Ring-Closing Metathesis in the Synthesis of Large and Medium-Sized Oxacycles. Application to the Synthesis of Polyoxygenated Macrocycles

Article abstract of DOI:10.1021/jo9901438

Ring-closing olefin metathesis (RCM) catalyzed by Grubbs's ruthenium benzylidene complex 1 is applied to the synthesis of unsaturated rings ranging in size from seven to thirteen members in trails-fused polyether systems. Reaction occurs with great efficiency in the cyclization of oxepene and oxocene rings, but as ring size increases, yields drop. The influence of the final double bond position is also studied. Better yields and milder reaction conditions are observed when an additional oxygen atom is introduced on the diene. This feature has promoted the application of this reaction to the synthesis of polyoxygenated macrocycles (with sizes ranging from 15 to 21 members), with excellent results.

Full text of DOI:10.1021/jo9901438

4798
J . Org. Chem. 1999, 64, 4798-4816
Rin g-Closin g Meta th esis in th e Syn th esis of La r ge a n d
Med iu m -Sized Oxa cycles. Ap p lica tion to th e Syn th esis of
P olyoxygen a ted Ma cr ocycles
Mercedes Delgado and J ulio D. Mart´ın*
Centro de Investigaciones Cientı´ficas Isla de La Cartuja, Instituto de Investigaciones Quı´micas, CSIC,
Sevilla, C) Ame´rico Vespucio, s/ n 41092 Seville, Spain
Received J anuary 26, 1999
Ring-closing olefin metathesis (RCM) catalyzed by Grubbs’s ruthenium benzylidene complex 1 is
applied to the synthesis of unsaturated rings ranging in size from seven to thirteen members in
trans-fused polyether systems. Reaction occurs with great efficiency in the cyclization of oxepene
and oxocene rings, but as ring size increases, yields drop. The influence of the final double bond
position is also studied. Better yields and milder reaction conditions are observed when an additional
oxygen atom is introduced on the diene. This feature has promoted the application of this reaction
to the synthesis of polyoxygenated macrocycles (with sizes ranging from 15 to 21 members), with
excellent results.
Sch em e 1
In tr od u ction
Synthetic organic chemists are continuously searching
for new methods and reactions which will allow them to
obtain the target molecules in as few steps as possible.
In this context, olefin metathesis1 has emerged as a very
powerful tool for carbon-carbon double bond formation.
The development of well-defined new catalysts2 capable
of effecting this reaction in a wide range of substrates
together with the tolerance shown by ruthenium alky-
lidene complexes such as 1 toward an ample range of
functional groups has allowed its application to several
total syntheses and to the preparation of many types of
substrates. These features are evident from many ex-
amples of the use of these catalysts in the formation of
fairly complex five-, six- and seven-membered carbo- and
heterocycles by ring-closing metathesis (RCM) of suitable
diolefin precursors.1,3 The formation of medium and large
ring systems, however, is yet largely unexplored. Despite
the extensive investigation during the past few years on
RCM, there are still a few aspects of this reaction which
remain unclear and cannot be predicted (e.g. geometry
of the resulting double bond, influence of steric environ-
ment of reacting olefins, etc.).
Our interest in developing methodologies for a rapid
access to molecules possessing a trans-fused polyether
structure resembling natural marine toxins such as
brevetoxins and ciguatoxins turned our attention toward
this reaction as an easy way to prepare these kinds of
compounds from appropriate precursors.4
Resu lts a n d Discu ssion
To assay the scope and limitations of RCM in the
cyclization of trans-fused polyether systems, a series of
simple precursors was prepared and reacted with a
catalytic amount of ruthenium complex 15 (Scheme 1).
In our models, we considered only terminal olefins on an
oxane ring, and we changed chain lengths to explore the
influence of ring size and steric environment of reacting
olefins.
(1) Recent reviews about olefin metathesis and its application to
organic synthesis: (a) Ivin, K. J .; Mol, J . C. Olefin Metathesis and
Metathesis Polymerization; Academic Press: San Diego, 1997. (b)
Schmalz, H.-G. Angew. Chem., Int. Ed. Engl. 1995, 34, 1833-1836.
(c) Schuster, M.; Blechert, S. Angew. Chem., Int. Ed. Engl. 1997, 36,
2036-2056. (d) Armstrong, S. K. J . Chem. Soc., Perkin Trans. 1 1998,
371-388. (e) Grubbs, R. H.; Chang, S. Tetrahedron 1998, 54, 4413-
4450.
P r ecu r sor Syn th esis. The starting material for the
preparation of the appropriate precursors was in all cases
(2R,3S)-2-(hydroxymethyl)tetrahydropyran-3-ol 2 avail-
(2) Molybdenum-based catalyst: (a) Schrock, R. R.; Murdzek, J .
S.; Bazan, G. C.; Robbins, J .; DiMare, M.; O’Regan, M. J . Am. Chem.
Soc. 1990, 112, 3875-3886. (b) Bazan, G. C.; Khosravi, E.; Schrock,
R. R.; Feast, W. J .; Gibson, V. C.; O’Regan, M. B.; Thomas, J . K.; Davis,
W. M. J . Am. Chem. Soc. 1990, 112, 8378-8387. (c) Bazan, G. C.;
Oskam, J . H.; Cho, H.-N.; Park, L.; Schrock, R. R. J . Am. Chem. Soc.
1991, 113, 6899-6907. Ruthenium-based catalysts: (d) Nguyen, S. T.;
J ohnson, L. K.; Grubbs, R. H. J . Am. Chem. Soc. 1992, 114, 3974-
3975. (e) Nguyen, S. T.; Grubbs, R. H. J . Am. Chem. Soc. 1993, 115,
9858-9859. (f) Wu, Z.; Nguyen, S. T.; Grubbs, R. H.; Ziller, J . W. J .
Am. Chem. Soc. 1995, 117, 5503-5511. (g) Schwab, P.; France, M. B.;
Ziller, J . W.; Grubbs, R. H. Angew. Chem., Int. Ed. Engl. 1995, 34,
2039-2041. (h) Schwab, P.; Grubbs, R. H.; Ziller, J . W. J . Am. Chem.
Soc. 1996, 118, 100-110.
(4) Examples of the use of RCM in the synthesis of trans-fused
polyethers: (a) Nicolaou, K. C.; Postema, M. H. D.; Claiborne, C. F. J .
Am. Chem. Soc. 1996, 118, 1565-1566. (b) Nicolaou, K. C.; Postema,
M. H. D.; Yue, E. W.; Nadin, A. J . Am. Chem. Soc. 1996, 118, 10335-
10336. (c) Clark, J . S.; Kettle, J . G. Tetrahedron Lett. 1997, 38, 123-
126. (d) Clark, J . S.; Kettle, J . G. Tetrahedron Lett. 1997, 38, 127-
130. (e) Oishi, T.; Nagumo, Y.; Hirama, M. Synlett 1997, 980-982. (f)
Oishi, T.; Nagumo, Y.; Hirama, M. J . Chem. Soc., Chem. Commun.
1998, 1041-1042. (g) Rainier, J . D.; Allwein, S. P. J . Org. Chem. 1998,
63, 5310-5311. (h) Clark, J . S.; Hamelin, O.; Hufton, R. Tetrahedron
Lett. 1998, 39, 8321-8324.
(3) Recent reviews about RCM: (a) Grubbs, R. H.; Miller, S. J .; Fu,
G. C. Acc. Chem. Res. 1995, 28, 446-452. (b) Hashimi, A. S. K. J . Prakt.
Chem. 1997, 339, 195-199.
(5) Delgado, M.; Mart´ın, J . D. Tetrahedron Lett. 1997, 38, 6299-
6300.
10.1021/jo9901438 CCC: $18.00 © 1999 American Chemical Society
Published on Web 06/06/1999

Ring-Closing Metathesis
J . Org. Chem., Vol. 64, No. 13, 1999 4799
Sch em e 2a
a
Key: (a) 1.0 equiv of TBDMSCl, 2.5 equiv of imidazole, DMAP catalyst, CH2Cl2, 0 °C, 4 h (92%); (b) for 4a (n ) 0): 10.0 equiv of allyl
bromide, 1.3 equiv of NaH, n-Bu4NI catalyst, THF, 0-25 °C, 8 h (88%); for 4b (n ) 2): 7.0 equiv of 5-bromo-1-pentene, 1.3 equiv of KH,
n-Bu4NI catalyst, THF, 0-25 °C, 8 h (72%); (c) 1.5 equiv of n-Bu4NF, THF, 25 °C, 2 h (5a : 98%, 5b: 98%); (d) (i) 3.0 equiv of SO3‚pyr,
5.0 equiv of NEt3, 15.0 equiv of DMSO, CH2Cl2, 0 °C, 2 h; (ii) 1.5 equiv of PPh3CH3Br, 1.4 equiv of n-BuLi, THF, 0-25 °C, 8 h (11a : 38%,
11b: 62%; 11c: 81%; 11d : 83%, two steps); (e) 1.0 equiv of 4-triisopropylsilyloxybutyraldehyde, 8-triisopropylsilyloxyoctanal, or
9-triisopropylsilyloxynonanal, p-TsOH catalyst, 4 Å molecular sieves, CH2Cl2, 25 °C, 8 h (6a : 95%, 6b: 87%, 6c: 84%); (f) 1.5 equiv of
n-Bu4NF, THF, 25 °C, 2 h (7a : 99%, 7b: 99%; 7c: 99%); (g) 2.0 equiv of I2, 3.0 equiv of imidazole, 3.0 equiv of PPh3, C6H6, 4 °C, 30 min
(8a : 85%, 8b: 86%, 8c: 86%); (h) 1.5 equiv of KO-t-Bu, THF, 25 °C, 30 min (9a : 92%; 9b: 97%; 9c: 97%); (i) 1.0 equiv of NaCNBH3, 1.0
equiv of TiCl4, CH3CN, 0-25 °C, 6 h (10a : 82%, 10b: 88%, 10c: 85%).
Sch em e 3a
able in three steps and excellent yields from tri-O-acetyl-
D-glucal.6 Selective protection of the primary hydroxyl
group with TBDMSCl, followed by O-alkylation of the
secondary hydroxyl group with either allyl bromide or
5-bromo-1-pentene and desilylation afforded alcohols 5a
and 5b. Ketalization of the aldehydes derived from 1,4-
butanediol, 1,8-octanediol, and 1,9-nonanediol (monopro-
tected as their TIPS ethers)7 with 2, catalyzed by
p-toluensulfonic acid, produced ketals 6a -c exclusively
as their R isomers8 in the newly formed asymmetric
center. Desilylation and transformation of the resultant
alcohols into their iodo derivatives9 followed by treatment
with tBuOK afforded compounds 9a -c, which gave
regioselectively the primary alcohols 10a -c upon treat-
ment with TiCl4/NaCNBH3.10 Oxidation of alcohols 5a ,b
and 10a -c followed by Wittig olefination of the resultant
aldehydes yielded dienes 11a -d 11 (Scheme 2).
Another series of dienic precursors 16a -d was pre-
pared starting from tosylates 13a , 13b, 14a , and 14b
(Scheme 3) by transformation into the corresponding
nitriles 15a -d , reduction with DIBAL,12 acid hydrolysis,
and Wittig olefination of the resultant aldehydes.
In our effort to explore the influence of steric environ-
ment of reacting olefins in RCM, three additional precur-
sors in which double bonds were further away from the
oxane ring were synthesized as described in Scheme 4.
A derivative of 2 in which the secondary hydroxyl group
a
Key: (a) 1.0 equiv of p-TsCl, 1.5 equiv of NEt3, DMAP catalyst,
CH2Cl2, 0-25 °C, 8 h (77%); (b) for 13a (n ) 0): 1.5 equiv of allyl
bromide, 1.2 equiv of NaH, n-Bu4NI catalyst, THF, 0-25 °C, 6 h
(93%); for 13b (n ) 2): 1.5 equiv of 5-bromo-1-pentene, 1.3 equiv
of KH, n-Bu4NI catalyst, THF, 0-25 °C, 6 h (78%); (c) 3.0 equiv of
KCN, DMSO, 50 °C, 6 h (15a : 98%, 15b: 98%, 15c: 98%, 15d :
98%); (d) (i) 1.5 equiv of DIBAL, Et2O, 0 °C, 5 h, (ii) aq HCl (1 N)
(iii) 1.5 equiv of PPh3CH3Br, 1.4 equiv of n-BuLi, THF, 0-25 °C,
8 h (16a : 38%, 16b: 39%; 16c: 48%; 16d : 53%, three steps); (e)
1.1 equiv of p-TsCl, 1.5 equiv of NEt3, DMAP catalyst, CH2Cl2,
0-25 °C, 8 h (14a : 92%, 14b: 96%).
(6) Nicolaou, K. C.; Hwang, C.-K.; Marron, B. E.; DeFrees, S. A.;
Couladourus, E. A.; Abe, Y.; Carroll, O. J .; Snyder, J . P. J . Am. Chem.
Soc. 1990, 112, 3040-3054.
(7) For the preparation of these aldehydes, see Supporting Informa-
tion.
(8) The configuration of the new asymmetric center was unequivo-
cally assigned by NOESY experiments.
(9) Garegg, P. J .; Samuelson, D. J . Chem. Soc., Perkin Trans. 1 1980,
2866-2869.
(10) Adam, G.; Seebach, D. Synthesis 1988, 373-375.
(11) Low yields obtained in the case of the smaller dienes are due
to the volatility of the products.
(12) Marshall, J . A.; Andersen, N. H.; Schlicher, J . W. J . Org. Chem.
1970, 35, 858-861.
is protected as its TBS ether 19 can be easily obtained
through a protection-deprotection sequence. Treatment
of this alcohol with I2/PPh3/Im, nucleophilic substitution
with cyanide anion, and reduction of the nitrile afforded

4800 J . Org. Chem., Vol. 64, No. 13, 1999
Delgado and Mart´ın
Sch em e 4a
Ta ble 1. Syn th esis of Oxep en e a n d Oxocen e Rin gs by
RCM
a
Key: (a) 1.1 equiv of BzCl, 3.0 equiv of NEt3, DMAP catalyst,
CH2Cl2, 0-25 °C, 4 h (98%); (b) 1.1 equiv of TBDMSCl, 2.5 equiv
of imidazole, DMAP catalyst, CH2Cl2, 25 °C, 4 h (97%); (c) 0.5 equiv
of NaOMe, MeOH, 25 °C, 2 h (99%); (d) 2.0 equiv of I2, 3.0 equiv
of imidazole, 3.0 equiv of PPh3, C6H6, 4 °C, 30 min (95%); (e) 3.0
equiv of KCN, DMSO, 50 °C, 5 h (99%); (f) (i) 1.5 equiv of DIBAL,
Et2O, 0 °C, 5 h, (ii) aq HCl (0.1 N), 4 °C (iii) 2.0 equiv of NaBH4,
MeOH, 0 °C, 1 h (42%, three steps); (g) 2.0 equiv of n-Bu3SnCH2-
CHdCH2, AIBN catalyst, C6H6, 80 °C, 6 h (24a : 71%, 24b: 68%);
(h) 1.5 equiv of n-Bu4NF, THF, 25 °C, 2 h (25a : 98%, 25b: 98%);
(i) for 26a (m ) 1): 1.5 equiv of allyl bromide, 1.2 equiv of NaH,
n-Bu4NI catalyst, THF, 0-25 °C, 6 h (83%); for 26b and 26c (m )
3): 1.5 equiv of 5-bromo-1-pentene, 1.2 equiv of KH, n-Bu4NI
catalyst, THF, 0-25 °C, 6 h (26b: 73%; 26c: 69%).
compound 22, which was transformed into its iodo
derivative 23. Iodo compounds 20 and 23 were subjected
to Keck13 reaction, followed by desilylation and O-
alkylation with either allyl bromide or 5-bromo-1-pen-
tene, affording dienes 26a -c.
Meta th esis Rea ction s. Treatment of the acyclic
precursors 11a -d , 16a -d and 26a -c with a catalytic
amount of 1 (Scheme 1) results in the formation of the
unsaturated oxacycles.
a
Reaction conditions: 0.2 mmol diene, 10 mol % of 1, 6 × 10-3
b
M, CH2Cl2, 25 °C, 4 h. Yields were determined by NMR.
As ring size increases, side reactions (such as isomeriza-
tion and dimerization) more effectively compete with
RCM. An extreme case is the oxotridecene ring, which
could not be obtained, and treatment of diene 16d with
1 only gave byproducts. These low yields are attributed
to the fact that for larger rings entropic factors do not
contribute to the formation of the reaction intermedi-
ates17 to the same extent as in their smaller analogues
and therefore side reactions are more favored.
Dependence on final double bond position and steric
environment of the reacting olefins is observed in these
larger systems. Two 11-membered cycles were prepared
between which the only difference was the final double
bond position (entry 3 versus entry 4, Table 2). When
reacting olefins are further away from the oxane ring,
RCM occur under higher dilution and lower temperature
conditions, although with no significant improvement in
yield. This result can be explained by a decrease in steric
congestion around the ruthenium atom in the reaction
intermediates in the latter case, which facilitates RCM.
In flu en ce of th e P r esen ce of a n Ad d ition a l Het-
er oa tom in th e Dien es in RCM. In our effort to
improve the yields of RCM in these latter cases, we
thought that the introduction of a second heteroatom on
the dienic precursors would facilitate the metathesis
Ruthenium-catalyzed RCM is most effective for the
cyclization of oxepene and oxocene rings (Table 1),
regardless of the position of the reacting olefins. Particu-
larly remarkable are the excellent yields with which
oxocene rings are obtained, the formation of eight-
membered rings from acyclic precursors being kinetically
and thermodynamically disfavored14 due to conforma-
tional and entropic factors and to the development of
transannular repulsions during the cyclization. The high
yields observed by us are due to the presence of the oxane
ring which acts as an element of conformational restric-
tion15,16 and facilitates the cyclization.
In the case of oxonene to oxotridecene rings (Table 2),
yields are substantially lower (below 45%) although the
reaction conditions are much stronger (higher catalyst
loading, higher temperatures, and longer reaction times).
(13) Keck, G. E.; Enholm, E. J .; Yates, J . B.; Wiley: M. R.
Tetrahedron 1985, 41, 4079-4094.
(14) Eliel, E. L.; Wilen, S. H. Stereochemistry of Organic Compounds;
J ohn Wiley and Sons: New York, 1994.
(15) Examples of formation of eight-membered rings by olefin
metathesis of acyclic precursors containing some conformational
restriction: (a) Linderman, R. J .; Siedlecki, J .; O’Neill, S. A.; Sun, H.
J . Am. Chem. Soc. 1997, 119, 6919-6920. (b) Crimmins, M. T.; Choy,
A. L. J . Org. Chem. 1997, 62, 7548-7549. (c) Visser, M. S.; Heron, N.
M.; Didiuk, M. T.; Sagal, J . F.; Hoveyda, A. H. J . Am. Chem. Soc. 1996,
118, 4291-4298.
(16) In the precursors of eight-membered rings in which the con-
formational restriction element is a preexisting cycle, RCM is more
effective when the two olefinic chains are in trans disposition on the
cycle than when they are cis: Miller, S. J .; Kim, S.-H.; Chen, Z.-R.;
Grubbs, R. H. J . Am. Chem. Soc. 1995, 117, 2108-2109.
(17) Detailed studies of RCM mechanism: (a) Dias, E. L.; Nguyen,
S. T.; Grubbs, R. H. J . Am. Chem. Soc. 1997, 119, 3887-3897. (b)
Aagaard, O. M.; Meier, R. J .; Buda, F. J . Am. Chem. Soc. 1998, 120,
7174-7182.

Ring-Closing Metathesis
J . Org. Chem., Vol. 64, No. 13, 1999 4801
Ta ble 2. P r ep a r a tion of Oxon en e-Oxod od ecen e Rin gs by RCM
which an additional oxygen atom was introduced to
explore the scope of this approach.
Precursors 37a , 37b, and 38a -c were easily obtained
by O-alkylation of 2, 5a and 10a (Scheme 5) with either
allyl bromide or 5-bromo-1-pentene. Treatment of 19 with
NaH/allyl bromide, followed by deprotection with TBAF
and O-alkylation with KH/5-bromo-1-pentene, afforded
compound 41.
F igu r e 1.
These compounds 37a , 37b, 38a -c, and 41 were
reacted with a catalytic amount of ruthenium catalyst
(1), and results are shown in Table 3.
through two effects: (i) stabilization of the electron-
deficient intermediates through their electron-donating
capacity and (ii) bringing together the olefin and the
carbene in the appropriate orientation for the formation
of the metallacyclobutane intermediate. This would lead
to an intermediate I1 as depicted in Figure 1. If the
stabilization became too strong, a chelate18 as I2 would
be formed, therefore inhibiting the reaction. The forma-
tion of either I1 or I2 cannot be predicted, and therefore
we synthesized a series of appropriate precursors in
With the introduction of an additional oxygen atom,
the reaction rate appears to be facilitated with improved
yields. Entry 1 is an exception: the expected nine-
membered ring does not form under these conditions, and
this may be due to the formation of a stable chelate such
as I2. On the other hand, the synthesis of a 13-membered
ring was achieved with the introduction of this element
of restriction.
Mild reaction conditions may be attributed solely to
the relief of steric effects around reacting olefins, this
reason alone could not justify the improvement of yields
seen when comparing the formation of 34 (entry 3, Table
2) and 44 (entry 4, Table 3), between which the only
difference is the presence of the additional oxygen atom
in the latter case. Only the formation of an intermediate
such as I1 could give a satisfactory explanation for the
formation of the latter with better yields.
(18) Examples of formation of chelates in RCM: (a) Kirkland, T.
A.; Grubbs, R. H. J . Org. Chem. 1997, 62, 7310-7318. (b) Ghosh, A.
K.; Capiello, J .; Shin, D. Tetrahedron Lett. 1998, 39, 4651-4654. (c)
Fu, G. C.; Grubbs, R. H. J . Am. Chem. Soc. 1992, 114, 7324-7325. (d)
Campagne, J .-M.; Ghosez, L. Tetrahedron Lett. 1998, 39, 6175-6178.
(e) Harrity, J . P. A.; La, D. S.; Cefalo, D. R.; Visser, M. S.; Hoveyda, A.
H. J . Am. Chem. Soc. 1998, 120, 2343-2351. (f) Feldman, J .; Murdzek,
J . S.; Davis, W. M.; Schrock, R. R. Organometallics 1989, 8, 2260-
2265. (g) Fu¨rstner, A.; Langemann, K. J . Am. Chem. Soc. 1997, 119,
9130-9136. (h) Kingsbury, J . S.; Harrity, J . P. A.; Bonitatebus, P. J .,
J r.; Hoveyda, A. H. J . Am. Chem. Soc. 1999, 121, 791-799.

4802 J . Org. Chem., Vol. 64, No. 13, 1999
Delgado and Mart´ın
Sch em e 5a
Ta ble 3. In flu en ce of a n Ad d ition a l Oxygen Atom in
RCM
a
Key: (a) for 37a : 3.0 equiv of allyl bromide, 2.2 equiv of NaH,
n-Bu4NI catalyst, THF, 0-25 °C, 6 h (73%); for 37b: 3.0 equiv of
5-bromo-1-pentene, 2.2 equiv of KO-t-Bu, THF, 65 °C, 6 h (62%);
(b) for 38b (m ) 1): 1.5 equiv of allyl bromide, 1.2 equiv of NaH,
n-Bu4NI catalyst, THF, 0-25 °C, 6 h (99%); for 38a and 38c (m )
3): 1.5 equiv of 5-bromo-1-pentene, 1.2 equiv of KH, n-Bu4NI
catalyst, THF, 0-25 °C, 6 h (38a : 73%; 38c: 72%); (c) 3.0 equiv
of allyl bromide, 1.2 equiv of NaH, n-Bu4NI catalyst, THF, 0-25
°C, 6 h (92%); (d) 1.5 equiv of n-Bu4NF, THF, 25 °C, 2 h (95%); (e)
2.0 equiv of 5-bromo-1-pentene, 1.2 equiv of KH, n-Bu4NI catalyst,
THF, 0-25 °C, 8 h (69%).
a
Reaction conditions: 0.2-0.4 mmol diene, 5-10 mol % of 1, 5
× 10-3 M, CH2Cl2, 25 °C, 2-4 h.
Again the position of the reacting double bonds has a
remarkable effect on yields, as can be seen by comparing
entries 3 and 4, Table 3: a change in the position of the
reacting olefins causes an improvement of approximately
40% in yield.18h
5 mol % of catalyst 1 in a few hours23 (Table 4). As we
had anticipated, reaction conditions were mild, and
(19) Examples of Z geometry in 9-and 10-membered rings obtained
by RCM: (a) Barrett, A. G. M.; Baugh, S. P. D.; Gibson, V. C.; Giles,
M. R.; Marshall, E. L.; Procopiou, P. A. Chem. Commun. 1996, 2231-
2232. (b) Crimmins, M. T.; Choy, A. L. J . Org. Chem. 1997, 62, 7548-
7549. (c) Sukkari, H. E.; Gesson, J .-P.; Renoux, B. Tetrahedron Lett.
1998, 39, 4043-4046. (d) Oishi, T.; Nagumo, Y.; Hirama. M. Chem.
Commun. 1998, 1041-1042. Example of E geometry in a 10-membered
ring: (e) Fink, B. E.; Kym, P. R.; Katzenellenbogen, J . A. J . Am. Chem.
Soc. 1998, 120, 4334-4344. (f) Sukkari, H. E.; Gesson, J .-P.; Renoux,
B. Tetrahedron Lett. 1998, 39, 4043-4046 (9-, 11-, and 15-membered
rings). (g) Fu¨rstner, A.; Kindler, N. Tetrahedron Lett. 1996, 37, 7005-
7008 (12-membered ring). (h) Borer, B. C.; Deerenberg, S.; Biera¨ugel,
H.; Pandit, U. K. Tetrahedron Lett. 1994, 35, 3191-3194 (13-membered
ring, Z). (i) Kim, S. H.; Figueroa, I.; Fuchs, P. L. Tetrahedron Lett.
1997, 38, 2601-2604 (13-membered ring, E). (j) Houri, A. F.; Xu, Z.;
Cogan, D. A.; Hoveyda, A. H. J . Am. Chem. Soc. 1995, 117, 2943-
2944 (14-membered ring, Z). (k) Fu¨rstner, A.; Langemann, K. J . Org.
Chem. 1996, 61, 3942-3943 (14-, 16-, and 20-membered rings). (l)
Ghosh, A. K.; Hussain, K. A. Tetrahedron Lett. 1998, 39, 1881-1884
(14-membered rings, Z, 15-membered rings, Z and 16-membered rings,
mixtures). (m) Ripka, A. S.; Bohacek, R. S.; Rich, D. H. Bioorg. Med.
Chem. Lett. 1998, 8, 357-360 (15-membered ring, mixtures). (n) Meng,
D.; Su, D.-S.; Balog, A.; Bertinato, P.; Sorensen, E. J .; Danishefsky, S.
J .; Zheng, Y.-H.; Chou, T.-C.; He, L.; Horwitz, S. J . Am. Chem. Soc.
1997, 119, 2733-2734.
A feature of RCM in our systems remains to be
analyzed: the geometry of the resultant double bond. For
ring size superior to nine, the two possible geometries
can occur. In our examples, 9- and 10-membered cycles
were obtained exclusively as their Z-isomers, while 11-
and 12-membered rings were formed as their E-isomers.
An E:Z mixture was obtained in the case of the 13-
membered ring. With the present level of knowledge it
is not possible to account for the results obtained. Double
bond geometry seems to depend on subtle stereoelectronic
effects which are not perfectly understood.19
Ap p lica tion to th e Syn th esis of P olyoxygen a ted
Ma cr ocyles. Our observation of the improvement of
yields in RCM with the presence of oxygen atoms in the
diene prompted us to apply this reaction to the synthesis
of polyoxygenated macrorings.20 Several appropriate
dienes were prepared to assay the effectiveness of this
t
approach (Scheme 6). Treatment of 2 with BuOK21 and
2 equiv of either allyl toluene p-sulfonates22 47, 48a , or
48b afforded the corresponding dienes 50, 51a , and 51b.
Another series of dienes was prepared starting from 5a
by O-alkylation with the appropriate allyl toluene p-
sulfonate 48b-d or 49,20 affording precursors 52a -c and
53 with good yields.
(20) Precedents in the application of RCM to the synthesis of crown
ethers: (a) Ko¨nig, B.; Horn, C. Synlett 1996, 1013-1014. (b) Marsella,
M. J .; Maynard, H. D.; Grubbs, R. H. Angew. Chem., Int. Ed. Engl.
1997, 36, 1101-1103.
(21) Czech, B. P.; Huh, H.; Bartsch, R. A. J . Org. Chem. 1992, 57,
725-728.
(22) For the preparation of allyl toluene p-sulfonates 47, 48a -d ,
and 49, see Supporting Information.
The expected polyoxygenated macrorings were ob-
tained by treatment of the synthesized precursors with
(23) Delgado, M.; Mart´ın, J . D. Tetrahedron Lett. 1997, 38, 8387-
8390.

Ring-Closing Metathesis
Sch em e 6a
J . Org. Chem., Vol. 64, No. 13, 1999 4803
rorings. The steric environment of the reacting olefins
plays an important role in RCM also.
Exp er im en ta l Section
1
Gen er a l. H NMR spectra were recorded on Bruker spec-
trometers Avance DPX 300 (300 MHz) or Avance DRX 500 (500
MHz). Chemical shifts are reported in parts per million from
tetramethylsilane with the solvent resonance as the internal
standard. Data are reported as follows: chemical shift, mul-
tiplicity (s ) singlet, d ) doublet, t ) triplet, q ) quartet, br
) broad, m ) multiplet), coupling constants (Hz), integration,
and assignment. 13C NMR spectra were recorded on Bruker
spectrometers Avance DPX 300 (75 MHz) or Avance DRX 500
(125 MHz) with complete proton decoupling. Chemical shifts
are reported in parts per million from tetramethylsilane with
the solvent as the internal reference. Data are reported as
follows: chemical shift, number of hydrogen atoms to which
that carbon is bonded (q ) CH3, t ) CH2, d ) CH and s ) C,
obtained by DEPT experiments), and assignment. Infrared (IR)
spectra were recorded on a Bruker Vector 22 spectrophotom-
eter, νmax in cm-1. High-resolution mass spectra were provided
by the Universities of Seville and Cordoba Mass Spectrometry
Facilities and were performed on Kratos MS 80 RFA, Finnigan
MAT 95 or Micromass AutoSpecQ spectrometers. Microanaly-
ses were performed on Leco CHNS-932 or Fisons EA1108
CHNS-0. Melting points were determined on a Buchi 241
apparatus and are uncorrected. Optical rotations were mea-
sured on a Perkin-Elmer 341 polarimeter, using the sodium
D line at 25 °C.
Thin-layer chromatography (TLC) was performed using
silica gel 60 F254 precoated plates with a fluorescent indicator.
Visualization was accomplished with one or more of the
following: UV light (254 nm), 10% ethanolic phosphomolybdic
acid or H2O:H2SO4:AcOH (1:4:20) solution and heat as a
developing agent. Flash column chromatography was carried
out with E. Merck silica gel (60, particle size 0.015-0.040 mm)
using appropriate mixtures of EtOAc and hexanes as eluents.
All chromatographic separations were monitored by TLC
analyses.
Bis(tricyclohexylphosphine)benzylidine ruthenium(IV) dichlo-
ride 1 was purchased from Strem Chemicals, stored in a
drybox, and used under argon atmosphere with standard
Schlenk techniques. All other reagents were purchased from
Aldrich and used without further purification unless otherwise
stated.
a
Key: (a) 2.2 equiv of KO-t-Bu, THF, 25 °C, 1 h; then 2.2 equiv
of tosylate, THF, 65 °C, 8 h (50: 47%, 51a : 54%; 51b: 52%); (b)
1.1 equiv of KO-t-Bu, THF, 25 °C, 1 h; then 1.1 equiv of tosylate,
THF, 25 °C, 8 h (52a : 82%, 52b: 87%; 52c: 85%; 53: 79%).
macrorings (with sizes ranging from 15 to 21 members)
were formed in good yields supporting our previous
observation of the positive effect of the presence of oxygen
atoms on RCM of this type of dienes. When reacting
olefins were further away from the oxane rings, yields
were lower than when they were closer, due to the greater
mobility of the chains (see entries 2 and 3 versus entries
4 and 6, Table 4).
All reactions were conducted in flame-dried glassware under
an inert atmosphere of dry argon. Tetrahydrofuran, diethyl
ether, and benzene were distilled from sodium metal/ben-
zophenone ketyl. Methylene chloride, acetonitrile, dimethyl
sulfoxide, and triethylamine were dried over CaH2 and dis-
tilled.
It is also worth noticing the selectivity shown by this
catalyst toward the olefin substitution degree in the last
entry of Table 4, in which only terminal olefins react,
demonstrating that the reaction is tolerant of other
olefins in the system, at least disubstituted ones, as in
the case of 53.
Gen er a l P r oced u r e for P r otection of Alcoh ols a s
TBDMS Eth er s. To a stirring solution of the corresponding
alcohol (2.5 mmol) in dry CH2Cl2 (12 mL) were added imidazole
(425 mg, 6.25 mmol, 2.5 equiv), TBDMSCl (413 mg, 2.75 mmol,
1.1 equiv), and a catalytic amount of DMAP at room temper-
ature. The reaction mixture was stirred until TLC showed no
remaining starting material and quenched by addition of NH4-
Cl saturated solution (10 mL). The two layers were separated,
and the organic layer was washed with brine and dried over
MgSO4. Solvent was removed under reduced pressure, and the
remaining oil was purified by flash chromatography. For the
monoprotection of the primary alcohol in 2, only 1.0 equiv of
TBSCl was used, and the reaction was carried out at 0 °C.
(2R ,3S )-2-(t er t -Bu t yld im e t h ylsilyloxym e t h yl)t e t r a -
h yd r op yr a n -3-ol (3): colorless oil. Rf ) 0.40 (silica, 20%
EtOAc in hexanes). [R]25D ) -11.8° (c 0.19, CHCl3). IR (CHCl3)
Con clu sion s
RCM has been applied to the synthesis of trans-fused
bicycles containing oxygens and is found to be very
effective for the synthesis of oxepene and oxocene rings.
As ring size increases, more difficulties are encountered
for the cyclization of the unsaturated rings. The introduc-
tion of an additional element of control (an oxygen atom
in the diene) is found to have a positive effect on the
efficiency of RCM, and, taking advantage of this effect,
this reaction is shown to be successful for the synthesis
of several ortho-condensed oxane-polyoxygenated mac-
νmax 3481, 2930, 2858, 1464, 1253, 1148, 837 cm-1 1H NMR
.
(500 MHz, CDCl3) δ 3.86 (m, 2H), 3.73 (br s, 1H, OH), 3.66
(dd, J ) 9.8, 8.5 Hz, 1H), 3.55 (dddd, J ) 10.3, 9.3, 4.6, 1.3
Hz, 1H), 3.31 (m, 1H), 3.15 (ddd, J ) 9.3, 8.5, 4.6 Hz, 1H),
2.08 (br dd, J ) 12.5, 3.2 Hz, 1H), 1.59 (m, 2H), 1.37 (m, 1H),
0.87 (s, 9H, (CH3)3CSi), 0.07 (s, 3H, CH3Si), 0.06 (s, 3H, CH3-

4804 J . Org. Chem., Vol. 64, No. 13, 1999
Ta ble 4. Ap p lica tion of RCM to Cr ow n Eth er Syn th esis
Delgado and Mart´ın
a
b
Reaction conditions: 0.2-0.4 mmol of diene, 5 mol % 1, 5 × 10-3 M, CH2Cl2, 25 °C, 2-4 h. E:Z ratio was determined by NMR and
GC.
Si). 13C NMR (125 MHz, CDCl3) δ 79.49 (d), 70.88 (d), 67.57
(t), 66.59 (t), 31.63 (t), 25.81 (q, (CH3)3CSi), 24.92 (t), 18.16 (s,
(CH3)3CSi), -5.57 (q, CH3Si), -5.64 (q, CH3Si). MS m/e (rel
1-pentene) were added and left overnight, allowing the tem-
perature to rise. The reaction mixture was cooled again to 0
°C, and water (2 mL) was added. The aqueous layer was
extracted with EtOAc (3 × 3 mL), and combined organic layers
were washed with brine and dried over MgSO4. Solvent was
removed in vacuo, and the residue was purified by flash
chromatography. In case of TBDMS-containing compounds, an
excess of the bromide was used (10.0 equiv in the case of allyl
bromide and 7.0 equiv in the case of 5-bromo-1-pentene) in
order to avoid migration of the TBDMS group.
t
t
intens) 245 ([M - 1]+, 2), 189 ([M - Bu]+, 38), 159 ([M - -
BuMe2]+, 15), 131 ([M - OSitBuMe2]+, 5). HRMS calcd for
C
12H26O3Si (M)+ 246.165123, found 246.163953. Anal. Calcd
for C12H26O3Si: C, 58.49; H, 10.63. Found: C, 58.38; H, 10.64.
Gen er a l P r oced u r e for O-Alk yla tion . In a typical ex-
perimental procedure, the corresponding alcohol (0.3 mmol)
was dissolved in dry THF (3 mL), and either allyl bromide or
5-bromo-1-pentene (0.45 mmol, 1.5 equiv) and a catalytic
amount of nBu4NI were added. The reaction mixture was cooled
to 0 °C and either NaH (0.36 mmol, 1.2 equiv, 60% dispersion
in mineral oil, in the case of allyl bromide) or KH (0.36 mmol,
1.2 equiv, 35% dispersion in mineral oil, in the case of 5-bromo-
(2′R,3′S)-(3′-Allyloxyt et r a h yd r op yr a n -2′-ylm et h oxy)-
ter t-bu tyld im eth ylsila n e (4a ): colorless oil. Rf ) 0.52 (silica,
10% EtOAc in hexanes). [R]25 ) +55.96° (c 0.2, CHCl3). IR
D
(CHCl3) νmax 3003, 2929, 2856, 1541, 1377, 1074, 838 cm-1
.
1H NMR (500 MHz, CDCl3) δ 5.87 (dddd, J ) 17.2, 10.4, 5.6,

Ring-Closing Metathesis
J . Org. Chem., Vol. 64, No. 13, 1999 4805
5.6 Hz, 1H), 5.22 (ddd, J ) 17.2, 1.5, 1.5 Hz, 1H), 5.11 (ddd, J
) 10.4, 1.5, 1.5 Hz, 1H), 4.07 (dddd, J ) 12.6, 5.6, 1.5, 1.5 Hz,
1H), 3.92 (dddd, J ) 12.6, 5.6, 1.5, 1.5 Hz, 1H), 3.88 (m, 1H),
3.83 (dd, J ) 11.2, 2.0 Hz, 1H), 3.77 (dd, J ) 11.2, 4.6 Hz,
1H), 3.28 (m, 2H), 3.12 (ddd, J ) 9.1, 4.6, 2.0 Hz, 1H), 2.20 (br
dd, J ) 12.4, 3.3 Hz, 1H), 1.62 (m, 2H), 1.33 (m, 1H), 0.87 (s,
9 H, (CH3)3CSi), 0.04 (s, 6H, 2 × CH3Si). 13C NMR (125 MHz,
CDCl3) δ 135.25 (d), 116.5 (t), 81.96 (d), 72.86 (d), 69.83 (t),
67.61 (t), 63.32 (t), 29.40 (t), 26.05 (q, (CH3)3CSi), 25.25 (t),
18.50 (s, (CH3)3CSi), -5.14 (q, CH3Si), -5.26 (q, CH3Si). Anal.
Calcd for C15H30O3Si: C, 62.89; H, 10.55. Found: C, 62.68; H,
10.62.
afforded a residue which was purified by flash chromatography
(silica, 5% EtOAc in hexanes).
(2′R,4′a R,8′a S)-[2-(Hexa h yd r op yr a n o[3,2-d ][1,3]d ioxin -
2′-yl)-p r op oxy]tr iisop r op ylsila n e (6a ): colorless oil. Rf )
0.26 (silica, 5% EtOAc in hexanes). [R]25 ) +2.90° (c 1.2,
D
CHCl3). IR (CHCl3) νmax 3008, 2946, 2867, 2338, 1465, 1385,
1
1341, 1261, 1219, 1148, 1106, 1013, 971, 883 cm-1. H NMR
(500 MHz, CDCl3) δ 4.58 (dd, J ) 5.2, 5.2 Hz, 1H), 4.04 (dd, J
) 10.4, 4.9 Hz, 1H), 3.87 (br dd, J ) 11.2, 4.5 Hz, 1H), 3.66
(dd, J ) 6.2, 6.2 Hz, 2H), 3.42 (m, 2H), 3.27 (ddd, J ) 11.2,
8.9, 4.2 Hz, 1H), 3.15 (ddd, J ) 10.0, 8.9, 4.9 Hz, 1H), 2.00 (br
d, J ) 12.1 Hz, 1H), 1.67 (m, 6H), 1.53 (dddd, J ) 12.1, 12.1,
11.2, 4.8 Hz, 1H), 1.02 (s, 21 H, 3 × (CH3)2CHSi, 3 ×
(CH3)2CHSi). 13C NMR (125 MHz, CDCl3) δ 102.56 (d), 77.97
(d), 74.28 (d), 68.95 (t), 68.01 (t), 63.12 (t), 31.04 (t), 28.79 (t),
27.67 (t), 25.53 (t), 18.03 (q, 3 × (CH3)2CHSi), 11.99 (d, 3 ×
(CH3)2CHSi). MS m/e (rel intens) 357 ([M - 1]+, 1). HRMS
calcd for C19H38O4Si (M)+: 358.25394, found 358.25574. Anal.
Calcd for C19H38O4Si: C, 63.64; H, 10.68. Found: C, 63.57; H,
10.92.
(2′R,3′S)-ter t-Bu tyld im eth yl(3′-p en t-4′′-en yloxytetr a h y-
d r op yr a n -2′-ylm eth oxy)sila n e (4b): colorless oil. Rf ) 0.69
(silica, 10% EtOAc in hexanes). [R]25 ) +49,39° (c 1.10,
D
CHCl3). IR (CHCl3) νmax 3002, 2857, 1640, 1463, 1361 cm-1
.
1H NMR (500 MHz, CDCl3) δ 5.78 (dddd, J ) 17.1, 10.2, 6.5,
6.5 Hz, 1H), 4.99 (d, J ) 17.1 Hz, 1H), 4.93 (d, J ) 10.2 Hz,
1H), 3.88 (br d, J ) 11.2 Hz, 1H), 3.84 (dd, J ) 11.2, 1.7 Hz,
1H), 3.74 (dd, J ) 11.2, 4.8 Hz, 1H), 3.56 (ddd, J ) 9.1, 6.5,
6.5 Hz, 1H), 3.30 (m, 2H), 3.16 (ddd, J ) 10.5, 9.1, 4.5 Hz,
1H), 3.09 (ddd, J ) 9.1, 4.8, 1.7 Hz, 1H), 2.19 (br d, J ) 12.3
Hz, 1H), 2.08 (m, 2H), 1.62 (m, 4H), 1.30 (dddd, J ) 12.3, 12.3,
10.5, 5.2 Hz, 1H), 0.88 (s, 9 H, (CH3)3CSi), 0.05 (s, 6H, 2 ×
CH3Si). 13C NMR (125 MHz, CDCl3) δ 138.30 (d), 114.71 (t),
82.07 (d), 73.32 (d), 68.05 (t), 67.61 (t), 63.48 (t), 30.34 (t), 29.36
(t), 29.31 (t), 26.06 (q, (CH3)3CSi), 25.26 (t), 18.51 (s, (CH3)3CSi),
-5.12 (q, CH3Si), -5.24 (q, CH3Si). MS m/e (rel intens) 315
([M + 1]+, 70). HRMS calcd for C17H35O3Si (M + H)+
315.235549, found 315.238184. Anal. Calcd for C17H34O3Si: C,
64.92; H, 10.90. Found: C, 64.64; H, 10.99.
(2′R,4′a S,8′a S)-[7-(Hexa h yd r op yr a n o[3,2-d ][1,3]d ioxin -
2′-yl)h ep tyloxy]tr iisop r op ylsila n e (6b): colorless oil. Rf )
0.42 (silica, 10% EtOAc in hexanes). [R]25 ) +2.49° (c 1.3,
D
CHCl3). IR (CHCl3) νmax 3010, 2943, 2866, 2342, 1465, 1146
1
cm-1. H NMR (500 MHz, CDCl3) δ 4.53 (dd, J ) 5.2, 5.2 Hz,
1H), 4.05 (dd, J ) 10.4, 4.9 Hz, 1H), 3.88 (br dd, J ) 11.5, 4.5
Hz, 1H), 3.66 (dd, J ) 6.6, 6.6 Hz, 2H), 3.42 (m, 2H), 3.27 (ddd,
J ) 11.2, 9.0, 4.2 Hz, 1H), 3.15 (ddd, J ) 9.9, 9.0, 4.9 Hz, 1H),
2.01 (br dd, J ) 12.0, 3.7 Hz, 1H), 1.74 (m, 2H), 1.57 (m, 3H),
1.50 (m, 2H), 1.34 (m, 2H), 1.27 (m, 6H), 1.03 (s, 21H, 3 ×
(CH3)2CHSi, 3 × (CH3)2CHSi). 13C NMR (125 MHz, CDCl3) δ
102.65 (d), 77.97 (d), 74.30 (d), 68.97 (t), 68.00 (t), 63.46 (t),
34.49 (t), 33.00 (t), 29.44 (t), 29.31 (t), 28.81 (t), 25.71 (t), 25.54
(t), 24.18 (t), 18.03 (q, 3 × (CH3)2CHSi), 12.04 (d, 3 ×
(CH3)2CHSi). MS m/e (rel intens) 413 ([M - 1]+, 8). HRMS
calcd for C23H46O4Si (M)+: 414.316539, found: 414.315868.
Gen er a l P r oced u r e for Dep r otection of Silyl Eth er s.
To a solution of the corresponding silyl ether (1.3 mmol) in
THF (3 mL) was added nBu4NF‚10 H2O (510 mg, 1.95 mmol,
1.5 equiv). When TLC showed that the reaction was complete,
solvent was removed under reduced pressure, and the residue
was purified by flash chromatography.
Calcd for
C
20H39O4Si (M - C3H7)+: 371.261764, found:
(2′R,3′S)-(3′-Allyloxyt et r a h yd r op yr a n -2′-yl)m et h a n ol
(5a ): colorless oil. Rf ) 0.36 (silica, 40% EtOAc in hexanes).
371.264656. Anal. Calcd for C23H46O4Si: C, 66.61; H, 11.18.
Found: C, 66.66; H, 11.35.
[R]25 ) +92.58° (c 1.30, CHCl3). IR (CHCl3) νmax 3588, 3482,
(2′R,4′a S,8′a S)-[8-(Hexa h yd r op yr a n o[3,2-d ][1,3]d ioxin -
D
3013, 2929, 2360, 2341 cm-1
.
1H NMR (500 MHz, CDCl3) δ
2′-yl)octyloxy]tr iisop r op ylsila n e (6c): colorless oil. Rf
)
5.83 (dddd, J ) 17.2, 10.4, 5.6, 5.6 Hz, 1H), 5.20 (ddd, J )
17.2, 1.6, 1.3 Hz, 1H), 5.10 (ddd, J ) 10.4, 1.3, 1.3 Hz, 1H),
4.05 (ddd, J ) 12.6, 5.6, 1.3 Hz, 1H), 3.88 (m, 2H), 3.78 (d, J
) 11.1 Hz, 1H), 3.63 (d, J ) 11.1 Hz, 1H), 3.32 (ddd, J ) 11.6,
11.6, 2.3 Hz, 1H), 3.22 (ddd, J ) 10.2, 9.3, 4.5 Hz, 1H), 3.15
(m, 1H), 2.40 (s, 1H, OH), 2.19 (br d, J ) 12.4 Hz, 1H), 1.59
(m, 2H), 1.32 (dddd, J ) 12.4, 12.4, 10.2, 4.5 Hz, 1H). 13C NMR
(125 MHz, CDCl3) δ 134.95 (d), 116.97 (t), 80.81 (d), 73.90 (d),
69.77 (t), 67.65 (t), 63.01 (t), 29.15 (t), 25.16 (t). MS m/e (rel
intens) 171 ([M - 1]+, 1). HRMS calcd for C9H16O3 (M)+:
172.109945, found 172.109014. Anal. Calcd for C9H16O3: C,
62.77; H, 9.36. Found: C, 62.62; H, 9.39.
0.41 (silica, 10% EtOAc in hexanes). [R]25 ) +2.07° (c 0.8,
D
CHCl3). IR (CHCl3) νmax 2942, 2866, 2360, 1465, 1238 cm-1
.
1H NMR (500 MHz, CDCl3) δ 4.53 (dd, J ) 5.2, 5.2 Hz, 1H),
4.06 (dd, J ) 10.4, 4.9 Hz, 1H), 3.89 (br dd, J ) 11.5, 4.5 Hz,
1H), 3.63 (dd, J ) 6.7, 6.7 Hz, 2H), 3.43 (m, 2H), 3.28 (ddd, J
) 11.3, 9.0, 4.2 Hz, 1H), 3.16 (ddd, J ) 10.0, 9.0, 4.9 Hz, 1H),
2.02 (br dd, J ) 12.1, 3.5 Hz, 1H), 1.75 (br s, 2H), 1.54 (br s,
5H), 1.31 (br s, 10H), 1.03 (s, 21H, 3 × (CH3)2CHSi, 3 ×
(CH3)2CHSi). 13C NMR (125 MHz, CDCl3) δ 102.68 (d), 77.98
(d), 74.30 (d), 68.98 (t), 68.02 (t), 63.50 (t), 34.52 (t), 33.03 (t),
29.50 (t), 29.40 (t), 29.36 (t), 28.81 (t), 25.80 (t), 25.54 (t), 24.23
(t), 18.04 (q, 3 × (CH3)2CHSi), 12.05 (d, 3 × (CH3)2CHSi). MS
m/e (rel intens) 427 ([M - 1]+, 7). HRMS calcd for C24H47O4Si
(M - H)+: 427.324364, found: 427.325450. Calcd for C21H41O4-
Si (M - C3H7)+: 385.277414, found: 385.279723. Anal. Calcd
for C24H48O4Si: C, 67.24; H, 11.28. Found: C, 67.20; H, 11.16.
P r ep a r a tion of (2′R,4′a R,8′a S)-3-(Hexa h yd r op yr a n o-
[3,2-d ][1,3]d ioxin -2′-yl)p r op a n -1-ol (7a ). This compound
was prepared from 6a following the procedure described above
for deprotection of silyl ethers. Noncrystalline white solid. Mp
(2′R,3′S)-(3′-P en t-4′′-en yloxytetr ah ydr opyr an -2′-yl)m eth -
a n ol (5b): colorless oil. Rf ) 0.48 (silica, 50% EtOAc in
hexanes). [R]25 ) +34.42° (c 1.05, CHCl3). IR (CHCl3) νmax
D
3589, 3482, 2943, 2872, 1350 cm-1. 1H NMR (500 MHz, CDCl3)
δ 5.76 (dddd, J ) 17.1, 10.2, 6.7, 6.7 Hz, 1H), 4.99 (d, J ) 17.1
Hz, 1H), 4.93 (d, J ) 10.2 Hz, 1H), 3.88 (br dd, J ) 11.3, 4.6
Hz, 1H), 3.81 (br d, J ) 11.5 Hz, 1H), 3.65 (m, 1H), 3.58 (ddd,
J ) 9.2, 6.4, 6.4 Hz, 1H), 3.33 (m, 2H), 3.15 (m, 2H), 2.23 (m,
2H), 2.07 (m, 2H), 1.61 (m, 4H), 1.32 (m, 1H). 13C NMR (125
MHz, CDCl3) δ 138.13 (d), 114.88 (t), 80.66 (d), 74.78 (d), 68.03
(t), 67.72 (t), 63.38 (t), 30.25 (t), 29.17 (t), 29.14 (t), 25.21 (t).
HRMS calcd for C11H21O3 (M + H)+: 201.149070, found
201.148695. Anal. Calcd for C11H20O3: C, 65.97; H, 10.07.
Found: C, 65.68; H, 10.26.
) 39 °C. Rf ) 0.26 (silica, 50% EtOAc in hexanes). [R]25
)
D
+1.90° (c 0.84, CHCl3). IR (CHCl3) νmax 3625, 3471, 3013, 2929,
2858, 1466, 1412, 1293, 1262 cm-1. 1H NMR (500 MHz, CDCl3)
δ 4.59 (dd, J ) 4.8, 4.6 Hz, 1H), 4.03 (dd, J ) 10.4, 4.9 Hz,
1H), 3.86 (br dd, J ) 11.5, 4.5 Hz, 1H), 3.58 (dd, J ) 6.1, 6.1
Hz, 2H), 3.41 (m, 2H), 3.28 (ddd, J ) 11.2, 9.0, 4.2 Hz, 1H),
3.13 (ddd, J ) 9.0, 9.0, 4.9, 1H), 2.29 (br s, 1H, OH), 1.99 (br
dd, J ) 12.1, 4.2 Hz, 1H), 1.69 (m, 6H), 1.52 (dddd, J ) 12.1,
12.1, 11.2, 5.1 Hz, 1H). 13C NMR (125 MHz, CDCl3) δ 102.18
(d), 78.01 (d), 74.05 (d), 68.92 (t), 68.03 (t), 62.51 (t), 31.15 (t),
28.71 (t), 27.16 (t), 25.46 (t). MS m/e (rel intens) 201 ([M -
1]+, 2). HRMS calcd for C10H17O4 (M - H)+: 201.112684,
found: 201.113410. Anal. Calcd for C10H18O4: C, 59.39; H,
8.97. Found: C, 59.23; H, 8.99.
Gen er a l P r oced u r e for Keta l F or m a tion . A solution of
2 (2.4 mmol) in dry CH2Cl2 (8 mL) was transferred to a flame-
dried flask with 4 Å molecular sieves. The corresponding
aldehyde (2.4 mmol, 1.0 equiv) dissolved in CH2Cl2 (4 mL) was
then added, followed by a catalytic amount of p-TsOH. The
reaction mixture was stirred overnight at room temperature.
Neutralization by addition of a few drops of NEt3, filtration
through a Celite pad, and removal of the solvent in vacuo

4806 J . Org. Chem., Vol. 64, No. 13, 1999
Delgado and Mart´ın
(2′R,4′a R,8′a S)-7-(Hexa h yd r op yr a n o[3,2-d ][1,3]d ioxin -
2′-yl)h ep ta n -1-ol (7b). This compound was prepared from 6b
following the procedure described above for deprotection of silyl
ethers. Colorless oil. Rf ) 0.36 (silica, 50% EtOAc in hexanes).
found: 367.077789. Anal. Calcd for C14H25O3I: C, 45.66; H,
6.84. Found: C, 45.69; H, 6.79.
(2R,4a R,8a S)-2-(8′-Iod ooctyl)h exa h yd r op yr a n o[3,2-d ]-
[1,3]d ioxin e (8c): colorless oil. Rf ) 0.35 (silica, 10% EtOAc
[R]25 ) +3.77° (c 0.7, CHCl3). IR (CHCl3) νmax 3626, 3013,
in hexanes). [R]25 ) +2.04° (c 1.32, CHCl3). IR (CHCl3) νmax
D
D
2934, 1466, 1387, 1042 cm-1
.
1H NMR (500 MHz, CDCl3) δ
3011, 2859, 1466, 1236, 1091, 1006, 967 cm-1. H NMR (500
1
4.52 (dd, J ) 5.2, 5.2 Hz, 1H), 4.04 (dd, J ) 10.4, 4.9 Hz, 1H),
3.87 (br dd, J ) 11.5, 4.5 Hz, 1H), 3.59 (dd, J ) 6.6, 6.6 Hz,
2H), 3.42 (m, 2H), 3.27 (ddd, J ) 11.2, 9.0, 4.2 Hz, 1H), 3.15
(ddd, J ) 10.0, 9.0, 4.9 Hz, 1H), 2.00 (br dd, J ) 12.0, 3.6 Hz,
1H), 1.73 (m, 2H), 1.54 (m, 5H), 1.33 (m, 9H). 13C NMR (125
MHz, CDCl3) δ 102.60 (d), 77.96 (d), 74.26 (d), 68.95 (t), 68.00
(t), 62.94 (t), 34.45 (t), 32.74 (t), 29.37 (t), 29.24 (t), 28.78 (t),
25.61 (t), 25.51 (t), 24.11 (t). MS m/e (rel intens) 259 ([M +
1]+, 16). HRMS calcd for C14H27O4 (M + H)+: 259.190935,
found: 259.189771; calcd for C14H25O4 (M - H)+: 257.175285,
found: 257.174785. Anal. Calcd for C14H26O4: C, 65.09; H,
10.14. Found: C, 65.09; H, 10.21.
MHz, CDCl3) δ 4.53 (dd, J ) 5.2, 5.2 Hz, 1H), 4.05 (dd, J )
10.4, 4.9 Hz, 1H), 3.88 (br dd, J ) 11.3, 4.5 Hz, 1H), 3.43 (m,
2H), 3.28 (ddd, J ) 11.3, 9.0, 4.2 Hz, 1H), 3.15 (m, 3H), 2.01
(br dd, J ) 12.0, 3.4 Hz, 1H), 1.75 (m, 4H), 1.55 (m, 3H), 1.35
(m, 4H), 1.26 (m, 6H). 13C NMR (125 MHz, CDCl3) δ 102.59
(d), 77.97 (d), 74.28 (d), 68.98 (t), 68.01 (t), 34.48 (t), 33.53 (t),
30.45 (t), 29.31 (t), 29.23 (t), 28.81 (t), 28.39 (t), 25.54 (t), 24.14
(t), 7.19 (t). MS m/e (rel intens) 383 ([M + 1]+, 100), 255 ([M -
HI]+, 12). HRMS calcd for C15H28O3I (M + H)+: 383.108322,
found: 383.108533. Anal. Calcd for C15H27O3I: C, 47.13; H,
7.12. Found: C, 47.21; H, 7.37.
Gen er a l P r oced u r e for Elim in a tion . The corresponding
(2′R,4′a R,8′a S)-8-(Hexa h yd r op yr a n o[3,2-d ][1,3]d ioxin -
2′-yl)octa n -1-ol (7c). This compound was prepared from 6c
following the procedure described above for deprotection of silyl
ethers. Colorless oil. Rf ) 0.41 (silica, 50% EtOAc in hexanes).
iodo compound (2.1 mmol) was dissolved in dry THF (21 mL)
and BuOK (353 mg, 3.15 mmol, 1.5 equiv) was added. After
t
stirring for 30 min, TLC showed that the reaction was complete
and it was quenched by addition of water (5 mL). The aqueous
layer was extracted with EtOAc (3 × 10 mL), and combined
organic layers were washed with brine and dried over MgSO4.
Solvent was removed in vacuo and the residue purified by flash
chromatography.
[R]25 ) +3.02° (c 0.7, CHCl3). IR (CHCl3) νmax 3619, 3012,
D
2859, 2361, 1541, 1340, 1091 cm-1. 1H NMR (500 MHz, CDCl3)
δ 4.52 (dd, J ) 5.2, 5.2 Hz, 1H), 4.04 (dd, J ) 10.4, 4.9 Hz,
1H), 3.87 (br dd, J ) 11.5, 4.6 Hz, 1H), 3.58 (dd, J ) 6.6, 6.6
Hz, 2H), 3.41 (m, 2H), 3.27 (ddd, J ) 11.3, 9.0, 4.2 Hz, 1H),
3.14 (ddd, J ) 9.9, 9.0, 4.9 Hz, 1H), 2.00 (br dd, J ) 12.0, 3.2
Hz, 1H), 1.73 (m, 2H), 1.54 (m, 6H), 1.30 (m, 10H). 13C NMR
(125 MHz, CDCl3) δ 102.63 (d), 77.96 (d), 74.27 (d), 68.95 (t),
68.01 (t), 62.96 (t), 34.48 (t), 32.77 (t), 29.42 (t), 29.37 (t), 29.29
(t), 28.79 (t), 25.71 (t), 25.52 (t), 24.17 (t). MS m/e (rel intens)
271 ([M - 1]+, 9). HRMS calcd for C15H28O4 (M)+: 272.198760,
found: 272.198196; calcd for C15H27O4 (M - H)+: 271.190935,
found: 271.191292. Anal. Calcd for C15H28O4: C, 66.14; H,
10.36. Found: C, 66.19; H, 10.43.
(2R ,4a R ,8a S )-2-Ally lh e x a h y d r o p y r a n o [3,2-d ][1,3]-
d ioxin e (9a ): colorless oil. Rf ) 0.39 (silica, 10% EtOAc in
hexanes). [R]25D ) +7.45° (c 1.37, CHCl3). IR (CHCl3) νmax 3082,
2950, 2871, 1644, 1433, 1371 cm-1. 1H NMR (500 MHz, CDCl3)
δ 5.78 (dddd, J ) 17.2, 10.2, 6.9, 6.9 Hz, 1H), 5.08 (m, 2H),
4.59 (dd, J ) 5.1, 5.1 Hz, 1H), 4.06 (dd, J ) 10.4, 4.9 Hz, 1H),
3.87 (br dd, J ) 11.2, 4.3 Hz, 1H), 3.42 (m, 2 H), 3.29 (ddd, J
) 11.3, 9.0, 4.3 Hz, 1H), 3.15 (ddd, J ) 9.9, 9.0, 4.9 Hz, 1H),
2.37 (dd, J ) 6.9, 5.1 Hz, 2H), 2.01 (br dd, J ) 12.2, 4.3 Hz,
1H), 1.73 (m, 2H), 1.54 (dddd, J ) 12.2, 12.2, 11.3, 5.0 Hz,
1H). 13C NMR (125 MHz, CDCl3) δ 132.58 (d), 117.67 (t), 101.75
(d), 78.03 (d), 74.11 (d), 69.00 (t), 68.00 (t), 39.07 (t), 28.74 (t),
25.51 (t). MS m/e (rel intens) 185 ([M + 1]+, 11). HRMS calcd
for C10H17O3 (M + H)+: 185.117769, found: 185.118326. Anal.
Calcd for C10H16O3: C, 65.19; H, 8.75. Found: C, 65.14; H,
8.83.
Gen er a l P r oced u r e for Iod in a tion of Alcoh ols. To a
stirring solution of the corresponding alcohol (2.3 mmol) in dry
benzene (23 mL) were added imidazole (470 mg, 6.9 mmol,
3.0 equiv), and PPh3 (1.8 g, 6.9 mmol, 3.0 equiv). The reaction
mixture was then cooled to 4 °C, and resublimed iodine (1.2
g, 4.6 mmol, 2.0 equiv) was added. After 30 min, TLC showed
no remaining starting material, and the mixture was filtered
through a Celite pad. Solvent was removed in vacuo, and the
residue was purified by flash chromatography.
(2R,4a R,8a S)-2-H ep t -6′-en ylh exa h yd r op yr a n o[3,2-d ]-
[1,3]d ioxin e (9b): colorless oil. Rf ) 0.36 (silica, 10% EtOAc
in hexanes). [R]25 ) +3.73° (c 0.7, CHCl3). IR (CHCl3) νmax
D
3012, 2861, 2340, 1638, 1466, 1439, 1341, 1264 cm-1. 1H NMR
(500 MHz, CDCl3) δ 5.77 (dddd, J ) 17.1, 10.2, 6.7, 6.7 Hz,
1H), 4.96 (d, J ) 17.1 Hz, 1H), 4.90 (d, J ) 10.2 Hz, 1H), 4.54
(dd, J ) 5.2, 5.2 Hz, 1H), 4.05 (dd, J ) 10.4, 4.9 Hz, 1H), 3.89
(br dd, J ) 11.3, 4.5 Hz, 1H), 3.43 (m, 2H), 3.28 (ddd, J )
11.2, 9.0, 4.2 Hz, 1H), 3.15 (ddd, J ) 10.0, 9.0, 4.9 Hz, 1H),
2.01 (m, 3H), 1.75 (m, 2H), 1.56 (m, 3H), 1.37 (m, 4H), 1.27
(m, 2H). 13C NMR (125 MHz, CDCl3) δ 139.03 (d), 114.21 (t),
102.60 (d), 77.98 (d), 74.29 (d), 68.98 (t), 68.01 (t), 34.45 (t),
33.63 (t), 28.91 (t), 28.81 (t), 28.75 (t), 25.54 (t), 24.05 (t). MS
m/e (rel intens) 239 ([M + 1]+, 7). HRMS calcd for C14H23O3
(M - H)+: 239.164720, found: 239.164556. Anal. Calcd for
(2R,4a R,8a S)-2-(3′-Iod op r op yl)h exa h yd r op yr a n o[3,2-d ]-
[1,3]d ioxin e (8a ): colorless oil. Rf ) 0.28 (silica, 10% EtOAc
in hexanes). [R]25 ) +2.65° (c 0.94, CHCl3). IR (CHCl3) νmax
D
3011, 2951, 1466, 1441, 1386, 1293 cm-1. H NMR (500 MHz,
1
CDCl3) δ 4.58 (dd, J ) 4.9, 4.9 Hz, 1H), 4.03 (dd, J ) 10.4, 4.9
Hz, 1H), 3.88 (br dd, J ) 11.2, 4.3 Hz, 1H), 3.41 (m, 2H), 3.27
(ddd, J ) 11.2, 8.9, 4.3 Hz, 1H), 3.14 (m, 3H), 2.00 (br dd, J )
12.1, 4.3 Hz, 1H), 1.92 (m, 2H), 1.73 (m, 4H), 1.52 (dddd, J )
12.1, 11.2, 11.2, 5.1 Hz, 1H). 13C NMR (125 MHz, CDCl3) δ
101.29 (d), 77.99 (d), 74.10 (d), 68.93 (t), 68.02 (t), 35.23 (t),
28.74 (t), 28.26 (t), 25.50 (t), 6.47 (t). MS m/e (rel intens) 311
([M - 1]+, 56), 185 ([M - I]+, 46). HRMS calcd for C10H16O3I
(M - H)+: 311.014422, found: 311.016322; calcd for C10H17O3
(M - I)+: 185.117770, found: 185.119141. Anal. Calcd for
C
14H24O3: C, 69.96; H, 10.07. Found: C, 69.91; H, 9.83.
(2R,4a R,8a S)-2-Oct-7′-en ylh exa h yd r op yr a n o[3,2-d ][1,3]-
C
10H17O3I: C, 38.48; H, 5.49. Found: C, 38.50; H, 5.48.
d ioxin e (9c): colorless oil. Rf ) 0.38 (silica, 10% EtOAc in
hexanes). [R]25D ) +3.44° (c 0.7, CHCl3). IR (CHCl3) νmax 3012,
(2R,4a R,8a S)-2-(7′-Iod oh ep tyl)h exa h yd r op yr a n o[3,2-d ]-
2932, 2360, 1639, 1236 cm-1 1H NMR (500 MHz, CDCl3) δ
.
[1,3]d ioxin e (8b): colorless oil. Rf ) 0.31 (silica, 10% EtOAc
in hexanes). [R]25 ) +2.02° (c 0.4, CHCl3). IR (CHCl3) νmax
5.77 (dddd, J ) 17.1, 10.2, 6.7, 6.7 Hz, 1H), 4.95 (d, J ) 17.1
Hz, 1H), 4.89 (d, J ) 10.2 Hz, 1H), 4.53 (dd, J ) 5.2, 5.2 Hz,
1H), 4.05 (dd, J ) 10.4, 4.9 Hz, 1H), 3.88 (br dd, J ) 11.4, 4.5
Hz, 1H), 3.42 (m, 2H), 3.28 (ddd, J ) 11.3, 9.0, 4.2 Hz, 1H),
3.15 (ddd, J ) 10.0, 9.0, 4.9 Hz, 1H), 2.00 (m, 3H), 1.74 (m,
2H), 1.55 (m, 3H), 1.35 (m, 4H), 1.28 (m, 4H). 13C NMR (125
MHz, CDCl3) δ 139.12 (d), 114.16 (t), 102.64 (d), 77.98 (d), 74.29
(d), 68.97 (t), 68.01 (t), 34.49 (t), 33.74 (t), 29.27 (t), 28.95 (t),
28.81 (t), 28.79 (t), 25.54 (t), 24.16 (t). MS m/e (rel intens) 253
([M - 1]+, 8). HRMS calcd for C15H26O3 (M)+: 254.188195,
found: 254.186673. Anal. Calcd for C15H26O3: C, 70.83; H,
10.30. Found: C, 70.82; H, 10.39.
D
3010, 2933, 2860, 2340, 1558, 1508, 1091, 966 cm-1. H NMR
1
(500 MHz, CDCl3) δ 4.54 (dd, J ) 5.2, 5.2 Hz, 1H), 4.06 (dd, J
) 10.4, 4.9 Hz, 1H), 3.89 (br dd, J ) 11.5, 4.5 Hz, 1H), 3.43
(m, 2H), 3.28 (ddd, J ) 11.2, 9.0, 4.2 Hz, 1H), 3.16 (m, 3H),
2.02 (br dd, J ) 12.1, 3.7 Hz, 1H), 1.75 (m, 4H), 1.56 (m, 3H),
1.36 (m, 4H), 1.29 (m, 4H). 13C NMR (125 MHz, CDCl3) δ
102.56 (d), 77.99 (d), 74.28 (d), 68.98 (t), 68.02 (t), 34.44 (t),
33.52 (t), 30.38 (t), 29.21 (t), 28.81 (t), 28.38 (t), 25.54 (t), 24.09
(t), 7.12 (t). MS m/e (rel intens) 367 ([M - 1]+, 9), 143 ([M -
C7H14I]+, 92). HRMS calcd for C14H25O3I (M)+: 368.084847,
found: 368.083679; calcd for C14H24O3I (M - H)+: 367.077022,

Ring-Closing Metathesis
J . Org. Chem., Vol. 64, No. 13, 1999 4807
Gen er a l P r oced u r e for t h e R ed u ct ive Op en in g of
Keta ls. A solution of the corresponding ketal (1.9 mmol) in
dry CH3CN (3.8 mL) was cooled to 0 °C, and NaCNBH3 (1.9
mL, 1.9 mmol, 1.0 equiv, 1 M solution in THF) was added
followed by recently distilled TiCl4 (209 µL, 1.9 mmol, 1.0
equiv). After stirring 6 h at that temperature, the reaction
mixture was poured onto a NaHCO3-saturated solution (4 mL)
and filtered through a Celite pad, washing thoroughly with
CH2Cl2. The combined organic layers were washed with brine
and dried over MgSO4. Solvent was removed under reduced
pressure, and the residue was purified by flash chromatogra-
phy (silica, 50% EtOAc in hexanes).
that temperature, the aldehyde (the residue from the previous
step) was added via cannula, dissolved in dry THF (2 mL).
Temperature was allowed to rise overnight. Water was added
to quench the reaction. The aqueous layer was extracted with
EtOAc (3 × 3 mL), and the combined organic layers were
washed with brine and dried over MgSO4. After removal of
the solvent, the residue was purified by flash chromatography.
(2R,3S)-3-Bu t-3′-en yloxy-2-vin yltetr ah ydr opyr an (11a):
colorless liquid. Rf ) 0.28 (silica, 5% EtOAc in hexanes). [R]25
D
) +54,82° (c 0.23, CHCl3). IR (CHCl3) νmax 3006, 2956, 1642,
1
1464, 1265 cm-1. H NMR (500 MHz, CDCl3) δ 5.98 (ddd, J )
17.2, 10.7, 5.5 Hz, 1H), 5.78 (dddd, J ) 17.2, 10.3, 6.7, 6.7 Hz,
1H), 5.32 (d, J ) 17.2 Hz, 1H), 5.17 (d, J ) 10.7 Hz, 1H), 5.05
(d, J ) 17.2 Hz, 1H), 5.00 (d, J ) 10.3 Hz, 1H), 3.91 (br dd, J
) 11.3, 4.1 Hz, 1H), 3.57 (m, 2H), 3.41 (dd, J ) 16.0, 6.9 Hz,
1H), 3.35 (ddd, J ) 11.3, 11.3, 3.2 Hz, 1H), 2.97 (ddd, J ) 10.0,
9.8, 4.3 Hz, 1H), 2.26 (ddd, J ) 6.9, 6.9, 6.7 Hz, 2H), 2.18 (br
dd, J ) 12.5, 3.5 Hz, 1H), 1.63 (m, 2H), 1.37 (dddd, J ) 12.5,
12.5, 10.0, 5.1 Hz, 1H). 13C NMR (125 MHz, CDCl3) δ 137.71
(d), 135.25 (d), 116.32 (t), 116.26 (t), 81.16 (d), 78.16 (d), 68.83
(t), 67.44 (t), 34.51 (t), 29.76 (t), 25.27 (t). MS m/e (rel intens)
182 (M+, 1). HRMS calcd for C11H18O2 (M)+: 182.130679,
found: 182.131248. Anal. Calcd for C11H18O2: C, 72.49; H,
9.95. Found: C, 72.58; H, 9.47.
(2′R,3′S)-(3′-Bu t-3′′-en yloxytetr ah ydr opyr an -2′-yl)m eth -
a n ol (10a ): colorless oil. Rf ) 0.45 (silica, 50% EtOAc in
hexanes). [R]25 ) +84.35° (c 1.51, CHCl3). IR (CHCl3) νmax
D
3590, 3491, 3081, 2945, 1641, 1464, 1438 cm-1. H NMR (500
1
MHz, CDCl3) δ 5.76 (dddd, J ) 17.2, 10.3, 6.7, 6.7 Hz, 1H),
5.05 (d, J ) 17.2 Hz, 1H), 5.00 (d, J ) 10.3 Hz, 1H), 3.87 (br
dd, J ) 11.3, 4.4 Hz, 1H), 3.78 (m, 1H), 3.63 (m, 2H), 3.35 (m,
2H), 3.16 (m, 2H), 2.32 (dd, J ) 6.2, 6.2 Hz, 1H, OH), 2.24 (m,
3H), 1.60 (m, 2H), 1.31 (m, 1H). 13C NMR (125 MHz, CDCl3)
δ 135.16 (d), 116.58 (t), 80.60 (d), 74.96 (d), 68.02 (t), 67.71 (t),
63.38 (t), 34.46 (t), 29.09 (t), 25.18 (t). MS m/e (rel intens) 186
(M+, 1). HRMS calcd for C10H18O3 (M)+: 186.12559, found:
186.12654. Anal. Calcd for
Found: C, 64.29; H, 9.93.
C10H18O3: C, 64.49; H, 9.74.
(2R,3S)-3-P en t-4′-en yloxy-2-vin yltetr ah ydr opyr an (11b):
colorless liquid. Rf ) 0.53 (silica, 10% EtOAc in hexanes). [R]25
D
(2′R,3′S)-(3′-Oct-7′′-en yloxytetr ah ydr opyr an -2′-yl)m eth -
a n ol (10b): colorless oil. Rf ) 0.56 (silica, 50% EtOAc in
hexanes). [R]25D ) +54.76° (c 0.8, CHCl3). IR (CHCl3) νmax 3588,
) +15.65° (c 0.6, CHCl3). IR (CHCl3) νmax 3009, 2927, 1454,
1
1247 cm-1. H NMR (500 MHz, CDCl3) δ 5.96 (ddd, J ) 17.4,
10.7, 5.5 Hz, 1H), 5.75 (dddd, J ) 17.1, 10.2, 6.7, 6.7 Hz, 1H),
5.31 (d, J ) 17.4 Hz, 1H), 5.15 (d, J ) 10.7 Hz, 1H), 4.97 (d,
J ) 17.1 Hz, 1H), 4.91 (d, J ) 10.2 Hz, 1H), 3.89 (br dd, J )
11.4, 4.5 Hz, 1H), 3.52 (m, 2H), 3.34 (m, 2H), 2.93 (ddd, J )
10.6, 9.0, 4.5 Hz, 1H), 2.17 (br dd, J ) 12.5, 2.9 Hz, 1H), 2.06
(m, 2H), 1.61 (m, 4H), 1.34 (dddd, J ) 12.5, 12.5, 10.6, 5.0 Hz,
1H). 13C NMR (125 MHz, CDCl3) δ 138.25 (d), 136.75 (d),
116.22 (t), 114.73 (t), 81.21 (d), 78.02 (d), 68.57 (t), 67.43 (t),
30.23 (t), 29.74 (t), 29.21 (t), 25.26 (t). MS m/e (rel intens) 196
(M+, 1). HRMS calcd for C12H20O2 (M)+: 196.146330, found:
196.146849. Anal. Calcd for C12H20O2: C, 73.43; H, 10.27.
Found: C, 73.52; H, 10.44.
2934, 1638, 1463, 1234 cm-1 1H NMR (500 MHz, CDCl3) δ
.
5.78 (dddd, J ) 17.2, 10.2, 6.7, 6.7 Hz, 1H), 4.96 (d, J ) 17.1
Hz, 1H), 4.90 (d, J ) 10.2 Hz, 1H), 3.89 (br dd, J ) 11.3, 4.6
Hz, 1H), 3.81 (m, 1H), 3.65 (m, 1H), 3.57 (ddd, J ) 9.1, 6.5,
6.5 Hz, 1H), 3.33 (m, 2H), 3.16 (m, 2H), 2.22 (br d, J ) 12.3
Hz, 1H), 2.17 (dd, J ) 6.2, 6.2 Hz, 1H, OH), 2.01 (ddd, J )
7.5, 7.5, 6.7 Hz, 2H), 1.66 (m, 2H), 1.52 (m, 2H), 1.33 (m, 7H).
13C NMR (125 MHz, CDCl3) δ 139.06 (d), 114.23 (t), 80.58 (d),
74.96 (d), 68.88 (t), 67.73 (t), 63.53 (t), 33.70 (t), 30.00 (t), 29.17
(t), 28.90 (t), 28.84 (t), 25.99 (t), 25.23 (t). MS m/e (rel intens)
242 (M+, 10). HRMS calcd for C14H26O3 (M)+: 242.188195,
found: 242.187541. Anal. Calcd for C14H26O3: C, 69.38; H,
10.81. Found: C, 69.45; H, 10.58.
(2R,3S)-3-Oct-7′-en yloxy-2-vin yltetr a h yd r op yr a n (11c):
colorless liquid. Rf ) 0.32 (silica, 5% EtOAc in hexanes). [R]25
D
(2′R,3′S)-(3′-Non -8′′-en yloxytetr ah ydr opyr an -2′-yl)m eth -
a n ol (10c): colorless oil. Rf ) 0.57 (silica, 50% EtOAc in
) +48.95° (c 1.1, CHCl3). IR (CHCl3) νmax 3079, 3007, 2858,
1640, 1463, 1085 cm-1. 1H NMR (500 MHz, CDCl3) δ 5.97 (ddd,
J ) 17.3, 10.7, 5.5 Hz, 1H), 5.77 (dddd, J ) 17.0, 10.2, 6.7, 6.7
Hz, 1H), 5.32 (d, J ) 17.3 Hz, 1H), 5.16 (d, J ) 10.7 Hz, 1H),
4.96 (d, J ) 17.1 Hz, 1H), 4.90 (d, J ) 10.2 Hz, 1H), 3.90 (br
dd, J ) 11.4, 4.4 Hz, 1H), 3.52 (m, 2H), 3.34 (m, 2H), 2.94
(ddd, J ) 10.5, 9.1, 4.4 Hz, 1H), 2.17 (br dd, J ) 12.4, 3.0 Hz,
1H), 2.01 (ddd, J ) 7.2, 7.2, 6.7 Hz, 2H), 1.61 (m, 2H), 1.48
(m, 2H), 1.31 (m, 7H). 13C NMR (125 MHz, CDCl3) δ 139.05
(d), 136.79 (d), 116.12 (t), 114.18 (t), 81.23 (d), 78.04 (d), 69.44
(t), 67.44 (t), 33.69 (t), 29.99 (t), 29.80 (t), 28.88 (t), 28.86 (t),
25.95 (t), 25.29 (t). MS m/e (rel intens) 238 (M+, 1). HRMS
calcd for C15H26O2 (M)+: 238.193280, found: 238.193776. Anal.
Calcd for C15H26O2: C, 75.58; H, 10.99. Found: C, 75.45; H,
11.19.
hexanes). [R]25 ) +55.08° (c 1.02, CHCl3). IR (CHCl3) νmax
D
3596, 3011, 2858, 1639, 1464, 1358 cm-1. H NMR (500 MHz,
1
CDCl3) δ 5.78 (dddd, J ) 17.2, 10.2, 6.7, 6.7 Hz, 1H), 4.96 (d,
J ) 17.1 Hz, 1H), 4.90 (d, J ) 10.2 Hz, 1H), 3.89 (br dd, J )
11.3, 4.5 Hz, 1H), 3.81 (m, 1H), 3.65 (m, 1H), 3.57 (ddd, J )
9.1, 6.5, 6.5 Hz, 1H), 3.33 (m, 2H), 3.16 (m, 2H), 2.23 (br d, J
) 12.3 Hz, 1H), 2.18 (dd, J ) 6.5, 6.5 Hz, 1H, OH), 2.01 (ddd,
J ) 7.5, 7.5, 6.7 Hz, 2H), 1.61 (m, 2H), 1.50 (m, 2H), 1.31 (m,
9H). 13C NMR (125 MHz, CDCl3) δ 139.13 (d), 114.16 (t), 80.60
(d), 74.96 (d), 68.91 (t), 67.71 (t), 63.53 (t), 33.75 (t), 30.04 (t),
29.26 (t), 29.17 (t), 29.04 (t), 28.85 (t), 26.07 (t), 25.23 (t). MS
m/e (rel intens) 256 (M+, 2), 225 ([M - CH2OH]+, 15). HRMS
calcd for C15H28O3 (M)+: 256.203845, found: 256.204205; calcd
for C14H25O2 (M - CH2OH)+: 225.185455, found 225.185322.
Anal. Calcd for C15H28O3: C, 70.27; H, 11.01. Found: C, 70.30;
H, 11.15.
Gen er a l P r oced u r e for Oxid a tion -Wittig Olefin a tion .
To a stirred solution of the alcohol (0.4 mmol) in CH2Cl2 (2
mL) were added NEt3 (280 µL, 2 mmol, 5.0 equiv) and dry
DMSO (425 µL, 6 mmol, 15.0 equiv). The reaction mixture was
cooled to 0 °C and SO3‚py (191 mg, 1.2 mmol, 3.0 equiv) was
added. After 2 h, the reaction was quenched by addition of
water, and the two layers were separated. The aqueous layer
was extracted with CH2Cl2 (3 × 3 mL), and the combined
organic layers were washed with brine and dried over MgSO4.
Solvent was removed under reduced pressure, and the residue
was used in the Wittig reaction without further purification.
For the Wittig olefination, a suspension of methyltriph-
enylphosphonium bromide (214 mg, 0.6 mmol, 1.5 equiv) in
THF (1 mL) was treated at 0 °C with nBuLi (243 µL, 0.56
mmol, 1.4 equiv, 2.3 M in hexanes). After stirring for 1 h at
(2R,3S)-3-Non -8′-en yloxy-2-vin yltetr ah ydr opyr an (11d):
colorless liquid. Rf ) 0.36 (silica, 5% EtOAc in hexanes). [R]25
D
) +48.61° (c 0.8, CHCl3). IR (CHCl3) νmax 3080, 2857, 1639,
1
1464 cm-1. H NMR (500 MHz, CDCl3) δ 5.97 (ddd, J ) 17.4,
10.7, 5.5 Hz, 1H), 5.77 (dddd, J ) 17.1, 10.2, 6.7, 6.7 Hz, 1H),
5.32 (d, J ) 17.4 Hz, 1H), 5.16 (d, J ) 10.7 Hz, 1H), 4.98 (d,
J ) 17.1 Hz, 1H), 4.94 (d, J ) 10.2 Hz, 1H), 3.91 (br dd, J )
11.4, 4.4 Hz, 1H), 3.52 (m, 2H), 3.34 (m, 2H), 2.94 (ddd, J )
10.6, 9.1, 4.5 Hz, 1H), 2.18 (br dd, J ) 12.5, 3.0 Hz, 1H), 2.01
(ddd, J ) 7.2, 7.2, 6.7 Hz, 2H), 1.63 (m, 2H), 1.49 (m, 2H),
1.35 (m, 3H), 1.27 (m, 6H). 13C NMR (125 MHz, CDCl3) δ
139.14 (d), 136.79 (d), 116.17 (t), 114.15 (t), 81.23 (d), 78.03
(d), 69.49 (t), 67.46 (t), 33.77 (t), 30.03 (t), 29.80 (t), 29.26 (t),
29.06 (t), 28.86 (t), 26.04 (t), 25.30 (t). MS m/e (rel intens) 252
(M+, 2). HRMS calcd for C16H28O2 (M)+: 252.208930, found:
252.207977. Anal. Calcd for C16H28O2: C, 76.14; H, 11.18.
Found: C, 76.22; H, 11.04.

4808 J . Org. Chem., Vol. 64, No. 13, 1999
Delgado and Mart´ın
Gen er a l P r oced u r e for Tosyla tion . To a stirred solution
of 2 (200 mg, 1.5 mmol) in dry CH2Cl2 (3 mL) were added NEt3
(315 µL, 2.25 mmol, 1.5 equiv) and a catalytic amount of
DMAP. After cooling to 0 °C, tosyl chloride (286 mg, 1.5 mmol,
1.0 equiv) was added, and the stirring reaction was allowed
to reach room-temperature overnight. Reaction was quenched
with water (1 mL), and the aqueous layer was extracted with
CH2Cl2 (3 × 2 mL). The combined organic layers were washed
with brine and dried over MgSO4. Solvent was removed in
vacuo, and the residue was purified by flash chromatography.
For alcohols 10a and 10c, the reaction was carried out with
1.2 equiv of tosyl chloride.
general procedure for tosylation). Colorless oil. Rf ) 0.43 (silica,
30% EtOAc in hexanes). [R]25 ) +44.52° (c 0.75, CHCl3). IR
D
(CHCl3) νmax 3031, 2859, 1603, 1443, 1363, 1290 cm-1. 1H NMR
(500 MHz, CDCl3) δ 7.78 (d, J ) 7.9 Hz, 2H, ArH), 7.30 (d, J
) 7.9 Hz, 2H, ArH), 5.70 (dddd, J ) 17.0, 10.4, 6.7, 6.7 Hz,
1H), 5.00 (m, 2H), 4.19 (m, 2H), 3.87 (br d, J ) 11.2 Hz, 1H),
3.56 (ddd, J ) 8.7, 6.6, 6.6 Hz, 1H), 3.25 (m, 3H), 3.12 (ddd, J
) 10.3, 9.8, 4.5 Hz, 1H), 2.41 (s, 3H, ArCH3), 2.19 (m, 3H),
1.58 (m, 2H), 1.26 (dddd, J ) 12.1, 12.1, 10.3, 4.8 Hz, 1H).
13C NMR (125 MHz, CDCl3) δ 144.57 (s, aromatic C),
135.07 (d), 133.21 (s, aromatic C), 129.70 (d, 2 aromatic C),
128.08 (d, 2 aromatic C), 116.45 (t), 78.45 (d), 73.10 (d), 69.84
(t), 67.94 (t), 67.76 (t), 34.40 (t), 29.09 (t), 25.92 (t), 21.65 (q,
ArCH3). MS m/e (rel intens) 340 (M+, 1). HRMS calcd for
C17H24O5S (M)+: 340.13445, found: 340.13526. Anal. Calcd for
Tolu en e-4-su lfon ic a cid (2′R,3′S)-3′-h yd r oxytetr a h y-
d r op yr a n -2′-ylm eth yl ester (12): colorless oil. Rf ) 0.54
(silica, 60% EtOAc in hexanes). [R]25D ) +8.54° (c 2.62, CHCl3).
1
IR (CHCl3) νmax 3616, 3548, 3028, 1599, 1451 cm-1. H NMR
C
17H24O5S: C, 59.98; H, 7.11; S, 9.42. Found: C, 59.59; H, 6.87;
S, 9.04.
P r ep a r a tion of Tolu en e-4-su lfon ic Acid (2′R,3′S)-3′-
(500 MHz, CDCl3) δ 7.78 (d, J ) 8.1 Hz, 2H, ArH), 7.31 (d, J
) 8.1 Hz, 2H, ArH), 4.30 (dd, J ) 11.0, 4.5 Hz, 1H), 4.19 (dd,
J ) 11.0, 1.5 Hz, 1H), 3.85 (br d, J ) 11.3 Hz, 1H), 3.52 (ddd,
J ) 10.2, 9.2, 5.0 Hz, 1H), 3.27 (ddd, J ) 11.3, 11.3, 3.7 Hz,
1H), 3.18 (ddd, J ) 9.2, 4.5, 1.5 Hz, 1H), 2.42 (s, 3H, ArCH3),
2.23 (br s, 1H, OH), 2.10 (br dd, J ) 12.3, 3.0 Hz, 1H), 1.66
(m, 2H), 1.39 (dddd, J ) 12.3, 12.3, 10.2, 5.6 Hz, 1H). 13C NMR
(125 MHz, CDCl3) δ 144.94 (s, aromatic C), 132.88 (s, aromatic
C), 129.87 (d, 2 aromatic C), 128.00 (d, 2 aromatic C), 80.19
(d), 71.93 (t), 69.81 (t), 65.84 (d), 32.36 (t), 25.41 (t), 21.66 (q,
ArCH3). MS m/e (rel intens) 269 ([M - OH]+, 1), 114 ([M -
TsOH]+, 20). HRMS calcd for C13H18O5S (M)+: 286.08750,
found: 286.08910. Anal. Calcd for C13H18O5S: C, 54.53; H,
6.34; S, 11.20. Found: C, 54.50; H, 6.42; S, 11.43.
Non -8′′-en yloxytetr a h yd r op yr a n -2′-ylm eth yl Ester (14b).
This compound was prepared from 10c as described above (see
general procedure for tosylation). Colorless oil. Rf ) 0.37 (silica,
20% EtOAc in hexanes). [R]25 ) +34.30° (c 1.8, CHCl3). IR
D
(CHCl3) νmax 3031, 2857, 1454, 1363 cm-1. 1H NMR (500 MHz,
CDCl3) δ 7.78 (d, J ) 8.1 Hz, 2 H, ArH), 7.30 (d, J ) 8.1 Hz,
2H, ArH), 5.79 (dddd, J ) 17.1, 10.2, 6.7, 6.7 Hz, 1H), 4.97 (d,
J ) 17.1 Hz, 1H), 4.91 (d, J ) 10.2 Hz, 1H), 4.19 (m, 2H), 3.82
(br dd, J ) 11.4, 4.4 Hz, 1H), 3.49 (ddd, J ) 9.0, 6.5, 6.5 Hz,
1H), 3.22 (m, 3H), 3.09 (ddd, J ) 10.0, 9.0, 4.6 Hz, 1H), 2.41
(s, 3H, ArCH3), 2.21 (br dd, J ) 12.3, 3.2 Hz, 1H), 2.02 (ddd,
J ) 7.5, 6.7, 6.7 Hz, 2H), 1.57 (m, 2H), 1.42 (m, 2H), 1.36 (m,
2H), 1.25 (m, 7H). 13C NMR (125 MHz, CDCl3) δ 144.50 (s,
aromatic C), 139.15 (d, C8′′), 133.26 (s, aromatic C), 129.66 (d,
2 aromatic C), 128.07 (d, 2 aromatic C), 114.19 (t), 78.55 (d),
73.02 (d), 69.87 (t), 68.85 (t), 67.78 (t), 33.77 (t), 30.00 (t), 29.30
(t), 29.13 (t), 29.05 (t), 28.88 (t), 26.04 (t), 24.84 (t), 21.63 (q,
ArCH3). MS m/e (rel intens) 410 (M+, 1). HRMS calcd for
P r ep a r a tion of Tolu en e-4-su lfon ic Acid (2′R,3′S)-3′-
Allyloxytetr a h yd r op yr a n -2′-ylm eth yl Ester (13a ). This
compound was prepared from 12 as described above (see
general procedure for O-alkylation). Colorless oil. Rf ) 0.34
(silica, 20% EtOAc in hexanes). [R]25 ) +39.91° (c 2.77,
D
CHCl3). IR (CHCl3) νmax 3029, 2858, 1452, 1189, 1097 cm-1
.
1H NMR (500 MHz, CDCl3) δ 7.75 (d, J ) 8.1 Hz, 2H, ArH),
7.28 (d, J ) 8.1 Hz, 2H, ArH), 5.76 (dddd, J ) 17.2, 10.5, 5.6,
5.6 Hz, 1H), 5.15 (d, J ) 17.2 Hz, 1H), 5.08 (d, J ) 10.5 Hz,
1H), 4.18 (m, 2H), 3.99 (dd, J ) 12.4, 5.6 Hz, 1H), 3.78 (m,
2H), 3.23 (m, 2H), 3.17 (ddd, J ) 10.5, 9.9, 4.5 Hz, 1H), 2.39
(s, 3H, ArCH3), 2.20 (dddd, J ) 12.4, 4.5, 3.1, 3.1 Hz, 1H), 1.55
(m, 2H), 1.26 (dddd, J ) 12.4, 12.4, 10.5, 4.5 Hz, 1H). 13C NMR
(125 MHz, CDCl3) δ 144.63 (s, aromatic C), 134.70 (d), 133.13
(s, aromatic C), 129.70 (d, 2 aromatic C), 127.95 (d, 2 aromatic
C), 116.90 (t), 78.41 (d), 72.51 (d), 69.79 (t), 69.56 (t), 67.73
(t), 29.08 (t), 24.78 (t), 21.60 (q, ArCH3). MS m/e (rel intens)
326 (M+, 1). HRMS calcd for C16H22O5S (M)+: 326.11880,
found: 326.11869. Anal. Calcd for C16H22O5S: C, 58.93; H,
6.80; S, 9.83. Found: C, 58.78; H, 6.91; S, 10.12.
C
22H34O5S (M)+: 410.212696, found: 410.212832. Anal. Calcd
for C22H34O5S: C, 64.36; H, 8.35; S, 7.81. Found: C, 64.42; H,
8.47; S, 7.89.
Gen er a l P r oced u r e for Nu cleop h ilic Su bstitu tion w ith
KCN. To a stirring solution of the corresponding tosylate or
iodo compound (0.5 mmol) in dry DMSO (1.7 mL) was added
KCN (98 mg, 1.5 mmol, 3.0 equiv), and the reaction mixture
was stirred at 50 °C for 6 h. Then it was allowed to cool, and
water was added to quench the reaction. The mixture was
diluted with EtOAc. The aqueous layer was extracted with
EtOAc (3 × 3 mL), and combined organic layers were dried
over MgSO4. After removal of the solvent, the residue was
purified by flash chromatography.
(2′R,3′S)-(3′-Allyloxyt e t r a h yd r op yr a n -2′-yl)a ce t on i-
tr ile (15a ): colorless oil. Rf ) 0.49 (silica, 25% EtOAc in
P r ep a r a tion of Tolu en e-4-su lfon ic Acid (2′R,3′S)-3′-
P en t-4′′-en yloxytetr ah ydr opyr an -2′-ylm eth yl Ester (13b).
This compound was prepared from 12 as described above (see
general procedure for O-alkylation). Colorless oil. Rf ) 0.41
hexanes). [R]25 ) +89.39° (c 1.45, CHCl3). IR (CHCl3) νmax
D
3020, 2948, 2865, 2254, 1464, 1268, 1212 cm-1. H NMR (500
1
MHz, CDCl3) δ 5.83 (dddd, J ) 17.1, 10.5, 5.5, 5.5 Hz, 1H),
5.21 (d, J ) 17.1 Hz, 1H), 5.14 (d, J ) 10.5 Hz, 1H), 4.07 (dd,
J ) 12.5, 5.5 Hz, 1H), 3.88 (m, 2H), 3.32 (ddd, J ) 11.9, 11.9,
3.5 Hz, 1H), 3.28 (ddd, J ) 9.5, 6.1, 3.5 Hz, 1H), 3.14 (ddd, J
) 10.5, 9.5, 4.5 Hz, 1H), 2.72 (dd, J ) 16.8, 3.5 Hz, 1H), 2.62
(dd, J ) 16.8, 6.1 Hz, 1H), 2.24 (br dd, J ) 12.2, 4.5 Hz, 1H),
(silica, 25% EtOAc in hexanes). [R]25 ) +44.17° (c 0.66,
D
CHCl3). IR (CHCl3) νmax 2928, 2360, 1639, 1456 cm-1. 1H NMR
(500 MHz, CDCl3) δ 7.77 (d, J ) 8.1 Hz, 2H, ArH), 7.30 (d, J
) 8.1 Hz, 2H, ArH), 5.75 (dddd, J ) 17.2, 10.2, 6.6, 6.6 Hz,
1H), 4.97 (d, J ) 17.1 Hz, 1H), 4.93 (d, J ) 10.2 Hz, 1H), 4.21
(dd, J ) 10.3, 2.1 Hz, 1H), 4.16 (dd, J ) 10.3, 5.0 Hz, 1H),
3.82 (br dd, J ) 11.4, 4.4 Hz, 1H), 3.51 (ddd, J ) 9.0, 6.4, 6.4
Hz, 1H), 3.22 (m, 3H), 3.09 (ddd, J ) 10.0, 9.0, 4.5 Hz, 1H),
2.40 (s, 3H, ArCH3), 2.21 (br dd, J ) 12.5, 3.3 Hz, 1H), 2.00
(dddd, J ) 7.5, 7.5, 6.6, 1.2 Hz, 2H), 1.56 (m, 4H), 1.24 (dddd,
J ) 12.5, 12.5, 10.0, 5.0 Hz, 1H). 13C NMR (125 MHz, CDCl3)
δ 144.60 (s, aromatic C), 138.13 (d), 133.14 (s, aromatic C),
129.72 (d, 2 aromatic C), 128.05 (d, 2 aromatic C), 114.83 (t),
78.51 (d), 73.01 (d), 69.87 (t), 67.91 (t), 67.79 (t), 30.22 (t), 29.10
(t), 29.07 (t), 24.81 (t), 21.64 (q, ArCH3). MS m/e (rel intens)
355 ([M + 1]+, 13). HRMS calcd for C18H27O5S (M + H)+:
355.157921, found: 355.156695. Anal. Calcd for C18H26O5S: C,
60.99; H, 7.93; S, 9.05. Found: C, 60.86; H, 8.10; S, 9.23.
P r ep a r a tion of Tolu en e-4-su lfon ic Acid (2′R,3′S)-3′-
Bu t-3′′-en yloxytetr a h yd r op yr a n -2′-ylm eth yl Ester (14a ).
This compound was prepared from 10a as described above (see
1.63 (m, 2H), 1.30 (dddd, J ) 12.2, 12.2, 10.5, 5.7 Hz, 1H). 13
C
NMR (125 MHz, CDCl3) δ 134.70 (d), 117.54 (s, RCN), 117.37
(t), 76.16 (d), 75.73 (d), 69.53 (t), 68.03 (t), 28.75 (t), 24.81 (t),
21.46 (t). MS m/e (rel intens) 181 (M+, 5). HRMS calcd for
C
10H15NO2 (M)+: 181.11028, found: 181.10971. Anal. Calcd
for C10H15NO2: C, 66.27; H, 8.34; N, 7.73. Found: C, 66.38;
H, 8.49; N, 7.79.
(2′R,3′S)-(3′-Bu t-3′′-en yloxytetr a h yd r op yr a n -2′-yl)a ce-
ton itr ile (15b): colorless oil. Rf ) 0.61 (silica, 30% EtOAc in
hexanes). [R]25 ) +79.04° (c 0.73, CHCl3). IR (CHCl3) νmax
D
3020, 2948, 2867, 2254, 1642 cm-1. 1H NMR (500 MHz, CDCl3)
δ 5.76 (dddd, J ) 17.0, 10.3, 6.7, 6.7 Hz, 1H), 5.07 (d, J ) 17.0
Hz, 1H), 5.03 (d, J ) 10.3 Hz, 1H), 3.92 (br d, J ) 11.0 Hz,
1H), 3.66 (ddd, J ) 9.1, 6.5, 6.5 Hz, 1H), 3.36 (m, 2H), 3.28
(ddd, J ) 9.3, 6.0, 3.6 Hz, 1H), 3.10 (ddd, J ) 10.1, 9.3, 4.4
Hz, 1H), 2.73 (dd, J ) 16.7, 3.6 Hz, 1H), 2.64 (dd, J ) 16.7,

Ring-Closing Metathesis
J . Org. Chem., Vol. 64, No. 13, 1999 4809
6.0 Hz, 1H), 2.27 (m, 3H), 1.68 (m, 2H), 1.30 (m, 1H). 13C NMR
(125 MHz, CDCl3) δ 135.07 (d), 117.65 (s, RCN), 116.93 (t),
76.39 (d), 76.19 (d), 68.10 (t), 67.90 (t), 34.39 (t), 28.81 (t), 24.87
(t), 21.54 (t). MS m/e (rel intens) 195 (M+, 2). HRMS calcd for
C11H17NO2 (M)+: 195.12593, found: 195.12644. Anal. Calcd
for C11H17NO2: C, 67.66; H, 8.77; N, 7.17. Found: C, 67.86;
H, 9.15; N, 7.27.
3.0 Hz, 1H), 2.98 (ddd, J ) 10.5, 9.3, 4.5 Hz, 1H), 2.59 (br d,
J ) 14.6 Hz, 1H), 2.29 (m, 2H), 2.20 (m, 2H), 1.62 (m, 2H),
1.31 (dddd, J ) 12.3, 12.3, 10.5, 5.1 Hz, 1H). 13C NMR (125
MHz, CDCl3) δ 135.44 (d), 135.31 (d), 116.52 (t), 116.35 (t),
80.51 (d), 77.34 (d), 68.27 (t), 67.80 (t), 36.65 (t), 34.57 (t), 29.28
(t), 25.39 (t). MS m/e (rel intens) 196 (M+, 2). HRMS calcd for
C12H20O2 (M)+: 196.146330, found: 196.145982. Anal. Calcd
for C12H20O2: C, 73.43; H, 10.27. Found: C, 73.62; H, 10.44.
(2R,3S)-2-Allyl-3-pen t-4′-en yloxytetr ah ydr opyr an (16c):
(2′R,3′S)-(3′-P en t -4′′-en yloxyt et r a h yd r op yr a n -2′-yl)-
a ceton itr ile (15c): colorless oil. Rf ) 0.64 (silica, 30% EtOAc
in hexanes). [R]25 ) +76.36° (c 1.1, CHCl3). IR (CHCl3) νmax
colorless liquid. Rf ) 0.55 (silica, 10% EtOAc in hexanes). [R]25
D
D
3023, 3007, 2928, 2857, 2253, 1640 cm-1. H NMR (500 MHz,
) +52.11° (c 0.7, CHCl3). IR (CHCl3) νmax 3079, 3004, 2856,
1
CDCl3) δ 5.77 (dddd, J ) 17.1, 10.2, 6.6, 6.6 Hz, 1H), 5.00 (d,
J ) 17.1 Hz, 1H), 4.95 (d, J ) 10.2 Hz, 1H), 3.92 (br d, J )
11.0 Hz, 1H), 3.60 (ddd, J ) 9.0, 6.3, 6.3 Hz, 1H), 3.32 (m,
3H), 3.09 (ddd, J ) 10.6, 9.1, 4.4 Hz, 1H), 2.73 (dd, J ) 16.7,
3.6 Hz, 1H), 2.64 (dd, J ) 16.7, 6.0 Hz, 1H), 2.27 (br d, J )
11.0 Hz, 1 H), 2.08 (ddd, J ) 6.8, 6.6, 6.6 Hz, 2H), 1.64 (m,
4H), 1.29 (m, 1H). 13C NMR (125 MHz, CDCl3) δ 137.96 (d),
117.64 (s, RCN), 115.00 (t), 76.24 (d), 76.20 (d), 68.13 (t), 68.05
(t), 30.32 (t), 29.05 (t), 28.84 (t), 25.16 (t), 21.49 (t). MS m/e
(rel intens) 210 ([M + 1]+, 93). HRMS calcd for C12H20NO2 (M
1641, 1464, 1437 cm-1 1H NMR (500 MHz, CDCl3) δ 5.87
.
(dddd, J ) 17.3, 10.2, 6.3, 6.3 Hz, 1H), 5.79 (dddd, J ) 17.1,
10.2, 6.6, 6.6 Hz, 1H), 5.02 (m, 4H), 3.87 (br d, J ) 11.2 Hz,
1H), 3.58 (ddd, J ) 9.1, 6.3, 6.3 Hz, 1H), 3.30 (m, 2H), 3.15
(ddd, J ) 9.0, 8.2, 3.0 Hz, 1H), 2.96 (ddd, J ) 10.5, 9.0, 4.5
Hz, 1H), 2.60 (br d, J ) 14.6 Hz, 1H), 2.20 (m, 2H), 2.11 (m,
2H), 1.62 (m, 4H), 1.29 (dddd, J ) 12.4, 12.4, 10.5, 5.1 Hz,
1H). 13C NMR (125 MHz, CDCl3) δ 138.27 (d), 135.45 (d),
116.55 (t), 114.81 (t), 80.55 (d), 77.23 (d), 68.09 (t), 67.87 (t),
36.68 (t), 30.34 (t), 29.36 (t), 29.28 (t), 25.41 (t). MS m/e
(rel intens) 210 (M+, 11). HRMS calcd for C13H22O2 (M)+:
210.161980, found: 210.162441. Anal. Calcd for C13H22O2: C,
74.24; H, 10.54. Found: C, 74.15; H, 10.63.
+ H)+: 210.149404, found: 210.149598. Anal. Calcd for C12H19
-
NO2: C, 68.87; H, 9.15; N, 6.69. Found: C, 68.52; H, 9.33; N,
6.63.
(2′R ,3′S )-(3′-Non -8′′-e n yloxyt e t r a h yd r op yr a n -2′-yl)-
a ceton itr ile (15d ): colorless liquid. Rf ) 0.39 (silica, 20%
EtOAc in hexanes). [R]25D ) +60.54° (c 1.3, CHCl3). IR (CHCl3)
(2R ,3S )-2-Ally l-3-n o n -8′-e n y lo x y t e t r a h y d r o p y r a n
(16d ): liquid. Rf ) 0.58 (silica, 10% EtOAc in hexanes). [R]25
D
) +40.40° (c 1.22, CHCl3). IR (CHCl3) νmax 3078, 3006, 2932,
2857, 1640, 1464, 1437, 1340 cm-1. 1H NMR (500 MHz, CDCl3)
δ 5.87 (dddd, J ) 17.3, 10.2, 6.5, 6.5 Hz, 1H), 5.78 (dddd, J )
17.1, 10.1, 6.7, 6.7 Hz, 1H), 5.07 (d, J ) 17.3 Hz, 1H), 5.03 (d,
J ) 10.2 Hz, 1H), 4.96 (d, J ) 17.1 Hz, 1H), 4.90 (d, J ) 10.1
Hz, 1H), 3.86 (br dd, J ) 11.2, 4.2 Hz, 1H), 3.55 (ddd, J ) 9.0,
6.4, 6.4 Hz, 1H), 3.29 (m, 2H), 3.14 (ddd, J ) 9.1, 8.2, 3.0 Hz,
1H), 2.94 (ddd, J ) 10.5, 9.1, 4.4 Hz, 1H), 2.59 (br d, J ) 13.1
Hz, 1H), 2.19 (m, 2H), 2.01 (m, 2H), 1.59 (m, 2H), 1.50 (m,
1
νmax 3022, 2932, 2858, 2254, 1639 cm-1. H NMR (500 MHz,
CDCl3) δ 5.78 (dddd, J ) 17.0, 10.2, 6.7, 6.7 Hz, 1H), 4.96 (d,
J ) 17.0 Hz, 1H), 4.90 (d, J ) 10.2 Hz, 1H), 3.92 (br dd, J )
11.3, 4.2 Hz, 1H), 3.58 (ddd, J ) 9.1, 6.5, 6.5 Hz, 1H), 3.32 (m,
3H), 3.08 (ddd, J ) 10.7, 9.2, 4.4 Hz, 1H), 2.73 (dd, J ) 16.7,
3.6 Hz, 1H), 2.63 (dd, J ) 16.7, 6.0 Hz, 1H), 2.26 (br dd, J )
12.5, 2.8 Hz, 1H), 2.01 (ddd, J ) 6.8, 6.6, 6.6 Hz, 2H), 1.66 (m,
2H), 1.50 (m, 2H), 1.35 (m, 2H), 1.28 (m, 7H). 13C NMR (125
MHz, CDCl3) δ 139.10 (d), 117.64 (s, RCN), 114.20 (t), 76.33
(d), 76.26 (d), 68.78 (t), 68.08 (t), 33.75 (t), 29.95 (t), 29.25 (t),
29.03 (t), 28.84 (t, 2 C), 26.08 (t), 24.91 (t), 21.47 (t). MS m/e
(rel intens) 265 (M+, 87). HRMS calcd for C16H27NO2 (M)+:
265.204179, found: 265.202854. Anal. Calcd for C16H27NO2:
C, 64.36; H, 10.25; N, 5.28. Found: C, 64.45; H, 10.36; N, 5.23.
Gen er a l P r oced u r e for Nitr ile Red u ction -Wittig Ole-
fin a tion . A solution of the corresponding nitrile (0.05 mmol)
in dry Et2O (4 mL) was cooled to 0 °C, and DIBAL (0.75 mL,
0.75 mmol, 1.5 equiv, 1.0 M in hexanes) was added. The
reaction mixture was stirred for 5 h, quenched by the addition
of 1 N HCl solution (1.5 mL), and filtered through a Celite
pad. The precipitate was thoroughly washed with EtOAc. The
organic layer was washed with NaHCO3 saturated solution
(2 × 4 mL) and dried over MgSO4. Solvent was removed in
vacuo, and the residue was used without further purification
in the Wittig olefination (procedure described above).
1
2H), 1.31 (m, 9H). H NMR (500 MHz, C6D6) δ 6.25 (dddd, J
) 17.2, 10.2, 7.0, 7.0 Hz, 1H), 5.85 (dddd, J ) 17.1, 10.2, 6.7,
6.7 Hz, 1H), 5.28 (d, J ) 17.2 Hz, 1H), 5.19 (d, J ) 10.2 Hz,
1H), 5.10 (d, J ) 17.1 Hz, 1H), 5.05 (d, J ) 10.2 Hz, 1H), 3.79
(br dd, J ) 11.2, 4.6 Hz, 1H), 3.49 (ddd, J ) 8.9, 6.4, 6.4 Hz,
1H), 3.30 (ddd, J ) 9.0, 8.8, 3.1 Hz, 1H), 3.22 (ddd, J ) 8.9,
6.5, 6.5 Hz, 1H) 3.13 (ddd, J ) 12.1, 11.2, 2.2 Hz, 1H), 2.99
(ddd, J ) 10.5, 9.0, 4.5 Hz, 1H), 2.85 (br d, J ) 14.3, 1H), 2.53
(ddd, J ) 14.3, 8.8, 7.0 Hz, 1H), 2.05 (m, 3H), 1.59 (m, 2H),
1.45 to 1.26 (m, 11H). 13C NMR (125 MHz, CDCl3) δ 139.12
(d), 135.46 (d), 116.46 (t), 114.16 (t), 80.59 (d), 77.21 (d), 68.94
(t), 67.84 (t), 36.66 (t), 33.76 (t), 30.11 (t), 29.39 (t), 29.28 (t),
29.05 (t), 28.86 (t), 26.14 (t), 25.43 (t). 13C NMR (125 MHz,
C6D6) δ 138.94 (d), 135.94 (d), 116.20 (t), 114.28 (t), 80.92 (d),
77.17 (d), 68.46 (t), 67.43 (t), 36.99 (t), 33.91 (t), 30.38 (t), 29.45
(t, 2 C), 29.21 (t), 29.04 (t), 26.38 (t), 25.58 (t). MS m/e (rel
intens) 266 (M+, 3). HRMS calcd for C17H30O2 (M)+: 266.224580,
found: 266.224616. Anal. Calcd for C17H30O2: C, 76.64; H,
11.35. Found: C, 76.81; H, 11.45.
(2R,3S)-2-Allyl-3-a llyloxytetr a h yd r op yr a n (16a ): color-
less liquid. Rf ) 0.58 (silica, 10% EtOAc in hexanes). [R]25
)
D
+34.50° (c 0.67, CHCl3). IR (CHCl3) νmax 3027, 3011, 2945,
P r ep a r a tion of Ben zoic Acid (2′R,3′S)-3′-Hyd r oxytet-
r a h yd r op yr a n -2′-ylm eth yl Ester (17). A solution of 2 (330
mg, 2.5 mmol) in dry CH2Cl2 was cooled to 0 °C, and NEt3
(1.05 mL, 7.5 mmol, 3.0 equiv), BzCl (319 µL, 2.75 mmol, 1.0
equiv), and a catalytic amount of DMAP were added. The
reaction was stirred at room temperature for 4 h and quenched
by the addition of 3 mL of NH4Cl saturated solution. The
aqueous layer was extracted with CH2Cl2 (2 × 3 mL). Com-
bined organic layers were dried over MgSO4, and solvent was
removed under reduced pressure. Purification by flash chro-
matography (using 40% EtOAc in hexanes as eluent) afforded
578 mg of the benzoate (98%). Noncrystalline white solid. Rf
) 0.41 (silica, 40% EtOAc in hexanes). [R]25D ) -9.31° (c 0.92,
CHCl3). IR (CHCl3) νmax 3618, 3500, 3026, 3014, 2341, 1708,
1
2857, 2360, 1644 cm-1. H NMR (500 MHz, CDCl3) δ 5.88 (m,
2H), 5.24 (d, J ) 17.2 Hz, 1H), 5.14 (d, J ) 10.4 Hz, 1H), 5.08
(d, J ) 17.2 Hz, 1H), 5.05 (d, J ) 10.2 Hz, 1H), 4.09 (dd, J )
12.7, 5.6 Hz, 1H), 3.90 (m, 2H), 3.30 (ddd, J ) 11.6, 11.6, 3.0
Hz, 1H), 3.18 (ddd, J ) 9.0, 9.0, 3.0 Hz, 1H), 3.04 (ddd, J )
10.4, 9.0, 4.5 Hz, 1H), 2.61 (br d, J ) 14.6 Hz, 1H), 2.21 (m,
2H), 1.61 (m, 2H), 1.32 (dddd, J ) 12.4, 12.4, 10.4, 5.0 Hz,
1H). 13C NMR (125 MHz, CDCl3) δ 135.38 (d), 135.10 (d),
116.86 (t), 116.58 (t), 80.49 (d), 76.71 (d), 69.83 (t), 67.82 (t),
36.66 (t), 29.36 (t), 25.39 (t). MS m/e (rel intens) 182 (M+, 2).
HRMS calcd for C11H18O2 (M)+: 182.130679, found: 182.132577.
Anal. Calcd for C11H18O2: C, 72.49; H, 9.95. Found: C, 72.57;
H, 10.12.
(2R ,3S )-2-Ally l-3-b u t -3′-e n y lo x y t e t r a h y d r o p y r a n
(16b): colorless oil. Rf ) 0.59 (silica, 10% EtOAc in hexanes).
1603 cm-1 1H NMR (500 MHz, CDCl3) δ 8.05 (br d, J ) 8.3
.
Hz, 2H, ArH), 7.53 (dd, J ) 7.4, 7.4 Hz, 1H, ArH), 7.41 (dd, J
) 8.3, 7.4 Hz, 2H, ArH), 4.78 (dd, J ) 12.2, 4.0 Hz, 1H), 4.41
(dd, J ) 12.2, 2.2 Hz, 1H), 3.39 (br dd, J ) 11.5, 4.0 Hz, 1H),
3.42 (m, 1H), 3.35 (m, 1H), 3.30 (ddd, J ) 9.3, 4.0, 2.2 Hz,
1H), 2.95 (br s, 1H, OH), 2.11 (br dd, J ) 12.5, 4.5 Hz, 1H),
1.64 (m, 2H), 1.45 (m, 1H). 13C NMR (125 MHz, CDCl3) δ
[R]25 ) +45.00° (c 0.31, CHCl3). IR (CHCl3) νmax 3007, 2943,
D
2360, 1642, 1435 cm-1. H NMR (500 MHz, CDCl3) δ 5.83 (m,
1
2H), 5.05 (m, 4H), 3.87 (br dd, J ) 11.5, 4.2 Hz, 1H), 3.63 (ddd,
J ) 9.0, 6.6, 6.6 Hz, 1H), 3.37 (ddd, J ) 9.0, 6.9, 6.9 Hz, 1H),
3.30 (ddd, J ) 11.5, 11.5, 3.1 Hz, 1H), 3.15 (ddd, J ) 9.3, 8.3,

4810 J . Org. Chem., Vol. 64, No. 13, 1999
Delgado and Mart´ın
167.69 (s, PhCOO), 133.26 (d, aromatic C), 129.94 (d, 2
aromatic C), 129.71 (s, aromatic C), 128.39 (d, 2 aromatic C),
81.20 (d), 68.05 (t), 66.17 (d), 64.81 (t), 32.01 (t), 25.38 (t). MS
m/e (rel intens) 236 (M+, 1). HRMS calcd for C13H16O4 (M)+:
236.10486, found: 236.10713. Anal. Calcd for C13H16O4: C,
66.10; H, 6.80. Found: C, 65.89; H, 7.09.
(c 0.88, CHCl3). IR (CHCl3) νmax 3022, 2954, 2931, 2859, 2360,
1
2341, 1464, 1362 cm-1. H NMR (500 MHz, CDCl3) δ 3.99 (br
dd, J ) 11.5, 4.5 Hz, 1H), 3.40 (ddd, J ) 10.5, 9.0, 4.6 Hz,
1H), 3.35 (ddd, J ) 11.5, 11.5, 2.8 Hz, 1H), 3.24 (ddd, J ) 9.0,
6.2, 3.5 Hz, 1H), 2.70 (dd, J ) 16.7, 3.5 Hz, 1H), 2.56 (dd, J )
16.7, 6.2 Hz, 1H), 2.03 (br d, J ) 12.8 Hz, 1H), 1.65 (m, 2H),
1.43 (dddd, J ) 12.8, 12.8, 10.8, 4.6 Hz, 1H), 0.85 (s, 9H, (CH3)3-
CSi), 0.08 (s, 3H, CH3Si), 0.06 (s, 3H, CH3Si). 13C NMR (125
MHz, CDCl3) δ 117.59 (s, RCN), 77.94 (d), 70.17 (d), 68.04 (t),
33.07 (t), 25.71 (q, (CH3)3CSi), 25.18 (t), 21.45 (t), 17.84 (s,
(CH3)3CSi), -3.92 (q, CH3Si), -4.85 (q, CH3Si). MS m/e (rel
intens) 256 ([M + 1]+, 100). HRMS calcd for C13H26NO2Si (M
P r ep a r a tion of Ben zoic Acid (2′R,3′S)-3′-(ter t-Bu tyld i-
m eth ylsilyloxy)tetr a h yd r op yr a n -2′-ylm eth yl Ester (18).
This compound was prepared from 17 according to the
procedure described above (see general procedure for protection
of alcohol as TBDMS ethers). Yield: 97%. Colorless oil. Rf )
0.41 (silica, 10% EtOAc in hexanes). [R]25 ) +46.41° (c 1.01,
D
CHCl3). IR (CHCl3) νmax 3023, 2954, 2858, 1717, 1603, 1453
cm-1. 1H NMR (500 MHz, CDCl3) δ 8.04 (br d, J ) 8.0 Hz, 2H,
ArH), 7.52 (dd, J ) 7.5, 7.5 Hz, 1H, ArH), 7.41 (dd, J ) 8.0,
7.5 Hz, 2H, ArH), 4.59 (dd, J ) 11.7, 2.0 Hz, 1H), 4.36 (dd, J
) 11.7, 5.5 Hz, 1H), 3.92 (br dd, J ) 11.7, 4.6 Hz, 1H), 3.63
(ddd, J ) 10.0, 9.8, 4.7 Hz, 1H), 3.37 (m, 2H), 2.07 (br dd, J )
12.5, 4.7 Hz, 1H), 1.67 (m, 2H), 1.48 (dddd, J ) 12.5, 12.5,
10.0, 4.7 Hz, 1H), 0.84 (s, 9H, (CH3)3CSi), 0.05 (s, 3H, CH3Si),
0.03 (s, 3H, CH3Si). 13C NMR (125 MHz, CDCl3) δ 166.58 (s,
PhCOO), 132.80 (d, aromatic C), 130.38 (s, aromatic C), 129.70
(d, 2 aromatic C), 128.25 (d, 2 aromatic C), 80.74 (d), 67.90
(t), 67.53 (d), 64.78 (t), 33.53 (t), 25.72 (q, (CH3)3CSi), 25.41
(t), 17.88 (s, (CH3)3CSi), -3.99 (q, CH3Si), -4.95 (q, CH3Si).
+ H)+: 256.173283, found: 256.173538. Anal. Calcd for C13H25
-
NO2Si: C, 61.13; H, 9.87; N, 5.48. Found: C, 61.11; H, 10.00;
N: 5.63.
P r ep a r a tion of (2′R,3′S)-2-[3′-(ter t-Bu tyld im eth ylsilyl-
oxy)tetr a h yd r op yr a n -2′-yl]eth a n ol (22). Nitrile 21 was
reduced to the corresponding aldehyde following the procedure
described above (see general procedure for nitrile reduction),
using for the acid hydrolysis HCl 0.1 N at 4 °C to avoid
deprotection of the silyl ether. The resultant aldehyde (without
further purification) was dissolved in MeOH, and NaBH4 (2.0
equiv) was added at 0 °C. When TLC showed that the reaction
had finished, solvent was removed in vacuo, and the residue
was dissolved in EtOAc. Water (3 mL) was added, and the
aqueous layer was extracted with EtOAc (3 × 3 mL). Combined
organic layers were dried over MgSO4, and solvent was
removed under reduced pressure. The residue was purified by
flash chromatography (30% EtOAc in hexanes) affording the
expected alcohol (42%). Colorless oil. Rf ) 0.26 (silica, 20%
t
MS m/e (rel intens) 293 ([M - Bu]+, 14). HRMS calcd for
t
C
15H21O4Si (M - Bu)+: 293.12091, found: 293.12121. Anal.
Calcd for C19H30O4Si: C, 65.10; H, 8.63. Found: C, 65.36; H,
8.87.
P r ep a r a tion of (2′R,3′S)-[3′-(ter t-Bu tyld im eth ylsilyl-
oxy)tetr a h yd r op yr a n -2′-yl]m eth a n ol (19). To a stirring
solution of benzoate 18 (832 mg, 2.38 mmol) in MeOH (5 mL)
was added MeONa (64 mg, 1.19 mmol, 0.5 equiv) at room
temperature. When TLC showed that all starting material has
disappeared, solvent was removed in vacuo, and the residue
was purified by flash chromatography, using first CH2Cl2 as
eluent and then 20% EtOAc in hexanes, yielding 580 mg (99%)
of 19. Colorless oil. Rf ) 0.60 (silica, 30% EtOAc in hexanes).
EtOAc in hexanes). [R]25 ) +50.47° (c 1.05, CHCl3). IR
D
(CHCl3) νmax 3504, 3009, 2956, 2858, 2360, 1464 cm-1. 1H NMR
(500 MHz, CDCl3) δ 3.86 (br dd, J ) 11.2, 4.1 Hz, 1H), 3.77
(m, 2H), 3.32 (m, 2H), 3.23 (ddd, J ) 9.0, 9.0, 2.7 Hz, 1H),
2.80 (dd, J ) 6.5, 4.4 Hz, 1H, OH), 2.00 (m, 2H), 1.62 (m, 3H),
1.40 (dddd, J ) 12.6, 12.6, 10.6, 5.5 Hz, 1H), 0.84 (s, 9H, (CH3)3-
CSi), 0.03 (s, 3H, CH3Si), 0.02 (s, 3H, CH3Si). 13C NMR (125
MHz, CDCl3) δ 83.80 (d), 71.00 (d), 67.74 (t), 61.80 (t), 34.08
(t), 33.37 (t), 25.77 (q, (CH3)3CSi), 25.46 (t), 17.93 (s, (CH3)3CSi),
-4.01 (q, CH3Si), -4.72 (q, CH3Si). MS m/e (rel intens)
261 ([M + 1]+, 1). HRMS calcd for C13H29O3Si (M + H)+:
261.188598, found: 261.188033. Anal. Calcd for C13H28O3Si:
C, 59.95; H, 10.84. Found: C, 59.95; H, 10.81.
[R]25 ) +50.5° (c 1.6, CHCl3). IR (CHCl3) νmax 3450, 2952,
D
2858, 1472, 1253 cm-1. H NMR (500 MHz, CDCl3) δ 3.88 (br
1
dd, J ) 11.1, 3.8 Hz, 1 H, He6′), 3.80 (dd, J ) 11.4, 2.6 Hz,
1H), 3.58 (dd, J ) 11.4, 5.9 Hz, 1H), 3.46 (ddd, J ) 10.6, 9.1,
4.7 Hz, 1H), 3.34 (dddd, J ) 11.1, 11.1, 5.0, 3.7 Hz, 1H), 3.12
(ddd, J ) 9.1, 5.9, 2.6 Hz, 1H), 1.99 (m, 2H,), 1.63 (m, 2H),
1.23 (dddd, J ) 12.3, 12.3, 10.6, 5.4 Hz, 1H), 0.85 (s, 9H, (CH3)3-
CSi), 0.04 (s, 6H, 2 × CH3Si). 13C NMR (125 MHz, CDCl3) δ
82.37 (d), 67.92 (d), 67.67 (t), 63.17 (t), 33.28 (t), 25.73 (q,
(CH3)3CSi), 25.48 (t), 17.90 (s, (CH3)3CSi), -4.10 (q, CH3Si),
P r ep a r a tion of (2R,3S)-ter t-Bu tyl-[2-(2′-iod oeth yl)tet-
r a h yd r op yr a n -3-yloxy]d im et h ylsila n e (23). This com-
pound was prepared according to the procedure described
above for the iodination of alcohols. Yield: 87%. Colorless oil.
Rf ) 0.49 (silica, 5% EtOAc in hexanes). [R]25 ) +57.35° (c
D
t
-4.93 (q, CH3Si). MS m/e (rel intens) 189 ([M - Bu]+, 14).
1.12, CHCl3). IR (CHCl3) νmax 3007, 2931, 1464, 1257, 1115
HRMS calcd for C12H27O3Si (M + H)+: 247.12290, found:
247.12370. Anal. Calcd for C12H26O3Si: C, 58.49; H, 10.63.
Found: C, 58.57; H, 10.72.
cm-1 1H NMR (500 MHz, CDCl3) δ 3.84 (br d, J ) 11.8 Hz,
.
1H), 3.27 (m, 4H), 3.05 (ddd, J ) 9.0, 9.0, 2.3 Hz, 1H), 2.33
(m, 1H), 1.97 (br dd, J ) 12.4, 2.9 Hz, 1H), 1.78 (m, 1H), 1.61
(m, 2H), 1.42 (m, 1H), 0.86 (s, 9H, (CH3)3CSi), 0.04 (s, 6H, 2 ×
CH3Si). 13C NMR (125 MHz, CDCl3) δ 82.22 (d), 70.93 (d), 67.77
(t), 36.78 (t), 33.56 (t), 25.79 (q, (CH3)3CSi), 25.65 (t), 17.94 (s,
(CH3)3CSi), 2.87 (t), -3.94 (q, CH3Si), -4.74 (q, CH3Si). MS
m/e (rel intens) 370 (M+, 1), 313 ([M - tBu]+, 100). HRMS calcd
for C13H27IO2Si (M)+: 370.082510, found: 370.081932. Anal.
Calcd for C13H27IO2Si: C, 42.16; H, 7.35. Found: C, 42.16; H,
7.37.
P r ep a r a t ion of (2R,3S)-ter t-Bu t yl(2-iod om et h ylt et -
r a h yd r op yr a n -3-yloxy)d im et h ylsila n e (20). This com-
pound was synthesized according to the method already
described (see procedure for iodination of alcohols). Yield: 95%.
Colorless oil. Rf ) 0.48 (silica, 5% EtOAc in hexanes). [R]25
)
D
+47.82° (c 1.38, CHCl3). IR (CHCl3) νmax 3006, 2955, 2858,
1463, 1217, 1111, 838 cm-1. 1H NMR (500 MHz, CDCl3) δ 3.94
(br dd, J ) 11.3, 4.5 Hz, 1H), 3.48 (dd, J ) 10.4, 2.7 Hz, 1H,
RCH2I), 3.38 (m, 2H), 3.31 (dd, J ) 10.4, 5.8 Hz, 1H, RCH2I),
2.80 (ddd, J ) 8.5, 5.8, 2.7 Hz, 1H), 2.00 (br dd, J ) 12.7, 4.7
Hz, 1H), 1.66 (m, 2H), 1.46 (dddd, J ) 12.7, 12.7, 10.6, 4.5 Hz,
1H), 0.86 (s, 9H, (CH3)3CSi), 0.09 (s, 3H, CH3Si), 0.06 (s, 3H,
CH3Si). 13C NMR (125 MHz, CDCl3) δ 80.81 (d), 71.21 (d), 67.98
(t), 33.15 (t), 25.79 (q, (CH3)3CSi), 25.49 (t), 17.88 (s, (CH3)3CSi),
9.33 (t), -3.85 (q, CH3Si), -4.49 (q, CH3Si). MS m/e (rel intens)
Gen er a l P r oced u r e for Keck Rea ction . To a stirring
solution of the corresponding iodo compound (0.7 mmol) in dry
benzene (2 mL) were added allyl tributyl tin (434 µL, 1.4 mmol,
2.0 equiv) and a catalytic amount of AIBN. After stirring at
80 °C overnight, solvent was removed under reduced pressure,
and the residue was purified by flash chromatography (silica,
2.5% EtOAc in hexanes).
357 ([M + 1]+, 2), 299 ([M - tBu]+, 10). HRMS calcd for C8H16
-
(2R,3S)-(2-Bu t -3′-en ylt et r a h yd r op yr a n -3-yloxy)-ter t-
bu tyld im eth ylsila n e (24a ): colorless oil. Rf ) 0.49 (silica,
IO2Si (M - tBu)+: 298.9964, found: 298.9970. Anal. Calcd for
C
12H25IO2Si: C, 40.45; H, 7.07. Found: C, 40.62; H, 7.23.
5% EtOAc in hexanes). [R]25 ) +38.16° (c 2.01, CHCl3). IR
D
P r ep a r a tion of (2′R,3′S)-[3′-(ter t-Bu tyld im eth ylsilyl-
(CHCl3) νmax 3003, 2930, 1640, 1463, 1362, 1258 cm-1. 1H NMR
(500 MHz, CDCl3) δ 5.81 (dddd, J ) 17.0, 10.2, 6.5, 6.5 Hz,
1H), 4.99 (d, J ) 17.0 Hz, 1H), 4.91 (d, J ) 10.2 Hz, 1H), 3.84
(br d, J ) 11.2 Hz, 1H), 3.26 (m, 2H), 2.98 (ddd, J ) 8.9, 8.9,
2.1 Hz, 1H), 2.21 (m, 1H), 2.07 (m, 1H), 1.97 (br dd, J ) 12.4,
oxy)tetr a h yd r op yr a n -2′-yl]a ceton itr ile (21). This com-
pound was prepared according to the procedure for nucleophilic
substitution with KCN described above. Yield: 99%. Colorless
oil. Rf ) 0.38 (silica, 15% EtOAc in hexanes). [R]25D ) +50.26°

Ring-Closing Metathesis
J . Org. Chem., Vol. 64, No. 13, 1999 4811
3.0 Hz, 1H), 1.88 (m, 1H), 1.60 (m, 2H), 1.39 (m, 2H), 0.86 (s,
9H, (CH3)3CSi), 0.04 (s, 6H, 2 × CH3Si). 13C NMR (125 MHz,
CDCl3) δ 138.88 (d), 114.29 (t), 82.04 (d), 71.37 (d), 67.77 (t),
33.72 (t), 31.48 (t), 29.56 (t), 25.81 (t), 25.77 (q, (CH3)3CSi),
17.98 (s, (CH3)3CSi), -3.94 (q, CH3Si), -4.71 (q, CH3Si). MS
2H), 2.07 (m, 1H), 1.94 (dddd, J ) 14.0, 9.3, 6.6, 2.5 Hz, 1H),
1.60 (m, 2H), 1.43 (dddd, J ) 14.0, 9.5, 9.3, 5.0 Hz, 1H), 1.31
(dddd, J ) 12.6, 12.6, 10.5, 4.9 Hz, 1H). 13C NMR (125 MHz,
CDCl3) δ 138.87 (d), 135.15 (d), 116.80 (t), 114.36 (t), 80.38
(d), 77.34 (d), 69.87 (t), 67.62 (t), 31.59 (t), 29.72 (t), 29.43 (t),
25.49 (t). MS m/e (rel intens) 196 (M+, 11). HRMS calcd for
C12H20O2 (M)+: 196.146330, found: 196.146954. Anal. Calcd
for C12H20O2: C, 73.43; H, 10.27. Found: C, 73.48; H, 10.36.
P r ep a r a tion of (2R,3S)-2-Bu t-3′′-en yl-3-p en t-4′-en yl-
oxytetr a h yd r op yr a n (26b). This compound was prepared
from 25a following the procedure described above for O-
alkylation. Yield: 73%. Colorless oil. Rf ) 0.55 (silica, 10%
EtOAc in hexanes). [R]25D ) +25.45° (c 0.5, CHCl3). IR (CHCl3)
t
m/e (rel intens) 270 (M+, 0.2), 213 ([M - Bu]+, 16). HRMS
t
calcd for C11H21O2Si (M - Bu)+: 213.1311, found: 213.1311.
Anal. Calcd for C15H30O2Si: C, 66.61; H, 11.18. Found: C,
66.61; H, 11.09.
(2R,3S)-ter t-Bu tyld im eth yl-(2-p en t-4′-en yltetr a h yd r o-
p yr a n -3-yloxy)sila n e (24b): colorless oil. Rf ) 0.50 (silica,
5% EtOAc in hexanes). [R]25 ) +35.22° (c 1.27, CHCl3). IR
D
(CHCl3) νmax 3003, 2858, 1639, 1463, 1362, 1219 cm-1. 1H NMR
(500 MHz, CDCl3) δ 5.78 (dddd, J ) 17.1, 10.2, 6.7, 6.7 Hz,
1H), 4.97 (d, J ) 17.1 Hz, 1H), 4.90 (d, J ) 10.2 Hz, 1H), 3.84
(br dd, J ) 11.5, 4.3 Hz, 1H), 3.26 (m, 2H), 2.96 (ddd, J ) 8.9,
8.9, 2.4 Hz, 1H), 2.03 (ddd, J ) 6.9, 6.7, 6.7 Hz, 2H), 1.96 (br
dd, J ) 12.5, 3.2 Hz, 1H), 1.81 (m, 1H), 1.61 (m, 3H), 1.39 (m,
2H), 1.28 (m, 1H), 0.86 (s, 9H, (CH3)3CSi), 0.03 (s, 6H, 2 ×
CH3Si). 13C NMR (125 MHz, CDCl3) δ 138.97 (d), 114.36 (t),
82.61 (d), 71.39 (d), 67.77 (t), 33.88 (t), 33.71 (t), 31.75 (t), 25.81
(q, (CH3)3CSi), 25.81 (t), 24.76 (t), 17.98 (s, (CH3)3CSi), -3.94
(q, CH3Si), -4.73 (q, CH3Si). MS m/e (rel intens) 284 (M+, 1),
269 ([M - CH3]+, 3). HRMS calcd for C16H32O2Si (M)+:
284.217159, found: 284.215645. Calcd for C15H29O2Si (M -
CH3)+: 269.193684, found 269.193001. Anal. Calcd for C16H32O2-
Si: C, 67.55; H, 11.34. Found: C, 67.42; H, 11.50.
1
νmax 3008, 2927, 2360, 2338, 1640 cm-1. H NMR (500 MHz,
CDCl3) δ 5.81 (m, 2H), 5.01 (m, 2H), 4.93 (m, 2H), 3.86 (br dd,
J ) 11.4, 4.4 Hz, 1H), 3.58 (ddd, J ) 9.2, 6.3, 6.3 Hz, 1H),
3.33 (m, 2H), 3.05 (ddd, J ) 9.0, 9.0, 2.6 Hz, 1H), 2.91 (ddd, J
) 10.6, 9.0, 4.4 Hz, 1H), 2.22 (m, 2H), 2.08 (m, 3H), 1.93 (m,
1H), 1.63 (m, 4H), 1.44 (m, 1H), 1.28 (dddd, J ) 12.5, 12.5,
10.6, 4.9 Hz, 1H). 13C NMR (125 MHz, CDCl3) δ 138.92 (d),
138.27 (d), 114.79 (t), 114.33 (t), 80.48 (d), 77.95 (d), 68.18 (t),
67.68 (t), 31.64 (t), 30.32 (t), 29.71 (t), 29.47 (t), 29.27 (t), 25.53
(t). MS m/e (rel intens) 224 (M+, 61), 182 ([M - C3H6]+, 11).
HRMS calcd for C14H24O2 (M)+: 224.177630, found: 224.177639.
Anal. Calcd for C14H24O2: C, 74.95; H, 10.78. Found: C, 75.02;
H, 10.86.
P r ep a r a tion of (2R,3S)-2-P en t-4′′-en yl-3-p en t-4′-en yl-
oxyt et r a h yd r op yr a n (26c). This compound was prepared
from 25b following the procedure described above for O-
alkylation. Yield: 73%. Colorless oil. Rf ) 0.58 (silica, 15%
P r ep a r a tion of (2R,3S)-2-Bu t-3′-en yltetr a h yd r op yr a n -
3-ol (25a ). Alcohol 25a was prepared from 24a following the
procedure described above for the deprotection of silyl ethers.
Yield: 98%. Colorless oil. Rf ) 0.57 (silica, 50% EtOAc in
hexanes). [R]25D ) +44.42° (c 0.5, CHCl3). IR (CHCl3) νmax 3623,
EtOAc in hexanes). [R]25 ) +41.26° (c 0.99, CHCl3). IR
D
(CHCl3) νmax 3079, 3004, 2942, 2857, 2360, 1639, 1439 cm-1
.
3079, 3013, 1640, 1235 cm-1
.
1H NMR (500 MHz, CDCl3) δ
1H NMR (500 MHz, CDCl3) δ 5.79 (m, 2H), 4.96 (m, 4H), 3.85
(br dd, J ) 11.4, 4.4 Hz, 1H), 3.57 (ddd, J ) 9.2, 6.3, 6.3 Hz,
1H), 3.29 (m, 2H), 3.03 (ddd, J ) 8.9, 8.9, 2.7 Hz, 1H), 2.89
(ddd, J ) 10.6, 8.9, 4.4 Hz, 1H), 2.17 (br dd, J ) 12.3, 3.1 Hz,
1H), 2.06 (m, 4H), 1.83 (m, 1H), 1.61 (m, 5H), 1.40 (m, 2H),
1.29 (m, 1H). 13C NMR (125 MHz, CDCl3) δ 139.01 (d), 138.28
(d), 114.76 (t), 114.30 (t), 81.01 (d), 77.92 (d), 68.15 (t), 67.69
(t), 33.93 (t), 31.82 (t), 30.32 (t), 29.47 (t), 29.28 (t), 25.52 (t),
24.83 (t). MS m/e (rel intens) 238 (M+, 17). HRMS calcd for
5.82 (dddd, J ) 17.1, 10.2, 6.7, 6.7 Hz, 1H), 5.02 (d, J ) 17.1
Hz, 1H), 4.94 (d, J ) 10.2 Hz, 1H), 3.88 (br d, J ) 11.3 Hz,
1H), 3.30 (m, 2H), 2.99 (ddd, J ) 9.0, 9.0, 2.5 Hz, 1H), 2.26
(m, 1H), 2.10 (m, 2H), 1.91 (dddd, J ) 14.1, 9.5, 6.8, 2.5 Hz,
1H), 1.68 (m, 2H), 1.50 (dddd, J ) 14.1, 9.5, 9.0, 5.1 Hz, 1H),
1.42 (d, J ) 5.5 Hz, 1H, OH), 1.37 (m, 1H). 13C NMR (125 MHz,
CDCl3) δ 138.68 (d), 114.60 (t), 81.69 (d), 70.52 (d), 67.51 (t),
33.02 (t), 31.33 (t), 29.54 (t), 25.66 (t). MS m/e (rel intens) 156
(M+, 46), 138 ([M - H2O]+, 7), 120 (7), 114 ([M - C3H6]+, 100).
HRMS calcd for C9H16O2 (M)+: 156.115030, found: 156.115170.
Calcd for C6H10O2 (M - C3H6)+: 114.068080, found 114.068691.
Anal. Calcd for C9H16O2: C, 69.19; H, 10.32. Found: C, 69.23;
H, 10.18.
C
15H26O2 (M)+: 238.193280, found: 238.193325. Anal. Calcd
for C15H26O2: C, 75.58; H, 10.99. Found: C, 75.72; H, 11.22.
Gen er a l P r oced u r e for Olefin Meta th esis. The amount
of catalyst necessary in each case was weighed and dissolved
in dry CH2Cl2 or benzene (see tables) in a flame-dried vessel.
A solution of the corresponding diene in CH2Cl2 or benzene
was then added dropwise via cannula to the above solution
under an atmosphere of dry argon (final concentration of diene
was 5 × 10-3 M). When addition finished, the vessel was
sealed, and the reaction mixture was stirred at room temper-
ature or at the temperature shown on the tables. Progress of
reaction was tested by TLC and NMR. When reaction finished
or when no further progress was observed, solvent was
removed in vacuo, and the residue was purified by flash
chromatography, affording the expected unsaturated cycle.
(Z)-(4aS,9aR)-3,4,4a,6,7,9a-Hexah ydr o-2H-1,5-dioxaben -
zocycloh ep ten e (27): colorless liquid. Rf ) 0.49 (silica, 10%
EtOAc in hexanes). [R]25D ) -9.58° (c 0.18, CHCl3). IR (CHCl3)
P r ep a r a t ion of (2R,3S)-2-P en t -4′-en ylt et r a h yd r op y-
r a n -3-ol (25b). Alcohol 25b was prepared from 24b following
the procedure described above for the deprotection of silyl
ethers. Yield: 98%. Colorless oil. Rf ) 0.59 (silica, 50% EtOAc
in hexanes). [R]25 ) +39.16° (c 0.63, CHCl3). IR (CHCl3) νmax
D
3620, 3068, 3010, 1640, 1230 cm-1. 1H NMR (500 MHz, CDCl3)
δ 5.79 (dddd, J ) 17.1, 10.2, 6.7, 6.7 Hz, 1H), 4.98 (d, J ) 17.1
Hz, 1H), 4.91 (d, J ) 10.2 Hz, 1H), 3.86 (br dd, J ) 11.3, 4.0
Hz, 1H), 3.27 (m, 2H), 2.96 (ddd, J ) 8.6, 8.6, 2.7 Hz, 1H),
2.06 (m, 3H), 1.82 (m, 1H), 1.63 (m, 3H), 1.55 (d, J ) 5.0 Hz,
1H, OH), 1.40 (m, 3H). 13C NMR (125 MHz, CDCl3) δ 138.86
(d), 114.48 (t), 82.29 (d), 70.50 (d), 67.53 (t), 33.84 (t), 32.98
(t), 31.52 (t), 25.66 (t), 24.70 (t). MS m/e (rel intens) 170 (M+,
25), 152 ([M - H2O]+, 9). HRMS calcd for C10H18O2 (M)+:
170.130679, found: 170.130856. Anal. Calcd for C10H18O2: C,
70.55; H, 10.66. Found: C, 70.32; H, 10.81.
1
νmax 3008, 2928, 2856, 1452 cm-1. H NMR (500 MHz, CDCl3)
δ 5.75 (dddd, J ) 12.1, 8.5, 3.5, 3.5 Hz, 1H, CHdCH), 5.58
(ddd, J ) 12.1, 2.3, 2.3 Hz, 1H, CHdCH), 4.00 (ddd, J ) 11.8,
3.5, 3.5 Hz, 1H), 3.86 (br dd, J ) 11.3, 3.9 Hz, 1H), 3.73 (br
dd, J ) 8.9, 2.3 Hz, 1H), 3.46 (ddd, J ) 11.8, 11.8, 1.7 Hz,
1H), 3.27 (m, 1H), 3.03 (ddd, J ) 11.0, 8.9, 4.6 Hz, 1H), 2.41
(dddd, J ) 13.5, 11.8, 3.5, 3.5 Hz, 1H), 2.06 (m, 2H), 1.64 (m,
2H), 1.42 (m, 1H). 13C NMR (125 MHz, CDCl3) δ 135.24 (d,
CHdCH), 127.54 (d, CHdCH), 82.39 (d), 78.80 (d), 71.03 (t),
67.39 (t), 31.85 (t), 31.10 (t), 25.40 (t). HRMS calcd for C9H15O2
(M+H)+: 155.10720, found: 155.10891. Anal. Calcd for
C9H14O2: C, 70.10; H, 9.15. Found: C, 69.87; H, 9.42.
P r ep a r a t ion of (2R,3S)-3-Allyloxy-2-b u t -3′′-en ylt et -
r a h yd r op yr a n (26a ). This compound was prepared from 25a
following the procedure described above for O-alkylation.
Yield: 83%. Colorless oil. Rf ) 0.53 (silica, 10% EtOAc in
hexanes). [R]25 ) +54.47° (c 0.44, CHCl3). IR (CHCl3) νmax
D
3080, 3008, 2928, 2360, 1640, 1454, 1262, cm-1. 1H NMR (500
MHz, CDCl3) δ 5.88 (dddd, J ) 17.2, 10.4, 5.6, 5.6 Hz, 1H),
5.82 (dddd, J ) 17.1, 10.2, 6.7, 6.7 Hz, 1H), 5.23 (d, J ) 17.2
Hz, 1H), 5.13 (d, J ) 10.4 Hz, 1H), 5.00 (d, J ) 17.1 Hz, 1H),
4.91 (d, J ) 10.2 Hz, 1H), 4.07 (dd, J ) 12.6, 5.6 Hz, 1H), 3.90
(dd, J ) 12.6, 5.6 Hz, 1H), 3.85 (br dd, J ) 11.5, 4.5 Hz, 1H),
3.28 (ddd, J ) 11.5, 11.5, 2.8 Hz, 1H), 3.07 (ddd, J ) 8.9, 8.9,
2.5 Hz, 1H), 2.99 (ddd, J ) 10.5, 8.9, 4.4 Hz, 1H), 2.22 (m,
(Z)-(4aS,9aR)-3,4,4a,6,9,9a-Hexah ydr o-2H-1,5-dioxaben -
zocycloh ep ten e (28): colorless liquid. Rf ) 0.49 (silica, 10%
EtOAc in hexanes). [R]25 ) -4.96° (c 0.4, CHCl3). IR (CHCl3)
D
νmax 3035, 3008, 2928, 2360, 1463 cm-1. H NMR (500 MHz,
1

4812 J . Org. Chem., Vol. 64, No. 13, 1999
Delgado and Mart´ın
CDCl3) δ 5.91 (m, 1H, CHdCH), 5.85 (dddd, J ) 11.1, 11.1,
2.7, 2.7 Hz, 1H, CHdCH), 4.19 (dd, J ) 14.9, 6.2 Hz, 1H), 3.99
(br dd, J ) 14.9, 3.8 Hz, 1H), 3.85 (br dd, J ) 11.1, 4,2 Hz,
1H), 3.30 (ddd, J ) 11.1, 11.1, 3.5 Hz, 1H), 3.21 (ddd, J ) 11.0,
8.8, 4.7 Hz, 1H), 3.02 (ddd, J ) 10.4, 8.8, 3.6 Hz, 1H), 2.49
(ddd, J ) 11.1, 8.1, 3.6 Hz, 1H), 2.35 (m, 1H), 2.06 (br dd, J )
12.5, 3.1 Hz, 1H), 1.69 (m, 2H), 1.46 (dddd, J ) 12.5,
12.5, 11.0, 5.4 Hz, 1H). 13C NMR (125 MHz, CDCl3) δ 131.94
(d, CHdCH), 128.70 (d, CHdCH), 83.30 (d), 78.51 (d), 67.55
(t), 67.49 (t), 35.11 (t), 31.32 (t), 25.83 (t). HRMS calcd for
C9H14O2 (M)+: 154.099379, found: 154.099948. Anal. Calcd
for C9H14O2: C, 70.10; H, 9.15. Found: C, 70.32; H, 9.34.
(Z)-(4a S,10a R)-2,3,4,4a ,6,7,8,10a -Octa h yd r o-1,5-d ioxa -
ben zocycloocten e (29): colorless liquid. Rf ) 0.50 (silica,
(Z)-(4a S,11a R)-3,4,4a ,6,7,8,11,11a -Octa h yd r o-2H-1,5-d i-
oxa ben zocyclon on en e (32): colorless liquid. Rf ) 0.55
(silica, 10% EtOAc in hexanes). [R]25 ) +26.78° (c 0.42,
D
CHCl3). IR (CHCl3) νmax 2949, 2853, 1648, 1600, 1443, 1328
cm-1
.
1H NMR (500 MHz, CDCl3) δ 5.63 (m, 2H, 2 × CHd
CH), 3.93 (ddd, J ) 11.0, 5.5, 5.5 Hz, 1H), 3.85 (br dd, J )
11.2, 4.2 Hz, 1H), 3.45 (m, 1H), 3.30 (ddd, J ) 11.2, 11.2, 3.7
Hz, 1H), 3.16 (ddd, J ) 9.1, 8.8, 3.9 Hz, 1H), 3.09 (ddd, J )
10.9, 9.1, 4.1 Hz, 1H), 2.73 (ddd, J ) 12.8, 9.1, 4.1 Hz, 1H),
2.38 (dddd, J ) 12.5, 9.0, 8.5, 3.6 Hz, 1H), 2.26 (m, 1H), 2.07
(m, 2H), 1.72 (m, 1H), 1.60 (m, 3H), 1.37 (m, 1H). 1H NMR
(500 MHz, C6D6) δ 5.90 (ddd, J ) 10.5, 10.5, 7.1 Hz, 1H,
CHdCH), 5.65 (ddd, J ) 10.5, 10.5, 7.1 Hz, 1H, CHdCH), 3.79
(m, 2H), 3.27 (m, 2H), 3.13 (m, 2H), 3.04 (ddd, J ) 13.5, 10.5,
3.5 Hz, 1H), 2.48 (m, 2H), 1.95 (m, 2H), 1.44 (m, 5H). 13C NMR
(125 MHz, CDCl3) δ 132.42 (d, CHdCH), 126.04 (d, CHdCH),
80.26 (d, 2C), 68.33 (t), 65.81 (t), 30.69 (t), 30.42 (t), 27.51 (t),
26.03 (t), 22.67 (t). 13C NMR (125 MHz, C6D6) δ 132.07 (d),
126.54 (d), 80.47 (d), 78.80 (d), 69.05 (t), 67.93 (t), 30.63 (t),
30.38 (t), 27.65 (t), 26.25 (t), 22.37 (t). HRMS calcd for
10% EtOAc in hexanes). [R]25 ) +14.69° (c 0.82, CHCl3). IR
D
(CHCl3) νmax 3026, 3009, 2946, 1464, 1354 cm-1. 1H NMR (500
MHz, CDCl3) δ 5.54 (m, 2H, 2 × CHdCH), 3.93 (dd, J ) 12.1,
5.6 Hz, 1H), 3.84 (m, 2H), 3.47 (ddd, J ) 12.1, 12.1, 3.8 Hz,
1H), 3.26 (m, 1H), 2.99 (ddd, J ) 10.7, 9.2, 4.6 Hz, 1H), 2.39
(dddd, J ) 13.2, 10.0, 10.0, 5.5 Hz, 1H), 2.07 (br dd, J ) 12.6,
2.9 Hz, 1H), 2.00 (m, 1H), 1.90 (m, 1H), 1.64 (m, 2H), 1.42 (m,
1H), 1.29 (dddd, J ) 13.5, 13.2, 4.6, 4.6 Hz, 1H). 1H NMR (500
MHz, C6D6) δ 5.97 (dd, J ) 11.0, 5.2 Hz, 1H, CHdCH), 5.44
(dddd, J ) 11.0, 10.5, 10.5, 1.9 Hz, 1H, CHdCH), 3.92 (m, 2H),
3.77 (br d, J ) 11.3 Hz, 1H), 3.39 (ddd, J ) 12.0, 12.0, 3.8 Hz,
1H), 3.07 (ddd, J ) 11.7, 11.7, 2.2 Hz, 1H), 3.00 (ddd, J ) 10.3,
9.1, 4.7 Hz, 1H), 2.54 (dddd, J ) 13.0, 10.5, 10.5, 5.5 Hz, 1H),
2.06 (m, 1H), 1.85 (m, 2H), 1.48 (m, 2H), 1.26 (br d, J ) 10.7
Hz, 1H), 1.06 (dddd, J ) 13.5, 13.0, 4.4, 3.8 Hz, 1H). 13C NMR
(125 MHz, CDCl3) δ 133.60 (d, CHdCH), 127.40 (d, CHdCH),
80.07 (d), 79.73 (d), 68.11 (t), 67.24 (t), 31.32 (t), 29.10 (t), 25.58
(t), 23.40 (t). 13C NMR (125 MHz, C6D6) δ 134.66 (d, CHdCH),
126.61 (d, CHdCH), 80.45 (d), 80.05 (d), 67.84 (t), 66.92 (t),
31.68 (t), 29.34 (t), 25.74 (t), 23.51 (t). MS m/e (rel intens) 168
(M+, 18). HRMS calcd for C10H16O2 (M)+: 168.115029, found:
168.116284. Anal. Calcd for C10H16O2: C, 71.39; H, 9.59.
Found: C, 71.55; H, 9.88.
C
11H18O2 (M)+: 182.130679, found: 182.131598. Anal. Calcd
for C11H18O2: C, 72.49; H, 9.95. Found: C, 72.56; H, 10.09.
(Z)-(4a S,12a R)-2,3,4,4a ,6,7,8,11,12,12a -Deca h yd r o-1,5-
d ioxa ben zocyclod ecen e (33): colorless oil. Rf ) 0.55 (silica,
10% EtOAc in hexanes). [R]25 ) +31.18° (c 0.24, CHCl3). IR
D
(CHCl3) νmax 3025, 3008, 2944, 2872, 1463 cm-1. 1H NMR (500
MHz, CDCl3) δ 5.52 (ddd, J ) 10.5, 8.4, 8.0 Hz, 1H, CHdCH),
5.27 (ddd, J ) 10.5, 9.6, 8.0 Hz, 1H, CHdCH), 3.80 (br dd, J
) 11.2, 4.1 Hz, 1H), 3.60 (ddd, J ) 8.2, 4.7, 4.7 Hz, 1H), 3.24
(m, 3H), 3.01 (ddd, J ) 10.6, 9.2, 4.9 Hz, 1H), 2.34 (m, 3H),
2.04 (m, 3H), 1.69 (m, 1H), 1.60 (m, 2H), 1.48 (m, 3H). 13C NMR
(125 MHz, CDCl3) δ 133.01 (d, CHdCH), 125.80 (d, CHdCH),
80.36 (d), 78.50 (d), 67.48 (t), 65.04 (t), 35.30 (t), 29.42 (t), 26.80
(t), 25.55 (t), 22.90 (t), 22.34 (t). HRMS calcd for
C
12H20O2 (M)+: 196.146330, found: 196.146987. Anal. Calcd
for C12H20O2: C, 73.43; H, 10.27. Found: C, 73.29; H, 10.39.
(E)-(4a S,13a R)-3,4,4a ,6,7,8,9,10,11,13a -Deca h yd r o-2H -
1,5-d ioxa ben zocyclou n d ecen e (34): colorless oil. Rf ) 0.56
(Z)-(4a S,10a R)-2,3,4,4a ,6,7,10,10a -Octa h yd r o-1,5-d ioxa -
ben zocycloocten e (30): colorless liquid. Rf ) 0.50 (silica,
(silica, 10% EtOAc in hexanes). [R]25 ) +22.09° (c 0.53,
D
10% EtOAc in hexanes). [R]25 ) +51.13° (c 1.01, CHCl3). IR
CHCl3). IR (CHCl3) νmax 3028, 3008, 2945, 2870, 1462, 1354
D
1
(CHCl3) νmax 2950, 2850, 1650, 1600, 1460, 1440 cm-1. 1H NMR
(500 MHz, CDCl3) δ 5.81 (m, 2H, 2 × CHdCH), 3.83 (br dd, J
) 11.4, 4.5 Hz, 1H), 3.72 (ddd, J ) 11.6, 5.6, 5.6 Hz, 1H), 3.52
(ddd, J ) 11.6, 5.6, 5.6 Hz, 1H), 3.28 (ddd, J ) 11.4, 11.4, 3.5
Hz, 1H), 3.14 (m, 2H), 2.58 (ddd, J ) 11.2, 8.0, 2.6 Hz, 1H),
2.26 (m, 3H), 1.98 (br d, J ) 12.2 Hz, 1H), 1.62 (m, 2H), 1.40
cm-1. H NMR (500 MHz, CDCl3) δ 5.79 (ddd, J ) 15.1, 11.0,
4.1 Hz, 1H, CHdCH), 5.37 (ddd, J ) 15.1, 9.0, 1.0 Hz, 1H,
CHdCH), 3.86 (br d, J ) 11.4 Hz, 1H), 3.67 (ddd, J ) 9.2, 3.6,
3.6 Hz, 1H), 3.48 (m, 2H), 3.32 (m, 1H), 2.92 (ddd, J ) 11.3,
9.2, 4.6 Hz, 1H), 2.31 (ddddd, J ) 13.1, 9.4, 4.1, 4.1, 1.0 Hz,
1H), 2.11 (br dd, J ) 12.4, 3.1 Hz, 1H), 1.95 (dddd, J ) 13.1,
12.4, 11.0, 4.5 Hz, 1H), 1.64 (m, 4H), 1.44 (m, 2H), 1.21 (m,
4H), 1.04 (m, 1H). 13C NMR (125 MHz, CDCl3) δ 136.25 (d,
CHdCH), 128.56 (d, CHdCH), 84.43 (d), 78.57 (d), 68.46 (t),
67.40 (t), 34.39 (t), 30.94 (t), 29.12 (t), 25.99 (t), 25.96 (t), 24.91
(t), 23.87 (t). MS m/e (rel intens) 210 (M+, 21), 153 ([M -
C4H9]+, 8). HRMS calcd for C13H22O2 (M)+: 210.161980,
found: 210.162152; calcd for C9H13O2 (M - C4H9)+: 153.091555,
found: 153.090822. Anal. Calcd for C13H22O2: C, 74.24; H,
10.54. Found: C, 74.55; H, 10.72.
1
(m, 1H). H NMR (500 MHz, C6D6) δ 5.95 (ddd, J ) 10.2, 9.2,
6.8 Hz, 1H, CHdCH), 5.70 (ddd, J ) 10.2, 9.5, 8.0 Hz, 1H,
CHdCH), 3.71 (br dd, J ) 11.3, 2.9 Hz, 1H), 3.62 (ddd, J )
10.7, 6.9, 3.6 Hz, 1H), 3.21 (m, 2H), 3.10 (ddd, J ) 9.4, 9.0, 4.5
Hz, 1H), 3.05 (m, 1H), 2.75 (ddd, J ) 13.3, 9.2, 3.8 Hz, 1H),
2.42 (ddd, J ) 13.3, 6.8, 6.5 Hz, 1H), 2.09 (m, 1H), 1.90 (m,
2H), 1.38 (m, 2H), 1.23 (m, 1H). 13C NMR (125 MHz, CDCl3)
δ 129.25 (d, CHdCH), 128.72 (d, CHdCH), 82.22 (d), 77.97
(d), 69.26 (t), 68.05 (t), 31.66 (t), 31.63 (t), 28.93 (t), 26.15 (t).
13C NMR (125 MHz, C6D6) δ 129.25 (d, CHdCH), 129.12 (d,
CHdCH), 82.69 (d), 77.93 (d), 69.10 (t), 67.67 (t), 31.82 (t, 2C),
29.27 (t), 26.38 (t). MS m/e (rel intens) 168 (M+, 25). HRMS
calcd for C10H16O2 (M)+: 168.11503, found: 168.11487. Anal.
Calcd for C10H16O2: C, 71.39; H, 9.59. Found: C, 71.32; H,
9.63.
(E)-(4a S,13a R)-3,4,4a ,6,7,8,11,12,13,13a -Deca h yd r o-2H-
1,5-d ioxa ben zocyclou n d ecen e (35): colorless oil. Rf ) 0.56
(silica, 10% EtOAc in hexanes). [R]25 ) +23.89° (c 0.35,
D
CHCl3). IR (CHCl3) νmax 3030, 3007, 2946, 2868, 1465, 1352
1
cm-1. H NMR (500 MHz, CDCl3) δ 5.45 (ddd, J ) 15.1, 10.5,
4.6 Hz, 1H, CHdCH), 5.32 (dddd, J ) 15.1, 10.8, 5.1, 1.2 Hz,
1H, CHdCH), 3.92 (br dd, J ) 9.5, 4.8 Hz, 1H), 3.82 (br dd, J
) 11.5, 4.4 Hz, 1H), 3.29 (ddd, J ) 11.5, 11.5, 3.0 Hz, 1H),
3.11 (m, 1H), 2.99 (m, 2H), 2.31 (br d, J ) 13.3 Hz, 1H), 2.19
(br dd, J ) 12.2, 3.1 Hz, 1H), 2.13 (m, 1H), 1.87 (m, 1H), 1.77
(m, 1H), 1.59 (m, 6H), 1.24 (m, 3H). 13C NMR (125 MHz,
CDCl3) δ 132.96 (d, CHdCH), 128.12 (d, CHdCH), 80.73 (d),
73.76 (d), 69.69 (t), 67.94 (t), 33.98 (t), 32.47 (t), 29.13 (t), 28.93
(t), 26.29 (t), 25.29 (t), 20.53 (t). HRMS calcd for
(Z)-(4a S,10a R)-2,3,4,4a ,6,9,10,10a -Octa h yd r o-1,5-d ioxa -
ben zocycloocten e (31): colorless liquid. Rf ) 0.50 (silica,
10% EtOAc in hexanes). [R]25 ) +34.17° (c 0.4, CHCl3). IR
D
(CHCl3) νmax 2949, 2847, 1651, 1600, 1459, 1443 cm-1. 1H NMR
(500 MHz, CDCl3) δ 5.77 (ddd, J ) 11.5, 9.0, 8.6 Hz, 1H, CHd
CH), 5.25 (br d, J ) 11.5 Hz, 1H, CHdCH), 4.44 (d, J ) 17.2
Hz, 1H), 4.06 (br dd, J ) 17.2, 3.7 Hz, 1H), 3.82 (br dd, J )
11.2, 4.4 Hz, 1H), 3.24 (m, 3H), 2.61 (m, 1H), 2.07 (m, 3H),
1.59 (m, 2H), 1.42 (m, 2H). 13C NMR (125 MHz, CDCl3) δ
131.06 (d, CHdCH), 126.91 (d, CHdCH), 79.78 (d), 77.97 (d),
69.32 (t), 67.42 (t), 34.09 (t), 30.64 (t), 25.66 (t), 22.56 (t). HRMS
calcd for C10H16O2 (M)+: 168.115029, found: 168.115942. Anal.
Calcd for C10H16O2: C, 71.39; H, 9.59. Found: C, 71.62; H,
9.64.
C
13H22O2 (M)+: 210.161980, found: 210.162008. Anal. Calcd
for C13H22O2: C, 74.24; H, 10.54. Found: C, 74.48; H, 10.82.
(E)-(4aS,14aR)-2,3,4,4a,6,7,8,9,10,11,12,14a-Dodecah ydr o-
1,5-d ioxa ben zocyclod od ecen e (36): colorless oil. Rf ) 0.57
(silica, 10% EtOAc in hexanes). [R]25D ) -2.53° (c 0.48, CHCl3).
1
IR (CHCl3) νmax 3009, 2946, 2872, 1463, 1355 cm-1. H NMR

Ring-Closing Metathesis
J . Org. Chem., Vol. 64, No. 13, 1999 4813
(500 MHz, CDCl3) δ 5.73 (ddd, J ) 15.1, 10.8, 4.0 Hz, 1H, CHd
CH), 5.35 (ddd, J ) 15.1, 8.8, 1.5 Hz, 1H, CHdCH), 3.87 (br
dd, J ) 11.1, 4.1 Hz, 1H), 3.76 (ddd, J ) 9.1, 4.1, 4.1 Hz, 1H),
3.49 (dd, J ) 9.1, 8.8 Hz, 1H), 3.33 (m, 1H), 3.20 (ddd, J )
9.1, 9.1, 2.5 Hz, 1H), 2.87 (ddd, J ) 10.9, 9.1, 4.5 Hz, 1H),
2.31 (m, 1H), 2.20 (br dd, J ) 12.5, 3.1 Hz, 1H), 1.91 (m, 1H),
1.65 to 0.85 (13H). 13C NMR (125 MHz, CDCl3) δ 137.64 (d,
CHdCH), 128.07 (d, CHdCH), 83.36 (d), 78.29 (d), 68.65 (t),
67.51 (t), 32.32 (t), 29.78 (t), 28.54 (t), 28.33 (t), 25.54 (t), 24.63
liquid. Rf ) 0.33 (silica, 15% EtOAc in hexanes). [R]25
)
D
+56.74° (c 1.6, CHCl3). IR (CHCl3) νmax 3082, 3009, 2944, 2861,
1
1642, 1464 cm-1. H NMR (500 MHz, CDCl3) δ 5.89 (dddd, J
) 17.2, 10.3, 5.8, 5.8 Hz, 1H), 5.77 (dddd, J ) 17.2, 10.3, 6.7,
6.7 Hz, 1H), 5.24 (d, J ) 17.2 Hz, 1H), 5.14 (d, J ) 10.3 Hz,
1H), 5.05 (d, J ) 17.2 Hz, 1H), 4.99 (d, J ) 10.3 Hz, 1H), 4.00
(m, 2H), 3.91 (br d, J ) 11.8 Hz, 1H), 3.63 (m, 2H), 3.55 (dd,
J ) 10.3, 5.1 Hz, 1H), 3.34 (m, 2H), 3.21 (m, 2H), 2.26 (m,
2H), 2.21 (br d, J ) 12.1 Hz, 1H), 1.63 (m, 2H), 1.31 (m, 1H).
13C NMR (125 MHz, CDCl3) δ 135.33 (d), 134.94 (d), 117.12
(t), 116.32 (t), 80.42 (d), 73.84 (d), 72.53 (t), 69.88 (t), 68.29
(t), 67.88 (t), 34.51 (t), 29.40 (t), 25.19 (t). MS m/e (rel
intens) 227 ([M+1]+, 50), 226 (M+, 81). HRMS calcd for
(t), 24.45 (t), 23.65 (t). HRMS calcd for
224.177630, found: 224.178159. Anal. Calcd for C14H24O2: C,
74.95; H, 10.78. Found: C, 75.04; H, 10.88.
C
14H24O2 (M)+:
P r ep a r a tion of (2R,3S)-3-Allyloxy-2-a llyloxym eth yltet-
r a h yd r op yr a n (37a ). This compound was prepared from 2
according to the procedure described above (see general
procedure for O-alkylation), using 3.0 equiv of allyl bromide
and 2.2 equiv of NaH. Yield: 73%. Colorless oil. Rf ) 0.31
(silica, 15% EtOAc in hexanes). [R]25D ) +57.28° (c 0.6, CHCl3).
C
13H22O3 (M)+: 226.156895, found: 226.157829. Anal. Calcd
for C13H22O3: C, 68.99; H, 9.80. Found: C, 68.98; H, 9.86.
P r ep a r a t ion of (2R,3S)-3-Bu t -3′-en yloxy-2-p en t -4′′′-
en yloxym eth yltetr a h yd r op yr a n (38c). This compound was
prepared from 10b according to the procedure described above
(see general procedure for O-alkylation). Yield: 72%. Colorless
1
IR (CHCl3) νmax 3009, 2944, 2860, 1647, 1458 cm-1. H NMR
(500 MHz, CDCl3) δ 5.88 (m, 2H), 5.23 (m, 2H), 5.13 (m, 2H),
4.02 (m, 3H), 3.91 (m, 2H), 3.66 (br d, J ) 10.3 Hz, 1H), 3.57
(dd, J ) 10.3, 4.5 Hz, 1H), 3.33 (m, 1H), 3.26 (m, 2H), 2.20 (br
d, J ) 12.4 Hz, 1H), 1.65 (m, 2H), 1.33 (m, 1H). 13C NMR (125
MHz, CDCl3) δ 135.09 (d), 134.92 (d), 117.08 (t), 116.69 (t),
80.46 (d), 73.31 (d), 72.52 (t), 69.90 (t), 69.85 (t), 67.87 (t), 29.48
(t), 25.19 (t). MS m/e (rel intens) 211 ([M - 1]+, 9). HRMS calcd
for C12H19O3 (M - H)+: 211.133419, found: 211.133021. Anal.
Calcd for C12H20O3: C, 67.89; H, 9.50. Found: C, 67.85; H,
9.53.
liquid. Rf ) 0.36 (silica, 15% EtOAc in hexanes). [R]25
)
D
+50.90° (c 1.5, CHCl3). IR (CHCl3) νmax 3080, 3007, 2944, 2866,
1
1640, 1440 cm-1. H NMR (500 MHz, CDCl3) δ 5.78 (m, 2H),
4.99 (m, 4H), 3.91 (br d, J ) 11.5 Hz, 1H), 3.62 (m, 2H), 3.54
(dd, J ) 10.4, 4.9 Hz, 1H), 3.48 (ddd, J ) 9.5, 6.7, 6.7 Hz, 1H),
3.36 (m, 3H), 3.20 (m, 2H), 2.26 (m, 2H), 2.21 (br d, J ) 12.3
Hz, 1H), 2.07 (m, 2H), 1.68 (m, 2H), 1.61 (m, 2H), 1.31 (m,
1H). 13C NMR (125 MHz, CDCl3) δ 138.39 (d), 135.31 (d),
116.33 (t), 114.56 (t), 80.49 (d), 73.85 (d), 71.02 (t), 70.61 (t),
68.33 (t), 67.87 (t), 34.54 (t), 38.28 (t), 29.42 (t), 28.72 (t), 25.20
(t). MS m/e (rel intens) 254 (M+, 11), 213 ([M - C3H5]+, 10).
HRMS calcd for C15H26O3 (M)+: 254.188195, found: 254.187764;
calcd for C12H21O3 (M - C3H5)+: 213.149070, found: 213.149290.
Anal. Calcd for C15H26O3: C, 70.83; H, 10.30. Found: C, 70.84;
H, 9.92.
P r ep a r a tion of (2R,3S)-3-P en t-4′-en yloxy-2-p en t-4′′′-
en yloxym eth yltetr a h yd r op yr a n (37b). This compound was
prepared from 2 according to the procedure described above
(see general procedure for O-alkylation), using 3.0 equiv of
5-bromo-1-pentene and 2.2 equiv of KO-t-Bu, and heating
overnight at 65 °C. Yield: 62%. Colorless oil. Rf ) 0.40 (silica,
P r ep a r a tion of (2R,3S)-(2-Allyloxym eth yltetr a h yd r o-
p yr a n -3-yloxy)-ter t-bu tyld im eth ylsila n e (39). This com-
pound was prepared from 19 according to the procedure
described above (see general procedure for O-alkylation).
Yield: 92%. Colorless oil. Rf ) 0.50 (silica, 15% EtOAc in
hexanes). [R]25D ) +45.86° (c 1.3, CHCl3). IR (CHCl3) νmax 3008,
15% EtOAc in hexanes). [R]25 ) +46.89° (c 0.72, CHCl3). IR
D
(CHCl3) νmax 3080, 3009, 2941, 2855, 1641, 1465 cm-1. 1H NMR
(500 MHz, CDCl3) δ 5.79 (m, 2H), 4.97 (m, 4H), 3.92 (br d, J
) 12.1 Hz, 1H), 3.65 (dd, J ) 10.4, 1.9 Hz, 1H), 3.57 (m, 2H),
3.49 (ddd, J ) 9.5, 6.7, 6.7 Hz, 1H), 3.42 (ddd, J ) 9.5, 6.8, 6.8
Hz, 1H), 3.33 (m, 2H), 3.23 (ddd, J ) 9.3, 5.2, 1.9 Hz, 1H),
3.18 (ddd, J ) 10.4, 9.3, 4.5 Hz, 1H), 2.21 (br dd, J ) 12.4, 2.9
Hz, 1H), 2.09 (m, 4H), 1.65 (m, 6H), 1.31 (dddd, J ) 12.4, 10.4,
10.4, 5.5 Hz, 1H). 13C NMR (125 MHz, CDCl3) δ 138.41 (d),
138.25 (d), 114.80 (t), 114.59 (t), 80.50 (d), 73.77 (d), 71.07 (t),
70.67 (t), 68.20 (t), 67.92 (t), 30.34 (t), 30.30 (t), 29.45 (t), 29.27
(t), 28.72 (t), 25.21 (t). MS m/e (rel intens) 268 (M+, 10). HRMS
calcd for C16H28O3 (M)+: 268.203845, found: 268.204862. Anal.
Calcd for C16H28O3: C, 71.60; H, 10.52. Found: C, 71.54; H,
10.68.
1
2952, 2931, 2858, 2360, 1472, 1463 cm-1. H NMR (500 MHz,
CDCl3) δ 5.89 (dddd, J ) 17.2, 10.4, 5.8, 5.8 Hz, 1H), 5.23 (d,
J ) 17.2 Hz, 1H), 5.13 (d, J ) 10.4 Hz, 1H), 3.98 (m, 2H), 3.90
(br dd, J ) 11.5, 4.5 Hz, 1H), 3.64 (dd, J ) 10.2, 1.8 Hz, 1H),
3.49 (m, 2H), 3.31 (ddd, J ) 11.5, 11.5, 2.4 Hz, 1H), 3.18 (ddd,
J ) 8.5, 8.0, 1.8 Hz, 1H), 1.98 (br d, J ) 12.3 Hz, 1H), 1.63 (m,
2H), 1.39 (m, 1H), 0.84 (s, 9H, (CH3)3CSi), 0.02 (s, 3H, CH3-
Si), 0.01 (s, 3H, CH3Si). 13C NMR (125 MHz, CDCl3) δ 134.89
(d), 117.21 (t), 81.98 (d), 72.56 (t), 69.96 (t), 67.89 (t), 67.32
(d), 33.53 (t), 25.76 (q, (CH3)3CSi), 25.40 (t), 17.90 (s, (CH3)3CSi),
-4.05 (q, CH3Si), -4.95 (q, CH3Si). MS m/e (rel intens) 285
([M - 1]+, 4). HRMS calcd for C15H31O3Si (M + H)+:
287.204249, found: 287.203597. Anal. Calcd for C15H30O3Si:
C, 62.89; H, 10.55. Found: C, 62.91; H, 10.38.
P r ep a r a tion of (2R,3S)-3-Allyloxy-2-p en t-4′′′-en yloxy-
m eth yltetr a h yd r op yr a n (38a ). This compound was pre-
pared from 5a according to the procedure described above (see
general procedure for O-alkylation). Yield: 73%. Colorless oil.
Rf ) 0.51 (silica, 20% EtOAc in hexanes). [R]25 ) +54.98° (c
P r ep a r a tion of (2R,3S)-2-Allyloxym eth yltetr a h yd r o-
p yr a n -3-ol (40). This compound was prepared from 39 ac-
cording to the procedure described above (see general proce-
dure for deprotection of silyl ethers). Yield: 95%. Colorless
D
0.74, CHCl3). IR (CHCl3) νmax 3081, 3009, 2941, 2857, 1640,
1
1464, 1329 cm-1. H NMR (500 MHz, CDCl3) δ 5.87 (dddd, J
) 17.2, 10.5, 5.6, 5.6 Hz, 1H), 5.78 (dddd, J ) 17.1, 10.2, 6.6,
6.6 Hz, 1H), 5.23 (d, J ) 17.2 Hz, 1H), 5.13 (d, J ) 10.5 Hz,
1H), 4.99 (d, J ) 17.1 Hz, 1H), 4.92 (d, J ) 10.2 Hz, 1H), 4.07
(dd, J ) 12.6, 5.6 Hz, 1H), 3.91 (m, 2H), 3.65 (br d, J ) 10.4
Hz, 1H), 3.56 (dd, J ) 10.4, 4.8 Hz, 1H), 3.50 (ddd, J ) 9.5,
6.7, 6.7 Hz, 1H), 3.41 (ddd, J ) 9.5, 6.8, 6.8 Hz, 1H), 3.32 (m,
1H), 3.27 (m, 2H), 2.21 (br d, J ) 12.3 Hz, 1H), 2.10 (m, 2H),
1.66 (m, 4H), 1.34 (m, 1H). 13C NMR (125 MHz, CDCl3) δ
138.39 (d), 135.10 (d), 116.72 (t), 114.59 (t), 80.49 (d), 73.34
(d), 71.04 (t), 70.59 (t), 69.93 (t), 67.89 (t), 30.38 (t), 29.49 (t),
28.72 (t), 25.20 (t). MS m/e (rel intens) 240 (M+, 8). HRMS
calcd for C14H24O3 (M)+: 240.172545, found: 240.171764. Anal.
Calcd for C14H24O3: C, 69.96; H, 10.07. Found: C, 69.99; H,
9.75.
liquid. Rf ) 0.23 (silica, 40% EtOAc in hexanes). [R]25
)
D
-2.97° (c 1.1, CHCl3). IR (CHCl3) νmax 3614, 3496, 3012, 2946,
2861 cm-1. 1H NMR (500 MHz, CDCl3) δ 5.88 (dddd, J ) 17.2,
10.5, 5.7, 5.7 Hz, 1H), 5.24 (d, J ) 17.2 Hz, 1H), 5.17 (d, J )
10.5 Hz, 1H), 4.01 (br d, J ) 5.7 Hz, 2H), 3.88 (br dd, J )
11.4, 4.4 Hz, 1H), 3.66 (dd, J ) 9.8, 5.0 Hz, 1H), 3.59 (dd, J )
9.8, 5.7 Hz, 1H), 3.52 (m, 1H), 3.31 (ddd, J ) 11.4, 11.4, 3.5
Hz, 1H), 3.22 (ddd, J ) 9.0, 5.7, 5.0 Hz, 1H), 2.74 (d, J ) 2.9
Hz, 1H, OH), 2.09 (br d, J ) 12.5 Hz, 1H), 1.65 (m, 2H), 1.39
(dddd, J ) 12.5, 12.5, 11.0, 5.5 Hz, 1H). 13C NMR (125 MHz,
CDCl3) δ 134.20 (d), 117.63 (t), 79.60 (d), 72.67 (t), 71.98 (t),
69.34 (d), 67.72 (t), 32.09 (t), 25.13 (t). MS m/e (rel intens) 171
([M - 1]+, 32). HRMS calcd for C9H15O3 (M - H)+: 171.102118,
found: 171.101957. Anal. Calcd for C9H16O3: C, 62.77; H, 9.36.
Found: C, 62.75; H, 9.63.
P r ep a r a tion of (2R,3S)-2-Allyloxym eth yl-3-bu t-3′-en yl-
oxytetr a h yd r op yr a n (38b). This compound was prepared
from 10b according to the procedure described above (see
general procedure for O-alkylation). Yield: 99%. Colorless
P r ep a r a t ion of (2R,3S)-2-Allyloxym et h yl-3-p en t -4′-
en yloxytetr a h yd r op yr a n (41). This compound was prepared

4814 J . Org. Chem., Vol. 64, No. 13, 1999
Delgado and Mart´ın
from 40 according to the procedure described above (see
30.13 (t), 29.15 (t), 25.58 (t). MS m/e (rel intens) 212 (M+, 30).
general procedure for O-alkylation). Yield: 69%. Colorless
HRMS calcd for C12H20O3 (M)+: 212.141245, found: 212.140259;
liquid. Rf ) 0.47 (silica, 20% EtOAc in hexanes). [R]25
)
calcd for C6H10O2 (M -
C5H8O)+: 114.068080, found:
114.068200. Anal. Calcd for C12H20O3: C, 67.89; H, 9.50.
Found: C, 67.97; H, 9.62.
D
+49.47° (c 0.5, CHCl3). IR (CHCl3) νmax 3081, 3009, 2865, 1640
cm-1. 1H NMR (500 MHz, CDCl3) δ 5.91 (dddd, J ) 17.3, 10.4,
5.8, 5.8 Hz, 1H), 5.78 (dddd, J ) 17.1, 10.2, 6.7, 6.7 Hz, 1H),
5.25 (d, J ) 17.3 Hz, 1H), 5.15 (d, J ) 10.4 Hz, 1H), 5.00 (d,
J ) 17.1 Hz, 1H), 4.94 (d, J ) 10.2 Hz, 1H), 4.01 (m, 2H), 3.92
(br d, J ) 11.8 Hz, 1H), 3.67 (dd, J ) 10.3, 1.8 Hz, 1H), 3.57
(m, 2H), 3.33 (m, 2H), 3.25 (ddd, J ) 9.3, 5.4, 1.8 Hz, 1H),
3.18 (ddd, J ) 10.0, 9.3, 4.5 Hz, 1H), 2.21 (br d, J ) 12.3 Hz,
1H), 2.09 (m, 2H), 1.62 (m, 4H), 1.31 (m, 1H). 13C NMR (125
MHz, CDCl3) δ 138.26 (d), 134.94 (d), 117.16 (t), 114.78 (t),
80.47 (d), 73.77 (d), 72.56 (t), 69.94 (t), 68.14 (t), 67.91 (t), 30.31
(t), 29.44 (t), 29.25 (t), 25.20 (t). MS m/e (rel intens) 240 (M+,
10), 198 ([M - C3H6]+, 10). HRMS calcd for C14H24O3 (M)+:
240.172545, found: 240.172242; calcd for C11H18O3 (M -
C3H6)+: 198.125595, found: 198.125529. Anal. Calcd for
P r epar ation of (E)-(4aS,14aR)-2,3,4,4a,7,10,11,12,14,14a-
Deca h yd r o-6H-1,5,13-tr ioxa ben zocyclod od ecen e (45). See
general procedure for metathesis. Colorless oil. Rf ) 0.22
(silica, 15% EtOAc in hexanes). [R]25 ) +41.90° (c 1.12,
D
CHCl3). IR (CHCl3) νmax 3009, 2944, 2865, 1602, 1332 cm-1
.
1H NMR (500 MHz, CDCl3) δ 5.61 (ddd, J ) 14.5, 9.4, 5.0 Hz,
1H, CHdCH), 5.28 (ddd, J ) 14.5, 6.4, 6.4 Hz, 1H, CHdCH),
3.94 (br dd, J ) 11.2, 4.5 Hz, 1H), 3.84 (ddd, J ) 9.9, 5.1, 4.4
Hz, 1H), 3.69 (m, 2H), 3.60 (m, 2H), 3.32 (m, 2H), 3.20 (ddd, J
) 9.9, 5.2, 5.2 Hz, 1H), 3.05 (br d, J ) 9.1 Hz, 1H), 2.35 (m,
1H), 2.24 (m, 2H), 2.04 (m, 2H), 1.67 (m, 4H), 1.19 (dddd, J )
1
12.6, 12.6, 11.4, 4.6 Hz, 1H). H NMR (500 MHz, C6D6) δ 5.74
(ddd, J ) 14.5, 9.1, 5.4 Hz, 1H, CHdCH), 5.35 (ddd, J ) 14.5,
6.5, 6.5 Hz, 1H, CHdCH), 3.88 (dd, J ) 9.2, 2.2 Hz, 1H), 3.84
(dd, J ) 11.2, 4.6 Hz, 1H), 3.77 (ddd, J ) 11.0, 9.0, 4.5 Hz,
1H), 3.67 (m, 2H), 3.51 (dd, J ) 9.2, 1.7 Hz, 1H), 3.42 (ddd, J
) 10.5, 6.2, 3.5 Hz, 1H), 3.20 (br d, J ) 9.0 Hz, 1H), 3.15 (m,
2H), 2.29 (m, 1H), 2.23 (m, 1H), 2.04 (m, 3H), 1.55 (m, 3H),
1.28 (br d, J ) 11.8 Hz, 1H), 1.13 (dddd, J ) 12.2, 11.8, 11.0,
4.2 Hz, 1H). 13C NMR (125 MHz, CDCl3) δ 134.25 (d, CHd
CH), 124.14 (d, CHdCH), 80.30 (d), 72.76 (t), 68.60 (d), 68.48
(t), 68.46 (t), 63.85 (t), 33.13 (t), 31.67 (t), 28.24 (t), 28.15 (t),
25.01 (t). 13C NMR (125 MHz, C6D6) δ 134.12 (d, CHdCH),
124.46 (d, CHdCH), 80.78 (d), 72.16 (t), 69.60 (d), 69.40 (t),
67.94 (t), 63.96 (t), 33.45 (t), 32.01 (t), 28.47 (t), 28.42 (t), 25.29
(t). MS m/e (rel intens) 226 (M+, 7). HRMS calcd for C13H22O3
(M)+: 226.156895, found: 226.156994; calcd for C6H10O2 (M
- C5H8O)+: 114.068080, found: 114.068200. Anal. Calcd for
C
14H24O3: C, 69.96; H, 10.07. Found: C, 69.82; H, 10.46.
P r ep a r a t ion of (Z)-(4a S,12a R)-2,3,4,4a ,7,10,12,12a -
Octa h yd r o-6H-1,5,11-tr ioxa ben zocyclod ecen e (42). See
general procedure for metathesis. Colorless oil. Rf ) 0.19
(silica, 15% EtOAc in hexanes). [R]25 ) +114.07° (c 0.7,
D
CHCl3). IR (CHCl3) νmax 3011, 2942, 2865, 1602, 1460 cm-1
.
1H NMR (500 MHz, CDCl3) δ 5.78 (dddd, J ) 11.1, 11.1, 5.0,
2.5 Hz, 1H, CHdCH), 5.66 (dddd, J ) 11.1, 6.0, 2.3, 1.6 Hz,
1H, CHdCH), 4.50 (dddd, J ) 14.3, 3.3, 2.5, 2.3 Hz, 1H), 4.07
(dd, J ) 10.2, 2.9 Hz, 1H), 3.95 (br dd, J ) 11.3, 4.4 Hz, 1H),
3.83 (dd, J ) 14.3, 6.0 Hz, 1H), 3.72 (m, 2H), 3.64 (ddd, J )
11.2, 9.2, 4.2 Hz, 1H), 3.46 (d, J ) 10.2 Hz, 1H), 3.34 (m, 2H),
3.13 (br dd, J ) 9.2, 2.7 Hz, 1H), 2.16 (br dd, J ) 12.1, 3.3 Hz,
1H), 1.74 (m, 3H), 1.34 (dddd, J ) 12.1, 11.2, 10.7, 5.4 Hz,
1H). 13C NMR (125 MHz, CDCl3) δ 134.46 (d, CHdCH), 127.82
(d, CHdCH), 81.06 (d), 70.04 (d), 68.43 (t), 67.06 (t), 66.03 (t),
65.48 (t), 29.25 (t), 28.64 (t), 25.89 (t). MS m/e (rel intens) 198
(M+, 17), 155 ([M - C2H3O]+, 8). HRMS calcd for C11H18O3
(M)+: 198.125595, found: 198.126341; calcd for C6H10O2 (M
- C5H8O)+: 114.068080, found: 114.068200. Anal. Calcd for
C
13H22O3: C, 68.99; H, 9.80. Found: C, 69.09; H, 9.97.
P r epa r a tion of (4aS,15aR)-2,3,4,4a ,6,7,8,11,12,13,15,15a -
d od eca h yd r o-1,5,14-tr ioxa ben zocyclotr id ecen e (46): See
general procedure for metathesis. Colorless oil. Z-isomer
(major): Rf ) 0.55 (silica, 30% EtOAc in hexanes). [R]25
)
D
C
11H18O3: C, 66.64; H, 9.15. Found: C, 66.72; H, 9.23.
+68.08° (c 0.84, CHCl3). IR (CHCl3) νmax 3007, 2943, 2867,
1
P r ep a r a tion of (E)-(4a S,13a R)-2,3,4,4a ,6,7,8,11,13,13a -
1602, 1464, 1371 cm-1. H NMR (500 MHz, CDCl3) δ 5.37 (m,
Deca h yd r o-1,5,12-tr ioxa ben zocyclou n d ecen e (43). See
general procedure for metathesis. Colorless oil. Rf ) 0.21
(silica, 25% EtOAc in hexanes). [R]25D ) -36.90° (c 0.7, CHCl3).
2H, CHdCH), 3.92 (br dd, J ) 11.4, 4.4 Hz, 1H), 3.72 (dd, J )
9.9, 2.5 Hz, 1H), 3.63 (ddd, J ) 10.4, 4.4, 4.4 Hz, 1H), 3.53 (m,
2H), 3.36 (m, 4H), 3.14 (ddd, J ) 9.3, 2.5, 2.5 Hz, 1H), 2.22
(m, 5H), 1.66 (m, 6H), 1.28 (dddd, J ) 12.4, 12.4, 11.2, 5.1 Hz,
1H). 13C NMR (125 MHz, CDCl3) δ 130.45 (d, CHdCH), 129.96
(d, CHdCH), 80.77 (d), 73.69 (d), 70.49 (t), 68.57 (t), 68.31 (t),
66.82 (t), 30.18 (t), 29.84 (t), 28.84 (t), 25.33 (t), 23.52 (t), 23.32
(t). MS m/e (rel intens) 240 (M+, 47), 181 ([M - C3H7O]+, 18).
HRMS calcd for C14H24O3 (M)+: 240.172545, found: 240.173652.
Anal. Calcd for C14H24O3: C, 69.96; H, 10.07. Found: C, 69.87;
H, 10.13. E-isomer (minor, selected data): Rf ) 0.54 (silica,
30% EtOAc in hexanes). 1H NMR (500 MHz, CDCl3) δ 5.46
(ddd, J ) 14.9, 7.1, 6.7 Hz, 1H, CHdCH), 3.08 (ddd, J ) 9.3,
2.3, 2.3 Hz, 1H). 13C NMR (125 MHz, CDCl3) δ 131.81 (d, CHd
CH), 128.74 (d, CHdCH), 81.27 (d), 73.15 (d), 71.44 (t), 70.24
(t), 68.20 (t), 67.82 (t), 31.39 (t), 30.14 (t), 28.91 (t), 28.52 (t),
28.08 (t), 25.52 (t).
IR (CHCl3) νmax 3007, 2945, 2866, 1458 cm-1 1H NMR (500
.
MHz, CDCl3) δ 5.74 (ddd, J ) 15.2, 10.7, 4.6 Hz, 1H, CHd
CH), 5.57 (dddd, J ) 15.2, 10.2, 5.0, 0.9 Hz, 1H, CHdCH),
4.14 (dd, J ) 11.8, 5.0 Hz, 1H), 3.96 (br dd, J ) 10.0, 4.5 Hz,
1H), 3.91 (br dd, J ) 11.2, 4.5 Hz, 1H), 3.73 (dd, J ) 11.5, 2.2
Hz, 1H), 3.68 (dd, J ) 11.5, 1.2 Hz, 1H), 3.45 (dd, J ) 11.8,
10.2 Hz, 1H), 3.28 (m, 2H), 2.99 (ddd, J ) 10.0, 10.0, 2.0 Hz,
1H), 2.90 (br d, J ) 9.2 Hz, 1H), 2.35 (dd, J ) 12.8, 4.6 Hz,
1H), 2.22 (br dd, J ) 12.0, 3.3 Hz, 1H), 1.92 (dddd, J ) 12.8,
10.7, 10.7, 4.0 Hz, 1H), 1.67 (m, 2H), 1.60 (m, 2H), 1.23 (m,
1H). 13C NMR (125 MHz, CDCl3) δ 138.00 (d, CHdCH), 124.60
(d, CHdCH), 80.68 (d), 72.09 (d), 71.15 (t), 67.40 (t), 68.42 (t),
65.21 (t), 33.58 (t), 29.02 (t), 28.77 (t), 24.90 (t). MS m/e (rel
intens) 212 (M+, 74). HRMS calcd for C12H20O3 (M)+:
212.141245, found: 212.141701; calcd for C6H10O2 (M -
C5H8O)+: 114.068080, found: 114.068200. Anal. Calcd for
P r ep a r a tion of (2R,3S)-3-(3′-a llyloxyp r op oxy)-2-(3iv-
a llyloxyp r op oxym eth yl)tetr a h yd r op yr a n (50). Gen er a l
P r oced u r e for Di-O-a lk yla tion w ith Tosyla tes. To a
stirring solution of 2 (0.4 mmol) in dry THF (2 mL) was added
tBuOK (99 mg, 0.88 mmol, 2.2 equiv). After 1 h at room
temperature, the corresponding tosylate (0.88 mmol, 2.2 equiv)
was added via cannula, dissolved in dry THF (2 mL), and the
reaction was heated overnight at 65 °C. Reaction mixture was
allowed to cool to room temperature, and water was added (2
mL). Aqueous layer was extracted with EtOAc (3 × 2 mL),
combined organic layers were dried over MgSO4, and solvent
was removed under reduced pressure. The residue was purified
by flash chromatography. Colorless oil. Rf ) 0.49 (silica, 30%
C
12H20O3: C, 67.89; H, 9.50. Found: C, 67.83; H, 9.59.
P r ep a r a tion of (E)-(4a S,13a R)-2,3,4,4a ,6,9,10,11,13,13a -
Deca h yd r o-1,5,12-tr ioxa ben zocyclou n d ecen e (44). See
general procedure for metathesis. Colorless oil. Rf ) 0.28
(silica, 25% EtOAc in hexanes). [R]25D ) +28.43° (c 1.5, CHCl3).
1
IR (CHCl3) νmax 3007, 2944, 2865, 1457, 1363 cm-1. H NMR
(500 MHz, CDCl3) δ 5.82 (ddd, J ) 15.2, 10.5, 4.5 Hz, 1H, CHd
CH), 5.54 (dddd, J ) 15.2, 10.3, 4.9, 1.0 Hz, 1H, CHdCH),
4.06 (dd, J ) 12.1, 4.9 Hz, 1H), 3.94 (br dd, J ) 10.0, 4.1 Hz,
1H), 3.90 (br dd, J ) 11.2, 4.4 Hz, 1H), 3.51 (m, 4H), 3.26 (ddd,
J ) 11.2, 11.2, 3.0 Hz, 1H), 2.97 (m, 2H), 2.31 (br dd, J ) 12.5,
4.5 Hz, 1H), 2.11 (br dd, J ) 12.6, 3.2 Hz, 1H), 1.92 (dddd, J
) 12.5, 10.6, 10.5, 3.6 Hz, 1H), 1.81 (m, 1H), 1.63 (m, 3H),
1.32 (dddd, J ) 12.6, 12.6, 11.4, 4.7 Hz, 1H). 13C NMR (125
MHz, CDCl3) δ 138.77 (d, CHdCH), 123.93 (d, CHdCH), 80.11
(d), 72.55 (t), 70.15 (d), 70.04 (t), 68.15 (t), 68.10 (t), 33.43 (t),
EtOAc in hexanes). [R]25 ) +49.32° (c 1.35, CHCl3). IR
D
(CHCl3) νmax 3083, 3008, 2866, 1454, 1422 cm-1. 1H NMR (500
MHz, CDCl3) δ 5.86 (m, 2H), 5.22 (m, 2H), 5.12 (m, 2H), 3.92
(m, 5H), 3.70 (m, 2H), 3.53 (m, 2H), 3.47 (m, 5H), 3.39 (ddd, J
) 9.2, 6.3, 6.3 Hz, 1H), 3.30 (m, 1H), 3.21 (ddd, J ) 9.3, 5.5,

Ring-Closing Metathesis
J . Org. Chem., Vol. 64, No. 13, 1999 4815
1.9 Hz, 1H), 3.14 (ddd, J ) 10.5, 9.3, 4.5 Hz, 1H), 2.20 (br dd,
J ) 12.4, 3.0 Hz, 1H), 1.85 (ddddd, J ) 6.5, 6.5, 6.5, 6.5, 1.6
Hz, 2H), 1.78 (dddd, J ) 6.3, 6.3, 6.3, 6.3 Hz, 2H), 1.59 (m,
2H), 1.30 (m, 1H). 13C NMR (125 MHz, CDCl3) δ 135.00 (d),
134.93 (d), 116.75 (t), 116.63 (t), 80.47 (d), 73.86 (d), 71.89 (t),
71.81 (t), 70.82 (t), 68.66 (t), 67.84 (t), 67.42 (t), 67.18 (t), 65.75
(t), 30.45 (t), 29.96 (t), 29.37 (t), 25.16 (t). HRMS (FAB) calcd
for C18H32O5Na (M + Na)+: 351.214744, found: 351.214036.
Anal. Calcd for C18H32O5: C, 65.82; H, 9.82. Found: C, 65.77;
H, 9.98.
(M + H)+: 345.227714, found: 345.225694. Anal. Calcd for
C
18H32O6: C, 62.77; H, 9.36. Found: C, 62.59; H, 9.51.
(2R,3S)-3-Allyloxy-2-(2′′′-{2iv-[2v-(2vi-a llyloxyet h oxy)-
eth oxy]eth oxy}eth oxym eth yl)tetr a h yd r op yr a n (52c): col-
orless oil. Rf ) 0.42 (silica, EtOAc). [R]25 ) +37.85° (c 1.22,
D
CHCl3). IR (CHCl3) νmax 3010, 2869, 1463, 1350 cm-1. 1H NMR
(500 MHz, CDCl3) δ 5.84 (m, 2H), 5.20 (m, 2H), 5.10 (m, 2H),
4.03 (br dd, J ) 12.6, 5.6 Hz, 1H), 3.96 (br d, J ) 5.7 Hz, 2H),
3.88 (m, 2H), 3.69 (dd, J ) 10.6, 1.2 Hz, 1H), 3.61 (m, 15H),
3.54 (m, 2H), 3.28 (m, 1H), 3.20 (m, 2H), 2.17 (br d, J ) 12.5
Hz, 1H), 1.57 (m, 2H), 1.30 (m, 1H). 13C NMR (125 MHz,
CDCl3) δ 135.11 (d), 134.77 (d), 117.04 (t), 116.70 (t), 73.24
(d), 72.21 (d), 71.17 (t), 70.80 (t), 70.61 (t), 70.59 (t), 70.55 (t),
70.44 (t), 69.93 (t), 69.41 (t), 67.79 (t), 29.48 (t), 25.18 (t). HRMS
(FAB) calcd for C18H33O6Na (M + Na)+: 411.2358738, found:
411.236023. Anal. Calcd for C20H36O7: C, 61.83; H, 9.34.
Found: C, 61.79; H, 9.50.
(2R ,3S )-3-(2′-Allyloxye t h oxy)-2-(2iv -a llyloxye t h oxy-
m eth yl)tetr a h yd r op yr a n (51a ): colorless oil. Rf ) 0.45
(silica, 50% EtOAc in hexanes). [R]25 ) +34.75° (c 0.51,
D
CHCl3). IR (CHCl3) νmax 3010, 2868, 2360, 1245, 1216 cm-1
.
1H NMR (500 MHz, CDCl3) δ 5.87 (m, 2H), 5.23 (m, 2H), 5.13
(m, 2H), 3.97 (m, 4H), 3.88 (br d, J ) 11.1 Hz, 1H), 3.72 (m,
2H), 3.65 (m, 3H), 3.57 (m, 2H), 3.51 (m, 3H), 3.26 (m, 3H),
2.19 (br dd, J ) 12.6, 2.8 Hz, 1H), 1.59 (m, 2H), 1.34 (m, 1H).
13C NMR (125 MHz, CDCl3) δ 134.88 (d), 134.79 (d), 116.91
(t), 116.84 (t), 80.41 (d), 74.34 (d), 72.15 (t), 72.13 (t), 71.22
(t), 70.82 (t), 69.72 (t), 69.40 (t), 68.50 (t), 67.80 (t), 29.43 (t),
25.22 (t). MS m/e (rel intens) 301 ([M + 1]+, 6). HRMS calcd
for C16H29O5 (M + H)+: 301.201499, found: 301.201031. Anal.
Calcd for C16H28O5: C, 63.97; H, 9.40. Found: C, 63.58; H,
9.82.
(2R ,3S )-3-Allyloxy-2-{3′′′-[2i v -(3v i -a llyloxyp r op oxy-
m eth yl)a llyloxy]p r op oxym eth yl}tetr a h yd r op yr a n (53):
colorless oil. Rf ) 0.50 (silica, 50% EtOAc in hexanes). [R]25
D
) +41.97° (c 1.35, CHCl3). IR (CHCl3) νmax 3009, 2945, 2865,
1
1647, 1455 cm-1. H NMR (500 MHz, CDCl3) δ 5.88 (m, 2H),
5.24 (m, 2H), 5.14 (m, 4H), 4.06 (br dd, J ) 12.6, 5.6 Hz, 1H),
3.92 (m, 8H), 3.66 (d, J ) 10.4 Hz, 1H), 3.57 (m, 2H), 3.49 (m,
7H), 3.33 (m, 1H), 3.24 (m, 2H), 2.21 (br d, J ) 12.8 Hz, 1H),
1.85 (m, 4H), 1.62 (m, 2H), 1.35 (m, 1H). 13C NMR (125 MHz,
CDCl3) δ 143.09 (s), 135.09 (d), 134.97 (d), 116.78 (t, 2C), 113.43
(t), 80.46 (d), 73.36 (d), 71.88 (t), 71.57 (t), 71.52 (t), 70.74 (t),
69.95 (t), 68.70 (t), 67.87 (t), 67.50 (t), 67.31 (t, 2C), 30.14 (t),
29.94 (t), 29.48 (t), 25.20 (t). MS m/e (rel intens) 398 (M+, 1),
357 ([M - C3H5]+, 2), 339 ([M - C3H7O]+, 7). HRMS calcd for
(2R,3S)-3-[2′-(2′′-Allyloxyeth oxy)eth oxy]-2-[2v-(2vi-a llyl-
oxyeth oxy)eth oxym eth yl]tetr a h yd r op yr a n (51b): color-
less oil. Rf ) 0.46 (silica, EtOAc). [R]25 ) +35.38° (c 0.85,
D
CHCl3). IR (CHCl3) νmax 3084, 3010, 1463, 1244 cm-1. 1H NMR
(500 MHz, CDCl3) δ 5.86 (dddd, J ) 17.2, 10.4, 5.6, 5.6 Hz,
2H), 5.22 (d, J ) 17.2 Hz, 2H), 5.13 (d, J ) 10.4 Hz, 2H), 3.97
(br d, J ) 5.6 Hz, 4H), 3.87 (br d, J ) 11.8 Hz, 1H), 3.72 (m,
2 H), 3.58 (m, 16H), 3.24 (m, 3H), 2.19 (br dd, J ) 12.3, 2.8
Hz, 1H), 1.58 (m, 2H), 1.32 (m, 1H). 13C NMR (125 MHz,
CDCl3) δ 134.84 (d), 134.80 (d), 117.04 (t), 117.03 (t), 74.35
(d), 72.25 (d), 71.24 (t, 2C), 70.89 (t), 70.84 (t), 70.65 (t), 70.60
(t), 70.49 (t), 69.49 (t), 69.47 (t), 68.45 (t), 67.78 (t), 65.84 (t),
29.43 (t), 25.22 (t). HRMS (FAB) calcd for C18H32O7Na (M -
C2H4+Na)+: 383.204573, found: 383.203854. Anal. Calcd for
C20H36O7: C, 61.83; H, 9.34. Found: C, 61.94; H, 9.32.
P r ep a r a tion of (2R,3S)-3-Allyloxy-2-[2′′′-(2iv-a llyloxy-
eth oxy)eth oxym eth yl]tetr a h yd r op yr a n (52a ). Gen er a l
P r oced u r e for O-Alk yla tion w ith Tosyla tes. To a stirring
C
22H38O6 (M)+: 398.266839, found: 398.267199; calcd for
C19H31O5 (M - C3H7O)+: 339.217149, found: 339.217046.
Anal. Calcd for C22H38O6: C, 66.30; H, 9.61. Found: C, 66.28;
H, 9.73.
P r epar ation of (4aS,19aR)-2,3,4,4a,7,8,10,13,16,17,19,19a-
d od eca h yd r o-6H ,15H -1,5,9,14,18-p en t a oxa b en zocyclo-
h ep ta d ecen e (54): E:Z 7:1. See general procedure for me-
tathesis. Colorless oil. IR (CHCl3) νmax 3018, 2945, 2872, 2361,
1603 cm-1. HRMS (FAB) calcd for C16H28O5Na (M + Na)+:
323.183444, found: 323.183291. Anal. Calcd for C16H28O5: C,
63.97; H, 9.40. Found: C, 63.99; H, 9.08. E-isomer (major):
1
Rf ) 0.16 (silica, 30% EtOAc in hexanes). H NMR (500 MHz,
t
CDCl3) δ 5.74 (m, 2H, CHdCH), 3.98 (m, 5H), 3.58 (m, 8H),
3.36 (m, 3H), 3.20 (ddd, J ) 9.3, 5.2, 1.8 Hz, 1H), 3.13 (ddd, J
) 10.5, 9.3, 4.5 Hz, 1H), 2.20 (br dd, J ) 12.3, 3.0 Hz, 1H),
solution of 5a (0.3 mmol) in dry THF (2 mL) was added BuOK
(37 mg, 0.33 mmol, 1.1 equiv). After 1 h at room temperature,
the corresponding tosylate (0.36 mmol, 1.2 equiv) was added
via cannula, dissolved in dry THF (2 mL), and the reaction
was stirred overnight at room temperature. The reaction
mixture was filtered through a Celite pad, and solvent was
removed under reduced pressure. The residue was purified by
flash chromatography. Colorless oil. Rf ) 0.35 (silica, 50%
1
1.77 (m, 4H), 1.60 (m, 2H), 1.28 (m, 1H). H NMR (500 MHz,
C6D6) δ: 5.77 (ddd, J ) 15.5, 5.1, 5.1 Hz, 1H, CHdCH), 5.69
(ddd, J ) 15.5, 5.3, 5.3 Hz, 1H, CHdCH), 4.06 (dd, J ) 13.1,
5.1 Hz, 1H), 3.93 (dd, J ) 13.6, 5.1 Hz, 1H), 3.86 (m, 2H), 3.79
(m, 3H), 3.72 (m, 1H), 3.60 (m, 5H), 3.44 (m, 2H), 3.34 (ddd, J
) 9.2, 4.5, 1.8 Hz, 1H), 3.28 (ddd, J ) 10.3, 9.2, 4.5 Hz, 1H),
3.12 (ddd, J ) 12.1, 12.1, 2.2 Hz, 1H), 2.04 (br d, J ) 10.6 Hz,
1H), 1.87 (m, 4H), 1.46 (m, 1H), 1.24 (m, 2H). 13C NMR (125
MHz, CDCl3) δ 130.60 (d, CHdCH), 129.48 (d, CHdCH), 80.50
(d), 73.61 (d), 71.67 (t), 70.60 (t), 70.38 (t), 68.29 (t), 67.90 (t),
66.67 (t), 66.24 (t), 65.65 (t), 30.49 (t), 30.37 (t), 29.30 (t), 25.11
(t). 13C NMR (125 MHz, C6D6) δ 130.51 (d, CHdCH), 129.71
(d, CHdCH), 81.41 (d), 73.71 (d), 71.73 (t), 70.58 (t), 70.09 (t),
68.17 (t), 67.40 (t), 66.37 (t), 66.07(t), 65.57 (t), 30.95 (t), 30.79
(t), 29.58 (t), 25.38 (t). Z-isomer (minor, selected data): 0.15
(silica, 30% EtOAc in hexanes). 13C NMR (125 MHz, CDCl3) δ
130.27 (d, CHdCH), 129.57 (d, CHdCH), 73.17 (d), 68.14 (t),
68.01 (t), 67.12 (t), 66.98 (t), 66.35 (t), 30.62 (t), 30.17 (t), 29.64
(t), 25.22 (t).
P r epa r a tion of (4aS,17aR)-2,3,4,4a ,6,7,9,12,14,15,17,17a -
d o d e c a h yd r o-1,5,8,13,16-p e n t a oxa b e n zoc y c lo p e n t a -
d ecen e (55): E:Z 4:1. See general procedure for metathesis.
Colorless oil. IR (CHCl3) νmax 3015, 2945, 2872, 2360, 1603,
1456, 1351 cm-1. HRMS (FAB) calcd for C14H24O5Na (M +
Na)+: 295.152144, found: 295.153863. Anal. Calcd for
C14H24O5: C, 61.74; H, 8.88. Found: C, 61.91; H, 8.61. E-isomer
(major): Rf ) 0.35 (silica, EtOAc). 1H NMR (500 MHz, CDCl3)
δ 5.84 (m, J ) 15.7 Hz, 2H, CHdCH), 4.06 (m, 2H), 3.97 (m,
3H), 3.91 (br d, J ) 11.5 Hz, 1H), 3.66 (m, 8H), 3.34 (m, 3H),
3.21 (ddd, J ) 10.4, 9.3, 4.5 Hz, 1H), 2.22 (br dd, J ) 12.3, 3.2
Hz, 1H), 1.61 (m, 2H), 1.32 (m, 1H). 13C NMR (125 MHz,
EtOAc in hexanes). [R]25 ) +39.33° (c 0.68, CHCl3). IR
D
(CHCl3) νmax 3084, 3009, 2868, 1463 cm-1. 1H NMR (500 MHz,
CDCl3) δ 5.86 (m, 2H), 5.22 (m, 2H), 5.11 (m, 2H), 4.05 (br dd,
J ) 12.7, 5.7 Hz, 1H), 3.97 (br d, J ) 5.7 Hz, 2H), 3.90 (m,
2H), 3.71 (dd, J ) 10.6, 1.2 Hz, 1H), 3.62 (m, 7H), 3.54 (m,
2H), 3.30 (m, 1H), 3.23 (m, 2H), 2.16 (br d, J ) 12.4 Hz, 1H),
1.59 (m, 2H), 1.32 (m, 1H). 13C NMR (125 MHz, CDCl3) δ
135.12 (d), 134.79 (d), 117.05 (t), 116.71 (t), 80.47 (d), 73.25
(d), 72.24 (t), 71.18 (t), 70.82 (t), 70.59 (t), 70.50 (t), 69.96 (t),
69.43 (t), 67.81 (t), 29.49 (t), 25.19 (t). HRMS (FAB) calcd for
C
16H28O5Na (M + Na)+: 323.183444, found: 323.182996. Anal.
Calcd for C16H28O5: C, 63.97; H, 9.40. Found: C, 63.70; H,
9.73.
(2R,3S)-3-Allyloxy-2-{2′′′-[2iv-(2v-a llyloxyeth oxy)eth oxy]-
eth oxym eth yl}tetr a h yd r op yr a n (52b): colorless oil. Rf )
0.53 (silica, EtOAc). [R]25 ) +40.86° (c 1.53, CHCl3). IR
D
(CHCl3) νmax 3084, 3010, 2868, 1463, 1265 cm-1. 1H NMR (500
MHz, CDCl3) δ 5.86 (m, 2H), 5.22 (m, 2H), 5.12 (m, 2H), 4.05
(br dd, J ) 12.7, 5.7 Hz, 1H), 3.98 (br d, J ) 5.7 Hz, 2H), 3.90
(m, 2H), 3.71 (dd, J ) 10.5, 1.4 Hz, 1H), 3.62 (m, 11H), 3.56
(m, 2H), 3.30 (m, 1H), 3.23 (m, 2H), 2.18 (br dd, J ) 12.4, 2.5
Hz, 1H), 1.59 (m, 2H), 1.33 (m, 1H). 13C NMR (125 MHz,
CDCl3) δ 135.12 (d), 134.78 (d), 117.07 (t), 116.73 (t), 80.47
(d), 73.26 (d), 72.23 (t), 71.18 (t), 70.81 (t), 70.64 (t, 2C), 70.58
(t), 70.46 (t), 69.95 (t), 69.43 (t), 67.81 (t), 29.49 (t), 25.19 (t).
MS m/e (rel intens) 345 ([M + 1]+, 6). HRMS calcd for C18H33O6

4816 J . Org. Chem., Vol. 64, No. 13, 1999
Delgado and Mart´ın
CDCl3) δ 129.73 (d, 2C, CHdCH), 80.28 (d), 74.14 (d), 70.93
(t), 70.84 (t), 70.37 (t), 70.24 (t), 69.70 (t), 69.42 (t), 67.83 (t),
67.78 (t), 28.99 (t), 25.00 (t). Z-isomer (minor, selected data):
0.34 (silica, EtOAc). 13C NMR (125 MHz, CDCl3) δ 5.72 (m, J
) 11.3 Hz, 2H, CHdCH). 13C NMR (125 MHz, CDCl3) δ 130.68
(d, CHdCH), 128.91 (d, CHdCH), 80.40 (d), 73.35 (d), 71.00
(t), 70.34 (t), 70.34 (t), 69.13 (t), 68.12 (t), 68.00 (t), 66.69 (t),
66.64 (t), 29.11 (t), 25.12 (t).
P r ep a r a tion of (4a S,23a R)-2,3,4,4a ,6,9,11,12,14,15,17,
18,20,21,23,23a-h exadecah ydr o-1,5,10,13,16,19,22-h eptaoxa-
ben zocycloh en eicosen e (59): E:Z 13:1. See general proce-
dure for metathesis. Colorless oil. Rf ) 0.20 (silica, EtOAc).
IR (CHCl3) νmax 3014, 2944, 2870, 2360, 1603, 1452 cm-1
.
HRMS (FAB) calcd for C18H32O7Na (M + Na)+: 383.204573,
found: 383.202856. Anal. Calcd for C18H32O7: C, 59.98; H,
8.95. Found: C, 59.99; H, 8.90. E-isomer (major): 1H NMR
(500 MHz, CDCl3) δ 5.81 (m, 2H, CHdCH), 4.14 (dd, J ) 12.5,
3.6 Hz, 1H), 4.04 (d, J ) 3.5 Hz, 2H), 3.93 (m, 2H), 3.70 (m,
18H), 3.33 (m, 2H), 3.20 (m, 1H), 2.19 (m, 1H), 1.65 (m, 2H),
P r ep a r a tion of (4a S,23a R)-2,3,4,4a ,6,7,9,10,12,15,17,18,
20,21,23,23a -h exa d eca h yd r o-1,5,8,11,16,19,22-h ep t a oxa -
ben zocycloh en eicosen e (56): E:Z 12:1. See general proce-
dure for metathesis. Colorless oil. Rf ) 0.20 (silica, EtOAc).
1
1.29 (m, 1H). H NMR (500 MHz, C6D6) δ 6.01 (ddd, J ) 15.6,
IR (CHCl3) νmax 2945, 2872, 2358, 1600, 1454, 1351 cm-1
.
HRMS (FAB) calcd for C18H32O7Na (M + Na)+: 383.204573,
found: 383.203250. Anal. Calcd for C18H32O7: C, 59.98; H,
8.95. Found: C, 59.95; H, 8.83. E-isomer (major): 1H NMR
(500 MHz, CDCl3) δ 5.81 (m, J ) 15.4 Hz, 2H, CHdCH), 4.01
(m, 4H), 3.90 (br d, J ) 11.9 Hz, 1H), 3.63 (m, 18H), 3.29 (m,
1H), 3.23 (m, 2H), 2.19 (br d, J ) 12.1 Hz, 1H), 1.61 (m, 2H),
1.34 (m, 1H). 13C NMR (125 MHz, CDCl3) δ 129.42 (d, CHd
CH), 129.30 (d, CHdCH), 80.54 (d), 74.11 (d), 71.30 (t), 71.14
(t), 70.83 (t), 70.78 (t), 70.77 (t), 70.69 (t, 2C), 70.65 (t), 69.38
(t), 69.31 (t) 68.76 (t), 67.89 (t), 29.51 (t), 25.27 (t). Z-isomer
(minor, selected data): 1H NMR (500 MHz, CDCl3) δ 5.71 (m,
2H, CHdCH), 4.14 (m, 4H). 13C NMR (125 MHz, CDCl3) δ
129.92 (d, CHdCH), 129.72 (d, CHdCH), 71.21 (t), 70.52 (t),
70.51 (t), 69.51 (t), 69.22 (t), 68.81 (t), 67.95 (t), 66.74 (t), 66.68
(t), 29.58 (t).
P r ep a r a tion of (4a S,17a R)-2,3,4,4a ,6,9,11,12,14,15,17,
17a -d od eca h yd r o-1,5,10,13,16-p en ta oxa ben zocyclop en ta -
d ecen e (57): E:Z 10:3. See general procedure for metathesis.
Colorless oil. Rf ) 0.34 (silica, EtOAc). IR (CHCl3) νmax 3015,
2944, 2360, 1603, cm-1. HRMS (FAB) calcd for C14H24O5Na
(M + Na)+: 295.152144, found: 295.151159. Anal. Calcd for
C14H24O5: C, 61.74; H, 8.88. Found: C, 61.74; H, 8.80. E-isomer
(major): 1H NMR (500 MHz, C6D6) δ 6.22 (m, J ) 15.7 Hz,
1H, CHdCH), 5.69 (ddd, J ) 15.7, 4.4, 4.4 Hz, 1H, CHdCH),
4.24 (br d, J ) 10.2 Hz, 1H), 4.09 (dd, J ) 10.2, 2.8 Hz, 1H),
3.99 (m, 2H), 3.89 (ddd, J ) 10.3, 9.5, 4.5 Hz, 1H), 3.82 (br dd,
J ) 11.3, 4.4 Hz, 1H), 3.66 (dd, J ) 10.1, 1.6 Hz, 1H), 3.54 (m,
7H), 3.40 (m, 2H), 3.28 (br d, J ) 9.5 Hz, 1H), 3.15 (ddd, J )
11.3, 11.3, 2.0 Hz, 1H), 2.11 (br dd, J ) 12.1, 3.4 Hz, 1H), 1.47
(m, 1H), 1.32 (m, 2H). 13C NMR (125 MHz, C6D6) δ 129.73 (d,
CHdCH), 129.06 (d, CHdCH), 81.10 (d), 71.27 (t), 71.25 (t),
71.16 (t), 70.54 (t), 70.39 (t), 70.16 (t), 69.57 (d), 67.71 (t), 66.97
(t), 28.74 (t), 25.32 (t). Z-isomer (minor, selected data): 1H
NMR (500 MHz, C6D6) 5.85 (m, J ) 11.2 Hz, 2H, CHdCH),
4.48 (ddd, J ) 11.8, 6.0, 6.0 Hz, 2H), 4.32 (dd, J ) 12.5, 3.8
Hz, 1H), 3.74 (ddd, J ) 10.7, 9.9, 4.5 Hz, 1H), 3.21 (br d, J )
9.2 Hz, 1H). 13C NMR (125 MHz, C6D6) δ 131.25 (d, CHdCH),
129.39 (d, CHdCH), 81.90 (d), 72.47 (t), 72.19 (d), 70.77 (t),
70.49 (t), 70.45 (t), 68.46 (t), 67.69 (t), 67.04 (t), 66.24 (t), 31.63
(t), 25.83 (t).
P r ep a r a tion of (4a S,20a R)-2,3,4,4a ,6,9,11,12,14,15,17,
18,20,20a -tetr a d eca h yd r o-1,5,10,13,16,19-h exa oxa ben zo-
cycloocta d ecen e (58): E:Z 8.5:1. See general procedure for
metathesis. Colorless oil. Rf ) 0.24 (silica, EtOAc). IR (CHCl3)
νmax 3016, 2945, 2361, 1603, 1456 cm-1. HRMS (FAB) calcd
for C16H28O6Na (M + Na)+: 339.178359, found: 339.176358.
Anal. Calcd for C16H28O6: C, 60.74; H, 8.92. Found: C, 60.74;
H, 9.23. E-isomer (major): 1H NMR (500 MHz, CDCl3) δ 5.87
(ddd, J ) 15.6, 5.8, 5.8 Hz, 1H, CHdCH), 5.77 (ddd, J ) 15.6,
5.0, 5.0 Hz, 1H, CHdCH), 4.14 (ddd, J ) 12.8, 5.8, 1.1 Hz,
1H), 4.08 (ddd, J ) 13.7, 5.0, 1.1 Hz, 1H), 4.01 (ddd, J ) 13.7,
5.0, 1.1 Hz, 1H), 3.91 (m, 2H), 3.72 (m), 3.62 (m) (14H), 3.38
(ddd, J ) 10.7, 9.3, 4.5 Hz, 1H), 3.32 (m, 1H), 3.20 (m, 1H),
2.19 (br dd, J ) 12.2, 3.0 Hz, 1H), 1.62 (m, 2H), 1.29 (m, 1H).
13C NMR (125 MHz, CDCl3) δ 129.72 (d, CHdCH), 129.10 (d,
CHdCH), 80.50 (d), 71.89 (d), 71.29 (t), 71.04 (t), 70.92 (t),
70.82 (t), 70.67 (t), 70.55 (t), 70.32 (t), 69.03 (t), 68.19 (t), 68.01
(t), 29.11 (t), 25.17 (t). Z-isomer (minor, selected data): 1H
NMR (500 MHz, CDCl3) δ 5.70 (ddd, J ) 11.1, 6.1, 6.1 Hz,
1H, CHdCH), 5.64 (ddd, J ) 11.1, 6.3, 6.3 Hz, 1H, CHdCH).
13C NMR (125 MHz, CDCl3) δ 131.33 (d, CHdCH), 128.35 (d,
CHdCH), 80.80 (d), 73.31 (d), 71.66 (t), 71.49 (t), 70.77 (t),
70.73 (t), 68.91 (t), 68.14 (t), 66.75 (t), 66.39 (t), 30.43 (t), 25.47
(t).
5.5, 5.5 Hz, 1H, CHdCH), 5.93 (ddd, J ) 15.6, 5.1, 5.1 Hz,
1H, CHdCH), 4.20 (ddd, J ) 12.8, 5.5, 1.0 Hz, 1H), 4.04 (d, J
) 5.1 Hz, 2H), 3.98 (m, 2H), 3.80 (m, 2H), 3.57 (m, 17H), 3.31
(ddd, J ) 9.2, 3.8, 1.8 Hz, 1H), 3.12 (ddd, J ) 12.6, 12.6, 2.2
Hz, 1H), 2.05 (m, 1H), 1.46 (m, 1H), 1.27 (m, 2H). 13C NMR
(125 MHz, CDCl3) δ 129.43 (d, CHdCH), 129.23 (d, CHdCH),
80.60 (d), 72.57 (d), 71.04 (t), 70.96 (t), 70.93 (t), 70.74 (t, 6C),
69.42 (t), 68.74 (t), 67.99 (t), 29.49 (t), 25.24 (t). 13C NMR (125
MHz, C6D6) δ 129.57 (d, CHdCH), 129.46 (d, CHdCH), 81.51
(d), 72.23 (d), 71.28 (t, 2C), 71.19 (t), 71.06 (t), 71.04 (t), 70.98
(t), 70.92 (t), 70.87 (t), 70.85 (t), 69.67 (t), 68.63 (t), 67.55 (t),
29.82 (t), 25.49 (t). Z-isomer (minor, selected data): 1H NMR
(500 MHz, CDCl3) δ 5.69 (m, 2H, CHdCH). 1H NMR (500 MHz,
C6D6) δ 5.86 (ddd, J ) 11.3, 6.0, 6.0 Hz, 1H, CHdCH), 5.79
(ddd, J ) 11.3, 6.2, 6.2 Hz, 1H, CHdCH), 4.30 (m), 3.25 (ddd,
J ) 9.2, 3.3, 1.8 Hz, 1H). 13C NMR (125 MHz, CDCl3) δ 130.30
(d, CHdCH), 128.87 (d, CHdCH), 80.69 (d), 73.03 (d), 71.33
(t), 70.58 (t), 69.51 (t), 66.72 (t), 65.23 (t), 29.65 (t), 25.31 (t).
13C NMR (125 MHz, C6D6) δ 130.64 (d, CHdCH), 128.77 (d,
CHdCH), 81.67 (d), 73.04 (d), 71.65 (t), 71.40 (t), 71.14 (t),
70.65 (t), 69.81 (t), 67.12 (t), 65.66 (t), 30.23 (t), 25.57 (t).
P r ep a r a tion of (4a S,23a R)-16-m eth ylen e-2,3,4,4a ,6,9,
12,13,16,17,20,21,23,23a -t et r a d eca h yd r o-11H ,15H ,19H -
1,5,10,14,18,22-h exa oxa ben zocycloh en eicosen e (60): E:Z
8:1. See general procedure for metathesis. Colorless oil. Rf )
0.27 (silica, 50% EtOAc in hexanes). IR (CHCl3) νmax 2958,
2928, 2363, 1463, 1262 cm-1. HRMS (FAB) calcd for C20H34O6-
Na (M + Na)+: 393.225309, found: 393.225578. Anal. Calcd
for C20H34O6: C, 64.84; H, 9.25. Found: C, 64.93; H, 9.37.
E-isomer (major): 1H NMR (500 MHz, CDCl3) δ 5.77 (m, J )
15.8 Hz, 2H, CHdCH), 5.13 (s, 1H, CdCH2), 5.12 (s, 1H, Cd
CH2), 4.14 (br d, J ) 11.2 Hz, 1H), 3.94 (m, 8H), 3.62 (m, 2H),
3.51 (m, 8H), 3.33 (m, 2H), 3.21 (ddd, J ) 9.3, 3.0, 3.0 Hz,
1H), 2.20 (br dd, J ) 12.3, 3.0 Hz, 1H), 1.89 (m, 2H), 1.80 (m,
2H), 1.65 (m, 2H), 1.33 (m, 1H). 13C NMR (125 MHz, CDCl3)
δ 143.41 (s, C)CH2), 129.55 (d, CHdCH), 129.25 (d, CHdCH),
113.72 (t, C)CH2), 80.50 (d), 72.99 (d), 71.86 (t), 71.34 (t), 70.73
(t), 70.50 (t), 68.91 (t), 68.58 (t), 68.06 (t), 66.93 (t), 66.84 (t),
66.34 (t), 30.15 (t), 29.98 (t), 29.52 (t), 25.25 (t). Z-isomer
(minor, selected data): 1H NMR (500 MHz, CDCl3) δ 5.69 (m,
2H, CHdCH). 13C NMR (125 MHz, CDCl3) δ 129.87 (d, CHd
CH), 129.39 (d, CHdCH), 114.35 (t), 80.59 (d), 72.99 (t), 71.93
(t), 68.64 (t), 67.84 (t), 67.36 (t), 65.07 (t), 30.14 (t), 29.94 (t),
29.88 (t), 25.34 (t).
Ack n ow led gm en t. MEC (Spain, PB97-1123) and
the Ramo´n Areces Foundation are gratefully acknowl-
edged for funding this work. We should like to thank
Prof. Ernesto Carmona’s group for helpful advice and
Dr. P. Nieto for some special NMR experiments.
Su p p or tin g In for m a tion Ava ila ble: Experimental pro-
cedures and characterization data for 4-triisopropylsilyloxy-
butyraldehyde, 8-triisopropylsilyloxyoctanal, 9-triisopropyls-
1
ilyloxynonanal, and compounds 47, 48a -d , and 49; H NMR
and 13C NMR spectra of new compounds. This material is
available free of charge via the Internet at http://pubs.acs.org.
J O9901438