Preparation of γ-siloxyallyltributylstannanes and their use in the synthesis of (±)-1-deoxy-6,8a-di-epi-castanospermine

Article abstract of DOI:10.1039/b409507c

γ-Siloxyallyltributylstannanes were selectively obtained as E or Z isomers from β-tributylstannylacrolein upon reaction with lithium or magnesium alkylcyanocuprates. The ability of the reagents to give a high syn selectivity when added to iminium salts ha

Full text of DOI:10.1039/b409507c

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A R T I C L E
Preparation of c-siloxyallyltributylstannanes and their use in the
synthesis of (±)-1-deoxy-6,8a-di-epi-castanospermine
Floris Chevallier,a Erwan Le Grognec,a Isabelle Beaudet,a Florian Fliegel,a Michel Evainb and
Jean-Paul Quintard*a
a
Laboratoire de Synthèse Organique, UMR CNRS 6513 and FR CNRS 2465,
Faculté des Sciences et des Techniques de Nantes, 2 rue de la Houssinière, BP 92208, 44322,
Nantes Cedex 3, France. E-mail: quintard@chimie.univ-nantes.fr; Fax: +33 2 51 12 54 02;
Tel: +33 2 51 12 54 08
b
Institut des Matériaux Jean Rouxel, UMR CNRS 6502, 2 rue de la Houssinière, BP 32229,
44322, Nantes Cedex 3, France
Received 24th June 2004, Accepted 1st September 2004
First published as an Advance Article on the web 29th September 2004
c-Siloxyallyltributylstannanes were selectively obtained as E or Z isomers from b-tributylstannylacrolein upon
reaction with lithium or magnesium alkylcyanocuprates. The ability of the reagents to give a high syn selectivity
when added to iminium salts has been used for the efficient synthesis of (±)-1-deoxy-6,8a-di-epi-castanospermine
from succinimide. The key step of the synthesis was the allylstannation of the N-allyliminium intermediate followed
by ring closing metathesis.
Introduction
In the course of our studies involving c-alkoxyallylstannanes
and c-siloxyallylstannanes in allylstannation reaction of
aldehydes and iminium salts, we pointed out possible effects
of an a-substituent relative to tin1 or stereoconvergent effects
when reactions were performed on chiral a-alkoxyaldehydes.2
These behaviours of heterosubstituted allylstannanes have
been reviewed by several groups with a special emphasis
on the crucial importance of the experimental conditions
on the stereochemistry of the reaction3–5 and exploited for
Scheme 1
syntheses in sugar series.6,7 As far as we are concerned,
we have recently been interested in the allylstannation of
Table 1 Synthesis of c-siloxyallyltributylstannanes
glyceraldehyde derivatives through aldopentose syntheses2
and in the already known allylstannation of iminium salts.8,9
Entry
R2Cu(CN)M2
R
Compound
Yield (E/Z)
We successfully applied these methods for the synthesis of
polyhydroxypiperidines.10 In the present paper, we report an
efficient synthesis of c-siloxyallyltributylstannanes and an
aspect of their use for the synthesis of (±)-1-deoxy-6,8a-di-epi-
castanospermine starting from succinimide.
1
2
3
4
5
6
Me2Cu(CN)Li2
Me
Me
Me
Me
Me
Ph
3
4
5
6
6
7
70% (92/8)
35% (20/80)
90% (75/25)
85% (85/15)
35% (15/85)
89% (90/10)
iPr2Cu(CN)(MgCl)2
nBu2Cu(CN)Li2
tBu2Cu(CN)Li2
tBu2Cu(CN)(MgCl)2
tBu2Cu(CN)Li2
Results and discussion
1. Synthesis of c-siloxyallyltributylstannanes
that the use of TBDPS (entry 6) does not change strongly the
stereoselectivity. These results could be explained by considering
the initial geometry of the intermediate adduct. The bidentate
nature of the magnesium might induce the Z isomer formation
through a chelation of 2 in a cisoid conformation while the
stereochemistry might essentially be controlled by steric effects
when lithium cuprates are involved (Scheme 2).
c-Siloxyallyltributylstannanes were previously obtained by
Marshall11 using the reaction of Bu3Sn(Bu)CuCNLi2 (Lipshutz
reagent)12 on a,b-enals and this reaction was shown to be also
possible when this organostannane reagent was allowed to
react with b-tributylstannylacrolein.13 Taking advantage of
the easy synthesis of b-tributylstannylacrolein diethylacetal14,15
which can be very efficiently deprotected upon treatment on
acidified silica, we extended this preparation to several c-
siloxyallylstannanes using 1,4-addition of cyanocuprates on b-
tributylstannylacrolein followed by subsequent quenching with
chlorosilanes (Scheme 1).
The obtained results are reported in Table
1 and
demonstrate an easier 1,4-addition of the cyanocuprates on
b-tributylstannylacrolein when compared to the possible
transmetalation reaction of the Csp2–Sn bond.16,17
High yields were obtained with lithium cyanocuprates
(entries 1,3,4,6), with a preference for E-siloxyallyltributyl-
stannanes, while magnesium cyanocuprates led to poor yields
with a reversed stereoselectivity (Z-siloxytributylstannanes
were obtained as major isomers) (entries 2,5). It must be noted
Scheme 2
2. Use for an expedious synthesis of (±)-1-deoxy-6,8a-di-epi-
castanospermine
The naturally occurring polyhydroxylated indolizine alkaloids,
represented by (+)-castanospermine 8 and (+)-6-epi-castanos-
permine 9 (Scheme 3), have been isolated from Castanospermum
3 1 2 8
O r g . B i o m o l . C h e m . , 2 0 0 4 , 2 , 3 1 2 8 – 3 1 3 3
T h i s j o u r n a l i s © T h e R o y a l S o c i e t y o f C h e m i s t r y 2 0 0 4

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australe18 and Alexa leiopetala.19 These indolizine alkaloids and
their derivatives were reported to display glycosidase inhibition
activity20,21 and are considered as potential antiviral, antitumor
and immunomodulating agents.22,23 With regards to their unique
24 h, allowed construction of the tetrahydro-indolizinone 12 in
over 80% yield. Subsequent dihydroxylation of 12 with OsO4/N-
methylmorpholine N-oxide at room temperature34 provided the
corresponding diol which was directly acetylated with Ac2O in
pyridine to afford 13 (purified by flash chromatography and
fully characterized) as shown in Scheme 6. The stereochemistry
properties, (+)-castanospermine
8 and (+)-6-epi-castanos-
permine 9 and their analogues have recently been synthesized
by several groups.24–28 Among these compounds (+)-1-deoxy-
6,8a-di-epi-castanospermine was shown to be an inhibitor of
a-L-fucosidase.29
1
of 13 was fully established on the basis of H NMR spectra,
COSY and NOESY homonuclear shift correlation spectra.
Scheme 3
In order to learn more about this type of molecule
both in terms of recognition and structure/reactivity
relationships in the area of glycosidase inhibitors, it appears of
high interest to synthesise natural and unnatural species in this
series with perfect control of the stereochemistry. Taking advan-
tage of the expected syn addition of c-siloxyallylstannanes on
iminium salts, this kind of skeleton seems likely to be obtained
through a combined allylstannation/ring closing metathesis
sequence starting from an N-allyl succinimide derivative. 1-
Allyl-5-ethoxy pyrrolidinone 11 was prepared in two steps from
commercially available succinimide (Scheme 4) according to
literature procedures.30,31 The succinimide was alkylated under
Mitsunobu conditions32 to furnish the corresponding imide
10, which was reduced by NaBH4 in dry ethanol to give the
intermediate a-ethoxy amide 11.33
Scheme 6
A NOE interaction between 8a-H and 5-H (Fig. 1) and
3
a vicinal coupling constant Jax-ax = 12 Hz (Fig. 2) strongly
support the stereochemistry of the obtained compound and the
syn selectivity of the allystannation reaction.
Fig. 1 NOE interaction observed on 13.
Scheme 4 a) PPh3, DEAD, CH2CH–CH2OH, THF (82%).
b) NaBH4, EtOH (65%).
The addition of c-siloxyallyltributylstannane 3E to the
iminium salt 11a formed in situ from the ethoxy amide 11 in the
presence of BF3·OEt2 (3 equiv.) in CH2Cl2 at −78 °C afforded
after 1 h, selectively, the expected adduct as a crude product 11b
after neutralization with NaHCO3 and washing (Scheme 5).
The use of c-siloxyallyltributylstannane 3E was preferred to the
others due to the ring-closing metathesis reaction facilitated by
the volatility of the rejected olefin.
This crude product (11b) upon treatment with Grubbs’
catalyst [(PCy3)2RuCl2(CHPh)] in refluxed CH2Cl2 during
Fig. 2 Meaningful coupling constants for compound 13.
This syn selectivity obtained from a cyclic iminium salt
generated from a-ethoxy amide appears to be similar to that
observed with N-acyl iminiums derived from non-cyclic
a-ethoxy carbamates.10 The NMR investigations were also
indicative of a dihydroxylation of 12 occurring on the face of
the double bond having a syn relationship to 8a-H and driven
by an anti effect of the TBDMS group. In addition, suitable
single crystals for an X-ray analysis were obtained for 13 from a
saturated ethyl acetate solution at room temperature (Fig. 3).35
The structural determination from radiocrystallographic analy-
sis was in full agreement with the stereochemistry determined in
solution. Finally, treatment of 13 by BH3·Me2S in THF reduced
the amide function and removed the acetyl protecting groups to
afford the indolizine 14 in 88% yield. The latter was converted
Scheme 5
O r g . B i o m o l . C h e m . , 2 0 0 4 , 2 , 3 1 2 8 – 3 1 3 3
3 1 2 9

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in hexanes or ether (1.39 mmol) was slowly added and HMPA
(208 mg, 1.16 mmol) was added 30 min later.
- Schlenk B: To a stirred, cooled (−78 °C) solution of b-
tributylstannylacrolein (200 mg, 0.58 mmol) in THF (15 mL)
was added triorganosilyl chloride (1.74 mmol). The solution
A was cannulated on B, the mixture was stirred from −78 °C
to −50 °C for 2 hours and quenched by a NaHCO3 saturated
aqueous solution. The mixture was extracted with diethyl ether
and the combined organic layers were washed with saturated
aqueous NaCl, dried over MgSO4, filtered and concentrated
under reduced pressure. The colourless oily product was
purified by flash chromatography on silica gel (hexanes–Et3N
98:2).
1-(tert-Butyldimethylsiloxy)-3-(tributylstannyl)-but-1-ene (E/Z
92/8, 193 mg, 70% yield) (3)11
IR mmax/cm−1 (neat): 2955, 2872, 1588, 1465, 1378, 1251, 980, 831,
1
768, 672. H NMR (CDCl3): Z isomer: 0.10 (6H, s), 0.80–0.91
(15H, m), 0.95 (9H, s), 1.20–1.60 (12H, m), 1.28 (3H, d, 3J = 7.5),
2.53 (1H, m, 4J = 1.0 3J = 7.5 and 3J = 10.9, 2JSn = 58), 4.47 (1H,
dd, 3J = 5.7 and 3J = 10.9, 3JSn = 18), 5.97 (1H, dd, 3J = 5.7 and
4J = 1.1, 4JSn = 22). E isomer: 0.10 (6H, s), 0.80–0.91 (15H, m),
Fig. 3 An ORTEP36 view of compound 13 with thermal ellipsoids
drawn at the 50% probability level (for clarity, only one of the two inde-
pendent molecules is shown).
3
0.92 (9H, s), 1.20–1.60 (12H, m), 1.26 (3H, d, J = 7.5), 1.97
(1H, m, 3J = 9.0 3J = 7.5 and 4J = 1.3, 2JSn = 61), 5.24 (1H, dd,
into (±)-1-deoxy-6,8a-di-epi-castanospermine 15 upon treat-
ment with tetrabutyl ammonium fluoride (95% yield).
3
3
3
3J = 9.0 and J = 11.8, JSn = 22), 6.10 (1H, dd, J = 11.8 and
4J = 1.3, JSn = 18). 13C NMR (CDCl3): Z isomer: −5.3, −5.0,
4
8.8 (3C, JSn = 293/284), 13.9 (3C), 16.4 (1JSn = 311), 18.5, 18.9
1
Conclusion
(2JSn = 18), 25.9 (3C), 27.7 (3C, JSn = 55), 29.5 (3C, JSn = 18),
117.3 (2JSn = 38), 133.4 (3JSn = 46). E isomer: −5.2 (2C), 8.5 (3C,
1JSn = 285/299), 13.7 (3C), 18.2, 18.4, 18.6 (1JSn = 304/318), 25.8
(3C), 27.6 (3C, 3JSn = 51), 29.3 (3C, 2JSn = 19), 118.2 (2JSn = 30),
135.6 (3JSn = 50). 119Sn NMR (CDCl3): Z isomer: −15.8.
E isomer: −17.9. MS (EI): organostannyl fragments: m/z
(%) = 476 (M+) (1), 419 (32), 291 (26), 235 (30), 179 (29);
organic fragments: m/z (%) = 185 (62), 73 (100).
3
2
The present work outlines an efficient route for the preparation
of c-siloxyallyltributylstannanes and underlines the useful-
ness of these tools to achieve syntheses in polyhydroxylated
indolizine alkaloids series. This point was illustrated by the
synthesis of (±)-1-deoxy-6,8a-di-epi-castanospermine which
was obtained through a syn allylstannation of a cyclic iminium
salt followed by a ring closing metathesis. A 34% overall yield
through the 8 steps was obtained from commercial succinimide
(63% on the last 6 steps). The stereochemistry of the obtained
product was unambiguously determined both by NMR analyses
and X-ray diffraction.
1-(tert-Butyldimethylsiloxy)-3-(tributylstannyl)-4-methyl-pent-
1-ene (E/Z 20/80, 102 mg, 35% yield) (4)
IR mmax/cm−1 (neat): 3020, 2957, 2929, 2857, 1640, 1464, 1258,
1
Experimental
General remarks
1093, 859, 837, 780, 673 cm−1. H NMR (CDCl3): Z isomer:
0.10 (6H, s), 0.70–1.00 (21H, m), 0.90 (9H, s), 1.20–1.60 (12H,
3
3
m), 1.88 (1H, m, J = 6.4), 2.49 (1H, dd, J = 7.8 and 11.7,
1H, 13Cand119SnspectrawererecordedonBrukerAC200, Bruker
Avance 300 or Bruker ARX 400 spectrometers. Chemical shifts
are given in ppm as d values relative to tetramethylsilane (1H, 13C)
or tetramethylstannane (119Sn) and coupling constants are given
in Hz. NMR data are given for spectra recorded at 300 K. Mass
spectra were obtained in CI or in EI mode (70 eV) with an HP
apparatus (Engine 5989A) in direct introduction mode and when
high resolution was desired HRMS data were obtained from the
CRUS in Rouen (Centre Régional Universitaire de Spectro-
scopie de l’Université de Rouen). IR spectra were recorded on
a Bruker IFS Vector 22 apparatus. Diethyl ether and THF were
distilled over sodium/benzophenone and CH2Cl2 was distilled
over CaH2 prior to use. Liquid chromatography separations
were achieved on silica gel Merck Geduran Si 60 (40–63 mesh),
TLC analyses on silica-coated plates (Merck Kieselgel 60F254).
The tributyltin hydride allowing the synthesis of the c-siloxy-
allylstannane was a Crompton product while n-butyllithium
was a Chemetall product.
2JSn = 61), 4.48 (1H, dd, 3J = 5.8 and 11.7, 3JSn = 19), 6.05 (1H,
3
4
d, J = 5.8, JSn = 20). E isomer: 0.10 (6H, s), 0.80–1.00 (30H,
m), 1.20–1.70 (14H, m), 5.21 (1H, dd, 3J = 11.4 and 12.3), 6.10
(1H, d, J = 11.4). 13C NMR (CDCl3): Z isomer: −5.3, −5.0,
3
1
8.9, 9.9 (3C, JSn = 282/296), 10.1, 13.9 (3C), 18.4, 25.9 (3C),
27.7 (3C, JSn = 55), 29.5 (3C, JSn = 19), 31.5 (2JSn = 14), 33.1
(1JSn = 300), 113.0 (2JSn = 39), 134.7 (3JSn = 50). E isomer: −5.04
(2C), 10.3 (3C, 1JSn = 300), 13.8 (3C), 18.5, 25.7 (2C), 25.8, 26.0
3
2
3
2
(3C), 27.7 (3C, JSn = 55), 29.4 (3C, JSn = 20), 114.9, 135.5.
119Sn NMR (CDCl3): Z isomer: −23.9. E isomer: −24.1. MS
(EI): organostannyl fragments: m/z (%) = 504 (M+) (1), 447
(4), 365 (1), 291 (17), 235 (34), 179 (37); organic fragments: m/z
(%) = 213 (70), 81 (16), 73 (100).
1-(tert-Butyldimethylsiloxy)-3-(tributylstannyl)-hept-1-ene (E/Z
75/25, 270 mg, 90% yield) (5)
IR mmax/cm−1 (neat): 3025, 2957, 2929, 2872, 2856, 1465, 1253,
1
1073, 837, 779, 664 cm−1. H NMR (CDCl3): Z isomer: 0.10
(6H, s), 0.70–1.00 (27H, m), 1.20–1.60 (18H, m), 2.55 (1H, dt,
3J = 5.8 and 3J = 11.1, 4JSn = 61), 4.42 (1H, dd, 3J = 5.7 and 11.1,
3JSn = 19), 6.01 (1H, d, 3J = 5.7, 4JSn = 21). E isomer: 0.10 (6H,
s), 0.70–1.00 (18H, m), 0.9 (9H, s), 1.20–1.60 (18H, m), 1.92 (1H,
dt, 3J = 5.8 and 3J = 10.0, 2JSn = 58), 5.07 (1H, dd, 3J = 10.0 and
General procedure for the synthesis of c-siloxyallyltributyl-
stannanes 3–7
The reagents were prepared in two different Schlenk tubes
A and B.
- Schlenk A: CuCN (62.7 mg, 0.7 mmol) was dried under
vacuum (0.1 mmHg, flame heater 250 °C, 15 min) before
addition of THF (10 mL). The mixture was cooled to −78 °C
and degassed. The alkyllithium or alkylmagnesium solution
3
3
4
11.5, JSn = 23), 6.10 (1H, d, J = 11.5, JSn = 20). 13C NMR
(CDCl3): Z isomer: −5.3, −5.0, 9.1 (3C), 13.9 (3C), 14.3, 18.4,
22.5, 23.0, 27.9 (3C), 29.5 (3C), 32.9, 33.2, 115.3, 134.2. E
isomer: −5.1 (2C), 8.8 (3C, 1JSn = 284/298), 13.8 (3C), 14.2, 18.5,
3 1 3 0
O r g . B i o m o l . C h e m . , 2 0 0 4 , 2 , 3 1 2 8 – 3 1 3 3

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22.5, 25.2 (1JSn = 280), 25.7 (3C), 27.6 (3C, 3JSn = 53), 29.4 (3C,
2JSn = 20), 32.3, 33.0, 116.5 (2JSn = 39), 136.4 (3JSn = 54). 119Sn
NMR (CDCl3): Z isomer: −19.7. E isomer: −20.2. MS (EI):
organostannyl fragments: m/z (%) = 518 (M+, 1), 461 (1), 365
(30), 291 (59), 235 (78), 179 (87), 121 (29); organic fragments:
m/z (%) = 75 (100).
(2 drops) in EtOH (30 mL) were slowly added HCl (2 drops
of a 2 M ethanol solution) every 10 min during a period of
2 h. The blue mixture was brought to pH 3–5 by addition
of 6 M aqueous HCl and was diluted with water (10 mL).
The mixture was extracted with CH2Cl2 and the combined
organic layers were washed with saturated aqueous NaHCO3,
dried over MgSO4, filtered and concentrated under reduced
pressure. Purification by flash chromatography on silica gel
(EtOAc–hexanes 4:6) afforded 11 (0.79 g, 65%) as a clear oil.
Rf = 0.20 (EtOAc–hexanes 4:6). IR mmax/cm−1 (neat): 2977, 2930,
1-(tert-Butyldimethylsiloxy)-3-(tributylstannyl)-4,4-dimethyl-
pent-1-ene (E/Z = 85/15, 255 mg, 85% yield) (6)
IR mmax/cm−1 (neat): 3023, 2956, 2928, 2858, 1464, 1149, 854,
780, 676 cm−1. 1H NMR (CDCl3): Z isomer: 0.10 (6H, s),
0.70–1.00 (24H, m), 1.15 (9H, s), 1.20–1.45 (12H, m), 2.71 (1H,
3
1700 cm−1. 1H NMR (CDCl3): 1.21 (3H, t, J = 6.9), 1.98–2.56
3
3
(4H, m), 3.48 (2H, q, J = 6.9), 3.60 (1H, dd, J = 6.9 and
2J = −15.3), 4.24 (1H, dm, 2J = −15.3), 4.93 (1H, brd, 3J = 6.0),
3
2
3
3
d, J = 12.3, JSn = 64), 4.58 (1H, dd, J = 6.0 and J = 12.3,
3
3
5.17 (1H, brd, J = 12.0), 5.24 (1H, brd, J = 18.6), 5.70–5.80
3JSn = 28), 6.11 (1H, d, 3J = 6.0, JSn = 20). E isomer: 0.13
4
(1H, m). 13C NMR (CDCl3): 15.2, 24.9, 28.9, 42.7, 61.7, 88.4,
(6H, s), 0.70–1.00 (33H, m), 1.25–1.53 (12H, m), 1.90 (1H,
+
117.7, 132.6, 174.7. MS (CI/NH3): m/z (%) = 187 (M + NH4 ,
3
2
3
3
d, J = 12.6, JSn = 61), 5.13 (1H, dd, J = 11.4 and J = 12.6,
3JSn = 25), 6.11 (1H, d, 3J = 11.4, 4JSn = 19). 13C NMR (CDCl3):
Z isomer: −5.2, −4.9, 10.9 (3C, 1JSn = 283/294), 13.9 (3C), 18.4,
25.9 (3C), 27.9 (3C), 29.7 (3C), 30.9 (3C), 34.1, 39.6 (1JSn = 302),
112.0 (2JSn = 38), 135.1 (3JSn = 49). E isomer: −5.0, −4.9, 10.7
18), 170 (M + H+, 100), 124 [(M + H+) − EtOH, 28]. HRMS:
calcd for C9H15NO2 169.1103, found 169.1107.
(rel-8R,8aR)-8-(tert-Butyldimethylsiloxy)-1,5,8,8a-tetrahydro-
2H-indolizin-3-one (12)
1
(3C, JSn = 283/294), 13.9 (3C), 18.5, 26.0 (3C), 27.8 (3C,
3JSn = 55), 29.5 (3C, JSn = 19), 30.9 (3C, JSn = 25), 34.2, 42.7
(1JSn = 313/326), 113.1 (2JSn = 35), 137.7 (3JSn = 59). 119Sn
NMR (CDCl3): Z isomer: −28.3. E isomer: −27.3. MS (EI):
organostannyl fragments: m/z (%) = 518 (M+, 1), 461 (4),
365 (1), 291 (30), 235 (33), 179 (28); organic fragments: m/z
(%) = 227 (92), 95 (31), 73 (100).
2
3
To a stirred, cooled (−78 °C) solution of 11 (500 mg, 2.95 mmol)
in dry CH2Cl2 (20 mL) were successively added BF3·OEt2 (1.26 g,
8.86 mmol) and 3E (1.40 g, 2.95 mmol). The reaction mixture
was stirred for 1 h at −78 °C, quenched with saturated aqueous
NaHCO3 and allowed to warm to ambient temperature. The
phases were separated and the aqueous phase was extracted
with dichloromethane. The combined organic layers were
dried over MgSO4, filtered and concentrated under reduced
pressure. The crude product was dissolved in dry degassed
dichloromethane and Grubbs’ catalyst (122 mg, 5 mol%) was
added. The mixture was refluxed for 24 h and then treated with
DMSO (500 lL). After 12 h at room temperature, the reaction
mixture was concentrated under reduced pressure. Purification
by flash chromatography on silica gel (EtOAc–hexanes 6:4) gave
12 (640 mg, 81%) as a clear oil. Rf = 0.18 (EtOAc–hexanes 6:4).
1-(tert-Butyldiphenylsiloxy)-3-(tributylstannyl)-4,4-dimethyl-
pent-1-ene (E/Z = 90/10, 331 mg, 89% yield) (7)
IR mmax/cm−1 (neat): 3072, 2956, 2884, 2857, 1641, 1663, 1141,
1
1115, 823, 700 cm−1. H NMR (CDCl3): Z isomer: 0.70–1.00
(15H, m), 0.99 (9H, s), 1.07 (9H, s), 1.31 (6H, m), 1.50 (6H, m),
3
3
3
2.90 (1H, d, J = 12.3, , JSn = 63), 4.58 (1H, dd, J = 5.7 and
3
3
4
12.3, , JSn = 22), 6.08 (1H, d, J = 5.7, , JSn = 18), 7.36–7.42
(6H, m), 7.70 (4H, d, J = 4.0). E isomer: 0.70–0.90 (15H, m),
3
1
IR mmax/cm−1 (neat): 2928, 1639, 1356, 1079 cm−1. H NMR
0.80 (9H, s), 1.06 (9H, s), 1.20–1.50 (12H, m), 1.79 (1H, d,
3J = 12.0), 5.20 (1H, dd, 3J = 11.5 and 3J = 12.8, 3JSn = 25), 6.13
(1H, d, 3J = 11.5, 4JSn = 19), 7.37–7.41 (6H, m), 7.68–7.72 (4H,
m). 13C NMR (CDCl3): Z isomer: 11.1 (3C, 1JSn = 282/294), 14.0
(CDCl3): 0.04 (3H, s, SiCH3), 0.08 (3H, s, SiCH3), 0.87 (9H,
5
s, (CH3)3), 2.00–2.17 (2H, m, H1+1), 2.33 (1H, m, J = 1.3,
2
3
5
3J = 4.4, J = −10.4 and J = 16.3, H2), 2.49 (1H, m, J = 1.5,
3
3
2
4J = 1.5, J = 7.8, J = 18.1 and J = −10.4, H2), 3.50 (1H, m,
3
2
(3C), 19.6, 27.0 (3C), 28.1 (3C, JSn = 57), 29.8 (3C, JSn = 19),
2J = −19.2, J = 5.1 and J = 1.5, H5), 3.67 (1H, m, J = 1.5,
3
5
4
31.2 (3C, JSn = 27), 34.5, 40.1 (1JSn = 310), 112.3 (2JSn = 37),
3
3J = 2.1, 3J = 4.7 and 3J = 8.7, H8a), 4.04 (1H, m, 4J = 1.6,
128.1 (4C), 130.1, 133.2, 133.3, 135.8 (6C), 136.6 (3JSn = 35).
3J = 2.5 and J = 4.7, H8), 4.40 (1H, ddd,4J = 3.3, J = 1.6 and
2J = −19.2, H5), 5.85 (1H, ddd, 4J = 3.3, 3J = 2.5 and 3J = 10.1,
H7), 5.91 (1H, m, 4J = 1.6, 3J = 1.6, 3J = 5.1 and 3J = 10.1, H6).
13C NMR (CDCl3): −4.6 (SiCH3), −3.7 (CH3Si), 18.2 (C(CH3)3),
19.8 (C1), 25.9 (3C, C(CH3)3), 30.5 (C2), 40.3 (C5), 58.5 (C8a),
65.9 (C8), 127.2 and 127.5 (C6+7), 174.9 (C3). MS (CI/NH3): m/z
(%) = 285 (M + NH4+, 15), 268 (M + H+, 100). HRMS: calcd for
C14H26NO2Si (M + H+) 268.1733, found 268.1726.
3
3
1
E isomer: 10.8 (3C, JSn = 284/296), 13.8(3C), 19.3, 26.6 (3C),
3
2
3
27.7 (3C, JSn = 56), 29.4 (3C, JSn = 18), 30.8 (3C, JSn = 24),
34.0, 42.5 (1JSn = 318), 113.2 (2JSn = 35), 127.7 (4C), 129.8 (2C),
133.3, 133.4, 135.5 (4C), 137.4 (3JSn = 59). 119Sn NMR (CDCl3):
Z isomer: −28.6. E isomer: −27.4. MS (EI): organostannyl
fragments: m/z (%) = 642 (M+, 3), 585 (100), 528 (6), 489 (16),
471 (13), 375 (15), 329 (11); organic fragments: m/z (%) = 351
(18), 230 (5), 173 (28), 75 (45).
(rel-6S,7S,8S,8aR)-8-(tert-Butyldimethylsiloxy)-6,7-diacetoxy-
hexahydro-indolizin-3-one (13)
N-Allyl-succinimide (10)30,31
DEAD (2.28 g, 13.1 mmol) was added to a stirred solution of
succinimide (1.00 g, 10.1 mmol), PPh3 (3.44 g, 13.1 mmol) and
allyl alcohol (0.70 g, 12.1 mmol) in THF (40 mL). After 24 h
at room temperature, the reaction mixture was concentrated
under reduced pressure and Et2O (10 mL) was added. After
precipitation of Ph3PO, the mixture was filtered and the sol-
vent was removed under reduced pressure. Purification by flash
chromatography on silica gel (EtOAc–hexanes 4:6) afforded
10 (1.15 g, 82%) as a clear oil. 1H NMR (CDCl3): 2.65 (4H, s),
4.01 (2H, brd, 3J = 6.0), 5.08 (1H, brd, 3J = 9.0), 5.11 (1H, brd,
To a stirred solution of 12 (200 mg, 0.75 mmol) in acetone
(9 mL) and water (3 mL) was added NMO (431 mg, 3.74 mmol)
and 2.5% OsO4 in t-BuOH (76 mg, 1 mol%). After 24 h at room
temperature, the reaction mixture was concentrated under
reduced pressure. The crude product was dissolved in pyridine
(4 mL) and acetic anhydride (2 mL) was added. After 1 h at
room temperature, the reaction mixture was concentrated under
reduced pressure. Purification by flash chromatography on
silica gel (EtOAc) afforded 13 (268 mg, 93%) as a white solid
(mp 129 °C). Rf = 0.41 (EtOAc). IR mmax/cm−1 (KBr) 2927, 2854,
1744, 1686, 1242 cm−1. 1H NMR (CDCl3): 0.10 (3H, s, SiCH3),
0.20 (3H, s, SiCH3), 0.91 (9H, s, (CH3)3), 1.89 (1H, m, H1), 2.00
(3H, s, CH3CO), 2.06 (1H, m, H1), 2.13 (3H, s, CH3CO), 2.39
3
3
3
3J = 17.4), 5.69 (1H, tdd, J = 6.0 J = 9.0 and J = 17.4). 13C
NMR (CDCl3): 28.1 (2C), 40.8, 118.1, 130.7, 176.8 (2C).
1-Allyl-5-ethoxy-pyrrolidin-2-one (11)30,31
2
3
(2H, m, H2), 2.99 (1H, dd, J = 12.0 and J = 12.0, H5), 3.77
3
3
3
To a stirred, cooled (−10 °C) solution of 10 (1.00 g, 7.19 mmol),
NaBH4 (1.09 g, 28.7 mmol) and bromocresol green indicator
(1H, dd, J = 1.8 and J = 3.6, H8), 3.85 (1H, ddd, J = 1.8,
3J = 3.6 and 3J = 8.7, H8a), 4.16 (1H, dd, 2J = 12.0 and 3J = 6.0,
O r g . B i o m o l . C h e m . , 2 0 0 4 , 2 , 3 1 2 8 – 3 1 3 3
3 1 3 1

View Article Online
3
3
3
were observed in the last difference Fourier synthesis. Final re-
finement details are given in the crystallographic data.
CCDC reference numbers 241959. See http://www.rsc.org/
suppdata/ob/b4/b409507c/ for crystallographic data in .cif or
other electronic format.
H5), 5.12 (1H, ddd, J = 3.0, J = 6.0 and J = 12.0, H6), 5.25
(1H, dd, J = 3.0 and J = 3.6, H7). 13C NMR (CDCl3): −5.1
(SiCH3), −4.7 (CH3Si), 17.8 (C(CH3)3), 18.4 (C1), 20.7 (CH3CO),
20.9 (CH3CO), 25.6 (3C, C(CH3)3), 30.6 (C2), 37.8 (C5), 55.7 (C8a),
64.5 (C6), 69.8 (C8), 70.1 (C7), 169.5 (CH3CO), 169.7 (CH3CO),
3
3
+
174.4 (C3). MS (CI/NH3): m/z (%) = 403 (M + NH4 , 61),
386 (M + H+, 100). HRMS: calcd for C18H32NO6Si (M + H+)
386.1999, found 386.1998.
Acknowledgements
The authors are grateful to the MESR and to the “Con-
seil Général de Loire Atlantique” for grants (F.C. and F.F.)
and to the CNRS for financial support. They also wish to
acknowledge Crompton GmbH and Chemetall GmbH for gifts
of organometallic starting materials.
(±)-8-(tert-Butyldimethylsiloxy)-1-deoxy-6,8a-di-epi-
castanospermine (14)
To a stirred solution of 13 (100 mg, 0.26 mmol) in THF (15 mL)
was added BH3·Me2S (1.30 mL of a 2 M toluene solution,
2.60 mmol). The mixture was refluxed for 30 min and water
was slowly added. The mixture was extracted with Et2O and
CH2Cl2. The combined organic layers were dried over MgSO4,
filtered and concentrated under reduced pressure. Purifica-
tion by flash chromatography on silica gel (EtOAc–hexanes
35:65) afforded 14 (66 mg, 88%) as a clear oil. Rf = 0.20
(EtOAc–hexanes 35:65). IR mmax/cm−1 (neat): 3384, 2956, 2923,
2857, 1259, 1063 cm−1. 1H NMR (CDCl3): 0.11 (3H, s, SiCH3),
0.12 (3H, s, SiCH3), 0.88 (9H, s, (CH3)3), 1.84 (2H, m, H1+2),
2.05 (1H, m, H2), 2.30 (1H, m, H1), 3.02 (2H, m, H3+5), 3.21
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3
(2H, m, H3+5), 3.45 (1H, m, H8a), 3.73 (1H, dd, J = 3.3 and
3J = 6.6, H7), 4.00 (1H, dd, 3J = 4.6 and 3J = 6.6, H8), 4.09 (1H,
m, H6). 13C NMR (CDCl3): −4.8 (SiCH3), −4.7 (CH3Si), 18.0
(C(CH3)3), 20.9 (C2), 24.5 (C1), 25.8 (3C, C(CH3)3), 55.0 (C5),
62.3 (C3), 64.7 (C6), 66.4 (C8a), 69.9 (C7), 71.4 (C8). MS (CI/NH3):
m/z (%) = 288 (M + H+, 100). HRMS: calcd for C14H30NO3Si
(M + H+) 288.1995, found 288.1995.
(±)-1-Deoxy-6,8a-di-epi-castanospermine (15)
To a stirred solution of 14 (50 mg, 0.17 mmol) in THF (2 mL)
was added TBAF (170 lL of a 1 M THF solution, 0.17 mmol).
After 1 h at room temperature, the reaction mixture was
concentrated under reduced pressure. Purification by flash chro-
matography on silica gel (EtOAc–MeOH 8:2) gave 15 (29 mg,
95%) as a clear oil. Rf = 0.42 (EtOAc–MeOH 8:2). IR mmax/cm−1
(neat): 3336, 2955, 2927, 2856, 1077 cm−1. 1H NMR (CD3OD):
1.89–2.08 (3H, m, H1+2+2), 2.41 (1H, m, H1), 2.93 (2H, m, H3+5),
3
3
3.27 (2H, m, H3+5), 3.42 (1H, dd, J = 3.4 and J = 8.0, H8a),
3
3
3
3.70 (1H, dd, J = 3.4 and J = 3.4, H8), 3.83 (1H, dd, J = 3.4
and 3J = 4.5, H7), 4.12 (1H, ddd, 3J = 2.7, 3J = 4.5 and 3J = 11.4,
H6). 13C NMR (CD3OD): 23.4 (C2), 26.1 (C1), 55.4 (C5), 59.7
(C3), 62.2 (C6), 64.9 (C8a), 71.8 (C7), 73.6 (C8). MS (CI/NH3): m/z
(%) = 174 (M + H+, 100). HRMS: calcd for C8H15NO3 173.1052,
found 173.1042.
Single crystal X-ray structure determination
Suitable single crystals of 13 were obtained by slow evaporation
of an ethyl acetate solution at room temperature. A first data
collection, carried out at room temperature on a Bruker-Nonius
KappaCCD diffractometer with graphite-monochromated
MoK-L2,3 radiation, led to a structure with very large atomic
displacement parameters, especially for carbon and oxygen
atoms of acetyl groups, suggesting static disorder. To improve
the resolution, a second data collection was realized at 100 K,
achieved by means of an Oxford cryostream cooler. A weak,
two-fold superstructure along the c axis was detected, indicating
possible resolution of the envisioned room temperature disor-
der. A model of the low temperature structure was found with
the Sir200037 direct methods. All subsequent calculations were
carried out with the Jana2000 program suite.38 All non-H atoms
were refined with anisotropic atomic displacement parameters.
H atoms were fully retrained in geometry (angles and distances),
except for those of four CH3 groups (C10a, C10b, C12a and
C12b) for which rotations around the C–C bonds were allowed.
Riding isotropic displacement parameter (×1.2) was used for all
H atoms. Meaningless residues in the [−0.40;0.64] e Å−3 range
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3 1 3 2
O r g . B i o m o l . C h e m . , 2 0 0 4 , 2 , 3 1 2 8 – 3 1 3 3

View Article Online
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35 Crystal data for 13, C18H31NO6Si, M = 385.5 g mol−1, monoclinic,
P21/n (n°14), a = 9.4422(8) Å, b = 33.148(6) Å, c = 13.6144(18) Å,
b = 105.373(8)°, V = 4108.8(10) Å3, Z = 8, D(calc.) = 1.2461(3),
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k(MoK-L2,3) = 0.71073 Å, l = 0.146 mm−1
,
F(000) = 1664,
T = 100 K, Rint(obs) = 0.054, R(obs) = 0.0534, Rw(obs) = 0.0979
for 11877 used reflections in the refinement and 6079 observed
reflections (I > 2r(I)), no. of refined parameters = 469.
38 V. Petricek and M. Dusek, JANA2000, a crystallographic
computing system, Institute of Physics, Academy of Sciences of the
Czech Republic, Prague, 2000.
O r g . B i o m o l . C h e m . , 2 0 0 4 , 2 , 3 1 2 8 – 3 1 3 3
3 1 3 3