Asymmetric total synthesis of (+)-swainsonine

Article abstract of DOI:10.1039/c0ob00388c

A concise asymmetric synthesis of (+)-swainsonine (ent-1) is described starting from 2, which was readily prepared from commercially available l-glutamic acid. The method features installation of the indolizidine ring via an intramolecular cyclisation of

Full text of DOI:10.1039/c0ob00388c

View Article Online / Journal Homepage / Table of Contents for this issue
Organic &
Biomolecular
Chemistry
Dynamic Article Links
Cite this: Org. Biomol. Chem., 2011, 9, 531
www.rsc.org/obc
PAPER
Asymmetric total synthesis of (+)-swainsonine†
Soontorn Chooprayoon, Chutima Kuhakarn, Patoomratana Tuchinda, Vichai Reutrakul and
Manat Pohmakotr*
Received 6th July 2010, Accepted 15th September 2010
DOI: 10.1039/c0ob00388c
A concise asymmetric synthesis of (+)-swainsonine (ent-1) is described starting from 2, which was
readily prepared from commercially available L-glutamic acid. The method features installation of the
indolizidine ring via an intramolecular cyclisation of a-sulfinyl carbanion as a key step.
(+)-Swainsonine was obtained in 11.8% overall yield in 10 steps.
Introduction
Results and discussion
Polyhydroxylated indolizidine alkaloids have attracted significant
attention from the synthetic community due to their interest-
ing structures and potent biological activities.1,2 Among those,
(-)-swainsonine (1) (Fig. 1), which was first isolated from the
fungus Rhizoctonia leguminicola3 and later found in several plants
and fungi,4 exhibits potent and selective glycosidase inhibitory
properties.5 It has also been tested as a treatment for cancer,
HIV and immunological disorders.6 Its biological importance
and interesting structure has triggered a number of synthetic
approaches toward the total syntheses of natural occurring
(-)-swainsonine (1) and its analogues7,8 as well as (+)-swainsonine
(ent-1) (Fig. 1).9 These classes of molecule are still attractive
targets for organic chemists to develop new synthetic strategies
and methodologies.
As shown in Scheme 1, the synthesis of (+)-swainsonine (ent-1)
commenced with chiral carboxylic acid 2, which was readily pre-
pared from L-glutamic acid by following the previously reported
procedure.13 The reaction of the carboxylic acid 2 with oxalyl
chloride in the presence of a catalytic amount of DMF followed by
treatment with 3-phenylsulfanyl-1-aminopropane afforded amide
3 in 67% yield. The requisite chiral hydroxyimide 4 was obtained
in 72% yield by treatment of the amide 3 with t-BuOK in
THF at -78 ◦C. The hydroxyl group of 4 was protected with a
TBS group under standard conditions which afforded 5 in 87%
yield. Subsequent sulfide oxidation with sodium metaperiodate
(NaIO4) in aqueous methanol furnished the prerequisite chiral
Fig. 1 Structures of (-)-swainsonine (1) and (+)-swainsonine (ent-1).
Our analysis of an efficient route to (+)-swainsonine (ent-1)
evolved from our previously reported work on intramolecular
cyclisation of an a-sulfinyl carbanion as a convenient strategy
for the preparation of 1-azabicyclic compounds.10 In the early
studies, we demonstrated the synthetic utility of this strategy for
syntheses of ( )-tashiromine, ( )-lupinine, ( )-epilupinine, and ( )-
indolizidines 167B and 209D.11,12 To further advance our synthetic
methodology, we describe herein a concise asymmetric synthesis
of (+)-swainsonine (ent-1) via an intramolecular cyclisation of an
a-sulfinyl carbanion.
Department of Chemistry and Center for Innovation in Chemistry, Faculty
of Science, Mahidol University, Rama VI Road, Bangkok, 10400, Thailand.
E-mail: scmpk@mahidol.ac.th; Fax: +66 2 354 7151; Tel: +66 2 201 5158
† Electronic supplementary information (ESI) available: 1H NMR, 13C
NMR, COSY-45 and HMQC spectra. See DOI: 10.1039/c0ob00388c
Scheme 1 Preparation of the starting chiral sulfinylimide 6 from
L-glutamic acid.
This journal is
The Royal Society of Chemistry 2011
Org. Biomol. Chem., 2011, 9, 531–537 | 531
©

View Article Online
sulfinylimide 6 in 90% yield as an inseparable mixture of two
diastereomers (Scheme 1).
8a and 8b [H2 (1 atm), PtO2 (cat.), EtOAc, 16 h] gave complete
recovery of the starting material. By performing the reaction under
4 atm of H2, both 8a and 8b underwent reductive deoxygenation of
the sulfoxide moiety to furnish the corresponding phenylsulfanyl
derivative in 58% yield. Similar results were observed when the
reaction was performed under 1 atm of H2 in the presence of
10 mol% of trifluoroacetic acid, affording the phenylsulfanyl
derivative in 50% yield.
Efforts to carry out the reduction using Et3SiH as a hydride
source under acidic conditions were briefly investigated. Under
the reaction conditions [Et3SiH (3 equiv), trifluoroacetic acid
(2 equiv), 0 C to rt, 16 h], the reaction of 8 as a diastereomeric
mixture yielded the required reduction product 9 in only 20%
yield along with a complex mixture of unidentified products.
The reactions employing NaBH4/MeOH, NaCNBH3/MeOH,
NaCNBH3/AcOH or NaCNBH3/AcOH/TFA (10 mol%) at
0 C to room temperature for 16 h did not give the reduction
product 9 but led to recovery of the starting material. Thankfully,
treatment of 8a or 8b using NaCNBH3/AcOH/TFA (10 mol%)
at 0 C followed by heating at 50 C for 5 h furnished the
respective product 9a or 9b in good yields, each as a single isomer
(Scheme 3).
Through extensive investigation of various experimental param-
eters, particularly the mole equivalents of lithium hexamethyldisi-
lazide (LHMDS) employed, we established that cyclisation of 6 to
give 7 required treatment of 6 with 2.2 equiv of LHMDS in THF
at -78 C followed by slowly warming up to room temperature for
16 h. Recovery of 6 was observed when LHMDS was utilised in
lesser amount. These results implied competitive proton abstrac-
tion that occurred preferentially at the a-imide proton rather than
the a-proton adjacent to the phenylsulfinyl moiety of sulfinylimide
6. Therefore, proton abstraction of the initially formed enolate 6A
by a second equivalent of LHMDS gave a-sulfinyl carbanion 6B
which readily underwent cyclisation to yield hydroxyindolizidine
amide 7. Formation of the enolate 6A was found crucial to protec-
tion of the carbonyl group at the 6-position from intramolecular
nucleophilic attack by the a-sulfinyl carbanion. On this basis,
cyclisation took place chemoselectively at the carbonyl carbon
at the 2-position. Without prior purification, the crude residue of
hydroxyindolizidine amide 7 was exposed to p-TsOH in refluxing
CH2Cl2 to afford, after column chromatography, 8a and 8b in 15%
and 65% yields, respectively. Poorer yields were obtained if the
reactions were carried out at room temperature even at longer
reaction time, leading to 8 in 25–30% yield. The structures of
compounds 8a and 8b were established by 1H NMR (500 MHz),
COSY-45 and HMQC spectra (see ESI†). Since the absolute
configurations at the sulfinyl groups of 8a and 8b could not be
determined, it was tentatively assumed that 8a and 8b possessed
R- and S-configurations, respectively, as shown in Scheme 2.
Scheme 3 Reduction of 8a and 8b to the corresponding sulfoxides 9a and
9b.
The stereoselectivity of the reduction was realised and the
stereochemical outcomes can be rationalized by Cieplak effect as
shown in Scheme 4.14 Facial selection of protonation was governed
by homoconjugative assistance of the lone-pair electrons of the
oxygen atom of the sulfinyl group (Cieplak effect) and minimized
steric interaction between the phenyl group and the silyloxy group.
As a result, 8a underwent protonation leading to an iminium
intermediate 8A. Subsequent trapping by a hydride from the
less sterically hindered face furnished the reduction product 9a
whose bridgehead hydrogen is trans relative to the silyloxy group.
According to the same reasons, protonation of 8b occurred from
the opposite face to that of 8a leading to an iminium intermediate
8B. A hydride approaches from the bottom face leading to the
reduction product 9b whose bridgehead hydrogen is cis relative
to the silyloxy group. The relative stereochemistries at the 8-
and 8a-position of 9a and 9b were assigned by means of NOE
experiments (See ESI†). It is worth mentioning that the relative
stereochemistries obtained in 9a and 9b also supported and were
Scheme 2 Intramolecular cyclisation of the a-sulfinyl carbanion derived
from 6 to 8a and 8b.
With success at the construction of the core indolizidine struc-
ture, conversion of the unsaturated phenylsulfinyl derivatives 8
into the corresponding saturated phenylsulfoxide 9 was attempted.
Initially, catalytic hydrogenation of a diastereomeric mixture of
532 | Org. Biomol. Chem., 2011, 9, 531–537
This journal is
The Royal Society of Chemistry 2011
©

View Article Online
subjected to reduction using LAH in refluxing THF to give 11
in 89% yield as a single isomer without contamination of the
isomer (Scheme 6). The facial selectivity in the osmylation of 10b
can be rationalised according to Hirama’s explanation.9 It is worth
mentioning that facial selection was governed by both 1,3-steric
interaction and 1,2-torsional strain. In this case, the oxidizing
agent approaches the double bond of 10b from the face opposite
to the two axially oriented allylic hydrogens (H3 and H8a) to avoid
the two 1,2-torsional strain since the 1,3-steric interaction is less
important when the reagent is small.
Scheme 6 Conversion of 10b to (+)-swainsonine (ent-1).
Finally, removal of the silyl group from protected swainsonine
11 was firstly carried out under standard conditions (TBAF, THF,
rt, 16 h). The 1H-NMR spectrum of crude product indicated the
characteristic signals of the expected (+)-swainsonine (ent-1) but
it was not possible to isolate it in pure form by using conventional
chromatography. Attempted deprotection using KF in aqueous
methanol at room temperature for 16 h led to recovery of the
starting compound 11. Fortunately, treatment of 11 with Dowex
50W-X8 (H+ form) in methanol at room temperature for 24 h
afforded 94% yield of (+)-swainsonine (ent-1). The 1H-NMR data
(see ESI†) as well as the optical rotation ([a]2D5 +78.97 (c 0.63,
MeOH)) of our synthesized product were consistent with the
values reported in the literature.9,15 The relative stereochemistries
at the 1-, 2-, 8- and 8a-positions of (+)-swainsonine (ent-1) were
assigned by the NOE experiments.
Scheme 4 Proposed transition states for the reduction of 8a and 8b to the
corresponding 9a and 9b.
in good agreement with the assumed absolute stereochemistries
assigned for the sulfinyl groups of 8a and 8b.
Removal of the phenylsulfinyl group in compounds 9a and 9b
was achieved by pyrolysis under refluxing toluene in the presence
of anhydrous CaCO3 to afford the corresponding compounds 10a
and 10b in 80% and 85% yields, respectively, as shown in Scheme 5.
The relative stereochemistries assigned to the 8- and 8a-positions
of 10a and 10b are based upon the NOE experiments (See ESI†).
Conclusions
The synthesis of (+)-swainsonine (ent-1) reported here is concise
and highly efficient. The synthetic strategy illustrates the utility
of a-sulfinyl carbanion cyclisation. We believe that this strategy
can be tailored to the preparation of a range of biologically
active polyhydroxylated indolizidine and quinolizidine alkaloids
by starting from appropriate chiral imides or lactams.
Experimental
Scheme 5 Sulfoxide elimination of 9a and 9b to 10a and 10b.
General
To complete the synthesis of (+)-swainsonine (ent-1), cis-
dihydroxylation of 10b with NMO and a catalytic amount of OsO4
in aqueous acetone provided the crude dihydroxylated product.
Without chromatographic purification, the crude mixture was
1
The H NMR spectra were recorded on a Bruker Avance-500
(500 MHz) spectrometer using tetramethylsilane as an internal
standard. The 13C NMR spectra were recorded on a Bruker
This journal is
The Royal Society of Chemistry 2011
Org. Biomol. Chem., 2011, 9, 531–537 | 533
©

View Article Online
Avance-500 (125 MHz) using residual non-deuterated solvent
peak as an internal standard. Assignments of individual sig-
nals were carried out using COSY, HMQC, HMBC, DEPT
experiments. The IR spectra were recorded on either a Jasco
A-302 or a Perkin Elmer 683 infrared spectrometer. The mass
spectra were recorded by using Thermo Finnigan Polaris Q mass
spectrometer. The high resolution mass spectra were recorded on
an MS Micromass model VQ-TOF2. Melting points were recorded
on a Buchi 501 Melting Point Apparatus and were uncorrected.
The optical rotations were recorded on a Jasco DIP-370 Digital
Polarimeter.
relative intensity)]: 280 (M+ + H, 46), 279 (M+, 25), 171 (10), 170
(100), 142 (7), 109 (5). HRMS (ESI-TOF) Calc. for C14H18NO3S
(M + H)+, 280.1007; found, 280.1016.
(S)-3-Hydroxy-1-(3-(phenylsulfanyl)propyl)piperidine-2,6-dione
(4)
To a suspension of potassium tert-butoxide (1.86 g, 16.6 mmol)
in THF (10 mL), was added a solution of 3 (8.0 g, 28.7 mmol)
in THF (80 mL) at -78 C under an argon atmosphere. After
being stirred for 3 h at -78 C, the reaction was quenched with
saturated NH4Cl solution and extracted with EtOAc (3 ¥ 60 mL).
The combined organic extracts were washed with H2O (3 ¥ 20 mL),
brine (20 mL), dried over anhydrous Na2SO4. Filtration followed
by removal of solvent gave a crude product, which was purified by
column chromatography (SiO2, 40% EtOAc in hexanes) to give a
white solid of 4 [5.8 g, 72% yield, m.p. 76.7–78.3 C, [a]2D4 -26.75 (c
0.88, CHCl3)]. 1H-NMR (500 MHz, CDCl3): d 7.35–7.26 (m, 4H,
ArH), 7.21–7.17 (m, 1H, ArH), 4.21 (ddd, J = 12.5, 5.5, 1.3 Hz,
1H, CH2CHOH), 3.95 (dt, J = 13.3, 6.8 Hz, 1H, NCHHCH2),
3.86 (dt, J = 13.3, 6.8 Hz, 1H, NCHHCH2), 3.53 (d, J = 1.3 Hz,
1H, OH), 2.90 (t, J = 7.3 Hz, 2H, CH2SPh), 2.89 (ddd, J = 18.0,
4.7, 2.6 Hz, 1H, COCHHCH2) 2.63 (ddd, J = 18.0, 13.8, 5.4 Hz,
1H, COCHHCH2), 2.36–2.31 (m, 1H, CH2CHHCHOH), 1.94–
1.84 (m, 3H, CH2CHHCHOH and NCH2CH2CH2). 13C-NMR
(125 MHz, CDCl3): d 175.2 (C O), 171.1 (C O), 136.0 (C),
129.8 (2 ¥ CH), 128.9 (2 ¥ CH), 126.3 (CH), 68.3 (CH), 39.6 (CH2),
31.6 (CH2), 30.8 (CH2), 27.4 (CH2), 25.3 (CH2). IR (film): n 3460
(O–H), 1731, 1674 cm-1. MS (EI) [m/z (% relative intensity)]: 280
(M+ + H, 35), 279 (M+, 42), 170 (100), 151 (10), 142 (28), 58 (7).
HRMS (ESI-TOF) Calc. for C14H18NO3S [M + H]+, 280.1007;
found, 280.0997.
(S)-5-Oxotetrahydrofuran-2-carboxylic acid (2)
To a solution of L-glutamic acid (18.0 g, 122.4 mmol) and NaNO2
(9.29 g, 134.6 mmol) in H2O (120 mL), was slowly added 2 N
H2SO4 (60 mL) at 0 C. After the mixture was allowed to stir at 0 C
for 3 h, it was slowly warmed up to room temperature and stirring
was continued for an additional 16 h. The resulting colorless
solution was concentrated until a white and sticky mixture was
obtained. The mixture was diluted using hot acetone followed
by filtration. The filtrate was concentrated to give a colorless
viscous liquid which was diluted with EtOAc. The EtOAc solution
was stirred in anhydrous Na2SO4 at room temperature for 16 h.
Filtration and removal of solvent furnished a white solid of
compound 2 [7.8 g, 49% yield, m.p. 71.2–72.4 C, [a]2D5 +9.17 (c 1.1,
MeOH)] [Lit.13b [a]2D0 +10.6 (c 5.0, MeOH)]. The spectroscopic data
are consistent with the literature.13b 1H-NMR (500 MHz, CDCl3):
d 8.84 (br s, 1H), 5.04–5.00 (m, 1H), 2.56–2.17 (m, 3H), 2.47–2.39
(m, 1H). 13C-NMR (125 MHz, CDCl3): d 175.9, 173.5, 75.1, 26.6,
25.8. IR (neat): n 3451 (O–H), 1760 (C O) cm-1. MS (EI) [m/z
(% relative intensity)]: 131 (M+ + H, 13), 86 (5), 85 (100), 59 (4),
58 (54), 55 (4).
(S)-3-(tert-Butyldimethylsilyloxy)-1-(3-(phenylsulfanyl)propyl)-
(S)-5-Oxo-N-(3-(phenylsulfanyl)propyl)tetrahydrofuran-2-
piperidine-2,6-dione (5)
carboxamide (3)
To a mixture of 4 (5.5 g, 19.7 mmol), imidazole (2.7 g, 39.0 mmol)
and a catalytic amount of N,N-dimethylaminopyridine (DMAP)
in CH2Cl2 (40 mL) at 0 C under an argon atmosphere, was
slowly added a solution of tert-butyldimethylchlorosilane (3.54 g,
23.6 mmol) in CH2Cl2 (20 mL). After being stirred at room
temperature overnight, water (10 mL) was added. The aqueous
phase was separated and the organic layer was washed with brine
(20 mL) and dried over anhydrous Na2SO4. Filtration followed by
removal of solvent gave a crude product, which was purified by
column chromatography (SiO2, 20% EtOAc in hexanes) to give
a colourless viscous liquid of 5 [6.74 g, 87% yield, [a]2D4 -10.83
A solution of carboxylic acid 2 (5.7 g, 44.0 mmol) and oxalyl
chloride (4.5 mL, 52.8 mmol) in CH2Cl2 (100 mL) in the presence
of a catalytic amount of N,N-dimethylformamide (DMF) was
stirred at room temperature for 3 h. An excess of oxalyl chloride
was removed in vacuo. The residue was dissolved in dry CH2Cl2
(90 mL). The resulting solution was brought to 0 C followed by
addition of triethylamine (7.3 mL, 52.8 mmol) and a solution of
3-(phenylsulfanyl)propan-1-amine (8.8 mL, 52.8 mmol) in CH2Cl2
(30 mL) under an argon atmosphere. After being stirred at room
temperature overnight (16 h), water (20 mL) was added. Layers
were separated and the aqueous phase was extracted with CH2Cl2
(4 ¥ 60 mL). The combined organic layers were washed with brine
(20 mL), dried over anhydrous Na2SO4, filtered and concentrated
to give a white solid of 3 [8.2 g, 67% yield, m.p. 77.3–77.9 C, [a]D24
-7.68 (c 0.86, CHCl3)]. 1H-NMR (500 MHz, CDCl3): d 7.35–7.28
(m, 4H), 7.22–7.18 (m, 1H), 6.59 (br s, 1H), 4.83 (t, J = 7.1 Hz,
1H), 3.49–3.37 (m, 2H), 2.94 (t, J = 7.1 Hz, 2H), 2.67–2.61 (m,
1H), 2.58–2.52 (m, 2H), 2.36–2.26 (m, 1H), 1.90–1.84 (m, 2H).
13C-NMR (125 MHz, CDCl3): d 175.6, 169.3, 135.7, 129.6, 129.0,
126.3, 77.4, 38.3, 31.3, 28.7, 27.5, 25.8. IR (neat): n 3367 (N–H),
1780 (C O, lactone), 1652 (C O, amide) cm-1. MS (EI) [m/z (%
1
(c 0.75, CHCl3)]. H-NMR (500 MHz, CDCl3): d 7.35–7.33 (m,
2H, ArH), 7.29–7.26 (m, 2H, ArH), 7.19–7.16 (m, 1H, ArH), 4.29
(dd, J = 8.0, 4.1 Hz, 1H, CH2CHOSi), 3.86 (t, J = 7.2 Hz, 2H,
NCH2CH2), 2.93–2.87 (m, 1H, COCHHCH2), 2.88 (t, J = 7.5 Hz,
2H, CH2SPh), 2.59 (ddd, J = 17.8, 8.1, 5.3 Hz, 1H, COCHHCH2),
2.06–1.97 (m, 2H, CH2CH2CHOSi), 1.85 (quint, J = 7.3 Hz, 2H,
NCH2CH2CH2), 0.96 (s, 9H), 0.14 (s, 3H), 0.13 (s, 3H).13C-NMR
(125 MHz, CDCl3): d 172.3 (C O), 171.8 (C O), 135.2 (C), 129.7
(2 ¥ CH), 128.9 (2 ¥ CH), 126.1 (CH), 69.3 (CH), 39.0 (CH2), 31.5
(CH2), 29.1 (CH2), 27.5 (CH2), 26.5 (CH2), 25.6 (3 ¥ CH3), 18.2
(C), -4.7(CH3), -5.4(CH3). IR (neat): n 1735, 1685 cm-1; MS (EI)
[m/z (% relative intensity)]: 394 (M+ + H, 5), 336 (47), 151 (100),
534 | Org. Biomol. Chem., 2011, 9, 531–537
This journal is
The Royal Society of Chemistry 2011
©

View Article Online
123 (20), 75 (4). HRMS (ESI-TOF) Calc. for C20H32NO3SSi [M +
H]+, 394.1872; found, 394.1795.
2.94–2.85 (m, 2H), 2.47 (ddd, J = 17.3, 4.8, 2.8 Hz, 1H), 2.17–2.12
(m, 1H), 2.07 (ddd, J = 15.7, 11.5, 8.2 Hz, 1H), 1.88–1.84 (m,
1H), 0.94 (s, 9H), 0.29 (s, 3H), 0.28 (s, 3H). 13C-NMR (125 MHz,
CDCl3): d 167.9, 148.8, 142.2, 130.6, 129.2, 124.2, 120.8, 60.0,
44.3, 28.8, 27.1, 25.7, 22.2, 18.0, -4.4, -4.8. IR (CHCl3): n 1667,
1627 cm-1. MS (EI) [m/z (% relative intensity)]: 391 (M+, 0.3),
334 (100), 229 (86), 225 (88), 210 (45), 188 (43), 150 (40), 75 (34);
HRMS (ESI-TOF) Calc. for C20H30NO3SSi [M + H]+, 392.1716;
found, 392.1722.
(3S)-3-(tert-Butyldimethylsilyloxy)-1-(3-(phenylsulfinyl)propyl)-
piperidine-2,6-dione (6)
A solution of 5 (6.7 g, 17.0 mmol) in MeOH (10 mL) was slowly
added to a suspension of NaIO4 (4.0 g, 18.7 mmol) in MeOH
(48 mL) and H2O (12 mL) at 0 C. The mixture was vigorously
stirred and slowly warmed up to room temperature overnight
(12 h). The precipitates of NaIO3 were filtered and washed with
EtOAc (3 ¥ 60 mL). The combined extracts were washed with
H2O (3 ¥ 20 mL), brine (20 mL) and dried over anhydrous
Na2SO4. Filtration followed by removal of solvent gave a crude
product, which was purified by column chromatography (SiO2,
70% EtOAc in hexanes) to afford a colourless viscous liquid of 6
F2 (more polar) was obtained as a colourless viscous liquid of
1
8b; [a]2D5 -32.82 (c 1.01, CHCl3). H-NMR (500 MHz, CDCl3):
d 7.58–7.50 (m, 2H), 7.49–7.29 (m, 3H), 5.18–5.17 (m, 1H), 3.87
(ddd, J = 12.0, 12.0, 6.7 Hz, 1H), 3.78 (ddd, J = 12.0, 12.0, 7.1 Hz,
1H), 2.83 (ddd, J = 16.1, 11.8, 7.1 Hz, 1H), 2.74 (ddd, J = 17.0,
12.5, 4.9 Hz, 1H), 2.44 (dt, J = 17.2, 3.8 Hz, 1H), 2.08–2.00 (m,
2H), 1.97–1.90 (m, 1H), 0.90 (s, 9H), 0.18 (s, 3H), 0.15 (s, 3H).
13C-NMR (125 MHz, CDCl3): d 167.7, 149.6, 141.6, 130.2, 129.0,
124.4, 120.4, 60.7, 44.3, 28.5, 27.0, 25.6, 22.2, 17.8, -4.40, -4.36. IR
(CHCl3): n 1671, 1628 cm-1. MS (EI) [m/z (% relative intensity)]:
391 (M+, 0.8), 334 (87), 225 (100), 170 (12), 125 (10); HRMS
(ESI-TOF) Calc. for C20H30NO3SSi [M + H]+, 392.1716; found,
392.1704.
1
as a mixture of two diastereomers (6.3 g, 90% yield). H-NMR
(500 MHz, CDCl3): d 7.63–7.61 (m, 4H), 7.53–7.49 (m, 6H), 4.31–
4.29 (m, 2H), 3.92–3.82 (m, 4H), 2.9–2.74 (m, 6H), 2.63–2.60
(m, 2H), 2.09–1.94 (m, 6H), 1.88–1.79 (m, 2H), 0.90 and 0.86 (s
each, 18H), 0.14 and 0.13 (s each, 12H). 13C-NMR (125 MHz,
CDCl3): d 172.46, 172.44, 171.85, 171.77, 143.6, 130.95, 130.93,
129.2, 124.02, 124.01, 69.22, 69.20, 54.74, 54.67, 38.58, 38.52,
29.14, 29.08, 26.4, 25.6, 21.1, 18.2, -4.7, -5.4. IR (neat): n 1732,
1682 cm-1. MS (EI) [m/z (% relative intensity)]: 410 (M+ + H, 6),
352 (42), 284 (21), 226 (53), 167 (100), 143 (11), 109 (9). HRMS
(ESI-TOF) Calc. for C20H32NO4SSi [M + H]+, 410.1821; found,
410.1833.
(1R,8S,8aR)-8-(tert-Butyldimethylsilyloxy)-1-((R)-
phenylsulfinyl)hexahydroindolizin-5(1H)-one (9a)
To a solution of 8a (0.7 g, 1.8 mmol) in AcOH (5 mL) in the
presence of a catalytic amount of TFA (0.02 mL) at 0 C under
an argon atmosphere, NaCNBH3 (0.4 g, 5.3 mmol) was gradually
added over 15 min. The mixture was stirred at 50 C for 5 h. The
resulting mixture was diluted with 1 N NaOH (5 mL) and H2O
(5 mL), and extracted with CH2Cl2 (3 ¥ 50 mL). The combined
organic extracts were washed with brine (20 mL) and dried over
anhydrous Na2SO4. Filtration followed by removal of solvent gave
a crude product, which was purified by column chromatography
(SiO2, 100% EtOAc) to afford a colourless viscous liquid of 9a
[0.5 g, 71% yield; 76% yield calculated based on the recovered 8a,
[a]2D5 -90.07 (c 0.95, CHCl3)] and 8a (34 mg). 1H-NMR (500 MHz,
CDCl3): d 7.67–7.65 (m, 2H), 7.58–7.52 (m, 3H), 4.55 (dt, J = 5.6,
3.0 Hz, 1H), 4.14 (ddd, J = 11.5, 8.6, 5.6 Hz, 1H), 3.77 (dd, J = 7.0,
3.1 Hz, 1H), 3.33 (app. q, J = 7.1 Hz, 1H), 3.26 (ddd, J = 11.5, 8.2,
6.7 Hz, 1H), 2.58 (dt, J = 17.7, 7.8 Hz, 1H), 2.43–2.33 (m, 2H),
2.22–2.15 (m, 1H), 1.95–1.87 (m, 2H), 0.99 (s, 9H), 0.27 (s, 3H),
0.22 (s, 3H). 13C-NMR (125 MHz, CDCl3): d 168.6, 144.6, 131.1,
129.4, 124.5, 66.4, 66.1, 62.7, 44.9, 29.3, 27.7, 26.1, 22.2, 18.2, -3.8,
-4.2. IR (CHCl3): n 1635 (C O) cm-1. MS (EI) [m/z (% relative
intensity)]: 394 (M+ + H, 6), 336 (68), 268 (57), 210 (50), 136 (100),
73 (43). HRMS (ESI-TOF) Calc. for C20H32NO3SSi [M + H]+,
394.1872; found, 394.1865.
(8S)-8-(tert-Butyldimethylsilyloxy)-1-(phenylsulfinyl)-2,3,7,8-
tetrahydroindolizin-5(6H)-ones (8a) and (8b)
A solution of 6 (6.2 g, 15 mmol) in THF (18 mL) was added
dropwise to a cooled (-78 C) THF (100 mL) solution of
LiHMDS [prepared by reacting n-BuLi (1.35 M in hexane; 25 mL,
33.75 mmol) with a solution of hexamethyldisilazane (HMDS)
(7.6 mL, 36.4 mmol) in THF (40 mL) at -78 C for 45 min] under
an argon atmosphere. The resulting mixture was stirred and slowly
warmed up from -78 C to room temperature overnight (15 h).
The resulting yellow solution was quenched with H2O (20 mL)
and extracted with EtOAc (3 ¥ 100 mL). The combined organic
extracts were washed with H2O (3 ¥ 20 mL), brine (20 mL) and
dried over anhydrous Na2SO4. Filtration followed by removal of
solvents furnished a crude residue of hydroxyindolizidine amide 7
(4.9 g) which was used in the next step without prior purification.
A crude residue of 7 (4.9 g) was diluted with CH2Cl2 (50 mL). To
the resulting solution was added a catalytic amount of p-TsOH and
the mixture was brought to refluxing temperature under an argon
atmosphere for 16 h. The resulting solution was diluted with H2O
(20 mL) and extracted with CH2Cl2 (3 ¥ 70 mL). The combined
organic extracts were washed with H2O (3 ¥ 20 mL), brine (20 mL)
and dried over anhydrous Na2SO4. Filtration followed by removal
of solvent gave a crude product, which was purified by column
chromatography (SiO2, 100% EtOAc) to afford colourless viscous
liquid of 8a (0.71 g, 15% yield) and 8b (3.07 g, 65% yield).
(1S,8S,8aS)-8-(tert-Butyldimethylsilyloxy)-1-((S)-phenylsulfinyl)-
hexahydroindolizin-5(1H)-one (9b)
By following the procedure described for 9a, a solution of 8b
(2.9 g, 7.4 mmol) in AcOH (20 mL) in the presence of a catalytic
amount of TFA (0.01 mL) at 0 C was treated with NaCNBH3
(4.9 g, 22.2 mmol) to give a crude product, which was purified by
column chromatography (SiO2, 100% EtOAc) to afford 8b (0.2 g)
and a colourless viscous liquid of 9b [1.97 g, 68% yield; 75% yield
F1 (less polar) was obtained as a colourless viscous liquid of
8a; [a]2D5 +40.04 (c 1.17, CHCl3). 1H-NMR (500 MHz, CDCl3): d
7.55–7.48 (m, 5H), 5.20 (dd, J = 4.0, 2.2 Hz, 1H), 3.91 (ddd, J =
12.0, 12.0, 5.6 Hz, 1H), 3.76 (ddd, J = 12.0, 12.0, 8.2 Hz, 1H),
This journal is
The Royal Society of Chemistry 2011
Org. Biomol. Chem., 2011, 9, 531–537 | 535
©

View Article Online
1
based on recovered 8b, [a]2D5 +132.14 (c 1,05, CHCl3)]. H-NMR
of aqueous NaHSO3 solution (3 mL), the mixture was stirred
for an additional 1 h at room temperature and extracted with
EtOAc (3 ¥ 50 mL). The combined organic extracts were dried
over anhydrous Na2SO4. Filtration followed by removal of solvent
gave the corresponding dihydroxlated product, which was used in
the next step without purification.
(500 MHz, CDCl3): d 7.70–7.68 (m, 2H), 7.56–7.29 (m, 3H), 4.80
(ddd, J = 10.4, 8.1, 3.8 Hz, 1H), 3.82 (dd, J = 8.2, 4.1 Hz, 1H),
3.54 (dd, J = 6.1, 4.3 Hz, 1H), 3.29 (t, J = 10.6 Hz, 1H), 3.16 (dd,
J = 18.5, 9.3 Hz, 1H), 2.55 (ddd, J = 17.8, 5.6, 3.4 Hz, 1H), 2.44
(ddd, J = 17.8, 11.9, 5.8 Hz, 1H), 2.16–2.10 (m, 1H), 1.94–1.73 (m,
3H), 0.94 (s, 9H), 0.29 (s, 3H), 0.19 (s, 3H). 13C-NMR (125 MHz,
CDCl3): d 168.3, 142.0, 132.1, 129.3, 125.6, 67.7, 66.6, 66.0, 43.0,
31.1, 29.6, 25.8, 23.7, 17.9, -4.4. IR (CHCl3): n 1635 (C O) cm-1.
MS (EI) [m/z (% relative intensity)]: 394 (M+ + H, 5), 336 (60),
268 (64), 210 (78), 136 (100), 108 (30), 73 (41). HRMS (ESI-
TOF) Calc. for C20H32NO3SSi [M + H]+, 394.1872; found, 394.
1909.
To a suspension of LiAlH4 (0.4 g, 10.5 mmol) in THF (30 mL),
the crude dihydroxylated product was added. The mixture was
heated at reflux for 16 h. Under ice cooling, the mixture was
quenched by careful addition of water (4.0 mL) and 1 N NaOH
(4.0 mL). The resulting mixture was filtered over a celite pad and
the filtrate was concentrated to afford a viscous liquid of 11 [0.45 g,
1
89% yield, [a]2D5 +29.34 (c 1.06, CHCl3)]. H-NMR (500 MHz,
CD3OD): d 4.19 (ddd, J = 7.9, 5.8, 2.3 Hz, 1H), 4.07 (dd, J =
5.9, 3.5 Hz, 1H), 3.89 (ddd, J = 10.3, 9.0, 4.8 Hz, 1H), 2.89 (br d,
J = 2.3 Hz, 1H), 2.87 (br d, J = 2.3 Hz, 1H), 2.42 (dd, J = 10.5,
7.8 Hz, 1H), 1.98–194 (m, 1H), 1.85 (td, J = 11.4, 3.1 Hz, 1H),
1.74 (dd, J = 8.9, 3.5 Hz, 1H), 1.66–1.51 (m, 2H), 1.23–1.14 (m,
1H), 0.89 (s, 9H), 0.12 (s, 3H), 0.09 (s, 3H). 13C-NMR (125 MHz,
CD3OD): d 75.5, 70.9, 70.0, 68.4, 63.0, 53.2, 35.2, 26.4, 24.5, 18.8,
-4.1, -4.5. IR (KBr): 3399 (O–H), 1472, 1247, 1112 cm-1. MS (EI)
[m/z (% relative intensity)]: 288 (M+ + H, 3), 230 (100), 212 (32),
138 (20), 120 (52), 116 (30), 75 (16). HRMS (ESI-TOF) Calc. for
C14H30NO3Si [M + H]+, 288.1995; found, 288.1961.
(8S,8aS)-8-(tert-Butyldimethylsilyloxy)-6,7,8,8a-
tetrahydroindolizin-5(3H)-one (10a)
A toluene (5 mL) solution of 9a (0.38 g, 0.97 mmol) in the
presence of CaCO3 (30 mg) was stirred at reflux under an argon
atmosphere for 16 h. CaCO3 was filtered off and the filtrate was
evaporated to dryness to give a crude product, which was purified
by preparative thin-layer chromatography (SiO2, 100% EtOAc)
to give a colourless viscous liquid of 10a [0.21 g, 80% yield, [a]D25
-53.73 (c 1.10, CHCl3)]. 1H-NMR (500 MHz, CDCl3): d 5.93–5.90
(m 1H), 5.69–5.66 (m, 1H), 4.53–4.48 (m, 1H), 4.37–4.35 (m, 1H),
4.24–4.22 (m, 1H), 4.05–4.01 (m, 1H), 2.49 (dt, J = 17.8, 9.1 Hz,
1H), 2.40 (ddd, J = 17.8, 6.7, 4.3 Hz), 1.94–1.90 (m, 2H), 0.82 (s,
9H), 0.05 (s, 3H), 0.08 (s, 3H). 13C-NMR (125 MHz, CDCl3): d
169.3, 127.3, 127.0, 68.9, 65.1, 53.3, 28.7, 26.7, 25.5, 17.9, -4.6,
-4.9. IR (CHCl3): n 1639 (C O) cm-1. MS (EI) [m/z (% relative
intensity)]: 267 (M+, 9), 242 (46), 224 (57), 210 (92), 196 (45),
150 (81), 122 (36), 81 (39), 75 (100). HRMS (ESI-TOF) Calc. for
C14H26NO2Si [M + H]+, 268.1733; found, 268.1730.
(+)-Swainsonine (ent-1)
A mixture of 11 (90 mg, 0.31 mmol) and a cation exchange
resin, Dowex 50W-X8 (H+ form), in MeOH was stirred at room
temperature for 24 h. The resin was filtered off and washed with
10% NH4OH (30 mL). The filtrate was evaporated to dryness
followed by lyophilization to give a white solid of (+)-swainsonine
(ent-1) [51 mg, 94% yield, m.p. 140–143 C, [a]2D5 +78.97 (c 0.63,
MeOH): Lit.9 m.p. 143–145 C, [a]D +83.3 (c 0.5, MeOH); Lit.15b
m.p. 142–143 C, [a]D +84.3 (c 1.02, H2O)].
(8S,8aR)-8-(tert-Butyldimethylsilyloxy)-6,7,8,8a-
tetrahydroindolizin-5(3H)-one (10b)9
1H-NMR (500 MHz, CD3OD): d 4.25–4.19 (m, 2H), 3.79 (ddd,
J = 11.2, 10.1, 4.6 Hz, 1H), 2.96–2.93 (m, 2H), 2.48 (dd, J = 10.4,
7.5 Hz, 1H), 2.04–2.01 (m, 1H), 1.96 (td, J = 11.9, 2.5 Hz, 1H), 1.82
(dd, J = 9.1, 3.0 Hz, 1H), 1.70–1.68 (m, 1H) 1.64–1.55 (m, 1H),
1.22 (qd, J = 12.9, 4.6 Hz, 1H). 13C-NMR (125 MHz, CD3OD): d
75.1, 70.6, 69.8, 66.8, 62.8, 53.0, 33.9, 24.3. IR (neat): n 3367 (O–
H), 1643, 1448, 1384, 1145, 1084 cm-1. MS (EI) [m/z (% relative
intensity)]: 173 (M+, 5), 155 (36), 120 (17), 110 (27), 96 (100), 84
(26), 68 (12). HRMS (ESI-TOF): Calc. for C8H16NO3 [M + H]+,
174.1125; found, 174.1150.
According to the procedure described for 10a, a toluene (15 mL)
solution of 9b (1.97 g, 5.0 mmol) in the presence of CaCO3
(100 mg) was stirred at reflux under an argon atmosphere for 16 h.
Purification by preparative thin-layer chromatography (SiO2,
100% EtOAc) yielded a colourless viscous liquid of 10b [1.07 g,
1
80% yield, [a]2D5 -53.73 (c 1.10, CHCl3)]. H-NMR (500 MHz,
CDCl3): d 5.96–5.90 (m, 2H), 4.50–4.46 (m, 1H), 4.17–4.14 (m,
1H), 4.06–4.03 (m, 1H), 3.57 (td, J = 9.5, 5.2 Hz, 1H), 2.63 (ddd,
J = 17.8, 8.5, 3.6 Hz, 1H), 2.42 (dt, J = 17.9, 8.5 Hz, 1H), 2.05–1.99
(m, 1H), 1.84–1.75 (m, 1H), 0.90 (s, 9H), 0.08 (s, 6H). 13C-NMR
(125 MHz, CDCl3): d 168.4, 128.5, 126.7, 71.1, 69.1, 53.2, 30.2,
29.7, 25.6, 17.9, -4.3, -4.8. IR (CHCl3): n 1638 (C O), 1613 cm-1.
MS (EI) [m/z (% relative intensity)]: 267 (M+, 9), 210 (100) 196
(29), 150 (44), 122 (29), 81 (31), 75 (71). HRMS (ESI-TOF) Calc.
for C14H26NO2Si [M + H]+, 268.1733; found, 268.1741.
Acknowledgements
Financial support from the Thailand Research Fund (to MP:
BRG49800005) and the Center for Innovation in Chemistry
(PERCH-CIC) is gratefully acknowledged.
Notes and references
(1R,2S,8S,8aR)-8-(tert-butyldimethylsilyloxy)-
1 (a) N. Asano, R. J. Nash, R. J. Molyneux and G. W. J. Fleet, Tetrahedron:
Asymmetry, 2000, 11, 1645–1680; (b) J. P. Michael, Nat. Prod. Rep.,
1997, 14, 619–636; (c) J. P. Michael, Nat. Prod. Rep., 2007, 24, 191–222.
2 (a) A. A. Watson, G. W. J. Fleet, N. Asano, R. J. Molyneux and R.
J. Nash, Phytochemistry, 2001, 56, 265–295; (b) M. S. M. Pearson, M.
Mathe’-Allainmat, V. Fargeas and J. Lebreton, Eur. J. Org. Chem., 2005,
2159–2191.
octahydroindolizine-1,2-diol (11)
To a solution of 10b (0.47 g, 1.75 mmol) in a 3 : 1 mixture of
acetone–H2O (6 mL) was added N-methylmorpholine N-oxide
(0.48 g, 3.5 mmol) and 4% aqueous OsO4, (1.0 mL). The reaction
mixture was stirred at room temperature for 3 h. After addition
536 | Org. Biomol. Chem., 2011, 9, 531–537
This journal is
The Royal Society of Chemistry 2011
©

View Article Online
3 (a) M. J. Schneider, F. S. Ungemach, H. P. Broquist and T. M. Harris,
Tetrahedron, 1983, 39, 29–32; (b) F. P. Guengerich, S. J. DiMari and H.
P. Broquist, J. Am. Chem. Soc., 1973, 95, 2055–2056.
4 (a) C. Tamerler and T. Kesharaz, Biotechnol. Lett., 1999, 21, 501–504;
(b) T. M. Ermayanti, J. A. McComb and P. A. O’Breien, Phytochemistry,
1994, 36, 313–317; (c) S. M. Colegate, P. R. Dorling and C. R. Huxtable,
Aust. J. Chem., 1979, 32, 2557–2264.
5 (a) P. R. Dorling, C. R. Huxtable and S. M. Colegate, Biochem. J.,
1980, 191, 649–651; (b) A. D. Elbein, R. Solf, P. R. Dorling and K.
Vosbeck, Proc. Natl. Acad. Sci. U. S. A., 1981, 78, 7393–7397; (c) G.
P. Kaushal, T. Szumilo, I. Pastuszak and A. D. Elbein, Biochemistry,
1990, 29, 2168–2176; (d) I. Pastuszak, G. P. Kaushal, K. A. Wall, Y. T.
Pan, A. Sturm and A. D. Elbein, Glycobiology, 1990, 1, 71–82.
6 (a) P. E. Goss, M. A. Baker, J. P. Carver and J. W. Dennis, Clin. Cancer
Res., 1995, 1, 935–944; (b) P. E. Goss, C. L. Reid, D. Bailey and J.
W. Dennis, Clin. Cancer Res., 1997, 3, 1077–1086; (c) J. W. Dennis,
Cancer Res., 1986, 46, 5131–5136; (d) S. L. White, K. Schweitzer, M.
J. Humphries and K. Olden, Biochem. Biophys. Res. Commun., 1988,
150, 615–625.
8 For recent examples and leading references for the synthesis of
polyhydroxylated indolizidine alkaloids, see: (a) J. Ceccon, G. Danoun,
A. E. Green and J.-F. Poisson, Org. Biomol. Chem., 2009, 7, 2029–2031;
(b) S. R. Angle, D. Bensa and D. S. Belanger, J. Org. Chem., 2007, 72,
5592–5597; (c) R. Ben-Othman, M. Othman, K. Ciamala, M. Knorr,
C. Strohmann and B. Decroix, Tetrahedron, 2009, 65, 4846–4854; (d) D.
Baumann, K. Bennis, I. Ripoche, V. The´ry and Y. Troin, Eur. J. Org.
Chem., 2008, 5289–5300; (e) G.-F. Shi, J.-Q. Li, X.-P. Jiang and Y.
Cheng, Tetrahedron, 2008, 64, 5005–5012; (f) X.-P. Jiang, Y. Cheng,
G.-F. Shi and Z.-M. Kang, J. Org. Chem., 2007, 72, 2212–2215; (g) S.
Hanessian, E. Therrien, J. S. Warrier and G. Charron, Heterocycles,
2006, 70, 461–476; (h) E. M. Sletten and L. J. Liotta, J. Org. Chem.,
2006, 71, 1335–1343; (i) N. Langlois, B. K. LeNguyen, P. Retailleau,
C. Tarnus and E. Salomon, Tetrahedron: Asymmetry, 2006, 17, 53–
60; (j) L. Cronin and P. V. Murphy, Org. Lett., 2005, 7, 2691–2693;
(k) Z. Zhao, L. Song and P. S. Mariano, Tetrahedron, 2005, 61, 8888–
ˇ
8894; (l) K. Kadlecˇ´ıkova´, V. Dalla, S. Marchal´ın, B. Decroix and P.
Baran, Tetrahedron, 2005, 61, 4743–4754; (m) L. Song, E. N. Duesler
and P. S. Mariano, J. Org. Chem., 2004, 69, 7284–7293; (n) T. Ayad, Y.
Genisson and M. Baltas, Curr. Org. Chem., 2004, 8, 1211–1233; (o) S.
H. L. Verhelst, B. P. Martinez, M. S. M. Timmer, G. Lodder, G. A.
Van Der Marel, H. S. Overkleeft and J. H. Van Boom, J. Org. Chem.,
2003, 68, 9598–9603; (p) H. Razavi and R. Polt, J. Org. Chem., 2000,
65, 5693–5706; (q) A. Goti, M. Cacciarini, F. Cardona and A. Brandi,
Tetrahedron Lett., 1999, 40, 2853–2856; (r) M. J. Martin-Lo´pez, R.
Rodriguez and F. Bermejo, Tetrahedron, 1998, 54, 11623–11636; (s) J.
C. Carretero and R. G. Arraya´s, J. Org. Chem., 1998, 63, 2993–3005;
(t) W. H. Pearson and E. J. Hembre, J. Org. Chem., 1996, 61, 5546–5556;
(u) R. Rodr´ıguez and F. Bermejo, Tetrahedron Lett., 1996, 37, 5581–
5584; (v) M.-J. Blanco and F. J. Sardina, J. Org. Chem., 1996, 61, 4748–
4755; (w) D. Hendry, L. Hough and A. C. Richardson, Tetrahedron,
1988, 44, 6143–6152; (x) D. Hendry, L. Hough and A. C. Richardson,
Tetrahedron, 1988, 44, 6153–6168.
7 For reviews of the synthesis of swainsonine and analogues, see: (a) A.
E. Nemr, Tetrahedron, 2000, 56, 8579–8629; (b) S. G. Pyne, Curr. Org.
Synth., 2005, 3, 39–57 and references cited; (c) J. P. Michael, Nat. Prod.
Rep., 2008, 25, 139–165; (d) Y.-S. Tian, J.-E. Joo, B.-S. Kong, V.-T.
Pham, K.-Y. Lee and W.-H. Ham, J. Org. Chem., 2009, 74, 3962–3965;
(e) M. A. Alam, A. Kumar and Y. D. Vankar, Eur. J. Org. Chem., 2008,
4972–4980; (f) P. K. Sharma, R. N. Shah and J. P. Carver, Org. Process
Res. Dev., 2008, 12, 831–836; (g) K. S. Ajish Kumar, V. D. Chaudhari
and D. D. Dhavale, Org. Biomol. Chem., 2008, 6, 703–711; (h) G.-F. Shi,
J.-Q. Li, X.-P. Jiang and Y. Cheng, Tetrahedron, 2008, 64, 5005–5012;
(i) J. N. Abrams, R. S. Babu, H. Guo, D. Le, J. Le, J. M. Osbourn
and G. A. O’Doherty, J. Org. Chem., 2008, 73, 1935–1940; (j) H. Y.
Kwon, C. M. Park, S. B. Lee, J.-H. Youn and S. H. Kang, Chem.–Eur.
J., 2008, 14, 1023–1028; (k) H. Guo and G. A. O’Doherty, Tetrahedron,
2008, 64, 304–313; (l) J. Bi and V. K. Aggarwal, Chem. Commun., 2008,
120–122; (m) I. De´champs, D. G. Pardo and J. Cossy, Tetrahedron,
2007, 63, 9082–9091; (n) A. J. Murray, P. J. Parsons and P. Hitchcock,
Tetrahedron, 2007, 63, 6485–6492; (o) G. Pandey, D. G. Dumbre, S. Pal,
M. I. Khan and M. Shabab, Tetrahedron, 2007, 63, 4756–4761; (p) I.
De´champs, D. Gomez Pardo and J. Cossy, Arkivoc, 2007, v, 38–45; (q) J.
Ceccon, A. E. Greene and J.-F. Poisson, Org. Lett., 2006, 8, 4739–4742;
(r) C. W. G. Au and S. G. Pyne, J. Org. Chem., 2006, 71, 7097–7099;
(s) A. Tinarelli and C. Paolucci, J. Org. Chem., 2006, 71, 6630–6633;
(t) A. J. Murray and P. J. Parsons, Synlett, 2006, 1443–1445; (u) M.
Nath, R. Mukhopadhyay and A. Bhattacharjya, Org. Lett., 2006, 8,
9 T. Oishi, T. Iwakura and M. Hirama, Synlett, 1995, 404–406.
10 M. Pohmakotr, P. Numechai, S. Prateeptongkum, P. Tuchinda and V.
Reutrakul, Org. Biomol. Chem., 2003, 1, 3495–3497.
11 M. Pohmakotr, S. Prateeptongkum, S. Chooprayoon, P. Tuchinda and
V. Reutrakul, Tetrahedron, 2008, 64, 2339–2347.
12 M. Pohmakotr, A. Seubsai, P. Numechai and P. Tuchinda, Synthesis,
2008, 1733–1736.
13 (a) P.-Q. Huang, L.-X. Liu, B.-G. Wei and Y.-P. Ruan, Org. Lett.,
2003, 5, 1927–1929; (b) U. Rabid, R. M. Silverstein and L. R. Smith,
Tetrahedron, 1978, 34, 1449–1452.
14 A. S. Cieplak, Chem. Rev., 1999, 99, 1265–1336.
15 (a) H. Guo and G. A. O’Doherty, Tetrahedron, 2008, 64, 304–313;
(b) H. Guo and G. A. O’Doherty, Org. Lett., 2006, 8, 1609–1612.
ˇ
317–320; (v) K. Kadlecˇ´ıkova´, V. Dalla, S. Marchal´ın, B. Decroix and P.
Baran, Tetrahedron, 2005, 60, 4743–4754.
This journal is
The Royal Society of Chemistry 2011
Org. Biomol. Chem., 2011, 9, 531–537 | 537
©