Ruthenium catalyzed ring rearrangement: A rapid entry to substituted aza- and oxacycles

Article abstract of DOI:10.1016/S0040-4020(02)00832-3

A ring-closing metathesis (RCM) and a ring-opening metathesis (ROM) are combined in a domino process giving access to a variety of aza- and oxacyles, equipped with highly functionalized side chains, starting from readily accessible cyclopentenyl or cycloh

Full text of DOI:10.1016/S0040-4020(02)00832-3

Tetrahedron 58 (2002) 7503–7518
Ruthenium catalyzed ring rearrangement: a rapid entry to
substituted aza- and oxacycles
Huib Ovaa,a Christian Stapper,b Gijs A. van der Marel,a Hermen S. Overkleeft,a
Jacques H. van Booma and Siegfried Blechertb
,
*
aGorlaeus Laboratories, Leiden Institute of Chemistry, P.O. Box 9502, 2300 RA Leiden, The Netherlands
¨ ¨
Institut fur Chemie, Technische Universitat Berlin, Strasse des 17, Juni 135, D-10623 Berlin, Germany
b
Received 12 June 2002; revised 4 July 2002; accepted 5 July 2002
Abstract—A ring-closing metathesis (RCM) and a ring-opening metathesis (ROM) are combined in a domino process giving access to a
variety of aza- and oxacyles, equipped with highly functionalized side chains, starting from readily accessible cyclopentenyl or
cycloheptenyl ethers and amines. The role of different protective groups is examined as well as the influence of the relative configuration of
stereocenters of the substrate molecules. Substituted 2,5-dihydro-furans and -pyrroles, 1,2,5,6-tetrahydropyranes and -pyridines as well as
2,3,4,7-tetrahydrooxepines are available via this methodology. q 2002 Elsevier Science Ltd. All rights reserved.
1. Introduction
cyclopentene and cycloheptene derived precursors via
RRM.
A new method to convert enantiopure carbocycles into
substituted heterocycles comprising a combination of ring-
closing metathesis (RCM) and ring-opening metathesis
(ROM) in a single ring rearrangement, has recently
emerged.1 In this reaction, the chirality embedded in the
carbocyclic starting material is completely transferred into
the product side chain. Carbocyclic olefins are frequently
used precursors because the configuration of stereocenters
can easily be controlled. The effectiveness of ROM–RCM
was illustrated by the synthesis of different alkaloids and
heterocycles.2
2. Results and discussion
In a first study, protected O-allylcyclopentenetriols and
N-allylcyclopentenediols (Scheme 2) were subjected to the
olefin metathesis conditions. Palladium(0)-catalyzed allylic
amination of allylic carbonate 2 (derived from racemic or
enantiopure 14) with N-2-nitrobenzenesulfonyl N-allyl-
amine using [Pd2(dba)3]·CHCl3 and Trost’s ligand (R,R)-
85 in the presence of 3 equiv. of NEt3 afforded homo-
geneous 3 (e.e. .99.5%)6 in 95% yield.
The behavior of higher substituted cycloolefins in ring
rearrangement metathesis (RRM) reactions is of consider-
able interest (Scheme 1), since such substrates would give
access to chiral heterocyclic systems with densely sub-
stituted side chains of defined stereochemistry. Therefore,
the length of the side chains in the products can be
controlled by the size of the carbocyclic starting material.
The ring size of the heterocycle is dependent on the length
of the side chain in the substrate molecule.
It has been shown that 2, equipped with a bridging
isopropylidene acetal, does not undergo a ring rearrange-
ment probably for both steric and thermodynamic reasons:
The starting material 3 would be transformed, via a strained
tetracyclic intermediate, in a dioxolane product 17 that lacks
a thermodynamically favorable [5,5]-cis-fused bicyclic
system (Scheme 3).
We herein report on the synthesis of chiral 1,2,5,6-
tetrahydropyridines, 2,5-dihydro-1H-pyrroles, 1,2,5,6-tetra-
hydropyrans, 2,5-dihydro-1H-furans,3 2,5-dihydro-1H-pyr-
rol-2-ylmethyl-2,3,4,7-tetrahydrooxepines and 1,2,5,6-
tetrahydropyridylmethyl-2,3,4,7-tetrahydrooxepines from
The latter barrier can be avoided by the use of acyclic
Keywords: asymmetric synthesis; rearrangement; ruthenium; heterocycles.
*
Corresponding author. Tel.: þ49-30-31422255; fax: þ49-30-31423619;
e-mail: blechert@chem.tu-berlin.de
Scheme 1. ROM–RCM sequence.
0040–4020/02/$ - see front matter q 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020(02)00832-3

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H. Ovaa et al. / Tetrahedron 58 (2002) 7503–7518
Scheme 2. Reagents and conditions: (a) MeOCOCl, CH2Cl2/pyridine, 08C, 97%; (b) [Pd2(dba)3]·CHCl3, (R,R)-8, N-nosyl-N-allylamine, NEt3, THF, 210 to
08C, 95%; (c) HOAc/H2O, 1008C; (d) Ac2O, pyridine, 99%; (e) TBSCl, imidazole, DMF, !5: 83%, !10: 82%, !13: 70%; (f) [Ru] (5 mol%), CH2Cl2, C2H4,
!11: 100%, !16: 96%; (g) allyl bromide, NaH, DMF, 08C, 95%; (h) p-MeOC6H4CH2Cl, NaH, DMF, 08C, 97%; (i) DDQ, CH2Cl2/H2O, 08C, 99%;
(j) Pd(OAc)2, dppp, 3-methoxyallene, NEt3, CH3CN, reflux, 97%.
protective groups. Deacetalization of 3 was followed by
peracetylation giving 4 in 99% yield. Under ring rearrange-
ment conditions, the dihydro-1H-pyrrole 6, however, was
found to be in an equilibrium with the starting diacetate 4
dihydropyrrole 7 was obtained in the subsequent ring
rearrangement step.
We next focused our attention to the synthesis of
monocyclic oxacycles (i.e. ethers and acetals) via ring
rearrangement. Cyclopentenylalcohol 1 was therefore
alkylated with allyl bromide giving 9 (95%). In analogy to
3, allyl ether 9 does not undergo ring rearrangement either.
Moreover, when a solution of [Ru] catalyst and 9 was boiled
under reflux in the absence of ethylene, a product resulting
1
(6/4¼7:3) as determined by H NMR spectrum. In earlier
studies, we have shown that bulky O-protective groups can
shift the RRM equilibrium quantitatively to the product-
side.7 Therefore, the sterically more hindered TBDMS
group was used. TBDMS ether 5 (83%) was obtained by a
deacetalization and persilylation sequence. A 96% yield of

H. Ovaa et al. / Tetrahedron 58 (2002) 7503–7518
7505
Scheme 3. Postulated tetracyclic [Ru]-intermediate.
from homodimerization by cross-metathesis (CM) was
isolated as a single isomer in 26% yield (50% of 9 was
reisolated). Deacetalization of 9 and persilylation of the
resulting free diol afforded ether 10 (82%). Ring rearrange-
ment of 10 gave the expected dihydrofuran 11 in
quantitative yield.
The allylic acetal 15 was synthesized in order to obtain
lactols by ring rearrangement. Protective group manipula-
tions of 1 and subsequent palladium(II) catalyzed reaction
of the resulting alcohol 14 with methoxyallene8 afforded
two diastereomers of acetal 15 in 97% yield. The ring
rearrangement gave the acid labile9 acetal 16 in 96% yield.
This demonstrates the general applicability of substituted
side chains in such RRM reactions.
The ease of formation of five-membered aza- and oxacycles,
raised the question whether also six- or seven-membered
rings could be obtained in this manner. For a pilot study
(Scheme 4), the amines 19 and 21 and the ethers 27 and 29
were synthesized the same way as 4 and 9 from 2 and 1,
respectively. Ring rearrangement of 19 and 27 proceeded
quantitatively to afford tetrahydropyridine 22 and tetra-
hydropyran 30, respectively. In addition, we established that
differentiation between the two acetate groups in 22, which
improves its synthetic potential, could easily be effected by
a deprotection–silylation procedure to afford 24. The
identity of 24 was further established by reacetylation to 25.
In the case of the pentenylamine 21 and of the pentenylether
29, ring rearrangement under the olefin metathesis con-
ditions failed. The equilibria are on the side of the starting
materials. The ring strains of seven-membered heterocycles
Scheme 4. Reagents and conditions: (a) [Pd2(dba)3]·CHCl3, (R,R)-8,
N-nosyl-N-(but-3-enyl)-amine NEt3, THF, 210 to 08C, !18: 93%, or
[Pd2(dba)3]·CHCl3, dppb, N-nosyl-N-(pent-4-enyl)-amine, NEt3, THF, 210
to 08C, !20: 100%; (b) HOAc/H2O, 1008C; (c) Ac2O, pyridine, !19: 99%,
!21: 100%; (d) [Ru] (5 mol%), CH2Cl2, C2H4, !22: 100%, !30: 100%;
(e) NaOMe, MeOH, 93%; (f) TBSCl, imidazole, DMF, !24: 95%, !27:
82%, !29: 87%; (g) but-3-enyl bromide, KH, DMPU/THF, 08C, !26:
65%, or pent-4-enyl bromide, KH, DMPU/THF, 08C, !28: 96%.
Scheme 5. Synthesis of indolizidine 33. Reagents and conditions:
(a) HOAc/H2O, 808C; TBSCl, imidazole, DMF, rt, 75%; (b) [Ru]
(4 mol%), CH2Cl2, C2H4, rt, 100%; (c) K2OsO4·2H2O, NMO, acetone/H2O,
rt, 80%; (d) NaIO4, MeOH/H2O, 08C; NaBH4 (aq.), 08C, 99%; (e) TsCl,
pyridine, DMAP, rt, 71%; (f) PhSH, K2CO3, DMF, 08C; (g) TBAF, THF, rt
(87% steps f and g).

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H. Ovaa et al. / Tetrahedron 58 (2002) 7503–7518
Scheme 6. Reagents and conditions: (a) EtOCOCl, CH2Cl2/pyridine, 08C to rt, !35: 92%, !37: 89%; (b) [Pd2(dba)3]·CHCl3, dppb, allylamine, THF, rt, 80%;
(c) [Ru] (5 mol%), CH2Cl2, !38: 80%, !41: 92%, !47: 94%, !48: 86%, !49: 92%; (d) [Pd2(dba)3]·CHCl3, dppb, N-tosyl-N-allylamine, NaH, THF/DMF
(3:1), 508C, 82%; (e) benzoyl chloride, CH2Cl2, DMAP, rt, 91%; (f) N-nosyl-N-alkenylamine, PPh3, DEAD, THF, 08C to rt, !42: 93%, !43: 89%, !45: 74%;
(g) PhSH, K2CO3, DMF, 708C then benzyl chloroformate, 08C, !44: 87%, !46: 78%.
are obviously much higher than those of the cyclopentene
starting materials.
ring rearrangement, access to a variety of heterocycles of
different size and substitution pattern.
In one example the indolizidine 33 (Scheme 5) could be
obtained in five steps from tetrahydropyridine 32, the
product of a quantitative RCM–ROM of 31 under influence
of Grubbs-I catalyst and ethylene.2a
At first, the synthesis of dihydropyrrole derivatives with
different configurations was examined. The amines 36, 37,
39, 40 and 42 were stereoselectively prepared starting from
34 either by h3-allyl-Pd(0) substitution of an allylic
carbonate or acetate or by Mitsunobu reaction of an allylic
alcohol. These substrates differ in the stereochemistry and
N- and O-protecting groups. A complete protection of free
alcohols or amines was necessary for the metathesis
reaction. In a pilot study, ring rearrangements starting
from the amine 36 or alcohol 39 proved to be abortive.
Coordination of the amino or hydroxyl group to the catalyst
may be responsible for the inhibition of the metathesis
reaction.
In order to enable the formation of larger heterocyclic ring
systems, i.e. tetrahydroazepines or -oxepines, higher
cycloolefins should be employed. An increase in free
energy of the starting material should shift the equilibrium
to the product side. In a further study, the ring size of the
starting compounds was varied giving access to larger
heterocycles and longer side chains. Besides substituted
cyclohexenes, especially chiral substituted cycloheptenes
were taken into account as interesting starting materials for
natural product synthesis. We concentrated our investi-
gations on the ring sizes accessible from cycloheptene
precursors, on the influences of different N-protective
groups and on different configurations of the stereocenters.
In the current study, we restricted ourselves to N-hetero-
cyclic systems. Compound 34 (Scheme 6) was considered as
a suitable precursor because it can easily be prepared in both
enantiomeric forms from tropone10 according to literature
protocols. Simple derivatizations of 34 should give, after
Ring rearrangement of the protected amines 37, 40 and 42
gave the desired dihydropyrroles 38 (80%), 41 (92%) and 47
(94%). Tetrahydropyridines were also accessible via this
method: the but-3-enylamines 43 and 44 gave the desired
products 48 (86%) and 49 (92%). We found that the
N-benzyloxycarbonyl protected amine 44 gave better yields
than the N-nosyl protected derivative 43, consistent with the
results of former studies.11 Compound 44 (87%) was easily
prepared from 43 in a one-pot procedure with PhSH and

H. Ovaa et al. / Tetrahedron 58 (2002) 7503–7518
7507
K2CO3 in DMF at 708C12 followed by addition of benzyl
chloroformate at 08C. Generally, it was established that
RRM of cycloheptenylamines does not require the addition
of ethylene, provided that reactions are carried out in boiling
dichloromethane.
demonstrated gives access to an array of enantiopure,
substituted heterocycles that cannot easily be obtained by
other methods. The concept of tandem ring rearrangement is
currently being extended to other ring sizes and substitution
patterns for natural product synthesis.
As outlined above, the synthesis of tetrahydroazepines from
cycloheptene precursors was considered a promising goal.
Thus, the pent-4-enylamines 45 and 46 were prepared and
subjected to the olefin metathesis conditions, but the
reaction failed. The rearrangement equilibrium is still on
the side of the starting material.
3. Experimental
1H NMR spectra (200, 400, 500 MHz) and 13C NMR spectra
(50, 100, 125 MHz) were recorded on either a BRUKER AC
200 or 400 or a BRUKER DRX 500 spectrometer. Mass
spectra were obtained by electron impact (EI/CI) at 70 eV
on a FINNIGAN MAT 95 SQ and IR spectra by attenuated
total reflectance (ATR) on a NICOLET FT-IR 750
spectrometer. Optical rotations were determined on a
PERKIN–ELMER 341 polarimeter using a 10 cm path
length cell. Flash chromatography (FC) was performed on
MERCK silica gel 60 (0.040–0.063 mm). MTBE¼methyl
tert-butyl ether. Chemicals were purchased from ALDRICH
or MERCK and were used without further purification.
In order to enable seven-membered ring formation to be
productive in preparative terms via RRM strategy, it was
decided to combine ring-rearrangement with RCM in order
to provide an additional thermodynamic sink13 (i.e. removal
of ethylene liberated in this tandem process may shift the
equilibrium in favor of the desired product). Therefore,
allyloxy substituted cycloheptenylamines 53–55 (Scheme
7) were prepared from 42–44 by desilylation (!50–52)
and subsequent O-allylation.14 Subjecting 53–55 to
Grubbs’ catalyst [Ru] in boiling dichloromethane afforded
substituted tetrahydrooxepines 56 (93%), 57 (74%) and 58
(92%).
3.1. General procedures
(A) Palladium catalyzed allylic aminations using the ligand
(R,R)-8. The appropriate allylic carbonate (1 mmol),
N-nosyl alkenylamine (1.3 mmol) and Et3N (3 mmol)
were dissolved in THF (5 mL) and cooled to 2108C. In a
separate (Schlenk) flask [Pd2(dba)3]·CHCl3 (40 mg,
0.038 mmol) and ligand (R,R)-8 (106 mg, 0.153 mmol)
were dissolved in THF (4 mL) and stirred until the solution
became red–orange (30 min). Quantities of this stock
solution of catalyst (0.010 M in Pd) were added dropwise
to the cooled reaction mixture by a syringe and were stirred
overnight at 08C, the reaction mixture was then allowed to
warm slowly to rt. Reaction progress was monitored by 1H
NMR spectra of small aliquots that are taken from the
reaction mixture and concentrated under reduced pressure.
Upon completion, the reaction mixture was concentrated
under reduced pressure and purified by FC (MTBE/hexane
or (CH2Cl2).
In conclusion, it has been shown that derivatives of
cyclopentenyl alcohol 1 and cycloheptenyl alcohol 34 can
serve as a platform, capable of undergoing ruthenium
catalyzed ring rearrangements to give five-, six- and seven-
membered heterocycles. Furthermore, it was established
that the equilibrium reached in this, in principle reversible
reaction, is dependent on the choice of protecting groups.
Substituted tetrahydrooxepines can be obtained provided
the ring rearrangement is accompanied by an additional
thermodynamic driving force (RCM). The method thus
(B) Deacetalization of compounds 3, 9, 12, 18, 20, 26 and
28. Isopropylidene moieties were removed by dissolving
1 mmol of compound in acetic acid (4 mL) followed by
slow addition of water (1 mL). The solution was heated to
80–1008C for 20–30 min. Reaction progress was moni-
tored by TLC (MTBE). Upon completion, the reaction
mixture was concentrated under high vacuum and directly
used in the next step without further purification.
(C) Acetylation to compounds 4, 19, 21, 25. Alcohols or
diols (1 mmol) were dissolved in pyridine (2 mL) and acetic
anhydride (1 mL) was added. Reactions were monitored by
TLC (MTBE). Upon completion, toluene was added (5 mL)
and the solution was concentrated under reduced pressure.
This process was repeated twice. FC (MTBE–hexane)
afforded the homogeneous acetylated compounds.
(D) Mono- or bis-silylation to compounds 5, 10, 13, 24, 27,
and 29. Alcohols or diols (1 mmol) and imidazole
(10 equiv.) were dissolved in DMF (5 mL); tert-butyl
dimethylsilanyl chloride (TBDMSCl, 2.2–2.3 mmol) was
Scheme 7. Reagents and conditions: (a) TBAF, THF, 08C, !50: 85%,
!51: 89%, !52: 88%; (b) allyl trichloroacetimidate, cat. CF3SO3H,
CH2Cl2/cyclohexane (1:1), rt, !53: 52%, !54: 38%, !55: 37%; (c) [Ru]
(5 mol%), CH2Cl2, reflux, !56: 93%, !57: 74%, !58: 92%.

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H. Ovaa et al. / Tetrahedron 58 (2002) 7503–7518
added in one portion and the solution was stirred overnight.
Reaction progress was monitored by TLC (MTBE–
hexane). Heating the DMF solutions to 508C, generally
completes the reactions in one hour, without deterioration in
yield. After completion, hexane and MTBE were added and
the solution was poured into water and extracted twice with
water. The organic layer was separated, dried (MgSO4),
filtered and concentrated under reduced pressure. FC
(MTBE–hexane) gave the homogeneous target compounds.
replaced by a tosyl group ((i) PhSH, K2CO3, DMF. (ii) TsCl,
pyr.) in order to facilitate separation of the enantiomers on a
Chiralcel OD Gold column (0.5% i PrOH in hexane,
0.9 mL/min, 218 nm).
3.1.3. N-Allyl-N-{(1R,4R,5S )-4,5-isopropylidenedioxy-
cyclopent-2-enyl)}-(4-methylbenzene)
sulfonamide.
Compound 3 (85 mg, 0.22 mmol) was dissolved in DMF
(2 mL). K2CO3 (61 mg, 0.5 mmol) was added followed by
PhSH (300 mL, 1 M in DMF). The suspension was quickly
heated using a heat gun until gas evolution occurred. After
5 min, the mixture was cooled and 1 M NaOH and Et2O
were added. The organic phase was separated and extracted
with 0.1 M HCl. The aqueous phase was separated and
immediately made basic by the addition of 1 M NaOH. The
aqueous phase was extracted with Et2O. This whole process
was repeated on the combined aqueous phases. Combined
organic phases were dried (Na2SO4), filtered and concen-
trated. The residue was dissolved in pyridine (1 mL), and
tosyl chloride (65 mg, 0.34 mmol) was added. The mixture
was heated to 508C for 2 h after which MTBE and a
saturated NH4Cl solution were added. The organic phase
was separated and washed with additional NH4Cl solution
and brine, then, it was separated, dried (MgSO4), filtered
and concentrated. The product (Rf¼0.25 MTBE/hexane 1:4
v/v) was purified by FC (10!20% MTBE in hexane) to
afford the homogeneous title compound (60 mg, 75%).
(E) RCM–ROM (ring rearrangement) of compounds 4, 5,
10, 15, 19, 27 and 31. The substrate (1 mmol) was
transferred into a BRAUN MB 150B glove box15 and
dissolved in dry CH2Cl2; ethylene gas (25 mL) was bubbled
through the stirred solution slowly by a syringe and Grubbs’
pre-catalyst Cl2(PCy3)2RuvCHPh [Ru] 20–25 mg
(4–5 mol%) was added. Reaction progress was monitored
by NMR spectra of small aliquots that were taken from the
reaction mixture and concentrated under reduced pressure.
1
Typically, solutions were stirred overnight upon which H
NMR spectra revealed total transformation of all starting
material. The solutions were taken out of the glove box,15
concentrated and purified by FC (MTBE–hexane).
3.1.1. (2)-Carbonic acid (1R,4R,5R )-4,5-isopropylidene-
dioxycyclopent-2-enyl ester methyl ester [(2)-2]. Alcohol
1 (372.5 mg, 2.35 mmol) was dissolved in CH2Cl2 (10 mL)
and pyridine (1 mL) and cooled to 08C. Methyl chloro-
formate (270 mL, 3.5 mmol) was added. After 1 h, TLC
analysis (MTBE) showed complete conversion to a less
polar product. The mixture was poured into saturated NH4Cl
solution and extracted with MTBE. The organic phase was
subsequently washed with water, dried (MgSO4), filtered
and concentrated. FC (15% MTBE in hexane) gave
homogeneous carbonate 2 (495.6 mg, 97%). 1H NMR
(400 MHz): d 6.14 (d, J¼6 Hz, 1H), 5.90 (dd, J¼6, 2 Hz,
1H), 5.50 (d, J¼2 Hz, 1H), 5.24 (d, J¼6 Hz, 1H), 4.61 (d,
J¼6 Hz, 1H), 3.78 (s, 3H), 1.30 (s, 3H), 1.28 (s, 3H); 13C
NMR (CDCl3): d 155.1, 138.3, 130.6, 112.3, 86.3, 83.9,
83.0, 54.9, 27.2, 25.7; IR: n 3066, 1749, 1257, 928,
A similar procedure was used for the racemate, the
enantiomers of which could be separated on a Chiralcel
OD Gold column (0.5% i PrOH in hexane, 0.9 mL/min,
218 nm, DRt¼2 min.). The e.e. of the levorotatory title
compound was determined to be higher than 95%. This
compound had a retention time of ,20 min, whereas the
enantiomer had a retention time of ,22 min. 1H NMR
(500 MHz, CDCl3): d 7.75 (d, J¼7 Hz, 2H), 7.29 (d,
J¼7 Hz, 2H), 5.98 (m, 1H), 5.73 (m, 1H), 5.45 (m, 1H), 5.10
(m, 3H), 4.89 (s, 1H), 4.40 (d, J¼8 Hz, 1H), 3.67 (dd, J¼7,
16 Hz, 1H), 3.55 (dd, J¼7, 16 Hz, 1H), 2.40 (s, 3H), 1.29,
1.30 (2s, 6H); 13C NMR (CDCl3): d 143.4, 137.5, 136.2,
134.6, 129.6, 127.4, 117.9, 111.3, 84.3, 82.8, 69.8, 48.4,
27.2, 25.4, 21.5; [a ]2D0¼235.28 (c 1, CHCl3).
867 cm21
;
HRMS: calcd for C9H11O5 [M2CH3]þ:
199.0606, found: 199.0607; [a]2D0¼2160.48 (c 1, CHCl3).
3.1.2. N-Allyl-N-{(1R,4R,5S )-4,5-isopropylidenedioxy-
cycopent-2-enyl)}-2-nitrobenzene sulfonamide (3). Pd
catalyzed allylic amination of 2 using ligand (R,R)-8
according to method A followed by purification by silica
gel chromatography (0!5% MeOH in CH2Cl2) gave
homogeneous compound 3, 629 mg (95%). The e.e. was
determined by chiral HPLC of the corresponding 4-methyl-
benzene sulfonamide and compared with the racemate
(prepared with the dppb ligand, 70% yield). 1H NMR
(400 MHz, CDCl3): d 8.16 (m, 1H), 7.68 (m, 3H), 6.03 (dt,
J¼2, 6 Hz, 1H), 5.79 (m, 1H), 5.64 (dd, J¼3, 9 Hz, 1H),
5.15 (m, 3H), 4.89 (d, J¼2 Hz, 1H), 4.57 (d, J¼8 Hz, 1H),
3.90 (tdd, J¼2, 7, 16 Hz, 1H), 3.68 (dd, J¼7, 16 Hz, 1H),
1.29, 1.30 (2s, 6H); 13C NMR (CDCl3): d 147.8, 137.0,
134.3, 133.7, 131.7, 131.6, 130.5, 124.2, 118.7, 111.5, 84.3,
83.3, 69.8, 48.6, 27.2, 25.2; IR: n 3084, 1543, 1372,
1164 cm21; HRMS: calcd for C16H17N2O6S [M2CH3]þ:
379.0807, found 379.0810.
3.1.4. Acetic acid (1S,2R,5R )-2-acetoxy-5-[allyl-(2-nitro-
benzenesulfonyl)-amino]-cyclopent-3-enyl ester (4).
Methods B and C with 3 gave 4 in 99% yield after FC
(MTBE). 1H NMR (500 MHz, CDCl3): d 8.04 (m, 1H), 7.67
(m, 3H), 5.96 (m, 2H), 5.71 (m, 1H), 5.61 (m, 1H), 5.19 (m,
2H), 5.09 (m, 2H), 3.81 (m, 2H), 1.98 (s, 3H), 1.94 (s, 3H);
13C NMR (CDCl3): d 170.0, 169.8, 147.8, 133.3, 136.1,
134.0, 133.8, 131.7, 131.4, 131.2, 124.4, 118.5, 72.8, 72.4,
65.5, 47.4, 20.6, 20.3; IR: n 3080, 1743, 1543, 1371, 1242,
1165; HRMS: calcd for C18H20N2O8S [M]þ: 424.0940,
found: 424.0942.
3.1.5. N-Allyl-N-{(1R,4R,5S )-4,5-bis-(tert-butyl-di-
methylsilanyloxy)-cyclopent-2-enyl}-2-nitrobenzene sul-
fonamide (5). Methods B and D with 3 (66.9 mg,
0.17 mmol) gave 5 (84 mg; 83%) after FC (10!50%
1
MTBE in hexane). Rf¼0.5 (MTBE/hexane 1/1). H NMR
(400 MHz, CDCl3): d 8.05 (m, 1H), 7.64 (m, 3H), 5.97 (dt,
J¼2, 6 Hz, 1H), 5.82 (m, 1H), 5.76 (dd, J¼2, 7 Hz, 1H),
5.10 (m, 2H), 4.95 (m, 1H), 4.47 (dd, J¼3, 8 Hz, 1H), 4.10
For the determination of the e.e. of 3 the nosyl group was

H. Ovaa et al. / Tetrahedron 58 (2002) 7503–7518
7509
(t, J¼6 Hz, 1H), 3.89 (m, 2H), 0.86, 0.90 (2s, 18H), 0.07,
0.06, 0.05, 0.04 (4s, 12H); 13C NMR (CDCl3): d 135.3,
133.6, 133.3, 131.5, 131.4, 124.1, 117.9, 75.8, 73.8, 65.5,
47.7, 26.0, 25.8, 18.2, 17.9, 23.7, 24.0, 24.1; IR: n 3081,
1546, 1361, 1167 cm21; HRMS: calcd for C26H44N2O6SSi2
[M]þ: 568.2459, found: 568.2458.
[MþNa]þ. HRMS: calcd for C20H40O3Si2 [M]þ:
384.2516, found: 384.2515.
3.1.10. (1)-(R )-2-[(1S,2R )-1,2-Bis-(tert-butyl-dimethyl-
silanyloxy)-but-3-enyl]-2,5-dihydrofuran
[(1)-11)].
Method E with compound 10 (390 mg) gave 11 (390 mg,
100%), after FC (0!15% MTBE in hexane) Rf¼0.60
1
3.1.6. Acetic acid (1S,2R )-2-acetoxy-1-[(R )-1-(2-nitro-
benzenesulfonyl)-2,5-dihydro-1H-pyrrol-2-yl]-but-3-
enyl ester (6). Method E with compound 4 gave after FC
(MTBE) an inseparable mixture (180 mg, 100%) of 4 and
(MTBE/hexane 1/9 v/v). H NMR (500 MHz, CDCl3): d
5.89 (m, 1H), 5.75 (m, 1H), 5.85 (m, 1H), 5.19 (d, J¼17 Hz,
1H), 5.10 (d, J¼11 Hz, 1H), 4.90 (m, 1H), 4.62 (m, 2H),
4.18 (dt, J¼1, 7.5 Hz, 1H), 3.55 (t, J¼5 Hz, 1H), 0.79 (s,
9H), 0.72 (s, 9H), 0.16 (s, 3H), 0.08 (s, 6H), 0.05 (s, 3H); 13C
NMR (CDCl3): d 139.3, 134.6, 127.5, 115.8, 86.9, 78.5,
75.3, 75.1, 26.0, 25.95, 18.25, 18.2, 24.1, 24.4, 24.8,
24.0; IR: n 3078, 1253, 1130, 1079 cm21; MS (CI): m/z
407.2 [MþNa]þ; HRMS: calcd for C19H37O3Si2
1
product 6 (4/6¼28:72). H NMR (500 MHz, CD2Cl2): d
7.96 (m, 1H), 7.68 (m, 2H), 7.61 (m, 1H), 5.01 (m, 1H), 5.86
(m, 1H), 5.74 (m, 1H), 5.31 (m, 3H), 5.16 (m, 1H), 5.04 (m,
1H), 4.36 (m, 1H), 4.09 (m, 1H), 2.06 (s, 3H), 2.04 (s, 3H);
13C NMR (CDCl3): d 170.1, 169.5, 149.0, 133.9, 132.2,
131.5, 130.6, 128.0, 126.6, 124.1, 119.9, 73.4, 72.5, 66.7,
55.8, 20.9, 20.7.
[M2CH3]þ:
m/z
369.2281,
found:
369.2287;
[a ]2D0¼þ61.48 (c 1, CHCl3).
3.1.7. (R )-2-[(1S,2R)-1,2-Bis-(tert-butyl-dimethylsilanyl-
oxy)-but-3-enyl]-1-(2-nitrobenzenesulfonyl)-2,5-dihy-
3.1.11. (3R,4S,5R )-3-(4-Methoxybenzyloxy)-4,5-(isopro-
pylidenedioxy)-cyclopent-1-ene (12). Compound
1
dro-1H-pyrrole (7). Method
E
with
5
(330 mg,
(502 mg, 3.17 mmol), was dissolved in DMF (10 mL) and
cooled to 08C. NaH (60% in mineral oil, 200 mg, 5 mmol)
was added followed by 4-methoxybenzyl chloride
(0.39 mL, 3.8 mmol). After 1 h a few drops of MeOH
were added and the solution was allowed to warm to rt over
30 min. Et2O and water were added. The organic phase was
separated and washed with two portions of water. The
organic phase was separated, dried (MgSO4), filtered and
concentrated. FC (25% MTBE in hexane) afforded homo-
geneous 12 (856 mg (97%). 1H NMR (200 MHz, CDCl3): d
7.29 (d, J¼7 Hz, 2H), 6.88 (d, J¼7 Hz, 2H), 6.03 (m, 1H),
5.91 (m, 1H), 5.28 (m, 1H), 4.47 (m, 3H), 3.82 (m, 1H), 3.80
(s, 3H), 1.41 (s, 3H), 1.37 (s, 3H); 13C NMR (CDCl3): d
135.4, 133.1, 129.8, 129.3, 113.7, 109.0, 87.7, 84.1, 83.2,
71.2, 55.1, 27.1, 25.5; IR: n 3062, 1612, 1513, 1369, 1247,
1027, 1048, 1036 cm21; HRMS: calcd for C16H20O4 [M]þ:
276.1362, found: 276.1366.
0.58 mmol), gave 7 in 96% yield after FC (10!50%
MTBE in hexane). Rf¼0.35 (MTBE/hexane 1:1). 1H
NMR (400 MHz, CD2Cl2): d 7.72 (m, 1H), 7.58 (m, 3H),
5.82 (m, 1H), 5.78 (m, 1H), 5.59 (m, 1H), 5.01 (m, 2H), 4.61
(m, 1H), 4.23 (m, 1H), 4.20 (m, 1H), 4.12 (dd, J¼2, 5 Hz,
1H), 4.08 (m, 1H), 0.82, 0.80 (2s, 18H), 0.04 (s, 6H), 0.02,
20.04 (2s, 6H); 13C NMR (CDCl3): d 137.8, 133.6, 131.5,
129.7, 128.5, 124.34, 124.27, 115.9, 78.5, 74.5, 70.4,
56.2, 25.95, 25.87, 18.2, 18.1, 24.3, 24.5, 24.6, 25.0;
IR: n 3078, 1544, 1372, 1349, 1162 cm21; HRMS: calcd
for C25H41N2O6SSi2 [M2CH3]þ: 553.2223 found:
553.2222.
3.1.8. (3R,4S,5R )-3-Allyloxy-4,5-isopropylidenedioxy-
cyclopent-1-ene (9). Compound 1 (0.87 g, 5.6 mmol) in
DMF or THF (25 mL) was cooled to 08C. Allyl bromide
(720 mg, 6 mmol) was added followed by NaH (60% in
mineral oil, 280 mg, 7 mmol). After 30 min, a few drops of
MeOH were added. After 10 min, water (100 mL) and Et2O
(100 mL) were added. The organic phase was separated and
washed with two portions of water then it was separated,
dried (MgSO4) and concentrated in vacuo. FC (10!50%
MTBE in hexane) afforded homogeneous (volatile) 9
3.1.12. (3R,4S,5R )-4,5-Bis-(tert-butyl-dimethylsilanyl-
oxy)-3-(4-methoxybenzyloxy)-cyclopentene (13). Acetal
12 (0.83 g, 3 mmol) was dissolved in HOAc (4 mL), the
solution was heated to 758C and water (1 mL) was added.
The resulting solution was kept at 758C for 20 min after
which toluene was added. Then, the solution was evaporated
in vacuo and dried under high vacuum. Method D then gave
the homogeneous 13 (0.99 g, 70%) after FC. 1H NMR
(500 MHz, CDCl3): d 7.29 (d, J¼7 Hz, 2H), 6.90 (d,
J¼7 Hz, 2H), 5.96 (m, 2H), 4.54 (d, J¼12 Hz, 1H), 4.52 (m,
3H), 4.04 (m, 1H), 3.85 (s, 3H), 0.95 (s, 9H), 0.89 (s, 9H),
0.11, 0.12, 0.09, 0.07 (4s, 12H); 13C NMR (CDCl3): d 159.1,
134.7, 133.9, 130.7, 129.3, 113.7, 87.5, 78.9, 74.7, 71.9,
55.3, 26.0, 18.3, 24.3, 24.8; IR: n 3061, 1613, 1514, 1361,
1
(1.05 g, 5.3 mmol, 95%). H NMR (400 MHz, CDCl3): d
6.04 (d, J¼6 Hz, 1H), 5.94 (m, 2H), 5.26 (m, 3H), 4.56 (d,
J¼6 Hz, 1H), 4.48 (s, 1H), 4.12 (m, 1H), 4.05 (m, 1H), 1.43,
1.36 (2s, 6H); 13C NMR (CDCl3): d 135.6, 134.3, 133.0,
117.3, 111.6, 88.0, 84.1, 83.1, 70.5, 27.2, 25.5.
3.1.9. (3R,4S,5R )-3-Allyloxy-4,5-bis-(tert-butyl-di-
methylsilanyloxy)-cyclopent-1-ene (10). Compound 9
(117 mg, 0.62 mmol) was treated according to methods B
and D to give after FC (0!10% MTBE in hexane)
homogeneous 10 (195 mg, 82%). Rf¼0.65 (MTBE/hexane
1/9 v/v). 1H NMR (400 MHz, CDCl3): d 5.97 (m, 3H), 5.32
(m, 1H), 5.18 (m, 1H), 4.53 (ddd, J¼1, 3, 6 Hz, 1H), 4.45
(m, 1H), 4.09 (dt, J¼1, 6 Hz, 2H), 3.86 (t, J¼5 Hz, 1H),
0.92 (s, 9H), 0.88 (s, 9H), 0.14, 0.13, 0.10, 0.08 (4s, 12H);
13C NMR (CDCl3): d 135.1, 134.6, 133.8, 116.7, 87.5, 78.8,
74.7, 71.2, 26.0, 18.3, 24.3, 24.4, 24.8; IR: n 3096, 3077,
1547, 1373, 1253, 1171 cm21; MS (CI): m/z 407.3
1249, 1156, 1125, 1083 cm21
;
HRMS: calcd for
C25H44O4Si2 [M]þ: 464.2778, found: 464.2775.
3.1.13. (1R,4R,5S )-4,5-Bis-(tert-butyl-dimethylsilanyl-
oxy)-cyclopent-2-enol (14). Compound 13 (196.3 mg,
0.425 mmol) was dissolved in CH2Cl2 (3 mL) and water
was added (3 mL). This mixture was cooled to 08C and
DDQ (110 mg, 0.51 mmol) was added. After stirring
vigorously for 20 min, the mixture was extracted with
water and MTBE/hexane (1/1 v/v). The organic phase was

7510
H. Ovaa et al. / Tetrahedron 58 (2002) 7503–7518
separated, dried (MgSO4), filtered and concentrated.
Purification by column chromatography (50!100%
CH2Cl2 in hexanes) gave homogeneous 14 (144.2 mg,
afford homogeneous 182a (72.54 g, 93%). 1H NMR
(400 MHz, CDCl3): d 8.08, (m, 1H), 7.67 (m, 2H), 7.58
(m, 1H), 6.02 (ddd, J¼7, 4, 2 Hz, 1H), 5.65 (m, 2H), 5.20
(m, 1H), 5.04 (m, 1H), 5.01 (m, 1H), 4.81 (d, J¼1 Hz, 1H),
4.51 (d, J¼4 Hz, 1H), 3.36 (m, 1H), 2.99 (m, 1H), 2.26 (m,
2H), 1.36 (s, 3H), 1.24 (s, 3H); 13C NMR (CDCl3): d 148.0,
136.6, 134.1, 133.4, 133.6, 131.6, 131.5, 124.0, 117.4,
111.5, 84.1, 83.2, 70.5, 46.2, 34.9, 27.1, 25.4; IR: n 3078,
1544, 1372, 1163 cm21; HRMS: calcd for C17H19N2O6S
[M2CH3]þ: 379.0964, found: 379.0962; [a]2D0¼233.38 (c
1, CHCl3). Replacement of ligand (R,R )-8 by the ligand
dppb leads to the formation of racemic 18.
1
99%) which was directly used in the next step. H NMR
(500 MHz, CDCl3): d 5.96 (m, 2H), 4.52 (m, 3H), 4.04 (m,
1H), 0.95 (s, 9H), 0.89 (s, 9H), 0.11, 0.12, 0.09, 0.07 (4s,
12H); HRMS: calcd for C17H36O3Si2 [M]þ: 344.2203,
found: 344.2209.
3.1.14. (3R,4S,5R )-3,4-Bis-(tert-butyl-dimethylsilanyl-
oxy)-5-(1-methoxy-allyloxy)-cyclopent-1-ene (15). Alcohol
14 (135 mg, 0.39 mmol) was dissolved in MeCN (3 mL)
and Et3N (1 mL); dppp (10 mg) and Pd(OAc)2 (10 mg) were
subsequently added. The solution was heated under reflux,
and methoxyallene (0.150 mL) was added. The solution was
refluxed for 1 h after which TLC indicated complete
consumption of all starting materials. The mixture was
cooled to rt and hexane was added. This mixture was poured
into water. The organic layer was separated, dried
(Na2SO4), filtered and concentrated. FC (10% MTBE–1%
Et3N in hexane) gave 15 (157 mg, 97%) as an inseparable
mixture (1:1) of diastereomers. 1H NMR (400 MHz,
CDCl3): d 6.01 (m, 1H), 5.95 (m, 1H), 5.92 (m, 2H), 5.81
(m, 2H), 5.25–5.43 (m, 4H), 4.99 (m, 1H), 4.96 (m, 1H),
4.68 (m, 1H), 4.63 (m, 1H), 4.52 (m, 1H), 4.47 (m, 1H), 4.00
(t, J¼5 Hz, 1H), 3.86 (t, J¼5 Hz, 1H), 3.34 (s, 3H), 3.27
(s, 3H), 0.94 (s, 9H), 0.92 (s, 9H), 0.87 (s, 18H), 0.03–0.10
(5s, 24H); 13C NMR (CDCl3): d 135.6, 135.2 (2C), 134.8,
134.4, 133.8, 118.7, 118.6, 103.7, 101.7, 86.2, 83.2, 79.1,
78.7, 74.6, 74.2, 52.8, 51.8, 26.0, 18.3, 24.2, 24.3, 24.8;
HRMS: calcd for C21H42O4Si2 [M]þ: 414.2622, found:
414.2627.
3.1.17. Acetic acid (1S,2R,5R )-2-acetoxy-5-[allyl-(2-
nitrobenzenesulfonyl)-amino]-cyclopent-3-enyl ester
(19). Methods B and C with 18 gave 19 in 99% yield after
FC (MTBE). 1H NMR (500 MHz, CDCl3): d 8.04 (m, 1H),
7.67 (m, 3H), 5.96 (m, 2H), 5.71 (m, 1H), 5.61 (m, 1H), 5.19
(m, 2H), 5.09 (m, 2H), 3.81 (m, 2H), 1.98 (s, 3H), 1.94 (s,
3H); 13C NMR (CDCl3): d 170.0, 169.8, 147.8, 136.1,
134.0, 133.8, 133.3, 131.7, 131.4, 131.2, 124.4, 118.5, 72.8,
72.4, 65.5, 47.4, 20.6, 20.3; IR: n 3080, 1743, 1543, 1371,
1242, 1165 cm21; HRMS: calcd for C18H20N2O8S [M]þ:
424.0940, found: 424.0942.
For the determination of the e.e. of 18 the nosyl group was
replaced by a tosyl group ((i) PhSH, K2CO3, DMF. (ii) TsCl,
pyr.) in order to facilitate separation of the enantiomers on a
Chiralcel OD Gold column (0.5% i PrOH in hexane,
0.9 mL/min, 218 nm).
3.1.18. N-But-3-enyl-N-[(1R,4R,5S )-4,5-isopropylidene-
dioxycyclopent-2-enyl] 4-methylbenzene sulfonamide.
Compound 18 (90 mg, 0.23 mmol) was dissolved in DMF
(2 mL). Thiophenol (300 mL, 1 M in DMF) and K2CO3
(61 mg, 0.5 mmol) were added and the mixture was heated
to ,1508C. The reaction was allowed to stand for 5 min and
extracted with 1 M NaOH and Et2O. The organic phase was
separated and extracted with 0.1 M HCl. The aqueous phase
was separated and immediately made basic with 1 M NaOH
and extracted with Et2O. This process was repeated once
and the combined organic phases were dried (Na2SO4),
filtered and concentrated to give the free amine that was
immediately used in the next step [1H NMR (400 MHz,
CDCl3): d 5.92 (m, 1H), 5.87 (m, 1H), 5.77 (m, 1H), 5.23 (d,
J¼5 Hz, 1H), 5.09 (m, 2H), 4.42 (d, J¼5 Hz, 1H), 3.78 (s,
1H), 2.81 (m, 1H), 2.74 (m, 1H), 2.48 (m, 2H), 1.40 (s, 3H),
1.35 (s, 3H); 13C NMR (CDCl3): d 136.1, 134.8, 133.2,
116.6, 84.1, 83.2, 70.5, 46.9, 34.9, 27.3, 25.6]. The amine
was dissolved in pyridine (1 mL) and tosyl chloride (60 mg,
0.31 mmol) was added. The solution was heated to 508C for
2 h and concentrated under reduced pressure. MTBE and a
saturated NH4Cl solution were added. The organic phase
was separated, dried (MgSO4), filtered and concentrated.
Column chromatography (CH2Cl2) gave the homogeneous
title compound (67 mg, 78%). 1H NMR (400 MHz, CDCl3):
d 7.77 (d, J¼7 Hz, 2H), 7.31 (d, J¼7 Hz, 2H), 6.02 (m, 1H),
5.67 (m, 1H), 5.58 (m, 1H), 5.16 (d, J¼4 Hz, 1H), 5.04 (m,
2H), 4.88 (s, 1H), 4.36 (d, J¼4 Hz, 1H), 3.09 (m, 1H), 2.76
(m, 1H), 2.43 (s, 3H), 2.29 (m, 1H), 2.36 (m, 1H), 1.39 (s,
3H), 1.27 (s, 3H); 13C NMR (CDCl3): d 137.2, 135.9, 131.6,
129.6, 127.4, 117.1, 111.3, 84.2, 82.5, 70.3, 45.7, 35.4, 27.2,
25.3, 21.5.
3.1.15. (R )-2-[(1S,2R )-1,2-Bis-(tert-butyl-dimethylsil-
anyloxy)-but-3-enyl]-5-methoxy-2,5-dihydro-furan (16).
Method E with 15 gave compound 16 (124 mg, 96%) as an
inseparable mixture (1:1) of diastereomers after FC
(10!50% MTBE in hexane containing 1% Et3N),
1
Rf¼0.35 (MTBE/hexane/Et3N 100/100/1 v/v/v). H NMR
(500 MHz, CDCl3): d 6.14 (m, 2H), 5.83 (m, 2H), 5.75 (m,
3H), 5.66 (m, 1H), 5.19 (m, 2H), 5.12 (m, 2H), 5.06 (m, 1H),
4.65 (m, 1H), 4.27 (m, 1H), 4.19 (m, 1H), 3.72 (dd, J¼1,
5 Hz, 1H), 3.54 (dd, J¼2, 3 Hz, 1H), 0.89 (s, 9H), 3.72 (s,
3H), 3.88 (s, 3H), 0.82 (s, 9H), 0.88 (s 18H), 0.08, 0.07,
0.06, 0.03, 20.04, 20.05, 20.06, 20.08 (8s, 24H); 13C
NMR (CDCl3): d 139.5, 138.3, 134.1, 132.9, 127.0, 126.6,
116.2, 116.1, 109.7, 109.0, 87.7, 86.2, 79.9, 78.8, 75.6, 75.0,
55.2, 53.6, 25.9, 25.85, 18.0; HRMS: calcd for C21H42O4Si2
[M]þ: 414.2622, found: 414.2622.
3.1.16. (2)-N-But-3-enyl-N-((1R,4R,5S )-4,5-isopropyl-
idenedioxycyclopent-2-enyl)-2-nitrobenzene sulfona-
mide [(2)-18]. Carbonate 2 (1.50 g, 6.94 mmol) and
N-(2-nitrobenzenesulfonyl)-N-but-3-enylamine
(2.00 g,
7.80 mmol) were dissolved in THF (25 mL) and Et3N
(3 mL). This solution was degassed and cooled to 2108C.
Ligand (R,R)-8 (100 mg) and of [Pd2(dba3)]·CHCl3 (50 mg)
were dissolved in a little THF and stirred for 1 h, after which
this solution was slowly added to the mixture at 2108C. The
mixture was stirred for 18 h at 08C after which NMR
analysis of a small sample showed that the reaction was
complete. The solution was concentrated and purified by
column chromatography (0!5% MeOH in CH2Cl2) to

H. Ovaa et al. / Tetrahedron 58 (2002) 7503–7518
7511
An identical procedure was used for the preparation of a
racemate from racemic 18. Enantiomers of racemic 18 were
separated on a CHIRALCEL OD Gold column (0.5%
i PrOH in hexane). The difference in retention time was ca.
5 min. The racemate was compared with the 4-methyl-
benzene sulfonamide described above. The e.e. was
determined to be .99.5% (determined by comparison of
the enantiopure compound with a mixture of the enantiopure
compound and 0.5% of the racemate).
3.1.21. rac-(1R,4R,5S )-N-[4,5-Bis-(tert-butyl-dimethyl-
silanyloxy)-cyclopent-2-enyl]-N-pent-4-enyl-2-nitroben-
zenesulfonamide (21). Methods B and D with 20 (48.4 mg,
0.118 mmol) gave rac-21 (70.0 mg, 99%) after FC (33%
MTBE in hexane). 1H NMR (500 MHz, CD2Cl2) d 7.99 (m,
1H), 7.65 (m, 2H), 7.60 (m, 1H), 5.98 (td, J¼2, 6 Hz, 1H),
5.75 (dd, J¼2, 7 Hz, 1H), 5.72 (m, 1H), 4.97 (m, 2H), 4.88
(m, 1H), 4.48 (dd, J¼3, 7 Hz, 1H), 4.01 (t, J¼6 Hz, 1H),
3.22 (m, 1H), 3.13 (m, 1H), 1.98 (m, 2H), 1.70 (m, 1H), 1.56
(m, 1H), 0.89, 0.86 (2s), 0.07, 0.06, 0.05, 0.04 (4s, 12H).
3.1.19. N-(2-Nitrobenzenesulfonyl)-N-pent-4-enyl amine.
Nosylamine (2.0 g, 9.9 mmol) was dissolved in CH2Cl2
(10 mL) and Et3N (2 mL). Di-tert-butyldicarbonate (2.15 g,
9.9 mmol) was added followed by a catalytic amount (1 mg)
of DMAP. After 2 h additional CH2Cl2 was added and the
mixture was poured into a saturated NH4Cl solution. The
organic phase was separated, dried (MgSO4), filtered and
concentrated under high vacuum. The product was suffi-
ciently pure to use it directly in the subsequent Mitsunobu
reaction. (If desired, it could be purified by dissolving in
CH2Cl2 and extraction into 0.1 M NaOH followed by
acidification with 1 M HCl to pH 6 and back-extraction into
CH2Cl2. This process must be repeated three times on the
aqueous phases to get a yield exceeding 90%.) The crude
NsNHBoc was dissolved in THF (25 mL) and pent-4-enol
(1.12 g, 13 mmol) was added, followed by PPh3 (5 g,
20 mmol) and DEAD (2.61 g, 2.33 mL, 15 mmol). The
solution was stirred overnight. CH2Cl2 was added and the
organic phase was washed subsequently with 1 M NaOH
and water, then it was dried (MgSO4), filtered and
concentrated. Et2O (10 mL) and hexane (10 mL) were
subsequently added to give white crystals which were
filtered off and discarded. The filtrate was concentrated and
the product could be used directly in the next step. [It
could also be purified by column chromatography
(CH2Cl2).] The crude product was dissolved in CH2Cl2
(5 mL), TFA (5 mL) was added and the solution was stirred
for 4 h after which TLC (CH2Cl2) indicated complete
consumption of all starting material into a polar compound.
Column chromatography (CH2Cl2) afforded the homo-
geneous title compound in 89% yield over three steps
3.1.22. (1)-Acetic acid (1S,2R )-2-acetoxy-{[(R )-1-(2-
nitrobenzenesulfonyl)-1,2,5,6-tetrahydropyridin-2-yl]-
methyl}-allyl ester [(1)-22]. Method E with 19 gave 22
1
(794 mg, 100%) after FC (MTBE). H NMR (500 MHz,
CD2Cl2): d 7.99 (m, 1H), 7.66 (m, 2H), 7.57 (m, 1H), 5.97
(m, 1H), 5.84 (m, 1H), 5.72 (m, 1H), 5.46 (m, 2H), 5.39 (dd,
J¼2, 8 Hz, 1H),), 5.27 (dd, J¼2, 8 Hz, 1H), 4.50 (m, 1H),
3.83 (dd, J¼4, 14 Hz, 1H), 3.39 (ddd, J¼6, 10, 14 Hz, 1H),
2.06 (s, 3H), 2.02 (s, 3H), 1.86 (m, 2H); 13C NMR (CDCl3):
d 170.3, 169.7, 148.0, 134.0, 133.5, 131.6, 131.0, 130.7,
128.2, 124.1, 122.8, 72.7, 72.4, 54.0, 39.0, 23.1, 21.5, 20.9,
20.7; IR: n 3091, 3038, 1743, 1545, 1372, 1239, 1220,
1171 cm21
;
HRMS: calcd for C19H22N2O8S [M]þ:
438.1097, found: 438.1099; [a]2D0¼þ243.78 (c 1, CHCl3).
3.1.23. (1S,2R )-1-[(R )-1-(2-Nitrobenzenesulfonyl)-
1,2,5,6-tetrahydropyridin-2-yl]-but-3-ene-1,2-diol (23).
To a solution compound 22 (34.4 mg, 0.081 mmol) in
MeOH (1 mL) was added a catalytic amount of NaOMe
(,3 mg). After 30 min 22 was transformed into a polar
product according to TLC (MTBE). Additional MeOH was
added and the solution was neutralized by the addition of
Amberlyst 15-Hþ resin until neutral pH, filtered and
concentrated. FC (EtOAc) gave the homogeneous 23
1
(25.7 mg, 93%). H NMR (500 MHz, CD2Cl2): d 8.03 (m,
1H), 7.66 (m, 2H), 7.57 (m, 1H), 5.97 (m, 1H), 5.83 (m, 1H),
5.65 (m, 1H), 5.33 (m, 2H), 4.97 (m, 1H), 4.19 (m, 1H), 3.98
(m, 1H), 3.65 (m, 1H), 3.54 (m, 1H), 1.98 (m, 2H); 13C
NMR (CDCl3): d 148.0, 136.0, 133.8, 133.2, 131.7, 130.5,
127.7, 124.1, 124.0, 118.5, 75.5, 72.4, 54.9, 40.2, 23.0; IR: n
3525, 3093, 1543, 1373, 1346, 1162 cm21; HRMS: calcd
for C15H19N2O8S [MH]þ: 355.0938, found: 355.0964.
1
based on nosylamine. H NMR (400 MHz, CDCl3) d 8.14
(m, 1H), 7.87 (m, 1H), 7.75 (m, 2H), 5.70 (m, 1H), 5.38 (bt,
1H), 4.98 (m, 2H), 3.10 (m, 2H), 2.08 (m, 2H), 1.64 (m, 2H);
13C NMR (CDCl3) d 136.4, 133.4, 132.4, 130.4, 125.3,
115.2, 43.4, 30.3, 28.2.
3.1.24. (1S,2R )-2-(tert-Butyl-dimethylsilanyloxy)-1-[(R)-
1-(2-nitrobenzenesulfonyl)-1,2,5,6-tetrahydropyridin-2-
yl]-but-3-en-1-ol (24). Crude 23 was prepared from 22
(524.4 mg, 1.19 mmol) as described above (but not
purified). Method D then gave after FC (MTBE) homo-
geneous 24 (590 mg, 95%) as a white foam. 1H NMR
(500 MHz, CD2Cl2): d 8.11 (m, 1H), 7.64 (m, 2H), 7.60 (m,
1H), 5.87 (m, 1H), 5.84 (m, 1H), 5.68 (m, 1H), 5.27 (m, 2H),
4.29 (m, 1H), 4.24 (m, 1H), 4.00 (m, 1H), 3.64 (m, 1H), 3.29
(m, 1H), 2.57 (bs, 1H, OH), 2.19 (m, 1H), 1.94 (m, 1H), 0.92
(s, 9H), 0.08 (s, 3H), 0.05 (s, 3H); 13C NMR (CDCl3): d
147.9, 134.0, 136.5, 133.3, 131.4, 130.9, 127.2, 124.2,
123.9, 117.4, 75.5, 75.3, 55.7, 39.1, 25.8, 24.2, 18.1, 24.5,
24.8.
3.1.20. rac-(1R,4R,5S)-N-(4,5-Isopropylidenedioxycyclo-
pent-2-enyl)-N-pent-4-enyl-2-nitrobenzenesulfon-amide
(20). The methyl carbonate 2 (268 mg, 1.24 mmol) was
treated with N-nosyl-N-pent-4-enylamine (391 mg,
1.40 mmol) according to method A using the dppb ligand.
Purification by column chromatography (25!0% hexane in
CH2Cl2) gave racemic 20 (502 mg, 100%). 1H NMR
(400 MHz, CDCl3) d 8.11 (m, 1H), 7.65 (m, 3H), 1.25,
1.36 (2s, 6H), 6.04 (dt, J¼2, 6 Hz, 1H), 5.75 (m, 1H), 5.68
(dd, J¼3, 9 Hz), 4.96–5.05 (m, 2H), 5.22 (m, 1H), 4.83 (d,
J¼2 Hz, 1H), 4.49 (d, J¼8 Hz, 1H), 3.30 (m, 1H), 2.93 (m,
1H), 2.01 (m, 2H), 1.60 (m, 2H); 13C NMR (CDCl3) d 137.2,
136.7, 133.6, 131.6, 131.1, 124.1, 115.5, 111.6, 84.3, 83.3,
70.5, 46.4, 30.9, 29.7, 27.3, 25.5; IR: n 3075, 1544, 1372,
1163 cm21; HRMS: calcd for C16H17N2O6S [M2CH3]þ
393.1120, found: 393.1121.
3.1.25. Acetic acid (1S,2R )-2-(tert-butyl-dimethylsilanyl-
oxy)-1-[(R )-1-(2-nitrobenzenesulfonyl)-1,2,5,6-
tetrahydropyridin-2-yl]-but-3-enyl ester (25). Acetyl-
ation of 24 (590 mg, 1.26 mmol) according to method C

7512
H. Ovaa et al. / Tetrahedron 58 (2002) 7503–7518
gave homogeneous 25 (610 mg, 95%) after purification by
FC (MTBE/hexane 1/1 v/v). 1H NMR (500 MHz, CD2Cl2):
d 7.97 (m, 1H), 7.66 (m, 2H), 7.58 (m, 1H), 5.89 (m, 1H),
5.75 (m, 2H), 5.27 (m, 2H), 5.02 (m, 1H), 4.56 (m, 1H), 4.31
(m, 1H), 3.80 (m, 1H), 3.34 (m, H), 2.00 (s, 3H), 1.87 (m,
2H), 0.90 (s, 9H), 0.08 (s, 3H), 0.02 (s, 3H); 13C NMR
(CDCl3): d 170.3, 147.9, 134.4, 137.0, 133.3, 131.5, 130.6,
127.2, 124.3, 123.9, 116.9, 75.2, 74.1, 54.2, 38.9, 25.7, 23.5,
20.7, 18.1, 24.6, 24.9.
(200 MHz, CDCl3) d 5.71–5.80 (m, 3H), 4.98 (m, 2H), 4.49
(ddd, J¼1, 2.5, 5 Hz, 1H), 4.37 (dd, J¼1, 5 Hz, 1H), 3.92 (t,
J¼5 Hz, 1H), 3.56 (dt, J¼1, 6.5 Hz, 2H), 2.11 (m, 2H), 1.67
(m, 2H), 0.92 (s, 9H), 0.90 (s, 9H), 0.12, 0.10, 0.07, 0.06 (4s,
12H); 13C NMR (CDCl3) d 138.3, 134.5, 134.9, 114.7, 87.7,
78.8, 74.7, 69.5, 30.3, 26.3, 26.0, 18.3, 24.3, 24.4, 24.8.
3.1.30. (1)-(R )-2-[(1S,2R )-1,2-Bis-(tert-butyl-dimethyl-
silanyloxy)-but-3-enyl]-2,5-dihydro-6H-pyrane [(1)-
30]. Method E with 27 (117 mg, 0.291 mmol) gave 30
1
3.1.26. (3R,4S,5R )-3-But-3-enyloxy-4,5-isopropylidene-
dioxycyclopentene (26). Compound
(117 mg, 100%) after FC (0!5% EtOAc in PE). H NMR
1
(164.7 mg,
(300 MHz, CDCl3): d 5.85 (m, 2H), 5.67 (m, 1H), 5.17 (m,
2H), 4.28 (m, 2H), 4.01 (m, 1H), 3.63 (m, 2H), 2.23 (m, 1H),
1.96 (m, 1H), 0.89 (s, 9H), 0.87 (s, 9H), 0.06 (s, 3H), 0.04 (s,
6H), 0.02 (s, 3H); 13C NMR (CDCl3): d 139.4, 128.5, 125.8,
116.0, 86.9, 74.3, 74.1, 63.3, 26.0, 25.9, 25.3, 18.3, 18.2,
23.8, 24.1, 24.4, 24.9; MS (CI): m/z 399.2 [MþH]þ,
421.2 [MþNa]þ; HRMS: calcd for C21H42O3Si2 [M]þ:
398.2673, found: 398.2673; [a ]2D0¼þ40.98 (c 1, CHCl3).
1.06 mmol) was dissolved in THF (3 mL) and DMPU
(1 mL) and cooled to 08C. KH (35% slurry in oil, washed
with n-pentane) was added (,1 equiv.), followed by but-3-
enyl bromide (300 mL). This addition was repeated every
2 h (four times in total) while the solution was kept at 08C.
The mixture was allowed to warm to rt and stirred
overnight. The mixture was extracted three times with
Et2O and water. The organic phase was separated, dried
(MgSO4), filtered and concentrated in vacuo. FC (10!20%
3.1.31. (2)-N-But-30-enyl-N-((1R,4R,5S )-4,5-bis-(tert-
butyl-dimethylsilanyloxy)-cyclopent-2-enyl) 2-nitroben-
zene sulfonamide [(2)-31]. Compound 18 (78.0 mg,
0.197 mmol) was dissolved in HOAc (2 mL) and heated
to 808C, water (0.4 mL) was then added slowly. After
20 min, 18 had disappeared according to TLC analysis.
Toluene (2 mL) was added and the solution was concen-
trated to yield the diol [1H NMR (400 MHz, CDCl3): d 8.11
(m, 1H), 7.71 (m, 2H), 7.64 (m, 1H), 6.07 (m, 1H), 5.83 (dd,
J¼8, 2 Hz, 1H), 5.68 (m, 1H), 5.02 (m, 2H), 4.80 (m, 1H),
4.64 (d, J¼5 Hz, 1H), 4.10 (t, J¼5 Hz, 1H), 3.51 (br s, 1H),
3.25 (m, 2H), 3.01 (br s, 1H), 2.50 (m, 2H); 13C NMR
(CDCl3): d 148.4, 135.4, 134.1, 133.8, 133.1, 133.5, 131.9,
131.1, 124.2, 117.5, 74.1, 72.9, 69.5, 45.0, 35.2]. The diol
was dissolved in DMF (3 mL), and imidazole (48 mg,
0.8 mmol) was added followed by TBDMSCl (89 mg,
0.59 mmol). The mixture was stirred overnight, or 1 h at
508C on larger scales without deterioration in yield, after
which the reaction was complete as judged by TLC. Hexane
was added and the reaction mixture was washed twice with
water, dried (MgSO4), filtered and concentrated. FC
(0!10% MTBE in hexane) afforded pure 31 (85.2 mg,
1
EtOAc in PE) gave homogeneous 26 (136.5 mg, 65%). H
NMR (CDCl3): d 6.04 (m, 1H), 5.80 (m, 1H), 5.78 (m, 1H),
5.08 (m, 1H), 5.24 (d, J¼6 Hz), 4.54 (d, J¼6 Hz, 1H), 4.43
(s, 1H), 3.62 (m, 2H), 2.32 (m, 2H), 1.37, 1.41 (2s, 6H).
3.1.27. (3R,4S,5R )-3-(But-3-enyloxy)-4,5-bis-(tert-butyl-
dimethylsilanyloxy)-cyclopentene (27). Methods B and D
with 26 (148 mg, 0.37 mmol) afforded after FC (0!5%
EtOAc in PE) homogeneous 27 (122 mg, 82%) as an oil
which was directly used in the next step (27!30). 1H NMR
(200 MHz, CDCl3): d 5.84 (m, 2H), 5.75 (m, 1H), 5.07 (m,
2H), 4.53 (ddd, J¼2, 4, 5 Hz, 1H), 4.41 (m, 1H), 3.86 (t,
J¼5 Hz, 1H), 3.59 (m, 2H), 2.33 (m, 2H), 0.93 (s, 9H), 0.89
(s, 9H), 0.11, 0.10, 0.07, 0.06 (4s, 12H); 13C NMR (CDCl3):
d 135.2, 134.4, 133.9, 116.3, 87.7, 78.8, 74.6, 69.6, 34.6,
26.0, 18.3, 24.3 (2), 24.8 (4).
3.1.28. (3R,4S,5R )-3,4-Isopropylidenedioxy-5-(pent-4-
enyloxy)-cyclopentene (28). Compound
1
(185 mg,
1.18 mmol) was dissolved in THF (3 mL) and DMPU
(1 mL) and cooled to 08C. 1.5 equiv. of KH (35 mass%
slurry in mineral oil) and 210 mL of pent-4-enyl bromide
were subsequently added. After 1 h, a similar quantity of
KH was added and the solution was allowed to warm to rt
and stirred overnight. Excess KH was destroyed with a few
drops of MeOH and the mixture was stirred for 30 min.
Water and Et2O were added, the organic phase was
separated and washed with an additional portion of water,
then it was separated, dried (MgSO4), filtered and
concentrated. FC (10!20% EtOAc in PE) afforded
homogeneous 28 (255 mg, 96%) as an oil. 1H NMR
(200 MHz, CDCl3) d 6.04 (d, J¼4 Hz, 1H), 5.80 (dd,
J¼4, 7 Hz, 1H), 5.76 (m, 1H), 5.26 (d, J¼6 Hz, 1H), 5.08
(m, 2H), 4.53 (d, J¼6 Hz, 1H), 3.63 (m, 2H), 4.41 (s, 1H),
1.66 (m, 2H), 2.11 (m, 2H), 1.36, 1.41 (2s, 6H); 13C NMR
(CDCl3) d 137.9, 135.2, 133.1, 114.7, 111.4, 88.5, 84.0,
83.0, 68.8, 30.1, 28.8, 27.1, 25.4.
1
75%). H NMR (500 MHz, CDCl3): d 8.02 (m, 1H), 7.62
(m, 3H), 5.96 (m, 1H), 5.81 (m, 1H), 5.68 (m, 1H), 5.03 (m,
2H), 4.89 (m, 1H), 4.47 (m, 1H), 4.01 (m, 1H), 3.35 (m, 1H),
3.20 (m, 1H), 2.37 (m, 1H), 2.24 (m, 1H), 0.88 (s, 9H), 0.80
(s, 9H), 0.07 (s, 9H), 0.03 (s, 3H); 13C NMR (CDCl3): d
148.3, 134.8, 134.7, 134.4, 133.5, 133.3, 131.5, 131.2,
124.2, 117.2, 75.9, 73.7, 67.9, 44.8, 35.3, 26.0, 25.9, 18.2,
18.0, 24.8, 23.9, 23.8, 23.6; IR: n 3077, 1546, 1371,
1252, 1167, 1117 cm21; HRMS: calcd for C26H43N2O6SSi2
[M2CH3]þ: 567.2380, found: 567.2385; [a]2D0¼271.28 (c
1, CHCl3).
3.1.32. (1)-(R )-6-[(1S,2R )-1,2-Bis-(tert-butyl-dimethyl-
silanyl)oxy-but-3-enyl]-1-(2-nitrobenzenesulfonyl)-
1,2,3,6-tetrahydropyridine [(1)-32].2a Compound 31
(245 mg) was treated according to method E. The solution
was stirred overnight after which the reaction was complete
as determined by NMR spectrum. The solution was
concentrated and purified by FC (0!20% MTBE in hexane)
to give 32 (245 mg, 100%). 1H NMR (500 MHz, CDCl3): d
7.91 (m, 1H), 7.62 (m, 2H), 7.51 (m, 1H), 5.94 (ddd, J¼17,
3.1.29. (3R,4S,5R )-3,4-Bis-(tert-butyl-dimethylsilanyl-
oxy)-5-(pent-40-enyloxy)-cyclopentene (29). Methods B
and D with 28 (255 mg, 1.14 mmol) gave after FC (0!5%
1
EtOAc in PE) homogeneous 29 (404 mg, 87%). H NMR

H. Ovaa et al. / Tetrahedron 58 (2002) 7503–7518
7513
1
10, 8 Hz, 1H), 5.77 (m, 1H), 5.67 (m, 1H), 5.22 (d,
J¼17 Hz, 1H), 5.10 (d, J¼10 Hz, 1H), 4.50 (m, 1H), 4.35
(dd, J¼2, 8 Hz, 1H), 3.87 (dd, J¼2, 8 Hz, 1H), 3.97 (dd,
J¼14, 4 Hz, 1H), 3.41 (ddd, J¼16, 10, 6 Hz, 1H), 1.82 (m,
2H), 0.91 (s, 9H), 0.89 (s, 9H), 0.09, 0.08, 0.06, 0.04 (4s,
12H); 13C NMR (CDCl3): d 148.3, 134.5, 137.7, 133.3,
131.3, 130.4, 125.9, 125.6, 123.8, 116.5, 78.9, 76.6, 57.2,
40.2, 26.1, 22.9, 18.4, 18.3, 24.0, 24.4, 24.5, 24.6;
HRMS: calcd for C26H43N2O6SSi2 [M2CH3]þ: 567.2380;
found: 567.2388; [a ]2D0¼þ189.48 (c 1, CHCl3).
2-yl]-propyl ester. H NMR (500 MHz, CDCl3): d 7.92 (d,
J¼8 Hz, 1H), 7.76 (d, J¼8 Hz, 2H), 7.66 (m, 2H), 7.55 (d,
J¼8 Hz, 1H), 7.32 (d, J¼8 Hz, 2H), 5.77 (m, 2H), 4.39 (m,
1H), 4.26 (dd, J¼10, 3 Hz, 1H), 4.04 (dd, J¼8, 3 Hz, 1H),
3.97 (d, J¼5 Hz, 1H), 3.94 (m, 1H), 3.85 (dd, J¼10, 8 Hz,
1H), 3.23 (m, 1H), 2.44 (s, 3H), 1.84 (m, 2H), 0.86 (s, 9H),
0.84 (s, 9H), 0.09, 0.08, 0.07, 0.04 (4s, 12H). 13C NMR
(CDCl3): d 144.7, 133.7, 133.6, 132.8, 131.6, 130.4, 129.7,
128.0, 127.0, 124.1, 123.7, 79.1, 72.5, 71.8, 56.6, 40.2, 25.8
(2£t Bu), 22.9, 21.6, 18.0 (2C), 24.5, 24.6, 24.8, 25.0;
HRMS: calcd for C29H43N2O9S2Si2 [M2t Bu]: 683.1949,
found: 683.1955.
3.1.33. Preparation of 1,2,3,5,6,8a-hexahydroindolizi-
dine-1,2-diol 33 from 32. Compound 32 (400 mg,
0.687 mmol) was dissolved in acetone (7.5 mL) and water
(2.5 mL) was added. NMO (200 mg, 1.51 mmol) was
added, followed by a catalytic amount of potassium osmate
dihydrate (,1 mg). The solution was stirred for 2 days after
which consumption of 32 was complete as judged by TLC.
MTBE and brine were added, the organic phase was
separated, washed with brine, dried (MgSO4) and concen-
trated. FC (MTBE) gave 357 mg (80%) of the diol (3R,4S ),
bis-(tert-butyl-dimethylsilanyloxy)-4-[(R )-1-(2-nitro-
benzenesulfonyl)-1,2,5,6-tetrahydropyridin-2-yl]-butane-
1,2-diol as a single diastereomer. 1H NMR (500 MHz,
CDCl3): d 7.91 (d, J¼8 Hz, 1H), 7.62 (m, 2H), 7.51 (d,
J¼8 Hz, 1H), 5.89 (m, 1H), 5.75 (m, 1H), 4.65 (m, 1H), 4.04
(m, 1H), 4.01 (m, 1H), 3.94 (m, 1H), 3.88 (m, 1H), 3.83 (m,
1H), 3.69 (m, 1H), 3.26 (m, 1H), 1.86 (m, 2H), 0.97 (s, 9H),
0.92 (s, 9H), 0.18, 0.17, 0.14, 0.11 (4s, 12H). 13C NMR
(CDCl3): d 148.0, 134.2, 133.4, 131.3, 130.2, 126.9, 124.7,
123.6, 77.7, 74.4, 72.6, 57.1, 63.8, 39.1, 26.0, 25.9, 22.7,
18.1, 18.0, 23.6, 24.0, 24.8, 25.3; IR: n 3546, 3442,
1547 cm21. The diol (70 mg, 0.107 mmol) was dissolved in
MeOH (5 mL), cooled to 08C and 350 mL of NaIO4 (0.5 M
in water) were added slowly. After 30 min, NaBH4 (19 mg)
dissolved in water (250 mL) was added. After 3 min, excess
NaBH4 was destroyed by addition of acetone (50 mL). The
mixture was poured into water and extracted with MTBE.
The organic phase was dried (MgSO4) and concentrated. FC
(MTBE) gave 63 mg (99%) of (2R,3S)-2,3-bis-(tert-butyl-
dimethylsilanyl)oxy-3-[(R )-1-(2-nitrobenzenesulfonyl)-
1,2,5,6-tetrahydropyridin-2-yl]-propan-1-ol. 1H NMR
(400 MHz, CDCl3): d 7.93 (d, J¼8 Hz, 1H), 7.65 (m, 2H),
7.54 (d, J¼8 Hz, 1H), 5.81 (m, 2H), 4.49 (m, 1H), 4.00 (d,
J¼6 Hz, 1H), 3.97 (m, 1H), 3.93 (m, 1H), 3.77 (m, 1H), 3.67
(m, 1H), 3.33 (m, 1H), 1.84 (m, 2H), 0.93 (s, 9H), 0.91 (s,
9H), 0.15, 0.14 (2s, 6H), 0.11 (s, 6H). 13C NMR (CDCl3): d
148.1, 133.9, 133.5, 131.5, 130.3, 126.4, 124.7, 123.9, 78.8,
74.9, 64.1, 56.9, 40.2, 26.0, 25.9, 22.9, 18.2, 18.1, 24.2,
24.3, 24.8, 24.9; IR: n 3554, 3435, 1547 cm21; HRMS:
calcd for C26H46O7SSi2 [MHþ]: 587.2643, found:
587.2649.
The tosylate (30 mg, 0.04 mmol) was dissolved in DMF
(2 mL) and cooled to 08C, K2CO3 (100 mg, 1 mmol) was
added, followed by slow addition of thiophenol (1.2 mL of a
0.05 M solution in DMF). After 30 min the mixture was
concentrated. Column chromatography (0!10% MTBE in
CH2Cl2) gave 15.4 mg (99%) of (1S,2R,8aR)-1,2-bis-(tert-
butyl-dimethylsilanyl)oxy-1,2,3,5,6,8a-hexahydroindolizi-
1
dine. H NMR (500 MHz, C6D6): d 5.88 (m, 1H), 5.67 (d,
J¼10 Hz, 1H), 4.08 (m, 1H), 3.70 (t, J¼4 Hz, 1H), 3.52 (m,
1H), 3.28 (dd, J¼8, 7 Hz, 1H), 2.92 (m, 1H), 2.87 (m, 1H),
2.79 (t, J¼8 Hz, 1H), 1.98 (m, 2H), 1.03 (s, 9H), 0.97 (s,
9H), 0.18, 0.08, 0.07, 0.03 (4s, 12H). 13C NMR (C6D6): d
126.8, 126.3, 75.8, 73.8, 60.6, 58.3, 48.7, 26.0 (2£t Bu),
23.5, 18.3 (2C), 24.1, 24.6 (2C), 24.9; HRMS: calcd for
C20H41NO2Si2 [Mþ]: 383.2676, found: 383.2677.
The silyl ether (52.0 mg, 0.135 mmol) was dissolved in THF
(8 mL), TBAF (6.4 mL, 0.05 M in THF) was added and the
solution was stirred overnight. Chromatography over
DOWEX-WX8-(Hþ-form) with MeOH and then 0!25%
ammonium hydroxide gave 20.0 mg (88%) of homogenous
(þ)-(1S,2R,8aR )-1,2,3,5,6,8a-hexahydroindolizidine-1,2-
diol [(þ)-33]. 1H NMR (500 MHz, MeOD): d 5.92 (m, 1H),
5.76 (dd, J¼5, 1 Hz, 1H), 4.26 (dd, J¼7, 4 Hz, 1H), 4.04 (t,
J¼2 Hz, 1H), 3.35 (m, 1H), 3.12 (dd, J¼6, 3 Hz, 1H), 3.03
(m, 1H), 2.81 (m, 2H), 2.22 (m, 1H), 2.11 (m, 1H). 13C
NMR (MeOD): d 126.8, 123.2, 71.9, 70.3, 62.3, 58.1, 47.8,
23.0; IR: n 3278, 3034, 1661, 1598, 1138 cm21. HRMS:
calcd for C8H13NO2 [Mþ]: 155.0946, found: 155.0948;
[a ]2D0¼þ45.98 (c 0.46, MeOH).
3.1.34. (1)-(1S,3R,5R )-3-(tert-Butyl-dimethylsilanyl-
oxy)-5-ethoxycarbonyloxy-cyclohept-6-enyl acetate
[(1)-35). To a solution of compound 34 (300 mg,
1.00 mmol, prepared starting from tropone according to
Ref. 10) in CH2Cl2 (10 mL) was added ethyl chloroformate
(220 mg, 2.00 mmol), then pyridine (160 mg, 2.00 mmol)
was added dropwise at 08C. The solution was allowed to
warm to rt and stirred for 18 h. MTBE (20 mL) and water
(10 mL) were added and the phases separated. The aqueous
phase was extracted with MTBE (3£10 mL), the combined
organic phases were washed with water (10 mL) and brine
(10 mL), dried over MgSO4 and concentrated in vacuo. The
residue was purified by FC (cyclohexane/MTBE 20:1)
giving 35 (343 mg, 92%) as a colorless oil. Rf¼0.58
The alcohol was dissolved inn pyridine (3 mL), cooled to
08C and tosyl chloride (95 mg, 0.5 mmol) was added,
followed by a catalytic amount of DMAP. The solution was
allowed to warm to rt and stirred overnight. MTBE was
added, the mixture was subsequently washed with a
saturated NH4Cl solution and water. The organic phase
was separated, dried (MgSO4) and concentrated. FC (MTBE
0!20% in hexane) gave 161 mg (71%) of p-toluenesulfonic
acid (2R,3S )-2,3-bis-(tert-butyl-dimethylsilanyl)oxy-3-
[(R )-1-(2-nitrobenzenesulfonyl)-1,2,5,6-tetrahydropyridin-
1
(cyclohexane/MTBE 10:1). H NMR (200 MHz, CDCl3):
d 5.57–5.78 (m, 2H), 5.20–5.30 (m, 1H), 5.06–5.19 (m,
1H), 4.22 (q, J¼7 Hz, 2H), 3.88–4.04 (m, 1H), 1.97–2.10
(m, 2H), 2.02 (s, 3H), 1.60–1.94 (m, 2H), 1.32 (t, J¼7 Hz,
3H), 0.97 (s, 9H), 0.08 (s, 6H); 13C NMR (CDCl3): d 169.9,

7514
H. Ovaa et al. / Tetrahedron 58 (2002) 7503–7518
154.2, 131.8, 131.3, 72.4, 68.6, 68.1, 64.0, 41.9, 41.85,
25.6, 21.1, 17.9, 14.1, 4.9; IR: n 1744, 1371, 1262,
1239, 1095, 1029, 837, 777 cm21; MS (1008C): m/z (%)
373 (,1) [MHþ], 241 (7), 223 (100), 161 (25), 109 (53);
HRMS: calcd for C18H33O6Si [MHþ]: 373.2046, found:
373.2049. Anal. calcd for C18H33O6Si: C, 58.06%; H,
8.60%. Found: C, 57.95%; H, 8.56%; [a]2D0¼þ0.868 (c
1.05, CHCl3).
Found: C, 60.62%; H, 8.45%; N, 3.71%; [a]2D0¼2598 (c
0.70, CHCl3).
3.1.37. (1)-(2R )-N-Ethoxycarbonyl-2-[(2S,4S )-4-acet-
oxy-2-(tert-butyl-dimethylsilanyloxy)-hex-5-enyl]-2,5-
dihydro-1H-pyrrole [(2)-38]. A solution of 37 (20 mg,
0.05 mmol) and [Ru] (2 mg, 5 mol%) in dry CH2Cl2 (5 mL)
was refluxed under N2 atmosphere for 12 h. The solution
was concentrated in vacuo, the residue was purified by FC
(cyclohexane/MTBE 3:1) affording 38 (16 mg, 80%) as a
brown oil. Rf¼0.33 (cyclohexane/MTBE 3:1). 1H NMR
(500 MHz, CDCl3): d 5.68–5.85 (m, 3H), 5.30–5.39 (m,
1H), 5.12–5.30 (m, 2H), 4.40–4.56 (m, 1H), 3.98–4.30 (m,
4H), 3.73–3.97 (m, 1H), 2.00–2.22 (m, 1H), 2.05 (s, 3H),
1.81–1.94 (m, 1H), 1.71–1.82 (m, 1H), 1.57–1.66 (m, 1H),
1.76–1.94 (m, 2H), 1.20–1.35 (m, 3H), 0.88 (s, 9H), 0.06
(s, 6H); 13C NMR (CDCl3): (rotameric mixture) d 170.2,
155.0, 154.8, 136.7, 136.4, 131.2, 130.8, 124.8, 124.4, 117.2,
116.8, 72.1, 72.0, 67.7, 67.4, 62.9, 62.2, 61.2, 60.9, 53.5, 53.0,
43.0, 42.6, 42.4, 42.1, 25.9, 21.3, 18.0, 14.9, 24.1, 24.4; IR:
3.1.35. (2)-(1S,3R,5R )-3-(tert-Butyl-dimethylsilanyl-
oxy)-5-N-allylamino-cyclohept-6-enyl acetate [(2)-36].
To a solution of carbonate 35 (300 mg, 0.80 mmol) and
allylamine (183 mg, 4.0 mmol) in THF (10 mL) were added
under an N2 atmosphere [Pd2(dba)3]·CHCl3 (21 mg,
0.020 mmol, 2.5 mol%) and dppb (34 mg, 0.080 mmol,
10 mol%) as solids. The solution was stirred for 2 h at rt,
then diluted with MTBE (20 mL) and washed with water
(3£10 mL). The aqueous phases were back extracted with
MTBE (10 mL). The combined organic phases were then
washed with brine (10 mL), dried over MgSO4 and the
solvent was evaporated in vacuo. FC [cyclohexane/MTBE
4:1 (3% NEt3)] afforded 36 (306 mg, 80%) as a colorless oil.
n 3082, 1742, 1704, 1415, 1381, 1237, 1108, 837, 774 cm21
;
MS (708C): m/z (%) 411 (,1) [Mþ], 294 (3), 140 (100), 117
(5), 68 (23). HRMS: calcd for C21H37O5NSi [Mþ]: 411.2441,
found: 411.2450. Anal. calcd for C21H37NO5Si: C, 61.31%;
H, 9.00%; N, 3.41%. Found: C, 60.94%; H, 8.98%; N,
3.60%; [a]2D0¼þ14.48 (c 0.50, CHCl3).
1
Rf¼0.41 [cyclohexane/MTBE 4:1 (5% NEt3)]; H NMR
(200 MHz, CDCl3): d 5.68–5.98 (m, 2H), 5.50–5.61 (m,
1H), 5.30–5.43 (m, 1H), 5.01–5.22 (m, 2H), 4.12–4.29 (m,
1H), 3.49–3.62 (m, 1H), 3.12–3.34 (m, 2H), 2.00–2.16 (m,
1H), 2.03 (s, 3H), 1.74–1.94 (m, 3H), 0.98 (br s, 1H), 0.86
(s, 9H), 0.03, 0.04 (2s, 6H); 13C NMR (CDCl3): d 170.2,
136.8, 135.6, 132.3, 115.8, 69.1, 65.6, 50.8, 49.7, 42.0, 41.8,
25.7, 21.3, 18.0, 24.8, 24.75; IR: n 3078, 1739, 1369,
1241, 1075, 1024, 836, 775 cm21; MS (708C): m/z (%)¼339
(,1) [Mþ], 279 (30), 222 (34), 148 (40), 117 (41), 75 (100),
HR-MS: calcd for C18H33NO3Si [Mþ]: 339.2230, found
339.2224. Anal. calcd for C18H33NO3Si: C, 63.72%, H,
9.73%; N, 4.13%. Found C, 63.71%, H, 9.83%, N, 4.39%.
[a ]2D0¼245.68 (c 0.56, CHCl3).
3.1.38. (2)-(1R,3R,5S )-5-(N-Allyl-N-(4-methylbenzene-
sulfonyl)-amino)-3-(tert-butyl-dimethylsilanyloxy)-
cyclohept-6-enol [(2)-39]. Dry THF (15 mL) was added to
acetate 34 (610 mg, 2.03 mmol), N-allyl-N-tosylamide
(500 mg, 2.37 mmol) and NaH (60% suspension in mineral
oil, 90 mg, 2.25 mmol). DMF (4–5 mL) was then added to
the suspension until the solution became clear. Under N2
atmosphere [Pd2(dba)3]·CHCl3 (52 mg, 0.051 mmol,
2.5 mol%) and dppb (90 mg, 0.21 mmol, 10 mol%) were
added as solids. The solution was stirred for 30 min at 508C.
After addition of water (50 mL) the solution was extracted
with MTBE (3£20 mL). The combined organic phases were
washed with brine (20 mL), dried over MgSO4 and
concentrated in vacuo. The residue was purified by FC
(cyclohexane/MTBE 3:1) affording 39 (755 mg, 82%) as
3.1.36. (2)-Acetic acid (1S,3R,5R )-3-(tert-butyl-
dimethylsilanyloxy)-5-(N-allyl-N-ethoxycarbonyl-
amino)-cyclohept-6-enyl ester [(2)-37). To a solution of
amine 36 (300 mg, 0.88 mmol) in CH2Cl2 (10 mL) were
sequentially added ethyl chloroformate (110 mg, 1.0 mmol)
and pyridine (200 mg, 2.5 mmol) under N2 atmosphere. The
solution was stirred for 12 h, diluted with MTBE (20 mL)
and washed with water (3£10 mL). The aqueous phases
were extracted with MTBE (10 mL), the combined organic
phases were washed with brine (10 mL), dried over MgSO4
and concentrated in vacuo. The residue was purified by FC
(cyclohexane/MTBE 4:1) giving 37 (321 mg, 89%) as a
1
yellow oil. Rf¼0.27 (cyclohexane/MTBE 3:1). H NMR
(200 MHz, CDCl3): d 7.64–7.72 (m, 2H), 7.21–7.31 (m,
2H), 5.89–6.10 (m, 1H), 5.57–5.70 (m, 1H), 5.38–5.50 (m,
1H), 5.24–5.36 (m, 1H), 5.08–5.17 (m, 1H), 4.74–4.80 (m,
1H), 4.02–4.22 (m, 4H), 3.90–4.02 (m, 1H), 2.20–2.60 (m,
3H), 2.40 (s, 3H), 1.70–1.84 (m, 1H), 0.84 (s, 9H), 0.05 (s,
6H); 13C NMR (CDCl3): d 143.0, 137.7, 136.3, 131.5,
129.5, 128.0, 126.2, 116.5, 72.6, 67.9, 62.3, 47.7, 41.5, 34.7,
25.6, 21.4, 17.8, 25.2, 25.3; IR: n 3488, 3081, 3035, 1598,
1338, 1255, 1159, 1091, 1025, 837, 712, 662; MS (2108C):
m/z (%) 433 (2) [Mþ2H2O], 394 (21), 183 (100), 91 (88);
HRMS: calcd for C23H35NO3SSi [Mþ2H2O): 433.2107,
found: 433.2101. Anal. calcd for C23H37NO4SSi: C,
61.20%; H, 8.20%; N, 3.14%. Found: C, 61.28%; H,
8.00%; N, 3.11%; [a]2D0¼21038 (c 0.47, CHCl3).
1
colorless oil. Rf¼0.69 (cyclohexane/MTBE 1:1); H NMR
(500 MHz, CDCl3): (rotameric mixture) d 5.75–5.95 (m,
1H), 5.54–5.74 (m, 2H), 5.29–5.40 (m, 1H), 5.07–5.24 (m,
2H), 4.65–4.83 (m, 1H), 4.06–4.30 (m, 3H), 3.82–4.03 (m,
1H), 3.62–3.75 (m, 1H), 2.00–2.48 (m, 2H), 2.05 (s, 3H),
1.76–1.94 (m, 2H), 1.25 (t, J¼7 Hz, 3H), 0.86 (s, 9H), 0.03
(s, 6H); 13C NMR (CDCl3): (rotameric mixture) d 170.3,
156.0, 135.6, 135.1, 132.0, 116.6, 68.7, 65.0, 61.4, 51.9,
51.4, 48.5, 42.5, 42.2, 41.9, 25.8, 21.4, 18.0, 14.7, 24.7,
24.8; IR: n 3080, 1740, 1701, 1369, 1240, 1078, 1023, 836,
775 cm21; MS (1058C): m/z (%) 411 (,1) [Mþ], 354 (100),
294 (53), 220 (51), 117 (74); HRMS: calcd for
C21H37NO5Si [Mþ]: 411.2441, found: 411.2442. Anal.
calcd for C21H37NO5Si: C, 61.31%; H, 9.00%; N, 3.41%.
3.1.39. (1)-(1R,3R,5S )-5-(N-Allyl-N-(4-methylbenzene-
sulfonyl)-amino)-3-(tert-butyl-dimethylsilanyloxy)-
cyclohept-6-enyl benzoate [(2)-40]. To a solution of
alcohol 39 (220 mg, 0.49 mmol) and DMAP (500 mg,
4.09 mmol) in CH2Cl2 (20 mL) was added benzoyl chloride

H. Ovaa et al. / Tetrahedron 58 (2002) 7503–7518
7515
(140 mg, 0.1 mmol) and stirred at rt for 15 h. The solution
was concentrated in vacuo. FC of the residue
(cyclohexane/CH2Cl2 1:1) yielded 40 (247 mg, 91%) as a
white solid. Rf¼0.30 (cyclohexane/MTBE 4:1). H NMR
HRMS: calcd for C23H33N2O7SSi [Mþ2CH3]: 509.1778,
found: 509.1772. Anal. calcd for C24H36N2O7SSi: C,
54.96%; H, 6.87%; N, 5.34%. Found: C, 55.12%; H,
6.74%; N, 5.41%; [a ]2D0¼2318 (c 0.46, CHCl3).
1
(200 MHz, CDCl3): d 7.90–7.97 (m, 2H), 7.65–7.74 (m,
2H), 7.25–7.56 (m, 5H), 5.78–5.92 (m, 1H), 5.52–5.75 (m,
1H), 5.30–5.37 (m, 1H), 5.10–5.12 (m, 1H), 4.82–5.03 (m,
3H), 3.96–4.12 (m, 1H), 3.66–3.96 (m, 2H), 2.40–2.58 (m,
1H), 2.46 (s, 3H), 2.20–2.36 (m, 2H), 2.00–2.14 (m, 1H),
0.78 (s, 9H), 0.00, 0.01 (2s, 6H); 13C NMR (CDCl3): d
165.1, 143.4, 137.2, 135.1, 133.0, 130.6, 129.9, 129.7,
129.4, 128.3, 127.4, 127.2, 116.4, 74.8, 68.4, 58.6, 47.7,
40.8, 37.4, 25.6, 21.5, 17.9, 24.9; IR: n 3068, 3027, 1720,
1346, 1271, 1163, 1091, 1027, 837, 712 cm21; MS (1908C):
m/z (%) 498 (7) [Mþ2C4H9], 433 (63), 302 (51), 278 (45),
146 (86), 105 (100); HRMS: calcd for C26H32NO5SSi
[Mþ2C4H9]: 498.1770, found: 498.1769. Anal. calcd for
C30H41NO5SSi: C, 64.86%; H, 7.39%; N, 2.52%. Found: C,
65.34%; H, 7.45%; N, 2.62%; [a ]2D0¼þ548 (c 0.51, CHCl3).
3.1.42. (2)-(1S,3S,5S)-5-(N-But-3-enyl-N-(2-nitrobenze-
nesulfonyl)-amino)-3-(tert-butyl-dimethylsilanyloxy)-
cyclohept-6-enyl acetate [(2)-43]. Compound 34 (1.79 g,
5.95 mmol),
N-but-3-enyl-N-nosylamide
(2.00 g,
7.75 mmol) and PPh3 (3.10 g, 11.8 mmol) were dissolved
in dry THF (60 mL); DEAD (1.80 g, 10.3 mmol) were
added dropwise at 08C. After stirring at rt for 18 h, the
solution was concentrated in vacuo and the residue was
purified by FC (cyclohexane/MTBE 4:1) yielding 43
(2.80 g, 89%) as light yellow oil. Rf¼0.54 (cyclohexane/
MTBE 1:1). 1H NMR (200 MHz, CDCl3): d 8.02–8.11 (m,
1H), 7.58–7.72 (m, 3H), 5.52–5.84 (m, 3H), 5.24–5.36 (m,
1H), 5.00–5.13 (m, 2H), 4.74–4.87 (m, 1H), 4.17–4.30 (m,
1H), 3.18–3.48 (m), 1.96–2.58 (m, 5H), 2.05 (s, 3H), 1.76–
1.94 (m, 1H), 0.84 (s, 9H), 0.02 (s, 6H); 13C NMR (CDCl3):
d 170.1, 148.1, 134.4, 133.8, 133.5, 133.45, 131.6, 131.2,
124.1, 117.2, 68.1, 64.4, 52.8, 45.0, 42.2, 41.9, 35.5, 25.7,
21.2, 18.0, 24.9; IR: n 3078, 1739, 1546, 1372, 1240, 1164,
1085, 1023, 837, 777 cm21; MS (2108C): m/z (%) 481 (12)
[Mþ2C4H9], 421 (17), 186 (86), 161 (46), 91 (70), 75
(100); HRMS: calcd for C21H29N2O7SSi [Mþ2C4H9]:
481.1465, found: 481.1461. Anal. calcd for C25H38N2O7-
SSi: C, 55.76%; H, 7.06%; N, 5.20%. Found: C, 55.11%; H,
7.18%; N, 5.67%; [a ]2D0¼2268 (c 0.90, CHCl3).
3.1.40. (2)-(2S )-N-(4-Methylbenzenesulfonyl)-2-
[(2R,4R )-4-benzoyloxy-2-(tert-butyl-dimethylsilanyl-
oxy)-hex-5-enyl]-2,5-dihydro-1H-pyrrole [(2)-41]. Com-
pound 40 (12 mg, 0.022 mmol) and [Ru] (1 mg, 5 mol%) in
dry CH2Cl2 (2 mL) were refluxed under N2 atmosphere for
12 h. The solution was concentrated in vacuo, the residue
was purified by FC (cyclohexane/MTBE 3:1) affording 41
(11 mg, 92%) as a brown oil. Rf¼0.19 (cyclohexane/MTBE
1
4:1). H NMR (200 MHz, CDCl3): d 7.97–8.06 (m, 2H),
7.60–7.70 (m, 2H), 7.36–7.56 (m, 3H), 7.16–7.28 (m, 2H),
5.66–5.97 (m, 3H), 5.40–5.50 (m, 1H), 4.90–5.20 (m, 3H),
4.08–4.24 (m, 1H), 3.82–4.06 (m, 2H), 2.22–2.56 (m, 2H),
2.39 (s, 3H), 1.94–2.12 (m, 1H), 1.70–1.98 (m, 1H), 0.86
(s, 9H), 0.03 (s, 6H); 13C NMR (CDCl3): d 165.9, 143.4,
134.8, 134.6, 132.9, 130.4, 129.7, 128.3, 127.5, 127.45,
125.9, 116.4, 73.2, 69.6, 69.2, 56.2, 40.5, 36.7, 25.8, 21.5,
18.1, 24.6, 24.7; IR: n 3071, 3031, 1718, 1350, 1273,
1164, 1092, 1069, 836, 711, 667 cm21; MS (1808C): m/z
(%) 498 (11) [Mþ2C4H9], 222 (100), 179 (25), 105 (95), 91
(27). HRMS: calcd for C26H32NO5SSi [Mþ2C4H9]:
498.1770, found: 498.1773; [a]2D0¼21198 (c 0.50, CHCl3).
3.1.43. (2)-(1S,3S,5S)-5-(N-But-3-enyl-N-benzyloxycar-
bonyl-amino)-3-(tert-butyl-dimethylsilanyloxy)-cyclo-
hept-6-enyl acetate [(2)-44]. To a suspension of 43
(380 mg, 0.71 mmol) and K2CO3 (450 mg, 3.26 mmol) in
dry DMF (10 mL) was added PhSH (150 mg, 1.36 mmol).
The solution was stirred for 1 h at 708C, then cooled to 08C.
Under vigorous stirring benzyl chloroformate (250 mg,
1.47 mmol) was added. After 2 h, water (20 mL) and MTBE
(20 mL) were added, the organic phase was separated and
the aqueous phase was extracted twice with MTBE (10 mL).
The combined organic phases were washed with brine
(20 mL), dried over MgSO4 and concentrated in vacuo. The
residue was purified by FC (cyclohexane/MTBE 5:1) giving
44 (301 mg, 87%) as a pale yellow oil. Rf¼0.46 (cyclo-
hexane/MTBE 3:1). 1H NMR (200 MHz, CDCl3):
(rotameric mixture) d 7.20–7.39 (m, 5H), 5.49–5.90 (m,
3H), 5.24–5.44 (m, 1H), 4.94–5.18 (m, 4H), 4.48–4.70 (m,
1H), 4.10–4.30 (m, 1H), 3.12–3.46 (m, 2H), 1.72–2.53 (m,
6H), 2.06 (s, 3H), 0.86 (s, 9H), 0.04 (s, 6H); 13C NMR
(CDCl3): (rotameric mixture) d 170.2, 155.6, 136.8, 135.8,
135.2, 131.5, 128.4, 127.8, 127.7, 116.7, 68.6, 66.9, 65.0,
52.7, 52.0, 46.6, 42.7, 42.5, 41.7, 34.1, 33.5, 25.7, 21.3,
17.9, 24.8, 24.9; IR: n 3067, 3033, 1737, 1701, 1239,
1072, 1022, 1004, 910, 836, 775, 698 cm21; MS (1908C):
m/z (%) 430 (37) [Mþ2C4H9], 386 (18), 91 (100); HRMS:
calcd for C23H32NO5Si [Mþ2C4H9]: 430.2050, found:
430.2053. Anal. calcd for C27H41N2O5Si: C, 66.53%; H,
8.42%; N, 2.87%. Found: C, 66.17%; H, 8.23%; N, 3.11%;
[a ]2D0¼2608 (c 0.76, CHCl3).
3.1.41. (2)-(1S,3S,5S)-5-(N-Allyl-N-(2-nitrobenzenesul-
fonyl)-amino)-3-(tert-butyl-dimethylsilanyloxy)-cyclo-
hept-6-enyl acetate [(2)-42]. Compound 34 (2.60 g,
8.71 mmol), N-allyl-N-nosylamide (2.74 g, 11.3 mmol)
and PPh3 (5.71 g, 21.8 mmol) were dissolved in dry THF
(60 mL); DEAD (3.03 g, 17.4 mmol) was added dropwise at
08C. After stirring at rt for 18 h, the solution was
concentrated in vacuo and the residue was purified by FC
(cyclohexane/MTBE 4:1) yielding 42 (4.25 g, 93%) as light
1
yellow oil. Rf¼0.53 (cyclohexane/MTBE 1:1). H NMR
(500 MHz, CDCl3): d 8.00–8.03 (m, 1H), 7.61–7.70 (m,
3H), 5.76–5.87 (m, 1H), 5.60–5.65 (m, 1H), 5.49–5.55 (m,
1H), 5.24–5.30 (m, 1H), 5.15–5.23 (m, 1H), 5.05–5.10 (m,
1H), 4.82–4.88 (m, 1H), 4.18–4.25 (m, 1H), 3.97–4.05 (m,
1H), 3.77–3.86 (m, 1H), 1.97–2.20 (m, 3H), 2.04 (s, 3H),
1.78–1.88 (m, 1H), 0.85 (s, 9H), 0.02 (s, 6H); 13C NMR
(CDCl3): d 170.2, 148.1, 135.6, 134.7, 133.9, 133.6, 133.2,
131.7, 131.5, 124.3, 118.1, 68.3, 64.6, 53.3, 48.1, 42.2, 42.1,
25.8, 21.3, 18.1, 24.8; IR: n 3092, 3027, 1740, 1545, 1371,
1242, 1165, 1087, 1024, 837, 777 cm21; MS (2008C): m/z
(%) 509 (1) [Mþ2CH3], 467 (51), 186 (96), 147 (100);
3.1.44. (2)-(1S,3S,5S )-5-(N-Pent-4-enyl-N-(2-nitroben-
zenesulfonyl)-amino)-3-(tert-butyldimethyl-silanyloxy)-
cyclohept-6-enyl acetate [(2)-45]. To a solution of 34

7516
H. Ovaa et al. / Tetrahedron 58 (2002) 7503–7518
(300 mg, 1.0 mmol), PPh3 (524 mg, 2.00 mmol) and
N-pent-4-enyl-N-nosylamide (405 mg, 1.49 mmol) in dry
THF (10 mL) was added dropwise at 08C DEAD (300 mg,
1.70 mmol). After stirring at rt for 18 h, the solution was
concentrated in vacuo and the residue was purified by FC
(cyclohexane/MTBE 4:1) to afford 45 (408 mg, 74%) as
light yellow oil. Rf¼0.57 (cyclohexane/MTBE 1:1). 1H
NMR (200 MHz, CDCl3): d 8.00–8.08 (m, 1H), 7.56–7.72
(m, 3H), 5.48–5.85 (m, 3H), 4.92–5.05 (m, 2H), 4.72–4.82
(m, 1H), 4.12–4.30 (m, 1H), 3.10–3.40 (m, 2H), 1.60–2.26
(m, 8H), 2.05 (s, 3H), 0.84 (s, 9H), 0.04 (s, 6H); 13C NMR
(CDCl3): d 170.1, 148.0, 137.2, 134.3, 133.7, 133.5, 133.4,
131.5, 131.0, 124.1, 115.2, 68.0, 64.4, 52.7, 45.2, 42.1, 41.8,
31.0, 30.2, 25.7, 21.1, 17.9, 25.0; IR: n 3077, 1739, 1546,
1372, 1240, 1164, 1085, 1023, 837, 777 cm21; MS (2208C):
m/z (%) 537 (1) [Mþ2CH3], 495 (9), 361 (100); HRMS:
calcd. for C25H37N2O7SSi [Mþ2CH3]: 537.2091, found:
537.2087. Anal. calcd for C26H40N2O7SSi: C, 56.52%; H,
7.25%; N, 5.07%. Found: C, 55.81%; H, 7.43%; N, 5.27%;
[a ]2D0¼224.88 (c 0.40, CHCl3).
0.18 mmol) and [Ru] (7 mg, 5 mol%) afforded after 3 h 47
(87 mg, 94%) as a light brown oil. Rf¼0.28 (cyclo-
1
hexane/MTBE 1:1). H NMR (200 MHz, CDCl3): d 7.82–
7.93 (m, 1H), 7.55–7.70 (m, 3H), 5.66–5.87 (m, 3H), 5.12–
5.38 (m, 3H), 4.63–4.77 (m, 1H), 4.10–4.36 (m, 2H), 3.93–
4.06 (m, 1H), 2.12–2.26 (m, 1H), 2.06 (s, 3H), 1.59–2.00
(m, 3H), 0.89 (s, 9H), 0.05, 0.07 (s, 6H); 13C NMR (CDCl3):
d 170.1, 148.7, 136.4, 133.5, 132.1, 131.6, 131.0, 129.8,
124.2, 123.9, 116.8, 71.5, 67.3, 65.8, 54.9, 43.8, 42.1, 25.8,
21.1, 17.9, 24.35, 24.4; IR: n 3091, 1738, 1547, 1372,
1361, 1239, 1171, 1092, 836, 776 cm21; MS (2108C): m/z
(%) 524 (39) [MHþ], 411 (74), 407 (30), 253 (100), 186
(70); HRMS: calcd for C24H37N2O7SSi [MHþ]: 525.2091,
found: 525.2101. Anal. calcd for C24H36N2O7SSi: C,
54.96%; H, 6.87%; N, 5.34%. Found: C, 54.87%; H,
6.71%; N, 5.49%; [a]2D0¼þ1308 (c 0.43, CHCl3).
3.2.2. (1)-(2S )-N-(2-Nitrobenzenesulfonyl)-2-[(2S,4S )-
4-acetoxy-2-(tert-butyl-dimethylsilanyloxy)-hex-5-enyl]-
1,2,5,6-tetrahydropyridine [(1)-48]. Compound 43
(54 mg, 0.10 mmol) and [Ru] (5 mg, 5 mol%) afforded
after 12 h 48 (46 mg, 86%) as a brown oil. Rf¼0.31
3.1.45. (2)-(1S,3S,5S )-5-(N-Pent-4-enyl-N-benzyloxy-
carbonyl-amino)-3-(tert-butyl-dimethylsilanyloxy)-
cyclohept-6-enyl acetate [(2)-46]. To a suspension of 45
(165 mg, 0.30 mmol) and K2CO3 (200 mg, 1.53 mmol) in
dry DMF (5 mL) was added PhSH (65 mg, 0.60 mmol). The
solution was stirred for 1 h at 708C, then cooled to 08C.
Under vigorous stirring benzyl chloroformate (110 mg,
0.65 mmol) was added. After 2 h water (20 mL) and MTBE
(20 mL) were added, the organic phase was separated and
the aqueous phase was extracted twice with MTBE (10 mL).
The combined organic phases were washed with brine
(20 mL), dried over MgSO4 and concentrated in vacuo. The
residue was purified by FC (cyclohexane/MTBE 5:1) to give
46 (117 mg, 78%) as a pale yellow oil. Rf¼0.36 (cyclo-
hexane/MTBE 4:1). 1H NMR (200 MHz, CDCl3):
(rotameric mixture) d 7.22–7.40 (m, 5H), 5.46–5.92 (m,
3H), 5.24–5.42 (m, 1H), 4.90–5.16 (m, 4H), 4.44–4.68 (m,
1H), 4.09–4.30 (m, 1H), 3.06–3.37 (m, 2H), 1.48–2.52 (m,
8H), 2.07 (s, 3H), 0.86 (s, 9H), 0.02 (s, 6H); 13C NMR
(CDCl3): (rotameric mixture) d 170.3, 155.6, 136.8, 136.0,
135.2, 131.6, 128.5, 127.9, 127.8, 115.1, 68.7, 67.1, 65.1,
52.7, 46.6, 42.7, 42.5, 41.8, 31.2, 25.8, 21.4, 18.0, 24.7,
24.8; IR: n 3069, 3032, 1737, 1702, 1240, 1076, 1022,
1004, 910, 837, 775, 698 cm21; MS (1308C): m/z (%) 444
(10) [Mþ2C4H9], 250 (7), 117 (9), 91 (100); HRMS: calcd
for C24H34NO5Si [Mþ2C4H9]: 444.2206, found: 444.2209.
Anal. calcd for C28H43NO5Si: C, 67.07%; H, 8.58%; N,
2.79%. Found: C, 66.92%; H, 8.35%; N, 2.95%;
[a ]2D0¼262.48 (c 0.47, CHCl3).
1
(cyclohexane/MTBE 1:1). H NMR (500 MHz, CDCl3): d
7.95–8.00 (m, 1H), 7.54–7.67 (m, 3H), 5.62–5.83 (m, 3H),
5.31–5.39 (m, 1H), 5.22–5.27 (m, 1H), 5.15–5.20 (m, 1H),
4.45–4.53 (m, 1H), 3.95–4.02 (m, 1H), 3.85–4.94 (m, 1H),
3.17–3.26 (m, 1H), 1.60–2.15 (m, 6H), 2.09 (s, 3H), 0.93
(s, 9H), 0.12, 0.15 (s, 6H); 13C NMR (CDCl3): d 170.4,
148.7, 136.5, 134.4, 133.3, 131.5, 130.4, 128.6, 124.5,
124.0, 116.8, 71.5, 66.8, 52.2, 42.4, 42.2, 38.4, 26.0, 23.4,
21.2, 18.1, 24.35, 24.4; IR: n 3092, 3035, 1738, 1547,
1372, 1359, 1239, 1170, 1104, 837, 777 cm21; MS (1808C):
m/z (%) 481 (,1) [Mþ2C4H9], 267 (100), 186 (52), 117
(19); HRMS: calcd for C21H29N2O7SSi [Mþ2C4H9]:
481.1465, found: 481.1467. Anal. calcd for C25H38N2O7-
SSi: C, 55.76%; H, 7.06%; N, 5.20%. Found: C, 55.41%; H,
7.16%; N, 5.26%; [a]2D0¼þ1168 (c 0.46, CHCl3).
3.2.3. (1)-(2S )-N-Benzyloxycarbonyl-2-[(2S,4S )-4-acet-
oxy-2-(tert-butyl-dimethylsilanyloxy)-hex-5-enyl]-
1,2,5,6-tetrahydropyridine [(1)-49]. Compound 44
(98 mg, 0.20 mmol) and [Ru] (10 mg, 5 mol%) afforded
after 6 h 49 (90 mg; 92%) as a brown oil. Rf¼0.33
(cyclohexane/MTBE 3:1). 1H NMR (200 MHz, CDCl3):
(rotameric mixture) d 7.26–7.40 (m, 5H), 5.63–5.85 (m,
3H), 5.33–5.40 (m, 1H), 5.09–5.26 (m, 4H), 4.45–4.65 (m,
1H), 4.05–4.24 (m, 1H), 3.85–3.92 (m, 1H), 2.85–2.97 (m,
1H), 2.17–2.30 (m, 1H), 1.66–2.06 (m, 5H), 2.00 (s, 3H),
0.92 (s, 9H), 0.09 (s, 6H); 13C NMR (CDCl3): (rotameric
mixture) d 169.7, 155.2, 137.1, 136.7, 128.4, 127.9, 127.9,
116.7, 71.8, 66.5, 67.0, 50.2, 42.3, 42.1, 37.3, 25.7, 24.9,
20.9, 18.0, 24.2, 24.4; IR: n 3090, 3067, 3033, 1740, 1700,
1428, 1242, 1093, 1024, 837, 776, 698 cm21; MS (1508C):
m/z (%) 430 (3) [Mþ2C4H9], 117 (14), 91 (100); HRMS:
calcd for C23H32NO5Si [Mþ2C4H9]: 430.2050, found:
430.2048. Anal. calcd for C27H41NO5Si: C, 66.53%; H,
8.42%; N, 2.87%. Found: C, 66.33%; H, 8.66%; N, 3.17%;
[a ]2D0¼þ988 (c 1.13, CHCl3).
3.2. General procedure for the preparation of 47–49
from 42–44
The acetate 42, 43 or 44 (0.10 mmol) and [Ru] (5 mol.%) in
dry CH2Cl2 (2 mL) were refluxed under N2 atmosphere. The
solution was concentrated in vacuo, the residue was purified
by FC (cyclohexane/MTBE 3:1) to give the products 47, 48
or 49.
3.3. General procedure for the preparation of 50–52
from 42–44
3.2.1. (1)-(2S )-N-(2-Nitrobenzenesulfonyl)-2-[(2S,4S )-
4-acetoxy-2-(tert-butyl-dimethylsilanyloxy)-hex-5-enyl]-
2,5-dihydro-1H-pyrrole [(1)-47]. Compound 42 (92 mg,
To a solution of the TBDMS ether 42, 43 or 44 (50 mmol) in

H. Ovaa et al. / Tetrahedron 58 (2002) 7503–7518
7517
dry THF (5 mL) was added TBAF solution (1.0 mL, 1 M in
3.4. General procedure for the preparation of 53–55
from 50–52
THF) dropwise at 08C and stirred for 1 h at 08C. Water
(10 mL) was added and the solution was extracted with
MTBE (3£10 mL). The combined organic layers were
washed with brine (15 mL), dried over MgSO4 and
concentrated in vacuo. The residue was purified by FC
(cyclohexane/MTBE 1:1 [50, 51] or 2:1 [52]) to give 50–
52.
To a solution of 50, 51 or 52 (0.20 mmol) in
cyclohexane/CH2Cl2 (1:1, 2 mL) at 08C allyl trichloroaceta-
midate (1.0 mmol) and one drop of trifluormethane sulfonic
acid were added and the solution was stirred at rt for 1 day.
The solvents were distilled off and the residue was purified
by FC (cyclohexane/MTBE 1:1) to give 53, 54 or 55.
3.3.1. (2)-(1S,3S,5S )-5-(N-Allyl-N-(2-nitrobenzenesul-
fonyl)-amino)-3-hydroxycyclohept-6-enyl acetate [(2)-
50]. Compound 42 (360 mg, 0.69 mmol) gave 50 (240 mg,
85%) as a pale yellow oil. Rf¼0.14 (cyclohexane/MTBE
3.4.1. (2)-(1S,3S,5S )-3-Allyloxy-5-(N-allyl-N-(2-nitro-
benzenesulfonyl)-amino)-cyclohept-6-enyl acetate [(2)-
53]. Compound 50 (87 mg, 0.21 mmol) gave 53 (49 mg,
52%) as pale yellow oil. Rf¼0.27 (cyclohexane/MTBE 1:1).
1H NMR (200 MHz, CDCl3): d 8.00–8.09 (m, 1H), 7.54–
7.73 (m, 3H), 5.48–5.94 (m, 4H), 4.98–5.36 (m, 5H), 4.68–
4.85 (m, 1H), 3.76–4.06 (m, 5H), 1.70–2.38 (m, 4H), 2.02
(s, 3H); 13C NMR (CDCl3): d 170.3, 147.9, 135.3, 134.6,
134.5, 133.5, 133.4, 133.0, 131.7, 131.6, 124.1, 118.2,
116.8, 70.4, 69.1, 68.3, 53.2, 47.8, 38.7, 37.5, 21.1; IR: n
3081, 3023, 1732, 1544, 1371, 1242, 1165, 1025, 852,
742 cm21; MS (1408C): m/z (%) 450 (,1) [Mþ], 333 (98),
264 (28), 204 (79), 186 (100), 146 (78), 120 (57), 91 (80);
HRMS: calcd for C21H26N2O7S [Mþ]: 450.1461, found:
450.1463; [a ]2D0¼2218 (c 0.89, CHCl3).
1
1:2). H NMR (500 MHz, CDCl3): d 8.03–8.09 (m, 1H),
7.60–7.72 (m, 3H), 5.75–5.84 (m, 1H), 5.64–5.68 (m, 1H),
5.55–5.62 (m, 1H), 5.23–5.30 (m, 1H), 5.14–5.23 (m, 1H),
5.04–5.10 (m, 1H), 4.89–4.94 (m, 1H), 4.22–4.30 (m, 1H),
3.94–3.99 (m, 1H), 3.79–3.88 (m, 1H), 1.98–2.40 (m, 4H),
2.03 (s, 3H), 1.80–1.91 (m, 1H); 13C NMR (CDCl3): d
170.3, 147.9, 135.2, 134.4, 133.8, 133.7, 133.6, 132.0,
131.6, 124.3, 118.4, 68.4, 64.2, 52.9, 47.9, 42.3, 40.3, 21.4;
IR: n 3528, 3092, 3025, 1730, 1543, 1372, 1347, 1242,
1163, 1025, 852, 741 cm21; MS (1908C): m/z (%) 410 (3)
[Mþ], 224 (27), 186 (100), 164 (94); HRMS: calcd for
C18H22N2O7S [Mþ]: 410.1148, found: 410.1151. Anal.
calcd for C18H22N2O7S: C, 52.81%; H, 5.38%; N, 6.85%.
Found: C, 52.66%; H, 5.39%; N, 6.97%; [a ]2D0¼250.18 (c
0.66, CHCl3).
3.4.2. (2)-(1S,3S,5S)-3-Allyloxy-5-(N-(but-3-enyl)-N-(2-
nitrobenzenesulfonyl)-amino)-cyclohept-6-enyl acetate
[(2)-54]. Compound 51 (120 mg, 0.28 mmol) afforded 54
(50 mg, 38%) as pale brown oil. Rf¼0.22 (cyclohexane/
MTBE 1:1). 1H NMR (200 MHz, CDCl3): d 8.00–8.09 (m,
1H), 7.54–7.73 (m, 3H), 5.53–5.92 (m, 4H), 4.99–5.39 (m,
5H), 4.68–4.80 (m, 1H), 3.76–4.00 (m, 3H), 3.26–3.38 (m,
2H), 1.70–2.50 (m, 6H), 2.05 (s, 3H); 13C NMR (CDCl3): d
170.3, 148.0, 134.6, 134.4, 133.7, 133.5, 133.3, 131.7,
131.5, 131.45, 124.1, 117.3, 116.9, 70.3, 69.1, 68.3, 53.9,
44.8, 38.7, 37.5, 35.5, 21.2; IR: n 3080, 1732, 1542, 1373,
1240, 1165, 1026, 852, 741 cm21; MS (2008C): m/z (%) 423
(5) [Mþ2C3H5], 209 (100), 109 (55); HRMS: calcd for
C19H23N2O7S [Mþ2C3H5]: 423.1226, found: 423.1221;
[a ]2D0¼221.48 (c 0.83, CHCl3).
3.3.2. (2)-(1S,3S,5S )-5-(N-(But-3-enyl)-N-(2-nitro-
benzenesulfonyl)-amino)-3-hydroxycyclohept-6-enyl
acetate [(2)-51]. Compound 43 (270 mg, 0.50 mmol) gave
51 (190 mg, 89%) as a pale yellow oil. Rf¼0.14 (cyclo-
hexane/MTBE 1:1). 1H NMR (500 MHz, CDCl3): d
8.05–8.11 (m, 1H), 7.58–7.72 (m, 3H), 5.57–5.74 (m,
3H), 5.27–5.34 (m, 1H), 5.00–5.08 (m, 2H), 4.85–4.91 (m,
1H), 4.24–4.33 (m, 1H), 3.23–3.38 (m, 2H), 1.98–2.45 (m,
6H), 2.04 (s, 3H), 1.83–1.94 (m, 1H); 13C NMR (CDCl3): d
170.3, 148.1, 134.4, 134.2, 133.2, 133.8, 133.4, 131.9,
131.4, 124.3, 117.5, 68.3, 64.2, 52.6, 44.9, 42.2, 40.3, 35.5,
21.3; IR: n 3524, 3075, 1730, 1543, 1372, 1347, 1239, 1161,
1025, 852, 740 cm21; MS (1908C): m/z (%) 383 (100)
[Mþ2C3H5], 347 (49), 186 (66), 109 (98); HRMS: calcd for
C16H19N2O7S [Mþ2C3H5]: 383.0913, found: 383.0913;
[a]2D0¼258.78 (c 0.62, CHCl3).
3.4.3. (2)-(1S,3S,5S )-3-Allyloxy-5-(N-(but-3-enyl)-N-
benzyloxycarbonyl-amino)-cyclohept-6-enyl acetate
[(2)-55]. Compound 52 (100 mg, 0.32 mmol) gave 55
(49 mg, 37%) as pale brown oil. Rf¼0.52 (cyclohexane/
MTBE 1:1). 1H NMR (200 MHz, CDCl3): (rotameric
mixture) d 7.20–7.40 (m, 5H), 5.52–6.00 (m, 4H), 4.92–
5.48 (m, 7H), 4.40–4.79 (m, 1H), 3.78–4.11 (m, 3H), 3.12–
3.36 (m, 2H), 1.80–2.46 (m, 6H), 2.06 (s, 3H); 13C NMR
(CDCl3): (rotameric mixture) d 170.2, 155.7, 136.7, 135.4,
135.2, 134.8, 131.9, 128.4, 127.9, 127.8, 127.6, 116.7,
116.65, 71.1, 69.2, 68.7, 67.0, 52.8, 46.3, 38.5, 38.1, 34.2,
33.6, 21.2; IR: n 3065, 3031, 1734, 1696, 1415, 1237, 1022,
916, 697 cm21; MS (1708C): m/z (%) 372 (2) [Mþ2C3H5],
354 (2), 312 (4), 109 (8), 91 (100); HRMS: calcd for
C21H26NO5 [Mþ2C3H5]: 372.1811, found: 372.1815;
[a ]2D0¼257.58 (c 0.48, CHCl3).
3.3.3. (2)-(1S,3S,5S )-5-(N-(But-4-enyl)-N-benzyloxycar-
bonyl-amino)-3-hydroxycyclohept-6-enyl acetate [(2)-
52]. Compound 44 (152 mg, 0.31 mmol) gave 52 (102 mg,
88%) as a pale yellow oil. Rf¼0.24 (cyclohexane/MTBE
1
1:1). H NMR (200 MHz, CDCl3): (rotameric mixture) d
7.21–7.37 (m, 5H), 5.50–5.88 (m, 3H), 5.24–5.39 (m, 1H),
4.92–5.16 (m, 4H), 4.52–4.91 (m, 1H), 4.17–4.32 (m, 1H),
3.06–3.42 (m, 2H), 2.10–2.43 (m, 5H), 2.04 (s, 3H),
1.78–2.06 (m, 2H); 13C NMR (CDCl3): (rotameric
mixture) d 170.1, 155.8, 136.5, 135.8, 135.0, 132.3, 131.4,
128.4, 127.9, 127.7, 116.7, 68.6, 67.0, 64.5, 51.6, 46.5,
45.0, 41.9, 41.8, 40.3, 34.4, 33.5, 21.1; IR: n 3448,
3067, 3032, 1732, 1696, 1418, 1239, 1021, 970,
698 cm21; MS (1708C): m/z (%) 373 (1) [Mþ], 332 (15),
143 (30), 138 (22), 91 (100); HRMS: calcd for C21H27NO5
[Mþ]: 373.1889, found: 373.1889; [a]2D0¼278.28 (c 0.62,
CHCl3).
3.5. General procedure for the preparation of 56–58
from 53–55
Compounds 53, 54 or 55 (0.11 mmol) and [Ru] (5 mol%)

7518
H. Ovaa et al. / Tetrahedron 58 (2002) 7503–7518
were refluxed in dry CH2Cl2 (2 mL) under N2 atmosphere.
The solution was concentrated in vacuo, the residue was
purified by FC (cyclohexane/MTBE 3:1) to give 56, 57 or
58.
Acknowledgments
This work was financially supported by the Netherlands
Foundation for Chemical Research (NWO-CW) and the
Fonds der Chemischen Industrie.
3.5.1. (1)-(2S,4S )-2-[(2S )-(N-(2-Nitrobenzenesulfonyl)-
2,5-dihydro-1H-pyrrol-2-ylmethyl)]-2,3,4,7-tetrahydro-
oxepin-4-yl acetate [(1)-56]. Compound 53 (49 mg,
0.11 mmol) and [Ru] (5 mg, 5 mol%) gave after 8 h 56
(42 mg, 93%) as a light brown oil. Rf¼0.17 (cyclohexane/
MTBE 1:1). 1H NMR (500 MHz, CDCl3): d 7.87–7.92 (m,
1H), 7.57–7.73 (m, 3H), 5.58–5.87 (m, 5H), 4.80–4.89 (m,
1H), 4.00–4.38 (m, 5H), 2.14–2.25 (m, 1H), 2.07 (s, 3H),
1.87–2.00 (m, 3H); 13C NMR (CDCl3): d 170.4, 148.8,
133.6, 132.0, 131.6, 131.4, 131.1, 130.6, 129.9, 124.3,
124.1, 73.1, 69.4, 67.9, 66.0, 55.2, 42.8, 40.4, 21.4; IR: n
3096, 3026, 1730, 1544, 1371, 1355, 1242, 1168, 1127,
1095, 1028, 852, 743, 654 cm21; MS (2208C): m/z (%) 423
(,1) [MHþ], 363 (25), 253 (94), 236 (26), 186 (100);
HRMS: calcd for C19H23N2O7S [MHþ]: 423.1226, found:
423.1227; [a]2D0¼þ1398 (c 1.07, CHCl3).
References
1. For recent reviews see: (a) Trnka, T. M.; Grubbs, R. H. Acc.
Chem. Res. 2001, 34, 18. (b) Fu¨rstner, A. Angew. Chem. Int.
Ed. Engl. 2000, 39, 3013. (c) Blechert, S. Pure Appl. Chem.
1999, 71(8), 1393.
2. (a) Ovaa, H.; Stragies, R.; van der Marel, G. A.; van Boom,
J. H.; Blechert, S. Chem. Commun. 2000, 1501. (b) Voigtmann,
U.; Blechert, S. Org. Lett. 2000, 2, 3971. (c) Voigtmann, U.;
Blechert, S. Synthesis 2000, 6, 893. (d) Stragies, R.; Blechert,
S. J. Am. Chem. Soc. 2000, 122, 9584. (e) Buschmann, N.;
Ru¨ckert, A.; Blechert, S. J. Org. Chem. 2002, 67, 4325.
3. Adams, J. A.; Gair-Ford, J.; Stamatos, P. J.; Hoveyda, A. H.
J. Org. Chem. 1999, 64, 9690.
3.5.2. (1)-(2S,4S )-2-[(2S )-(N-(2-Nitrobenzenesulfonyl)-
1,2,5,6-tetrahydropyrid-2-ylmethyl)]-2,3,4,7-tetrahydro-
oxepin-4-yl acetate [(1)-57]. Compound 54 (48 mg,
0.11 mmol) and [Ru] (5 mg, 5 mol%) gave after 1 day 57
(35 mg, 74%) as a brown oil. Rf¼0.11 (cyclohexane/MTBE
4. Ovaa, H.; Codee, J. D. C.; Lastdrager, B.; Overkleeft, H. S.;
van der Marel, G. A.; van Boom, J. H. Tetrahedron Lett. 1998,
39, 7987.
5. For a review on asymmetric transition metal catalyzed allylic
alkylations see: Trost, B. M.; van Vranken, D. L. Chem. Rev.
1996, 96, 395.
1
1:1). H NMR (500 MHz, CDCl3): d 7.97–8.01 (m, 1H),
7.54–7.70 (m, 3H), 5.62–5.77 (m, 5H), 4.60–4.66 (m, 1H),
4.25–4.32 (m, 1H), 4.10–4.18 (m, 1H), 3.86–4.03 (m, 2H),
3.20–3.30 (m, 1H), 1.80–2.20 (m, 5H), 2.05 (s, 3H), 1.62–
1.73 (m, 1H); 13C NMR (CDCl3): d 170.4, 148.2, 134.2,
133.3, 131.4, 130.9, 130.4, 130.2, 128.6, 124.5, 123.9, 72.0,
69.5, 68.5, 51.9, 41.4, 40.5, 38.4, 23.3, 21.4; IR: n 3093,
3032, 2924, 2853, 1730, 1543, 1371, 1355, 1242, 1162,
1125, 1109, 1028, 852, 745, 676 cm21; MS (1908C): m/z
(%) 437 (,1) [MHþ], 377 (28), 267 (55), 186 (100), 95
(41); HRMS: calcd for C20H25N2O7S [MHþ]: 437.1382,
found: 437.1388; [a]2D0¼þ1508 (c 0.2, CHCl3).
6. For determination of the enantiomeric excess the nosyl group
was replaced by a tosyl group ((i) PhSH, K2CO3, DMF.
(ii) TsCl, pyridine) in order to facilitate separation of the
enantiomers on a Chiralcel OD Gold column (0.5% iPrOH in
hexane, 0.9 mL/min, 218 nm).
7. Stragies, R.; Blechert, S. Tetrahedron 1999, 55, 8179.
8. (a) Rutjes, F. P. J. T.; Kooistra, T. M.; Hiemstra, H.;
Schoemaker, H. E. Synlett 1998, 192. (b) Ovaa, H.;
Leeuwenburgh, M. A.; van der Marel, G. A.; van Boom,
J. H. Tetrahedron Lett. 1998, 39, 3025.
9. 2-Methoxy-2,5-dihydrofuran 16 rearranges to afford a tetra-
hydrofuran with loss of methanol under the influence of silica
gel. Solutions of 16 must therefore be kept basic (little Et3N)
during work-up and purification by column chromatography in
order to prevent this elimination reaction.
3.5.3. (1)-(2S,4S )-2-[(2S )-(N-benzyloxycarbonyl-
1,2,5,6-tetrahydropyrid-2-ylmethyl)]-2,3,4,7-tetrahydro-
oxepin-4-yl acetate [(1)-58]. Compound 55 (22 mg,
0.053 mmol) and [Ru] (2 mg, 5 mol%) gave after 12 h 58
(19 mg, 92%) as a brown oil. Rf¼0.40 (cyclohexane/MTBE
10. Johnson, C. R.; Golebiowski, A.; Steensma, D. H. J. Am.
Chem. Soc. 1992, 114, 9414.
1
1:1). H NMR (500 MHz, CDCl3): (rotameric mixture) d
11. Stragies, R.; Blechert, S. J. Am. Chem. Soc. 2000, 122, 9584.
12. For the deprotection protocol see: Fukuyama, T.; Joe, C.-K.;
Cheung, M. Tetrahedron Lett. 1995, 52, 1922.
7.26–7.39 (m, 5H), 5.45–5.83 (m, 5H), 5.10–5.23 (m, 2H),
4.56–4.80 (m, 1H), 3.42–4.43 (m, 3H), 3.69–3.75 (m, 2H),
2.84–2.98 (m, 1H), 1.78–2.35 (m, 4H), 2.04 (s, 3H), 1.57–
1.66 (m, 1H); 13C NMR (CDCl3): (rotameric mixture) d
170.4, 155.8, 155.4, 137.0, 136.7, 130.8, 130.4, 129.7,
129.2, 128.5, 127.8, 128.1, 125.4, 124.8, 73.1, 72.7, 69.8,
69.5, 69.3, 68.3, 67.3, 67.0, 50.1, 50.0, 41.0, 40.9, 40.8,
40.7, 37.4, 37.0, 25.1, 24.6, 21.4; IR: n 3064, 3031, 1734,
1695, 1420, 1238, 1095, 1026, 698 cm21; MS (1608C): m/z
(%) 386 (,1) [MHþ], 216 (40), 172 (49), 166 (20), 91
(100); HRMS: calcd for C22H28NO5 [MHþ]: 386.1967,
found: 386.1970; [a]2D0¼þ998 (c 0.39, CHCl3).
13. Zuercher, W. J.; Hashimoto, M.; Grubbs, R. H. J. Am. Chem.
Soc. 1996, 118, 6634.
14. Wessel, H.-P.; Iversen, T.; Bundle, D. R. J. Chem. Soc., Perkin
Trans. 1 1985, 2247.
15. Instead of working in a glove box, Schlenk technique may also
be used. Solid Grubbs catalyst [Ru] can be handled in air.