Diastereoselectivity in a ring closing metathesis reaction with a remote stereogenic centre leading to quaternary dihydropyrans

Article abstract of DOI:10.1016/S0040-4020(00)00150-2

Starting from α-allyloxy esters, divinyl carbinols with diastereotopic vinyl groups become accessible. Diastereoselectivity for ring closing metathesis reactions of these trienes was investigated. Formation of a spirocyclic derivative proceeds with signif

Full text of DOI:10.1016/S0040-4020(00)00150-2

TETRAHEDRON
Pergamon
Tetrahedron 56 (2000) 2421–2426
Diastereoselectivity in a Ring Closing Metathesis Reaction
with a Remote Stereogenic Centre Leading to
Quaternary Dihydropyrans
*
Bernd Schmidt and Markus Westhus
¨
Universitat Dortmund, Fachbereich Chemie, Organische Chemie I, Otto-Hahn-Straße 6, D-44227 Dortmund, Germany
Received 13 January 2000; accepted 16 February 2000
Abstract—Starting from a-allyloxy esters, divinyl carbinols with diastereotopic vinyl groups become accessible. Diastereoselectivity for
ring closing metathesis reactions of these trienes was investigated. Formation of a spirocyclic derivative proceeds with significant diastereo-
selectivity, and a mechanistic proposal for the diastereoselective formation of spirocyclic derivatives is presented. ᭧ 2000 Elsevier Science
Ltd. All rights reserved.
Introduction
The objective of this study is to find out if significant dia-
stereoselectivity in the formation of dihydropyrans requires
the presence of an adjacent stereogenic centre, or if remote
stereocentres will also lead to a significant diastereo-
selection. Scheme 1 schematically illustrates the different
approaches.
The discovery of ruthenium carbene complexes as efficient
catalysts for ring closing metathesis by Grubbs et al.1–3 has
led to a manifold of different applications of this synthetic
method.4–6 Thus, over the past few years ring closing
metathesis turned out to be an efficient tool for the prepara-
tion of medium-sized and large carba- and heterocycles. In
the field of heterocyclic chemistry the majority of contribu-
tions deal with the synthesis of oxa- and azacycles, and
many efforts were made to develop synthetic methodologies
for suitably functionalized precursors. If metathesis pre-
cursors are chiral (racemic or non-racemic) and contain
diastereotopic vinyl or allyl groups, ring closing metathesis
may in principle become a diastereoselective process. The
first example for this approach was described by Blechert et
al. for a highly diastereoselective ring closing metathesis
leading to five membered azacycles.7 More recently
decaline derivatives8 and oxepines annellated to a carbo-
hydrate scaffold9 were synthesized via diastereoselective
ring closing metathesis. A diastereoselective synthesis of
dihydropyrans with two adjacent stereogenic centres start-
ing from a-hydroxy esters was investigated by us.10
Results and Discussion
The metathesis precursors required for this study were
prepared starting from allylic alcohol 1.11 Alkylation of 1
with ethyl-2-bromoacetate in the presence of NaH as a base
has to be carried out at 0ЊC, otherwise a Wittig rearrange-
ment leading to a a-hydroxy ester 3 occurs. Treatment of 3
with excess vinylmagnesium chloride yields the divinyl-
carbinol 4, along with 10% of the ketone 5, resulting from
a 1,4-addition. The yield of 4 and 5 is quantitative, however,
isolation of 4a by column chromatography leads to a
decrease of the yield to 52%, probably due to acid mediated
decomposition of the divinylcarbinol. Variation of the steric
demand of the hydroxy substituent in 4a was achieved by
introduction of different protecting groups. This derivatization
Scheme 1.
Keywords: diastereoselectivity; dihydropyrans; metathesis reaction.
* Corresponding author. Tel.: ϩ49-231-7553850; fax: ϩ49-231-7555363; e-mail: bschmidt@citrin.chemie.uni-dortmund.de
0040–4020/00/$ - see front matter ᭧ 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020(00)00150-2

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B. Schmidt, M. Westhus / Tetrahedron 56 (2000) 2421–2426
results, whereas for the benzyl- and TBDMS derivative
the cis-isomer is very slightly preferred (Scheme 3).
Comparison of these results to those obtained by ourselves
for dihydropyrans and by Lautens for substituted cyclo-
hexenes8 suggests, that a substituent in the neighbouring
position to the newly formed stereogenic centre is required
to obtain a significant diastereoselectivity, whereas a 1,4-
distance of the two stereocentres does not seem to cause a
noticeable diastereoselection. If, however, tetraene 4d
reacts with the ruthenium catalyst, the spirocycles 7 are
formed in a diastereomeric ratio of 7:1 (Scheme 4).12 This
is surprising, since the allyl substituent in 4d is definitely
sterically less demanding than a benzyl- or a TBDMS group,
and hence should not lead to any diastereoselection. 7b may
also be prepared from cis-6a by allylation to give ether 8 and
subsequent ring closing metathesis, whereas this option
does not exist for the trans-diastereomer, which rapidly
decomposes upon attempted allylation. The relative con-
figuration of 7a and 7b was elucidated by NOESY experi-
ments conducted for both diastereomers. In both cases a
NOE interaction between H2 and H6ax indicates that the
sterically demanding aryl substituent adopts an equatorial
position. In the minor diastereomer 7b an additional NOE
between H6ax and the olefinic hydrogen of the dihydrofuran
Scheme 2. (i) NaH (1.3 equiv.), THF, 65ЊC, then 0ЊC, add ethyl-2-bromo-
propionate (1.3 equiv.), 20 min (76%); (ii) NaH (1.3 equiv.), THF, 65ЊC,
then 0ЊC, add ethyl-2-bromopropionate (1.3 equiv.), 30 min., add NaH
(1.3 equiv.), 2 h; (iii) H2CvCHMgCl, Et2O, Ϫ60ЊC, (52% of 4a); (iv)
NaH (3 equiv.), THF, 65ЊC, 1 h, then benzyl bromide (3 equiv.), 65ЊC,
2 h (88%); (v) NaH (3 equiv.), THF, 65ЊC, 1 h, then TBDMSCl
(3 equiv.), 65ЊC, 10 min. (86%); (vi) NaH (3 equiv.), THF, 65ЊC, 1 h,
then allyl bromide (3 equiv.), 65ЊC, 2 h (78%).
Scheme 3. (i) Cl2(PCy3)2RuvCHPh, 7 mol% (84% yield) for 6a, 7 mol% (81% yield) for 6b, 10 mol% (80% yield) for 6c.
requires rather harsh conditions (excess of base, high
temperatures, prolonged reaction times), nevertheless no
isomerization of the allylic double bond into conjugation
with the aromatic substituent is observed (Scheme 2).
fragment is observed, which is completely missing for the
major isomer 7a (Scheme 4).
What is the origin of the diastereoselectivity in the forma-
tion of 7? To answer this question, we first investigated
whether the five- or the six-membered ring is formed first.
For this purpose, we conducted the ring closing metathesis
of 4d as an NMR-tube experiment in C6D6. After 1 h the
starting material is nearly completely consumed, and a 1:1
mixture of the two diastereomeric dihydrofurans 9a,b is
formed. The second metathesis step is very slow and leads
to the formation of the spirocycles in a 7:1 ratio of dia-
stereomers. From these observations it may be concluded
that 9a cyclizes much faster than 9b. Via a ring-opening/
ring closing metathesis sequence13 9b can be converted to
9a, thereby restoring the equilibrium mixture. It was not
possible to detect deviations from the 1:1 diastereomeric
ratio of the intermediate 9 during the NMR-tube experi-
ment, suggesting that the ring opening metathesis leading
to equilibration is fast compared to the second ring closing
metathesis step. No interconversion of 7a into 7b and vice
versa was observed upon exposure to the Grubbs’ catalyst,
suggesting that ring closure of the six-membered ring is
irreversible. The mechanistic proposal is summarized in
Scheme 5.
If trienes 4a–c are subjected to ring closing metathesis, only
very poor diastereoselectivities are observed. In the case of
4a an easily separable 2:3 mixture of cis- and trans-6a
Scheme 4. (i) Cl2(PCy3)2RuvCHPh, 15 mol%, 7a:7bˆ7:1 (84%). (ii)
NaH, THF, 65ЊC, 1 h, then allyl bromide, 65ЊC, 2 h (85%); (iii)
Cl2(PCy3)2RuvCHPh, 5 mol% (83%).

B. Schmidt, M. Westhus / Tetrahedron 56 (2000) 2421–2426
2423
added dropwise. After stirring at 0ЊC for 2 h the reaction
was completed (TLC, hexanes/MTBE 5:1). Aqueous
workup, followed by chromatography on silica (hexanes/
MTBE 5:1), yielded 3.80 g (76%) of 2. Anal.: Found: C,
67.0; H, 7.3, Calcd for C14H18O4 C, 67.2; H, 7.3. LRMS
1
(EI): m/z 250 (Mϩ, 28), 163 (100), 147 (51). H NMR: d
7.21 (d, 1, Jˆ8.8 Hz, Ar), 6.80 (d, 1, Jˆ8.8 Hz, Ar), 5.90
(ddd, 1, Jˆ17.1 Hz, 10.3, 6.8, –CHv), 5.20 (dm, 1, Jˆ
17.1 Hz, CH2), 5.15 (dm, 1, Jˆ10.3 Hz, CH2), 4.80 (d, 1,
Jˆ6.8 Hz, OCHAr), 4.12 (q, 2, Jˆ7.0 Hz, OEt), 3.99 (d, 1,
Jˆ16.3 Hz, OCHHCO2Et), 3.94 (d, 1, Jˆ16.3 Hz, OCHH-
CO2Et), 3.71 (s, 3, OMe), 1.18 (t, 3, Jˆ7.0 Hz, Et). 13C
NMR: d 170.4 (0), 159.3 (0), 137.8 (1), 131.8 (0), 128.3
(1), 116.9 (2), 113.8 (1), 82.5 (1), 65.2 (2), 60.6 (2), 55.1 (3),
14.1 (3). IR (NaCl, neat) 2987 (w), 1753 (s), 1733 (s), 1611
(w), 1512 (s), 1248 (s), 1202 (s), 1118 (s), 1033 (s).
(E)-2-Hydroxy-5-(4-methoxyphenyl)-pent-4-enoic acid
ethyl ester (3). To a solution of alcohol 1 (3.60 g,
22.0 mmol) in dry THF (50 mL) was added NaH (1.20 g,
60% dispersion in mineral oil, 30.0 mmol) and heated to
reflux for 30 min. The mixture was cooled to 0ЊC and
ethyl 2-bromoacetate was added. After 20 min at 0ЊC
another portion of NaH (1.20 g, 60% dispersion in mineral
oil, 30.0 mmol) was added and the mixture was stirred at
room temperature for 2 h. After aqueous workup and chro-
matography a-hydroxy ester 3 was isolated in 2.15 g (38%)
yield. LRMS (EI): m/z 250 (Mϩ, 10), 232 (10), 147 (100).
1H NMR: d 7.16 (d, 2, Jˆ8.8 Hz, Ar), 6.72 (d, 1, Jˆ8.8 Hz,
Ar), 6.32 (d, 1, Jˆ15.7, ArCHv), 5.95 (ddd, 1, Jˆ15.7, 7.3,
7.3 Hz, ArCHvCH–), 4.23–4.07 (3, OCHH, CHOH), 3.68
(s, 3, OMe), 2.86 (d, 1, Jˆ6.0 Hz, OH), 2.59 (dddd, 1, Jˆ
14.1 Hz, 7.3, 4.8, 1.5, CHHCH(OH)), 2.47 (dddd, 1, Jˆ
14.1, 7.3, 7.3, 1.3 Hz, CHHCH(OH)), 1.18 (t, 3, Jˆ
7.0 Hz, Et). 13C NMR: d 174.4 (0), 158.9 (0), 133.0 (1),
129.8 (0), 127.3 (1), 121.5 (1), 113.8 (1), 70.3 (1), 61.6
(2), 55.2 (3), 38.0 (2), 14.2 (3). IR (NaCl, neat) 3470 (s),
2982 (s), 2837 (m), 1739 (s), 1732 (s), 1608 (s), 1513 (s),
1250 (s), 1177 (s), 1032 (s), 969 (s), 839 (m).
Scheme 5. Proposed mechanism for the formation of 7a,b.
In conclusion we have shown that diastereoselective ring
closing metathesis leading to dihydropyrans with a 1,4-
distance of the stereogenic centres can not be achieved by
increasing the size of the substituents, whereas conforma-
tional rigidity, e.g. by incorporating one of the stereocentres
into a cycle, may lead to stereodifferentiation. The forma-
tion of the dihydrofuran ring is fast and reversible by ring
opening/ring closing metathesis, which allows an inter-
conversion of the intermediates. Formation of the six-
membered ring was found to be slow and irreversible.
Application of this concept to the stereoselective synthesis
of 2,5-difunctionalized dihydropyrans is currently under
investigation.
Experimental
General remarks
All experiments were conducted in dry reaction vessels in
an atmosphere of dry argon. Solvents were purified by
standard procedures. H NMR spectra were recorded at
1-[1-(4-Methoxyphenyl)allyloxy]-2-vinyl-but-3-en-2-ol
(4a). A solution of vinyl–magnesium chloride in THF
(23.0 mL, 1.7 M, 40.0 mmol) was added dropwise at
Ϫ60ЊC to a solution of the ester 3 (3.20 g, 12.8 mmol) in
ether (100 mL). The mixture was stirred for 1 h, then
warmed to room temperature and stirring was continued
for 2 h. The reaction was poured onto aqueous NH4Cl solu-
tion (50 mL), the aqueous layer was separated and extracted
with MTBE; the combined organic layers were dried with
MgSO4. After evaporation of the solvent, the residue was
purified by column chromatography on silica using hexanes/
MTBE mixtures of increasing polarity as eluent. Yield:
1.70 g (52%). Anal.: Found: C, 73.9; H, 7.7, Calcd for
C16H20O3 C, 73.8; H, 7.7. LRMS (EI): m/z Mϩ not observed,
147 (100). 1H NMR: d 7.21 (d, 2, Jˆ8.8 Hz, Ar), 6.86 (d, 2,
Jˆ8.8 Hz, Ar), 5.93–5.86 (3, –CHvCH2), 5.35 (dd, 1,
Jˆ17.3, 1.4 Hz, –CHvCH2), 5.32 (dd, 1, Jˆ17.3, 1.4 Hz,
–CHvCH2), 5.22 (ddd, 1, Jˆ17.3, 1.5, 1.5 Hz,
CHCHvCH2), 5.18–5.15 (3, –CHvCH2), 4.72 (d, 1,
Jˆ6.5 Hz, ArCHO), 3.78 (s, 3, OMe), 3.43 (d, 1,
Jˆ9.2 Hz, OCHH), 3.34 (d, 1, Jˆ9.2 Hz, OCHH). 13C
NMR: d 159.2 (0), 139.8 (1), 139.7 (1), 138.6 (1), 132.6
(0), 128.1 (1), 116.1 (2), 114.7 (2), 114.7 (2), 113.8 (1),
1
400 MHz in CDCl3 with CHCl3 as internal standard
(dˆ7.24). 13C NMR spectra were recorded at 100 MHz in
CDCl3 with CDCl3 as internal standard (dˆ77.0). J values
are given in Hz. The number of coupled protons was
analysed by DEPT experiments and is denoted by a number
in parentheses following the dC value. The NMR tube
experiments were carried out in C6D6 at 500 MHz (1H
NMR). IR spectra were recorded as films on NaCl plates
or as KBr disks. The peak intensities are defined as very
strong (vs), strong (s), medium (m), and weak (w). Mass
spectra were obtained at 70 eV. Alcohol 1 was prepared
according to a literature procedure.11 The ruthenium catalyst
Cl2(PCy3)2RuvCHPh was prepared following Grubbs’
procedure.3
[1-(4-Methoxyphenyl)-allyloxy]acetic acid ethyl ester
(2). To a solution of alcohol 1 (3.28 g, 20 mmol) in THF
(80 mL) was added NaH (1.44 g, 50% suspension in mineral
oil, 30 mmol). The mixture was heated to reflux until the
evolution of hydrogen gas finished, cooled to 0ЊC, and ethyl
bromoacetate (3.33 mL, 30 mmol) in THF (20 mL) was

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B. Schmidt, M. Westhus / Tetrahedron 56 (2000) 2421–2426
83.1 (1), 75.4 (0), 74.1 (2), 55.2 (3). IR (NaCl, neat)
3555 (m), 2934 (m), 1610 (s), 1512 (s), 1088 (s), 926 (s),
831 (m).
CHCHvCH2), 5.32 (ddd, 1, Jˆ17.3, 1.3, 1.3 Hz,
–CHCHvCH2), 5.23 (ddd, 1, Jˆ10.3, 1.3, 1.3 Hz,
–CHCHvCH2), 5.18–5.12 (4, –CHvCH2), 4.70 (d, 1,
Jˆ6.5 Hz, OCHCHvCH2), 3.40 (d, 1, Jˆ9.3 Hz, OCHH),
3.31 (d, 1, Jˆ9.3 Hz, OCHH), 3.79 (s, 3, OMe), 0.89 (s, 9,
tert-Bu), 0.06 (s, 3, Si(CH3)2), 0.05 (s, 3, Si(CH3)2). 13C
NMR: d 159.0 (0), 140.9 (1), 140.8 (1), 139.2 (1), 133.1
(0), 128.1 (1), 115.7 (2), 114.8 (2), 114.8 (2), 113.7 (1), 83.2
(1), 77.8 (0), 75.2 (2), 55.2 (3), 26.0 (3), 18.5 (0), 2.1 (3), 2.1
(3). IR (NaCl, neat) 2956 (m), 2929 (m), 2856 (m), 1511 (s),
1249 (s), 1093 (m), 1040 (m), 836 (m), 776 (m).
1-[1-(4-Methoxyphenyl)allyloxy]-hex-5-en-2-one
(5).
Colourless liquid, separated from the triene 10a by column
chromatography. Yield: 0.31 g (9%). LRMS (EI): m/z Mϩ
not observed, 147 (100). 1H NMR: d 7.23 (d, 2, Jˆ8.8 Hz,
Ar), 6.85 (d, 2, Jˆ8.8 Hz, Ar), 5.92 (ddd, 1, Jˆ17.1 Hz,
10.3, 6.5, –CHCHvCH2), 5.76 (dddd, 1, Jˆ17.0, 10.0,
6.4, 6.4 Hz, –CH2CHvCH2), 5.25 (d, 1, Jˆ17.1 Hz,
CHvCH2), 5.19 (d, 1, Jˆ10.3 Hz, CHvCH2), 4.99 (dm,
1, Jˆ17.0 Hz, CHvCH2), 4.93 (dm, 1, Jˆ10.0, CHvCH2),
4.72 (d, 1, Jˆ6.5 Hz, ArCHO), 3.98 (d, 1, Jˆ17.0 Hz,
OCHHCvO), 3.92 (d, 1, Jˆ17.0 Hz, OCHHCvO), 3.76
(s, 3, OMe), 2.58–2.53 (2, CHH), 2.33–2.25 (2, CHH).
13C NMR: d 208.4 (0), 159.3 (0), 138.0 (1), 136.9 (1),
131.9 (0), 128.2 (1), 116.7 (2), 115.3 (2), 113.9 (1), 82.8
(1), 73.3 (2), 55.2 (3), 38.2 (2), 27.1 (2). IR (NaCl, neat)
3078 (m), 2934 (m), 1720 (s), 1611 (s), 1512 (s), 1248 (s),
1105 (s), 1035 (s), 919 (s).
1-[1-(2-Allyloxy-2-vinyl-but-3-enyloxy)-allyl]-4-methoxy-
benzene (4d). 4d was obtained from triene 4a (0.83 g,
3.2 mmol) and allyl bromide (0.43 mL, 5.0 mmol) follow-
ing the procedure given above for the preparation of 4b
(TLC: hexanes/MTBE 10:1). Yield: 0.75 g (78%). LRMS
(EI): m/z Mϩ not observed, 147 (100). 1H NMR: d 7.21 (d,
2, Jˆ8.5 Hz, Ar), 6.83 (d, 2, Jˆ8.5 Hz, Ar), 5.96–5.82 (4,
–CHvCH2), 5.32–5.22 (5, –CHvCH2), 5.20 (ddd, 1,
Jˆ17.1, 1.4, 1.4 Hz, –CHvCH2), 5.12 (dm, 1, Jˆ
10.3 Hz, –CHvCH2), 5.07 (dddd, 1, Jˆ10.3, 1.5, 1.5,
1.5 Hz, –CHvCH2), 4.73 (d, 1, Jˆ6.5 Hz, OCHCHvCH2),
3.91 (ddd, 2, Jˆ5.3, 1.5, 1.5 Hz, OCHHCHvCH2), 3.76 (s,
3, OMe), 3.49 (d, 1, Jˆ9.8 Hz, OCHH), 3.41 (d, 1,
Jˆ9.8 Hz, OCHH). 13C NMR: d 159.0 (0), 139.0 (1),
137.9 (1), 137.9 (1), 135.8 (1), 133.1 (0), 128.1 (1), 116.9
(2), 116.8 (2), 115.8 (2), 115. 5 (2), 113.7 (1), 83.0 (1), 80.6
(0), 73.8 (2), 64.7 (2), 55.2 (3). IR (NaCl, neat) 3082 (m),
2909 (m), 1836 (m), 1611 (s), 1511 (s), 1105 (s), 925 (s),
829 (s).
1-[1-(2-Benzyloxy-2-vinyl-but-3-enyloxy)-allyl]-4-methoxy-
benzene (4b). To a solution of 4a (0.30 g, 1.2 mmol) in
THF (10 mL) was added NaH (160 mg, 60% dispersion in
mineral oil, 4.0 mmol). The mixture was refluxed for
30 min, and then benzyl bromide (0.50 mL, 4.2 mmol)
was added, and the mixture was again refluxed, until the
starting material was completely consumed as indicated
by TLC (hexanes/MTBE 10:1). The reaction was quenched
by addition of water (10 mL). The mixture was extracted
with MTBE and dried over MgSO4. Evaporation of the
solvent and flash chromatography yields 0.37 g (88%) of
4b. Anal.: Found: C, 78.0; H, 7.4, Calcd for C23H26O3 C,
78.8; H, 7.5. LRMS (EI): m/z (Mϩ not observed), 162 (30),
147 (100), 91 (54). 1H NMR: d 7.33–7.12 (7, Ar, Ph), 6.82
(d, 2, Jˆ8.8 Hz, Ar), 5.97 (dd, 1, Jˆ17.5, 10.5 Hz,
–CHvCH2), 5.95 (dd, Jˆ17.5, 10.5 Hz, –CHCH2), 5.86
(ddd, 1, Jˆ17.1, 10.3, 6.3 Hz, CHCHvCH2), 5.34 (dd, 1,
Jˆ17.5, 1.5 Hz, –CHvCH2), 5.33 (dd, 1, Jˆ17.5, 1.5 Hz,
–CHvCH2), 5.30 (dd, 1, Jˆ10.5, 1.5 Hz, –CHvCH2), 5.28
(dd, 1, Jˆ10.5, 1.5 Hz, –CHvCH2), 5.21 (ddd, 1, Jˆ17.1,
1.5, 1.5 Hz, –CHCHvCH2), 5.12 (ddd, 1, Jˆ10.3, 1.5,
1.5 Hz, –CHCHvCH2), 4.74 (d, 1, Jˆ6.3 Hz, ArCHO),
4.46–4.44 (2, OCHHPh), 3.74 (s, 3, OMe), 3.55 (d, 1,
Jˆ10.0 Hz, OCHH), 3.47 (d, 1, Jˆ10.0, OCHH). 13C
NMR: d 1159.0 (0), 139.6 (0), 139.0 (1), 137.9 (1), 137.9
(1), 133.1 (0), 128.1 (1), 128.1 (1), 127.1 (1), 127.0 (1),
117.1 (2), 117.1 (2), 115.8 (2), 113.7 (1), 83.0 (1), 80.7
(0), 73.8 (2), 65.5 (2), 55.2 (3). IR (NaCl, neat) 3029 (m),
2951 (m), 2933 (m), 1610 (s), 1511 (s), 1248 (s), 1089 (s),
929 (s).
(3R* 6S*-6-(4-methoxyphenyl)-3-vinyl-3,6-dihydro-2H-
pyran-3-ol (cis-6a) and (3R* 6R*)-6-(4-methoxyphenyl)-
3-vinyl-3,6-dihydro-2H-pyran-3-ol (trans-6a). To a solu-
tion of the triene 4a (0.34 g, 1.3 mmol) in DCM (15 mL)
was added the Grubbs’ catalyst (0.075 g, 7 mol%) and the
mixture was stirred at ambient temperature for 24 h leading
to a 2:3 mixture of diastereomers. Evaporation of the solvent
followed by column chromatography on silica (hexanes/
MTBE mixtures of increasing polarity) gave the diastereo-
isomers in 84% yield. Diastereomer cis-6a: colourless
liquid, 0.10 g. Anal.: Found: C, 72.2; H, 6.9, Calcd for
C14H16O3 C, 72.4; H, 6.9. LRMS (EI): m/z 232 (Mϩ, 5%),
215 (100), 202 (30), 121 (40). 1H NMR: d 7.28 (d, 2, Jˆ8.8,
Ar), 6.88 (d, 2, Jˆ8.8 Hz, Ar), 5.95 (d, 1, Jˆ10.5 Hz, H3),
5.92 (dd, 1, Jˆ10.5, 1.0 Hz, H4), 5.88 (dd, 1, Jˆ17.3 Hz,
10.8, CHCHvCH2), 5.41 (dd, 1, Jˆ17.3, 1.3 Hz,
CHvCH2), 5.24 (d, 1, Jˆ10.8, 1.3 Hz, CHvCH2), 5.00 (s
(br), 1, H2), 3.86 (dd, 1, Jˆ11.5, 1.0 Hz, H6), 3.78 (s, 3,
OMe), 3.68 (d, 1, Jˆ11.5 Hz, H6), 2.46 (s, 1, OH). 13C
NMR: d 159.6 (0), 138.7 (1), 131.9 (0), 131.8 (1), 130.1
(1), 128.7 (1), 115.8 (2), 114.0 (1), 76.4 (1), 74.2 (2), 68.0
(0), 55.3 (3). IR (NaCl, neat) 3427 (s br), 2959 (m), 1611 (s),
1514 (s), 1247 (s), 1175 (s), 1080 (s), 821 (s). Diastereomer
trans-6a: colourless liquid, 0.16 g. LRMS (EI): m/z 232
tert-Butyl-{1-[1-(4-methoxyphenyl)-allyloxymethyl]-1-
vinylallyloxy}-dimethylsilane (4c). 4c was obtained from
triene 4a (0.44 g, 1.7 mmol) and tert-butyldimethylsilyl
chloride (0.75 g, 5.1 mmol) following the procedure given
above for the preparation of 4b (TLC: hexanes/MTBE
50:1). Yield: 0.54 g (86%). LRMS (EI): m/z 374 (Mϩ,
1
(Mϩ, 5%), 215 (50), 202 (60), 121 (100). H NMR: d 7.19
(d, 2, Jˆ8.8 Hz, Ar), 6.82 (d, 2, Jˆ8.8 Hz, Ar), 5.95 (dd, 1,
Jˆ17.3, 10.8, CHvCH2), 5.90 (dd, 1, Jˆ10.3, 2.0 Hz,
H3,4), 5.82 (dd, 1, Jˆ10.3, 1.8 Hz, H3,4), 5.33 (dd, 1,
Jˆ17.3, 0.8 Hz, CHvCH2), 5.16 (d, 1, Jˆ10.8, 0.8 Hz,
CHvCH2), 5.06 (dd, 1, Jˆ2.0, 1.8 Hz, H2), 3.73 (s, 3,
OMe), 3.69 (d, 1, Jˆ11.3 Hz, H6), 3.54 (d, 1, Jˆ11.3 Hz,
1
Ͻ1%), 259 (6%, Mϩ-TBDMS), 147 (100). H NMR: d
7.23 (d, 2, Jˆ8.5 Hz, Ar), 6.87 (d, 2, Jˆ8.5 Hz, Ar), 6.03
(dd, 1, Jˆ17.3, 10.5 Hz, –CHvCH2), 5.96 (dd, Jˆ17.3,
10.5 Hz, –CHvCH2), 5.90 (ddd, 1, Jˆ17.1, 10.3, 6.5 Hz,

B. Schmidt, M. Westhus / Tetrahedron 56 (2000) 2421–2426
2425
H6), 2.21 (s, 1, OH). 13C NMR: d 159.5 (0), 140.1 (1), 131.4
(0), 130.4 (1), 130.3 (1), 129.2 (1), 115.0 (2), 113.9 (1), 75.1
(1), 71.4 (2), 68.5 (0), 55.3 (3). IR (NaCl, neat) 3418 (s br),
2958 (s), 1611 (s), 1513 (s), 1247 (s), 1174 (s), 1085 (s),
1035 (s), 732 (s).
(3R*, 6R*)-3-Allyloxy-6-(4-methoxyphenyl)-3-vinyl-3,6-
dihydro-2H-pyran (8). 8 was obtained from cis-6a
(0.20 g, 0.8 mmol) and allyl bromide (0.20 mL, 2.4 mmol)
following the procedure given above for the preparation of
4b–d (TLC: hexanes/MTBE 10:1). Yield: 0.20 g (85%).
LRMS (EI): m/z 272 (Mϩ, 12%), 242 (43), 201 (77), 135
1
3-Benzyloxy-6-(4-methoxyphenyl)-3-vinyl-3,6-dihydro-
2H-pyran (6b). 6b was obtained from triene 4b (0.16 g,
0.4 mmol) and the Grubbs’ catalyst (0.026 g, 7 mol%)
following the procedure given above for the preparation
of dihydropyrans 6a as an inseparable 1:1 mixture of
diastereoisomers. Yield: 0.12 g (81%). LRMS (EI): m/z
Mϩ not observed. 1H NMR: d 7.38–7.10 (7, Ar, Ph),
6.88–6.82 (2, Ar), 6.13–5.83 (3, –CHvCH2, H3,4), 5.42
(dd, 1, Jˆ17.5, 1.3 Hz, –CHvCH2), 5.37 (dd, 1, Jˆ17.5,
1.3 Hz, –CHvCH2), 5.33 (dd, Jˆ10.6, 1.5 Hz, –CHCH2),
5.26 (dd, 1, Jˆ10.3, 1.5 Hz, –CHvCH2), 5.07 (s, 1, H2),
4.98 (s, 1, H2), 4.71 (d, 1, Jˆ11.5 Hz, OCHHPh), 4.64 (d, 1,
Jˆ11.5 Hz, OCHHPh), 4.61 (d, 1, Jˆ11.6 Hz, OCHHPh),
4.56 (d, 1, Jˆ11.6 Hz, OCHHPh), 4.12 (dd, 1, Jˆ12.2,
1.0 Hz, H6), 3.88 (d, 1, Jˆ11.3 Hz, H6), 3.83 (d, 1,
Jˆ11.3 Hz, H6), 3.75 (s, 3, OMe), 3.68 (d, 1, Jˆ12.2 Hz,
H6). 13C NMR: d 159.5 (0), 159.5 (0), 139.9 (1), 139.5 (0),
139.3 (1), 139.2 (0), 134.2 (1), 132.3 (1), 132.2 (0), 131.9
(0), 129.0 (1), 128.8 (1), 128.4 (1), 128.1 (1), 127.5 (1),
127.3 (1), 127.2 (1), 127.1 (1), 127.1 (1), 126.6 (1), 117.3
(2), 116.5 (2), 113.9 (1), 113.8 (1), 76.0 (1), 75.8 (1), 73.5
(0), 72.6 (0), 72.5 (2), 70.3 (2), 66.3 (2), 65.3 (2), 55.2 (3),
55.2 (3). IR (NaCl, neat) 1611 (m), 1513 (s), 1248 (s), 1093
(s), 1035 (m), 829 (m), 734 (m).
(49), 55 (100). H NMR: d 7.31 (d, 2, Jˆ8.5 Hz, Ar), 6.88
(d, 2, Jˆ8.5 Hz, Ar), 6.10 (dd, 1, Jˆ10.3, 1.5 Hz, H3,4),
5.96 (dddd, 1, Jˆ17.2, 10.5, 5.3, 5.3 Hz, OCHHCHvCH2),
5.88 (dm, 1, Jˆ10.3 Hz, H3,4), 5.84 (dd, 1, Jˆ17.6 Hz,
10.8, CHvCH2), 5.37 (dd, 1, Jˆ17.6, 0.8 Hz, CHvCH2),
5.30 (dddd, 1, Jˆ17.2, 1.8, 1.8, 1.8 Hz, OCHHCHvCH2),
5.26 (d, 1, Jˆ10.8 Hz, 0.8, CHvCH2), 5.13 (dddd, 1,
Jˆ10.3 Hz, 1.8, 1.8, 1.8, OCHHCHvCH2), 4.98 (s, 1,
H2), 4.20 (ddm, 1, Jˆ12.6, 5.3 Hz, OCHHCHvCH2),
4.11 (ddm, 1, Jˆ12.6, 5.3 Hz, OCHHCHvCH2), 4.05 (d,
1, Jˆ12.0 Hz, H6), 3.78 (s, 3, OMe), 3.65 (d, 1, Jˆ12.0 Hz,
H6). 13C NMR: d 159.4 (0), 139.3 (1), 135.8 (1), 134.0 (1),
132.2 (0), 128.8 (1), 126.6 (1), 116.4 (2), 115.9 (2), 113.9
(1), 75.9 (1), 72.4 (0), 72.3 (2), 65.3 (2), 55.2 (3). IR (NaCl,
neat) 2958 (m), 2838 (m), 1612 (s), 1514 (s), 1249 (s), 1173
(m), 1089 (s), 1036 (m), 926 (m).
(5R*, 8S*)-8-(4-Methoxyphenyl)-1,7-dioxaspiro[4,5]deca-
3,9-diene (7a). To a solution of the tetraene (0.30 g,
1.0 mmol) in toluene (15 mL) was added the Grubbs’ cata-
lyst (0.123 g, 15 mol%). The mixture was heated to reflux
for 18 h, the solvent was evaporated and the residue purified
by column chromatography to give 7a (0.18 g, 72%) along
with the (5S*, 8S*)-diastereoisomer 7b (0.03 g, 12%).
LRMS (EI): m/z 245 (Mϩϩ1, 10%), 214 (100), 121 (50).
1H NMR (C6D6): d 7.26 (d, 2, Jˆ8.8 Hz, Ar), 6.82 (d, 2,
Jˆ8.8 Hz, Ar), 5.88 (ddd, 1, Jˆ5.9, 2.0, 2.0 Hz, H40), 5.87
(dm, Jˆ10.3 Hz, H4), 5.66 (dd, 1, Jˆ10.3, 2.0 Hz, H3), 5.45
(ddd, 1, Jˆ5.9, 2.0, 2.0 Hz, H30), 4.97 (dd, 1, Jˆ2.0, 2.0 Hz,
H2), 4.51 (ddd, 1, Jˆ13.0, 2.0, 2.0 Hz, H50), 4.42 (ddd, 1,
Jˆ13.0, 2.0, 2.0 Hz, H50), 4.01 (d, 1, Jˆ10.8 Hz, H6eq),
3.97 (d, 1, Jˆ10.8 Hz, H6ax), 3.32 (s, 3, OMe). 13C NMR
(C6D6): d 159.9 (0, COMe), 133.4 (0, ipsoC), 131.8 (1, C40),
130.6 (1, C3), 129.9 (1, C4), 129.0 (1, Ar), 127.0 (1, C30),
114.1 (1, Ar), 84.9 (0, C5), 76.2 (1, C2), 74.8 (2, C50),
72.5 (2, C6), 54.7 (3, OMe). IR (NaCl, neat) 2960 (m),
2853 (m), 1610 (m), 1513 (s), 1249 (s), 1080 (s), 1033 (s),
829 (m).
tert-Butyl-[6-(4-methoxyphenyl)-3-vinyl-3,6-dihydro-
2H-pyran-yloxy]-dimethyl-silane (6c). 6c was obtained
from triene 4c (0.15 g, 0.4 mmol) and the Grubbs’ catalyst
(0.033 g, 10 mol%) following the procedure given above for
the preparation of dihydropyrans 6a as an inseparable 2:1
mixture of diastereoisomers. Yield: 0.11 g (80%). LRMS
(EI): m/z 346 (Mϩ, 1%), 289 (Mϩ-tert-Bu, 39), 121 (100).
IR (NaCl, neat) 2956 (m), 2929 (m), 2856 (m), 1611 (m),
1511 (s), 1249 (s), 1106 (s), 1040 (m), 836 (m), 776 (m).
NMR-data of the major isomer cis-6c: 1H NMR: d 7.27 (d,
2, Jˆ8.8 Hz, Ar), 6.89 (d, 2, Jˆ8.8 Hz, Ar), 6.06 (dd, 1,
Jˆ17.2 Hz, 10.5, –CHvCH2), 5.87 (dd, 1, Jˆ10.2, 1.3 Hz,
H3,4), 5.83 (ddd, 1, Jˆ10.2, 1.7, 1.3 Hz, H3,4), 5.38 (dd, 1,
Jˆ17.2, 1.5 Hz, –CHvCH2), 5.17 (dd, 1, Jˆ10.5, 1.5 Hz,
–CHvCH2), 5.08 (s, 1, H2), 3.80 (s, 3, OMe), 3.81–3.79 (1,
H6 overlapped by OMe), 3.67 (d, 1, Jˆ10.7 Hz, H6ax), 0.91
(s, 9, tert-Bu), 0.16 (s, 3, Si(CH3)2), 0.15 (s, 3, Si(CH3)2).
13C NMR: d 159.4 (0), 142.3 (1), 132.3 (0), 130.9 (1), 129.8
(1), 128.8 (1), 114.0 (2), 113.8 (1), 76.0 (1), 73.0 (2), 71.0
(0), 55.2 (3), 25.8 (3), 18.2 (0), 2.2 (3), 2.3 (3). NMR-data of
the minor isomer trans-6c: 1H NMR: d 7.34 (d, 2, Jˆ8.7 Hz,
Ar), 6.91 (d, 2, Jˆ8.7 Hz, Ar), 5.99 (dd, 1, Jˆ10.2, 2.0 Hz,
H3), 5.92 (dd, 1, Jˆ17.0, 10.5 Hz, –CHvCH2), 5.88 (dd, 1,
Jˆ10.2, 2.0 Hz, H4), 5.36 (dd, 1, Jˆ17.2, 1.5 Hz,
–CHvCH2), 5.17 (dd, 1, Jˆ10.5, 1.5 Hz, –CHvCH2),
5.01 (dd, 1, Jˆ2.0, 2.0 Hz, H2), 3.82 (s, 3, OMe), 3.81–
3.79 (1, H6 overlapped by OMe), 3.36 (d, 1, Jˆ11.5 Hz,
H6ax), 0.91 (s, 9, tert-Bu), 0.13 (s, 3, Si(CH3)2), 0.11 (s, 3,
Si(CH3)2). 13C NMR: d 159.3 (0), 141.8 (1), 132.2 (0),
130.7 (1), 130.3 (1), 128.8 (1), 114.3 (2), 113.7 (1),
75.3 (1), 73.1 (2), 70.6 (0), 55.2 (3), 25.8 (3), 18.2
(0), 2.2 (3), 2.3 (3).
(5R*, 8R*)-8-(4-Methoxyphenyl)-1,7-dioxaspiro[4,5]deca-
3,9-diene (7b). To a solution of the dihydropyran 8
(0.15 g, 0.6 mmol) in DCM (15 mL) was added the Grubbs’
catalyst (0.025 g, 5 mol%). The mixture was stirred at
ambient temperature for 24 h. The solvent was evaporated
and the residue purified by column chromatography to give
7b (0.12 g, 83%). LRMS (EI): m/z 245 (Mϩϩ1, 15), 214
(100), 121 (35). 1H NMR: d 7.31 (d, 2, Jˆ8.5 Hz, Ar), 6.85
(d, 2, Jˆ8.5 Hz, Ar), 6.03 (dm, 1, Jˆ6.3 Hz, H40), 5.93 (dd,
Jˆ10.3, 1.8 Hz, H3), 5.82 (dm, 1, Jˆ10.3 Hz, H4), 5.67
(ddd, 1, Jˆ6.3, 2.8, 2.3 Hz, H30), 4.97 (s, 1, H2), 4.75
(ddd, 1, Jˆ13.1, 2.0, 2.0 Hz, H50), 4.67 (dm, 1,
Jˆ13.0 Hz, H50), 3.87 (d, 1, Jˆ11.8 Hz, H6eq), 3.76 (s, 3,
OMe), 3.63 (d, 1, Jˆ11.8 Hz, H6ax). 13C NMR: d 159.3 (0,
COMe), 132.2 (1, C3), 132.1 (0, ipsoC), 129.4 (1, C30),
129.2 (1, C40), 128.9 (1, Ar), 127.8 (1, C4), 113.7 (1, Ar),
83.9 (0, C5), 75.3 (1, C2), 74.6 (2, C50), 70.3 (2, C6), 55.2

2426
B. Schmidt, M. Westhus / Tetrahedron 56 (2000) 2421–2426
(3, OMe). IR (KBr, neat) 2956 (m), 2838 (s), 1612 (s), 1513
(s), 1248 (s), 1075 (s), 1034 (s), 831 (s), 810 (s).
References
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NMR-tube experiment
RCM of tetraene 10d. Tetraene 10d (28 mg) was dissolved
in C6D6 (1.0 mL) in an NMR tube under an argon atmo-
1
sphere. The Grubbs’ catalyst (8 mg) was added and H
NMR spectra were recorded at 500 MHz after 10, 45, 70,
100 min, 10 and 48 h. NMR data of 2-[1-(4-methoxyphe-
nyl)-allyloxymethyl]-2-vinyl-2,5-dihydrofuran (9) (1:1
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6. Fu¨rstner, A. Synlett 1999, 1523–1533.
1
mixture of diastereomers): H NMR (C6D6): d 7.28 (d, 2,
7. Huwe, C. M.; Velder, J.; Blechert, S. Angew. Chem. 1996, 108,
2542–2544; Angew. Chem., Int. Ed. Engl. 1996, 35, 2376–2378.
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1999, 40, 5405–5408.
Jˆ8.8 Hz, Ar), 7.27 (d, 2, Jˆ8.8 Hz, Ar), 6.81 (d, 2,
Jˆ8.8 Hz, Ar), 6.81 (d, 2, Jˆ8.8 Hz, Ar), 6.18 (dd, 1,
Jˆ17.3, 10.8 Hz, –CHCH2), 6.10 (dd, 1, Jˆ17.3, 10.8 Hz,
–CHCH2), 6.00–5.89 (2, CHCHvCH2), 5.79–5.75 (2,
–HCvCH), 5.55–5.44 (4, –HCvCH–ϩvCH2), 5.27
(ddd, 1, Jˆ17.3, 1.5, 1.5 Hz, vCH2), 5.25 (ddd, 1,
Jˆ17.3, 1.5, 1.5 Hz, vCH2), 5.12 (dd, 1, Jˆ10.8, 2.0,
vCH2), 5.08 (dd, 1, Jˆ10.8, 2.0 Hz, vCH2), 5.08–5.03
(2, vCH2), 4.75–4.70 (2, OCHAr), 4.65–4.47 (2,
OCHHCHv), 3.62–3.50 (2, OCHHCq), 3.32 (s, 3, OMe).
13C NMR (C6D6): d 159.7 (0), 159.6 (0), 139.9 (1), 139.9
(1), 139.7 (1), 139.6 (1), 133.6 (0), 133.5 (0), 130.4 (1),
130.4 (1), 128.5 (1), 128.4 (1), 126.9 (1), 126.9 (1), 115.3
(2), 115.1 (2), 114.1 (1), 114.1 (1), 113.7 (2), 113.7 82), 92.4
(0), 92.4 (0), 83.2 (1), 83.2 (1), 75.3 (2), 75.3 (2), 74.2 (2),
74.1 (2), 54.7 (3), 54.7 (3).
10. Schmidt, B.; Wildemann, H. Synlett 1999, 1591–1593.
11. Jurd, L.; Roitman, J. N. Tetrahedron 1978, 34, 57–62.
12. For the formation of spirocyclic systems using one or two
RCM steps, see: Maier, M. E.; Bugl, M. Synlett 1998, 1390–
1392; van Hooft, P. A. V.; Leeuwenburgh, M. A.; Overkleeft,
H. S.; van der Marel, G. A.; van Boeckel, C. A. A.; van Boom,
J. H. Tetrahedron Lett. 1998, 39, 6061–6064; Holt, D. J.; Barker,
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Russell, D. R.; Ghosh, S. Angew. Chem. 1998, 110, 3486–3488;
Angew. Chem., Int. Ed. Engl. 1998, 37, 3298–3300; Bassindale,
M. J.; Hamley, P.; Leitner, A.; Harrity, J. P. A. Tetrahedron Lett.
1999, 40, 3247–3250; Grigg, R.; Sridharan, V.; York, M.
Tetrahedron Lett. 1998, 39, 4139–4142; Holt, D. J.; Barker,
W. D.; Jenkins, P. R; Panda, J.; Ghosh, S. J. Org. Chem. 2000,
65, 482–493.
Acknowledgements
This work was generously supported by the Fonds der
Chemischen Industrie and the Deutsche Forschungsge-
meinschaft. B. S. thanks Prof. Dr P. Eilbracht for support
and encouragement.
13. A ring opening/ring closing metathesis sequence was recently
exploited for the synthesis of piperidine derivatives starting from
cyclopentenes: Stragies, R.; Blechert, S. Tetrahedron 1999, 55,
8179–8188.