Asymmetric formal synthesis of (-)-swainsonine by a highly regioselective and diastereoselective allylic amination using chlorosulfonyl isocyanate

Article abstract of DOI:10.1002/ejoc.201300308

A concise asymmetric formal synthesis of (-)-swainsonine from readily available D-erythronolactone is described. The key steps include a highly diastereoselective amination of a chiral benzylic ether, which occurs with the retention of stereochemistry using chlorosulfonyl isocyanate, and a palladium-catalyzed decarboxylative N-allylation of an allyl carbamate. Copyright

Full text of DOI:10.1002/ejoc.201300308

FULL PAPER
DOI: 10.1002/ejoc.201300308
Asymmetric Formal Synthesis of (–)-Swainsonine by a Highly Regioselective
and Diastereoselective Allylic Amination Using Chlorosulfonyl Isocyanate
Qing Ri Li,[a][‡] Guang Ri Dong,[a][‡] Sook Jin Park,[a] Yong Rae Hong,[a] In Su Kim,[a] and
Young Hoon Jung*[a]
Keywords: Synthesis design / Nitrogen heterocycles / Alkaloids / Amination / Allylation / Diastereoselectivity
A concise asymmetric formal synthesis of (–)-swainsonine
from readily available -erythronolactone is described. The
key steps include a highly diastereoselective amination of a
chiral benzylic ether, which occurs with the retention of
stereochemistry using chlorosulfonyl isocyanate, and a palla-
dium-catalyzed decarboxylative N-allylation of an allyl carb-
amate.
D
and interesting biological activities, several methods have
been developed for the synthesis of 1.[14–18] Given the struc-
tural relationship of swainsonine to carbohydrates[15] and
α-amino acids,[16] it is not surprising that most of the syn-
theses use these compounds as starting materials. One syn-
thesis relies on a series of asymmetric synthetic reactions to
construct the stereogenic centers.[17] In a recent example
that uses a carbohydrate as a chiral pool, Wardrop and co-
workers reported the total synthesis of 1 from 2,3-O-iso-
propylidene-d-erythrose through the diastereoselective ad-
dition of an acylnitrenium ion to an alkene to form the
pyrrolidine framework.[15h] In another example that uses a
chiral pool, Chemla et al. described the asymmetric total
synthesis of 1 from readily available d-erythronolactone
through the addition of allenylmetals to chiral α,β-alkoxy
sulfinylimines.[15i] In a representative example of an asym-
metric synthesis, Ham and co-workers demonstrated the
asymmetric total synthesis of 1 through a palladium-cata-
lyzed formation of an oxazoline, a diastereoselective dihy-
droxylation, and a diastereoselective allylation reaction as
the key steps.[17k] Bates and Dewey reported the asymmetric
formal synthesis of 1 that started from tetrahydrofuran and
employed a gold-catalyzed allene cyclization and palla-
dium-catalyzed alloc contraction as the key steps.[18d]
Introduction
Polyhydroxylated indolizidine alkaloids are among the
most interesting discoveries in the field of natural prod-
ucts.[1] They are widely distributed in many plants and mi-
croorganisms and have been reported to exhibit a range of
biological activities that include immunoregulatory, anti-
HIV, and anticancer activities.[2] Consequently, a variety of
natural or non-natural polyhydroxylated indolizidine alka-
loids have been prepared and evaluated for their clinical
applications.[3] (–)-Swainsonine (1, see Figure 1) is a polyhy-
droxylated indolizidine alkaloid that was isolated first from
the fungal plant pathogen Rhizoctonia leguminicola[4] and
later from the Australian plant Swainsona canescens,[5] the
North American spotted locoweed plant Astragalus lentig-
inosus,[6] and the fungus Metarhizium anisoplia.[7] (–)-
Swainsonine is a potent inhibitor of the Golgi enzyme α-
mannosidase II, an enzyme required for the maturation of
N-linked oligosaccharides of newly formed glycoproteins.[8]
Compound 1 is also reported to block lysosomal α-manno-
sidase, which causes the accumulation of oligomannoside
chains in cells exposed to the drug.[9] Furthermore, this mo-
lecule exhibits interesting activity against some mammalian
tumor cell lines[10] and possesses immunomodulatory and
antiviral activities.[11,12] Although the structurally related
indolizidine alkaloid (+)-castanospermine (2) has received
considerable attention as an immunoregulatory sub-
stance,[13] the synthesis and biological evaluation of swain-
sonine and analogues thereof have been the subjects of in-
tensive research. Because of the unique structural features
Figure 1. Structures of (–)-swainsonine (1), (+)-castanospermine
(2), and (–)-lentiginosine (3).
[a] School of Pharmacy, Sungkyunkwan University,
Suwon 440-746, Republic of Korea
Fax: +82-31-290-7773
E-mail: yhjung@skku.edu
Homepage: http://pharm.skku.edu/
[‡] These authors contributed equally
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201300308.
As part of an ongoing research program that is aimed at
developing asymmetric total syntheses of biologically active
alkaloids,[19] we recently described a facile strategy for the
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Y. H. Jung et al.
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construction of the indolizidine alkaloid (–)-lentiginosine of cis and trans isomers (cis/trans, 1:2) in 83% yield. We
(3) based on the regioselective and diastereoselective allylic then sought the selective reduction of α,β-unsaturated ester
amination of polybenzyl ethers using chlorosulfonyl isocy- 7 to give saturated primary alcohol 9, which left the internal
anate (CSI).[20] In connection with our previous work re- alkene intact and was accomplished in either a single step
garding the stereoselective amination of various allylic or over two consecutive steps. An attempt to perform a one-
ethers using CSI, we herein describe an asymmetric formal pot reduction of α,β-unsaturated ester 7 with LiAlH4 af-
synthesis of (–)-swainsonine (1) that starts from commer- forded a 1:1 mixture of the desired saturated alcohol 9 and
cially available d-erythronolactone. The key steps include a the undesired allylic alcohol concomitant with ester 8 in a
highly stereoselective amination of 1,2-anti-substituted 71% combined yield. In view of these unsuccessful results,
benzyl ether using chlorosulfonyl isocyanate and a palla- we changed our synthetic plan to a two-step transforma-
dium-catalyzed decarboxylative N-allylation of an allyl tion, which involved a partial reduction of the olefin in α,β-
carbamate.
unsaturated ester 7 and subsequent reduction of the ester
group. After an extensive screening of the optimal reaction
conditions, we found that a combination of sodium borohy-
dride and cuprous chloride in the presence of cyclohexene
Results and Discussion
The total synthesis of indolizidine alkaloid 1 was furnished our desired α,β-saturated ester 8 in 95% yield.[22]
achieved by starting with 4, which was prepared from com- The reduction of ester 8 under standard conditions
mercially available d-erythronolactone according to a litera- [LiAlH4, tetrahydrofuran (THF)] afforded primary alcohol
ture report (see Scheme 1).[21] The reduction of lactone 4 9, which was subjected to an Appel reaction (PPh3, CBr4,
with diisobutylaluminum hydride (DIBAL-H) in CH2Cl2 at and Et3N) to furnish compound 10 in 87% yield.
–78 °C followed by a Wittig reaction of the resulting lactol
Next, the diastereoselectivity of the reaction of 10 and
afforded olefin 5 as an inseparable mixture of cis and trans chlorosulfonyl isocyanate was examined under various con-
isomers (cis/trans, 1.9:1) in 79% yield. The isomerization of ditions, and the selected results are summarized in Table 1.
the olefin in the diastereomeric mixture of 5 by treatment As shown in Entry 1, the reaction in dichloromethane at
with 2,2Ј-azobis(isobutyronitrile) (AIBN) and thiophenol 0 °C gave the desired product 11 and its diastereomer in a
exclusively gave trans olefin 6. The homologation of two ratio of 10:1. After screening different solvents under other-
carbons to construct the piperidine ring was performed by wise identical conditions, toluene was found to be most ef-
the oxidation of alcohol 6 and a subsequent Wittig reaction fective for this reaction. As shown in Entry 4, the reaction
using a stabilized ylide to afford 7 as a separable mixture in toluene exclusively afforded compound 11 in 83% yield
Scheme 1.
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Asymmetric Formal Synthesis of (–)-Swainsonine
Scheme 3.
with an excellent diastereoselectivity (dr 16:1). The dia- were unsuccessful and led to recovery of most of the start-
stereoselectivity of compound 11 can be explained by a ing material or decomposition of the starting material.[23]
neighboring group effect, whereby the orientation of the
Thus, we focused our synthetic protocol to the removal
NHCbz (Cbz = benzyloxycarbonyl) group retains the origi- of the Cbz and benzyl protecting groups followed by an
nal configuration by double inversion of the configura- intramolecular cyclization to obtain the piperidine ring (see
tion.[19]
Scheme 3). To our delight, the treatment of 11 with BCl3 in
dichloromethane removed the Cbz and benzyl groups fol-
lowed by an intramolecular cyclization to provide piper-
idine 14. To obtain target compound 16 for the formal syn-
thesis of (–)-swainsonine (1), the introduction of a tert-but-
yldimethylsilyl (TBS) group to 14 and subsequent N-allyl-
ation was performed under standard reaction conditions.
However, the direct N-allylation of 15 by using allyl iodide
or allyl bromide provided poor yields of the desired com-
pound 16 (see Table 3). On the other hand, the introduction
of an allyloxycarbonyl group (see Table 3, Entry 5) followed
by a palladium-catalyzed decarboxylative N-allylation[24] of
allyl carbamate 17 proved to be a highly satisfactory route,
which provided compound 16 in 85% yield. The spectro-
scopic data and the specific rotation of 16 were in full agree-
ment with the reported literature value.[18a]
Table 1. Selected results for optimization of the diastereoselective
amination of 10.[a]
Entry
Solvent
Time [h]
% Yield[b]
dr[c]
1
2
3
4
CH2Cl2
CCl4
n-hexane
toluene
10
18
24
12
87
75
85
83
10:1
10:1
12:1
16:1
[a] Reagents and conditions: (i) 10 (1 equiv.), chlorosulfonyl isocy-
anate (3 equiv.), Na2CO3 (4.5 equiv.), solvent (0.25 m), 0 °C;
(ii) aqueous saturated solution of Na2SO3, room temp., 12 h.
[b] Isolated yield by flash column chromatography. [c] Dia-
stereomeric ratio (dr) was determined by H NMR analysis of the
crude reaction mixture.
1
First, we envisioned the selective removal of the Cbz pro-
tecting group in compound 12 to give piperidine 13, which
can then be converted into the indolizidine framework
through an N-allylation and a ring-closing metathesis reac-
tion (see Scheme 2). Thus, compound 11 was treated with
KOtBu to afford compound 12, which was then subjected
to various reaction conditions to remove the Cbz protecting
group as shown in Table 2. Nevertheless, these attempts
Table 3. Reaction conditions for allylation and allyloxycarbonyl-
ation of 15.
Entry Reaction conditions
% Yield
16[a]
17[a]
1
allyl iodide, K2CO3, MeCN, 50 °C,
10 h
6
2
3
4
5
allyl iodide, KOtBu, 80 °C, 10 h
allyl bromide, NaH, DMF,[b] r. t., 10 h
allyl iodide, NaH, DMF, r. t.., 10 h
allyl chloroformate, Na2CO3, CH2Cl2,
r. t., 4 h
4
5
10
83
[a] Isolated yield by flash column chromatography. [b] DMF =
N,N-dimethylformamide.
Scheme 2.
Table 2. Reaction conditions for removing Cbz protecting group of
12.
Conclusions
Entry Reaction conditions
% Yield
n.r.[a]
In summary, we have described a concise formal synthe-
sis of (–)-swainsonine from readily available d-erythrono-
lactone in 11 linear steps (13.4% overall yield) through a
highly diastereoselective amination of a chiral benzylic
ether, which occurs with the retention of stereochemistry
using chlorosulfonyl isocyanate, and a palladium-catalyzed
1
2
3
LiOH (10 equiv.), 1,4-dioxane/H2O (4:1),
120 °C, 18 h
KOH (10 equiv.), 1,4-dioxane/H2O (4:1),
120 °C, 18 h
n.r.
Pd(OAc)2, Et3SiH, Et3N, CH2Cl2, reflux, 24 h n.r.
[a] n.r.: no reaction.
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Y. H. Jung et al.
FULL PAPER
cal ionization (CI)]: calcd. for C25H25O3 [M – H]+ 373.1806; found
373.1804.
decarboxylative N-allylation of an allyl carbamate. It is be-
lieved that this synthetic strategy can be applied to the prep-
aration of a broad range of biologically active compounds
that contain a chiral amine moiety.
(2R,3S,E)-2,3-Bis(benzyloxy)-5-phenylpent-4-en-1-ol (6): To
a
stirred solution of 5 (4.5 g, 12.0 mmol) in anhydrous benzene
(120 mL) were added PhSH (0.6 mL, 6.0 mmol) and AIBN
(394 mg, 2.4 mmol) at room temperature under N2. The reaction
mixture was heated at reflux for 3 h. The resulting mixture was
cooled to room temperature and concentrated in vacuo. The resi-
due was purified by flash column chromatography (n-hexanes/
EtOAc, 4:1) to afford 6 (3.78 g, 10.08 mmol, 84% yield) as a color-
less syrup; Rf = 0.26 (n-hexanes/EtOAc, 4:1). [α]2D2 = +51.8 (c = 2.5,
Experimental Section
General Methods: Commercially available reagents were used with-
out additional purification, unless otherwise stated. All reactions
were performed under an inert atmosphere of nitrogen or argon.
The 1H and 13C NMR spectroscopic data were recorded with a
Varian Unit 500 MHz spectrometer using CDCl3 solutions, and the
chemical shifts are reported in parts per million (ppm) relative to
the residual CHCl3 δH (δ = 7.26 ppm for 1H NMR) and CDCl3
δC (δ = 77.0 ppm for 13C NMR) as internal standards. Resonance
patterns are reported with the notations s (singlet), d (doublet), t
(triplet), q (quartet), and m (multiplet). In addition, the notation
br. is used to indicate a broad signal. Coupling constants (J) are
reported in Hertz (Hz). IR spectra were recorded with a Bruker
Infrared spectrophotometer and are reported in cm–1. Optical rota-
tions were measured with a Jasco P1020 polarimeter. Thin layer
chromatography was carried out using plates coated with Kieselgel
60F254 (Merck). For flash column chromatography, E. Merck Kie-
selgel 60 (230–400 mesh) was used. High resolution mass spectra
were recorded with a JEOL JMS-600 spectrometer.
CHCl ). IR (neat): ν = 3448, 3030, 2872, 1721, 1602, 1494, 1452,
˜
3
1365, 1094, 971, 747, 697, 610 cm–1. 1H NMR (500 MHz, CDCl3):
δ = 2.23 (br. s, 1 H), 3.60–3.63 (m, 1 H), 3.79 (br. s, 2 H), 4.11–
4.14 (m, 1 H), 4.45 (d, J = 11.5 Hz, 1 H), 4.59–4.71 (m, 2 H), 6.18
(dd, J = 16.0, 8.0 Hz, 1 H), 6.63 (d, J = 16.0 Hz, 1 H), 7.20–7.43
(m, 15 H) ppm. 13C NMR (125 MHz, CDCl3): δ = 62.4, 70.9, 73.1,
80.8, 81.5, 126.8, 127.3, 127.9, 128.0, 128.1, 128.2, 128.3, 128.7,
128.8, 128.9, 134.6, 136.6, 138.3, 138.4 ppm. HRMS (CI): calcd.
for C25H25O3 [M – H]+ 373.1806; found 373.1804.
(4R,5S,6E)-Methyl 4,5-Bis(benzyloxy)-7-phenylhepta-2,6-dienoate
(7): To a stirred solution of oxalyl chloride (2 m in CH2Cl2,
10.6 mL, 21.15 mmol) in dry CH2Cl2 (60 mL) at –78 °C was added
DMSO (3.3 mL, 47 mmol) in CH2Cl2 (10 mL) over 20 min, and the
mixture was stirred for 40 min. Then, alcohol 6 (3.52 g, 9.4 mmol)
in CH2Cl2 (10 mL) was added over 30 min, and the mixture was
stirred for an additional 1 h. Triethylamine (7.2 mL, 51.7 mmol) in
CH2Cl2 (10 mL) was added over 20 min, and the white slurry was
stirred for 30 min at –78 °C. To the reaction mixture was added
methyl(triphenylphosphoranylidene) acetate (7.3 g, 21.6 mmol) in
one portion, and the resulting mixture was stirred for 12 h as it
warmed to room temperature. Water (50 mL) was added to the
reaction mixture, and the two layers were separated. The aqueous
layer was extracted with CH2Cl2 (3ϫ75 mL). The combined or-
ganic layers were washed with brine, dried with MgSO4, and con-
centrated in vacuo. The residue was purified by flash column
(2R,3S)-2,3-Bis(benzyloxy)-5-phenylpent-4-en-1-ol (5): To a stirred
solution of 4 (9.0 g, 30.0 mmol) in dichloromethane (300 mL) co-
oled to –78 °C was added DIBAL-H (1.0 m in toluene, 42 mL). The
resulting solution was mixed at –78 °C for 1 h and then was
quenched with a mixture of Na2SO4·10H2O/Celite (2:1) until mix-
ing became difficult. At this time, the cooling bath was removed,
and a sufficient amount of dichloromethane was added to afford a
vigorously stirring solution. The stirring was then continued for
10 h. The solution was then filtered, and the filter cake was washed
with EtOAc (2ϫ500 mL). Concentration of the filtrate afforded
the crude lactol (8.8 g) as an oil, which was used without further
purification. To a stirred solution of dimethyl sulfoxide (DMSO,
10.4 mL, 146.5 mmol) in anhydrous THF (100 mL) was added
NaH (60% in mineral oil, 3.5 g, 87.9 mmol) at 0 °C under N2. The
reaction mixture was stirred for 1 h at room temperature and then
cooled to 0 °C. Benzyltriphenylphosphonium chloride (34.2 g,
87.9 mmol) was added in one portion, and the reaction mixture
was stirred for 2 h at room temperature and then cooled to 0 °C.
A solution of lactol (8.8 g, 29.3 mmol) in anhydrous THF (46 mL)
was slowly added, and the reaction mixture was stirred for 12 h at
room temperature. After cooling, the reaction mixture was
quenched with an aqueous saturated solution of NH4Cl (50 mL).
The aqueous layer was extracted with EtOAc (200 mL), and the
organic layer was washed with H2O and brine, dried with MgSO4,
and concentrated in vacuo. The residue was purified by flash col-
umn chromatography (n-hexanes/EtOAc, 4:1) to afford 5 (8.87 g,
23.7 mmol, 79% yield; cis/trans, 1.9:1) as a colorless syrup; Rf =
0.26 (n-hexanes/EtOAc, 4:1). 1H NMR (500 MHz, CDCl3): δ =
2.18–2.38 (m, 1 H), 3.59–3.63 (m, 1 H), 3.76–3.83 (m, 2 H), 4.11–
4.14 (m, 0.34 H), 4.17 (d, J = 11.5 Hz, 0.66 H), 4.44 (d, J = 11.5 Hz,
0.34 H), 4.51–4.73 (m, 3.66 H), 5.69 (dd, J = 11.5, 10.0 Hz, 0.66
H), 6.18 (dd, J = 16.0, 7.5 Hz, 0.34 H), 6.63 (d, J = 16.0 Hz, 0.34
H), 6.88 (d, J = 11.5 Hz, 0.66 H), 7.08–7.42 (m, 15 H) ppm. 13C
NMR (125 MHz, CDCl3): δ = 62.4, 62.7, 70.5, 70.9, 73.1, 74.6,
80.9, 81.1, 81.5, 126.9, 127.3, 127.6, 127.8, 127.9, 128.0, 128.1,
128.2, 128.3, 128.4, 128.5, 128.6, 128.7, 128.8, 128.9, 129.1, 129.2,
130.2, 134.5, 135.0, 136.7, 138.0, 138.3, 138.4 ppm. HRMS [chemi-
chromatography (n-hexanes/EtOAc, 8:1) to afford
7 (3.34 g,
7.80 mmol, 83% yield; cis/trans, 1:2) as a colorless oil. Data for cis
isomer: Rf = 0.37 (n-hexanes/EtOAc, 8:1). [α]2D2 = –2.3 (c = 1.2,
CHCl ). IR (neat): ν = 3258, 3030, 2862, 1723, 1495, 1452, 1199,
˜
3
1074, 825, 772, 697 cm–1. 1H NMR (500 MHz, CDCl3): δ = 3.64
(s, 3 H), 4.12–4.15 (m, 1 H), 4.54–4.71 (m, 4 H), 5.34–5.37 (m, 1
H), 5.96 (d, J = 11.5 Hz, 1 H), 6.19–6.28 (m, 2 H), 6.54 (d, J =
16.0 Hz, 1 H), 7.22–7.39 (m, 15 H) ppm. 13C NMR (125 MHz,
CDCl3): δ = 51.5, 70.7, 72.0, 76.9, 116.5, 122.3, 126.7, 126.9, 127.6,
127.7, 127.8, 127.9, 128.4, 128.7, 133.9, 136.8, 138.7, 138.8, 147.2,
166.4 ppm. Data for trans isomer: Rf = 0.35 (n-hexanes/EtOAc,
8:1). [α]2D2 = +23.1 (c = 1.0, CHCl ). IR (neat): ν = 3258, 2864,
˜
3
1724, 1452, 1274, 1219, 1170, 1072, 772, 697 cm–1. 1H NMR
(500 MHz, CDCl3): δ = 3.76 (s, 3 H), 4.02–4.13 (m, 2 H), 4.44–
4.68 (m, 4 H), 6.09–6.18 (m, 2 H), 6.61 (d, J = 15.5 Hz, 1 H), 7.01
(dd, J = 16.0, 6.5 Hz, 1 H), 7.18–7.40 (m, 15 H) ppm. 13C NMR
(125 MHz, CDCl3): δ = 51.8, 70.8, 71.9, 80.6, 81.9, 123.3, 126.6,
126.9, 127.8, 127.9, 128.0, 128.1, 128.2, 128.5, 128.6, 128.8, 134.7,
136.6, 138.0, 138.3, 145.8, 166.7 ppm. HRMS (CI): calcd. for
C28H27O4 [M – H]+ 427.1919; found 427.1909.
(4R,5S,E)-Methyl 4,5-Bis(benzyloxy)-7-phenylhept-6-enoate (8): To
a stirred solution of α,β-unsaturated ester 7 (3.0 g, 7.0 mmol) in
MeOH (117 mL) were added NaBH4 (1.32 g, 35 mmol), CuCl
(0.55 g, 5.6 mmol), and cyclohexene (2.8 mL, 28 mmol) at –78 °C.
The reaction was stirred at –78 °C for 24 h, and during this period
of time, it turned from green to brown. Then, the reaction mixture
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Asymmetric Formal Synthesis of (–)-Swainsonine
was concentrated in vacuo. The residue was partitioned between a
saturated aqueous solution of NH4Cl (50 mL) and Et2O (150 mL).
The organic layer was separated, and the aqueous layer was ex-
tracted with Et2O (4ϫ120 mL). The organic layer was dried with
MgSO4 and concentrated in vacuo. The residue was purified by
flash column chromatography (n-hexanes/EtOAc, 8:1) to afford 8
(2.86 g, 6.65 mmol, 95% yield) as a colorless oil; Rf = 0.30 (n-hex-
and the reaction mixture was stirred at room temperature for 1 h.
This mixture was added to chlorosulfonyl isocyanate (1.2 mL,
14.2 mmol) at 0 °C under N2. It was stirred at 0 °C for 12 h and
then quenched with H2O (3 mL). The aqueous layer was extracted
with EtOAc (2ϫ30 mL). The organic layer was added to a solution
of aqueous saturated Na2SO3 (30 mL), and the reaction mixture
was stirred at room temperature for 12 h. The organic layer was
washed with H2O and brine, dried with MgSO4, and concentrated
in vacuo. The residue was purified by flash column chromatog-
anes/EtOAc, 8:1). [α]2D2 = +68.7 (c = 1.4, CHCl ). IR (neat): ν =
˜
3
3259, 3029, 2863, 1737, 1603, 1495, 1447, 1364, 1218, 1171, 1077,
772, 698, 611 cm–1. 1H NMR (500 MHz, CDCl3): δ = 1.89–1.99 raphy (n-hexanes/EtOAc, 5:1) to afford 11 (2.0 g, 3.93 mmol, 83%
(m, 2 H), 2.34–2.47 (m, 2 H), 3.60 (s, 3 H), 3.61–3.65 (m, 1 H), yield) as a pale yellow syrup; Rf = 0.32 (n-hexanes/EtOAc, 5:1).
3.99–4.01 (m, 1 H), 4.49 (dd, J = 12.0, 11.5 Hz, 2 H), 4.67–4.73 [α]2D2 = +22.2 (c = 0.4, CHCl ). IR (neat): ν = 3259, 1720, 1219,
˜
3
1
(m, 2 H), 6.24 (dd, J = 16.0, 8.0 Hz, 1 H), 6.61 (d, J = 16.0 Hz, 1
1074, 773 cm–1. H NMR (500 MHz, CDCl3): δ = 1.65–1.75 (m, 2
H), 7.24–7.42 (m, 15 H) ppm. 13C NMR (125 MHz, CDCl3): δ = H), 1.94 (br. s, 2 H), 3.37 (br. s, 2 H), 3.60 (br. s, 1 H), 4.51 (br. s,
26.6, 30.3, 51.7, 70.6, 73.1, 80.6, 82.3, 126.8, 127.2, 127.7, 127.8,
127.9, 128.1, 128.3, 128.5, 128.6, 128.8, 134.5, 136.7, 138.7, 138.8,
174.3 ppm. HRMS (CI): calcd. for C28H29O4 [M – H]+ 429.2058;
found 429.2066.
1 H), 4.55–4.64 (m, 2 H), 5.07–5.13 (m, 3 H), 6.17 (dd, J = 16.0,
7.5 Hz, 1 H), 6.58 (br. s, 1 H), 7.22–7.37 (m, 15 H) ppm. 13C NMR
(125 MHz, CDCl3): δ = 28.9, 29.4, 33.7, 55.7, 67.1, 72.4, 80.3,
121.3, 125.5, 126.8, 128.0, 128.1, 128.3, 128.8, 133.3, 136.7,
156.0 ppm. HRMS (CI): calcd. for C28H31BrNO3 [M + H]+
508.1483; found 508.1487.
(4R,5S,E)-4,5-Bis(benzyloxy)-7-phenylhept-6-en-1-ol (9): To
a
stirred solution of 8 (2.8 g, 6.5 mmol) in anhydrous THF (43 mL)
was added LiAlH4 (0.74 g, 19.5 mmol) at 0 °C under N2. The reac-
tion mixture was stirred at room temperature for 4 h and then was
carefully quenched with H2O (5 mL) and HCl (1 m solution,
10 mL). The aqueous layer was extracted with EtOAc (3ϫ20 mL).
The organic layer was washed with H2O and brine, dried with
MgSO4, and concentrated in vacuo. The residue was purified by
flash column chromatography (n-hexanes/EtOAc, 2:1) to afford 10
(2.54 g, 6.31 mmol, 97% yield) as a colorless oil; Rf = 0.33 (n-hex-
(2S,3R)-Benzyl 3-(Benzyloxy)-2-styrylpiperidine-1-carboxylate (12):
To a stirred solution of 11 (1.8 g, 3.54 mmol) in THF (18 mL) was
slowly added potassium tert-butoxide (0.47 g, 4.2 mmol) at 0 °C
under N2. The reaction mixture was stirred at room temperature
for 2 h and then was quenched with H2O (10 mL). The aqueous
layer was extracted with EtOAc (30 mL). The organic layer was
washed with H2O, dried with MgSO4, and concentrated in vacuo.
The residue was purified by flash column chromatography (n-hex-
anes/EtOAc, 8:1) to afford 12 (1.2 g, 2.80 mmol, 79% yield) as a
colorless syrup; Rf = 0.30 (n-hexanes/EtOAc, 8:1). [α]2D3 = +49.3 (c
anes/EtOAc, 2:1). [α]2D2 = +59.2 (c = 1.2, CHCl ). IR (neat): ν =
˜
3
3259, 3029, 2866, 1495, 1452, 1362, 1218, 1066, 971, 772, 697,
613 cm–1. 1H NMR (500 MHz, CDCl3): δ = 1.56–1.73 (m, 4 H), = 2.3, CHCl ). IR (neat): ν = 3029, 2947, 1697, 1650, 1496, 1424,
˜
3
3.60–3.64 (m, 3 H), 4.02 (dd, J = 8.0, 4.0 Hz, 1 H), 4.45–4.76 (m,
4 H), 6.26 (dd, J = 16.0, 8.5 Hz, 1 H), 6.61 (d, J = 16.0 Hz, 1 H),
1307, 1264, 1199, 1127, 874, 750 cm–1. 1H NMR (500 MHz,
CDCl3): δ = 1.42 (br. s, 1 H), 1.60–1.71 (m, 1 H), 1.89–2.15 (m, 2
7.20–7.42 (m, 15 H) ppm. 13C NMR (125 MHz, CDCl3): δ = 27.9, H), 3.05 (t, J = 10.0 Hz, 1 H), 3.64 (br. s, 1 H), 4.09–4.17 (m, 1 H),
29.1, 63.2, 70.7, 73.1, 81.6, 82.5, 126.8, 127.4, 127.7, 127.8, 127.9,
128.0, 128.3, 128.5, 128.6, 128.8, 134.4, 136.7, 138.7, 138.8 ppm.
HRMS (CI): calcd. for C27H31O3 [M + H]+ 403.2280; found
403.2273.
4.52–4.67 (m, 2 H), 5.09–5.22 (m, 2 H), 5.25 (br. s, 1 H), 6.10 (dd,
J = 16.0, 5.0 Hz, 1 H), 6.45 (d, J = 16.0 Hz, 1 H), 7.18–7.44 (m,
15 H) ppm. 13C NMR (125 MHz, CDCl3): δ = 19.8, 25.0, 40.0,
67.4, 70.5, 74.9, 77.1, 125.4, 126.6, 127.6, 127.7, 127.8, 127.9, 128.0,
128.5, 128.6, 128.7, 128.8, 128.9, 132.3, 136.8, 137.2, 138.8,
156.6 ppm. HRMS (EI): calcd. for C28H29NO3 [M]+ 427.2147;
found 427.2136.
[(3S,4R,E)-7-Bromo-1-phenylhept-1-ene-3,4-diyl]bis(oxy)bis(meth-
ylene)dibenzene (10): To a stirred solution of 9 (2.3 g, 5.71 mmol)
in anhydrous CH2Cl2 (29 mL) were added PPh3 (4.94 g,
18.8 mmol), CBr4 (3.1 g, 9.42 mmol), and Et3N (14 mL) at 0 °C
under N2. The reaction mixture was stirred at 0 °C for 3 h and then
quenched with H2O (10 mL). The aqueous layer was extracted with
(2S,3R)-2-Styrylpiperidin-3-ol (14): To a stirred solution of 11
(0.54 g, 1.061 mmol) in anhydrous CH2Cl2 (21 mL) was added BCl3
(1.0 m in CH2Cl2, 66 mL) at –78 °C. The reaction mixture was
CH2Cl2 (2ϫ20 mL). The organic layer was washed with H2O and stirred at –78 °C for 24 h and then quenched with MeOH (20 mL).
brine, dried with MgSO4, and concentrated in vacuo. The residue
was purified by flash column chromatography (n-hexanes/EtOAc,
10:1) to afford 10 (2.31 g, 4.97 mmol, 87% yield) as a colorless oil;
Rf = 0.32 (n-hexanes/EtOAc, 10:1). [α]2D3 = +57.1 (c = 1.0, CHCl3).
The resulting mixture was stirred at –78 °C for an additional 1 h.
The resulting mixture was warmed to room temperature and con-
centrated in vacuo. The residue was purified by ion-exchange resin
DOWEX 50WX8–100 (NH4OH, 0.5 m solution) to afford 14
(123 mg, 0.605 mmol, 57% yield) as a white solid; m.p. 174.6 °C.
Rf = 0.13 (CH2Cl2/CH3OH/NH4OH, 90:10:0.15). [α]2D7 = +66.4 (c
IR (neat): ν = 3259, 3061, 3029, 2926, 2864, 1739, 1602, 1495, 1452,
˜
1
1363, 1256, 1207, 1098, 1029, 971, 742 cm–1. H NMR (500 MHz,
CDCl3): δ = 1.71–2.04 (m, 4 H), 3.32–3.37 (m, 2 H), 3.58–3.61 (m, = 0.4, CH OH). IR (neat): ν = 3269, 2926, 2826, 1354, 1070, 924,
˜
3
1 H), 3.98–4.01 (m, 1 H), 4.44 (d, J = 12.0 Hz, 1 H), 4.56 (d, J = 864, 744, 692 cm–1. H NMR (500 MHz, CD3OD): δ = 1.59–1.67
1
12.0 Hz, 1 H), 4.68–4.73 (m, 2 H), 6.26 (dd, J = 16.0, 8.0 Hz, 1 H), (m, 1 H), 1.77–1.85 (m, 1 H), 2.01–2.09 (m, 1 H), 2.13–2.18 (m, 1
6.62 (d, J = 16.0 Hz, 1 H), 7.25–7.43 (m, 15 H) ppm. 13C NMR
(125 MHz, CDCl3): δ = 29.1, 30.0, 34.2, 70.6, 73.0, 80.8, 82.3,
126.8, 126.9, 127.3, 127.7, 127.8, 127.9, 128.1, 128.3, 128.5, 128.6,
128.8, 134.5, 136.7, 138.7 ppm. HRMS (CI): calcd. for C27H28BrO2
[M – H]+ 463.1273; found 463.1273.
H), 3.01–3.02 (m, 1 H), 3.31 (t, J = 3.0 Hz, 2 H), 3.33–3.37 (m, 1
H), 3.66 (t, J = 8.4 Hz, 1 H), 3.73–3.78 (m, 1 H), 6.29 (dd, J =
16.0, 8.2 Hz, 1 H), 6.89 (d, J = 16.0 Hz, 1 H), 7.29–7.39 (m, 3 H),
7.45–7.51 (m, 2 H) ppm. 13C NMR (125 MHz, CD3OD): δ = 20.4,
30.3, 43.0, 63.2, 67.7, 121.4, 126.7, 128.6, 128.7, 135.7, 138.3 ppm.
HRMS (EI): calcd. for C13H17NO [M]+ 203.1310; found 203.1312.
Benzyl
(3S,4R,E)-4-(Benzyloxy)-7-bromo-1-phenylhept-1-en-3-yl-
carbamate (11): To a stirred solution of 10 (2.2 g, 4.73 mmol) in
(2S,3R)-3-(tert-Butyldimethylsilyloxy)-2-styrylpiperidine (15): To a
anhydrous toluene (19 mL) was added Na2CO3 (2.3 g, 21.3 mmol), stirred solution of 14 (349 mg, 0.837 mmol) in anhydrous CH2Cl2
Eur. J. Org. Chem. 2013, 4427–4433
© 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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4431

Y. H. Jung et al.
FULL PAPER
(11 mL) were added 2,6-lutidine (0.44 mL, 1.842 mmol) and
TBSOTf (0.790 mL, 1.675 mmol) at 0 °C. The reaction mixture was
stirred at 0 °C for 5 h and then was quenched with a solution of
aqueous saturated NaHCO3 (10 mL). The aqueous layer was ex-
tracted with CH2Cl2 (20 mL). The combined organic layers were
dried with MgSO4 and concentrated in vacuo. The residue was
purified by flash column chromatography (CH2Cl2/CH3OH/
NH4OH, 90:10:0.15) to afford 15 (242 mg, 0.762 mmol, 91% yield)
as a colorless oil; Rf = 0.42 (CH2Cl2/CH3OH/NH4OH, 90:10:0.15).
Supporting Information (see footnote on the first page of this arti-
1
cle): H and 13C NMR spectra for all compounds.
Acknowledgments
This work was supported by the Postdoctoral Research Program
of Sungkyunkwan University (2012) and the National Research
Foundation of Korea (NRF-2012-002506) and funded by the Min-
istry of Education, Science, and Technology, Korea.
[α]2D7 = +185.9 (c = 0.03, CHCl ). IR (neat): ν = 2926, 2854, 1739,
˜
3
1464, 1364, 1253, 1099, 969, 926, 837, 776, 747 cm–1. 1H NMR
(500 MHz, CDCl3): δ = 0.04 (s, 3 H), 0.07 (s, 3 H), 0.88 (s, 9 H),
1.45–1.50 (m, 1 H), 1.74–1.80 (m, 2 H), 2.04–2.08 (m, 2 H), 2.68
(dt, J = 11.8, 2.8 Hz, 1 H), 3.08 (d, J = 11.8 Hz, 1 H), 3.13 (t, J =
7.8 Hz, 1 H), 3.44–3.46 (m, 1 H), 6.31 (dd, J = 16.0, 7.1 Hz, 1 H),
6.60 (d, J = 16.0 Hz, 1 H), 7.24–7.40 (m, 5 H) ppm. 13C NMR
(125 MHz, CDCl3): δ = –4.3, –4.1, 18.2, 25.3, 26.0, 26.0, 29.9, 34.8,
45.9, 66.1, 72.9, 126.4, 127.5, 128.7, 131.7, 137.3 ppm. HRMS (EI):
calcd. for C19H31NOSi [M]+ 317.2175; found 317.2177.
[1] A. A. Watson, G. W. J. Fleet, N. Asano, R. J. Molyneux, R. J.
Nash, Phytochemistry 2001, 56, 265.
[2] For selected reviews, see: a) E. B. de Melo, A. da Sil-
veria Gomes, I. Carvalho, Tetrahedron 2006, 62, 10277; b) S.
Gerber-Lemaire, L. Juillerat-Jeanneret, Mini-Rev. Med. Chem.
2006, 6, 1043; c) N. Asano, Glycobiology 2003, 13, 93R; d)
V. H. Lillelund, H. H. Jensen, X. F. Liang, M. Bols, Chem. Rev.
2002, 102, 515.
[3] For a selected review, see: J. P. Michael, Nat. Prod. Rep. 2007,
24, 191.
(2S,3R)-Allyl
3-(tert-Butyldimethylsilyloxy)-2-styrylpiperidine-1-
[4] a) F. P. Guengerich, S. J. DiMari, H. P. Broquist, J. Am. Chem.
Soc. 1973, 95, 2055; b) M. J. Schneider, F. S. Ungemach, H. P.
Broquist, T. M. Harris, Tetrahedron 1983, 39, 29.
[5] S. M. Colegate, P. R. Dorling, C. R. Huxtable, Aust. J. Chem.
1979, 32, 2257.
[6] R. J. Molyneux, L. F. James, Science 1982, 216, 190.
[7] M. Hino, O. Nakayama, Y. Tsurumi, K. Adachi, T. Shibata,
H. Terano, M. Kohsaka, H. Aoki, H. Imanaka, J. Antibiot.
1985, 38, 926.
[8] a) A. D. Elbein, R. Solf, P. R. Dorling, K. Vosbeck, Proc. Natl.
Acad. Sci. USA 1981, 78, 7393; b) D. R. Tulsiani, T. M. Harris,
O. Touster, J. Biol. Chem. 1982, 257, 7936.
[9] a) P. E. Goss, C. L. Reid, D. Bailey, J. W. Dennis, Clin. Cancer
Res. 1997, 3, 11077; b) I. Cenci di Bello, G. Fleet, S. K.
Namgoong, K. Tadano, B. Winchester, Biochem. J. 1989, 259,
855.
[10] J. Y. Sun, H. Yang, S. Miao, J. P. Li, S. W. Wang, M. Z. Zhu,
Y. H. Xie, J. B. Wang, Z. Liu, Q. Yang, Phytomedicine 2009,
16, 1070.
[11] a) T. Kino, N. Inamura, K. Nakahara, S. Kiyoto, T. Goto, H.
Terno, M. Kohsaka, H. Aoki, H. Imanaka, J. Antibiot. 1985,
38, 936; b) M. J. Humphries, K. Matsumoto, S. L. White, R. J.
Molyneux, K. Olden, Cancer Res. 1988, 48, 1410.
[12] A. D. Elbein, P. R. Dorling, K. Vosbeck, M. Horisberger, J.
Biol. Chem. 1982, 257, 1573.
[13] For isolation of 2, see: a) L. D. Hohenschutz, E. A. Bell, P. J.
Jewess, D. P. Leworthy, R. J. Pryce, E. Arnold, J. Clardy, Phyto-
chemistry 1981, 20, 811; for biologial activity of 2, see: b) R. A.
Gruters, J. J. Neefjes, M. Tersmette, R. E. Y. de Goede, A. Tulp,
H. G. Huisman, F. Miedema, H. L. Ploegh, Nature 1987, 330,
74.
carboxylate (17): To a stirred solution of 15 (51 mg, 0.161 mmol)
in anhydrous CH2Cl2 (1.1 mL) were added allyl chloroformate
(0.05 mL, 0.481 mmol) and sodium carbonate (426 mg,
0.402 mmol) at room temperature. The reaction mixture was stirred
at room temperature for 4 h and then was quenched with a solution
of saturated aqueous NH4Cl (3 mL). The resulting mixture was
then diluted with CH2Cl2 (5 mL). The mixture was washed with
H2O, dried with MgSO4, and concentrated in vacuo. The residue
was purified by flash column chromatography (n-hexanes/EtOAc,
20:1) to afford 17 (53.8 mg, 0.134 mmol, 83% yield) as a colorless
oil; Rf = 0.41 (n-hexanes/EtOAc, 10:1). [α]2D7 = +224.6 (c = 0.1,
CHCl ). IR (neat): ν = 2952, 2929, 2856, 1701, 1465, 1417, 1375,
˜
3
1252, 1197, 1129, 1091, 1304, 964, 923, 891, 836 cm–1. 1H NMR
(500 MHz, CDCl3): δ = 0.07 (s, 3 H), 0.09 (s, 3 H), 0.89 (s, 9 H),
1.35 (d, J = 13.1 Hz, 1 H), 1.64–1.69 (m, 2 H), 1.98–2.02 (m, 1 H),
2.98 (dt, J = 13.3, 2.9 Hz, 1 H), 2.95–3.01 (m, 1 H), 4.12 (d, J =
12.6 Hz, 1 H), 4.55–4.65 (m, 2 H), 4.88 (br. s, 1 H), 5.16–5.19 (m,
1 H), 5.27–5.31 (m, 1 H), 5.91–5.96 (m, 1 H), 6.13 (dd, J = 16.1,
5.2 Hz, 1 H), 6.46 (dd, J = 16.1, 1.8 Hz, 1 H), 7.22–7.38 (m, 5
H) ppm. 13C NMR (125 MHz, CDCl3): δ = –4.7, –4.6, 18.3, 19.2,
25.9, 27.8, 39.9, 60.0, 66.1, 68.9, 117.2, 125.4, 126.5, 127.9, 128.8,
132.0, 133.5, 136.8, 156.4 ppm. HRMS (EI): calcd. for
C23H35NO3Si [M]+ 401.2386; found 401.2384.
(2S,3R)-1-Allyl-3-(tert-butyldimethylsilyloxy)-2-styrylpiperidine
(16): To a stirred solution of 17 (38.3 mg, 0.095 mmol) in THF
(2.5 mL) was added tetrakis(triphenylphosphane)palladium
(11 mg, 0.01 mmol) at room temperature. The reaction mixture was
stirred at room temperature for 5 h and then concentrated in vacuo.
The residue was purified by flash chromatography (n-hexanes/
EtOAc, 20:1) to afford 16 (28.9 mg, 0.081 mmol, 85%) as a color-
less oil; Rf = 0.28 (n-hexanes/EtOAc, 20:1). [α]2D7 = +73.6 (c = 1.3,
[14] For reviews about the synthesis of (–)-swainsonine, see: a)
M. D. López, J. Cobo, M. Nogueras, Curr. Org. Chem. 2008,
12, 718; b) S. Pyne, Curr. Org. Synth. 2005, 2, 39; c) A.
El Nemr, Tetrahedron 2000, 56, 8579.
[15] For recent selected examples of the total synthesis of (–)-swain-
sonine, see: a) S. A. Miller, A. R. Chamberlin, J. Am. Chem.
Soc. 1990, 112, 8100; b) W. H. Pearson, K.-C. Lin, Tetrahedron
Lett. 1990, 31, 7571; c) S. H. Kang, G. T. Kim, Tetrahedron
Lett. 1995, 36, 5049; d) W. H. Pearson, E. J. Hembre, J. Org.
Chem. 1996, 61, 7217; e) H. Zhao, S. Hans, X. Cheng, D. R.
Mootoo, J. Org. Chem. 2001, 66, 1761; f) W. H. Pearson, Y.
Ren, J. D. Powers, Heterocycles 2002, 58, 421; g) P. K. Sharma,
R. N. Shah, J. P. Carver, Org. Process Res. Dev. 2008, 12, 831;
h) D. J. Wardrop, E. G. Bowen, Org. Lett. 2011, 13, 2376; i) J.
Louvel, F. Chemla, E. Demont, F. Ferreira, A. Pérez-Luna,
Org. Lett. 2011, 13, 6452.
CHCl ). IR (neat): ν = 3079, 3027, 2929, 2790, 2709, 1739, 1642,
˜
3
1600, 1494, 1463, 1360, 1253, 1101, 969, 916, 836 cm–1. H NMR
1
(500 MHz, CDCl3): δ = –0.14 (s, 3 H), –0.01 (s, 3 H), 0.77 (br. s, 9
H), 1.31–1.39 (m, 1 H), 1.54–1.62 (m, 1 H), 1.68–1.72 (m, 1 H),
1.96–2.01 (m, 2 H), 2.60 (t, J = 8.7 Hz, 1 H), 2.80 (dd, J = 13.9,
8.2 Hz, 1 H), 2.95 (d, J = 11.5 Hz, 1 H), 3.47–3.52 (m, 2 H), 5.08–
5.13 (m, 2 H), 5.81–5.89 (m, 1 H), 6.00 (dd, J = 15.9, 9.0 Hz, 1 H),
6.52 (dd, J = 15.9 Hz, 1 H), 7.18–7.36 (m, 5 H) ppm. 13C NMR
(125 MHz, CDCl3): δ = –4.3, –4.2, 18.1, 23.6, 25.9, 34.3, 41.8, 51.9,
58.8, 72.2, 73.3, 117.9, 126.4, 127.4, 128.7, 129.1, 129.3, 130.8,
134.2, 135.2, 137.2 ppm. HRMS (EI): calcd. for C22H35NOSi
[M]+ 357.2488; found 357.2492.
[16] For recent selected examples of the total synthesis of (–)-swain-
sonine, see: a) N. Ikota, A. Hanaki, Chem. Pharm. Bull. 1990,
4432
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© 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2013, 4427–4433

Asymmetric Formal Synthesis of (–)-Swainsonine
38, 2712; b) M. Naruse, S. Aoyagi, C. Kibayashi, J. Org. Chem.
1994, 59, 1358; c) M.-J. Blanco, F. J. Sardina, J. Org. Chem.
1996, 61, 4748; d) I. Déchamps, D. G. Pardo, J. Cossy, ARKI-
VOC 2007, 5, 38.
Tetrahedron: Asymmetry 2010, 21, 1563; g) S. N. Murthy,
Y. V. D. Nageswar, Synthesis 2011, 755.
[19] I. S. Kim, O. P. Zee, Y. H. Jung, Org. Lett. 2006, 8, 4101.
[20] For a review, see: a) I. S. Kim, Y. H. Jung, Heterocycles 2011,
83, 2489; for recent examples, see: b) I. S. Kim, Q. R. Li, G. R.
Dong, S. H. Woo, H.-j. Park, O. P. Zee, Y. H. Jung, Synlett
2008, 2985; c) I. S. Kim, Q. R. Li, G. R. Dong, Y. C. Kim, Y. J.
Hong, M. Lee, K.-W. Chi, J. S. Oh, Y. H. Jung, Eur. J. Org.
Chem. 2010, 1569; d) S. H. Lee, I. S. Kim, Q. R. Li, G. R.
Dong, L. S. Jeong, Y. H. Jung, J. Org. Chem. 2011, 76, 10011;
e) G. R. Dong, S. M. Hong, S. I. Kim, I. S. Kim, Y. H. Jung,
Eur. J. Org. Chem. 2012, 4200; f) S. J. Kim, T. H. Jeon, I. S.
Min, I. S. Kim, Y. H. Jung, Tetrahedron Lett. 2012, 53, 3680;
g) S. H. Lee, S. J. Park, I. S. Kim, Y. H. Jung, Tetrahedron 2013,
69, 1877.
[17] For recent selected examples of the total synthesis of (–)-swain-
sonine, see: a) T. Punniyamurthy, R. Irie, T. Katsuki, Chirality
2000, 12, 464; b) N. Buschmann, A. Rückert, S. Blechert, J.
Org. Chem. 2002, 67, 4325; c) K. B. Lindsay, S. G. Pyne, J. Org.
Chem. 2002, 67, 7774; d) K. B. Lindsay, S. G. Pyne, Aust. J.
Chem. 2004, 57, 669; e) L. Song, E. N. Duesler, P. S. Mariano,
J. Org. Chem. 2004, 69, 7284; f) R. Martín, C. Murruzzu, M. A.
Pericás, A. Riera, J. Org. Chem. 2005, 70, 2325; g) G.
Heimgärtner, D. Raatz, O. Reiser, Tetrahedron 2005, 61, 643;
h) H. Guo, G. A. O’Doherty, Org. Lett. 2006, 8, 1609; i) J.
Ceccon, A. E. Greene, J.-F. Poisson, Org. Lett. 2006, 8, 4739;
j) G.-F. Shi, J.-Q. Li, X.-P. Jiang, Y. Cheng, Tetrahedron 2008,
64, 5005; k) Y.-S. Tian, J.-E. Joo, B.-S. Kong, V.-T. Pham, K.-
Y. Lee, W.-H. Ham, J. Org. Chem. 2009, 74, 3962; l) S. Choop-
rayoon, C. Kuhakarn, P. Tuchinda, V. Reutrakul, M. Pohmak-
otr, Org. Biomol. Chem. 2011, 9, 531.
[21] J. A. Marshall, B. M. Seletsky, G. P. Luke, J. Org. Chem. 1994,
59, 3413.
[22] L. J. Baird, M. S. M. Timmer, P. H. Teesdale-Spittle, J. E. Har-
vey, J. Org. Chem. 2009, 74, 2271.
[23] For the selective cleavage of a Cbz protecting group, see: a)
S. R. Angel, D. O. Arnaiz, Tetrahedron Lett. 1989, 30, 515; b)
M. Sakatani, N. Kurokawa, Y. Ohfune, Tetrahedron Lett. 1986,
27, 3753; c) P. Wipf, Y. Uto, Tetrahedron Lett. 1999, 40, 5165.
[18] For recent selected examples of the formal synthesis of (–)-
swainsonine, see: a) C. W. G. Au, S. G. Pyne, J. Org. Chem.
2006, 71, 7097; b) I. Déchamps, D. G. Pardo, J. Cossy, Tetrahe-
dron 2007, 63, 9082; c) H. Kwon, C. Park, S. Lee, J.-H. Youn, [24] For selected examples, see: a) C. Torque, B. Sueur, J. Cabou,
S. Kang, Chem. Eur. J. 2008, 14, 1023; d) R. W. Bates, M. R.
Dewey, Org. Lett. 2009, 11, 3706; e) H. G. Choi, J. H. Kwon,
J. C. Kim, W. K. Lee, H. Eum, H.-J. Ha, Tetrahedron Lett.
2010, 51, 3284; f) S. J. Oxenford, S. P. Moore, G. Carbone, G.
Barker, P. O’Brien, M. R. Shipton, J. Gilday, K. R. Campos,
H. Bricout, F. Hapiot, E. Monflier, Tetrahedron 2005, 61, 4811;
b) P. Gomez-Martinez, M. Dessolin, F. Guibé, F. Albericio, J.
Chem. Soc. Perkin Trans. 1 1999, 2871.
Received: March 1, 2013
Published Online: May 31, 2013
Eur. J. Org. Chem. 2013, 4427–4433
© 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
4433