Stereoselective allylic transposition by means of allylic n-pentenyl ethers. Part 2: Synthesis of nitrogen heterocycles

Article abstract of DOI:10.1016/S0040-4020(01)00602-0

Stereospecific synthesis of optically active substituted pyrrolidines, and piperidines was studied via an intramolecular allylic rearrangement by means of allylic n-pentenyl ethers as leaving groups when reacting with halonium ions.

Full text of DOI:10.1016/S0040-4020(01)00602-0

TETRAHEDRON
Pergamon
Tetrahedron 57 (2001) 6229±6238
Stereoselective allylic transposition by means of allylic n-pentenyl
ethers. Part 2: Synthesis of nitrogen heterocyclesq
a
a
a
 Â
Âb
Franck Chouteau, Khadija Addi, Michel Benechie, Thierry Prange
and FrancËoise Khuong-Huua,p
aCentre National de la Recherche, Institut de Chimie des Substances Naturelles, Avenue de la Terrasse, 91198 Gif-sur-Yvette, France
b
 Â
Chimie Structurale Biomoleculaire (UPRS A 7031 CNRS), UFR Biomedicale, 93017 Bobigny Cedex, France
Received 25 January 2001; revised 21 May 2001; accepted 29 May 2001
AbstractÐStereospeci®c synthesis of optically active substituted pyrrolidines, and piperidines was studied via an intramolecular allylic
rearrangement by means of allylic n-pentenyl ethers as leaving groups when reacting with halonium ions. q 2001 Elsevier Science Ltd. All
rights reserved.
1. Introduction
The products so far obtained were unique,1,4,5 with satisfac-
tory yields. Therefore the syntheses of ®ve- and six-
membered nitrogen heterocycles were performed using
this strategy (Scheme 2). In the present paper, our main
results were presented.4,6
In a previous paper,1 we reported the stereospeci®c synth-
esis of 1,3-diols and of substituted oxygen heterocycles,
using a stereoselective intramolecular allylic substitution
where n-pentenyl ethers served as switch for the generation
of an allylic cation on subjection to haloniums ions2
(Scheme 1, Eq. (1)). The starting material was acyclic,
and the success of these reactions required the presence of
a n-pentenyloxy moiety a to a double bond, the presence of
a chiral substituent a0 to the same double bond and the
participation of an internal nucleophile [carbonate (Scheme
1, Eq. (2)), benzyl ether (Scheme 1, Eq. (3)). The installa-
tion of a removable ligand on the double bond, generating
an 1,3 allylic strain3 between this ligand and the chiral
substituent, favoured the nucleophilic attack on the opposite
side to the substituent (Scheme 1, Eqs. (2) and (3)). The
geometry of the new created halogenated double bond
was Z, providing an E double bond after replacement of
the vinylic ligand by hydrogen.1,4,5 As shown in Scheme
1, the substrates undergoing the nucleophilic attack, were
a mixture of epimers, differing for the con®guration at the
carbon bearing the leaving group. The fact that both epimers
led to a Z con®guration of the newly formed double bond,
suggested that leaving group departure preceded nucleo-
phile attack (SN10 like mechanism).
2. Results and discussion
Starting from 1-tosyloxy-2(R)-hydroxy-3(S)-methyl-6(RS)-
pentenyloxy-hept-4-yne (1), previously described,1,7 the
pyrrolidine 2 and the piperidine 3 were ®rst prepared.
On the one hand, the epoxyde 4 was transformed to the azide
5 by re¯uxing in EtOH in the presence of NaN3. Reduction
of 5 by LiAlH4 in ether yielded the amine 6 which was regio
and stereoselectively stannylated (7) using radical condi-
tions,8 before its transformation into the p-toluenesulfona-
mide 8. This N-substitution was chosen on the basis of the
results obtained by Tamaru et al.9 which showed that sulfon-
amides were convenient nucleophiles for intramolecular
haloamidation. Di-sym-collidine iodonium perchlorate was
used as iodonium ions source because it was reported to
ensure better results and shorter reaction time.10 Thus,
when 8 was reacted with di-sym-collidine iodonium
perchlorate in CHCl3 at 08C for 3 h, the pyrrolidine 94 was
obtained in 88% yield. 2D NOESY experiment showed nOe
interactions between H-3 and CH3-9 and between H-5 and
the same CH3, thus con®rming the expected trans relation-
ship between the side chain and the methyl group. This
compound was a mixture of conformers due to interaction
between the iodine atom and the sulfonamido group as
q See Ref. 1.
Keywords: n-pentenyl ethers; stereoselection; intramolecular allylic substi-
tution; pyrrolidines; piperidines; 1,3-allylic effect.
Corresponding author. Tel.: 133-1-69-82-3025; fax: 133-1-69-07-7247;
e-mail: francoise.khuong@icsn.cnrs-gif.fr
1
shown by duplication of some signals in the H- and 13C
p
NMR spectra. Synthesis of the (3R,4S,5R)-pyrrolidine 2 was
achieved by halogen±metal exchange using t-butyllithium
0040±4020/01/$ - see front matter q 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020(01)00602-0

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F. Chouteau et al. / Tetrahedron 57 (2001) 6229±6238
Scheme 1.
followed by acidic work-up.1,11 Coupling constants of
the ole®nic protons in the H NMR spectrum indicated
as shown by coupling constants (JH2±H3ˆ2.5 Hz, JH3±
1
ˆ4 Hz) when the conformation of 14a is also a ¯at
H4
an E geometry for the double bond (JH6,H7ˆ16 Hz)
chair but with pseudo-equatorial substituents (JH2±
ˆ7.5 Hz, JH3±H4ˆ7.5 Hz). Molecular modelisation
(Scheme 3).
H3
con®rmed that these conformations corresponded to the
lowest energy ones.
On the other hand, the epoxyde 4 was stannylated under
radical conditions8 to give 10 together with some amounts
(6%) of its regioisomer 11. Opening of epoxyde 10 by KCN
in EtOH furnished the nitrile 12 which was further reduced
to the amine 13a with LiAlH4. After transformation into the
p-toluenesulfonamide 13b, the allylic substitution reaction
was investigated. When treated with 3 equiv. of di-sym-
collidine iodonium perchlorate in CHCl3, 13b afforded the
expected piperidine 14a in low yield (12% yield). Suspect-
ing the possible intervention of the free hydroxyl, the
secondary alcohol was protected as trimethylsilyl ether
(13d) after tin/halogen exchange that was performed
with 1 equiv. of N-iodosuccinimide (13c). Reaction of
13d with di-sym-collidine iodonium perchlorate
provided the piperidine 14b in 54% yield. 2D NOESY
experiment showed interactions of H-2 with CH3-10 and
H-5b and of H-4 with H-5b, demonstrating the trans
relationship between the side chain and the methyl
group. Vinylic iodine removal by reaction with t-BuLi
and subsequent protonation4,6 gave the (2S,3S,4S)-piper-
idine 3 (Scheme 4). In 1H NMR spectrum of 3, the
coupling constants of the ole®nic protons con®rmed
the E geometry of the double bond (JH7,H8ˆ15.5 Hz).
The conformation of the piperidine ring of 3 is a ¯at
chair with pseudo-axial substituents at C-2, C-3 and C-4
The interest for polyhydroxylated piperidines as antiviral
and antitumor agents is well known,12 wherefore, we studied
the capacity of our technology to provide such compounds,
with a versatile side chain at C-2, starting from a substrate
where the alkyl group of the precedent strategy would
be replaced by an hydroxyl for generating the 1,3-allylic
strain.
Sugars are convenient chiral starting materials to synthesize
compounds with vicinal hydroxyls of various stereochem-
istry. Examination of the literature showed that lactols could
be ef®ciently opened by hydroxylamines to give precursors
of primary amines.13 Thus, 5-O-dimethyl-t-butylsilyl-2,3-
isopropylidene-d-ribonolactone14 was chosen as chiral start-
ing material and was reduced to 15 with DIBAH. This lactol
when treated with hydroxylamine gave 16 as syn/anti
isomers. After reduction of the oximes with LiBH4, the
amine 17a was transformed to the corresponding p-toluene-
sulfonamide 17b. After desylilation of the primary hydrox-
yl, periodate oxidation of the vic-diol 17c led to the
carbinolamine 18 as single isomer which was stereoselec-
tively opened by 1-lithio-3-pentenyloxy-butyne to give 19.
The stereochemistry of the hydroxyl group at C-4 of 19 was
Scheme 2.

F. Chouteau et al. / Tetrahedron 57 (2001) 6229±6238
6231
Scheme 3. (a) 1% NaOMe in MeOH, rt, 1 h, quantitative; (b) NaN3, 7 equiv., EtOH, re¯ux, 5 h, 97%; (c) LiAlH4, 1.2 equiv., ether, rt, 93%; (d) HsnBu3,
1 equiv. AIBN cat., 908C, 3 h, 78%; (e) ClTs 1 equiv., CH2Cl2:pyridine 2/1, rt, overnight, 83%; (f) [I(B2)ClO4, 3 equiv., CHCl3, 08C, 3 h, 88%; (g) t-BuLi
2 equiv., THF, 2788C, 1 h then 10% aqueous HCl 2788C to rt, 77%.
deduced from a crystallographic study of compound 21c
subsequently obtained. To introduce the removable ligand
on the triple bond, regioselective iodation of the triple bond
was studied and realized according to Denmark's modi®ca-
tion15 of Corey's procedure16 using Red Alw as reducing
agent. Vinylic iodide 20a was obtained in 82% yield.
After silylation of the free hydroxyl as TBDMS ether, the
vinylic iodide 20b when treated with di-sym-collidine±
iodonium perchlorate provided the piperidine 21a in 66%
yield. A small amount (13%) of epoxyde 22a was also
formed. Migration of the dimethyl-t-butylsilyl group from
oxygen to nitrogen, allowed nucleophilic attack to the
double bond by the oxygen atom. With 20a, the compound
having a free hydroxyl at C-4, the allylic substitution
reaction took place to give the piperidine 21b and the
epoxyde 22b in 36 and 24% yield, respectively. 2D
NOESY spectrum of 21b showed nOe interaction between
H-2 and C(3)±OH indicating a trans relationship between
the side chain and this hydroxyl, but the con®guration of
C-3 could not be attributed by this procedure because H-3
did not present any nOe interaction. Therefore, a crystal-
lographic study of ester 21c was performed and allowed to
set the 3R con®guration at C-3 and to con®rm the Z con®g-
uration of the halogenated double bond (Fig. 1).17 We tested
the reduction of the vinylic iodine under different
conditions, starting from piperidines 21a and 21b. When
lithium/iodine exchange was tested with 21a by treatment
by t-butylithium, the major product was the piperidine 23a
resulting from acetone elimination after deprotonation at
C-6, followed by lithium/iodine exchange. Steric hindrance
of the side chain due to the bulky silyl group allowed the
organometallic agent to attack the proton at C-6 before
iodine/lithium exchange. Furthermore, the allene 24
(78%), the piperidine 25 (18%) and the dehydropiperidine
Scheme 4. (a) Bu3SnH, 1 equiv., AIBN catalytic, 908C, 3 h, 69%; (b) KCN 3 equiv., EtOH, 458C, 7 h, 97%; (c) LiAlH4, 2 equiv., ether, rt, 2 h, 90%; (d) ClTs,
1 equiv., CH2Cl2/ py 2/1, rt, overnight, 95%; (e) NIS, 1 equiv., CH2Cl2, rt, 1 h, 73%; (f) ClSiMe3, 1.2 equiv., Et3N 3 equiv., THF, rt, overnight, 95%; (g) di-
sym-collidine iodonium perchlorate, 3 equiv., CHCl3, 08C, 1 h, 54%; (h) t-BuLi, 2 equiv., THF, 2788C, 1 h, 60%.

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F. Chouteau et al. / Tetrahedron 57 (2001) 6229±6238
Figure 1. Crystal structure of 21c.
23b (2%) were formed from the reaction of 21b having
a free hydroxyl at C-4 with t-butyllithium followed by
protonation. In this case, hydrogenolysis of 21b in the
presence of palladium on charcoal18 was found to be
the best method to obtain 25 (80% yield). Finally,
hydrolysis of isopropylidene group performed with 1N
HCl led to the triol 26 (8.6% from d-ribonolactone)
(Scheme 5).6
3. Conclusions
The introduction of a 1,3-allylic strain during an intramole-
cular allylic substitution using a pentenyl ether as leaving
group in the presence of haloniums has proved to be an
interesting versatile methodology to synthesize polyfunctio-
nalized nitrogen heterocycles. In the examples studied, the
overall yields obtained with ®ve- and six-membered rings
Scheme 5. (a) NH2OH, HOAc, 2 equiv., py, 2 equiv., MeOH, rt, 16 h, 98%; (b) LiBH4, 2 equiv., THF, re¯ux, 16 h, 84%; (c) ClTs, 1 equiv., Net3 1.2 equiv.,
CH2Cl2, 08C, 2 h, 57%; (d) Bu4NF.3H2O, 1.2 equiv., THF, rt, 1 h, 82%; (e) NaIO4, 2 equiv., pH 5.6 acetate buffer, EtOH, rt, 1 h, 98%; (f) 1-lithio-3-
pentenyloxy-propyne, 2.1 equiv., THF, 2788C to rt, 16 h, 95%; (g) Red Alw, 3 equiv., ether, 08C then rt, 16 h, then EtOAc, 15 min, then 2788C, I2
2 equiv. in THF, 2 78 to 258C, 2 h, 82%; (h) TBDMSCl, 2.5 equiv., imidazole, 5 equiv., THF, 95%; (i) I(B2)ClO4, 3 equiv., CHCl3, 08C, 1 h, 66%; (j)
Bu4NF, 1.2 equiv., THF, rt, 1 h, 85%; (k) H2, Pd/c, quinoline, MeOH, 80%; (l) 1N HCl, THF, rt, 1 h, 78%.

F. Chouteau et al. / Tetrahedron 57 (2001) 6229±6238
6233
were satisfying and the cyclisation step was always stereo-
selective.
extracted three times with ether. The ethereal solutions
washed with brine and dried on MgSO4 were evaporated
under reduced pressure to give a residue which was
chromatographed on silicagel column to give 1 eluted by
heptane/ether 8/2 (11.57 g, 70%), as an oil, HR CI MS:
calcd for C20H29O5S (MH1) 381.1736, found 381.1770; IR
(neat) nmax: 3487, 1650 cm21; 1H NMR (CDCl3, 250 MHz)
d 1.21 (3H, d, Jˆ7 Hz), 1.32 (3H, d, Jˆ6.5 Hz), 1.65 (2H,
qn, Jˆ7 Hz), 2.11 (2H, q, Jˆ7 Hz), 2.45 (3H, s), 2.49 (1H,
d, Jˆ5 Hz, OH), 2.58 (1H, qn, Jˆ7 Hz), 3.31 (1H, m,
Jˆ11.5, 7, 1.5 Hz), 3.61 (1H, m, Jˆ11.5, 7, 2 Hz), 3.71
(1H, m), 4.07 (2H, m), 4.30 (1H, dd, Jˆ10, 3 Hz), 4.96
(1H, dd, Jˆ10.5, 1.5 Hz), 5.02 (1H, dd, Jˆ17, 1.5 Hz),
5.81 (1H, ddt, Jˆ17, 10.5, 7 Hz), 7.36 (2H, d, Jˆ8 Hz),
7.81 (2H, d, Jˆ8 Hz); 13C NMR (CDCl3, 62.5 MHz) d
17.0, 21.6, 22.2, 28.8, 29.3, 30.3, 65.2, 67.9, 72.4, 72.5,
83.3, 84.7, 114.7, 128.0, 129.9, 132.6, 138.2, 145.1.
4. Experimental
4.1. General experimental procedures
Melting points (mps) were determined in capillary tubes and
are uncorrected. Optical rotations, [a]D, were measured at
room temperature, in CHCl3 with 0.5% EtOH, on a
PERKIN±ELMER 241 polarimeter. IR spectra were deter-
mined with a NICOLET FT-IR 205 spectrometer. 1H NMR
spectra were performed in CDCl3, unless otherwise stated,
chemical shifts d were expressed in ppm, coupling constants
in Hz, and registered with BRUKER WP-250, WP-300 or
WP-400 instruments. 13C NMR spectra were recorded on
Bruker WP-300 or WP-250. Mass spectra (MS) were run on
AEI MS-50 or AEI MS-9 spectrographs. Column chromato-
graphy were performed on Merck Kieselgel 60, ¯ash
column chromatography on Merck Kieselgel 60H. Analyti-
cal thin layer chromatography was carried out using silica
Gel pre-coated foils, visualization using spraying 50%
aqueous H2SO4 and heating.
4.2.2. (2R,3S)-2-[4RS-(Pent-4-enyloxy)-1-methyl-pent-3H-
ynyl]-oxirane (4). A solution of 1 (5.38 g, 14 mmol) in
MeOH (40 mL) was added to a 2% methanolic solution of
MeONa. After 1 h at room temperature, standard work-up
gave 4 (2.85 g, 98%) as an oil, used without further puri®-
cation, anal. calcd for C13H20O3 %: C 74.75, H 9.68, O
15.37, found: C 74.75, H 9.75, O 15.24; IR (neat) nmax
:
2237, 1637, 1272 cm21; H NMR (CDCl3, 250 MHz) d
1.29 (3H, d, Jˆ7 Hz), 1.38 (3H, d, Jˆ6.5 Hz), 1.67 (2H,
qn, Jˆ7 Hz), 2.12 (2H, q, Jˆ7 Hz), 2.51 (1H, dq, Jˆ7,
1 Hz), 2.67 (1H, dd, Jˆ5, 2.5 Hz), 2.77 (1H, t, Jˆ5 Hz),
2.90 (1H, m), 3.35 (1H, dt, Jˆ9, 7 Hz), 3.67 (1H, dt, Jˆ9,
7 Hz), 4.11 and 4.12 (1H, 2q, Jˆ6.5 Hz), 4.95 (1H, dd,
Jˆ10.5, 1.5 Hz), 5.02 (1H, dd, Jˆ17, 1.5 Hz), 5.81 (1H,
ddt, Jˆ17, 10.5, 7 Hz); 13C NMR (CDCl3, 62.5 MHz) d
18.0, 22.5, 29.0, 29.3, 30.4, 46.4, 54.9, 65.4, 68.0, 82.7,
84.1, 114.8, 138.4.
1
Crystallographic data were registered with a Philips
PW1100 diffractometer using the Mo Ka radiation
Ê
(lˆ0.707 A) with a graphite monochromator. The structure
was resolved by Patterson methods and the shelxl
program19 was used for the structure re®nements.
Standard work-up means quenching of the reaction by
NH4Cl aqueous solution, extraction by ether or CH2Cl2,
washing of the organic phase with brine, drying on
MgSO4 and evaporation under vacuum.
4.2.3. (2R,3S,6RS)-1-Azido-3-methyl-6-(pent-4-enyloxy)-
hept-4-yn-2-ol (5). NaN3 (1.24 g, 12.2 mmol) was added to
a solution of 4 (0.40 g, 1.92 mmol) in EtOH (30 mL) and the
resulting mixture was re¯uxed for 5 h. Standard work-up
(CH2Cl2) led to a residue which was puri®ed by silica gel
column chromatography with CH2Cl2/MeOH 99/1 as eluent
to give 5 (0.47 g, 97% yield) as an oil, CI MS: MH1 252;
anal. calcd for C13H21N3O2 %: C 62.10, H 8.42, N 16.73, O
12.73; found %: C 62.11, H 8.42, N 16.63, O 12.95; IR
4.2. General procedure for the cyclization reaction
[I(B)2]ClO4 (3 equiv.) was added, at 08C, to a solution of
sulfonamide (1 equiv.) in dry CHCl3 under inert atmo-
sphere. The reaction mixture was stirred at 08C. After
completion of the reaction as monitored by TLC, CH2Cl2
was added and the resulting solution was washed succes-
sively with 10% Na2S2O7 and NH4Cl solutions. The aqueous
phases were further extracted twice with CH2Cl2. The
combined organic phases were dried on MgSO4 and evapo-
rated under reduced pressure to give a crude reaction
mixture which was puri®ed by silica gel column chromato-
graphy.
(neat) nmax 3435, 2100, 1642, 1098 cm21
;
1H NMR
(CDCl3, 300 MHz), d: 1.2 (3H, d, Jˆ7 Hz), 1.3 (3H, d,
Jˆ6.5 Hz), 1.7 (2H, qun, Jˆ7.5 Hz), 2.1 (2H, q, Jˆ7 Hz),
2.6±2.7 (1H, m, Jˆ7, 2 Hz), 3.3 and 3.6 (2H, 2 m), 3.5 and
3.7 (ABX, Jˆ13, 7, 5 Hz), 3.6±3.7 (1H, m), 4,1 (1H, qd,
Jˆ6.5, 2 Hz), 5.0 (2H, 2d, Jˆ18, 11 Hz), 5.8 (1H, m);.13C
NMR, (CDCl3, 75 MHz) d: 17.0, 22.4, 28.8, 30.3, 30.6,
55.1, 65.4, 68.0, 73.8, 83.4, 85.1, 114.8, 138.2.
4.2.1. (2R,3S,6RS)-4-Methylbenzenesulfonic acid 6-[pent-
4-enyloxy]-3-methyl-2-hydroxy-(hept-4-yn)-yl ester (1).
n-BuLi (33.5 mL of 1.3 M solution in hexane, 43.5 mmol)
was added to a solution of 3-(penten-4-yloxy)-but-1-yne
(6 g, 43.5 mmol) in ether (120 mL) at 2788C under inert
atmosphere. After 15 min, Me3Al (26.1 mL of 2 M solution
in toluene, 46.1 mmol) was added. The mixture was stirred
at 2408C for 1 h and then cooled at 2788C. A solution of
(2S,3S)-2-(4-methylbenzenesulfonyloxymethyl)-3-methyl-
oxirane (10.5 g, 43.5 mmol) in toluene (120 mL) and
BF3´OEt2 (4.7 mL, 43.5 mmol) were successively added.
After 4 h at 2788C, the reaction was quenched with satu-
rated NH4Cl solution and the organic products were
4.2.4. (2R,3S,6RS)-1-Amino-3-methyl-6-(pent-4-enyloxy)-
hept-4-yn-2-ol (6). LAH (28 mg, 0.71 mmol) was added
to a solution of 5 (150 mg, 0.59 mmol) in ether (15 mL),
under inert atmosphere, at room temperature. The mixture
was stirred for 5 h, then saturated Na2SO4 solution was
added. The precipitate was ®ltered off, washed with
CH2Cl2 and the solution evaporated to dryness to give 6
(125 mg, 93%) as an oil used without further puri®cation,
C13H23NO2, CI MS: MH1 226; 1H NMR (CDCl3,

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F. Chouteau et al. / Tetrahedron 57 (2001) 6229±6238
300 MHz), d: 1.2 (3H, d, Jˆ7 Hz), 1.3 (3H, d, Jˆ6.5 Hz),
1.6 (2H, qun, Jˆ7 Hz), 2.1 (2H, q, Jˆ7 Hz), 2.5 (3H, m,
with NH2), 2.7 and 3.0 (2H,ABX, Jˆ13, 8, 3 Hz), 3.3 (1H,
m, C±2H), 3.3 and 3.6 (2H, 2dt, Jˆ9, 7 Hz), 4.1 (1H, qd,
Jˆ6.5, 1.5 Hz) 4.9 (2H, 2d, Jˆ18, 11 Hz) 5,8 (1H, m); 13C
NMR (CDCl3, 75 MHz) d: 17.4, 22.4, 28.8, 30.3, 36.9, 44.8,
65.3, 67.8, 74.6, 82.6, 86.2, 114.6, 138.2.
pentane, 33 mL) was added to a solution of 9 (14 mg,
0.033 mmol) in anhydrous THF (5 mL),under inert atmo-
sphere, at 2788C. After 1 h at 2788C, the reaction was
quenched at this temperature with a 10% aqueous HCl solu-
tion. After standard work-up (ether), the crude reaction
mixture was puri®ed on silica gel column (CH2Cl2/MeOH
95/5) to give 2 (7 mg, 77%), as an oil, HR EI MS: calcd for
C15H21O3NS 295.1242 (M1), found 295.1235; IR (neat)
1
4.2.5. (2R,3S,6RS)-1-Amino-3-methyl-6-(pent-4-enyloxy)-
5-tri-n-butylstannyl-hept-4Z-en-2-ol (7). HsnBu3 (0.3 mL,
0.88 mmol) and catalytic amount AIBN were added to 6
(0.2 g, 0.88 mmol) under inert atmosphere and the mixture
was stirred for 3 h at 908C and then poured on a silica gel
column to give 7 (357 mg, 78% yield) by elution with tolu-
ene/CH2Cl2 8/2, C25H51O2NSn, CI MS: MH1 517 with 118Sn
nmax 3437, 1637, 1349, 1159, 1098, 660 cm21; H NMR
(CDCl3, 300 MHz) d: 0.8 (3H, d, Jˆ7 Hz), 1.7 (3H, dd,
Jˆ6, 1.5 Hz), 1.85 (1H, m), 2.4 (3H, s), 3.3 (1H, m), 3.5
(1H, t, Jˆ7 Hz), 3.6 (2H, m), 5.4 (1H, dd, Jˆ16, 7 Hz), 5.6
(1H, dq, Jˆ16, 6 Hz), 7.3 (2H, d, Jˆ8 Hz), 7.8 (2H, d,
Jˆ8 Hz).
1
and 519 with 120Sn; H NMR (CDCl3, 250 MHz), d: 0.9
4.2.9. (2R,3S)-2-[4RS-(Pen-4-enyloxy)-3-tri-n-butylstan-
nyl-1-methyl-pent-2Z-enyl]-oxirane (10) and (2R,3S)-2-
[4RS-(pen-4-enyloxy)-2-tri-n-butylstannyl-1-methyl-pent-
2Z-enyl]-oxirane (11). Bu3SnH (1.55 mL, 5.76 mmol) and
AIBN (20 mg, catalytic) was added to n (1 g, 4.8 mmol) and
the mixture was stirred for 3 h at 908C under inert atmo-
sphere. After cooling at room temperature, the mixture was
poured on a silicagel column. Elution with heptane/CH2Cl2
95/5 gave 10 (1.66 g, 69 %) and 11 (0.15 g, 6%).
(9H, t, Jˆ7 Hz), 1.0 (3H, 2d, Jˆ7 Hz), 1.1 (3H, d,
Jˆ6 Hz), 1.3 and 1.4 (18H, 2 m,), 1.6 (2H, m), 2.0 (3H,
m), 3.1±3.4 (4H, m), 3.6 (1H, m), 3.8 (1H, q, Jˆ6 Hz),
4.9±5.0 (2H, m), 5.7±5.8 (1H, m), 9.0 (1H, d, Jˆ10 Hz);
13C NMR (CDCl3, 62.5 MHz), d: 11.3, 13.7, 17.7, 22.8,
27.5, 29.3 29.3, 30.6, 43.3, 45.9, 67.6 and 67.7 (C-10),
76.2, 83.6, 114,5, 138.5, 142.5 and 142.8 (C-4), 148.5.
4.2.6. (2R,3S,6RS)-N-[-2-Hydroxy-3-methyl-6-(pent-4-
enyloxy)-5-tri-n-butylstannyl-hept-4Z-enyl]-4-methyl-
benzenesulfonamide (8). TsCl (36 mg, 0.19 mmol) was
added to a solution of 7 (100 mg, 0.19 mmol) in pyridine
(3 mL) and CH2Cl2 (6 mL) and the solution let overnight at
room temperature before standard work-up (CH2Cl2). Chro-
matographic puri®cation on silica gel column of the crude
residue gave 8 (107 mg, 83%) as an oil, C32H57O4NSSn, CI
MS: MH1 672 with 120Sn; IR (neat) nmax 3456, 3289, 1447,
1328, 1152, 1096 cm21; 1H NMR (CDCl3, 250 MHz) d 0.8
(9H, m), 0.9 (3H, d, Jˆ7 Hz), 1.1 (3H, d, Jˆ6 Hz), 1.2±1.5
(18H, m), 1.6 (2H, m), 2.1 (3H, m), 2.6 and 3.1 (2H, 2 m),
3.3 (2H, m), 3.5 (1H, m), 3.8 (1H, q, Jˆ6 Hz), 4.9±5.1 (2H,
m), 5.1±5.2 (1H, m, NH), 5.7±5.9 (1H, m), 5.9 (1H, d,
Jˆ10 Hz), 7.3 (2H, d, Jˆ8 Hz), 7.7 (2H, d, Jˆ8 Hz); 13C
NMR (CDCl3, 62.5 MHz) d 11.3, 13.7, 17.6, 21.5, 22.6,
27.5, 29.3, 29.3, 30.5, 43.3, 47.6 and 47.7 (C-1), 67.7 and
67.8 (C-10), 74.5, 83.4, 114.6, 127.1, 129.8, 136.8, 138.5,
140.8 and 141.1 (C-4), 143.6, 150.6.
10: oil, anal. calcd for C25H4802Sn %: C 60.12, H 9.61, O
6.41, found %: 60.15, 9.68, O 6.41; IR (neat) nmax 1637,
1
1265 cm21; H NMR (CDCl3, 250 MHz) d 0.89 (9H, t,
Jˆ7 Hz), 0.94 (6H, t, Jˆ7 Hz), 1.04 and 1.08 (3H, 2d,
Jˆ7 Hz), 1.14 and 1.16 (3H, 2d, Jˆ6.5 Hz), 1.32 (6H, tt,
Jˆ7 Hz), 1.48 (6H, m), 1.62 (2H, qn, Jˆ7 Hz), 2.08 (2H, q,
Jˆ7 Hz), 2.52 (1H, dd, Jˆ4.5, 3.5 Hz), 2.69 (1H, dd, Jˆ4.5,
4 Hz), 2.80 (1H, m), 3.20 (1H, dt, Jˆ9, 7 Hz), 3.35 (1H, dt,
Jˆ9, 7 Hz), 3.83 (1H, q, Jˆ6.5 Hz), 4.93 (1H, dd, Jˆ10.5,
1.5 Hz), 5.0 (1H, dd, Jˆ17, 1.5 Hz), 5.80(1H, ddt, Jˆ17, 10.5,
7 Hz), 5.99 and 6.01 (1H, 2d, Jˆ10 Hz); 13C NMR (CDCl3,
62.5 MHz) d 11.3, 13.7, 17.6 and 17.7 (C-8), 22.8, 27.5, 29.2,
30.6, 40.6 and 40.7 (C-3), 46.0, 56.0, 67.5 and 67.6 (C-10),
83.5, 114.5, 138.5, 140.4 and 140.6 (C-4), 149.5.
11: oil, C25H48O2Sn, IC MS: MH1 501 with 120Sn; IR (neat)
n
max 1637, 1265 cm21; 1H NMR (CDCl3, 250 MHz) d 0.90
(9H, t, Jˆ7 Hz), 0.94 (6H, t, Jˆ7 Hz), 1.14 and 1.16 (3H,
2d, Jˆ7 Hz), 1.22 (3H, dd, Jˆ6.5, 1.5 Hz), 1.34 (6H, tt,
Jˆ7 Hz), 1.49 (6H, m), 1.66 (2H, qn, Jˆ7 Hz), 2.11 (2H,
q, Jˆ7 Hz), 2.21 (1H, dq, Jˆ7, 2 Hz), 2.44 (1H, dd, Jˆ5,
3 Hz), 2.70 (1H, dd, Jˆ5, 4 Hz), 2.90 (1H, m), 3.29 (1H, dt,
Jˆ9.5, 7 Hz), 3.41 (1H, dt, Jˆ9.5, 7 Hz), 3.71 (1H, m), 4.94
(1H, dd, Jˆ10.5, 1.5 Hz), 5.01 (1H, dd, Jˆ17, 1.5 Hz), 5.81
(1H, ddt, Jˆ17, 10.5, 7 Hz), 6.01 (1H, dq, Jˆ4, 1.5 Hz); 13C
NMR (CDCl3, 62.5 MHz) d 11.3, 13.7, 18.1, 22.0 and 22.2
(C-7), 27.5, 29.2, 30.4, 44.4, 46.0, 56.3 and 56.4 (C-2), 67.4,
78.1, 114.7, 138.3, 143.6, 146.9.
4.2.7. (3R,4S,5R)-5-(1-Iodo-prop-1Z-enyl)-4-methyl-1-(4-
methylbenzenesulfonyl)-pyrrolidin-3-ol (9). A solution of
8 (44 mg, 0.065 mmol) was treated according to the general
procedure to give 9, as an oil, (24 mg, 88 %), [a]Dˆ245.2
(CHCl3, c 1.4); HR CI MS: calcd for C15H20O3NSI 422.0288
(MH1), found 422.0315; IR (neat) nmax 3437, 1637, 1349,
1
1159, 1098, 660 cm21; H NMR, (CDCl3, 250 MHz) d:
mixture of conformers, 0.9 (3H, d, Jˆ6.5 Hz), 1.7 and 1.8
(3H, 2d, Jˆ6, 7 Hz), 2.1 (1H, m), 2.4 (3H, 2s), 3.2 (1H,
ABX, Jˆ10, 8 Hz), 3.5 (1H, d, Jˆ8 Hz), 3.6 (1H, m), 3.8
(1H, ABX, Jˆ10, 6 Hz), 6.0 (maj) and 6.4 (min) (1H, 2q,
Jˆ6, 7 Hz), 7.3 (2H, 2d, Jˆ9 Hz), 7.8 and 7.9 (2H, 2d,
Jˆ8 Hz); 13C NMR (CDCl3, 250 MHz) d: 14.6, 21.6,
24.1, 47.6, 54.3, 73.9, 74.4, 121.4, 127.7, 129.6, 129.8,
133.2, 143.6, 157.3; 2D NOESY (CDCl3, 400 MHz): nOe
H5±H9, H3±H9.
4.2.10. (3S,4S,7RS)-7(Pent-4-enyloxy)-6-tri-n-butylstan-
nyl-4-methyl-3-hydroxy-hept-5Z-enyl-1-nitrile 12.
A
solution of 10 (3.2 g, 6.4 mmol) and KCN (0.6 g, 9 mmol)
in EtOH (100 mL) was warmed at 458C for 16 h. After
cooling, a saturated aqueous NaHCO3 solution was added
and the organic products were extracted three times with
CH2Cl2. The organic phases washed with brine and dried
on MgSO4 were evaporated under reduced pressure to give a
residue which was chromatographed on silica gel column
4.2.8. (3R,4S,5S) 5-(Pro-5E-enyl)-4-methyl-1-(toluene-4-
sulfonyl)-pyrrolidin-3-ol (2). t-BuLi (2 M solution in

F. Chouteau et al. / Tetrahedron 57 (2001) 6229±6238
6235
(heptane/ether 9/1) to give 12 (3.37 g, 97%) as an oil, anal.
calcd for C26H49NO2Sn%: C 59.3, H 9.38, found %: C 59.5,
H 9.59; IC MS: MH1 528 with 120Sn; IR (neat) nmax 3460,
2258, 1641 cm21; 1H NMR (CDCl3, 250 MHz) d 0.89 (9H,
t, Jˆ7 Hz), 0.94 (6H, t, Jˆ7 Hz), 1.07 and 1.10 (3H, 2d,
Jˆ7 Hz), 1.15 and 1.17 (3H, 2d, Jˆ6.5 Hz), 1.35 (6H, tt,
Jˆ7 Hz), 1.49 (6H, m), 1.64 (2H, qn, Jˆ7 Hz), 2.06±2.22
(3H, m), 2.33±2.44 (2H, m), 2.54 (1H, dd, Jˆ10, 4 Hz),
3.22 (1H, dt, Jˆ9, 7 Hz), 3.33 (1H, dt, Jˆ9, 7 Hz), 3.76
(1H, m), 3.84 (1H, dq, Jˆ6.5, 2 Hz), 4.97 (1H, dd,
Jˆ10.5, 1.5 Hz), 5.03 (1H, dd, Jˆ17, 1.5 Hz), 5.81 (1H,
ddt, Jˆ17, 10.5, 7 Hz), 5.94 (1H, dd, Jˆ4, 2 Hz); 13C
NMR (CDCl3, 62.5 MHz) d 11.4, 13.8, 17.2, 22.7, 24.5
and24.6 (C-2), 27.6, 29.2, 29.4, 30.6, 44.6, 67.8 and 68.0
(C-10), 72.0, 83.3 and 83.4 (C-7), 114.8, 118.3, 138.5, 140.0
and 140.4 (C-4), 151.7.
4.2.13. (3S,4S,7RS)-N-[3-Hydroxy-4-methyl-6-iodo-7-
(pent-10-enyloxy)-oct-5Z-enyl]-4-methyl-benzenesulfon-
amide 13c. NIS (1.07 g, 4.7 mmol) was added to 13b (2.5 g,
3.65 mmol) in anhydrous THF (80 mL) at 08C and under
inert atmosphere. The solution was stirred for 1 h at 08C and
standard work-up (ether) followed by ¯ash chromatography
with CH2Cl2/MeOH 99/1 as eluent, gave 13c as an oil,
C21H32NO4SI; CI MS: MH1 522, 436; IR (neat) nmax
3476, 3284, 1638, 1594, 1450, 1329, 1156, 1097, 912,
1
812 cm21; H NMR (CDCl3, 250 MHz) d: 0.98 and 1.0
(3H, 2d, Jˆ7 Hz, CH3-9), 1.18 and 1.19 (3H, 2d, Jˆ6 Hz,
CH3-8), 1.63 (4H, m), 2.09 (2H), 2.41 (3H, s), 2.54 (2H with
OH), 2.98 (1H, m, Jˆ9, 7, 4 Hz), 3.14 (2H, m), 3.36 (2H,
m), 3.62 (2H, m), 4.91 (1H, dd, Jˆ10.5, 1.5 Hz), 5.0 (1H,
dd, Jˆ17, 1.5 Hz), 5.36 (1H, t, Jˆ4 Hz, NH), 5.67 (1H, dd,
Jˆ10, 1 Hz), 5.78 (1H, ddt, Jˆ17, 10.5, 7 Hz), 7.29 (2H, d,
Jˆ8 Hz), 7.72 (2H, d, Jˆ8 Hz); 13C NMR (CDCl3, 75 MHz)
d; 15.0, 21.6, 22.5, 28.9, 30.5, 33.8, 41.0, 46.6, 67.6 and
67.8 (C-10), 72.9 and 73.2 (C-3), 81.3 and 81.5 (C-7), 114.8,
116.4, 127.2, 129.8, 131.6, 138.4, 138.5, 143.5.
4.2.11. (3S,4S,7RS)-1-Amino-4-methyl-7-(pent-4-enyloxy)-
6-tri-n-butylstannyl-oct-5Z-en-3-ol (13a). LAH (480 mg,
2 equiv.) was added to a solution of 12 (3.35 g, 6.35 mmol)
in anhydrous ether (350 mL) at room temperature. The
suspension was stirred for 2 h before addition of saturated
aqueous Na2SO4 solution. The precipitate was ®ltered off,
washed with ether and evaporation of the ethereal phase
gave 13a (3.03 g, 90% yield) as an oil, which was used
without further puri®cation, C26H53NO2Sn, CI MS: MH1
532 with 120Sn; IR (neat) nmax 3410, 1590, 1262,
4.2.14. (2R,3S,4S)-3-Methyl-2-(1-iodo-prop-1Z-enyl)-1-
(toluene-4-sulfonyl)-piperidin-4-ol (14a). TMSCl
(0.55 mL, 2.4 mmol), Et3N (0.65 mL, 2.6 mmol) and cata-
lytic DMAP were successively added to a solution of 13c
(312 mg, 0.6 mmol) in anhydrous THF (10 mL). The
mixture was stirred at rt for 1 h and after addition of aqueous
saturared NaHCO3, standard work-up (ether) gave 13d wich
was cyclized according to the general procedure to provide
14b (118 mg, 54%) as an oil, [a]Dˆ133 (CHCl3, c 1); EI
MS: M1 507, m/z 380, IR (neat) nmax 3468, 1638, 1598,
1494, 1454, 1343, 1155, 1090, 812 cm21. Bu4NF´3H2O
(109 mg, 0.29 mmol) was added to a solution of 14b
(150 mg, 0.29 mmol) in THF at rt. The mixture was stirred
for 1 h before standard work-up (CH2Cl2) which gave 14a
(120 mg, 95%), as an oil, HR CI MS: calcd for C16H23NO3Si
1
740 cm21; H NMR (CDCl3, 250 MHz) d: 0.89 (9H, t,
Jˆ7 Hz), 0.94 (6H, t, Jˆ8 Hz), 1.08 and 1.10 (3H, 2d,
Jˆ7 Hz, CH3-9), 1.17 and 1.19 (3H, 2d, Jˆ6.5 Hz, CH3-
8), 1,35 (6H, m), 1.45 (8H, m), 1.63 (2H, qn, Jˆ7 Hz),
2.0 (4H, m with OH), 2.81 (2H, m, NH2), 3.22 (2H, m),
3.38 (2H, m), 3.63 (1H, m), 3.84 (1H, dq, Jˆ6.5, 2 Hz), 4.95
(2H, dd, Jˆ10.5, 1.5 Hz), 5.01 (1H, dd, Jˆ17, 1.5 Hz), 5.81
(1H, ddt, Jˆ10.5, 17, 7 Hz), 6,0 (1H, dd, Jˆ10, 2 Hz); 13C
NMR (CDCl3, 62.5 MHz) d: 11.3, 13.7, 17.1, 22.8, 27.5, 29.2,
29.3, 30.6, 35.9, 41.2, 45.6, 67.5 and 67.6 (C-10), 77.1, 83.7,
114.5, 138.5, 143.5 and 143.9 (C-5), 147.8.
1
436.0445 (MH1), found 436.0481; H NMR (CDCl3,
250 MHz) d: 0.92 (3H, d, Jˆ7 Hz), 1.50 (1H, m), 1.66
(3H, d, Jˆ6.5 Hz), 1.74 (1H, broad s, OH), 2.15 (1H, m),
2.33 (1H, sex, Jˆ7 Hz), 2.40 (3H, s), 3.60 (3H, m), 3.88
(1H, d, Jˆ7 Hz), 5.78 (1H, q, Jˆ6.5 Hz), 7.28 (2H, d,
Jˆ8 Hz), 7.62 (2H, Jˆ8 Hz); 13C NMR (CDCl3, 75 MHz)
d: 15.8, 21.6, 21.8, 30.8, 39.0, 39.7, 66.9, 69.7, 111.2, 127.4,
129.4, 132.8, 137.8, 143.2; 2D NOESY (CDCl3, 400 MHz):
nOe H2±H4, H4±H10.
4.2.12. (3S,4S,7RS)-N-[3-Hydroxy-4-methyl-7-(pent-10-
enyloxy)-6-tri-n-butylstannyl-oct-5Z-enyl]-4-methyl-
benzenesulfonamide 13b. TsCl (1.5 g, 7.9 mmol) was
added to a solution of 13a (3 g, 5.668 mmol) in CH2Cl2/
pyridine 2/1 (350 mL) at room temperature and let to
react overnight. Standard work-up (CH2Cl2) led to 13b
(3.68 g, 95% yield) after silica gel chromatography of the
crude extract with CH2Cl2/MeOH 99/1 as eluent,
C33H59NO4SSn; EI MS: M1 684, m/z 629; IR (neat) nmax
3483, 3291, 2924, 1639, 1612, 1599, 1454, 1417, 1095, 905,
4.2.15. (2S,3S,4S)-3-Methyl-2-(prop-E-enyl)-1-(4-methyl-
benzenesulfonyl)-piperidin-4-ol (3). t-BuLi (0.5 mL of
1.5 M solution in pentane, 0.75 mmol) was added to a solu-
tion of 14a (115 mg, 0.26 mmol) in THF (15 mL) at 2788C
under inert atmosphere. After 1 h at 2788C, AcOH (30 mL)
was added and the solution was allowed to warm up to rt,
before standard work-up (ether) which provided 3 (48 mg,
60%), as an oil, after silica gel column chromatography
(heptane/AcOEt 8/2), [a]Dˆ29 (CHCl3, c 1.3); EI MS:
1
809 cm21; H NMR (CDCl3, 250 MHz), d: 0.94 (9H, t,
Jˆ7 Hz), 0.99 (6H, t, Jˆ7 Hz), 1.03 and 1.07 (3H, 2d,
Jˆ7 Hz, CH3-9), 1.2 (3H, d, Jˆ6 Hz), 1.37 (6H, tt,
Jˆ7 Hz), 1.4±1.52 (8H, m), 1.69 (2H, qn, Jˆ7 Hz), 1.99
(1H, d, Jˆ6.5 Hz, OH), 2.15 (3H, m), 2.49 (3H, s), 2.99 (1H,
m, Jˆ9, 7 Hz), 3.20 (2H, m), 3.32 (1H, m, Jˆ9, 7, 4 Hz),
3.52 (1H, m), 3.8 (1H, dq, Jˆ6, 1 Hz), 4.95 (1H, dd, Jˆ10.5,
1.5 Hz), 5.01 (1H, dd, Jˆ17, 1.5 Hz), 5.14 (1H, t, Jˆ4 Hz,
NH), 5.81 (1H, ddt, Jˆ17, 10.5, 7 Hz), 5.9 (1H, dd, Jˆ10,
1 Hz), 7.31 (2H, d, Jˆ8 Hz) 7.75 (2H, d, Jˆ8 Hz); 13C
NMR (CDCl3, 50 MHz) d: 11.3, 13.6, 16.9, 21.4, 22.6,
27.4, 29.1, 29.1, 30.4, 33.6, 41.5, 44.8, 67.6 and 67.8
(C-10), 74.5, 83.4 and 83.7 (C-7), 114.4, 127.1, 129.6,
138.3, 141.1 and 141.6 (C-5), 143.2, 149.9.
1
M1 309, m/z 268; IR (neat) nmax 3476, 1665 cm21; H
NMR, (CDCl3, 250 MHz) d: 1.02 (3H, d, Jˆ7 Hz), 1.18
(1H, s, OH), 1.44 (3H, dd, Jˆ6.5, 2.5 Hz), 1.55 (1H, m),
1.77 (1H, m), 1.93 (1H, m), 2.41 (3H, 2 s), 3.26 (1H, td,
Jˆ11.5, 3 Hz), 3.38 (1H, td, Jˆ11.5, 3.5 Hz), 3.64 (1H, qn,
Jˆ4 Hz), 3.96 (1H, dd, Jˆ8, 2.5 Hz), 5.26 (1H, dq, Jˆ6.5,
15.5 Hz), 5.60, (1H, ddq, Jˆ15.5, 8, 2.5 Hz), 7.25 (2H, d,
Jˆ8 Hz), 7.61 (2H, d, Jˆ8 Hz); 13C NMR, (CDCl3,

6236
F. Chouteau et al. / Tetrahedron 57 (2001) 6229±6238
1
62.5 MHz) d: 16.8, 17.5, 21.5, 28.7, 37.9, 41.6, 61.1, 69.9,
127.6, 128.8), 129.1, 129.7, 137.1, 142.8; 2D NOESY
(CDCl3, 400 MHz): nOe H4±H10, H4±H5b, H2±H10,
H2±H5b, H7±H9.
1595, 1497, 1474, 1463, 1230, 1150, 897, 825 cm21; H
NMR (CDCl3, 250 MHz) d: 1.23 (3H, s), 1.27 (3H, s),
2.38 (3H, s), 2.99 (1H, ABX, Jˆ13, 7.5 Hz), 3.19 (1H,
ABX, Jˆ13, 6 Hz) 3.43±3.52 (2H, m), 3.68 (1H, m), 3.92
(1H, dd, Jˆ9, 6 Hz), 4.13 (1H, dt, Jˆ7.5, 6 Hz), 4.40 (3H,
broads, OH, NH), 7.26(2H, d,Jˆ8 Hz), 7.66(2H, d,Jˆ8 Hz);
13C NMR (CDCl3, 75 MHz) d: 21.3, 25.7, 28.3, 44.5, 65.2,
70.8, 77.4, 77.6, 110.0, 128.1, 130.7, 138.9, 144.7.
4.2.16. 5S-[2-(tert-Butyldimethylsilanyloxy)-1R-hydroxy-
ethyl]-2,2-dimethyl-[1,3]-dioxolane-4S-carbaldehyde
oxime (16). A solution of hydroxylamine acetate (442 mg,
5.56 mmol), pyridine (0.45 mL, 5.56 mmol) and 1516
(845 mg, 2.78 mmol) in MeOH (24 mL) was kept at rt for
16 h. After standard work-up (CH2Cl2) 16 (mixture of
isomers) (869 mg, 98%) was obtained as crystals, mp 60±
648C, and was used without further puri®cation, anal. calcd
for C14H29NO5Si%: C 52.63, H 9.16, N 4.39; found %: C
52.83, H 8.98, N 4.34; IR (CHCl3) nmax 3381, 2952, 2861,
1644, 1462, 1384, 1265, 920, 846; 1H NMR (CDCl3,
300 MHz) d: 0.10 (6H, s), 0.90 (9H, s), 1.37 (3H, s), 1.48
(3H, s), 3.08 (1H, s, OH), 3.68 (2H, m), 3.83 (1H, t,
Jˆ7.5 Hz), 4.18 (1H, dd, Jˆ6.5, 6 Hz anti), 4.3 (1H, t,
Jˆ6.5 Hz syn), 4.89 (1H, dd, Jˆ7.5 Hz, J0ˆ6.5 Hz anti),
5.4 (1H, t, Jˆ6.5 Hz syn), 6.92 (1H, d, Jˆ6.5 Hz syn),
7.51 (1H, d, Jˆ7.5 Hz anti), 8.73 (1H, s, N±OH); 13C
NMR (CDCl3, 75 MHz) d: 20.5, 18.3, 25.3, 25.8, 27.7,
64.5, 69.3, 75.3 (anti), 75.5 (syn), 77.1 (anti), 77.6 (syn),
109.8, 148.3 (anti), 150.0 (syn).
4.2.19. (2S,3S,4S)-3,4-Isopropylidenedioxy-1-(4-methyl-
benzenesulfonyl)-pyrrolidin-2-ol (18). A solution of
NaIO4 (2.63 g, 12.29 mmol) in aqueous pH 5 solution
(55 mL) was added to a solution of 17c (2.12 g,
6.14 mmol) in EtOH (80 mL). The mixture was stirred for
1 h at rt before addition of aqueous Na2S2O7 solution
followed by standard work-up (CH2Cl2) to give 18
(1.88 g, 98%) used without further puri®cation, crystals,
mp 101±1028C (MeOH/heptane), [a]Dˆ221 (CHCl3, c
0.5), anal. calcd for C14H19NO5S %: C 53.66, H 6.12, N
4.41, S 10.21; found %: C 53.83, H 6.34, N 4.43, S 10.31;
HR CI MS calcd for C14H20NO5S (MH1) 314.1062, found
314.1054; IR (neat) nmax 3226, 3025, 1602, 1459, 1377,
1172, 1163, 1116, 1029 cm21
;
1H NMR (CDCl3
250 MHz) d: 1.10 (3H, s), 1.22 (3H, s), 2.41 (3H, s), 3.25
(1H, broad s, OH), 3.54 (1H, d, Jˆ11.5 Hz), 3.77 (1H, dd,
Jˆ11.5, 4.5 Hz), 4.54 (1H, d, Jˆ6 Hz), 4.78 (1H, dd, Jˆ6,
4.5 Hz), 5.38 (1H, s), 7.30 (2H, d, Jˆ8 Hz), 7.77 (2H, d,
Jˆ8 Hz); 13C NMR, (CDCl3, 75 MHz) d: 21.3, 24.3, 25.7,
52.1, 78.2, 85.1, 87.6, 111.6, 127.0, 129.4, 136.5, 143.6. 2D
NOESY (CDCl3, 400 MHz): nOe H5b±H4, H3±H4, H2±H3.
4.2.17. 5S-[2-(tert-Butyldimethylsilanyloxy)-1R-hydroxy-
ethyl]-4S-methylamino-2,2-dimethyl-[1,3]-dioxolane
(17a). LiBH4 (28 mg, 1.28 mmol) was added to a solution of
16 (205 mg, 0.64 mmol) in THF (4 mL). The mixture was
re¯uxed for 16 h. After cooling, standard work-up (CHCl3)
followed by silica gel column chromatography (CH2Cl2/
MeOH 9/1) gave 17a (164 mg, 84%), as an oil, [a]Dˆ13
(CHCl3, c 0.7), HR CI MS calcd for C14H32NO4Si (MH1)
306.2100, found 306.2077; IR (neat) nmax 3367, 3297, 2991,
4.2.20. 5S-[4RS-(Pentenyloxy)-1R-hydroxybut-2-ynyl]-
[2,2-dimethyl-(1,3)-dioxolan-4S-ylmethyl]-4-methyl-
benzenesulfonamide (19). nBuLi (7.56 mL of 1.3 M
solution in hexane) was added to a solution of 3-penteny-
loxy-but-1-yne (1.36 g, 9.8 mmol) in THF (38 mL) at
2788C under inert atmosphere. After 15 min, 18 (1.47 g,
4.68 mmol) in THF solution (16 mL) was slowly added.
The solution was warmed up to rt and kept to react at this
temperature for 16 h. Quenching with aqueous NH4Cl solu-
tion was followed by standard work-up (ether). The crude
reaction mixture was chromatographed on silica gel
comumn to give 19 eluted by CH2Cl2/MeOH 99/1 (2.0 g,
95%), as an oil, HR CI MS: calcd for C23H34NO6S
452.2106, found 452.2096; IR (neat) nmax 3455, 3285,
3075, 2986, 1641, 1599, 1451, 1383, 1373, 1161, 1095,
1
1602, 1470, 1463, 1163, 1055, 1006, 848 cm21; H NMR
(CDCl3, 250 MHz) d: 0.09 (6H, s), 0.91 (9H, s), 1.33 (3H,
s), 1.40 (3H, s), 2.70 (3H, broad s, OH, NH2), 2.93 (1H,
ABX, Jˆ12.5, 7.5 Hz), 3.04 (1H, ABX, Jˆ12.5, 7.5 Hz),
3.68±3.78 (2H, m), 3.86 (1H, m), 4.11±4.22 (2H, m); 13C
NMR (CDCl3, 75 MHz) d: 25.2, 18.6, 26.1, 26.5, 28.2,
41.7, 65.1, 69.7, 77.4, 78.5, 108.8.
4.2.18. 5S-[2-(tert-Butyldimethylsilanyloxy)-1R-hydroxy-
ethyl]-2,2-dimethyl-[1,3]-dioxolan-4S-ylmethyl-(4-meth-
yl)-benzenesulfonamide (17c). Net3 (0.6 mL, 8.9 mmol)
and TsCl (1.42 g, 7.44 mmol) were added to a solution of
17a (2.27 g, 7.44 mmol) in CH2Cl2 (40 mL) at 08C. The
mixture was stirred for 2 h before addition of aqueous
NaHCO3 solution. Standard work-up (CH2Cl2) led to 17b
(1.94 g, 57%), as crystals, mp 1058C (heptane/ether), after
silica gel column chromatography (CH2Cl2/heptane 1/1),
[a]Dˆ120 (CHCl3, c 1.4), anal. calcd for C21H37NO6SSi%:
C 54.88, H 8.12, N 3.05, S 6.96; found %: C 54.75, H 8.01,
N 2.98, S 6.88; IR (neat) nmax 3531, 3270 cm21. A sample of
17b (1.87 g, 4.07 mmol) in THF was desilylated with
Bu4NF´3H2O (1.54 g, 4.88 mmol) to give 17c (1.15 g,
82%), after silica gel column chromatography (CH2Cl2/
MeOH 95/5), as crystals, mp 153±1558C (MeOH/heptane),
[a]Dˆ227 (MeOH, c 1.2), anal. calcd for C15H23NO6S %:
C 52.16, H 6.72, N 4.06, S 9.26; found %: C 52.21, H 6.79,
N 3.84, S 9.21; HR CI MS calcd for C15H24NO6S (MH1)
346.1324, found 346.1355; IR (neat) nmax 3531, 3269, 2906,
1075, 913, 815 cm21; H NMR (CDCl3, 250 MHz) d: 1.29
1
(3H, s), 1.35 (3H, s), 1.38 (3H, d, Jˆ6.5 Hz), 1.65 (2H, qn,
Jˆ7 Hz), 2.12 (1H, q, Jˆ7 Hz), 2.40 (3H, s), 3.28 (2H, q,
Jˆ6.5 Hz), 3.36 and 3.67 (2H, ABX2Y, Jˆ11.5, 7, 2.5 Hz),
4.06±4.18 (2H, m), 4.26 (1H, q, Jˆ6.5 Hz), 4.46 (1H, d,
Jˆ4 Hz), 4.94 (1H, dd, Jˆ10.5, 1.5 Hz), 5.0 (1H, dd, Jˆ17,
1.5 Hz), 5.20 (1H, t, Jˆ6.5 Hz, NH), 5.81 (1H, ddt, Jˆ17,
10.5, 7 Hz), 7.30 (2H, d, Jˆ8 Hz), 7.73 (2H, d, Jˆ8 Hz); 13C
NMR (CDCl3, 75 MHz) d: 21.6, 21.9, 25.3, 27.6, 28.8, 30.3,
42.7, 61.3, 65.3, 68.3, 75.9, 78.6, 82.4, 87.3, 109.1, 114.8,
127.1, 129.8, 137.0, 138.3, 143.5.
4.2.21. 5S-[4RS-(Pentenyloxy)-1R-hydroxybut-3-iodo-2-
enyl]-[2,2-dimethyl-(1,3)-dioxolan-4S-ylmethyl]-4-meth-
yl-benzenesulfonamide (20a). Red Alw (2.46 mL of 65%
solution in toluene, 1.26 mmol) was added to a solution of
19 (190 mg, 0.42 mmol) in ether (5 mL) at 08C under inert

F. Chouteau et al. / Tetrahedron 57 (2001) 6229±6238
6237
atmosphere. The mixture was stirred for 16 h at rt before
addition of EtOAc (40 mL). After 15 min at rt, the mixture
was cooled to 2788C and after addition of a solution of I2
(214 mg, 0.84 mmol) in THF (4 mL) was warmed up to
258C for 2 h. Quenching successively by aqueous
Na2S2O7 and NH4Cl solutions (6 mL of each) was followed
by ®ltration of the mixture upon Celitew. The solution was
extracted with CH2Cl2. The organic phase washed, dried on
MgSO4 and evaporated gave 20a (234 mg, 96% yield)
which was used witout further puri®cation, as an oil HR
CI MS: calcd for C23H33NO6SI 562.1126, found 562.1106;
IR (neat) nmax 3364, 3018, 2987, 1641, 1600, 1384, 1373,
d: 0.07 (3H, s), 0.16 (3H, s), 0.85 (9H, s), 1.32 (3H), 1.47
(3H, s,), 1.63 (3H, d, Jˆ6.5 Hz), 2.41 (3H, s), 3.15 (1H,
ABX, Jˆ14.0, 10.5 Hz), 3.84 (2H, m), 4.05 (2H, m), 4.47
(1H, m), 5.97 (1H, q, Jˆ6.5 Hz), 7.25 (2H, d, Jˆ8 Hz), 7.61
(2H, d, Jˆ8 Hz); 13C NMR (CDCl3, 62.5 MHz) d: 27.2,
19.0, 20.6, 21.4, 24.6, 25.9, 27.0, 44.7, 65.6, 72.3, 74.2,
78.5, 108.0, 111.6, 127.7, 129.4, 135.8, 138.5, 144.9.
4.2.24. X-Ray crystallographic data of 21c. 21a was
acetylated (Ac2O, pyridine, DMAP) to provide 21c, as a
crystalline material (MeOH). Orthorombic, space group
Ê
Ê
P212121, Zˆ4, aˆ19.470(5), bˆ14.960(4), cˆ7.957(3) A,
Ê 3
1161, 1095, 1074, 767 cm21; H NMR (CDCl3, 250 MHz)
Vˆ2317.6 A , dCˆ2.03 g cm23
,
l(Mo Ka)ˆ0.707 A,
1
d: 1.22 (3H, d, Jˆ6.5 Hz), 1.27 (3H, s), 1.32 (3H, s), 1.67
(2H, qn, Jˆ7), 2.15 (1H, q, Jˆ7 Hz), 2.42 (3H, s), 3.15±
3.54 (6H, m with OH), 4.09 and 4.12 (1H, 2t, Jˆ5.5 Hz),
4.25 (1H, m), 4.46 (1H, ddd, Jˆ8, 6, 5.5 Hz), 4.97 (1H, dd,
Jˆ10.5, 1.5 Hz), 5.02 (1H, dd, Jˆ17, 1.5 Hz), 5.27 (1H, t,
Jˆ6.5 Hz, NH), 5.81 (1H, ddt, Jˆ17, 10.5, 7 Hz), 6.06 and
6.09 (1H, 2d, Jˆ8 Hz), 7.32 (2H, d, Jˆ8 Hz), 7.76 (2H, d,
Jˆ8 Hz); 13C NMR (CDCl3, 75 MHz) d: 21.6, 22.1, 25.5,
27.9, 28.9, 30.5, 42.7, 68.1, 73.1, 75.9, 78.1, 81.3, 108.8,
114.8, 120.6, 127.2, 129.9, 134.5 and 135.1 (C-5), 137.1,
138.4, 143.6.
6402 intensities measured of which 1935 were unique.
Re®nments of 293 variables converged to R1(F)ˆ0.0740
for 1846 F0$4d(F0) wR2(F2)ˆ0.0780 for all data. The resi-
dual electron density in the last Fourier map was found
between 20.54 and 0.56 e2.
4.2.25. (4S,5R,6R)-1-p-Toluenesulfonylamido-5-(tert-
butyldimethylsilylanyloxy)-6-[prop-E-enyl]-2,3-dehy-
dropiperidin-4-ol (23). t-BuLi (0.1 mL of 1.5 M solution in
pentane was added to a solution of 21a (48 mg, 0.08 mmol)
in ether at 2788C, under inert atmosphere. The mixture was
stirred for 1 h at 2788C before addition of AcOH, warming
up to rt, standard work-up (ether) and silica gel column
chromatography (CH2Cl2/MeOH 99/1) to give 23 (16 mg,
42%) as an oil, [a]Dˆ130 (CHCl3, c 0.6), HR CI MS: calcd
for C21H32NO3SSi (MH1) 406.1872, found 406.1905; IR
(neat) nmax 3453, 2930, 1650, 1598, 1354, 1167, 1089,
4.2.22. 5S-[4RS-(Pentenyloxy)-1R-(tert-butyl-dimethylsil-
anyloxy)-but-3-iodo-3Z-enyl]-[2,2-dimethyl-(1,3)-dioxo-
lan-4S-ylmethyl]-4-methyl-benzenesulfonamide (20b).
Imidazole (526 mg, 7.75 mmol) and TBDMSCl (5.82 mg,
3.87 mmol) were added to a solution of 20a (895 mg,
1.55 mmol) in DMF (3 mL) at rt. The mixture was stirred
for 16 h at rt before addition of H2O standard work-up
(ether) which led to 20b (1.02 g, 95 %) which was used
without further puti®cation, EI MS: M1 693, m/z 678; IR
(neat) nmax 3291, 2935, 1642, 1598, 1380, 1373, 1327,
1037, 739 cm21 1H NMR (CDCl3, 250 MHz) d: 0.13
;
(6H, s), 0.88 (9H, s), 1.61 (3H, dd, Jˆ6.5, 1.5 Hz), 2.07
(1H, d, Jˆ10.5 Hz, OH), 2.41 (3H, s), 3.82 (1H, dd,
Jˆ4.0, 2.0 Hz), 4.12 (1H, m), 4.55 (1H, m), 4.74 (1H, dd,
Jˆ8.5, 2 Hz), 5.01 (1H, ddq, Jˆ15.5, 7.5, 1.5 Hz), 5.60 (1H,
ddq, Jˆ15.5, 6.5, 1 Hz), 6.61 (1H, d, Jˆ8.5 Hz), 7.27 (2H,
d, Jˆ8 Hz), 7.66 (2H, d, Jˆ8 Hz); 13C NMR (CDCl3,
62.5 MHz) d: 20.5, 17.7, 18.3, 21.6, 26.0, 61.8, 63.1,
79.5, 106.7, 124.4, 127.5, 129.6, 130.1, 137.8, 143.1.
1332 cm21
.
4.2.23. (2S,3R,4S,5S)-2-[1-Iodo-prop-1Z-enyl]-3-(tert-
butylsilanyloxy)-4,5-isopropylidenedioxy-1-(4-methyl-
benzenesulfonyl)-piperidine (21a) and (2S,3R,4S,5S)-4,5-
epoxy-2,3-isopropylidenedioxy-6-iodo-oct-6Z-en-1-(4-
methyl-benzenesulfonyl)-1-(tert-byutyldimethylsilanyl)-
1-amine (22). 20b (78 mg, 0.1 mmol) was cyclized accord-
ing to the general procedure to give 21a (45 mg, 66%) and
22a (9 mg, 13%).
4.2.26. 5S-[1R-Hydroxybut-3-allenyl]-[2,2-dimethyl-
(1,3)-dioxolan-4S-ylmethyl]-4-methyl-benzenesulfon-
amide (24). 21a (114 mg, 0.19 mmol) was desilylated
(Bu4NF´6H2O, THF) to provide 21b (81 mg, 85%) as crys-
tals, mp 2058C MeOH/heptane), [a]Dˆ131 (CHCl3, c 1.5);
CI MS: 494 (MH1), 476, 366; anal. calcd for C18H24NO5SI
%: C 43.81, H 4.91, N 2.84, S 6.48, found C 44.01, H 5.05,
21a. Oil [a]Dˆ131 (CHCl3, c 0.9), HR CI MS: calcd for
C24H39NO5SSiI (MH1) 608.1365, found 608.1375; IR
(neat) nmax 3379, 3018, 1640, 1598, 1384, 1258, 1158,
1
N 2.83, S 6.71; IR (neat) nmax 3469, 1645 cm21; H NMR
(CDCl3, 250 MHz) d: 1.38 (3H, s), 1.62 (3H, d, Jˆ6.5 Hz),
1.64 (3H, s), 2.0 (1H, d, Jˆ3 Hz, OH), 2.41 (3H, s), 3.31
(1H, ABX, Jˆ15, 2 Hz), 3.88 (1H, d, Jˆ8 Hz), 4.13 (1H,
dd, Jˆ15, 2 Hz), 4.17 (1H, d, Jˆ8.5 Hz), 4.41 (1H, dt,
Jˆ8.5, 2 Hz), 4.59 (1H, dd, Jˆ8, 3 Hz), 6.12 (1H, q,
Jˆ6.5 Hz), 7.21 (2H, d, Jˆ8 Hz), 7.55 (2H, d, Jˆ8 Hz);
13C NMR (CDCl3, 62.5 MHz) d: 21.5, 21.6, 24.4, 25.7,
44.8, 63.3, 69.0, 73.0, 73.2, 110.5, 110.9, 127.7, 129.0,
136.9, 137.0, 142.7. 21b (81 mg, 0.16 mmol) was treated
with t-BuLi as described above to give to give 23b (1 mg,
2%) 24 (38 mg, 78%), and 25 (9 mg, 18%) after silica gel
column chromatography (heptane/AcOEt 3/7).
1
1120, 1061, 933 cm21; H NMR (CDCl3, 300 MHz) d:
0.02 (3H, s), 0.10 (3H, s), 0.85 (9H, s), 1.35 (3H, s), 1.57
(3H, d, Jˆ6.5 Hz), 1.66 (3H, s), 2.39 (3H, s), 3.35 (1H,
ABX, Jˆ14.5, 2 Hz), 3.88 (1H, dd, Jˆ8.5, 2 Hz), 4.03
(1H, d, Jˆ14.5 Hz), 4.27 (1H, d, Jˆ8.5 Hz), 4.32 (1H, dd,
Jˆ8.5, 2.5 Hz), 4.40 (1H, dd, Jˆ8.5 Hz, J0ˆ2.5 Hz), 6.03
(1H, q, Jˆ6.5 Hz), 7.19 (2H, d, Jˆ8 Hz), 7.55 (2H, d,
Jˆ8 Hz); 13C NMR (CDCl3, 62.5 MHz) d: 24.1, 18.1,
21.3, 21.6, 24.4, 25.7, 25.8, 45.3, 63.4, 70.1, 73.6, 74.3,
109.9, 111.6, 127.8, 128.9, 136.0, 139.4, 142.5.
22. Oil [a]Dˆ118 (CHCl3, c 1.7), HR CI MS: calcd for
(neat) nmax 1642, 1253 cm21; H NMR (CDCl3, 300 MHz)
C24H39NO5SSiI (MH1) 608.1365, found 608.1375; IR
24. Oil [a]Dˆ23 (CHCl3, c 1.6), HR CI MS: calcd for
1
C18H26NO5S (MH1) 368.1531, found 368.1516; IR (neat)

6238
F. Chouteau et al. / Tetrahedron 57 (2001) 6229±6238
2. Zu-Fan, W.; Mootoo, D. R.; Fraser-Reid, B. Tetrahedron Lett.
max 3470, 3283, 1967, 1598, 1383, 1218, 1151, 1094, 1071,
n
866 cm21; 1H NMR (CDCl3, 250 MHz) d: 1.30 (3H, s), 1.34
(3H, s), 1.71 (3H, dd, Jˆ6.5, 3.5 Hz), 2.13 (1H, broad s,
OH), 2.44 (3H, s), 3.22 (2H, m), 3.89 (1H, dd, Jˆ9, 6 Hz),
4.07 (1H, m), 4.25 (1H, q, Jˆ6 Hz), 5.38 (3H, m), 7.31 (2H,
d, Jˆ8 Hz), 7.75 (2H, d, Jˆ8 Hz); 13C NMR (CDCl3,
62.5 MHz) d: 14.2, 21.5, 25.4, 27.8, 42.6, 67.0, 76.1,
79.6, 91.1, 92.7, 108.7, 127.0, 129.7, 137.0, 143.4, 202.7.
1988, 29, 6549±6552. Mootoo, D. R.; Date, V.; Fraser-Reid,
B. J. Am Chem. Soc. 1988, 110, 2662±2663.
3. Hoffmann, R. W. Chem. Rev. 1989, 89, 1841±1860.
Â
4. Addi, K. PhD thesis, Universite de Paris VI, Paris, 10 February
1995.
5. For the transformation of A to B (Eq. (3)), acidic work-up
(10% aqueous HCl) afforded B as a pure compound of
which the stereochemistry of the double bond is E. If after
addition of t-BuLi, work-up treatment consists by addition of
water alone, a 75/25 mixture of E and Z ole®ns was obtained.
The opening of the intermediate lithio derivative into an
alkoxy-allene followed by a non-selective recyclisation
explains this result,1 according to the precedent experiments
of Alexakis et al. cf: Alexakis, A. A.; Mangeney, P.; Normant,
J. F. Tetrahedron Lett. 1985, 26, 4197±4200. Alexakis, A.;
Marek, I.; Mangeney, P.; Normant, J. F. J. Am. Chem. Soc.
1990, 112, 8042±8047.
25. Oil [a]Dˆ122 (CHCl3, c 0.5), HR CI MS: calcd for
C18H26NO5S (MH1) 368.1531, found 368.1516; IR (neat)
nmax 3470, 1599, 1383, 1378 cm21 1H NMR (CDCl3,
;
250 MHz) d: 1.36 (3H, s), 1.48 (3H, s), 1.65 (3H, dd,
Jˆ6.5, 1.5 Hz), 2.25 (1H, d, Jˆ4 Hz, OH), 2.41 (3H, s),
3.48 (2H, d, Jˆ5 Hz), 3.81 (1H, dt, Jˆ4, 3.5 Hz), 4.35
(3H, m), 5.20 (1H, ddq, Jˆ15.0, 7.0, 1.5 Hz), 5.81 (1H,
ddq, Jˆ15.0, 6.5, 1 Hz), 7.27 (2H, d, Jˆ8 Hz), 7.66 (2H,
d, Jˆ8 Hz); 13C NMR (CDCl3, 62.5 MHz) d:17.4, 21.6,
24.8, 26.3, 44.3, 58.4, 69.2, 72.1, 110.0, 127.3, 127.8,
129.4, 130.5, 135.9, 143.1.
Â
6. Chouteau, F. PhD thesis, Universite de Paris-Sud, Centre
d'Orsay, 17 November 2000.
 Â
7. Skrydstrup, T.; Benechie, M.; Khuong-Huu, F. Tetrahedron
Lett. 1990, 31, 7145±7148.
4.2.27. Hydrogenolysis of 21b. A solution of 21b (49.4 mg,
0.1 mmol), AcONa (50 mg) and quinoline (I drop) in MeOH
(10 mL) was stirred under H2 atmosphere in the presence of
10% palladium on charcoal (10 mg). After absorption of
1 equiv. of H2, the catalysor was ®ltered off and the ®ltrate
diluted with H2O was extracted by CH2Cl2. Vacuum
evaporation of the organic layer led to a residue which
was puri®ed by ¯ash chromatography (CH2Cl2/MeOH 95/
5) to give 25 (30 mg, 80 %).
8. Nativi, C.; Taddei, M. J. Org. Chem. 1988, 53, 820±826.
9. Tamaru, Y.; Kawamura, S.; Tanak, K.; Yoshida, Z.
Tetrahedron Lett. 1984, 25, 1063±1066.
10. Lemieux, R. W.; Morgan, A. R. Can. J. Chem. 1965, 43,
2190±2198. Carlsohn, H. Angew. Chem. 1933, 46, 747.
 Â
11. Benechie, M.; Skrydstrup, T.; Khuong-Huu, F. Tetrahedron
Lett. 1991, 32, 7535±7537.
12. Asano, N.; Nash, R. J. .; Molyneux, R. J.; Fleet, G. W. J.
Tetrahedron: Asymmetry 2000, 11, 1645±1680.
13. Clauss, R.; Hunter, R. J. Chem. Soc., Perkin Trans. 1 1997,
71±76.
4.2.28. (2R,3R,4S,5S)-1-(4-Methylbenzenesulfonyl)-2-
[prop-E-enyl]-piperidine-3,4,5-triol (26). 1N HCl
(0.2 mL) was added to a solution of 25 (8 mg, 0.02 mmol)
in THF (0.2 mL). After 1 h at rt, alcalinisation by NaHCO3
and standard work-up (CH2Cl2) 26 was obtained (5 mg,
78%) as an oil [a]Dˆ19 (CHCl3, c 0.2), EI MS: m/z 312
14. Wilcox, J. C. Y.; Long, G. W.; Suh, H. Tetrahedron Lett.
1984, 25, 395±398.
15. Denmark, S. E.; Jones, T. K. J. Org. Chem. 1982, 47, 4595±
4597.
(M215); IR (neat) nmax 3402 cm21 1H NMR (CDCl3,
;
16. Corey, E. J.; Katzenellenbogen, J. A.; Posner, G. H. J. Am.
Chem. Soc. 1967, 89, 4245±4247.
250 MHz), d: 1.65 (3H, dd, Jˆ6.5, 1.5 Hz), 2.42 (3H, s),
2.93 (2H, m, OH), 3.19 (1H, d, Jˆ13 Hz), 3.56 (2H, m),
3.91 (3H, m), 4.77 (1H, broad s, OH), 5.20 (1H, ddq,
Jˆ15.0, 6.0, 1.5 Hz), 5.68 (1H, ddq, Jˆ15.0, 6.5, 1 Hz),
7.28 (2H, d, Jˆ8 Hz), 7.73 (2H, d, Jˆ8 Hz); 13C NMR
(CDCl3, 62.5 MHz) d:17.5, 21.6, 46.2, 58.7, 66.5, 69.0,
73.3, 127.7, 129.6, 131.1, 135.9, 143.1.
17. Crystallographic data for the structure reported in this paper
have been deposited in the Cambridge Crystallographic Data
Centre and allocated the deposition number CCDC 160962.
Copies of the data can be obtained, free of charge, on
application to the Director CCDC, 12 Union Road, Cambridge
CB2 1EZ, UK (Fax: 144-0-1223-336033 or e-mail:
deposit@ccdc.cam.ac.uk).
18. Boyd, D. R.; Sharma, N. D.; Barr, S. A.; Dalton, H.; Chima, J.;
Whited, G.; Seemayer, R. J. Am. Chem. Soc. 1994, 116, 1147±
1148.
References
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È
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1. Part 1: Stereoselective allylic transposition by means of
 Â
n-pentenyl ethers, Addi, K.; Skrydstrup, T.; Benechie, M.;
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