Diastereoselective Ring-Closing Metathesis in the Synthesis of Dihydropyrans

Article abstract of DOI:10.1021/jo005534x

An investigation into the factors influencing the diastereochemical outcome of the ring-closing metathesis based synthesis of dihydropyrans is presented in this paper. Divinyl carbinols derived from α-hydroxy carboxylic acid esters are elaborated to trienes with two diastereotopic vinyl moieties. Depending on the steric demand of the oxo substituent of the divinyl carbinol moiety (either unprotected OH, TBDMS, or benzyl ether) different diastereomers are preferrably formed upon ring-closing metathesis. An extension to diastereoselective double ring-closing metathesis in the formation of spirocycles has also been investigated.

Full text of DOI:10.1021/jo005534x

J . Org. Chem. 2000, 65, 5817-5822
5817
Dia ster eoselective Rin g-Closin g Meta th esis in th e Syn th esis of
Dih yd r op yr a n s
Bernd Schmidt* and Holger Wildemann
Universita¨t Dortmund, Fachbereich Chemie, Organische Chemie, Otto-Hahn-Strasse 6,
D-44227 Dortmund, Germany
bschmidt@citrin.chemie.uni-dortmund.de
Received J une 2, 2000
An investigation into the factors influencing the diastereochemical outcome of the ring-closing
metathesis based synthesis of dihydropyrans is presented in this paper. Divinyl carbinols derived
from R-hydroxy carboxylic acid esters are elaborated to trienes with two diastereotopic vinyl moieties.
Depending on the steric demand of the oxo substituent of the divinyl carbinol moiety (either
unprotected OH, TBDMS, or benzyl ether) different diastereomers are preferrably formed upon
ring-closing metathesis. An extension to diastereoselective double ring-closing metathesis in the
formation of spirocycles has also been investigated.
Sch em e 1
In tr od u ction
The application of ring-closing metathesis1,2 to the syn-
thesis of unsaturated oxacycles3,4 has been investigated
by several groups over the past few years. Examples are
the formation of spirocyclic dihydropyrans and dihydro-
furans5,6 and trans-fused polyether fragments7-11 on
carbohydrate scaffolds. Our own contributions to the field
started with a project directed to the utilization of ring-
closing metathesis for the synthesis of C-glycosides.12,13
With a view toward the synthesis of structural elements
of polyether natural products,14 we became interested in
the synthesis of di- and tetrahydropyrans with a qua-
ternary center in the 3-position.15 In principle, one can
imagine two different strategies to obtain such prod-
ucts: either an enone I is cyclized to a dihydropyranone
II, followed by addition of an appropriately substituted
organometallic reagent R3M to give the dihydropyran III,
or the ester IV is converted to a carbinol V by subsequent
addition of a vinylmetal compound and the organome-
tallic reagent R3M, followed by ring-closing metathesis
to give III (Scheme 1).
acid because the catalytic activity of the ruthenium
carbene intermediate is significantly reduced by forma-
tion of a chelate.16-19 Thus, from the viewpoint of catalytic
efficiency, the second route seems to be more promising.
In this case, it is particularly interesting to investigate
the ring-closing metathesis of those substrates that result
when R3 ) vinyl, because the two vinyl moieties of the
divinyl carbinol V are diastereotopic and the ring-closing
metathesis step may in principle become diastereoselec-
tive. Compared to the number of publications on olefin
metathesis in general, comparatively few contributions
have addressed stereoselective variants so far. Enanti-
oselective ring-closing metathesis reactions using chirally
modified catalysts have been conducted as kinetic resolu-
tions20,21 or as desymmetrization reactions.22 A stereose-
lective synthesis of 2,5-disubstituted five membered
azacycles represents the first diastereoselective ring-
closing metathesis reaction.23 Recently, Lautens et al.
Ring-closing metathesis of enones such as I normally
requires higher catalyst loadings and addition of a Lewis-
* To whom correspondence should be addressed. Fax: +49 (231)-
7555363. E-mail: bschmidt@citrin.chemie.uni-dortmund.de.
(1) Armstrong, S. K. J . Chem. Soc., Perkin Trans. 1 1998, 371-388.
(2) Grubbs, R. H.; Chang, S. Tetrahedron 1998, 54, 4413-4450.
(3) Elliott, M. C. J . Chem. Soc., Perkin Trans. 1 1998, 4175-4200.
(4) Elliott, M. C. J . Chem. Soc., Perkin Trans. 1 2000, 1291-1318.
(5) Holt, D. J .; Barker, W. D.; J enkins, P. R.; Panda, J .; Ghosh, S.
J . Org. Chem. 2000, 65, 482-493.
(6) Leeuwenburgh, M. A.; Appeldoorn, C. C. M.; van Hooft, P. A.
V.; Overkleeft, H. S.; van der Marel, G. A.; van Boom, J . H. Eur. J .
Org. Chem. 2000, 873-877.
(7) Leeuwenburgh, M. A.; Kulker, C.; Overkleeft, H. S.; van der
Marel, G. A.; van Boom, J . H. Synlett 1999, 1945-1947.
(8) Clark, J . S.; Kettle, J . G. Tetrahedron 1999, 55, 8231-8248.
(9) Clark, J . S.; Hamelin, O. Angew. Chem., Int. Ed. 2000, 39, 372-
374.
(16) Ramachandran, P. V.; Reddy, M. V. R.; Brown, H. C. Tetrahe-
dron Lett. 2000, 41, 583-586.
(17) Ghosh, A. K.; Cappiello, J .; Shin, D. Tetrahedron Lett. 1998,
39, 4651-4654.
(18) Ghosh, A. K.; Bilcer, G. Tetrahedron Lett. 2000, 41, 1003-1006.
(19) Ghosh, A. K.; Wang, Y. Tetrahedron Lett. 2000, 41, 2319-2322.
(20) Fujimura, O.; Grubbs, R. H. J . Am. Chem. Soc. 1996, 118,
2499-2500.
(21) Alexander, J . B.; La, D. S.; Cefalo, D. R.; Hoveyda, A. H.;
Schrock, R. R. J . Am. Chem. Soc. 1998, 120, 4041-4042.
(22) Weatherfield, G. S.; Ford, J . G.; Alexanian, E. J .; Schrock, R.
R.; Hoveyda, A. H. J . Am. Chem. Soc. 2000, 122, 1828-1829.
(23) Huwe, C. M.; Velder, J .; Blechert, S. Angew. Chem., Int. Ed.
Engl. 1996, 35, 2376-2378.
(10) Eriksson, L.; Guy, S.; Perlmutter, P. J . Org. Chem. 1999, 64,
8396-8398.
(11) Delgado, M.; Mart´ın, J . D. J . Org. Chem. 1999, 64, 4798-4816.
(12) Schmidt, B.; Sattelkau, T. Tetrahedron 1997, 53, 12991-13000.
(13) Schmidt, B. Org. Lett. 2000, 2, 791-794.
(14) Dutton, C. J .; Banks, B. J .; Cooper, C. B. Nat. Prod. Rep. 1995,
12, 165-181.
(15) Schmidt, B.; Wildemann, H. Synlett 1999, 1591-1593.
10.1021/jo005534x CCC: $19.00 © 2000 American Chemical Society
Published on Web 08/17/2000

5818 J . Org. Chem., Vol. 65, No. 18, 2000
Schmidt and Wildemann
Sch em e 3a
Sch em e 2a
a
Key: (i) NaH, THF, 65 °C, then R′-X, 65 °C (see Table 1).
Ta ble 1. Yield s a n d Nu m ber in g System for Tr ien es (cf.
Sch em e 3)
starting
entry
material
R
R′-X
Bn-Br
TBDMS-Cl
All-Br
Bn-Br
TBDMS-Cl
All-Br
product
yield (%)
a
Key: (i) Ag2O, allyl bromide, ether, 20 °C (2a : 80%; 2b: 99%);
(ii) H2CdCHMgCl (2 equiv.), ether, -78 °C (4a : 63%; 4b: 44%);
(iii) H2CdCHMgCl (3 equiv), ether, -78 °C (3a : 65%; 3b: 31%);
(iv) NaH, allyl bromide, THF, 0 °C, 12h (4a : 51%).
1
2
3
4
5
6
4a
4a
4a
4b
4b
4b
Me
Me
Me
Ph
Ph
Ph
(S)-5a
(S)-6a
(S)-7a
rac-5b
rac-6b
rac-7b
55
61
71
63
52
85
reported the formation of cis- and trans-decalin systems
via a stereoselective double ring-closing metathesis reac-
tion.24 A metathesis-based approach to the AB ring
fragment of Ciguatoxin includes the diastereoselective
formation of an oxepine.25 Diastereoselective spirocycle
assembly by double ring-closing metathesis was very
recently achieved by others26 and by ourselves.27
Sch em e 4a
In this paper, we describe our results on the stereose-
lectivity of ring-closing metathesis reactions in the
synthesis of dihydropyrans with functionalizable sub-
stituents.
a
Key: (i) Cl2(Cy3P)2RudCHPh (A) (3 mol %), CH2Cl2, 20 °C
(see Table 2).
Resu lts a n d Discu ssion
Ta ble 2. Resu lts for Dia ster eoselective RCM Rea ction s
(See Sch em e 4)
Divinylcarbinols 4 required for this study were syn-
thesized starting from the commercially available R-hy-
droxy carboxylic acid esters (S)-ethyl lactate (1a ) and DL-
methyl mandelate (1b) (Scheme 2).
starting
yield
entry material
R
R′
product (2S,3S)/(2S,3R) (%)
1
2
3
4
5
6
4a
5a
6a
4b
5b
6b
Me
Me Bn
Me TBDMS (2S)-10a
Ph
Ph Bn
Ph TBDMS rac-10b
H
(2S)-8a
(2S)-9a
3:1
1:3
1:2
4:1
<1:10
1:6
66
45
91
56
62
87
O-Allylation of 1a ,b was achieved without racemization
or other undesired side reactions using allyl bromide and
silver oxide.28 Addition of 2 equiv of vinylmagnesium
chloride to the esters 2a ,b provides divinyl carbinols 4a ,b,
along with minor amounts of the corresponding buten-
ones resulting from a 1,4-addition of the second equiva-
lent of the vinyl Grignard reagent. Alternatively, we
investigated the route via the diols 3a ,b. Addition of
excess vinylmagnesium chloride to esters 1a ,b provides
the diols 3a ,b. Methyl derivative 3a 29 is obtained with
none or very small amounts of the corresponding 1,4-
addition product, whereas from mandelic acid ester a 1:1
mixture of 3b and the butenone results. Selective ally-
lation of the secondary alcohol functionality in 3a is
achieved by treatment with one equivalent of sodium
hydride and allyl bromide at 0 °C. The reaction proceeds
with quantitative yield. The divinyl carbinol moiety is
obviously rather sensitive, however, which leads to a
significant decrease of the yield if analytically pure
material is required. Surprisingly, the allylation step
completely fails if methyl mandelate is employed. In this
case a viscous residue is obtained containing no low-
molecular weight products. Thus, for preparative pur-
H
rac-8b
rac-9b
poses 4a is most conveniently prepared via diol 3a ,
whereas 4b is best obtained from 2a .
A set of substituted metathesis precursors is obtained
from 4a ,b by introducing various hydroxy protecting
groups of different steric demand. Functionalization of
the tertiary alcohol as a benzyl, TBDMS, or allyl ether
requires excess of base, elevated temperatures, and
prolonged reaction times; nevertheless, the sensitive
allyloxy and divinyl carbinol moieties are not affected by
these rather harsh conditions. Scheme 3 and Table 1
summarize this synthetic step.
Ring-closing metathesis reactions of the trienes 4, 5
and 6 proceeds at ambient temperature in the presence
of 3 mol % of Grubbs' catalyst Cl2(Cy3P)2RudCHPh (A).
Diastereomeric ratios were determined prior to workup
by means of HNMR spectroscopy. Conversion to the
product is normally quantitative; the yields reported here
refer to the amount of material isolated after chroma-
tography on silica. From ring-closing metathesis of the
unprotected divinyl carbinols preferrably the (2S*, 3S*)-
isomers of 8a ,b result, whereas upon introduction of a
benzyl or TBDMS protecting group the (2S*,3R*)-isomers
are preferred (Scheme 4 and Table 2). Two-dimensional
NOE spectroscopy was used to determine the relative
stereochemistry: interactions between H2 and the pro-
tons of the exo-vinyl moiety are indicative of the (2S*,3S*)-
stereochemistry. Deprotection of the ring-closing metath-
esis products 10a ,b resulting from the TBDMS ethers
(24) Lautens, M.; Hughes, G. Angew. Chem., Int. Ed. 1999, 38, 129-
131.
(25) Oguri, H.; Sasaki, S.; Oishi, T.; Hirama, M. Tetrahedron Lett.
1999, 40, 5405-5408.
(26) Wallace, D. J .; Cowden, C. J .; Kennedy, D. J .; Ashwood, M. S.;
Cottrell, I. F.; Dolling, U.-H. Tetrahedron Lett. 2000, 41, 2027-2029.
(27) Schmidt, B.; Westhus, M. Tetrahedron 2000, 56, 2421-2426.
(28) Aurich, H. G.; Biesemeier, F.; Boutahar, M. Chem. Ber. 1991,
124, 2329-2334.
(29) Yoshimitsu, T.; Ogasawara, K. J . Chem. Soc., Chem. Commun.
1994, 2197-2199.

Ring-Closing Metathesis Dihydropyran Synthesis
J . Org. Chem., Vol. 65, No. 18, 2000 5819
Sch em e 5a
Sch em e 6a
a
Key: (i) Cl2(Cy3P)2RudCHPh (A) (6 mol %), DCM, 20 °C.
yields mainly the alcohols (2S*,3R*)-8a ,b. In contrast to
methyl mandelate (1b), ethyl lactate (1a ) was used in
enantiomerically pure form. To find out if any racemiza-
tion occurs during the sequence from 1a to 4a , NMR-
shift experiments were conducted for the 3:1 mixture of
(2S,3S)- and (2S, 3R)-4a at 400 MHz using the europium-
(III) [heptafluoropropylhydroxymethylene)camphorate]
(Eu(hfc)3) reagent. Racemic 4a was required in order to
find conditions where sufficient separation of relevant
signals (most conveniently the doublets of the methyl
group are observed) is achieved. Therefore, (S)-ethyl
lactate was allylated under strongly basic conditions
(sodium hydride) to give rac-2a , from which rac-4a was
obtained as outlined above. By these shift-experiments
it was possible to demonstrate that both the material
obtained via 2a and the material obtained via 3a are
enantiomerically pure.
a
Key: (i) B (8 mol %), toluene, 110 °C.
Sch em e 7a
1,2-Stereoinduction is more efficient for the phenyl
derivatives 4b-6b due to the higher steric demand of
the phenyl substituent compared to the methyl group.
The stereochemical results can be understood if one
assumes a trans-orientation of the substituent at C2 and
the sterically more demanding substituent at C3 in the
transition state. For the unprotected derivatives 4a ,b,
this is obviously the vinyl moiety, whereas the oxo-
substituent becomes more demanding upon derivatiza-
tion as benzyl or TBDMS ether.
Allyl ethers 7a ,b are substrates for a double ring-
closing metathesis leading to spirocyclic systems 11a ,b
(Scheme 5). The reaction proceeds only with poor or
moderate yield due to competing intermolecular metath-
esis. However, in both cases only one diastereoisomer was
isolated and it was not possible to detect the other
diastereomer from the reaction mixture.
Naturally, in double ring-closing metathesis reactions
the question arises: “Which ring is closed first?” We were
unable to isolate any intermediates; however, if the
dihydrofuran is formed first, this step might be reversible
via a ring opening/ring-closing metathesis sequence.
There have been several reports in the literature on
ROM/RCM-sequences when strained five-membered rings
are involved.30-32 The yield for the methyl derivative is
particularly disappointing. We repeated this experiment
using a novel carbene complex B, which was originally
assigned an allenylidene type structure.33-35 In our
hands, ring-closing metathesis using this complex pro-
ceeds very rapidly at elevated temperatures. When the
tetraene 7a is subjected to the conditions, mainly unde-
a
Key: (i) NaH, allyl bromide, THF, 65 °C (76%); (ii) Cl2(Cy3P)2-
RudCHPh (3 mol %), DCM, 20 °C, then column chromatography
on silica ((5S, 6S)-11a (14%), ((5R, 6S)-11a (19%)).
fined oligomeric products result. The only isolable low
molecular weight product is a single diastereomer of
dihydropyran 12a ; its formation is obviously the result
of a sequential double bond isomerization to an enol ether
intermediate, followed by a Claisen rearrangement
(Scheme 6).
We finally investigated a two step procedure to the
spirocyclic system 11a . Starting from 8a ((2S,3S):(2S,3R)
) 3:1) allylation is achieved using the procedure for
functionalization of trienes 4a ,b. Ring-closing metathesis
of dihydropyran 13a ((2S,3S):(2S,3R) ) 3:1) proceeds
smoothly in the presence of 3 mol % of Grubbs’ catalyst
to produce a 3:1 mixture of spirocycles (5S,6S)-11a and
(5R,6S)-11a . This experiment illustrates that, in contrast
to five membered rings, formation of the dihydropyran
is obviously not reversible under the conditions. Other-
wise, one would expect an isomerization to the (5R,6S)-
diastereomer. The two diastereomers of 11a thus ob-
tained are separable by column chromatography. The
major diastereomer (5S,6S)-11a decomposes to a large
extent on silica, however, so that the pure compound is
obtained only with significant loss of material. Surpris-
ingly, (5R,6S)-11a appears to be stable under these
conditions (Scheme 7).
Exp er im en ta l Section
(30) Zuercher, W. J .; Hashimoto, M.; Grubbs, R. H. J . Am. Chem.
Soc. 1996, 118, 6634-6640.
Instrumentation, product identification and general experi-
mental methods have been described previously.36 Whenever
a signal assignment for NMR-spectra is given, this is based
on 2D methods (H,H-COSY, NOESY and HMQC, respectively).
Signal assignment for cyclic products follows a numbering
scheme where the oxygen atom is numbered 1 and the
(31) Stragies, R.; Blechert, S. Tetrahedron 1999, 55, 8179-8188.
(32) Adams, J . A.; Ford, J . G.; Stamatos, P. J .; Hoveyda, A. H. J .
Org. Chem. 1999, 64, 9690-9696.
(33) Harlow, K. J .; Hill, A. F.; Wilton-Ely, J . D. E. T. J . Chem. Soc.,
Dalton Trans. 1999, 285-291.
(34) Fu¨rstner, A.; Hill, A. F.; Liebl, M.; Wilton-Ely, J . D. E. T. Chem.
Commun. 1999, 601-602.
(35) Fu¨rstner, A.; Thiel, O. R. J . Org. Chem. 2000, 65, 1738-1742.
(36) Schmidt, B. J . Chem. Soc., Perkin Trans. 1 1999, 2627-2637.

5820 J . Org. Chem., Vol. 65, No. 18, 2000
Schmidt and Wildemann
R-carbon atom bearing a substituent C2. The number of
coupled protons was analyzed by DEPT experiments and is
denoted by a number in parentheses following the δc value.
Gen er a l P r oced u r e for th e P r ep a r a tion of Allyloxy
Ester s 2a ,b. To a solution of the R-hydroxy ester (96 mmol)
in ether (200 mL) was added silver oxide (44.5 g, 192 mmol)
and allyl bromide 12.4 mL, 144 mmol). The mixture was
stirred for 2 days at 20 °C in the dark. The solids were filtered
off, and the solvent was evaporated. The residue is normally
analytically pure.
114.6 (2), 80.1 (1), 77.7 (0), 70.6 (2), 14.1 (3); [R]26D ) +19.6° (c
1.42, CHCl3). Anal. Calcd for C10H16O2: C, 71.4; H, 9.6.
Found: C, 71.4; H, 9.6.
r a c-3-(1-Allyloxyph en ylm eth yl)pen ta-1,4-dien -3-ol (4b).
Starting from 2b (3.7 g, 18 mmol), 1.8 g (44%) of 4b was
obtained: IR (neat) 706 s, 925 s, 3470 bm; MS m/z (rel
intensity) 213 (M+ - 17, 20), 157 (40), 105 (100); 1H NMR
(CDCl3, 400 MHz) δ 7.40-7.30 (5H), 5.98 (dd, 1H, J ) 17.3,
10.8 Hz), 5.94 (dd, 1H, J ) 17.3, 10.8 Hz), 5.90 (dddd, 1H, J )
17.3, 10.3, 6.0, 5.0 Hz), 5.33 (dd, 1H, J ) 17.3, 1.5 Hz), 5.31
(dd, 1H, J ) 17.3, 1.5 Hz), 5.24 (dddd, 1H, J ) 17.3, 3.5, 1.5,
1.5 Hz), 5.20 (dd, 1H, J ) 10.8, 1.5 Hz), 5.18 (dddd, 1H, J )
10.3, 3.5, 1.5, 1.5 Hz), 5.16 (dd, 1H, J ) 10.8, 1.5 Hz), 4.32 (s,
1H), 4.00 (dddd, 1H, J ) 12.8, 5.0, 1.5, 1.5 Hz), 3.79 (dddd,
1H, J ) 12.8, 6.0, 1.5, 1.5 Hz), 2.72 (s, 1H); 13C NMR (CDCl3,
100 MHz) δ 139.0 (1), 138.5 (1), 136.8 (0), 134.3 (1), 128.6 (1),
128.0 (1), 127.8 (1), 117.1 (2), 114.8 (2), 114.7 (2), 86.9 (1), 77.5
(0), 69.9 (2). Anal. Calcd for C15H18O2: C, 78.2; H, 7.9. Found:
C, 78.3; H, 7.9.
Alter n a tive P r ep a r a tion of (S)-4a . To a solution of (S)-
3a (1.00 g, 7.8 mmol) in dry THF (50 mL) was added at 0 °C
NaH (0.31 g, 60% dispersion in mineral oil, 7.8 mmol) followed
by allyl bromide (1.0 mL, 11.7 mmol). Stirring was continued
at this temperature for 2 h, and then the mixture was allowed
to warm to ambient temperature and stirred for 12 h. Aqueous
workup, followed by chromatography on silica, gives 0.67 g
(51%) of (S)-4a .
Gen er a l P r oced u r e for th e F u n ction a liza tion of Di-
vin ylca r bin ols 4. To a solution of the corresponding divinyl-
carbinol 4 (11 mmol) in dry THF (50 mL) was added NaH (1.30
g, 60% dispersion in mineral oil, 33 mmol), and the mixture
was heated to reflux for 30 min. After the mixture was cooled
to ambient temperature, the corresponding alkyl bromide or
silyl chloride (16 mmol) was added, and the reaction mixture
was again refluxed until the starting material was fully
consumed, as indicated by TLC. Aqueous workup, followed by
chromatography on silica, gives the functionalized derivatives
9-11.
(S)-2-Allyloxyp r op ion ic Acid Eth yl Ester (2a ).28 Start-
ing from (S)-ethyl lactate (1a ) (10.0 g, 96 mmol), 12.0 g (80%)
of 2a was obtained: 1H NMR (CDCl3, 400 MHz) δ 5.83 (dddd,
1H, J ) 17.3, 10.6, 6.0, 5.5 Hz), 5.20 (dddd, 1H, J ) 17.3, 3.0,
1.5, 1.5 Hz), 5.10 (dddd, 1H, J ) 10.6, 3.0, 1.3, 1.3 Hz), 4.16-
4.09 (2H), 4.05 (dddd, 1H, J ) 12.6, 5.5, 1.5, 1.5 Hz), 3.92 (q,
1H, J ) 7.0 Hz), 3.85 (dddd, 1H, J ) 12.6, 6.0, 1.3, 1.3 Hz),
1.32 (d, 3H, J ) 7.0 Hz), 1.20 (t, 3H, J ) 7.3 Hz; 13C NMR
(CDCl3, 100 MHz) δ 173.2 (0), 134.1 (1), 117.6 (2), 73.9 (1),
71.0 (2), 60.7 (2), 18.6 (3), 14.1 (3).
r a c-Allyloxy-2-p h en yla cetic Acid Meth yl Ester (2b).
Starting from DL-methyl mandelate (1b) (3.0 g, 18 mmol), 3.7
g (99%) of 2b was obtained: IR (neat) 699 s, 1173 s, 1755 s,
2865 w; MS m/z (rel intensity) 207 (M+ + 1, <5), 147 (95), 105
(100); 1H NMR (CDCl3, 400 MHz) δ 7.48-7.43 (2H), 7.37-7.30
(3H), 5.93 (dddd, 1H, J ) 17.3, 10.3, 6.0, 5.5 Hz), 5.28 (dddd,
1H, J ) 17.3, 1.5, 1.5, 1.5 Hz), 5.21 (ddm, 1H, J ) 10.3, 1.3
Hz), 4.94 (s, 1H), 4.06-4.03 (2H), 3.80 (s, 3H); 13C NMR
(CDCl3, 100 MHz) δ 171.0 (0), 136.1 (0), 133.6 (1), 128.5 (1),
128.4 (1), 127.1 (1), 118.0 (2), 79.5 (1), 70.2 (2), 52.0 (3). Anal.
Calcd for C12H14O3: C, 69.9; H, 6.8. Found: C, 69.4; H, 6.8.
Gen er a l P r oced u r e for th e P r ep a r a tion of Divin yl-
ca r bin ols. Vinylmagnesium chloride (21 mL 1.7 M solution
in THF, 36 mmol) was added dropwise to a solution of the
corresponding ester (12 mmol) in ether at -78 °C. The mixture
was stirred at this temperature for 1 h and then at 20 °C for
12 h. After aqueous workup, the residue was purified by
column chromatography on silica.
(S)-3-Vin ylp en t-4-en e-2,3-d iol (3a ).29 Starting from 1a
(17.4 g, 147 mmol), 12.2 g (65%) of 3a was obtained: IR (neat)
930 s, 1001 s, 3430 bs; MS m/z (rel intensity) 111 (M+ - 17,
(S )-[1-(1-Allyloxye t h yl)-1-vin yla llyloxym e t h yl]b e n -
zen e (5a ). Starting from 4a (2.00 g, 11.9 mmol), 2.08 g (55%)
of 5a was obtained: IR (neat) 935 s, 1113 s, 3089 m; MS m/z
(rel intensity) 259 (M+ + 1, <5), 151 (100), 133 (70); 1H NMR
(CDCl3, 400 MHz) δ 7.35-7.18 (5H), 5.97 (dd, 2H, J ) 17.8,
11.0 Hz), 5.87 (dddd, 1H, J ) 17.3, 10.5, 5.5, 5.5 Hz), 5.39 (dd,
1H, J ) 11.0, 1.5 Hz), 5.35 (dd, 1H, J ) 11.0, 1.5 Hz), 5.34
(dd, 1H, J ) 17.8, 1.5 Hz), 5.33 (dd, 1H, J ) 17.8, 1.5 Hz),
5.22 (dddd, 1H, J ) 17.3, 1.5, 1.5, 1.5 Hz), 5.09 (dddd, 1H, J
) 10.5, 1.5, 1.5, 1.5 Hz), 4.40 (d, 1H, J ) 12.3 Hz), 4.36 (d,
1H, J ) 12.3 Hz), 4.11 (dddd, 1H, J ) 13.1, 5.5, 1.5, 1.5 Hz),
4.06 (dddd, 1H, J ) 13.1, 5.5, 1.5, 1.5 Hz), 3.51 (q, 1H, J ) 6.3
Hz), 1.06 (d, 3H, J ) 6.3 Hz); 13C NMR (CDCl3, 100 MHz) δ
139.8 (0), 137.8 (1), 135.9 (1), 135.5 (1), 128.1 (1), 126.9 (1),
126.8 (1), 118.3 (2), 117.5 (2), 116.2 (2), 83.7 (0), 81.1 (1), 71.6
1
10), 83 (20), 55 (100); H NMR (CDCl3, 400 MHz) δ 5.95 (dd,
1H, J ) 17.3, 10.8 Hz), 5.93 (dd, 1H, J ) 17.3, 10.8 Hz), 5.38
(dd, 1H, J ) 17.3, 1.3 Hz), 5.35 (dd, 1H, J ) 17.3, 1.3 Hz),
5.23 (dd, 1H, J ) 10.8, 1.3 Hz), 5.22 (dd, 1H, J ) 10.8, 1.3
Hz), 3.67 (dq, 1H, J ) 6.5, 4.3 Hz), 2.45 (s (br), 1H), 2.24 (s
(br.), 1H), 1.12 (d, 3H, J ) 6.5 Hz); 13C NMR (CDCl3, 100 MHz)
δ 140.0 (1), 138.0 (1), 115.7 (2), 115.3 (2), 78.4 (0), 72.7 (1),
16.8 (3); [R]23 ) +5.1° (c 1.66, DCM). Anal. Calcd for
D
C7H12O2: C, 65.6; H, 9.4. Found: C, 65.6; H, 9.5.
r a c-1-P h en yl-2-vin ylbu t-3-en -1,2-d iol (3b). Starting from
DL-methyl mandelate (1b) (2.0 g, 12 mmol), 0.7 g (31%) of 3b
was obtained: IR (neat) 1050 s, 3448 bm; MS m/z (rel
intensity) 173 (M+ - 17, 40), 105 (70), 55 (100); 1H NMR
(CDCl3, 400 MHz) δ 7.23-7.19 (5H), 5.83 (dd, 1H, J ) 17.3,
10.8 Hz), 5.77 (dd, 1 H, J ) 17.3, 10.8 Hz), 5.29 (dd, 1H, J )
17.3, 1.3 Hz), 5.16 (dd, 1H, J ) 17.3, 1.3 Hz), 5.14 (dd, 1H, J
) 10.8, 1.3 Hz), 5.08 (dd, 1H, J ) 10.8, 1.3 Hz), 4.48 (d, 1H, J
) 3.5 Hz), 2.93 (d, 1H, J ) 3.5 Hz), 2.48 (s, 1H); 13C NMR
(CDCl3, 100 MHz) δ 139.3 (1), 138.7 (0), 137.8 (1), 127.8 (1),
127.8 (1), 127.6 (1), 115.7 (2), 115.2 (2), 79.4 (1), 78.4 (0). Anal.
Calcd for C12H14O2: C, 75.8; H, 7.4. Found: C, 75.6; H, 7.4.
(S)-3-(1-Allyloxyeth yl)p en ta -1,4-d ien -3-ol (4a ). Starting
from 2a (6.0 g, 42 mmol), 4.4 g (63%) of 4a was obtained: IR
(neat) 924 s, 1091 s, 3464 bm; MS m/z (rel intensity) 163 (M+
+ 1, <5), 95 (90), 55 (100); 1H NMR (CDCl3, 400 MHz) δ 5.92
(dd, 1H, J ) 17.3, 10.3 Hz), 5.91 (dd, 1H, J ) 17.3, 10.8 Hz),
5.82 (dddd, 1H, J ) 17.3, 10.3, 6.0, 5.5 Hz), 5.31 (dd, 1H, J )
17.3, 1.5 Hz), 5.29 (dd, 1H, J ) 17.3, 1.5 Hz), 5.19 (dddd, 1H,
J ) 17.3, 3.0, 1.5, 1.5 Hz), 5.13 (dd, 1H, J ) 10.8, 1.5 Hz),
5.13 (dd, 1H, J ) 10.8, 1.5 Hz), 5.09 (dddd, 1H, J ) 10.3, 3.0,
1.5, 1.5 Hz), 4.05 (dddd, 1H, J ) 12.8, 5.5, 1.5, 1.5 Hz), 3.87
(dddd, 1H, J ) 12.8, 6.0, 1.5, 1.5 Hz), 3.35 (q, 1H, J ) 6.3 Hz),
2.53 (s (br.), 1H), 1.07 (d, 3H, J ) 6.3 Hz); 13C NMR (CDCl3,
100 MHz) δ 139.9 (1), 138.8 (1), 134.8 (1), 116.8 (2), 114.7 (2),
(2), 65.3 (2), 15.2 (3); [R]20 ) + 10.8° (c 2.10, CHCl3). Anal.
D
Calcd for C17H22O2: C, 79.0; H, 8.6. Found: C, 78.7; H, 8.8.
r a c-(1-Allyloxy-2-p h en ylm et h oxy-2-vin ylb u t -3-en yl)-
b en zen e (5b). Starting from 4b (1.90 g, 8.3 mmol), 1.66 g
(63%) of 5b was obtained: IR (neat) 700 s, 733 s, 1097 s, 3063
m; MS m/z (rel intensity) 294 (M+ - 26, 20), 91 (10), 58 (100);
1H NMR (CDCl3, 400 MHz) δ 7.31-7.15 (10H), 6.12 (dd, 1H,
J ) 17.8, 11.0 Hz), 5.81 (dddd, 1H, J ) 17.3, 10.5, 5.8, 5.0
Hz), 5.62 (dd, 1H, J ) 17.8, 11.0 Hz), 5.34 (dd, 1H, J ) 11.0,
1.5 Hz), 5.26 (dd, 1H, J ) 17.8, 1.5 Hz), 5.25 (dd, 1H, J ) 11.0,
1.5 Hz), 5.17 (dddd, 1H, J ) 17.3, 1.5, 1.5, 1.5 Hz), 5.16 (dd,
1H, J ) 17.8, 1.5 Hz), 5.06 (dddd, 1H, J ) 10.5, 1.5, 1.5, 1.5
Hz), 4.39 (d, 1H, J ) 12.5 Hz), 4.38 (s, 1H), 4.32 (d, 1H, J )
12.5 Hz), 3.95 (dddd, 1H, J ) 13.1, 5.0, 1.5, 1.5 Hz), 3.77 (dddd,
1H, J ) 13.1, 5.8, 1.5, 1.5 Hz); 13C NMR (CDCl3, 100 MHz) δ
139.8 (0), 137.9 (0), 137.6 (1), 135.7 (1), 134.9 (1), 129.3 (1),
128.0 (1), 127.5 (1), 127.2 (1), 126.7 (1), 126.7 (1), 118.2 (2),
118.1 (2), 116.5 (2), 87.4 (1), 83.1 (0), 70.2 (2), 65.3 (2). Anal.
Calcd for C22H24O2: C, 82.5; H, 7.5. Found: C, 82.8; H, 7.7.
(S)-[1-(1-Allyloxyeth yl)-1-vin yla llyloxy]-ter t-bu tyld im -
eth ylsila n e (6a ). Starting from 4a (2.00 g, 11.9 mmol), 2.04
g (61%) of 6a was obtained: IR (neat) 776 s, 930 s, 1101 s,

Ring-Closing Metathesis Dihydropyran Synthesis
J . Org. Chem., Vol. 65, No. 18, 2000 5821
1961 s; MS m/z (rel intensity) 281 (M+ + 1, <5), 225 (100), 95
(30); 1H NMR (CDCl3, 400 MHz) δ 6.01 (dd, 1H, J ) 17.3, 10.5
Hz), 5.87 (dddd, 1H, J ) 17.3, 10.3, 5.5, 5.5 Hz), 5.35 (dd, 1H,
J ) 17.3, 2.3 Hz), 5.30 (dd, 1H, J ) 17.3, 2.3 Hz), 5.26-5.20
(3H), 5.11 (dddd, 1H, J ) 10.3, 1.5, 1.5, 1.5 Hz), 4.06 (dddd,
1H, J ) 13.1, 5.5, 1.5, 1.5 Hz), 3.93 (dddd, 1H, J ) 13.1, 5.5,
1.5, 1.5 Hz), 3.34 (q, 1H, J ) 6.3 Hz), 1.06 (d, 3H, J ) 6.3 Hz),
0.89 (s, 9H), 0.05 (s, 3H), 0.03 (s, 3H); 13C NMR (CDCl3, 100
MHz) δ 142.2 (1), 138.8 (1), 135.5 (1), 116.7 (2), 116.2 (2), 115.9
(2), 81.3 (1), 80.1 (0), 70.9 (2), 26.1 (3), 18.7 (0), 14.4 (3), -1.7
intensity) 123 (M+ - 17, 84), 95 (75), 81 (100); 1H NMR (CDCl3,
400 MHz) δ 5.92 (ddd, 1H, J ) 10.0, 4.0, 3.5 Hz, H5), 5.80
(ddd, 1H, J ) 10.0, 1.5, 1.5 Hz, H4), 5.78 (dd, 1H, J ) 17.6,
10.8 Hz, HCdCH2), 5.36 (dd, 1H, J ) 17.6, 1.5 Hz, H2CdCH),
5.20 (dd, 1H, J ) 10.8, 1.5 Hz, H2CdCH), 4.22 (ddd, 1H, J )
16.8, 3.5, 1.8 Hz, H6), 4.16 (ddd, 1H, J ) 16.8, 4.0, 1.5 Hz,
H6), 3.50 (q, 1H, J ) 6.3 Hz, H2), 2.58 (s (br.), 1H, HO-), 1.21
(d, 3H, J ) 6.3 Hz, H3C-); 13C NMR (CDCl3, 100 MHz) δ 139.5
(1), 130.7 (1), 128.2 (1), 115.0 (2), 77.7 (1), 70.0 (0), 65.7 (2),
14.1 (3); [R]26 ) +150.2° (c 1.64, CHCl3). NMR-data of the
D
(3), -2.0 (3); [R]20 ) + 3.7° (c 1.64, CHCl3). Anal. Calcd for
minor diastereomer (2S,3R)-8a : 1H NMR (CDCl3, 400 MHz)
δ 5.96 (dd, 1H, J ) 17.6, 10.8 Hz, HCdCH2), 5.79 (ddd, 1H, J
) 10.3, 2.3, 2.3 Hz, H4/H5), 5.58 (ddd, 1H, J ) 10.3, 2.3, 2.3
Hz, H4/H5), 5.28 (dd, 1H, J ) 17.8, 1.3 Hz, H2CdCH), 5.21
(dd, 1H, J ) 10.8, 1.3 Hz, H2CdCH), 4.18 (dm, 1H, J ) 16.8
Hz, H6), 4.14 (dm, 1H, J ) 16.8 Hz, H6), 3.54 (q, 1H, J ) 6.3
Hz, H2), 2.46 (s (br), 1H, HO-), 1.13 (d, 3H, J ) 6.3 Hz, H3C-
); 13C NMR (CDCl3, 100 MHz) δ 138.3 (1), 131.0 (1), 126.2 (1),
114.4 (2), 77.0 (1), 71.9 (0), 65.2 (2), 14.8 (3).
D
C16H30O2Si: C, 68.0; H, 10.7. Found: C, 67.8; H, 10.6.
r a c-[1-(1-Allyloxy-1-p h en ylm et h yl)-1-vin yla llyloxy]-
ter t-bu tyld im eth ylsila n (6b). Starting from 4b (1.90 g, 8.3
mmol), 1.47 g (52%) of 6b was obtained: IR (neat) 776 s, 836
s, 3089 w; MS m/z (rel intensity) 287 (M+ - 57, 60), 157 (90),
1
73 (100); H NMR (CDCl3, 400 MHz) δ 7.47-7.39 (5H), 6.47
(dd, 1H, J ) 17.3, 10.8 Hz), 6.01 (dddd, 1H, J ) 17.8, 10.5,
5.8, 5.0 Hz), 6.00 (dd, 1H, J ) 17.3, 10.8 Hz), 5.44 (dd, 1H, J
) 17.3, 1.5 Hz), 5.42 (dd, 1H, J ) 17.3, 1.5 Hz), 5.39 (dd, 1H,
J ) 10.8, 1.5 Hz), 5.36 (ddm, 1H, J ) 17.8, 1.5 Hz), 5.35 (dd,
1H, J ) 10.8, 1.5 Hz), 5.26 (ddm, 1H, J ) 10.5, 1.5 Hz), 4.36
(s, 1H), 4.07 (dddd, 1H, J ) 12.8, 5.0, 1.5, 1.5 Hz), 3.91 (dddd,
1H, J ) 12.8, 5.8, 1.5, 1.5 Hz), 1.02 (s, 9H), 0.20 (s, 3H), 0.00
(s, 3H); 13C NMR (CDCl3, 100 MHz) δ 140.3 (1), 138.8 (1), 138.1
(0), 134.9 (1), 129.3 (1), 127.5 (1), 127.1 (1), 116.6 (2), 116.5
(2), 116.3 (2), 88.3 (1), 79.8 (0), 70.1 (2), 26.2 (3), 18.8 (0), -1.7
(3), -2.0 (3). Anal. Calcd for C21H32O2Si: C, 73.2; H, 9.4.
Found: C, 73.2; H, 9.4.
(2S*,3S*)- a n d (2S*,3R*)-2-P h en yl-3-vin yl-3,6-d ih yd r o-
2H-p yr a n -3-ol (8b). Starting from 4b (3.69 g, 16.0 mmol), 2.80
g (86%) of crude 8b was obtained as a 4:1 mixture of (2S*,3S*)-
8b and (2S*,3R*)-8b. Separation of the diastereomers by
careful chromatography gives 1.42 g (44%) of (2S*,3S*)-8b and
0.39 g (12%) of (2S*,3R*)-8b: IR (neat) 700 s, 1068 s, 3464
bm; MS m/z (rel intensity) 185 (M+ - 17, 100), 167 (60), 105
(100); NMR data for (2S*,3S*)-8b: 1H NMR (CDCl3, 400 MHz)
δ 7.30-7.20 (5H, Ph), 5.96 (ddd, 1H, J ) 10.0, 3.8, 1.8 Hz,
H5), 5.81 (ddd 1H, J ) 10.0, 2.0, 2.0 Hz, H4), 5.73 (dd, 1H, J
) 17.8, 10.5 Hz, HCdCH2), 5.10 (dd, 1H, J ) 17.8, 1.5 Hz,
H2CdCH), 5.09 (dd, 1H, J ) 10.5, 1.5 Hz, H2CdCH), 4.37 (s,
1H, H2), 4.36 (dm, 1H, J ) 16.8 Hz, H6ax), 4.23 (dm, 1H, J )
16.8 Hz, H6eq), 1.85 (s (br), 1H, HO-); 13C NMR (CDCl3, 100
MHz) δ 140.0 (1), 136.7 (0), 130.1 (1), 128.8 (1), 127.8 (1), 127.7
(1), 127.6 (1), 115.5 (2), 83.7 (1), 70.7 (0), 66.5 (2). NMR-data
for (2S*,3R*)-8b: 1H NMR (CDCl3, 400 MHz) δ 7.31-7.20 (5H,
Ph), 5.82 (ddm, 1H, J ) 10.3, 2.0 Hz, H5), 5.80 (dd, 1H, J )
17.3, 10.5 Hz, HCdCH2), 5.64 (ddm, 1H, J ) 10.3, 2.0 Hz, H4),
4.99 (dm, 1H, J ) 17.3 Hz, H2CdCH), 4.95 (dm, 1H, J ) 10.5
Hz, H2CdCH), 4.42 (s, 1H, H2), 4.33 (ddd, 1H, J ) 16.8, 2.0,
2.0 Hz, H6), 4.28 (ddd, 1H, J ) 16.8, 2.0, 2.0 Hz, H6), 1.72 (s
(br), 1H, HO-); 13C NMR (CDCl3, 100 MHz) δ 138.8 (1), 137.2
(0), 130.8 (1), 127.8 (1), 127.2 (1), 127.6 (1), 126.3 (1), 114.4
(2), 82.7 (1), 72.7 (0), 66.4 (2).
(S)-3-Allyloxy-3-(1-a llyloxyeth yl)p en ta -1,4-d ien e (7a ).
Starting from 4a (3.06 g, 18.2 mmol), 2.68 g (71%) of 7a was
obtained: IR (neat) 920 s, 1100 s, 2934 m; MS m/z (rel
intensity) 209 (M+ + 1, <5), 151 (60), 95 (100); 1H NMR
(CDCl3, 400 MHz) δ 5.97-5.82 (4H), 5.35 (dd, 1H, J ) 11.0,
1.5 Hz), 5.32 (dd, 1H, J ) 11.0, 1.5 Hz), 5.31-5.25 (3H), 5.22
(dddd, 1H, J ) 17.1, 1.5, 1.5, 1.5 Hz), 5.10 (dddd, 1H, J ) 17.8,
1.5, 1.5, 1.5 Hz), 5.07 (dddd, 1H, J ) 10.3, 1.5, 1.5, 1.5 Hz),
4.09 (dddd, 1H, J ) 12.8, 5.5, 1.5, 1.5 Hz), 4.04 (dddd, 1H, J
) 12.8, 5.5, 1.5, 1.5 Hz), 3.85 (dddd, 1H, J ) 13.3, 5.0, 1.5, 1.5
Hz), 3.81 (dddd, 1H, J ) 13.3, 5.0, 1.5, 1.5 Hz), 3.46 (q, 1H, J
) 6.3 Hz), 1.09 (d, 3H, J ) 6.3 Hz; 13C NMR (CDCl3, 100 MHz)
δ 137.8 (1), 135.8 (1), 135.7 (1), 135.5 (1), 118.0 (2), 117.2 (2),
116.2 (2), 114.9 (2), 83.4 (0), 80.9 (1), 71.5 (2), 64.4 (2), 15.0
(3); [R]20 ) +5.2° (c 2.14, CHCl3). Anal. Calcd for C13H20O2:
D
C, 75.0; H, 9.7. Found: C, 75.3; H, 9.7.
(2S,3R)-3-Ben zyloxy-2-m eth yl-3-vin yl-3,6-d ih yd r o-2H-
p yr a n (9a ). Starting from 5a (0.40 g, 1.5 mmol), 9a was
obtained as a 3:1 mixture of (2S,3R)- and (2S,3S)-diastereo-
mers. Analytically pure (2S,3R)-9a (0.20 g, 56%) was obtained
by careful column chromatography on silica: IR (neat) 696 m,
1116 s, 2981 m; MS m/z (rel intensity) 123 (M+ - 107, 35), 91
r a c-(1,2-Bis-a llyloxy-2-vin ylb u t -3-en yl)ben zen e (7b).
Starting from 4b (2.50 g, 10.9 mmol), 2.50 g (85%) of 7b was
obtained: IR (neat) 919 s, 1070 s, 2921 m; MS m/z (rel
intensity) 271 (M+ + 1, 10), 105 (100), 83 (70); 1H NMR (CDCl3,
400 MHz) δ 7.37-7.20 (5H), 6.07 (dd, 1H, J ) 17.5, 11.0 Hz),
5.84 (ddm, 1H, J ) 17.3, 10.5 Hz), 5.79 (ddm, 1H, J ) 17.5,
10.5 Hz), 5.64 (dd, 1H, J ) 17.5, 11.0 Hz), 5.32 (dd, 1H, J )
11.0, 1.5 Hz), 5.22 (dd, 1H, J ) 11.0, 1.5 Hz), 5.21 (ddm, 1H,
J ) 17.5, 1.5 Hz), 5.17 (ddm, 1H, J ) 17.3, 1.5 Hz), 5.12 (dd,
1H, J ) 17.5, 1.5 Hz), 5.07 (ddm, 1H, J ) 10.5, 1.5 Hz), 5.01
(dd, 1H, J ) 17.5, 1.5 Hz), 5.00 (ddm, 1H, J ) 10.5, 1.5 Hz),
4.34 (s, 1H), 3.95 (dddd, 1H, J ) 13.1, 5.0, 1.5, 1.5 Hz), 3.90
(dddd, 1H, J ) 13.1, 5.5, 1.5, 1.5 Hz), 3.81 (dddd, 1H, J ) 13.1,
5.0, 1.5, 1.5 Hz), 3.76 (dddd, 1H, J ) 13.1, 6.0, 1.5, 1.5 Hz);
13C NMR (CDCl3, 100 MHz) δ 137.9 (0), 137.5 (1), 135.7 (1),
135.7 (1), 134.9, (1), 129.2 (1), 127.9 (1), 127.4 (1), 117.9 (2),
117.8 (2), 116.4 (2), 114.7 (2), 87.2 (1), 82.9 (0), 70.1 (2), 64.4
(2). Anal. Calcd for C18H22O2: C, 80.0; H, 8.2. Found: C, 79.8;
H, 8.5.
Gen er a l P r oced u r e for th e Rin g-Closin g Meta th esis
Rea ction . The corresponding metathesis precursor (5.8 mmol)
was dissolved in dry, deoxygenated CH2Cl2 (20 mL) under an
atmosphere of dry argon. The ruthenium catalyst (146 mg, 3
mol %) was added, and the solution stirred at 20 °C for 12 h.
Evaporation of the solvent followed by flash chromatography
on silica yields the dihydropyrans.
(2S,3S)- a n d (2S,3R)-2-Meth yl-3-vin yl-3,6-d ih yd r o-2H-
p yr a n -3-ol (8a ). Starting from 4a (0.83 g, 5.9 mmol), 0.55 g
(66%) of 8a was obtained as a 3:1 mixture of the diastereo-
mers: IR (neat) 993 s, 1065 s, 2938 m, 3442 bs; MS m/z (rel
1
(100), 81 (30); H NMR (CDCl3, 400 MHz) δ 7.43-7.35 (5H,
Ph), 6.01 (ddd, 1H, J ) 10.3, 3.0, 2.0 Hz, H4/H5), 5.98 (dd,
1H, J ) 17.8, 10.3 Hz, HCdCH2), 5.87 (ddd, 1H, J ) 10.3, 2.0,
2.0 Hz, H4/H5), 5.36 (dd, 1H, J ) 17.8, 1.8 Hz, H2CdCH), 5.35
(dd, 1H, J ) 10.3, 1.8 Hz, H2CdCH), 4.61 (d, 1H, J ) 11.8 Hz,
H2C-C), 4.54 (d, 1H, J ) 11.8 Hz, H2C-C), 4.26 (ddd, 1H, J
) 16.8, 2.0, 2.0 Hz, H6), 4.18 (ddd, 1H, J ) 16.8, 3.0, 2.0 Hz,
H6), 3.84 (q, 1H, J ) 6.5 Hz, H2), 1.23 (d, 3H, J ) 6.5 Hz,
H3C-); 13C NMR (CDCl3, 100 MHz) δ 139.4 (0), 137.5 (1), 129.0
(1), 128.3 (1), 127.6 (1), 127.2 (1), 127.0 (1), 117.7 (2), 77.4 (0),
74.4 (1), 65.8 (2), 64.8 (2), 15.2 (3); [R]20 ) +34.1° (c 1.60,
D
CHCl3). Anal. Calcd for C15H18O2: C, 78.2; H, 7.9. Found: C,
77.6; H, 7.8.
(2S*,3R*)-3-Ben zyloxy-2-p h en yl-3-vin yl-3,6-d ih yd r o-
2H-p yr a n (9b). Starting from 5b (0.40 g, 1.3 mmol), 9b was
obtained as a 9:1 mixture of diastereomers. Analytically pure
(2S,3R)-9b (0.23 g, 62%) was obtained by careful column
chromatography on silica: IR (neat) 698 s, 1140 m, 3030 m;
MS m/z (rel intensity) 294 (M+ + 2, 25), 176 (20), 58 (100); 1H
NMR (CDCl3, 400 MHz) δ 7.38-7.19 (10H, Ph), 6.02 (ddd, 1H,
J ) 10.3, 2.3, 2.3 Hz, H4/H5), 5.92 (ddd, 1H, J ) 10.3, 2.3, 2.3
Hz, H4/H5), 5.448 (dd, 1H, J ) 17.5, 10.5 Hz, HCdCH2), 5.20
(dd, 1H, J ) 17.5, 1.8 Hz, H2CdCH), 5.18 (dd, 1H, J ) 10.5,
1.8 Hz, H2CdCH), 4.71 (s, 1H, H2), 4.58 (d, 1H, J ) 11.8 Hz,
H2C-C), 4.52 (d, 1H, J ) 11.8 Hz, H2C-C), 4.31 (dd, 2H, J )

5822 J . Org. Chem., Vol. 65, No. 18, 2000
Schmidt and Wildemann
2.3, 2.3 Hz, H6); 13C NMR (CDCl3, 100 MHz) δ 139.2 (0), 137.9
(0), 137.7 (1), 128.7 (1), 128.3 (1), 128.2 (1), 127.7 (1), 127.5
(1), 127.3 (1), 127.1 (1), 126.9 (1), 118.6 (2), 79.6 (1), 78.1 (0),
65.5, 64.6 (2). Anal. Calcd for C20H20O2: C, 82.2; H, 6.9.
Found: C, 82.2; H, 7.0.
12.8, 2.5, 2.0 Hz, H2C-O); 13C NMR (CDCl3, 100 MHz) δ 138.7
(0), 130.6 (1), 128.7 (1), 127.3 (1), 127.1 (1), 127.1 (1), 126.9
(1), 126.0 (1), 89.2 (0), 81.4 (1), 75.2 (2), 66.3 (2).
Attem p ted Rin g-Closin g Meta th esis of Tetr a en e 7a
Usin g Ru th en iu m Ca ta lyst B. To a solution of 7a (0.40 g,
2.1 mmol) in toluene (50 mL) was added the ruthenium
complex B (0.106 g, 8 mol %). The mixture was heated to reflux
until the starting material was fully consumed. Only 12a (20
mg, 6%) was isolated. NMR data for 2-methyl-4-(2-methyl-6H-
pyran-3-ylide)butyraldehyde (12a ): 1H NMR (CDCl3, 400
MHz) δ 9.65 (d, 1H, J ) 1.3 Hz, HCdO), 6.45 (dm, 1H, J )
10.3 Hz, H4), 5.88 (ddd, 1H, J ) 10.3, 4.3, 2.8 Hz, H5), 5.20
(dd, 1H, J ) 7.8, 7.3 Hz, HCdC), 4.25 (s, 2H, H6), 4.18 (q, 1H,
J ) 6.5 Hz, H2), 2.51 (ddm, 1H, J ) 14.8, 7.3 Hz, H2C-CH-
CHdO), 2.43 (qm, 1H, J ) 6.8 Hz, HC-CdO), 2.25 (dd, 1H, J
) 14.8, 7.8 Hz, H2C-CH-CHdO), 1.33 (d, 3H, J ) 6.5 Hz, H3C-
), 1.10 (d, 3H, J ) 6.8 Hz, H3C-); 13C NMR (CDCl3, 100 MHz)
δ 204.4 (0), 136.3 (0), 128.1 (1), 120.9 (1), 120.0 (1), 72.5 (1),
63.9 (2), 46.6 (1), 27.3 (2), 18.2 (3), 13.1 (3).
(2S,3R)- a n d (2S,3S)-ter t-Bu tyld im eth yl(2-m eth yl-3-
vin yl-3,6-d ih yd r o-2H-p yr a n -3-yloxy)sila n e (10a ). Starting
from 6a (0.50 g, 1.8 mmol), 10a was obtained as an inseparable
2:1 mixture of diastereomers. Analytically pure 10a (0.41 g,
91%) was obtained by column chromatography on silica: IR
(neat) 775 s, 836 s, 1252 s, 2931 s; MS m/z (rel intensity) 253
(M+ - 1, 100), 169 (30), 75 (90); [R]20D ) +86.8° (c 1.62, CHCl3).
NMR data for (2S,3R)-10a : 1H NMR (CDCl3, 400 MHz) δ 5.87
(dd, 1H, J ) 17.3, 10.5 Hz, HCdCH2), 5.74 (ddd, 1H, J ) 10.3,
2.0, 2.0 Hz, H4/H5), 5.63 (ddd, 1H, J ) 10.3, 2.0, 2.0 Hz, H4/
H5), 5.25 (dd, 1H, J ) 17.3, 2.0 Hz, H2CdCH), 5.11 (dd, 1H, J
) 10.5, 2.0 Hz, H2CdCH), 4.17 (dm, 1H, J ) 16.8 Hz, H6),
4.10 (dm, 1H, J ) 16.8 Hz, H6), 3.51 (q, 1H, J ) 6.3 Hz, H2),
1.09 (d, 3H, J ) 6.3 Hz, H3C-CH), 0.88 (s, 9H, (H3C)3-C), 0.09
(s, 3H, H3C-Si), 0.07 (s, 3H, H3C-Si); 13C NMR (CDCl3, 100
MHz) δ 139.3 (1), 131.6 (1), 125.9 (1), 114.3 (2), 77.4 (1), 74.7
(0), 65.7 (2), 25.8 (3), 18.3 (0), 15.1 (3), -2.0 (3), -2.3 (3). NMR
data for (2S,3S)-10a : 1H NMR (CDCl3, 400 MHz) δ 5.89 (ddd,
1H, J ) 10.3, 1.8, 1.8 Hz, H4/H5), 5.71 (dm, 1H, J ) 10.3 Hz,
H4/H5), 5.70 (dd, 1H, J ) 17.1, 10.5 Hz, HCdCH2), 5.30 (dd,
1H, J ) 17.1, 1.8 Hz, H2CdCH), 5.07 (dd, 1H, J ) 10.5, 1.8
Hz, H2CdCH), 4.17 (dm, 1H, J ) 16.8 Hz, H6), 4.10 (dm, 1H,
J ) 16.8 Hz, H6), 3.34 (q, 1H, J ) 6.3 Hz, H2), 1.12 (d, 3H, J
) 6.3 Hz, H3C-CH), 0.90 (s, 9H, (H3C)3-C), 0.05 (s, 3H, H3C-
Si), 0.03 (s, 3H, H3C-Si); 13C NMR (CDCl3, 100 MHz): δ 142.3
(1), 129.8 (1), 129.1 (1), 114.1 (2), 77.9 (1), 72.4 (0), 65.4 (2),
26.1 (3), 18.6 (0), 14.4 (3), -2.0 (3), -2.5 (3).
(2S*,3R*)-ter t-Bu t yld im et h yl(2-p h en yl-3-vin yl-3,6-d i-
h yd r o-2H-p yr a n -3-yloxy)sila n e (10b). Starting from 6b
(0.30 g, 0.9 mmol), 10b was obtained as an inseparable 6:1
mixture of diastereomers. Analytically pure (2S*,3R*)-10b
(0.24 g, 87%) was obtained by column chromatography on
silica: IR (neat) 700 m, 1094 s, 1255 s, 2930 s; MS m/z (rel
intensity) 316 (M+ - 1, <5), 299 (100), 154 (40); 1H NMR
(CDCl3, 400 MHz) δ 7.32-7.28 (2H, Ph), 7.22-7.10 (3H, Ph),
5.85 (ddd, 1H, J ) 10.3, 2.5, 2.5 Hz, H4/H5), 5.71 (ddd, 1H, J
) 10.3, 2.5, 2.5 Hz, H4/H5), 5.39 (dd, 1H, J ) 17.5, 10.5 Hz,
HCdCH2), 5.03 (dd, 1H, J ) 17.5, 1.8 Hz, H2CdCH), 5.01 (dd,
1H, J ) 10.5, 1.8 Hz, H2CdCH), 4.42 (s, 1H, H2), 4.25 (dd,
2H, J ) 2.5, 2.5 Hz, H6), 0.82 (s, 9H, (H3C)3-C), 0.04 (s, 3H,
H3C-Si), -0.14 (s, 3H, H3C-Si); 13C NMR (CDCl3, 100 MHz) δ
139.8 (1), 137.9 (0), 130.9 (1), 127.9 (1), 127.2 (1), 127.0 (1),
126.3 (1), 116.1 (2), 83.6 (1),, 75.4 (0), 66.4 (2), 25.9 (3), 18.3
(0), -2.0 (3), -2.2 (3). Anal. Calcd for C19H28O2Si: C, 72.1; H,
8.9. Found: C, 71.5; H, 8.7.
(2S,3S)- a n d (2S,3R)-3-Allyloxy-2-m eth yl-3-vin yl-3,6-
d ih yd r o-2H-p yr a n (13a ). Starting from 8a (0.74 g, 5.3 mmol,
3:1 mixture of diastereomers) and allyl bromide following the
general procedure for the functionalization of trienes 4, 0.72
g (76%) of 13a was obtained: IR (neat) 709 s, 1077 s, 1112 s,
2984 m; MS m/z (rel intensity) 181 (M+ + 1, 2), 123 (M+
-
O-allyl, 90), 55 (100). Anal. Calcd for C11H16O2: C, 73.3; H,
8.9. Found: C, 72.5; H, 8.6. NMR data for (2S,3S)-13a : 1H
NMR (CDCl3, 400 MHz) δ 6.08 (1H, J ) 10.3, 3.8, 1.8 Hz),
5.94-5.80 (1H), 5.72 (dd, 1H, J ) 17.3, 11.0 Hz), 5.66 (ddd,
1H, J ) 10.3, 2.3, 2.0 Hz), 5.28-5.20 (2H), 5.13 (dd, 1H, J )
11.0, 1.5 Hz), 4.20 (ddd, 1H, J ) 16.8, 3.8, 2.0 Hz), 4.16-3.93
(3H), 3.43 (q, 1H, J ) 6.5 Hz), 1.20 (d, 3H, J ) 6.5 Hz); 13C
NMR (CDCl3, 100 MHz) δ 140.5 (1), 135.9 (1), 131.1 (1), 126.7
(1), 115.7 (2), 115.0 (2), 78.6 (1), 74.3 (0), 65.5 (2), 65.4 (2),
14.4 (3). NMR data for (2S,3S)-13a : 1H NMR (CDCl3, 400
MHz) δ 3.68 (q, 1H, J ) 6.5 Hz), 1.12 (d, 3H, J ) 6.5 Hz); 13
C
NMR (CDCl3, 100 MHz) δ 137.4 (1), 135.6 (1), 128.8 (1), 127.5
(1), 117.3 (2), 115.5 (2), 77.1 (1), 74.3 (1), 65.6 (2), 63.8 (2),
15.0 (3).
(5S,6S)-6-Meth yl-1,7-dioxaspir o[4,5]deca-3,9-dien e (11a).
Starting from 13a (0.32 g, 1.8 mmol, 3:1 mixture of diastere-
omers) and catalyst A (43 mg, 3 mol %), following the general
procedure for the ring-closing metathesis reaction, 0.29 g
(100%) of crude 11a (3:1 mixture of diastereomers) was
obtained. Separation of the diastereoisomers by column chro-
matography on silica leads to partial decomposition of the
major diastereomer: yield (5S,6R)-11a (50 mg, 19%, minor
isomer) and (5S,6S)-11a (38 mg, 14%, major isomer); IR (neat)
1080 s, 1122 s, 2979 m; MS m/z (rel intensity) 151 (M+ - 1,
1
5), 135 (60), 108 (100); H NMR (CDCl3, 400 MHz) δ 5.97 (d,
(5R,6S)-6-Meth yl-1,7-dioxaspir o[4.5]deca-3,9-dien e (11a).
Starting from 7a (1.27 g, 6.1 mmol), 11a (0.15 g, 16%) was
obtained as a single diastereoisomer, along with oligomeriza-
tion products: IR (neat) 1080 s, 1122 s, 2979 m; MS m/z (rel
intensity) 151 (M+ - 1, 5), 135 (60), 108 (100); 1H NMR (CDCl3,
400 MHz) δ 5.94 (dm, 1H, J ) 6.3, 1.5, 1.5 Hz), 5.77 (ddd, 1H,
J ) 10.3, 3.0, 1.8 Hz), 5.75 (ddd, 1H, J ) 6.3, 2.5, 2.5 Hz),
5.69 (dm, 1H, J ) 10.3 Hz), 4.73 (ddd, 1H, J ) 12.8, 2.3, 1.8
Hz), 4.62 (ddd, 1H, J ) 12.8, 2.3, 1.8 Hz), 4.24 (ddd, 1H, J )
16.8, 2.3, 1.8 Hz), 4.15 (ddd, 1H, J ) 16.8, 3.0, 1.8 Hz), 3.68
(q, 1H, J ) 6.3 Hz), 1.13 (d, 3H, J ) 6.3 Hz); 13C NMR (CDCl3,
100 MHz) δ 129.8 (1), 128.6 (1), 127.4 (1), 126.1 (1), 88.4 (0),
1H, J ) 6.3, 1.5, 1.5 Hz), 5.90 (ddd, 1H, J ) 10.3, 3.0, 1.8 Hz),
5.64 (dm, 1H, J ) 10.0 Hz), 5.50 (ddd, 1H, J ) 6.3, 2.5, 2.5
Hz), 4.74 (ddd, 1H, J ) 13.0, 2.0, 2.0 Hz), 4.57 (ddd, 1H, J )
13.0, 2.0, 2.0 Hz), 4.18 (ddd, 1H, J ) 16.8, 3.5, 1.5 Hz), 4.05
(ddd, 1H, J ) 16.8, 1.8, 1.8 Hz), 3.56 (q, 1H, J ) 6.3 Hz), 1.14
(d, 3H, J ) 6.3 Hz); 13C NMR (CDCl3, 100 MHz) δ 129.7 (1),
129.1 (1), 128.8 (1), 127.8 (1), 86.4 (0), 76.2 (1), 76.0 (2), 65.2
(2), 14.1 (3); [R]20 ) +106.5° (c 1.85, CHCl3).
D
Dep r otection of TBDMS Eth er s 10a ,b. To a solution of
the corresponding TBDMS-ether (0.5 mmol) in THF (10 mL)
was added TBAF (0.27 g, 0.8 mmol). The mixture was stirred
until the starting material was fully consumed. Aqueous
workup and evaporation of all volatiles provided the crude
alcohols 8a and 8b, respectively. NMR spectra of the com-
pounds are identical with those of the minor isomers obtained
from ring-closing metathesis of 4a ,b.
75.5 (1), 75.0 (2), 65.6 (2), 15.4 (3); [R]20 ) +23.5° (c 1.00,
D
CHCl3).
(5R*,6S*)-6-P h en yl-1,7-d ioxa sp ir o[4.5]d eca -3,9-d ien e
(11b). Starting from 7b (0.50 g, 1.9 mmol), 11b (0.17 g, 43%)
was obtained as a single diastereoisomer, along with oligo-
merization products: IR (neat) 706 s, 1026 s, 1087 s, 2936 m;
MS m/z (rel intensity) 213 (M+ - 1, <5), 197 (30), 108 (100);
1H NMR (CDCl3, 400 MHz): δ 7.33 (2H, J ) 7.8 Hz, o-H, Ph),
7.25-7.16 (3H, m-H, p-H, Ph), 5.79 (ddd, 1H, J ) 10.3, 2.3,
2.3 Hz, H5), 5.73 (ddd, 1H, J ) 10.3, 2.0, 2.0 Hz, H4), 5.62
(ddd, 1H, J ) 6.3, 2.5, 2.5 Hz, HCdC), 5.51 (d, 1H, J ) 6.3
Hz, HCdCHHO), 4.60 (s, 1H, H2), 4.49 (ddd, 1H, J ) 12.5,
2.5, 2.0 Hz, H2C-O), 4.34-4.29 (2H, H6), 4.09 (ddd, 1H, J )
Ack n ow led gm en t . We thank the Deutsche For-
schungsgemeinschaft and the Fonds der Chemischen
Industrie for generous financial support. B.S. thanks
Prof. Dr. P. Eilbracht for his support and interest in this
project.
J O005534X