Ring-opening-ring-closing metathesis of bicyclo[2.2.2]octenes: A novel synthesis of decalins and hydrindanes

Article abstract of DOI:10.1016/S0040-4039(02)00905-X

Bicyclo[2.2.2]octenes containing an olefinic side-chain undergo ring-opening-ring-closing metathesis to give decalins and hydrindanes in reasonable yields.

Full text of DOI:10.1016/S0040-4039(02)00905-X

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 43 (2002) 5357–5359
Ring-opening–ring-closing metathesis of bicyclo[2.2.2]octenes:
a novel synthesis of decalins and hydrindanes
Timothy L. Minger and Andrew J. Phillips*
Department of Chemistry and Biochemistry, University of Colorado, Boulder, CO 80309-0215, USA
Received 12 April 2002; accepted 7 May 2002
Abstract—Bicyclo[2.2.2]octenes containing an olefinic side-chain undergo ring-opening–ring-closing metathesis to give decalins
and hydrindanes in reasonable yields. © 2002 Elsevier Science Ltd. All rights reserved.
In recent years, ring-closing metathesis (RCM) has
garnered widespread interest as a powerful new syn-
thetic method for the synthesis of cyclic olefins from
(Scheme 1), and in this letter we report our preliminary
studies.
1
acyclic diene precursors. This attention has been
Our initial studies focused on substrates readily pre-
underpinned in large part by the efforts of the Grubbs
and Schrock research groups who have pioneered
research into well-defined transition metal alkylidene
complexes for metathesis reactions. These studies have
led to functional group tolerant ruthenium and moly-
bdenum alkylidene catalysts that can effect cyclization
of a diverse range of substrates under mild reaction
conditions.
pared by a two step sequence involving SnCl -mediated
4
Diels–Alder cycloaddition between 1,3-cyclohexadiene
and acrolein to give 1 in 97% yield, followed by addi-
tion of vinylmagnesium bromide which provided a
diastereomeric mixture of allylic alcohols 2 (66%, dr=
8
3
:1, Scheme 2). This mixture of alcohols was also
readily oxidized by the Swern protocol to give enone 3.
At this juncture we were able to examine the reactivity
of substrates 2 and 3 towards Grubbs’ ruthenium
One of the original applications for these catalysts was
9
alkylidenes. Preliminary studies employing carbene 6
the ring-opening metathesis polymerization of strained2
failed to give any of the desired ring-opened–ring-
closed products. Gratifyingly, we quickly discovered
that the heterocyclic carbene-substituted ruthenium
cyclic olefins such as norbornene or cyclooctadiene.
Given the diverse (primarily cycloaddition) methods
available for the synthesis of bridged bicyclic ring sys-
tems, surprisingly scant attention has been paid to the
development of tandem sequences based around an
10
alkylidene 7 mediated the desired transformation to
give cis-hydrindane 4 in 69% yield (Scheme 2, 2“4).
3
OH
initial ring-opening of a strained ring system. Notable
H
OH
H
H
exceptions to this generalization include studies from
the Snapper group on ring-opening reactions of
2-5% cat
n = 0
(
)n
4
5
cyclobutenes and from Blechert on ring-opening reac-
tions of functionalized norbornenes. Hoveyda and
Schrock have also developed asymmetric ring-opening
H
2-5% cat
6
metathesis reactions of norbornenes. As part of syn-
n = 1
thetic studies on terpenoid natural products we have
investigated the tandem ring-opening–ring-closing
metathesis of bicyclo[2.2.2]octenes as a novel entry to
N
N
Mes
Mes
Ph
7
OH
Cl
cat =
H
H
Ru
Cl
functionalized decalin and hydrindane ring systems
PCy3
H
*
0
Corresponding author. Fax: 1-303-4925894; e-mail: andrew.phillips
colorado.edu
Scheme 1. A ring-opening–ring-closing metathesis approach
to decalins and hydrindanes.
@
040-4039/02/$ - see front matter © 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(02)00905-X

5
358
T. L. Minger, A. J. Phillips / Tetrahedron Letters 43 (2002) 5357–5359
OH
O
H
H
H
i
CHO
ii
iii
1
2
3
iv
v
H
H
N
N
O
PCy3
Ru
OH
Mes
Cl
Mes
Cl
Cl
H
H
Ru
Ph
Cl
Ph
4
5
PCy3
PCy3
6
7
Scheme 2. Reagents and conditions: (i) H CꢀCHCHO, SnCl , CH Cl , −78“−30°C, 97%; (ii) H CꢀCHMgBr, THF, −78°C, 3 h,
2
4
2
2
2
6
5%; (iii) (COCl) , DMSO, Et N, CH Cl , −78°C, 41%; (iv) 2% cat. 7, CH Cl , rt, 1.5 h, 93% [69% without initial sparging with
2 3 2 2 2 2
H CꢀCH ]; (v) 5% cat. 7, CH Cl , rt, 3 h, 56%.
2
2
2
2
The major competitive reaction was simple dimeriza-
tion of the starting material to produce material that
was not reactive under the reaction conditions.
A number of other compounds were also suitable sub-
12
strates for the reaction (Table 1). Cyclization proceeds
readily in the presence of 2–5 mol% of catalyst 7 to give
both cis and trans hydrindanes (2“4, 3“5 and entries
1–2) as well as cis and trans decalins (entries 3–6).
Cyclization to give hydrindane ring systems proceeds
readily at room temperature, whereas cyclization to
give decalins required higher temperature—typically
toluene at reflux.
This side reaction could be readily suppressed by initially
sparging the reaction with ethylene, followed by stirring
under nitrogen. This simple modification raised the
yield of 4 to 93%, and was also general in terms of its
11
positive effect on yields for other substrates.
Table 1. Ring-opening–ring-closing metathesis of bicycle[2.2.2]octenes to give hydrindanes and decalins. Catalyst in all cases
is 7

T. L. Minger, A. J. Phillips / Tetrahedron Letters 43 (2002) 5357–5359
5359
In summary, we have demonstrated that ruthenium
alkylidene 7 is a competent catalyst for ring-opening–
ring-closing metathesis of bicyclo[2.2.2]octenes, and this
provides a novel approach to the synthesis of function-
alized decalins and hydrindane ring systems. Further
studies on the generality of this transformation and
applications to natural products synthesis are underway
and will be reported in due course.
6. Asymmetric ring-opening–cross metathesis: La, D. S.;
Sattely, E. S.; Ford, J. G.; Schrock, R. R.; Hoveyda, A.
H. J. Am. Chem. Soc. 2001, 123, 7767 and references
cited therein.
7. Grubbs and co-workers have examined the ring-opening
metathesis polymeriziation of bicyclo[2.2.2]octadienes,
see: Conticello, V. P.; Gin, D. L.; Grubbs, R. H. J. Am.
Chem. Soc. 1992, 114, 9708.
1
8
9
. All new compounds were fully characterized by H and
13
C NMR, HRMS and IR.
Acknowledgements
. Schwab, P.; France, M. B.; Ziller, J. W.; Grubbs, R. H.
Angew. Chem., Int. Ed. Engl. 1995, 34, 2039.
0. Scholl, M.; Ding, S.; Lee, C. W.; Grubbs, R. H. Org.
Lett. 1999, 1, 953.
We thank the University of Colorado for support of
this research.
1
1
1. Representative experimental procedure: Grubbs’ catalyst 7
(
4.8 mg, 2 mol%) was dissolved in CH Cl (2 mL) and
2 2
References
added by syringe to a solution of alcohol 2 (48 mg, 0.29
mmol) in CH Cl (28 mL). Substrate concentration in the
2
2
1
. For two recent reviews, see: (a) Trnka, T. M.; Grubbs, R.
H. Acc. Chem. Res. 2001, 34, 18; (b) F u¨ rstner, A. Angew.
Chem., Int. Ed. Engl. 2000, 39, 3013.
. For the original report describing tandem ring-opening–
ring-closing metathesis on 5,6-bis-allyloxymethyl-bicyclo-
resulting solution was 0.01 M. This solution was then
sparged with ethylene three times over a 30 min period
for ꢀ60 s each time. At 30 min, the remaining ethylene
was purged from the solution with nitrogen and the
reaction was stirred at room temperature under a nitro-
gen atmosphere for 1 h [1.5 h total reaction time]. The
solvent was then removed by rotary evaporation and the
residue was purified by flash chromatography on SiO2
2
[
2.2.1]hept-2-enes, see: Zuercher, W. J.; Hashimoto, M.;
Grubbs, R. H. J. Am. Chem. Soc. 1996, 118, 6634. For
other recent papers involving ring-opening metathesis see
(
a) Kitamura, T.; Mori, M. Org. Lett. 2001, 3, 1161; (b)
Smulik, J. A.; Diver, S. T. Tetrahedron Lett. 2001, 42,
71; (c) Arjona, O.; Cs a´ ky, A. G.; Murcia, M. C.;
Plumet, J., Mula, M. B. J. Organomet. Chem. 2001, 627,
05 and references cited therein.
with hexanes/ethyl acetate (4:1) to give 4 as a colorless oil
1
(
45 mg, 93%). H NMR (CDCl , 500 MHz, major
3
1
diastereoisomer of a 3:1 mixture of diastereoisomers): l
0
2
4
4
.98–1.10 (m, 2H), 1.50–1.63 (m, 2H), 1.81–1.90 (m, 2H),
.46 (ddd, 1H, J=5.5, 11.5, 18.0 Hz), 2.63–2.65 (m, 1H),
.80–4.85 (m, 1H), 4.86 (1H, ddd, J=1.0, 2.5, 10.5 Hz),
.94 (1H, ddd, J=1.5, 3.0, 17.5), 5.64–5.67 (m, 2H), 5.73
1
3
. For overviews, see: Alkene Metathesis in Organic Synthe-
sis; F u¨ rstner, A., Ed.; Springer-Verlag: Berlin, 1998 and
Ivin, K. J. and Mol, J. C. Olefin Metathesis and Metathe-
sis Polymerization; Academic Press: San Diego, 1997.
. (a) Randall, M. L.; Tallarico, J. A.; Snapper, M. L. J.
Am. Chem. Soc. 1995, 117, 9610; (b) Snapper, M. L.;
Tallarico, J. A.; Randall, M. L. J. Am. Chem. Soc. 1997,
13
(
1H, ddd, J=6.5, 10.0, 17.0 Hz); C NMR (CDCl , 125
3
MHz) l 26.7, 28.4, 32.2, 39.8, 41.2, 45.7, 83.4, 112.2,
4
+
1
32.3, 141.6, 144.4; MS/HRMS: calcd for C H O (M )
11 16
164.1201, found 164.1195; IR (thin film): 991.17, 1015.63,
−
1
1
19, 1478; (c) Tallarico, J. A.; Randall, M. L.; Snapper,
2854.36, 2923.67, 3331.37 cm .
M. L. Tetrahedron 1997, 53, 16511; (d) Limanto, J.;
Snapper, M. L. J. Am. Chem. Soc. 2000, 122, 8071.
. Stragies, R.; Blechert, S. Synlett 1998, 169.
12. Substrates were prepared by sequences analogous to that
shown in Scheme 2. The details will be reported in a full
paper.
5