Metalated epoxides as carbenoids. Competing C-H and C = C insertion in α-alkoxy epoxide systems

Article abstract of DOI:10.1016/j.tet.2003.10.011

In a reinvestigation of the reactivity of carbenoids derived from epoxides, we studied the factors that could influence the chemoselectivity of the carbenoid insertion into vicinal C-H or C = C bond in cyclic α-alkoxy epoxides bearing an alkenyl side chai

Full text of DOI:10.1016/j.tet.2003.10.011

Tetrahedron 59 (2003) 9701–9706
Metalated epoxides as carbenoids. Competing C–H and CvC
insertion in a-alkoxy epoxide systems
a
b
b
Luc Dechoux,a Claude Agami, Eric Doris and Charles Mioskowski
,
,
*
*
a
` ´ ´ ´ ˆ
Laboratoire de Synthese Asymetrique associe au CNRS, Universite Pierre et Marie Curie, UMR 7611, 4, Place Jussieu Bat. F case 47,
75005 Paris, France
Departement de Biologie Joliot-Curie, CEA/Saclay, Service de Marquage Moleculaire et de Chimie Bioorganique, Bat. 547,
91191 Gif sur Yvette Cedex, France
b
´
´
ˆ
Received 2 July 2003; revised 19 September 2003; accepted 1 October 2003
Abstract—In a reinvestigation of the reactivity of carbenoids derived from epoxides, we studied the factors that could influence the
chemoselectivity of the carbenoid insertion into vicinal C–H or CvC bond in cyclic a-alkoxy epoxides bearing an alkenyl side chain. This
reaction gives access to bi- or tricyclic systems, respectively.
q 2003 Elsevier Ltd. All rights reserved.
1. Introduction
The nucleophilic attack of base on the oxirane ring (since
the lithium base can also act as a nucleophile) is a known
route to substituted alcohols2 (Scheme 1, path A). This
reaction usually proceeds through a SN2 type process at the
less hindered carbon atom. The second well known reaction
involving an epoxide and a strong base is b-elimination3
which provides easy access to allylic alcohols4 (Scheme 1,
path B). This reaction, which takes place via syn
Epoxides are versatile intermediates of wide scope and
applicability in synthetic organic chemistry. Their chemical
reactivity is due, in part, to the basicity of the oxygen atom
but also to the ring strain of the three-membered hetero-
cycle. Under the influence of a strong organolithium base,
the oxirane ring may engage in various types of reactions.1
Scheme 1.
Keywords: carbenoids; cycloaddition; cyclopropanes; epoxides; insertion.
*
Corresponding authors. Tel./fax: þ33-1-44-27-26-20; e-mail: dechoux@ccr.jussieu.fr
0040–4020/$ - see front matter q 2003 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2003.10.011

9702
L. Dechoux et al. / Tetrahedron 59 (2003) 9701–9706
Scheme 2.
elimination,5 may afford optically active alcohols when a
chiral base is used on meso substrates.6 The third possibility
that is depicted in Scheme 1 is the direct metallation of the
oxirane ring which produces a carbenoid species7 (path C).
We and others have surveyed the diverse behavior of these
epoxide-derived carbenoids.8 The metalated epoxide can be
trapped by various electrophiles9 (path D), but it may also
undergo b-elimination10 to provide, after hydrolysis, a
ketone (path E). We found that the carbene character of the
key intermediate (resulting from the carbon–oxygen bond
cleavage) depended on the solvent11 (path F). This
intermediate may engage in reactions similar to a carbene.
These include dimerizations,12 C–H insertions,13 [2þ1]
cycloadditions14 (path I). However, it may also rearrange
via a hydride-1,2-shift15 (path G). This leads to the
formation of a ketone. The last example illustrated in
Scheme 1 is the reductive alkylation of the starting
epoxide16 (path H). This reaction takes place by insertion
of the carbene-like species into the carbon–lithium bond of
the base, followed by instantaneous lithium oxide
elimination to afford substituted alkenes.
(Scheme 2, pathway E). In particular, the influence of the
length of the alkene side chain, the size of the carbocycle
and the solvent effect were studied.
2. Results and discussion
Initially, substituted cyclic a-methoxy epoxides were
synthesized according to Scheme 3. The nuclephilic
addition of different alkene-Grignard reagents on cyclo-
alkenone oxides 1 afforded syn a-hydroxy epoxides 2 in
nearly quantitative yield. The syn selectivity of this process
has already been observed and commented on by others.23
Protection of the hydroxyl group of 2 by methyl iodide
furnished the starting ether-epoxides 3. Five and six-
membered ring epoxides were prepared by this route.
The reactivity of these epoxide-derived carbenoids in
substituted cyclic systems is different. Indeed, we demon-
strated that in cyclic a-hydroxy epoxides, an alkyl 1,2-shift
lead to a,b-unsaturated ketones (Scheme 2, path A).17 Also,
we showed that the insertion of the organolithium reagent,
followed by alkoxide elimination, was predominant in
a-alkoxy epoxides (pathway B).18 The latter route produced
allylic alcohols in high yield. An enantioselective version of
this process has recently been developed by Hodgson et al.19
However, in some instances, we observed the formation of
cyclopropanes which arose from the insertion of the
carbenoid into an adjacent C–H bond (path C).20 Finally,
when R1¼alkyl and R2¼vinyl, an intramolecular [2þ1]
cycloaddition afforded a highly strained tricyclic inter-
mediate (path D).21 The facile hydrolysis of this
intermediate under mildly acidic conditions provided a
novel route to spirocyclopropanes.22
Scheme 3.
As already mentioned in the introduction, carbenoids
derived from a-methoxy epoxides can undergo either
[2þ1] cycloadditions (when adjacent to a CvC bond) or
insertion into a neighboring C–H bond. The influence of the
alkene side chain on the product distribution was studied by
reacting epoxy ethers 3 with n-butyllithium in pentane, at
room temperature (see Section 4). Pentane was chosen as
solvent since we demonstrated in a previous investigation
that it was the solvent of choice to minimize insertion of the
carbenoid into the C–Li bond of the base (reductive
alkylation process).20 The results are summarized in Table 1.
Obviously, when the vinyl-substituted five-membered ring
epoxy ether (Table 1, entry a) was reacted under the above
mentioned conditions, the only product that was detected
resulted from the insertion of the carbenoid into the CvC
bond. This product is however, highly unstable and readily
undergoes ring opening by a SE2 type process to cleanly
The objective of this article is to report our investigations on
the factors that govern the chemoselectivity of the carbenoid
intermediate towards insertion into C–H or CvC bonds

L. Dechoux et al. / Tetrahedron 59 (2003) 9701–9706
Table 1. : Examples of reactivity of various cyclic epoxy ether 3
Entry Substrate 3
9703
Product 4
Yielda
a
88b
b
61
c
d
e
,25c
47
37
f
57d
a
Isolated yield.
b
c
d
Yield of rearranged spiro product.
1H NMR spectroscopy yield.
Combined yield.
give a spiro cyclopropane. Surprisingly, the corresponding
six-membered ring substrate (Table 1, entry b) failed to
react in a similar fashion. Rather, a product that results from
SN2 prime attack of the lithium base on the vinylogous
system was obtained.24 The same holds true when the more
basic tert-butyllithium was used giving alkene 4b as a 50:50
mixture of Z and E isomers (entry b). This difference in
reactivity between five- and six-membered ring systems can
be attributed, in part, to the specific conformation of the
latter substrate in which the leaving methoxy group is able
to adopt an axial position. This is favorable to the syn SN2
prime process. When an allyl side chain was introduced on
the starting epoxy ether (entry c), C–H insertion was
predominant. By 1H NMR spectroscopy we detected the two
diastereomers of the cyclopropane ring together with C–Li
insertion products. No product arising from CvC insertion
was observed. The intramolecular C–H insertion is
probably favored due to allylic activation of the C–H
membered ring epoxy ether (entry e). The cyclopropanes
were obtained in each case as single diastereomers. This
result can be ascribed to the geometric constraint of the
tricyclic system that precludes formation of other dia-
stereoisomers. Finally, the last example illustrated in Table 1
is the pentenyl substituted substrate which reacted with the
C–H bond to give the inserted product in 57% yield as a
60:40 mixture of trans and cis isomers (entry f).25 In this
example, the carbenoid is too far from the CvC bond to
react by cycloaddition. Intramolecular C–H insertion was
therefore favored.
It is to be noted that we observed, in most of the examples
studied, the formation of a product that arises from insertion
of butyllithium in the carbenoid species (Scheme 4). This
afforded cyclic allylic alcohols 5a–e after MeOLi
elimination. This reductive alkylation process, which was
1
bond. The yield (determined by H NMR spectroscopy) of
this transformation appears however to be poor (,25%) and
our attempts to isolate the compounds of interest by
chromatography resulted in decomposition of the labile
cyclopropane. The incorporation of a homo-allyl side chain
next to the methoxy group (entry d) permitted [2þ1]
cycloaddition of the carbenoid species with the proximal
CvC bond. The same reactivity was observed with the six-
Scheme 4.

9704
L. Dechoux et al. / Tetrahedron 59 (2003) 9701–9706
originally described by us,18 is also competing with C–H
and CvC insertions.
(m, 1H). 13C NMR (CDCl3): d¼18.1, 30.7, 34.0, 41.4, 64.7,
68.3, 80.3, 118.8, 134.4.
4.2.4. 2-But-3-enyl-5-methyl-2-hydroxy-6-oxa-
bicyclo[3.1.0]hexane (2d).17 (Oil, 81%) 1H NMR
(CDCl3): d¼1.40 (s, 3H), 1.47–1.62 (m, 4H), 1.90–2.01
(m, 2H), 2.12–2.20 (m, 2H), 3.08 (s, 1H), 4.92–5.07 (m,
2H), 5.74–5.96 (m, 1H). 13C NMR (CDCl3): d¼18.1, 27.6,
30.8, 34.1, 35.6, 64.3, 68.4, 80.2, 114.7, 138.6.
3. Conclusion
The chemoselective intramolecular carbenoid insertion into
C–H and CvC bonds in cyclic a-alkoxy epoxides allows
the synthesis of bi- and tri-cyclic systems, respectively. If
the vicinal C–H bond is allylic (as in substrate 3c) or if there
is at least four carbon atoms between the carbenoid and the
double bond, C–H insertion takes place selectively. In other
cases, [2þ1] cycloaddition, leading to tricyclic systems, is
the sole intramolecular reaction.
4.2.5. 2-Hydroxy-5-methyl-2-pent-4-enyl-6-oxa-
1
bicyclo[3.1.0]hexane (2f). (Oil, 95%) H NMR (CDCl3):
d¼1.41 (s, 3H), 1.44–1.61 (m, 5H), 1.68 (m, 1H), 1.95 (m,
2H), 2.06–2.15 (m, 2H), 3.06 (s, 1H), 4.93–5.03 (m, 2H),
5.81 (m, 1H). 13C NMR (CDCl3): d¼19.0, 22.4, 30.7, 33.7,
34.1, 35.7, 64.2, 68.4, 80.2, 114.8, 138.4.
4.3. General procedure for the synthesis of a-methoxy
epoxides 3a–f
4. Experimental
4.1. General
Synthesis of 2-methoxy-5-methyl-2-prop-2-enyl-6-oxa-
bicyclo[3.1.0]hexane (3c). Crude alcohol 2c (0.25 g,
1.62 mmol, 1 equiv.) was taken up in 16 mL THF and
NaH (0.078 g of a 60% suspension in oil, 1.2 equiv.) was
added portionwise. After 5 min., methyl iodide (0.16 mL,
1.6 equiv.) was added dropwise. The mixture was stirred at
room temperature for 3 h. The reaction was then quenched
with H2O and extracted twice with CH2Cl2. The combined
organic layers were dried over MgSO4 and concentrated
under reduced pressure. The crude product was chromato-
graphed on silica (EtOAc/hexane, 5:95) to yield pure 3c (oil,
0.20 g, 73%).
1H and 13C NMR spectra were respectively recorded on a
Bruker ARX 250 spectrometer at 250 and 62.9 MHz;
chemical shifts are reported in ppm from TMS. All reaction
were performed under argon. Column chromatography were
performed on silica gel, 230–400. TLC were run on Merck
Kieselgel 60F254 plates. THF was distilled from sodium/
benzophenone ketyl. Pentane was dried by distillation over
Na.
4.2. General procedure for the synthesis of a-hydroxy
epoxides 2a–f
4.3.1. 2-Methoxy-5-methyl-2-vinyl-6-oxabicyclo[3.1.0]-
1
Synthesis of 2-hydroxy-5-methyl-2-Prop-2-enyl-6-oxa-
bicyclo[3.1.0]hexane (2c). Allylmagnesium bromide
(2 mL of 2.0 M soln/diethyl ether, 1.12 equiv.) was added
dropwise at 08C to a solution of 3-methyl cyclopentenone
oxide (0.200 g, 1.78 mmol, 1 equiv.) in 18 mL of THF. The
mixture was stirred for 30 min at 08C, quenched with
saturated NH4Cl and extracted three times with CH2Cl2.
The combined organic layers were dried over MgSO4 and
concentrated under reduced pressure. The crude product
was used without further purification in the next step (oil,
0.25 g, 91%).
hexane (3a).22 (Oil, 85%). H NMR (CDCl3): d¼1.31 (s,
3H), 1.41–1.70 (m, 3H), 1.85–1.96 (m, 1H), 3.18 (s, 1H),
3.20 (s, 3H), 5.07 (d, J¼17.8 Hz, 1H), 5.16 (d, J¼10.3 Hz
1H), 5.73 (dd, J¼10.3, 17.8 Hz, 1H). 13C NMR (CDCl3):
d¼17.8, 29.6, 30.1, 52.3, 62.6, 63.7, 84.9, 115.7, 138.6.
4.3.2. 2-Methoxy-6-methyl-2-vinyl-7-oxabicyclo[4.1.0]-
1
heptane (3b). (Oil, 79%). H NMR (CDCl3): d¼1.15 (m,
1H), 1.36 (s, 3H), 1.46 (m, 1H), 1.59–1.89 (m, 4H), 3.01 (s,
1H), 3.34 (s, 3H), 5.20 (d, J¼14.8 Hz, 1H), 5.35 (d,
J¼9.1 Hz 1H), 5.82 (dd, J¼14.8, 9.1 Hz, 1H). 13C NMR
(CDCl3): d¼17.8, 24.3, 28.4, 30.2, 51.0, 60.1, 61.7, 76.9,
117.0, 140.2.
4.2.1. 2-Hydroxy-5-methyl-5-vinyl-6-oxa-bicyclo[3.1.0]-
1
hexane (2a). (Oil, 85%). H NMR (CDCl3): d¼1.39 (s,
3H), 1.40 (m, 3H), 1.94 (m, 1H), 3.05 (s, 1H), 5.07 (d,
J¼10.8 Hz, 1H), 5.16 (d, J¼17.6 Hz 1H), 5.73 (dd, J¼10.8,
17.6 Hz, 1H). 13C NMR (CDCl3): d¼17.3, 29.8, 34.2, 63.6,
66.9, 78.5, 113.4, 138.6.
4.3.3. 2-Methoxy-5-methyl-2-prop-2-enyl-6-oxa-
1
bicyclo[3.1.0]hexane (3c). (Oil, 73%). H NMR (CDCl3):
d¼1.34 (s, 3H), 1.62 (m, 2H), 1.90 (m, 2H), 2.25 (m, 2H),
3.05 (s, 1H), 3.28 (s, 3H), 5.02 (m, 2H), 5.77 (m, 1H).
4.2.2. 2-Hydroxy-6-methyl-2-vinyl-7-oxa-bicyclo[4.1.0]-
1
4.3.4. 2-But-3-enyl-2-methoxy-5-methyl-6-oxa-
1
bicyclo[3.1.0]hexane (3d). (Oil, 76%) H NMR (CDCl3):
d¼1.55 (s, 3H), 1.58–1.78 (m, 5H), 2.07 (m, 1H), 2.27 (m,
2H), 3.25 (s, 1H), 3.46 (s, 3H), 5.06–5.21 (m, 2H), 5.96 (m,
1H). 13C NMR (CDCl3): d¼18.0, 27.1, 28.3, 30.0, 32.9,
51.6, 61.8, 65.1, 84.1, 114.5, 138.5.
heptane (2b). (Oil, 64%). H NMR (CDCl3): d¼1.35 (s,
3H), 1.45 (m, 1H), 1.50–1.78 (m, 3H), 1.87–1.95 (m, 2H),
2.91 (s, 1H), 5.20 (d, J¼10.7 Hz, 1H), 5.35 (d, J¼17.7 Hz
1H), 5.95 (dd, J¼10.7, 17.7 Hz, 1H). 13C NMR (CDCl3):
d¼16.7, 24.0, 28.9, 34.4, 62.0, 65.2, 70.7, 114.6, 141.5.
4.2.3. 2-Hydroxy-5-methyl-2-prop-2-enyl-6-oxa-
1
4.3.5. 2-But-3-enyl-2-methoxy-7-oxabicyclo[4.1.0]hep-
tane (3e). (Oil, 70%) 1H NMR (CDCl3): d¼1.05–1.30
(m, 2H), 1.40–1.55 (m, 3H), 1.60–2.15 (m, 5H), 2.93 (d,
bicyclo[3.1.0]hexane (2c). (Oil, 91%). H NMR (CDCl3):
d¼1.56 (s, 3H), 1.57–1.78 (m, 3H), 1.90 (m, 1H), 2.20–
2.35 (m, 2H), 3.03 (s, 1H), 5.04–5.12 (m, 2H), 5.75–5.90

L. Dechoux et al. / Tetrahedron 59 (2003) 9701–9706
9705
J¼4 Hz, 1H), 3.16 (m, 1H), 3.29 (s, 3H), 4.87–5.02 (m,
2H), 5.77 (m, 1H). 13C NMR (CDCl3): d¼16.7, 23.5, 26.8,
29.2, 34.1, 50.2, 53.1, 56.4, 74.4, 114.5, 138.6.
2.22 (m, 1H), 4.84–4.97 (m, 2H), 5.76 (m, 1H). 13C NMR
(CDCl3): d¼14.0, 23.4, 24.5, 26.0, 28.4, 31.2, 32.1, 32.9,
40.1, 85.4, 114.5, 138.2, 138.5, 141.0.
4.3.6. 2-Methoxy-5-methyl-2-pent-4-enyl-6-oxa-
1
bicyclo[3.1.0]hexane (3f). (Oil, 87%) H NMR (CDCl3):
d¼1.39 (s, 3H), 1.41–1.63 (m, 7H), 1.92 (m, 1H), 2.06 (m,
2H), 3.09 (s, 1H), 3.32 (s, 3H), 4.94–5.04 (m, 2H), 5.79 (m,
1H). 13C NMR (CDCl3): d¼18.1, 22.1, 28.4, 30.1, 33.3,
34.1, 51.6, 61.8, 65.3, 84.3, 114.8, 138.4.
4.4.6. 6-Methoxytricyclo[7.1.0.0.3.5]decan-2-ol (4e). (Oil,
1
37%) H NMR (CDCl3): d¼0.23 (m, 2H), 0.80 (ddd, J¼4,
7.2, 11.2 Hz, 1H), 1.23 (m, 2H), 1.58 (m, 1H), 1.61–1.75
(m, 4H), 1.77–1.93 (m, 3H), 3.14 (s, 3H), 3.40 (dt, J¼2.7,
9.2 Hz, 1H), 4.75 (d, J¼9.2 Hz, OH). 13C NMR (CDCl3):
d¼6.5, 13.7, 18.5, 20.7, 25.1, 26.4, 28.7, 32.9, 51.7, 73.8,
91.5. HRMS calcd for C10H15O2 (Mþ2Me) 167.1072;
found 167.1072.
4.4. A typical experimental procedure is given for
products obtained in entry d, Table 1
4.4.7. 6-But-3-enyl-1-butylcyclohex-2-enol (5e). (Oil,
1
Under Ar, at room temperature n-BuLi (0.69 mL of a 1.6 M
solution in hexanes, 2 equiv.) was added dropwise, over a
period of 20 min, to a stirred solution of 2-but-3-enyl-2-
methoxy-5-methyl-6-oxabicyclo[3.1.0]hexane 3d (0.1 g,
0.55 mmol, 1 equiv.) in 11 mL of anhydrous pentane. The
mixture was stirred at room temperature for 5 min. The
reaction was then quenched with H2O, extracted twice with
CH2Cl2, dried over MgSO4, filtered, and evaporated under
reduced pressure. The crude product was chromatographed
over silica (EtOAc/hexane, 2:8) to yield two products (4d:
CvC insertion product and 5d: C–Li insertion product).
46%) H NMR (CDCl3): d¼0.83 (t, J¼6.8 Hz, 3H), 1.21–
1.35 (m, 5H), 1.54–1.71 (m, 4H), 1.89 (m, 1H), 1.95–2.12
(m, 6H), 3.98 (brs, 1H), 4.85–4.97 (m, 2H), 5.74 (m, 1H).
13C NMR (CDCl3): d¼14.1, 17.9, 23.1, 29.5, 29.7, 31.7,
32.1, 32.5, 32.6, 67.1, 114.4, 133.2, 134.7, 138.6. HRMS
calcd for C14H24O (Mþ) 208.1827; found 208.1816.
4.4.8. (cis)-6-But-3-enyl-5-methoxy-2-methyl-
bicyclo[3.1.0]hexan-2-ol (4f). (Oil, 24%) 1H NMR
(CDCl3): d¼0.63 (m, 1H), 1.02 (d, J¼3 Hz, 1H), 1.10 (m,
1H), 1.16 (s, 3H), 1.34 (m, 1H), 1.50–1.61 (m, 2H), 1.84
(dd, J¼8, 12 Hz, 1H), 2.07–2.16 (m, 2H), 2.18 (m, 1H),
3.28 (s, 3H), 4.86–4.99 (m, 2H), 5.76 (m, 1H). 13C NMR
(CDCl3): d¼25.1, 25.8, 27.2, 27.5, 33.9, 37.0, 39.8, 55.8,
73.3, 79.2, 114.7, 138.7.
4.4.1. 7-Hydroxy-7-methyl-spiro[2.4]heptan-4-one (4a).
Phenyllithium in Et2O (0.05 M) was used as base in this
case as recently reported.22 The isolated product in this case
is the rearranged spiro cyclopropane product (oil, 88%). 1H
NMR (CDCl3): d¼0.91 (m, 4H), 1.12 (s, 3H), 1.59 (s, OH),
1.98 (m, 1H), 2.11–2.31 (m, 2H), 2.53 (m, 1H). 13C NMR
(CDCl3): d¼12.5, 17.0, 24.9, 36.0, 36.8, 39.8, 76.4, 218.1.
4.4.9. (trans)-6-But-3-enyl-5-methoxy-2-methyl-
bicyclo[3.1.0]hexan-2-ol (4f0). (Oil, 33%) 1H NMR
(CDCl3): d¼1.20 (s, 3H), 1.23–1.55 (m, 5H), 1.84 (m,
1H), 2.02 (dd, J¼7.8, 12.2 Hz, 1H), 2.18 (m, 2H), 2.32 (m,
1H), 3.30 (s, 3H), 4.97–5.08 (m, 2H), 5.85 (m, 1H). 13C
NMR (CDCl3): d¼23.2, 25.7, 26.0, 28.7, 34.8, 39.8, 39.9,
55.4, 73.5, 79.2, 115.0, 138.7.
4.4.2. 1-Butyl-2-methyl-5-vinylcyclopent-2-enol (5a).
1
(Oil, 10%) H NMR (CDCl3): d¼0.82 (t, J¼6.7 Hz, 3H),
1.23 (s, 3H), 1.35–2.45 (m, 10H), 4.99–5.08 (m, 2H), 6.54
(m, 1H). 13C NMR (CDCl3): d¼13.9, 23.3, 24.5, 25.9, 27.9,
33.1, 39.6, 85.2, 114.7, 131.6, 135.5, 146.0.
Acknowledgements
4.4.3. (Z and E)-6-But-3-enyl-2-methyl-7-oxabicyclo-
[4.1.0]heptane (4b). tert-Butyllithium (0.1 M in THF) was
used as base in this case (oil, 61%). The product that results
from SN2 prime nucleophilic attack was obtained as a
mixture of Z and E diastereomers. 1H NMR (CDCl3):
d¼0.87 (s, 9H), 0.89 (s, 9H), 1.37 (s, 2£3H), 1.40–1.78 (m,
2£3H), 1.94 (m, 2£2H), 2.08 (m, 2£1H), 2.15 (m, 2£1H),
2.27 (m, 2£1H), 3.19 (s, 1H), 3.46 (s, 1H), 5.65 (m, 2£1H).
13C NMR (CDCl3): d¼18.8, 20.3, 23.2, 23.6, 29, 3 (2C),
29.5, 30.0, 30.3, 30.7, 31.3, 31.6, 40.7, 41.7, 57.5 (2C), 64.4
(2C), 129.9, 130.3, 133.7, 133.8.
Dr Jerry J. Harnett is gratefully acknowledged for reviewing
this manuscript.
References
1. Gorzynski-Smith, J. Synthesis 1984, 629–656.
2. Lipshutz, B. H.; Koslowski, J.; Wilhelm, R. S. J. Am. Chem.
Soc. 1982, 104, 2305–2307. Reich, H. J.; Sanders, A. W.;
Fiedler, A. T.; Bevan, M. J. J. Am. Chem. Soc. 2002, 124,
13386–13387.
4.4.4. 5-Methoxy-2-methyl-tricyclo[6.1.0.0.3.4]nonan-2-
1
ol (4d). (Oil, 47%) H NMR (CDCl3): d¼0.73 (m, 2H),
3. Buchenan, J. G.; Sable, H. Z. Selective Organic
Transformation; Thyagarajan, B. S., Ed.; Wiley: New York,
1972; Vol. 2, p 1.
0.90 (s, 3H), 1.05 (m, 1H), 1.33–1.45 (m, 2H), 1.63–1.76
(m, 3H), 1.87 (m, 1H), 2.02 (m, 1H), 2.15 (m, 1H), 3.02 (brs,
1H), 3.16 (s, 3H). 13C NMR (CDCl3): d¼7.9, 22.1, 22.7,
25.4, 29.9, 30.1, 40.8, 46.6, 51.8, 78.5, 95.0. HRMS calcd
for C10H15O2 (Mþ2Me) 167.1072; found 167.1089.
4. Simpkins, N. S.; Cox, P. J. Tetrahedron: Asymmetry 1991, 2,
1–26. O’Brien, P. J. O’Brien. Chem. Soc., Perkin Trans. 1
1998, 1439–1458. Eames, J. Eur. J. Org. Chem. 2002,
393–401.
4.4.5. 3-But-3-enyl-2-butyl-1-methylcyclopent-2-enol
1
5. Mordini, A.; Ben Rayana, E.; Margot, C.; Schlosser, M.
Tetrahedron 1990, 46, 2401–2410.
6. Sodergren, M. J.; Anderson, P. G. J. Am. Chem. Soc. 1998,
(5d). (Oil, 26%) H NMR (CDCl3): d¼0.83 (t, J¼7 Hz,
3H), 1.23 (s, 3H), 1.28–1.39 (m, 4H), 1.75–2.07 (m, 9H),

9706
L. Dechoux et al. / Tetrahedron 59 (2003) 9701–9706
120, 10760–10761. O’Brien, P.; Poumellec, P. J. Chem. Soc.,
16. Doris, E.; Dechoux, L.; Mioskowski, C. Tetrahedron Lett.
1994, 35, 7943–7946.
Perkin Trans. 1 1998, 2435–2441. Hodgson, D. M.; Gibbs,
A. R.; Drew, M. G. B. J. Chem. Soc., Perkin Trans. 1 1999,
3579–3590. Magnus, A.; Bertilsson, S. K.; Anderson, P. G.
Chem. Soc. Rev. 2002, 31, 223–229.
17. Doris, E.; Dechoux, L.; Mioskowski, C. J. Am. Chem. Soc.
1995, 117, 12700–12704.
18. Dechoux, L.; Doris, E.; Mioskowski, C. Chem. Commun.
1996, 549–550. Hodgson, D. M.; Stent, M. A. H.; Wilson,
F. X. Org. Lett. 2001, 3, 3401–3403.
7. Crandall, J. K.; Apparu, M. Org. React. 1983, 345–443.
8. Doris, E.; Dechoux, L.; Mioskowski, C. Synlett 1998,
337–343. Satoh, T. Chem. Rev. 1996, 96, 3303–3325.
Hodgson, D. M.; Gras, E. Synthesis 2002, 1625–1642.
9. Hodgson, D. M.; Norsikian, S. L. M. Org. Lett. 2001, 3,
461–463. Yamauchi, Y.; Katagiri, T.; Uneyama, K. Org. Lett.
2002, 4, 173–176. Capriati, V.; Florio, S.; Luisi, R.;
Salomone, A. Org. Lett. 2002, 4, 2445–2448. Hodgson,
D. M.; Reynolds, N. J.; Coote, S. J. Tetrahedron Lett. 2002, 43,
7895–7897. Hodgson, D. M.; Gras, E. Angew. Chem. Int. Ed.
2002, 41, 2376–2378.
19. Hodgson, D. M.; Maxwell, C. R.; Miles, T. J.; Paruch, E.;
Stent, M. A. H.; Matthews, I. R.; Wilson, F. X.; Witherington,
J. Angew. Chem. Int. Ed. 2002, 41, 4313–4316. Hodgson,
D. M.; Stent, M. A. H.; Stefane, B.; Wilson, F. X. Org. Biomol.
Chem. 2003, 1, 1139–1150.
20. Dechoux, L.; Agami, C.; Doris, E.; Mioskowski, C. J. Org.
Chem. 1999, 64, 9279–9280.
21. Agami, C.; Dechoux, L.; Doris, E.; Mioskowski, C.
Tetrahedron Lett. 1997, 38, 4071–4074.
10. Crandall, J. K.; Chang, L. H. J. Org. Chem. 1967, 32,
435–439.
22. Dechoux, L.; Agami, C.; Doris, E.; Mioskowski, C. Eur. J. Org.
Chem. 2001, 4107–4110.
´
23. Sepulveda, J.; Soriano, C.; Roquet-Jalmar, J.; Mestres, R.;
11. Doris, E.; Mioskowski, C.; Dechoux, L.; Agami, C. J. Org.
Chem. 1998, 63, 3808–3809.
Riego, J. Bull. Chem. Soc. Fr. 1987, 189–192.
12. Loshe, P.; Loner, H.; Acklin, P.; Sternfeld, F.; Pfaltz, A.
Tetrahedron Lett. 1991, 32, 615.
24. For a discussion on the relative a-acidities of cyclopentene-
and cyclohexene-oxides see: Morgan, K. M.; Gronert, S.
J. Org. Chem. 2000, 65, 1461–1466.
13. Hodgson, D. M.; Cameron, I. D. Org. Lett. 2001, 3, 441–444.
14. Crandall, J. K.; Lin, H. L. C. J. Am. Chem. Soc. 1967, 89,
4526–4727.
25. The stereochemical assignment of the two diastereomers 4f
and 4f0 was inferred by NMR spectroscopy (nOe experiments).
15. Apparu, M.; Barrelle, M. Tetrahedron 1978, 34, 1541–1546.