Combining ring-closing metathesis and hydroformylation strategies: A novel approach to spirocyclic γ-butyrolactones

Article abstract of DOI:10.1021/jo0157730

Di- or tetrahydropyrans with a vinyl side chain are obtained by diastereoselective ring-closing metathesis or by addition of vinylmagnesium chloride to an appropriately functionalized tetrahydropyranone. The resulting allylic alcohols are converted to spirocyclic hemiacetals under hydroformylation conditions. Oxidation yields the corresponding lactones.

Full text of DOI:10.1021/jo0157730

7658
J . Org. Chem. 2001, 66, 7658-7665
Com bin in g Rin g-Closin g Meta th esis a n d Hyd r ofor m yla tion
Str a tegies: A Novel Ap p r oa ch to Sp ir ocyclic γ-Bu tyr ola cton es
Bernd Schmidt,* Burkhard Costisella, Rafael Roggenbuck, Markus Westhus,
Holger Wildemann, and Peter Eilbracht
Universita¨t Dortmund, Fachbereich Chemie, Organische Chemie, Otto-Hahn-Strasse 6,
D-44227 Dortmund, Germany
bschmidt@chemie.uni-dortmund.de
Received May 19, 2001
Di- or tetrahydropyrans with a vinyl side chain are obtained by diastereoselective ring-closing
metathesis or by addition of vinylmagnesium chloride to an appropriately functionalized tetrahy-
dropyranone. The resulting allylic alcohols are converted to spirocyclic hemiacetals under
hydroformylation conditions. Oxidation yields the corresponding lactones.
Ch a r t 1
In tr od u ction
Spirocyclic γ-butyrolactones not only are widespread
in nature1-4 but have also played a key role as synthetic
intermediates.5-7 One example of a natural product with
a spirocyclic γ-butyrolactone moiety is the alkaloid ste-
motinine,8 and the antitumor antibiotic aranorosin may
serve as an example where a spirocyclic lactone has been
used as a key intermediate in the total synthesis9 (Chart
1). Furthermore, a variety of methods are available for
the conversion of γ-butyrolactones into R-methylene-γ-
butyrolactones.10 Spirocyclic, steroidal derivatives of
these compounds often show outstanding biological prop-
erties.3,4 In principle, one can imagine two different
strategies for the construction of spiro compounds: (i) the
conversion of a tetrafunctional acyclic compound into a
spirocyclic system in a one-pot reaction or (ii) the stepwise
formation of two carba- or heterocycles via a monocyclic
intermediate. A variety of methods for the synthesis of
lactones is available, for example, lactonization after
asymmetric dihydroxylation, iodolactonization, palladium-
catalyzed cyclization of allenic or homopropargylic car-
boxylic acids, or samarium-mediated addition of ketones
to acrylates. This subject has been reviewed several times
over the past few years.11-14
In this contribution, we present a novel concept for the
synthesis of spirocyclic lactones, which is based on a
ruthenium-catalyzed olefin metathesis and a rhodium-
catalyzed hydroformylation-acetalation sequence (Scheme
1).
* To whom correspondence should be addressed. Fax: +49 (231)
7555363.
(1) Nagahisa, M.; Koike, K.; Narita, M.; Ohmoto, T. Tetrahedron
1994, 50, 10859-10866.
(2) Koike, K.; Suzuki, Y.; Ohmoto, T. Phytochemistry 1994, 35, 701-
We demonstrate the utility of our approach for the
example of di- or tetrahydropyrans linked to lactones in
a spirocyclic fashion. Although this class of substances
might be interesting in itself,5,6 they may also serve, after
cleavage of the lactone, as intermediates in the synthesis
of pyran derivatives with functionalized side chains. This
structural element is found in several natural products
such as the pseudomonic acids.15
704.
(3) Sawant, M. S.; Katoch, R.; Trivedi, G. K.; Desai, U. R. J . Chem.
Soc., Perkin Trans. 1 1998, 843-846.
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The ring-closing olefin metathesis16-18 has become one
of the most powerful cyclization reactions since the
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10.1021/jo0157730 CCC: $20.00 © 2001 American Chemical Society
Published on Web 10/25/2001

Ring-Closing Metathesis and Hydroformylation
J . Org. Chem., Vol. 66, No. 23, 2001 7659
Sch em e 1
Resu lts a n d Discu ssion
P r ep a r a tion of Mon ocyclic P r ecu r sor s. Starting
from the protected allyl-homoallyl ether 2 (obtained by
benzylation of alcohols 1),26 we obtained the dihydro-
pyrans 3 by ring-closing metathesis. Epoxidation was
moderately diastereoselective for the methyl derivative
3a (diastereomeric ratio ) 2:1), whereas the phenyl
derivative 3b was obtained as a 6:1 mixture of diastereo-
isomers. Compound 4a was treated as a mixture of
diastereomers with benzylic alcohol in the presence of
borontrifluoride etherate. Upon chromatography, the
major isomer (3S*,4S*,6R*)-5a was isolated, which was
used for further transformations. In the case of epoxide
4b, the minor diastereomer was removed by flash chro-
matography. Epoxide cleavage under the same conditions
gave (3S*,4S*,6S*)-5b and (2S*,4R*,5R*)-5b as a 4.5:1
mixture of regioisomers. Oxidation of the hydroxyl func-
tionality was achieved using TPAP/NMO41 to yield the
ketones 6a ,b. Attack of vinylmagnesium chloride oc-
curred from the face opposite to the benzyloxy substituent
to give the tertiary allylic alcohols 7a ,b with high
diastereoselectivity (only one diastereomer was detected
introduction of highly efficient precatalysts by Schrock19
and Grubbs.20 The RCM reaction has been used in the
synthesis of spirocycles, either for cyclization of two rings
by double-ring-closing metathesis21-27 or by single-ring-
closing metathesis starting from an appropriately func-
tionalized monocyclic precursor.28-33
Hydroformylation of olefins not only is a well-estab-
lished method for the industrial production of aldehydes
but has also found interesting applications in organic
synthesis.34 The incorporation of a hydroformylation step
in sequential reactions has proven to be a particularly
valuable concept.35 For example, the hydroformylation of
an allylic or homoallylic alcohol yields hemiacetals via
formation of the primarily formed aldehydes.36-38 The
hemiacetals may be converted into cyclic enol ethers by
elimination39 or into lactones by oxidation.40
1
in the H NMR spectrum) (Scheme 2).
We have recently devised an alternative synthesis for
pyran derivatives with an exo-vinyl moiety. Ring-closing
metathesis of divinyl carbinols 8a and 8b gives dihydro-
pyrans 9a and 9b in diastereomeric ratios of 3:1 and 4:1,
respectively.27,42 Ring-closing metathesis of triene 10
yields dihydropyrans (5R*,8S*)-11 and (5S*,8S*)-11 as
an easily separable mixture of diastereomers (Scheme 3).
P r ep a r a tion of Sp ir ocyclic P r od u cts. Allylic alco-
hols 7a ,b were subjected to hydroformylation in the
presence of Rh(acac)(CO)2 (1.0 mol %) and BIPHEPHOS
(4.0 mol %)43 under 10 bar of carbon monoxide and 10
bar of hydrogen at 60 °C. Under these mild conditions,
hemiacetals 12a ,b result as mixtures of anomers, which
is indicated by signals at approximately 99 ppm in the
carbon NMR spectrum. Side products resulting from
formation of the branched aldehyde could not be detected.
The crude hemiacetals were oxidized to the lactones
13a ,b using TPAP/NMO. Compound (5R*,8R*,10S*)-13a
was obtained from 7a (single isomer), and 7b (mixture
of regioisomers) was converted to (5R*,8R*,10S*)-13b
and (5S*,6R*,9S*)-13b. The regioisomers were separated
by column chromatography and fully characterized
(Scheme 4).
Hydroformylation of dihydropyrans 9a , 9b, (5R*,8S*)-
11, and (5S*,8S*)-11 is highly regio- and chemoselective,
with only the exo-vinyl moiety being attacked under the
reaction conditions. The hemiacetals 12, 14, and 16 were
obtained as inseparable mixtures of anomers, which were
immediately oxidized to the corresponding lactones 13,
15, and 17 using the TPAP/NMO reagent combination.
Compounds 9a ,b were employed as 3:1 and 4:1 mixtures
of diastereoisomers. The resulting lactones (5S,6S)- and
(5R,6S)-15a and (5S*,6S*)- and (5R*,6S*)-15b could be
easily separated by flash chromatography on silica.
Compounds (3R*,6S*)-11 and (3S*,6S*)-11 were em-
ployed as single diastereomers. In these cases, single
isomers of the corresponding lactones (5R*,8S*)-17 and
(5S*,8S*)-17 were obtained (Scheme 5).
(19) Schrock, R. R.; Murdzek, J . S.; Bazan, G. C.; Robbins, J .;
DiMare, M.; O’Regan, M. J . Am. Chem. Soc. 1990, 112, 3875-3886.
(20) Fu, G. C.; Nguyen, S. T.; Grubbs, R. H.; Ziller, J . W. J . Am.
Chem. Soc. 1993, 115, 9856-9857.
(21) Bassindale, M. J .; Hamley, P.; Leitner, A.; Harrity, J . P. A.
Tetrahedron Lett. 1999, 40, 3247-3250.
(22) Wallace, D. J .; Cowden, C. J .; Kennedy, D. J .; Ashwood, M. S.;
Cottrell, I. F.; Dolling, U.-H. Tetrahedron Lett. 2000, 41, 2027-2029.
(23) Wallace, D. J .; Bulger, P. G.; Kennedy, D. J .; Ashwood, M. S.;
Cottrell, I. F.; Dolling, U.-H. Synlett 2001, 357-360.
(24) Wallace, D. J .; Goodman, J . M.; Kennedy, D. J .; Davies, A. J .;
Cowden, C. J .; Ashwood, M. S.; Cottrell, I. F.; Dolling, U.-H.; Reider,
P. J . Org. Lett. 2001, 3, 671-674.
(25) Schmidt, B.; Westhus, M. Tetrahedron 2000, 56, 2421-2426.
(26) Schmidt, B.; Wildemann, H. J . Chem. Soc., Perkin Trans. 1
2000, 2916-2925.
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5822.
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Tetrahedron Lett. 1999, 40, 3021-3024.
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van der Marel, G. A.; van Boeckel, C. A. A.; van Boom, J . H.
Tetrahedron Lett. 1998, 39, 6061-6064.
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van Boom, J . H. Tetrahedron Lett. 2001, 42, 1769-1772.
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3488.
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4139-4142.
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Rzychon, B. E.; Kranemann, C. L.; Rische, T.; Roggenbuck, R.; Schmidt,
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10732.
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7660 J . Org. Chem., Vol. 66, No. 23, 2001
Schmidt et al.
Sch em e 2a
a
Key: (i) NaH, BnBr, THF (90% of 2a , 91% of 2b); (ii) Cl2(Cy3P)2RudCHPh (1 mol %), DCM (81% of 3a , 88% of 2b); (iii) MCPBA, DCM
(91% of 4a , 99% of 4b); (iv) BnOH, BF3OEt2 (10 mol %), DCM, 0 °C, chromatography (57% of (3S*,4S*,6R*)-5a , 78% of (3S*,4S*,6S*)-5b
and (2S*,4R*,5R*)-5b) (4.5:1); (v) TPAP (5 mol %), NMO, 4 Å molecular sieve, DCM (84% of 6a , 82% of 6b); (vi) H2CdCHMgCl, ether,
-78 °C (66% of 7a , 89% of 7b).
Sch em e 3
the axially oriented H5 and one proton of the methylene
moiety of the lactone ring is indicative of the relative
configuration shown in Scheme 6.
NOE interactions for spirocyclic dihydropyrans 15 are
summarized in Scheme 7. A NOE interaction between
H6ax and H2 indicates that the phenyl moiety adopts a
pseudoequatorial position. In the case of (5S*,6S*)-15b,
a NOE interaction between H2 and one proton of the
methylene group of the lactone moiety is observed, which
is missing for the other diastereomer. For the (5R*,6S*)-
isomer, a NOE interaction between the ortho protons of
the phenyl group and one proton of the methylene group
is indicative for the proposed relative configuration. For
the methyl derivative 15a , analogous NOE interactions
were observed for the protons of the methyl group.
For dihydropyrans 17 with the spirocyclic junction in
the 5-position, NOE interactions of the protons H6ax and
H6eq with the methylene group of the lactone ring are
most indicative of the relative configuration. For both
diastereomers, a NOE effect is observed between the
singlet of H2 and one doublet of the H6-AB-system;
assignment of the corresponding signals to H6ax and
H6eq, respectively, is made on the basis of this inter-
action. In (5S*,8S*)-17, a NOE interaction between H6ax
and one proton of the methylene group of the lactone is
observed, whereas in (5R*,8S*)-17, H6eq interacts with
this CH2 group (Scheme 8).
In conclusion, we have developed a synthetic approach
toward bicyclic spiro compounds with a lactone moiety
linked to a six-membered oxacycle on the basis of ring-
closing metathesis and a hydroformylation-acetalation
sequence. Use of the BIPHEPHOS ligand system allows
the differentiation between exocyclic and endocyclic C-C
NOE Exp er im en ts. The relative configuration of all
spirocyclic products was investigated by one- or two-
dimensional NOE experiments conducted at 600 or 500
MHz, respectively. For spirocyclic tetrahydropyran 13a ,
NOE interactions between the methyl group in the
2-position and the proton H3ax and between the -CH2-
OBn moiety and the proton H6ax indicate that the
molecule preferably adopts the conformation depicted in
Scheme 6. One proton of the CH2 group of the lactone
moiety shows NOE interactions with both protons H6,
whereas the other proton of this CH2 group shows a NOE
interaction with H4. The phenyl analogue (5R*,8R*,-
10S*)-13b shows similar NOE interactions. Its regioiso-
mer (5S*,6R*,9S*)-13b adopts a conformation with the
phenyl substituent in an axial position: NOE interactions
between the ortho-H of the phenyl moiety and H6ax as
well as H3eq are observed. A NOE interaction between

Ring-Closing Metathesis and Hydroformylation
J . Org. Chem., Vol. 66, No. 23, 2001 7661
Sch em e 4a
dimensional NOESY spectra were obtained at 500 MHz with
a mixing time of 1.5 s.
2-Allyloxy-2-m eth yl-pen t-4-en yloxym eth ylben zen e (2a).
To a solution of the primary alcohol 1a (8.65 g, 55 mmol) in
THF (150 mL) was added NaH (60% dispersion in mineral oil,
6.65 g, 166 mmol). The mixture was heated to reflux for 30
min and cooled to ambient temperature. Benzyl bromide (9.9
mL, 83 mmol) was added, and the mixture was again refluxed
until the starting material was fully consumed as indicated
by TLC. After aqueous workup, the solvent was evaporated
and the residue was distilled (bp 130 °C, 0.4 mbar) to give
12.23 g (90%) of the benzyl ether 2a . IR (neat): 698 s, 1103 s,
1454 m, 2859 m, 2982 m. MS m/z (relative (rel) intensity): 247
1
(M+ + 1, <5), 131 (60), 91 (100). H NMR (400 MHz, CDCl3):
δ 7.27-7.17 (5H), 5.83 (dddd, 1H, J ) 17.1, 10.5, 5.3, 5.3 Hz),
5.73 (dddd, 1H, J ) 17.5, 10.5, 7.0, 7.0 Hz), 5.18 (dddd, 1H, J
) 17.1, 1.5, 1.5, 1.5 Hz), 5.03 (dddd, 1H, J ) 10.5, 1.5, 1.5, 1.5
Hz), 4.98 (dddd, 1H, J ) 17.5, 1.5, 1.5, 1.5 Hz), 4.94 (dddd,
1H, J ) 10.5, 1.5, 1.5, 1.5 Hz), 4.45 (s, 2H), 3.93 (m, 1H), 3.89
(dddd, 1H, J ) 11.8, 5.3, 1.5, 1.5 Hz), 3.32 (d, 1H, J ) 9.8 Hz),
3.25 (d, 1H, J ) 9.8 Hz), 2.30 (dddd, 1H, J ) 14.8, 7.0, 1.5, 1.5
Hz), 2.27 (dddd, 1H, J ) 14.8, 7.0, 1.5, 1.5 Hz), 1.10 (s, 3H).
13C NMR (100 MHz, CDCl3): δ 138.2 (0), 135.8 (1), 134.0 (1),
128.2 (1), 127.5 (1), 127.4 (1), 117.5 (2), 115.6 (2), 76.6 (0), 74.5
(2), 73.2 (2), 63.2 (2), 40.4 (2), 20.9 (3). Anal. Calcd for
C
16H22O2: C, 78.0; H, 9.0. Found: C, 77.6; H, 8.8.
2-Allyloxy-2-ph en yl-pen t-4-en yloxym eth ylben zen e (2b).
Following the procedure for the methyl analogue, we obtained
2b (16.0 g, 91%) from primary alcohol 1b (12.5 g, 57 mmol) as
a colorless liquid (bp 130 °C, 0.4 mbar). IR (neat): 699 s, 1072
s, 1103 s, 1496 m, 3075 m. MS m/z (rel intensity): 308 (M+
-
1, <5), 267 (5), 187 (25), 145 (25), 131 (80), 105 (80), 91 (100),
1
77 (25). H NMR (CDCl3, 400 MHz): δ 7.32-7.13 (10H), 5.82
(dddd, 1H, J ) 17.3, 10.3, 5.3, 5.3 Hz), 5.63 (dddd, 1H, J )
17.3, 10.3, 7.0, 7.0 Hz), 5.20 (dddd, 1H, J ) 17.3, 1.5, 1.5, 1.5
Hz), 5.04 (dddd, 1H, J ) 10.3, 1.5, 1.5, 1.5 Hz), 4.97 (dm, 1H,
J ) 17.3 Hz), 4.94 (dm, 1H, J ) 10.3 Hz), 4.42 (d, 1H, J )
12.8 Hz), 4.39 (d, 1H, J ) 12.8 Hz), 3.76 (dddd, 1H, J ) 12.8,
5.3, 1.5, 1.5 Hz), 3.73 (m, 1H), 3.70 (d, 1H, J ) 9.5 Hz), 3.59
(d, 1H, J ) 9.5 Hz), 2.75 (ddm, 1H, J ) 14.3, 7.0 Hz), 2.64
(ddm, 1H, J ) 14.3, 7.0 Hz). 13C NMR (CDCl3, 100 MHz): δ
142.2 (0), 138.2 (0), 135.2 (1), 133.5 (1), 128.2 (1), 128.0 (1),
127.5 (1), 127.5 (1), 127.1 (1), 126.6 (1), 117.9 (2), 115.7 (2),
80.3 (0), 73.3 (2), 73.3 (2), 63.8 (2), 40.3 (2). Anal. Calcd for
C
21H24O2: C, 81.8; H, 7.8. Found: C, 82.1; H, 7.8.
2-Ben zyloxym eth yl-2-m eth yl-3,6-dih ydr o-2H-pyr an (3a).
To a solution of 2a (5.00 g, 20 mmol) in DCM (50 mL) was
added Grubbs' catalyst (167 mg, 1 mol %). The reaction
mixture was stirred at ambient temperature until the starting
material was fully consumed as indicated by TLC. The solvent
was evaporated, and the residue was purified by flash chro-
matography on silica using 5:1 (v/v) cyclohexane/MTBE as the
eluent to give the dihydropyran 3a (3.60 g, 81%). IR (neat):
746 m, 1091 s, 1454 m, 2829 m, 3033 m. MS m/z (rel
intensity): 219 (M+ + 1, 40), 201 (30), 181 (60), 153 (70), 129
(100). 1H NMR (CDCl3, 400 MHz): δ 7.27-7.16 (5H), 5.67 (dm,
1H, J ) 10.3 Hz), 5.61 (dm, 1H, J ) 10.3 Hz), 4.53 (d, 1H, J
) 12.5 Hz), 4.48 (d, 1H, J ) 12.5 Hz), 4.11 (dm, 1H, J ) 16.8
Hz), 4.06 (dm, 1H, J ) 16.8 Hz), 3.33 (d, 1H, J ) 9.8 Hz), 3.24
(d, 1H, J ) 9.8 Hz), 2.13 (dm, 1H, J ) 17.5 Hz), 1.77 (dm, 1H,
J ) 17.5 Hz), 1.18 (s, 3H). 13C NMR (CDCl3, 100 MHz): δ 138.3
(0), 128.2 (1), 127.5 (1), 127.4 (1), 125.1 (1), 122.6 (1), 75.7 (2),
73.4 (2), 71.7 (0), 61.0 (2), 31.7 (2), 20.9 (3). Anal. Calcd for
a
Key: (i) Rh(acac)(CO)2 (1.0 mol %), BIPHEPHOS (4.0 mol %),
CO (10 bar), H2 (10 bar), dioxane; (ii) TPAP (5 mol %), NMO, 4 Å
molecular sieve, DCM (80% of 13a , 54% of 13b).
double bonds under hydroformylation conditions, making
spirocyclic dihydropyrans accessible. Further synthetic
applications for the combination of olefin metathesis and
hydroformylation strategies are currently under inves-
tigation in our laboratory.
Exp er im en ta l Section
Instrumentation, product identification, and general experi-
mental methods have been described previously.44 Hydro-
formylation reactions were conducted in steel pressure vessels
with a PTFE insert. Signal assignment for NMR spectra is
made on the basis of 2D methods (H, H-COSY) or NOE
experiments. Signal assignment for cyclic products follows a
numbering scheme where the oxygen atom is numbered 1 and
the R-carbon atom bearing a substituent is C2. The number
of coupled protons was analyzed by DEPT experiments and is
denoted by a number in parantheses following the δC value.
One-dimensional, gradient-selected NOE spectra were ob-
tained at 600 MHz with a mixing time of 800 ms. Two-
C
14H18O2: C, 77.0; H, 8.3. Found: C, 76.0; H, 8.1.
2-Ben zyloxym eth yl-2-ph en yl-3,6-dih ydr o-2H-pyr an (3b).
Following the procedure for the methyl analogue, we obtained
3b (4.0 g, 88%) from 2b (5.0 g, 16 mmol) after flash chroma-
tography as a colorless liquid. IR (neat): 699 s, 1097 s, 2851
m, 2936 m. MS m/z (rel intensity): 281 (M+ + 1, 10), 207 (40),
159 (50), 105 (100), 91 (40), 77 (40). 1H NMR (CDCl3, 400
MHz): δ 7.38-7.34 (d, 2H, J ) 7.5 Hz), 7.29-7.09 (8H), 5.78
(ddddd, 1H, J ) 10.3, 2.5, 2.5, 2.5, 2.5 Hz), 5.46 (ddddd, 1H, J
) 10.3, 2.5, 2.5, 2.5, 2.5 Hz), 4.49 (d, 1H, J ) 12.5 Hz), 4.36
(d, 1H, J ) 12.5 Hz), 4.11 (ddddd, 1H, J ) 17.0, 2.5, 2.5, 2.5,
2.5 Hz), 3.86 (ddddd, 1H, J ) 17.0, 2.5, 2.5, 2.5, 2.5 Hz), 3.52
(44) Schmidt, B. J . Chem. Soc., Perkin Trans. 1 1999, 2627-2637.

7662 J . Org. Chem., Vol. 66, No. 23, 2001
Schmidt et al.
Sch em e 5a
a
Key: (i) Rh(acac)(CO)2 (1.0 mol %), BIPHEPHOS (4.0 mol %), CO (10 bar), hydrogen (10 bar), dioxane; (ii) TPAP (5 mol %), NMO, 4
Å molecular sieve, DCM (52-81% over two steps).
Sch em e 6
Sch em e 7
Sch em e 8
4-Ben zyloxym et h yl-4-m et h yl-3,7-d ioxa b icyclo[4.1.0]-
h ep ta n e (4a ). To a solution of the dihydropyran 3a (2.65 g,
12.1 mmol) in DCM (50 mL) was added MCPBA (70% disper-
sion in water, 3.14 g, 18.2 mmol). The mixture was stirred until
the starting material was completely consumed as indicated
by TLC. The reaction mixture was diluted with MTBE and
washed with Na2SO3 solution and then Na2CO3 solution. The
organic layer was dried, filtered, and evaporated, and the
residue was purified by flash chromatography on silica to give
epoxide 4a (2.75 g, 97%) as a 2:1 mixture of diastereoisomers.
Spectroscopic data for the major (1S*,4R*,6R*)-isomer. IR
(neat): 739 s, 1110 s, 1454 m, 2862 m. MS m/z (rel intensity):
235 (M+ + 1, 10), 181 (10), 143 (15), 113 (85), 91 (100), 65 (20).
1H NMR (CDCl3, 400 MHz): δ 7.34-7.22 (5H), 4.52 (d, 1H, J
) 12.3 Hz), 4.45 (d, 1H, J ) 12.3 Hz), 4.02 (d, 1H, J ) 13.8
Hz), 3.95 (d, 1H, J ) 13.8 Hz), 3.32 (d, 1H, J ) 9.5 Hz), 3.29
(dd, 1H, J ) 9.8, 4.8 Hz), 3.20 (d, 1H, J ) 9.5 Hz), 3.04 (m,
1H), 1.89 (d, 1H, J ) 15.3 Hz), 1.63 (dd, 1H, J ) 15.3, 5.7 Hz),
(d, 1H, J ) 10.0 Hz), 3.37 (d, 1H, J ) 10.0 Hz), 2.70 (ddddd,
1H, J ) 17.8, 2.5, 2.5, 2.5, 2.5 Hz), 2.55 (ddddd, 1H, J ) 17.8,
2.5, 2.5, 2.5, 2.5 Hz). 13C NMR (CDCl3, 100 MHz): δ 140.9 (0),
138.2 (0), 128.2 (1), 128.1 (1), 127.5 (1), 127.4 (1), 127.3 (1),
126.8 (1), 125.7 (1), 122.8 (1), 76.3 (0), 77.1 (2), 73.4 (2), 61.7
(2), 28.3 (2). Anal. Calcd for C19H20O4: C, 81.4; H, 7.2. Found:
C, 81.1; H, 7.2.

Ring-Closing Metathesis and Hydroformylation
J . Org. Chem., Vol. 66, No. 23, 2001 7663
1
1.21 (s, 3H). 13C NMR (CDCl3, 100 MHz): δ 138.2 (0), 128.2
(1), 127.6 (1), 127.5 (1), 76.6 (2), 73.4 (2), 70.4 (0), 58.8 (2),
49.4 (1), 48.7 (1), 30.7 (2), 20.7 (3). Anal. Calcd for C14H18O3:
C, 71.8; H, 7.7. Found: C, 72.1; H, 7.6.
10), 323 (60), 233 (70), 181 (100), 144 (55), 113 (55). H NMR
(CDCl3, 400 MHz): δ 7.29-7.19 (10H), 4.73 (d, 1H, J ) 11.8
Hz), 4.49 (d, 1H, J ) 12.3 Hz), 4.46 (d, 1H, J ) 11.8 Hz), 4.43
(d, 1H, J ) 12.3 Hz), 4.43 (dd, 1H, J ) 12.5, 6.5 Hz), 4.13 (d,
1H, J ) 18.5 Hz), 4.08 (d, 1H, J ) 18.5 Hz), 3.38 (d, 1H, J )
9.5 Hz), 3.29 (d, 1H, J ) 9.5 Hz), 2.45 (dd, 1H, J ) 13.5, 6.5
Hz), 1.67 (dd, 1H, J ) 13.5, 12.5 Hz), 1.16 (s, 3H). 13C NMR
(CDCl3, 100 MHz): δ 209.9 (0), 137.8 (0), 137.6 (0), 128.4 (1),
128.3 (1), 127.8 (1), 127.8 (1), 127.7 (1), 127.6 (1), 76.7 (2), 76.5
(1), 75.6 (0), 73.5 (2), 72.2 (2), 68.6 (2), 36.9 (2), 22.7 (3).
(4S*,6S*)-4-Ben zyloxy-6-ben zyloxym eth yl-6-ph en yldih y-
d r op yr a n -3-on e (6b). Following the procedure for the methyl
analogue, we obtained 6b (0.90 g, 82%) from 5b (1.10 g, 2.7
mmol, 4.5:1 mixture of regioisomers). IR (neat): 699 s, 1101
(1S*,4S*,6R*)-4-Ben zyloxym eth yl-4-p h en yl-3,7-d ioxa -
bicyclo[4.1.0]h ep ta n e (4b). Following the procedure for the
methyl analogue, we obtained 4b (2.50 g, 99%) from 3b (2.39
g, 8.5 mmol) as a 6:1 mixture of diastereomers. The major
isomer was separated by flash chromatography as a colorless
solid (mp 69 °C). IR (KBr, disk): 699 m, 1104 s, 2858 m, 3028
m. MS m/z (rel intensity): 297 (M+ + 1, 10), 279 (15), 175 (100),
145 (20), 105 (30), 91 (40). 1H NMR (CDCl3, 400 MHz): δ 7.38-
7.10 (10H), 4.49 (d, 1H, J ) 12.5 Hz), 4.35 (d, 1H, J ) 12.5
Hz), 3.96 (d, 1H, J ) 13.5 Hz), 3.61 (d, 1H, J ) 13.5 Hz), 3.50
(d, 1H, J ) 10.0 Hz), 3.40 (d, 1H, J ) 6.5 Hz), 3.37 (d, 1H, J
) 10.0 Hz), 2.79 (d, 1H, J ) 4.3 Hz), 2.68 (dd, 1H, J ) 16.1,
6.0 Hz), 2.37 (d, 1H, J ) 16.1 Hz). 13C NMR (CDCl3, 100
MHz): δ 139.4 (0), 138.1 (0), 128.5 (1), 128.2 (1), 127.7 (1),
127.5 (1), 127.4 (1), 127.4 (1), 77.7 (2), 75.2 (0), 73.3 (2), 59.4
(2), 48.6 (1), 48.5 (1), 27.6 (2). Anal. Calcd for C19H20O3: C,
77.0; H, 6.8. Found: C, 76.8; H, 6.8.
(3S*,4S*,6R*)-4-Ben zyloxy-6-ben zyloxym eth yl-6-m eth -
yl-tetr a h yd r op yr a n -3-ol (5a ). To a solution of the epoxide
4a (2:1 mixture of diastereomers, 2.09 g, 8.9 mmol) and
benzylic alcohol (9.3 mL, 89.4 mmol) was added borontri-
fluoride etherate (0.1 mL, 0.8 mmol) at 0 °C. The mixture was
stirred at this temperature until the starting material was
completely consumed as indicated by TLC and diluted with
MTBE. The reaction was quenched with Na2CO3 solution, and
the mixture was dried with MgSO4, filtered, and evaporated.
Upon flash chromatography on silica, only the (3S*,4S*,6R*)-
isomer of 5a was isolated in pure form (1.73 g, 57%). IR
(neat): 698 s, 737 s, 1094 s, 1454 m, 2867 m, 2929 m, 3436 br
s. MS m/z (rel intensity): 341 (M+ - 1, <5), 221 (40), 167 (20),
91 (100), 65 (20). 1H NMR (CDCl3, 400 MHz): δ 7.36-7.26
(10H), 4.63 (d, 1H, J ) 11.5 Hz), 4.57 (d, 1H, J ) 12.3 Hz),
4.51 (d, 1H, J ) 12.3 Hz), 4.44 (d, 1H, J ) 11.5 Hz), 3.92 (dd,
1H, J ) 11.8, 4.0 Hz), 3.62 (ddd, 1H, J ) 7.5, 7.5, 4.0 Hz),
3.58 (ddd, 1H, J ) 9.0, 7.5, 4.0 Hz), 3.48 (dd, 1H, J ) 11.8, 7.5
Hz), 3.41 (d, 1H, J ) 9.5 Hz), 3.36 (d, 1H, J ) 9.5 Hz), 2.40
(bs, 1H), 2.21 (dd, 1H, J ) 13.8, 4.0 Hz), 1.42 (dd, 1H, J )
13.8, 9.0 Hz), 1.29 (s, 3H). 13C NMR (CDCl3, 100 MHz): δ 138.2
(0), 138.1 (0), 128.5 (1), 128.4 (1), 127.8 (1), 127.7 (1), 127.6
(1), 127.5 (1), 77.2 (0), 77.0 (1), 73.7 (2), 73.5 (2), 70.8 (2), 69.5
(1), 64.0 (2), 34.8 (2), 25.0 (3). Anal. Calcd for C21H26O4: C,
73.7; H, 7.7. Found: C, 73.3; H, 7.4.
(3S*,4S*,6S*)-4-Ben zyloxy-6-ben zyloxym eth yl-6-p h en -
yltetr a h yd r op yr a n -3-ol (5b). Following the procedure for the
methyl analogue, we obtained 5b (2.90 g, 78) from 4b (2.73 g,
9.2 mmol) as a 4.5:1 mixture of regioisomers. Spectroscopic
data were obtained from the mixture. IR (neat): 699 s, 1075
s, 1096 s, 2866 m, 3426 br s. 1H NMR (CDCl3, 400 MHz): δ
7.37 (d, 2H, J ) 7.5 Hz), 7.27-7.10 (6H), 7.02 (d, 2H, J ) 8.0
Hz), 4.49 (d, 1H, J ) 11.8 Hz), 4.42 (d, 1H, J ) 12.5 Hz), 4.35
(d, 1H, J ) 11.8 Hz), 4.31 (d, 1H, J ) 12.5 Hz), 3.97 (dd, 1H,
J ) 11.8, 3.5 Hz), 3.68 (ddd, 1H, J ) 7.3, 6.3, 4.3 Hz), 3.62
(dd, 1H, J ) 11.8, 6.0 Hz), 3.54 (ddd, 1H, J ) 6.3, 6.0, 3.5 Hz),
3.48 (d, 1H, J ) 10.0 Hz), 3.40 (d, 1H, J ) 10.0 Hz), 2.76 (bs,
1H), 2.60 (dd, 1H, J ) 14.3, 7.3 Hz), 1.92 (dd, 1H, J ) 14.3,
4.3 Hz). 13C NMR (CDCl3, 100 MHz): δ 143.2 (0), 138.2 (0),
137.9 (0), 128.3 (1), 128.2 (1), 127.9 (1), 127.5 (1), 127.5 (1),
127.3 (1), 126.9 (1), 126.0 (1), 78.1 (0), 76.4 (1), 75.8 (2), 73.4
(2), 70.7 (2), 68.6 (1), 64.3 (2), 32.2 (2). Anal. Calcd for
s, 1746 s, 2852 m, 3030 m. MS m/z (rel intensity): 403 (M+
1, <5), 292 (5), 264 (5), 219 (15), 189 (20), 115 (15), 91 (100),
65 (20). H NMR (CDCl3, 400 MHz): δ 7.33-7.11 (15H), 4.82
+
1
(dd, 1H, J ) 13.0, 6.3 Hz), 4.79 (d, 1H, J ) 11.8 Hz), 4.52 (d,
1H, J ) 11.8 Hz), 4.46 (d, 1H, J ) 12.3 Hz), 4.34 (d, 1H, J )
12.3 Hz), 4.14 (d, 1H, J ) 18.0 Hz), 3.95 (d, 1H, J ) 18.0 Hz),
3.50 (d, 1H, J ) 10.0 Hz), 3.33 (d, 1H, J ) 10.0 Hz), 2.99 (dd,
1H, J ) 13.0, 6.3 Hz), 2.20 (dd, 1H, J ) 13.0, 13.0 Hz). 13C
NMR (CDCl3, 100 MHz): δ 210.3 (0), 141.9 (0), 137.7 (0), 137.7
(0), 128.5 (1), 128.4 (1), 127.9 (1), 127.8 (1), 127.7 (1), 127.5
(1), 125.6 (1), 79.9 (0), 79.2 (2), 76.7 (1), 73.6 (2), 72.6 (2), 69.3
(2), 35.5 (2). Anal. Calcd for C26H26O4: C, 77.6; H, 6.5. Found:
C, 77.3; H, 6.3.
(3R*,4S*,6R*)-4-Ben zyloxy-6-ben zyloxym eth yl-6-m eth -
yl-3-vin yl-tetr ah ydr opyr an -3-ol (7a). Vinylmagnesium chlo-
ride (1.7 M solution in THF, 0.6 mL, 1.0 mmol) was added to
a solution of the ketone 6a (0.11 g, 0.3 mmol) in ether (10 mL)
at -78 °C. The mixture was stirred until the starting material
was fully converted and warmed to ambient temperature, and
the reaction was quenched with saturated NH4Cl solution. The
aqueous layer was extracted with MTBE, and the combined
organic extracts were dried with MgSO4. Upon flash chroma-
tography on silica, pure 7a (82 mg, 66%) was isolated. IR
(neat): 698 s, 1096 s, 1454 m, 2867 m, 3446 br s. MS m/z (rel
intensity): 351 (M+ - 17, 10), 333 (40), 243 (50), 153 (90), 91
(100). 1H NMR (CDCl3, 400 MHz): δ 7.27-7.18 (10H), 5.78
(dd, 1H, J ) 17.3, 10.8 Hz), 5.40 (d, 1H, J ) 17.3 Hz), 5.14 (d,
1H, J ) 10.8 Hz), 4.57 (d, 1H, J ) 14.5 Hz), 4.50 (d, 1H, J )
11.3 Hz), 4.46 (d, 1H, J ) 14.5 Hz), 4.39 (d, 1H, J ) 11.3 Hz),
3.59 (dd, 1H, J ) 9.0, 4.8 Hz), 3.52 (d, 1H, J ) 12.3 Hz), 3.49
(d, 1H, J ) 12.3 Hz), 3.34 (d, 1H, J ) 9.5 Hz), 3.29 (d, 1H, J
) 9.5 Hz), 2.61 (bs, 1H), 1.92 (dd, 1H, J ) 13.8, 4.8 Hz), 1.72
(dd, 1H, J ) 13.8, 9.0 Hz), 1.11 (s, 3H). 13C NMR (CDCl3, 100
MHz): δ 139.5 (1), 138.1 (0), 137.8 (0), 128.4 (1), 127.8 (1),
127.7 (1), 127.6 (1), 127.4 (1), 126.7 (1), 116.0 (2), 76.4 (1), 74.8
(2), 74.2 (0), 73.4 (2), 71.6 (0), 71.3 (2), 67.5 (2), 33.0 (2), 26.9
(3). Anal. Calcd for C23H28O4: C, 75.0; H, 7.7. Found: C, 74.9;
H, 7.8.
(3R*,4S*,6S*)-4-Ben zyloxy-6-ben zyloxym eth yl-6-p h en -
yl-3-vin yltetr a h yd r op yr a n -3-ol (7b). Following the proce-
dure for the methyl analogue, we obtained 7b (0.33 g, 89%)
from 6b (0.35 g, 0.9 mmol). IR (neat): 699 m, 1075 s, 1101 s,
1454 m, 3030 m, 3543 br s. MS m/z (rel intensity): 429 (M+
+
1, 15), 384 (20), 218 (25), 207 (100), 157 (30), 117 (35), 91 (75),
73 (55). 1H NMR (CDCl3, 400 MHz): δ 7.38 (d, 2H, J ) 7.5
Hz), 7.28-7.08 (11H), 6.93 (dd, 2H, J ) 7.5, 3.7 Hz), 6.00 (dd,
1H, J ) 17.3, 10.8 Hz), 5.48 (dd, 1H, J ) 17.3, 1.5 Hz), 5.19
(dd, 1H, J ) 10.8, 1.5 Hz), 4.49 (d, 1H, J ) 11.3 Hz), 4.43 (d,
1H, J ) 12.1 Hz), 4.34 (d, 1H, J ) 12.1 Hz), 4.28 (d, 1H, J )
11.3 Hz), 3.68 (d, 1H, J ) 12.0 Hz), 3.64 (dd, 1H, J ) 7.3, 4.0
Hz), 3.64 (d, 1H, J ) 12.0 Hz), 3.44 (d, 1H, J ) 10.3 Hz), 3.40
(d, 1H, J ) 10.3 Hz), 2.63 (bs, 1H), 2.40 (dd, 1H, J ) 14.3, 4.0
Hz), 2.27 (dd, 1H, J ) 14.3, 7.3 Hz). 13C NMR (CDCl3, 100
MHz): δ 143.1 (0), 139.1 (1), 138.0 (1), 137.6 (0), 128.2 (1),
128.2 (1), 128.1 (1), 128.0 (1), 127.7 (1), 127.6 (1), 127.5 (1),
127.5 (1), 127.4 (1), 126.8 (1), 125.3 (1), 116.0 (2), 77.6 (0), 77.3
(1), 76.8 (2), 73.4 (2), 71.2 (2), 70.8 (0), 67.3 (2), 31.1 (2).
Gen er a l P r oced u r e for th e P r ep a r a tion of Sp ir ocyclic
La ct on es. A solution of the allylic alcohol (3.0 mmol), Rh-
(acac)(CO)2 (1.0 mol %), and BIPHEPHOS (4.0 mol %) in
anhydrous dioxane (10 mL) was heated at 60 °C for 20 h under
C
26H28O4: C, 77.2; H, 7.0. Found: C, 76.8; H, 7.0.
(4S*,6R*)-4-Ben zyloxy-6-ben zyloxym eth yl-6-m eth yl-d i-
h yd r op yr a n -3-on e (6a ). To a solution of the alcohol (3S*,4S*,
6R*)-5a (2.12 g, 6.2 mmol) in DCM (20 mL) were added NMO
(1.09 g, 9.3 mmol) and powdered 4 Å molecular sieves (3.10
g). TPAP (0.11 g, 5 mol %) was added, and the mixture was
stirred at ambient temperature until the starting material was
completely consumed as indicated by TLC. The solvent was
evaporated, and the residue was filtered through a small pad
of silica. The organics were eluted with MTBE, and the solvent
was evaporated to give the ketone 6a (1.76 g, 84%). IR (neat):
699 m, 1101 s, 1725 s. MS m/z (rel intensity): 341 (M+ + 1,

7664 J . Org. Chem., Vol. 66, No. 23, 2001
Schmidt et al.
an atmosphere of carbon monoxide (10 bar) and hydrogen (10
bar) in an autoclave. The reaction mixture was filtered through
basic alumina, and all organics were eluted with MTBE and
then ethanol. The solvent was evaporated, and the crude
hemiacetals were redissolved in DCM (20 mL). Powdered
molecular sieve (4 Å, 2.00 g) and N-methyl morpholine-N-oxide
(0.53 g, 4.5 mmol) were added, followed by TPAP (53 mg, 5
mol %). The mixture was stirred at ambient temperature until
the starting material was completely converted as indicated
by TLC (3:1 (v/v) hexanes/ethyl acetate). The solvent was
evaporated to one-third of the original volume, and the residue
was filtered through a 5 cm pad of silica. The products were
eluted with MTBE and purified by flash chromatography, if
necessary.
Hz, (O)CCH2CH2-), 2.31 (d, 1H, J ) 15.0 Hz, H3ax), 2.05 (ddd,
1H, J ) 17.6, 10.8, 3.3 Hz, (O)CCH2CH2-), 1.69 (ddd, 1H, J )
13.1, 10.5, 3.3 Hz, (O)CCH2CH2-), 1.36 (ddd, 1H, J ) 13.1,
10.8, 10.0 Hz, (O)CCH2CH2-). 13C NMR (CDCl3, 100 MHz): δ
175.8 (0), 141.6 (0), 139.6 (0), 139.0 (0), 129.2 (1), 129.1 (1),
128.9 (1), 128.5 (1), 128.4 (1), 128.3 (1), 128.2 (1), 128.1 (1),
127.8 (1), 83.4 (0), 80.3 (2), 79.9 (0), 79.4 (1), 74.4 (2), 72.2 (2),
60.9 (2), 39.8 (2), 33.1 (2), 29.7 (2).
(5S,6S)-6-Meth yl-1,7-dioxaspir o[4,5]dec-9-en -2-on e ((5S,
6S)-15a ) a n d (5R,6S)-6-Meth yl-1,7-d ioxa sp ir o[4,5]d ec-9-
en -2-on e ((5R,6S)-15a ). The title compounds were obtained
from 9a (3:1 mixture of diastereoisomers, 1.3 g, 9.3 mmol) as
a 3:1 mixture of diastereoisomers. Separation of the diastere-
oisomers by column chromatography on silica gives (5S,6S)-
15a (0.95 g, 61%) and (5R,6S)-15a (0.31 g, 20%). Analytical
data for (5S, 6S)-15a . Mp ) 103 °C. IR (KBr, disk): 954 s,
1132 s, 1377 s, 1469 s, 1767 s, 2998 s. MS m/z (rel intensity):
168 (M+, 100), 108 (20). 1H NMR (CDCl3, 400 MHz): δ 6.02
(ddd, 1H, J ) 10.0, 3.3, 1.8 Hz, H5), 5.74 (ddd, 1H, J ) 10.0,
2.0, 2.0 Hz, H4), 4.22 (ddd, 1H, J ) 17.1, 3.3, 2.0 Hz, H6eq),
4.09 (ddd, 1H, J ) 17.1, 2.0, 2.0 Hz, H6ax), 3.62 (q, 1H, J )
6.5 Hz, H2), 2.64 (ddd, 1H, J ) 18.2, 10.5, 7.5 Hz, (O)CCH2-
CH2-), 2.56 (ddd, 1H, J ) 18.2, 9.8, 6.5 Hz, (O)CCH2CH2-),
2.12 (m, 1H, (O)CCH2CH2-), 2.01 (m, 1H, (O)CCH2CH2-), 1.24
(d, 3H, J ) 6.5 Hz, -CH3).13C NMR (CDCl3, 100 MHz): δ 176.2
(0), 130.7 (1), 126.4 (1), 80.9 (0), 75.4 (1), 64.1 (2), 29.9 (2),
(5R *,8R *,10S *)-10-Be n zyloxy-8-b e n zyloxym e t h yl-8-
m et h yl-1,7-d ioxa sp ir o[4.5]d eca n -2-on e (13a ). The title
compound was obtained from 7a (0.19 g, 0.5 mmol) following
the general procedure for the preparation of spirocyclic lac-
tones. Yield: 0.16 g (80%). IR (neat): 1077 s, 1218 m, 1454 m,
1727 m, 1770 s, 2930 m. 1H NMR (CDCl3, 600 MHz): δ 7.37-
7.24 (10H), 4.67 (d, 1H, J ) 12.2 Hz, -CH(4)OCHHPh), 4.53
(d, 1H, J ) 12.2 Hz, -CHHOCHHPh), 4.50 (d, 1H, J ) 12.2
Hz, -CHHOCHHPh), 4.41 (d, 1H, J ) 12.2 Hz, -CH(4)-
OCHHPh), 3.73 (d, 1H, J ) 12.7 Hz, H6), 3.72 (dd, 1H, J )
10.7, 4.4 Hz, H4), 3.70 (d, 1H, J ) 12.2 Hz, H6), 3.50 (d, 1H,
J
) 9.8 Hz, -CHHOCHHPh), 3.37 (d, 1H, J ) 9.8 Hz,
-CHHOCHHPh), 2.69 (ddd, 1H, J ) 18.0, 10.5, 9.0 Hz, (O)-
CCHHCHH-), 2.43 (ddd, 1H, J ) 18.0, 10.5, 4.0 Hz, (O)-
CCHHCHH-), 2.14 (dd, 1H, J ) 13.3, 4.4 Hz, H3eq), 1.92 (ddd,
1H, J ) 12.8, 10.5, 4.0 Hz, (O)CCHHCHH-), 1.82 (dd, 1H, J
) 13.3, 10.7 Hz, H3ax), 1.72 (ddd, 1H, J ) 12.8, 10.5, 9.0 Hz,
(O)CCHHCHH-), 1.21 (s, 3H, -CH3). 13C NMR (CDCl3, 100
MHz): δ 176.8 (0), 138.0 (0), 137.9 (0), 128.4 (1), 128.4 (1),
127.8 (1), 127.7 (1), 127.6 (1), 127.4 (1), 83.4 (0), 76.1 (2), 75.0
(0), 74.7 (2), 73.5 (2), 70.3 (2), 68.3 (2), 33.5 (2), 28.8 (2), 27.5
(2), 26.1 (2). Anal. Calcd for C24H28O5: C, 72.7; H, 7.1. Found:
C, 72.4; H, 7.1.
28.0 (2), 13.9 (3). [R]20 ) +171° (c 1.55, CH2Cl2). Anal. Calcd
D
for C9H12O3: C, 64.3; H, 7.2. Found: C, 64.3; H, 7.2. Analytical
data for (5R,6S)-15a . Mp ) 102 °C. IR (KBr, disk): 727 m,
959 s, 1069 s, 1227 s, 1759 s, 2999 s. MS m/z (rel intensity):
168 (M+, 100). 1H NMR (CDCl3, 400 MHz): δ 5.81 (ddd, 1H, J
) 10.3, 2.5, 1.3 Hz), 5.77 (ddd, 1H, J ) 10.3 Hz), 4.16 (dm,
1H, J ) 16.8 Hz), 4.06 (dm, 1H, J ) 16.8 Hz), 3.71 (q, 1H, J
) 6.5 Hz), 2.56 (ddd, 1H, J ) 18.4, 10.0, 4.8 Hz), 2.47 (ddd,
1H, J ) 18.4, 10.0, 8.6 Hz), 2.37 (ddd, 1H, J ) 13.3, 10.0, 4.8
Hz), 1.93 (ddd, 1H, J ) 13.3, 10.0, 8.6 Hz), 1.14 (d, 3H, J )
6.5 Hz, -CH3). 13C NMR (CDCl3, 100 MHz): δ 176.7 (0), 129.5
(1), 128.2 (1), 82.5 (0), 73.8 (1), 65.6 (2), 29.2 (2), 27.1 (2), 14.4
(5R *,8R *,10S *)-10-Be n zyloxy-8-b e n zyloxym e t h yl-8-
p h en yl-1,7-d ioxa sp ir o[4.5]d eca n -2-on e ((5R*,8R*,10S*)-
13b) a n d (5S*,6R*,9S*)-6-Ben zyloxy-9-ben zyloxym eth yl-
9-p h en yl-1,8-d ioxa sp ir o[4.5]d eca n -2-on e ((5S*,6R*,9S*)-
13b). The title compounds were obtained from 7b (0.53 g, 1.2
mmol) following the general procedure for the preparation of
spirocyclic lactones as a 4:1 mixture of regioisomers that were
separated by column chromatography. Data for (5R*,8R*,-
10S*)-13b. Yield: 0.14 g (44%). IR (neat): 1075 s, 1775 s, 3033
s. MS m/z (rel intensity): 337 (M+ - PhCH2OCH2-, 100%),
(3). [R]20 ) +161° (c 1.60, CHCl3). Anal. Calcd for C9H12O3:
D
C, 64.3; H, 7.2. Found: C, 64.2; H, 7.1.
(5S*,6S*)-6-P h en yl-1,7-d ioxa sp ir o[4,5]d ec-9-en -2-on e
((5S*,6S*)-15b) a n d (5R,6S)-6-P h en yl-1,7-d ioxa sp ir o[4,5]-
d ec-9-en -2-on e ((5R*,6S*)-15b). The title compounds were
obtained from 9b (0.60 g, 3.0 mmol) as a 4:1 mixture of
diastereoisomers. Separation of the diastereoisomers by col-
umn chromatography on silica gives (5S,6S)-15b (0.26 g, 38%)
and (5R*,6S*)-15b (0.10 g, 14%). Analytical data for (5S*,6S*)-
15b. Mp ) 164 °C. IR (KBr, disk): 708 s, 1032 s, 1201 s, 1456
229 (32), 91 (C7H7+, 98). H NMR (CDCl3, 400 MHz): δ 7.59
1
(d, 2H, J ) 8.0 Hz, Ph), 7.24 (dd, 2H, J ) 7.7, 7.7 Hz, Ph),
7.20-7.08 (11H, Ph), 4.39 (d, 1H, J ) 12.2 Hz, CH(4)OCH2-
Ph), 4.22 (d, 1H, J ) 12.2 Hz, CH(4)OCH2Ph), 4.19 (d, 1H, J
) 12.5 Hz, -CH2OCH2Ph), 4.17 (d, 1H, J ) 12.5 Hz, -CH2-
OCH2Ph), 3.77 (d, 1H, J ) 12.2 Hz, H6), 3.61 (dd, 1H, J ) 9.7,
4.2 Hz, H4), 3.51 (d, 1H, J ) 10.0 Hz, H6), 3.50 (d, 1H, J )
12.2 Hz, -CH2OCH2Ph), 3.40 (d, 1H, J ) 12.2 Hz, -CH2OCH2-
Ph), 2.44 (dd, 1H, J ) 13.5, 4.2 Hz, H3eq), 2.33 (ddd, 1H, J )
17.5, 10.5, 8.2 Hz, (O)CCH2CH2-), 2.26 (dd, 1H, J ) 13.5, 9.7
Hz, H3ax), 1.94 (ddd, 1H, J ) 17.5, 10.7, 4.7 Hz, (O)CCH2-
CH2-), 1.37 (ddd, 1H, J ) 13.0, 10.5, 4.7 Hz, (O)CCH2CH2-),
1.20 (ddd, 1H, J ) 13.0, 10.5, 8.2 Hz, (O)CCH2CH2-). 13C NMR
(CDCl3, 100 MHz): δ 176.7 (0), 143.7 (0), 137.9 (0), 137.8 (0),
128.4 (1), 128.3 (1), 128.0 (1), 127.7 (1), 127.6 (1), 127.5 (1),
127.4 (1), 127.1 (1), 125.1 (1), 83.4 (0), 78.2 (0), 76.4 (1), 75.6
(2), 73.5 (2), 70.6 (2), 67.9 (2), 33.2 (2), 28.7 (2), 27.8 (2). Data
for (5S*,6R*,9S*)-13b. Yield: 0.03 g (10%). IR (neat): 1096 s,
m, 1767 s, 2831 m, 2945 m. MS m/z (rel intensity): 231 (M+
+
1, 20), 157 (45), 141 (100). 1H NMR (CDCl3, 600 MHz): δ 7.44
(d, 2H, J ) 7.3 Hz, ortho-H, Ph), 7.37-7.32 (3H, Ph), 6.16 (ddd,
1H, J ) 10.3, 3.5, 1.5 Hz, H5), 5.84 (ddd, 1H, J ) 10.3, 2.0,
2.0 Hz, H4), 4.46 (ddd, 1H, J ) 17.2, 3.4, 2.0 Hz, H6eq), 4.42
(s, 1H, H2), 4.32 (ddd, 1H, J ) 17.2, 1.5, 1.5 Hz, H6ax), 2.24-
2.16 (2H, (O)CCH2CH2-), 2.01 (m, 1H, (O)CCH2CH2-), 1.49
(m, 1H, (O)CCH2CH2-). 13C NMR (CDCl3, 100 MHz): δ 176.2
(0), 135.4 (0), 131.9 (1), 128.9 (1), 128.7 (1), 128.4 (1), 127.5
(1), 83.1 (1), 80.3 (0), 66.1 (2), 30.0 (2), 27.9 (2). Anal. Calcd
for C14H14O3: C, 73.0; H, 6.1. Found: C, 73.0; H, 6.2. Analytical
data for (5R*,6S*)-15b. Mp ) 110 °C. IR (KBr, disk): 704 m,
1028 s, 1092 s, 1454 s, 1692 m, 1778 s, 2941 s. MS m/z (rel
intensity): 231 (M+ + 1, 100), 124 (55), 96 (47). 1H NMR
(CDCl3, 600 MHz): δ 7.41 (d, 2H, J ) 7.3 Hz, ortho-H, Ph),
7.37-7.29 (3H, Ph), 5.95 (ddd, 1H, J ) 10.3, 2.5, 2.0 Hz, H4,5),
5.90 (ddd, 1H, J ) 10.3, 2.0, 2.0 Hz, H4,5), 4.67 (s, 1H, H2),
4.40-4.33 (2H, H6), 2.33 (ddd, 1H, J ) 13.7, 10.7, 2.4 Hz, (O)-
CCH2CH2-), 2.03 (ddd, 1H, J ) 18.1, 10.7, 2.4 Hz, (O)CCH2-
CH2-), 1.86 (ddd, 1H, J ) 13.7, 10.5, 10.5 Hz, (O)CCH2CH2-
), 0.92 (ddd, 1H, J ) 18.1, 10.5, 10.5 Hz, (O)CCH2CH2-). 13C
NMR (CDCl3, 100 MHz): δ 177.0 (0), 136.0 (0), 130.0 (1), 128.5
(1), 128.3 (1), 128.0 (1), 126.6 (1), 82.5 (0), 78.5 (1), 66.3 (2),
28.4 (2), 27.9 (2). Anal. Calcd for C14H14O3: C, 73.0; H, 6.1.
Found: C, 72.8; H, 6.1.
1454 m, 1778 s, 2928 s. MS m/z (rel intensity): 336 (M+
-
PhCH2OCH3, 86%), 91 (C7H7+, 100). 1H NMR (CDCl3, 400
MHz): δ 7.58 (d, 2H, J ) 8.6 Hz, Ph), 7.41-7.06 (13H, Ph),
4.48 (d, 1H, J ) 12.3 Hz, -CH2OCH2Ph), 4.35 (d, 1H, J ) 12.3
Hz, -CH2OCH2Ph), 4.23 (d, 1H, J ) 12.3 Hz, -CH(4)OCH2-
Ph), 4.03 (d, 1H, J ) 12.3 Hz, -CH(4)OCH2Ph), 3.80 (dd, 1H,
J ) 10.8, 10.8 Hz, H6ax), 3.71 (dd, 1H, J ) 10.8, 4.8 Hz, H6eq),
3.51 (d, 1H, J ) 10.0 Hz, -CH2OCH2Ph), 3.32 (d, 1H, J ) 10.0
Hz, -CH2OCH2Ph), 3.24 (dd, 1H, J ) 10.8, 4.8 Hz, H5), 2.49
(d, 1H, J ) 15.0 Hz, H3eq), 2.43 (ddd, 1H, J ) 17.6, 10.0, 10.0
(5R*,8S*)-8-(4-Meth oxyp h en yl)-1,7-d ioxa sp ir o[4,5]d ec-
9-en -2-on e ((5R*,8S*)-17). The title compound was obtained

Ring-Closing Metathesis and Hydroformylation
J . Org. Chem., Vol. 66, No. 23, 2001 7665
from (3R*,6S*)-11 (0.50 g, 2.2 mmol) as a colorless solid (0.33
g, 58%). Purification was achieved by flash chromatography
on silica and recrystallization from DCM/hexane. Mp ) 64 °C.
IR (KBr, disk): 1032 s, 1244 s, 1304 s, 1514 s, 1612 s, 1775 s,
2838 m, 2959 s. MS m/z (rel intensity): 260 (M+, 76), 162 (61),
°C. IR (KBr, disk): 967 s, 1173 s, 1437 m, 1594 m, 1774 s,
2960 m. MS m/z (rel intensity): 260 (M+, 100), 229 (28), 162
1
(45), 135 (90). H NMR (CDCl3, 600 MHz): δ 7.29 (d, 2H, J )
8.5 Hz, ortho-H, Ar), 6.87 (d, 2H, J ) 8.5 Hz, meta-H, Ar),
6.03 (d, 1H, J ) 10.3, 2.0 Hz, H3), 5.90 (d, 1H, J ) 10.3 Hz,
H4), 5.03 (s, 1H, H2), 3.97 (d, 1H, J ) 11.7 Hz, H6eq), 3.77 (s,
3H, OMe), 3.66 (d, 1H, J ) 11.7, H6ax), 2.66 (ddd, 1H, J )
18.1, 10.0, 7.0 Hz, (O)CCH2CH2-), 2.59 (ddd, 1H, J ) 18.1,
10.0, 7.0 Hz, (O)CCH2CH2-), 2.15 (ddd, 1H, J ) 13.2, 10.0,
7.0 Hz, (O)CCH2CH2-), 2.10 (ddd, 1H, J ) 13.2, 10.0, 7.0 Hz,
(O)CCH2CH2-). 13C NMR (CDCl3, 100 MHz): δ 176.0 (0), 159.6
(0), 134.0 (1), 131.0 (0), 129.0 (1), 126.0 (1), 113.8 (1), 78.9 (0),
75.9 (1), 69.6 (2), 55.2 (3), 30.1 (2), 28.0 (2). Anal. Calcd for
1
135 (100). H NMR (CDCl3, 600 MHz): δ 7.21 (d, 2H, J ) 8.3
Hz, ortho-H, Ar), 6.87 (d, 2H, J ) 8.3 Hz, meta-H, Ar), 5.96
(d, 1H, J ) 10.7 Hz, H3,4), 5.93 (d, 1H, J ) 10.7 Hz, H3,4),
5.10 (s, 1H, H2), 3.86 (d, 1H, J ) 11.2 Hz, H6eq), 3.79 (d, 1H,
J ) 11.2, H6ax), 3.78 (s, 3H, OMe), 2.66-2.56 (2H, (O)CCH2-
CH2-), 2.45 (ddd, 1H, J ) 13.2, 8.3, 5.4 Hz, (O)CCH2CH2-),
2.18 (ddd, 1H, J ) 13.2, 9.8, 9.3 Hz, (O)CCH2CH2-). 13C NMR
(CDCl3, 100 MHz): δ 176.2 (0), 159.7 (0), 132.6 (1), 131.4 (0),
128.7 (1), 128.0 (1), 114.0 (1), 79.3 (0), 76.0 (1), 69.2 (2), 55.3
(3), 31.3 (2), 27.8 (2). Anal. Calcd for C15H16O4: C, 69.2; H,
6.2. Found: C, 68.9; H, 6.2.
C
15H16O4: C, 69.2; H, 6.2. Found: C, 69.0; H, 6.0.
(5S*,8S*)-8-(4-Meth oxyp h en yl)-1,7-d ioxa sp ir o[4,5]d ec-
9-en -2-on e ((5R*,8S*)-17). The title compound was obtained
from (5S*,8S*)-17 (0.80 g, 3.4 mmol) as a colorless solid (0.48
g, 54%). Purification was achieved by flash chromatography
on silica and recrystallization from DCM/hexane. Mp ) 218
Ack n ow led gm en t. We thank the Deutsche Fors-
chungsgemeinschaft and the Fonds der Chemischen
Industrie for generous financial support.
J O0157730