56.3,
9. Ernst, M.; Helmchen, G. Synthesis 2002, 1953.
52.9, 49.9, 48.7, 48.2, 46.0, 44.5, 42.1, 40.6, 39.9, 38.3, 37.6, 37.2, 34.2,
33.1, 30.9, 29.7, 28.7, 23.4, 21.9, 20.8, 19.6, 19.2, 18.9. HRMS for
C11H21NSO2$Naþ calcd 254.1191, found 254.1205.
10. Cossy, J.; Leblanc, C. Tetrahedron Lett. 1991, 32, 3051.
11. Vidari, G.; Tripolini, M.; Novella, P.; Allegrucci, P.; Garlaschelli, L. Tetrahedron:
Asymmetry 1997, 8, 2893.
12. Cid, M. M.; Pombo-Villar, E. Helv. Chim. Acta 1993, 76, 1591.
13. Kazmaier, U.; Krebs, A. Tetrahedron Lett. 1999, 40, 479.
14. Kazmaier, U.; Schneider, C. Synthesis 1998, 1321.
Acknowledgements
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This work was supported in part by the National Science
Foundation (CHE 9815208).
Supplementary data
Supplementary data associated with this article can be found in
the online version, at doi:10.1016/j.tet.2008.11.043.
References and notes
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