Synthesis of Cycloheptenols from Carbohydrates by Ring-Closing Metathesis

Full text of DOI:10.1021/jo000110o

5416
J . Org. Chem. 2000, 65, 5416-5419
stereocenters and/or protecting groups around the olefinic
Syn th esis of Cycloh ep ten ols fr om
bonds in the course of the ring-closing metathesis.7
For our initial studies we selected D-mannose as
starting material and the readily available derivative 12a
as key intermediate (Scheme 1). Allylmagnesium bromide
addition to this lactol gave the expected diol 2 as a
mixture of isomers [2a (C6R)/2b(C6S): 7/3)] in 85%
chemical yield, that were easily separated by flash
chromatography and independiently transformed. The
formation of major R isomers in the addition of Grignard-
like reagents to carbohydrate derived lactols is well
documented8 and has been used in several synthetic
schemes. From compound 2a , and following standard
protocols, the corresponding diacetylated 3a , dibenzy-
lated 4 and the silylated/acetylated 6, precursors were
easily obtained. Analogously, from compound 2b we
prepared the corresponding diacetylated 3b derivative.
All new molecules showed excellent analytical and spec-
troscopic data, in good agreement with the structures
shown in Scheme 1 (see the Su p p or tin g In for m a tion ).
With these compounds in our hands, we tested the
carbocyclization protocol. After some experimentation,
conditions were found to promote efficient ring-closing
reactions. The RCM of compounds 2-4 and 6, mediated
by benzylidenebis(tricyclohexylphosphine)dichlororuthe-
nium (7) as catalyst (10%), afforded the cycloheptenols
8-13 (Scheme 1) (see the Exp er im en ta l Section ).
Under these conditions, at room temperature and using
methylene chloride (0.02 M) as solvent, the free alcohol
2a gave the carbocycle 8 in a slow (7 days), incomplete,
and low-yielding reaction [45% (70%)].9 Conversely, its
epimer 2b gave the RCM product 9 after 6 h, in 85%
yield. Very interestingly, all the di-O-protected deriva-
Ca r boh yd r a tes by Rin g-Closin g Meta th esis
J ose´ Marco-Contelles* and Elsa de Opazo
Laboratorio de Radicales Libres (CSIC), C/ J uan de la
Cierva 3, 28006 Madrid, Spain
iqoc21@iqog.csic.es
Received J anuary 27, 2000
The metathesis reaction of suitable functionalized
dienes has resulted in an elegant and efficient strategy
for the synthesis of a variety of carbocyclic ring systems.1
In this context, the ring-closing metathesis (RCM) of
chiral, polyfunctionalized 1,ω-dienes, leading to densely
functionalized, enantiomerically pure cyclopentenes or
cyclohexenes, has been reported.2 Despite these efforts,
the ring-closing metathesis (RCM) of chiral, polyoxygen-
ated 1,8-nonadienes leading to polyfunctionalized cyclo-
heptene derivatives has remained unexplored.1f-i This is
surprising in view of the large number of natural
products containing a seven-membered-ring carbocycle
as structural motif3 with remarkable biological activi-
ties.4,5
We now report that a variety of cycloheptenols6 can
be synthesized in enantiomerically pure form, in high
chemical yield and extremely mild conditions, by ring-
closing metathesis of acyclic, chiral polyoxygenated 1,8-
nonadiene precursors derived from carbohydrates. In
addition, these results gave us the opportunity to describe
the critical effects of the absolute configurations at the
(1) Reviews: (a) Grubbs, R. H.; Chang, S. Tetrahedron 1998, 54,
4413. (b) Armstrong, S. K. J . Chem. Soc., Perkin Trans. 1 1998, 371.
(c) Schuster, M.; Blechert, S. Angew. Chem., Int. Ed. Engl. 1997, 36,
2036. (d) Grubbs, R. H.; Miller, S. J .; Fu, G. C. Acc. Chem. Res. 1995,
28, 446. (e) Schmalz, H.-G. Angew. Chem., Int. Ed. Engl. 1995, 34,
1833. For some examples of RCM leading to cycloheptenes, see: (f)
Forbes, M. D. E.; Patton, J . T.; Myers, T. L.; Maynard, H. D.; Smith,
W. D., J r.; Schultz, G. R.; Wagener, K. B. J . Am. Chem. Soc. 1992,
114, 10978. (g) Schneider, M. F.; J unga, H., Blechert, S. Tetrahedron
1995, 51, 13.003. (h) Fu, G. C.; Grubbs, R. H. J . Am. Chem. Soc. 1992,
114, 5426. (i) Maier, M. E.; Langenbacher, D.; Rebein, F. Liebigs Ann.
1995, 1843.
(2) (a) Ovaa, H.; Code´e, J . D. C.; Lastdrager, B.; Overkleeft, H. S.;
van der Marel, G. A.; van Boom, J . H. Tetrahedron Lett. 1998, 39, 7987.
(b) Ziegler, F. E.; Wang, Y. J . Org. Chem. 1998, 63, 7920. (c) Kornienko,
A.; d′Alarcao, M. Tetrahedron: Asymmetry 1999, 10, 827. (d) Sellier,
O.; Van de Weghe, P.; Le Nouen, D.; Strehler, C.; Eustache, J .
Tetrahedron Lett. 1999, 40, 853. (e) Kapferer, P.; Sarabia, F.; Vasella,
A. Helv. Chim. Acta 1999, 82, 645. (f) Ovaa, H.; Code´e, J . D. C.;
Lastdrager, B.; Overkleeft, H. S.; van der Marel, G. A.; van Boom, J .
H. Tetrahedron Lett. 1999, 40, 5063. (g) Hyldtoft, L.; Poulsen C. S.;
Madsen, R. Chem. Commun. 1999, 2101. (h) Sellier, O.; Van de Weghe,
P.; Eustache, J . Tetrahedron Lett. 1999, 40, 5859. (i) Seepersaud, M.;
Al-Abed, Y. Org. Lett. 1999, 1, 1463. (j) Lee, W.-W.; Chang, S.
Tetrahedron: Asymmetry 1999, 10, 4473. (k) Gallos, J . K.; Koftis, T.
V.; Sarli, V. C.; Litinas, K. E. J . Chem. Soc., Perkin Trans. 1 1999,
3075. (l) Callam, C. S.; Lowary, T. L. Org. Lett. 2000, 2, 167.
(3) (a) Molander, G. A. Acc. Chem. Res. 1998, 31, 603. (b) Wender,
P. A.; Husfeld, C. O.; Langkopf, E.; Love, J . A. J . Am. Chem. Soc. 1998,
120, 1940, and ref 3 cited therein. (c) Molander, G. A.; Sono, M.
Tetrahedron Lett. 1998, 54, 9289. (d) Malpass, J . R.; Wallis, A. L.
Tetrahedron 1998, 54, 3631. (e) Pearson, A. J .; Srinivasan, K. J . Org.
Chem. 1992, 57, 3965. (f) Vandewalle, M.; De Clercq, P. Tetrahedron
1985, 41, 1767. (g) Fraga, B. M. Nat. Prod. Rep. 1996, 13, 307.
(4) For the notorious seven-membered group of natural products
known as calystegines, see: Goldmann, A.; Milat, M. L.; Ducrot, P.
H.; Lallemand, J .-Y.; Maille, M.; Lepingle, A.; Charpin, I.; Tepfer, D.
Phytochemistry 1990, 29, 2125.
(5) A variety of synthetic methods have been reported for the
asymmetric synthesis of seven-membered carbocyclic frameworks. For
some leading references, see: (a) Barco, A.; Benetti, S.; De Risi, C.;
Marchetti, P.; Pollini, G. P.; Zanirato, V. Tetrahedron 1999, 55, 5923.
(b) Lautens, M.; Rovis, T. J . Am. Chem. Soc. 1997, 119, 11090. (c)
Yoshizaki, H.; Yoshioka, K.; Sato, Y.; Mori, M. Tetrahedron 1997, 53,
5433. (d) Barluenga, J .; Aznar, F.; Mart´ın, A.; Va´zquez, J . T. J . Am.
Chem. Soc. 1995, 117, 9419. (e) Gokhale, A. S.; Minidis, A. B. E.; Pfaltz,
A. Tetrahedron Lett. 1995, 36, 1831. (f) Enders, D.; Wiedemann, J .;
Bettray, W. Synlett 1995, 369. (g) Trost, B. M.; Organ, M. G. J . Am.
Chem. Soc. 1994, 116, 10320. (h) Faitg, T.; Soulie´, J .; Lallemand, J .-
Y.; Ricard, L. Tetrahedron: Asymmetry 1999, 10, 2165. (i) Soulie´, J .;
Faitg, T.; Betzer, J .-F.; Lallemand, J .-Y. Tetrahedron 1996, 52, 15137.
(j) Boyer, D.; Lallemand, J .-Y. Tetrahedron 1994, 50, 10443. (k) Duclos,
O.; Mondange, M.; Dure´ault, A.; Depezay, J . C. Tetrahedron Lett. 1992,
33, 8061. (l) J ohnson, C. R.; Bis, S. J . J . Org. Chem. 1995, 60, 615,
and for an excellent review on the synthesis of medium-sized rings
via free radicals: (m) Yet, L. Tetrahedron 1999, 55, 9349.
(6) For the synthesis of polyfunctionalized cycloheptanes from sugars
via 1,3-dipolar nitrone cycloaddition, see: Marco-Contelles, J .; de
Opazo, E. Tetrahedron Lett. 1999, 40, 4445.
(7) The role of the absolute configuration of the stereocenters around
the olefinic bonds and the strong effect of the free hydroxyl versus
protected O-groups in the RCM reactions have been observed before:
(a) Hammer, K.; Undheim, K. Tetrahedron 1997, 53, 5925. (b) Efskind,
J .; Romming, C.; Undheim, K. J . Chem. Soc., Perkin Trans. 1 1999,
1677. (c) Hammer, K.; Romming, C.; Undheim, K. Tetrahedron 1998,
54, 10837. (d) Holt, D. J .; Barker, W. D.; J enkins, P. R.; Davies, D. L.;
Garratt, S.; Fawcett, J .; Russell, D. R.; Ghosh, S. Angew. Chem., Int.
Ed. Engl. 1998, 37, 3298.
(8) (a) Buchanan, J . G.; Dunn, A, D.; Edgar, A. R. J . Chem. Soc.,
Perkin Trans. 1 1976, 68. (b) Shing, T. K. M.; Elsley, D. A.; Gillhouley,
J . G. Chem. Commun. 1989, 1280. (c) Carchon, G.; Chre´tien, F.;
Chapleur, Y. Carbohydr. Lett. 1996, 2, 17.
(9) The RCM reaction of precursor 2a using methylene chloride at
reflux gave the same result [45% (70%) after 7 days]. When toluene
was tested as solvent the yield [17% (26%) after 2 days] was worse
and extended decomposition was observed.
10.1021/jo000110o CCC: $19.00 © 2000 American Chemical Society
Published on Web 07/22/2000

Notes
J . Org. Chem., Vol. 65, No. 17, 2000 5417
Sch em e 1a
Sch em e 2a
a
Reagents: (a) AcOH/H2O (for 2a to 14a : 99%; for 2b to
14b: 99%); (b) Ac2O, py, rt (for 14a to 15a : 99%; for 14b to 15b:
99%).
Sch em e 3a
a
Reagents: (a) AcOH/H2O (for 8 to 18: 90%; for 9 to 19: 85%);
(b) Ac2O, py, rt (for 18 to 16: 98%; for 19 to 17: 81%).
a
Reagents: (a) CH2dCHCH2MgBr, THF, 0 °C (85%); (b) Ac2O,
py, rt (for 2a to 3a : 99%; for 2b to 3b: 90%); (c) BnBr, NaH, THF
(for 2a to 4: 99%); (d) (i) ClSitBuMe2, py (65%), (ii) Ac2O, py (99%)
[for 2a via 5 to 6).
these products were also obtained by acid hydrolysis and
acetylation of carbocycles 8 and 9 (Scheme 3), respec-
tively. The effect of the protected hydroxyl functions were
evident again when, in the standard metathesis condi-
tions, fully deprotected poliol precursors 14a and 14b
prooved to be very reluctanct to react and were recovered
unchanged, after one week reaction time.
From the results reported above several conclusions
can be drawn: (a) open chain or conformationally re-
stricted precursors are good substrates for the RCM
reaction; (b) the absolute stereochemistry at the “allyl-
part” of the 1,8-nonandiene precursor has a deep influ-
ence in the course of the RCM reaction; (c) the different
steric crowding around the olefinic bonds probably al-
lowed the first formal [2 + 2] cycloaddition/cycloreversion
tives 3a , 4, and 6, derived from 2a , afforded the carbocy-
clization products 10 (1 h, 95%), 12 (1 h, 90%), and 13
(40 min, 99%), respectively, in fast reactions in very good
chemical yields. In agreement with this and not surpris-
ingly, the diacetate precursor 3b, derived from compound
2b, gave the cycloheptenol derivative 11 in the fastest
reaction time (20 min) and in an equally high chemical
yield (96%).
To test the presumed entropic assistance to the cy-
clization process10 derived from the pre-exinting syn 1,3-
dioxolane ring at C4-C511 in our substrates, compounds
2a and 2b were submitted to acid hydrolysis and acety-
lation to give open-chain precursors 15a and 15b, via
alcohols 14a and 14b, respectively (Scheme 2) (see the
Su p p or t in g In for m a t ion ). To our great satisfaction,
products 15a and 15b, under the same experimental
conditions, afforded the carbocycles 16 (6 h, 90%) and 17
(2 h, 85%) in excellent yields and mild conditions (see
the Exp er im en ta l Section ). For correlation purposes,
(11) The importance of preexisting heterocycles in selected positions
and orientations on acyclic precursors for successful carbocyclization
processes has been demostrated in our laboratory: (a) Marco-Contelles,
J .; Ruiz, P.; Mart´ınez, L.; Mart´ınez-Grau, A. Tetrahedron 1993, 49,
6669. (b) Marco-Contelles, J .; Bernabe´, M.; Ayala, D.; Sa´nchez, B. J .
Org. Chem. 1994, 59, 1234 [for an application of the results reported
in this paper, see: (c) Go´mez, A. M.; Danelo´n, G. O.; Valverde, S.;
Lo´pez, J . C. J . Org. Chem. 1998, 63, 9626; Corrigendum: J . Org. Chem.
1999, 64, 7280]. (d) Marco-Contelles, J .; Pozuelo, C.; J imeno, M. L.;
Mart´ınez, L.; Mart´ınez-Grau, A. J . Org. Chem. 1992, 57, 2625. (e)
Marco-Contelles, J .; Mart´ınez-Grau, A. Chem. Soc. Rev. 1998, 27, 155.
(10) Edwards, S. D.; Lewis, T.; Taylor, R. J . K. Tetrahedron Lett.
1999, 40, 4267.

5418 J . Org. Chem., Vol. 65, No. 17, 2000
Notes
processes1 to take place at the less hindered C8)C9
bond;12 (d) these effects are minimized in protected
(acetylated or benzylated) derivatives, leading to differ-
ently protected cycloheptenols in good yields, in fast
reactions, under mild reaction conditions.
bocycle 9 (65 mg, 85%; flash chromatography, hexane/ethyl
acetate: 75/25): oil; [R]25D -10 (c 0.35, CHCl3); IR (KBr) υ 3400
(OH), 1640 cm-1 1H NMR (CDCl3) δ 5.57-5.45 (m, 2 H), 4.42
;
(br d, J ) 8.7 Hz, 1 H), 4.12 (dd, J ) 8.7 Hz, J ) 8.0 Hz, 1 H),
4.10-4.08 (m, 1 H), 4.04 (dd, J ) 9.5 Hz, J ) 8.0 Hz, 1 H), 2.69
(d, J ) 1.6 Hz, 1 H), 2.64 (d, J ) 1.7 Hz, 1 H), 2.47 (br d, J )
17.6 Hz, 1 H), 2.27-2.15 (m, 1 H), 1.48, 1.37 (s, s, 3 H, 3H); 13
C
The observations found in this work can be rationalized
in terms of the preferred conformations, due to possible
powerful coordination between the -OH at C-6 on the
RudC8 carbene,13 in the transition states for the RCM
reaction, that bring more reactive, closer and paralel the
double bonds to be metathesized, minimizing other
possible unfavorable interactions. Similarly, for the
protected acetyl derivatives (3a , 3b, 6, 15a and 15b) the
oxygen at the carbonyl is expected to effectively and
efficiently to coordinate with the ruthenium carbene
center in six-membered chelate structures promoting fast
RCM reactions. Identical observations have been reported
in other substrates,7 but to the best our knowledge these
critical structure-reactivity relationships have not been
described before in open-chain sugar templates.14
In summary, the results reported here are noteworthy
and constitute one of the best known synthetic alterna-
tives for the preparation of enantiomerically pure, highly
functionalized cycloheptene derivatives, comparing very
well with other methods, in terms of simplicity, efficiency
and chemical yields. These compounds, 8-13, 16-19, can
be considered as molecules (“homo-deoxy-conduritols”)15
with high potential biological and synthetic interest.
Work in this direction is beeing pursued in our laboratory
and will be reported in due course.
NMR (CDCl3) δ 129.9, 124.9, 108.9, 81.1, 80.1, 68.8, 68.5, 34.1,
27.7, 24.9. MS (70 eV) m/z 185 (M+ - 15, 9), 70 (100). Anal. Calcd
for C10H16O4: C, 59.98; H, 8.05. Found: C, 59.82; H, 8.33.
(1R,2R,3S,4R)-1,4-Di-O-acetyl-2,3-O-(1-m eth yleth yliden e)-
cycloh ep t-5-en e-1,2,3,4-tetr ol (10). Following the general
protocol for the RCM reactions compound 3a (92.2 mg, 0.29
mmol) gave carbocycle 10 (79.4 mg, 95%; flash chromatography,
hexane/ethyl acetate: 80/20): oil; [R]25D -58 (c 0.75, CHCl3); IR
1
(KBr) υ 1720 (OCOCH3), 1640 cm-1; H NMR (CDCl3) δ 5.80-
5.74 (m, 1 H), 5.58 (br dt, J ) 12.9 Hz, J ) 3.7 Hz, 1 H), 5.49-
5.41 (m, 2 H), 4.42-4.32 (m, 2 H), 2.71 (ddq, J ) 1.7 Hz, J ) 7.0
Hz, J ) 19.0 Hz, 1 H), 2.35 (br d, J ) 19.0 Hz, 1 H), 2.13 (s, 3
H), 2.12 (s, 3 H), 1.45, 1.35 (s, s, 3 H, 3H); 13C NMR (CDCl3) δ
170.1, 169.9, 127.6, 126.7, 108.9, 77.5, 76.9, 70.7, 69.4, 30.5, 26.5,
24.4, 21.2, 21.1; MS (70 eV) m/z 284 (M+, 1), 43 (100). Anal. Calcd
for C14H20O6: C, 59.14; H, 7.09. Found: C, 59.19; H, 6.85.
(1S,2R,3S,4R)-1,4-Di-O-acetyl-2,3-O-(1-m eth yleth yliden e)-
cycloh ep t-5-en e-1,2,3,4-tetr ol (11). Following the general
protocol for the RCM reactions compound 3b (84.7 mg, 0.26
mmol) gave carbocycle 11 (64.3 mg, 96%; flash chromatography,
hexane/ethyl acetate: 80/20): mp 88-90 °C; [R]25 -52 (c 0.67,
D
CHCl3); IR (KBr) υ 1720 (OCOCH3), 1640 cm-1; 1H NMR (CDCl3)
δ 5.67 (ds, J ) 9.9 Hz, J ) 2.3 Hz, 1 H), 5.56 (dqt, J ) 12.3 Hz,
J ) 3.1 Hz, 1 H), 5.33 (ds, J ) 12.3 Hz, J ) 1.3 Hz, 1 H), 5.23
(ddd, J ) 3.3 Hz, J ) 9.3 Hz, J ) 11.4 Hz, 1 H), 4.32 (dd, J )
6.7 Hz, J ) 9.3 Hz, 1 H), 4.22 (dd, J ) 6.7 Hz, J ) 9.9 Hz, 1 H),
2.47 (ddm, J ) 3.3 Hz, J ) 18.6 Hz, 1 H), 2.25 (ddm, J ) 11.4
Hz, J ) 18.6 Hz, 1 H), 2.10 (s, 3 H), 2.07 (s, 3 H), 1.43 and 1.34
(s, s, 3 H, 3H); 13C NMR (CDCl3) δ 170.0, 169.9, 128.9, 125.4,
109.7, 78.3, 77.4, 70.7, 70.6, 31.6, 27.5, 25.4, 21.2, 21.0; MS (70
eV) m/z 284 (M+, 1), 43 (100). Anal. Calcd for C14H20O6: C, 59.14;
H, 7.09. Found: C, 59.40; H, 7.25.
Exp er im en ta l Section
Gen er a l Meth od s. See ref 11d.
(1R,2R,3S,4R)-1,4-Di-O-ben zyl-2,3-O-(1-m eth yleth yliden e)-
cycloh ep t-5-en e-1,2,3,4-tetr ol (12). Following the general
protocol for the RCM reactions compound 4 (74.6 mg, 0.29 mmol)
gave carbocycle 12 (63 mg, 90%; flash chromatography, hexane/
Gen er a l P r otocol for th e Rin g-Closin g Meta th esis. A
degassed solution of the 1,8-diene precursor, in dry methylene
chloride (0.02 M), under argon, was treated with catalyst 7
(10%). The mixture was stirred at room temperature, until
complete reaction (TLC analysis). The solvent was removed and
the residue submitted to flash chromatography (eluting with
hexane/ethyl acetate mixtures) to isolate the pure cycloheptenols.
(1R,2R,3S,4R)-2,3-O-(1-Met h ylet h ylid en e)cycloh ep t -5-
en e-1,2,3,4-tetr ol (8). Following the general protocol for the
RCM reactions compound 2a (68.6 mg, 0.3 mmol) gave carbocycle
ethyl acetate: 85/15): oil; [R]25 -36 (c 0.58, CHCl3); IR (KBr)
D
υ 3010, 1650 cm-1; 1H NMR (CDCl3) δ 7.34-7.23 (m, 10 H), 5.62
(ddt, J ) 12.2 Hz, J ) 3.7 Hz, J ) 1.9 Hz, 1 H), 5.59 (br d, J )
12.2 Hz, 1 H), 4.69 (d, J ) 12.1 Hz, 1 H), 4.68 (d, J ) 12.2 Hz,
1 H), 4.67-4.65 (m, 1 H), 4.64 (d, J ) 12.1 Hz, 1 H), 4.60 (d, J
) 12.2 Hz, 1 H), 4.43 (t, J ) 7.8 Hz, 1 H), 4.25 (dd, J ) 7.8 Hz,
J ) 1.7 Hz, 1 H), 4.07 (ddd, J ) 6.6 Hz, J ) 3.2 Hz, J ) 1.7 Hz,
1 H), 2.59 (dddt, J ) 1.9 Hz, J ) 3.8 Hz, J ) 6.6 Hz, J ) 17.1
Hz, 1 H), 2.26 (br d, J ) 17.1 Hz, 1 H), 1.50 and 1.36 (s, s, 3 H,
3H); 13C NMR (CDCl3) δ 138.7, 137.5, 129.6, 128.2, 127.7-127.2
(12 C), 108.2, 79.6, 78.5, 75.8, 75.7, 72.2, 71.6, 31.3, 26.5, 24.2;
MS (70 eV) m/z 380 (M+, 1), 91 (100). Anal. Calcd for C24H28O4:
C, 75.76; H, 7.42. Found: C, 75.48; H, 7.22.
8
[27 mg, 45% (70%); flash chromatography hexane/ethyl
acetate: 75/25]: oil; [R]25D -43 (c 0.56, CHCl3); IR (KBr) υ 3400
(OH), 1640 cm-1; H NMR (CDCl3) δ 5.58 (br d, J ) 12.4 Hz, 1
1
H), 5.48 (br d, J ) 12.4 Hz, 1 H), 4.82 (br d, J ) 7.3 Hz, 1 H),
4.22-4.19 (m, 2 H), 4.09 (dd, J ) 9.1 Hz, J ) 7.3 Hz, 1 H), 2.67
(br s, 1 H), 2.65 (br d, J ) 19.0 Hz, 1 H), 2.49 (br s, 1 H), 2.28
(br d, J ) 19.0 Hz, 1 H), 1.54, 1.39 (s, s, 3 H, 3 H); 13C NMR
(CDCl3) δ 130.1, 124.3, 108.3, 81.7, 77.8, 69.4, 67.3, 31.2, 27.3,
24.7; MS (70 eV) m/z 185 (M+-15, 10), 70 (100). Anal. Calcd for
(1R,2R,3S,4R)-1-O-Acet yl-4-ter t-b u t yld im et h ylsilyl-2,3-
O-(1-m eth yleth ylid en e)cycloh ep t-5-en e-1,2,3,4-tetr ol (13).
Following the general protocol for the RCM reactions compound
6 (22.0 mg, 0.049 mmol) gave carbocycle 13 (17.6 mg, 99%; flash
C
10H16O4: C, 59.98; H, 8.05. Found: C, 59.72; H, 7.79.
(1S,2R,3S,4R)-2,3-O-(1-Met h ylet h ylid en e)cycloh ep t -5-
en e-1,2,3,4-tetr ol (9). Following the general protocol for the
RCM reactions compound 2b (85.7 mg, 0.39 mmol) gave car-
chromatography, hexane/ethyl acetate: 85/15): oil; [R]25 -11
D
(c 0.49, CHCl3); IR (KBr) υ 3010, 1640 cm-1; 1H NMR (CDCl3) δ
5.66 (ddd, J ) 7.5 Hz, J ) 3.7 Hz, J ) 1.5 Hz, 1 H), 5.59 (ddd,
J ) 13.1 Hz, J ) 4.6 Hz, J ) 2.0 Hz, 1 H), 5.56 (dt, J ) 13.1 Hz,
J ) 3.7 Hz, 1 H), 4.66 (br t, J ) 5.3 Hz, 1 H), 4.33 (t, J ) 7.6 Hz,
1 H), 4.29 (dd, J ) 8.0 Hz, J ) 1.5 Hz, 1 H), 2.64 (br dd, J ) 7.5
Hz, J ) 19.0 Hz, 1 H), 2.34 (dt, J ) 19.0 Hz, J ) 3.7 Hz, 1 H),
2.09 (s, 3 H), 1.44, 1.33 (s, s, 3 H, 3H), 0.92, 0.10 (s, 9 H; s, 6 H);
13C NMR (CDCl3) δ 170.0, 130.3, 126.7, 108.4, 79.8, 77.5, 70.4,
69.2, 31.2, 26.4, 25.8 (3 C), 24.2, 21.3, 18.2, -4.6, -4.8; MS (70
eV) m/z 356 (M+, 1), 181 (100). Anal. Calcd for C18H32O5Si: C,
60.64; H, 9.05. Found: C, 60.55; H, 9.32.
(12) The RCM reactions are very sensitive to steric hindrance close
to the double bonds to be metathesized: Fu¨rstner, A., Langemann, K.
Synthesis 1997, 792.
(13) Examples of formation of chelates in RCM: (a) Delgado, M.;
Mart´ın, J . D. J . Org. Chem. 1999, 64, 4798. (b) Fu¨rstner, A., Lange-
mann, K. J . Am. Chem. Soc. 1997, 119, 9130. (c) Kirkland, T. A.;
Grubbs, R. H. J . Org. Chem. 1997, 62, 7310. (d) Kingsbury, J . S.,
Harrity, J . P. A.; Bonitatebus, P. J . J r.; Hoveyda, A. H. J . Am. Chem.
Soc. 1999, 121, 791.
(14) See ref 2e for some recent, interesting results, regarding the
influence of the absolute stereochemistry of the different hydroxyl
protecting groups in sugar templates, on the course of RCM reactions.
(15) (a) Balci, M.; Sutbeyaz, Y.; Secen, H. Tetrahedron 1990, 46,
3715. (b) Vogel, P.; Fattori, D.; Gasparini, F.; Le Drian, C. Synlett 1990,
393.
(1R,2R,3S,4R)-1,2,3,4-Tet r a -O-a cet yl-cycloh ep t -5-en e-
1,2,3,4-tetr ol (16). Following the general protocol for the RCM
reactions compound 15a (24.9 mg, 0.069 mmol) gave carbocycle
16 (20.5 mg, 89%; flash chromatography, hexane/ethyl acetate:
70/30): oil; [R]25 + 10 (c 0.46, CHCl3); IR (KBr) υ 1720
D

Notes
J . Org. Chem., Vol. 65, No. 17, 2000 5419
(OCOCH3), 1640 cm-1; H NMR (CDCl3) δ 5.83 (ddd, J ) 10.3
Hz, J ) 4.0 Hz, J ) 2.6 Hz, 1 H), 5.73 (dddd, J ) 12.0 Hz, J )
6.7 Hz, J ) 4.1 Hz, J ) 2.6 Hz, 1 H), 5.55 (d, J ) 1.6 Hz, 1 H),
5.50 (dt, J ) 12.0 Hz, J ) 2.9 Hz, 1 H), 5.03 (dd, J ) 10.3 Hz,
J ) 2.3 Hz, 1 H), 4.86 (ddd, J ) 11.6 Hz, J ) 3.1 Hz, J ) 2.2 Hz,
1 H), 2.82-2.64 (m, 1 H), 2.16 (s, 3 H), 2.15-2.02 (m, 1 H), 2.01
(s, 3 H), 1.96 (s, 3 H), 1.95 (s, 3 H); 13C NMR (CDCl3) δ 169.9,
169.8, 169.7, 169.5, 131.7, 125.5, 72.0, 70.5, 69.4, 68.4, 26.6, 20.9
(2 C), 20.8, 20.6; MS (70 eV) m/z 183 (3), 43 (100). Anal. Calcd
for C15H20O8: C, 54.87; H, 6.14. Found: C, 54.69; H, 6.40.
(1S ,2R ,3S ,4R )-1,2,3,4-Te t r a -O-a ce t ylcycloh e p t -5-e n e -
1,2,3,4-tetr ol (17). Following the general protocol for the RCM
reactions compound 15b (31.4 mg, 0.088 mmol) gave carbocycle
17 (26 mg, 90%; flash chromatography, hexane/ethyl acetate:
70/30): oil; [R]25D -24 (c 0.3, CHCl3); IR (KBr) υ 1720 (OCOCH3),
1 H), 5.36 (dd, J ) 8.6 Hz, J ) 2.7 Hz, 1 H), 5.01 (dt, J ) 7.0 Hz,
J ) 5.4 Hz, 1 H), 2.50 (t, J ) 5.4 Hz, 1 H), 2.10 (s, 3 H), 2.09 (s,
3 H), 2.07 (s, 3 H), 2.03 (s, 3 H); 13C NMR (CDCl3) δ 169.7, 169.6
(2 C), 169.5, 129.9, 127.1, 71.9, 69.6, 69.3, 68.3, 27.8, 20.9, 20.8,
20.7 (2 C); MS (70 eV) m/z 183 (3), 43 (100). Anal. Calcd for
C15H20O8: C, 54.87; H, 6.14. Found: C, 54.80; H, 6.35.
1
Ack n ow led gm en t. E.O. thanks CAM for a pre-
doctoral fellowship.
Su p p or tin g In for m a tion Ava ila ble: Experimental pro-
cedures and characterization data for compounds 2a ,b-6,
14a ,b, 15a ,b, 18, and 19. This material is available free of
charge via the Internet at http:/pubs.acs.org.
1640 cm-1
;
1H NMR (CDCl3) δ 5.74 (dt, J ) 10.6 Hz, J ) 5.9
Hz, 1 H), 5.72-5.65 (m, 2 H), 5.43 (dd, J ) 7.0 Hz, J ) 2.7 Hz,
J O000110O