Intermolecular cyclopropanation versus CH insertion in Rh(II)-catalyzed carbenoid reactions

Article abstract of DOI:10.1016/S0040-4020(00)00076-4

The product ratio of intermolecular insertion and cyclopropanation in transition metal-catalyzed diazo decompositions depends strongly upon the metal, its ligands and upon the substituents of the diazo compound. Ethyl diazoacetate (2a) reacts with cyclohexene (1) almost exclusively by cyclopropanation. However, diazomalonate (2d) and methyl 2-diazophenylacetate (2e) in the presence of Rh(II) catalysts exhibit a marked tendency towards allylic CH insertion. With 1,4-cyclohexadiene (6), methyl 2- diazophenylacetate (2e) in the presence of chiral Rh(II) catalysts affords the allylic insertion product 7 in almost quantitative yield and with up to 74% ee. (C) 2000 Elsevier Science Ltd.

Full text of DOI:10.1016/S0040-4020(00)00076-4

TETRAHEDRON
Pergamon
Tetrahedron 56 (2000) 1725–1731
Intermolecular Cyclopropanation versus CH Insertion in
RhII-Catalyzed Carbenoid Reactions
*
Paul Mu¨ller and Sarah Tohill
Department of Organic Chemistry, University of Geneva, 30 Quai Ernest Ansermet, CH-1211 Geneva 4, Switzerland
Received 15 October 1999; accepted 28 January 2000
Abstract—The product ratio of intermolecular insertion and cyclopropanation in transition metal-catalyzed diazo decompositions depends
strongly upon the metal, its ligands and upon the substituents of the diazo compound. Ethyl diazoacetate (2a) reacts with cyclohexene (1)
almost exclusively by cyclopropanation. However, diazomalonate (2d) and methyl 2-diazophenylacetate (2e) in the presence of RhII catalysts
exhibit a marked tendency towards allylic CH insertion. With 1,4-cyclohexadiene (6), methyl 2-diazophenylacetate (2e) in the presence of
chiral RhII catalysts affords the allylic insertion product 7 in almost quantitative yield and with up to 74% ee. ᭧ 2000 Elsevier Science Ltd.
All rights reserved.
Introduction
for example, the product ratio is inverted in function of
the ligand. With caprolactam as ligand the main pathway
is cyclopropanation, but with perfluorobutyrate it is
aromatic substitution.7
The intermolecular addition of metal carbenoids to olefins
or acetylenes affords cyclopropanes or cyclopropenes,
respectively, in high yields and with almost perfect enan-
tioselectivity in selected cases.1 In contrast, until very
recently, efficient and enantioselective carbon hydrogen
bond-insertions of carbenoids were limited to intra-
molecular reactions.2 Intermolecular CH insertions of
carbenes and metal carbenoids have the reputation of
being unselective, resulting usually in mixtures of products3
and are, therefore, considered of no synthetic significance.1,4
In addition to their lack of selectivity, the intermolecular
carbenoid insertions suffer from competing secondary
reactions, such as formation of formal carbene dimers.
Recently, Davies and coworkers5 have shown that the
formation of carbene dimers is characteristic for monosub-
stituted diazo compounds such as ethyl diazoacetate; it does
not occur with carbene precursors carrying two organyl
substituents at the carbenic center, such as 2-diazophenyl-
acetates, diazovinylacetates or diazoacetoacetates. Enantio-
selective intermolecular insertions have been carried out
with methyl 2-diazophenylacetate into CH bonds of
cycloalkanes and cyclic ethers.6
Some time ago, we observed that the cyclopropanation of
cyclohexene (1) with dimethyl diazomalonate (2d) and
PhIˆC(COOMe)2 in the presence of RhII catalysts afforded
mixtures of products derived from intermolecular insertion
and cyclopropanation. The product ratio 3d/4d fluctuated
from 41:59 to 20:80 according to the reaction conditions.8
Subsequently, we found that the product ratio varied in
function of the structure of the diazo compound, the metal
atom of the catalyst, and of its ligands. The present investi-
gation was started with the objective of finding reaction
conditions under which intermolecular CH insertion of
cyclohexene and cyclohexadiene would be the predominant
pathway. Some of our results have been reported in pre-
liminary form since 1998.9
Results and Discussion
We have investigated the ratio for intermolecular insertion
vs. intermolecular cyclopropanation products upon reaction
of cyclohexene (1) with diazoacetate esters 2 by varying the
parameters which are known to influence carbene selec-
tivity.7,10 Reactions were carried out in CH2Cl2 at 25Њ
using 2% of catalyst and 10 equiv. of cyclohexene (1)
(Table 1) (Scheme 1).
The selectivity of metal carbenoids depends upon the metal,
its ligands, and upon the substituents of the carbene, and it
may be controlled by an appropriate selection of para-
meters.1 In RhII-catalyzed intramolecular competition reac-
tions between cyclopropanation and aromatic substitution
The CuI-catalyzed reaction of ethyl diazoacetate (EDA, 2a)
with 1 has been reported in the literature.11 It results essen-
tially in cyclopropanation and no insertion product 4a has
been detected. With [Rh2(OAc)4] as catalyst and EDA (2a)
Keywords: diazo decomposition; CH bond insertion; rhodium catalyst;
asymmetric induction.
* Corresponding author. Fax: ϩ41-22-328-7396;
e-mail: paul.muller@chiorg.unige.ch
0040–4020/00/$ - see front matter ᭧ 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020(00)00076-4

¨
P. Muller, S. Tohill / Tetrahedron 56 (2000) 1725–1731
1726
Table 1. Intermolecular insertion and cyclopropanation of cyclohexene (1) (conditions: syringe pump addition (12 h) of 2 (1.00 mmol) in CH2Cl2 (10.0 mL) to
1 (10.0 equiv.) in CH2Cl2 (5.0 mL) and 2% of catalyst at 25ЊC)
No.
R1
R2
Catalyst
Yield 3ϩ4, (%)
Ratio 3:4
ee of 3 (C2), (%)
Comment
Ref. [11]
2a
2a
2b
2b
2c
2d
2d
2d
2d
2d
2d
2e
2e
2e
2e
2e
2e
2f
H
H
H
H
Et
Et
[Cu(MeO)3PI]a
[Rh2(OAc)4]
[Rh2(OAc)4]
8.5
80
Ͻ5:95
20:80
67:33
33:67
-
–
–
–
–
DBMPb
DBMPb
Me
54c
70c
0
[Rh2(pfb)4]
Me
[Rh2(OAc)2]
COOMe
COOMe
COOMe
COOMe
COOMe
COOMe
Ph
Ph
Ph
Ph
Ph
Me
[Cu(MeO)3PI]a
[Cu(acac)2]
63
57
96
48
86
30
10:90
9:91
–
–
–
–
–
–
–
–
Ref. [11]
Ref. [8]
Ref. [8]
Med
Me
[Rh2(OAc)4]
[Rh2(pfb)4]
[Rh2{(Ϫ)-(S)-ptpa}4]
[Rh2{(R)-(Ϫ)-bnp}4]
[Rh2(OAc)4]
38:62
52:48
24:76
49:51
75:25
83:17
66:34
93:7
Me
Me
Me
Me
Me
Me
Me
Me
24% ee at C(30)
7% ee at C(30)
50c
36c
52c
50c
45c
33c
47
[Rh2(pfb)4]
[Rh2{(5S)-phox}4]
[Rh2{(2S)-mepy}4]
[Rh2{(Ϫ)-(S)-ptpa}4]
[Rh2{(4S)-dosp}4]
[Rh2(OAc)4]
4
dr 57:43, 4% ee at C(30)
dr 37:63; 10% ee at C(30)
dr 53:47; 5% ee at C(30)
dr 52:48; 5% ee at C(30)
45 (S)
53 (S)
75 (R)
–
50:50
80:20
69:31
Ph
4-NO2-Ph
Me
Me
a In neat cyclohexene (1), at reflux.
b DBMPˆ2,6-di-t-butyl-4-methylphenyl.
c In the presence of (2.0 g) of molecular sieves.
d With PhIˆC(COOMe)2 as carbene precursor.
Scheme 1.
the ratio of insertion/cyclopropanation is 20:80. Increasing
the steric bulk in the alcohol moiety of the diazoester
produces a significant increase in allylic substitution. Thus
with RˆDBMP (2,6-di-t-butyl-4-methylphenyl diazo-
acetate, (2b)) allylic insertion becomes predominant with
a 67:33 ratio of 3b/4b. A ratio 86:14 for the same reaction
and 66:34 for that of 2b with cyclopentene has been reported
by Doyle and coworkers.12 Upon changing the catalyst from
[Rh2(OAc)4] to [Rh2(pfb)4]13 (pfbˆperfluorobutyrate), the
ratio changed unexpectedly10 to 33:67. The reaction of

¨
P. Muller, S. Tohill / Tetrahedron 56 (2000) 1725–1731
1727
methyl 2-diazopropionate (2c)14 afforded neither insertion
nor cyclopropanation products, presumably owing to
competing 1,2-hydrogen migration of the intermediate
metallocarbene. Dimethyl diazomalonate (2d)15, in turn,
gave a ca. 10:90 ratio in favour of cyclopropanation in the
presence of Cu(I)-catalysts. The ratio changed to 32:68 with
[Rh2(OAc)4]8 and 52:48 with [Rh2(pfb)4]. The chiral RhII-
catalysts, [Rh2{(Ϫ)-ptpa}4]16 and [Rh2{(Ϫ)-bnp}4]17 had
only a limited effect on the chemoselectivity of the reaction,
and the enantioselectivity of the insertion was modest with
2d (Scheme 1).
important. The trend to a higher amount of insertion upon
going from CuI to RhII catalysts has been observed
frequently in carbenoid reactions.1,7 Insertion is particularly
predominant when the RhII carries electron-withdrawing
ligands,25 and this is also reproduced in the present investi-
gation, except in the case of 2b. The preference for insertion
observed with some of the chiral RhII catalysts, in turn, can
not be rationalized safely at present, and may be due to a
combination of steric and electronic effects.
Cyclohexa-1,4-diene (6) is known to react with ethyl
diazoacetate (2a) or diethyl diazomalonate (2c) in the
presence of copper powder or [CuCl], respectively, via
cyclopropanation.26 The presence of a second double bond
in 6 was expected to enhance the reactivity of the allylic
position, and have only a minor effect on the reactivity of
the double bonds. However, reaction of 6 with 2a in the
presence of [Rh2(OAc)4] at 25Њ afforded exclusively the
cyclopropane 8a. Ethyl 2-diazopropionate (2c), in turn,
reacted by insertion at the allylic position to afford 7c in
82% yield. The insertion product underwent dehydro-
genation upon standing, and was characterized as 2-methyl
2-phenylpropionate 9c, the methyl ester of hydratropic acid.
If equimolar ratios of 6 and 2c were used, no products of
cyclopropanation nor insertion were formed, presumably
owing to competing 1,2-hydrogen migration of the metal
carbenoid, as suggested for the reaction of 2c with 1. Effec-
tive RhII-catalyzed intramolecular carbenoid additions of
2-diazopropionates to olefins27 and intermolecular cyclo-
propenations of acetylenes28 have been reported, however.
Diazomalonate (2d) exhibited partial selectivity and yielded
a 66:34 ratio of insertion:cyclopropanation products. As
above, the insertion product 3d was isolated after aromati-
zation to dimethyl 2-phenylmalonate (9d). The most
striking results were again obtained with methyl 2-diazo-
phenylacetate (2e). Its decomposition in the presence of 6
(10 equiv.) and [Rh2(OAc)4] afforded the insertion product
7e in 95% yield. The cyclopropane 8e could not be detected
in the reaction mixture. The yield of 7e dropped only
slightly to 70% when equimolar ratios of 2e and 6 were
used (Scheme 2) (Table 2).
The highest chemoselectivity was observed with methyl
2-diazophenylacetate (2e)18 which afforded a ratio of
75:25 with [Rh2(OAc)4]. The introduction of a p-nitro
substituent into the phenyl ring (2f)19 had only a minor
effect on the product ratio. The insertion product 3e was
isolated as a mixture of 2 diasteromers in a 62:38 ratio.
The configuration of the cyclopropane 4e was assigned on
the grounds of the analogy with the general trend observed
in olefin cyclopropanations with 2e. The major cyclo-
propane isomer has the carboxylate group trans with respect
to the substituents of the olefin, which, in the case of cyclo-
hexene as substrate, corresponds to the carboxylate having
exo-configuration.20 Four chiral RhII catalysts were exam-
ined with respect to chemoselectivity with very variable
results. [Rh2{2S)-mepy}4]21 afforded a very high 93:7
ratio in favour of insertion, but the ratio with the sterically
crowded [Rh2{5R)-phox}4]22 was only 66:34, below that
found for [Rh2(OAc)4]. The proline derived [Rh2{(4S)-
dosp}4],23 in turn, produced a ratio of 80:20. The catalyst
of Ikegami, [Rh2{(Ϫ)-(S)-ptpa}4]16 was less efficient and led
to a product ratio of 50:50.
The diastereomer ratio of 4e (dr) was determined by GC
(methylsilicone column). Catalytic hydrogenation of 4e
afforded 5e, from which the enantiomeric excess at the
carbenic center (C(2)) was obtained by GC. By far the
highest ee (75%) was observed with [Rh2{(4S)-dosp}4].
The absolute configuration at C(2) of the major enantiomer
of 5e resulting from reaction with [Rh2(4S)-dosp}4] was
determined to be R by comparison of the optical rotation
of the product ([a]2D0ˆϪ27, cˆ0.50, CHCl3 for 75% ee)
with that reported in the literature for the R-enantiomer
([a]D25ˆϪ38.8 (cˆ20.0, CHCl3).6,24 The absolute configu-
ration of 5e resulting from the other reactions was assigned
on the grounds of the GC retention times (SUPELCO b-dex
120 column). The asymmetric induction at the allylic
position of the cyclohexene, C(30) in 3e, was calculated
from the enantiomer distribution, the ee at C(2) and the
diastereomer ratio. It was in the range of 4–10%. The abso-
lute configuration at the cyclohexene ring of 3e was not
determined.
The structure of the insertion products 7 was deduced from
their chemical behavior and from the NMR data. Thermal
aromatization of cyclohexa-1,4-dienes is a cis-stereo-
specific, symmetry-allowed process, while that of cyclo-
hexa-1,3-dienes occurs step-wise and requires higher
temperatures.29 The olefinic protons of 7c and d resonate
in the range of 5.55–5.88 ppm, in good agreement with
those of simple substituted cyclohexa-1,4-dienes.30 In the
case of 7e one of the olefinic protons occurs at slightly
higher field (5.19–5.22) and the others between 5.63 and
5.88 ppm. Similar shifts have been reported for insertion
products obtained from p-substituted phenyl diazoacetates
into cyclohexa-1,4-dienes.31 In contrast, the resonance lines
of the olefinic protons of substituted conjugated cyclohexa-
1,3-dienes are found in the range of 5.68–5.77 and 5.90–
6.00 ppm.31
The observed trends for the competition between inter-
molecular insertion and cyclopropanation appear to be
largely due to a steric effect, as evidenced by the strong
preference for insertion observed with 1b. The disubstituted
diazo compounds exhibit a stronger selectivity in favour of
insertion than their monosubstituted analogues, and the
presence of an electron-donating group (Ph) in the diazo-
acetate ester is more efficient than an electron acceptor
(COOR). This indicates that electronic effects are also
The asymmetric induction was investigated with RhII-
carboxamidate and carboxylate catalysts. The enantiomer
composition of the insertion product 7e of methyl 2-diazo-
phenylacetate 2e with 6 could not be determined directly,

¨
P. Muller, S. Tohill / Tetrahedron 56 (2000) 1725–1731
1728
Scheme 2.
Table 2. Intermolecular CH insertion of diazoesters 2 with cyclohexa-1,4-diene (6) (conditions as for Table 1)
2
R1
R2
Catalyst
Yield (%)
7:8
ee of 7 (%)
Comment
Ref. [26]
2a
2a
2c
2c
2d
2d0
2e
2e
2e
2e
2e
2e
2e
2e
2e
H
H
Et
Et
Et
Et
Me
Et
Me
Me
Me
Me
Me
Me
Me
Me
Me
Cu
48
90
82
0a
Ͻ5:95
Ͻ2:98
Ͼ98:2
[Rh2(OAc)4]
[Rh2(OAc)4]
[Rh2(OAc)4]
[Rh2(OAc)4]
CuCl
[Rh2(OAc)4]
[Rh2(OAc)4]
[Rh2{(2S)-mepy}4]
[Rh2{(Ϫ)-(S)-ptpa}4]
[Rh2{(4S)-dosp}4]
[Rh2{(4S)-dosp}4]
[Rh2{(4S)-dosp}4]
[Rh2{(4S)-tbsp}4]
[Rh2{(4S)-tbsp}4]
Me
Me
COOMe
COOEt
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
63
28
95
70a
98
98
98
50b
37c
98
86c
66:34
Ͻ5:95
Ͼ98:2
Ͼ98:2
Ͼ98:2
Ͼ98:2
Ͼ98:2
Ͼ98:2
Ͼ98:2
Ͼ98:2
Ͼ98:2
Ref. [26]
4
40 (S)
65 (R)
71 (R)
72 (R)
74 (R)
33 (R)
a 1 equiv. of 6.
b In pentane, 25ЊC.
c In CF3C6H5.
owing to its spontaneous aromatization to 9e upon standing.
The compound was therefore subjected to catalytic hydro-
genation and afforded the known cyclohexane derivative 5e6
from which ee and absolute configuration were obtained.
[Rh2{(4S)-dosp}4] produced 7e in practically quantitative
yield and with 65% ee in CH2Cl2. The ee increased to
71% and 72% in pentane and trifluorotoluene, respectively,
but the yields in these latter solvents were significantly
lower. The highest ee (74%) resulted from reaction with
[Rh2{(4S)-tbsp}4]. The Rh carboxylate catalyst of Ikegami,
and [Rh2{2S)-mepy}4] were less satisfactory with
respect to enantioselectivity, however. In all cases, the
absolute configuration of the insertion product 7e was
identical to that at C(2) of 3 when the same catalyst was
used.
cyclohexene, and react almost exclusively via insertion with
1,4-cyclohexadiene. These carbenes are less prone to
undergo dimer formation, and high yields of insertion
products may result even when a 1:1 ratio of substrate and
diazo compound is used. These results open new perspec-
tives for enantioselective CC-bond formation via intermo-
lecular carbenoid insertions.
The synthetic potential of intermolecular CH insertions of
metal carbenoids has been recognized by other researchers.
Davies32and Winkler33 reported the intermolecular insertion
of methyl 2-diazophenylacetate into N-BOC protected
cyclic amines as a key step in the asymmetric synthesis of
methylphenidate (Ritaline). While this manuscript was in
preparation, Davies also published efficient and highly
enantioselective CH insertions into the allylic positions of
cyclohexa-1,3- and 1,4-dienes and the former reaction
was exploited for a formal synthesis of (ϩ)-sertraline.31
Enantioselective intermolecular CH insertions were also
reported between allyl silyl ethers and methyl aryldiazo-
acetates.34
The present results show clearly that intermolecular car-
benoid insertions into CH bonds may be effected with
RhII-catalysts in acceptable yields. Carbenes carrying two
substituents at the carbenic center exhibit marked
preference for insertion rather than cyclopropanation with

¨
P. Muller, S. Tohill / Tetrahedron 56 (2000) 1725–1731
1729
Experimental
29.2 (d); 31.1 (d); 35.2 (q); 42.0 (t); 127.0 (d); 128.2 (d);
130.4 (d); 134.3 (d); 172.6 (s).
General
Dimethyl (cyclohexen-3-yl)malonate (3d).7a,11 IR
(CHCl3): 1735s. H NMR (400 MHz, CDCl3): 1.19–1.21
1
See Refs. 22 and 35.
(m, 1H); 1.37–1.41 (m, 1H); 1.43–1.53 (m, 2H); 1.63–
1.82 (mi, 2H); 2.71–2.74 (m, 1H); 3.13 (d, Jˆ8 Hz, 1H);
3.57 (s, 6H); 5.34–5.37 (m, 1H); 5.57–5.61 (m, 1H). 13C
NMR (100 MHz): 20.5 (t); 24.5 (t); 26.2 (t); 35.0 (d); 51.8
(d); 56.3 (q); 127.0 (d); 129.1 (d); 168.28 (s); 168.33 (s).
MS: 212 (Mϩ, 10), 81 (64).
Diazoacetates: Ethyl diazoacetate (2a), commercially avail-
able, was distilled before use. 2,6-Di-t-butyl-4-methyl-
phenyl diazoacetate (2b) was prepared according to Doyle
et al. 12 Methyl 2-diazopropionate (2c) was synthesized via
diazo transfer14 and dimethyl 2-diazomalonate (2d) was
obtained according to the procedure of Regitz et al.15
Methyl 2-diazophenylacetate (2e) was prepared via
Bamford–Stevens reaction from methyl a-oxophenyl-
acetate18 and the p-nitro derivative (methyl 2-diazo-
(p-nitrophenyl)diazoacetate via diazo transfer of methyl
p-nitrophenylacetate.19
Methyl 2-(cyclohexen-3-yl)-phenylacetate (3e). IR (CHCl3):
1
1700s. H NMR (400 MHz, CDCl3: 0.89–2.02 (m, 6H);
2.79–2.92 (m, 1H); 3.42 (d, Jˆ20 Hz, 1H); 3.68 (s, 3H);
5.16 (d, Jˆ20 Hz, 1H); 5.61–5.83(m, 1H); 7.22–7.39 (m,
5H). 13C NMR (100 MHz): 20.5 (t); 20.9 (t); 25.5 (d); 34.3
(t); 52.3 (q); 126.9 (d); 128.2 (d); 132.3 (d); 134.8 (d); 175.9
(s). MS: 230 (Mϩ, 2), 150 (88), 81 (100).
Catalysts: [Rh2(OAc)4] and [Cu(acac)2] are commercially
available. The other catalysts were synthesized according to
published procedures, as follows: [Rh2(pfb)4]: Ref. 13;
[Rh2{(Ϫ)-(S)-ptpa}4]: Ref. 16; [Rh2{(R)-(Ϫ)-bnp}4]: Ref.
17; [Rh2{(5S)-phox}4]: Ref. 22; [Rh2{(2S)-mepy}4]: Ref.
21; [Rh2{(4S)-dosp}4]: Ref. 23; [Rh2{(4S)-tbsp}4]: Ref. 36.
Methyl 2-(cyclohexen-3-yl)-p-nitrophenylacetate (3f). IR
1
(CHCl3): 1700s. H NMR (400 MHz, CDCl3): 0.84–2.11
(m, 6H); 2.84–2.95 (m, 1H); 3.44–3.51 (m, 1H); 3.69 (s,
3H); 5.08 (m, 1H); 5.58–5.86 (m, 1H); 7.51–7.58 (m, 2H);
8.16–8.22 (m, 2H). 13C NMR (100 MHz): 20.5 (t); 24.9 (t);
26.3 (d); 38.8 (d); 52.3 (d); 57.1 (q); 123.6 (d); 129.7 (d);
144.8 (s); 147.3 (s); 172.7 (s). MS: 275 (Mϩ, 2), 195 (14),
164 (12), 135 (13).
General procedure for catalyzed carbenoid reactions of
diazo acetates with olefins
The diazo compound (1.0 mmol) in anhydrous CH2Cl2
(10.0 mL) was added with stirring at room temperature by
means of a syringe pump and under inert atmosphere, to the
olefin (10.0 mmol) in anhydrous CH2Cl2 and the appropriate
catalyst (0.02 mmol) over a period of 12–16 h. After the
addition, stirring was continued until all of the diazo
compound had been consumed. The solvent and excess
olefin were removed in vacuo, and the residue was filtered
on a column of silica gel to remove the catalyst. The crude
product was purified by column chromatography, and the
product composition determined by capillary GC. For yields
and product composition: see Tables 1 and 2. Enantiomer
separation with SUPELCO Betadex 120 column. In the case
of 2b the reaction was carried out with 0.1 mmol.
7-exo-Ethoxycarbonylbicyclo[4.1.0]heptane (4a).37,38 IR
(CHCl3): 1708s. H NMR (400 MHz, CDCl3): 1.15–1.38
(m, 2H); 1.38 (t, Jˆ24 Hz, 3H); 1.55–1.62 (m, 2H); 1.62–
1.75 (m, 2H); 1.86–1.96 (m, 2H); 4.07–4.14 (q, Jˆ24 Hz,
2H).
1
(2,6-Di-tert-butyl-4-methylphenyl)-anti-7-bicyclo[4.1.0]-
1
heptanecarboxylate (4b).12 IR (CHCl3): 1703s. H NMR
(400 MHz, CDCl3): 1.36 (s, 18H); 1.56–1.91 (m, 10H); 2.31
(s, 3H); 7.11 (s, 2H). 13C NMR (100 MHz): 15.3 (s); 17.8 (t);
18.7 (t); 20.9 (d); 21.5 (t); 22.6 (q); 31.5 (q); 126.9 (d); 134.1
(d); 142.2 (d); 145.8 (d); 172.3 (s). MS (electrospray): 381
(MϩKϩ).
7,7-Dimethoxycarbonylbicyclo[4.1.0]heptane (4d).8a,39 IR
1
(CHCl3): 1735s. H NMR (400 MHz, CDCl3): 0.99–1.01
Product characterisation
(m, 2H); 1.24–1.29 (m, 2H); 1.81–1.99 (m, 6H); 3.68 (s,
3H); 3.78 (s, 3H). 13C NMR (100 MHz): 19.6 (d); 20.6 (d);
24.9 (d); 35.4 (t); 52.2 (s); 52.6 (s); 167.9 (s); 171.7 (s). MS:
212 (Mϩ, 17), 184 (31), 181 (51), 180 (100), 169 (50), 158
(28), 152 (80).
Most of the insertion and cyclopropanation products resul-
ting from the reactions are known in the literature, or are
derivatives of commercially available compounds. There-
fore only the most important characteristic data are reported
here.
r-7-Methoxycarbonyl-t-7-phenyl-t-bicyclo[4.1.0]heptane
(4e). IR (CHCl3): 1700s. 1H NMR (400 MHz, CDCl3):
0.52–0.64 (m, 2H); 1.18–1.45 (m, 2H); 1.69–1.79 (m,
2H); 1.91–2.06 (m, 4H); 3.54 (s, 3H); 7.27–7.38 (m, 5H).
13C NMR (100 MHz): 20.5 (t); 20.9 (t); 25.5 (d); 52.3
(q);126.9 (d); 128.2 (d); 132.3 (d); 134.8 (s); 175.9 (s).
MS: 230 (Mϩ, 100), 198 (82), 169 (29), 142 (32), 141
(27), 129 (39), 128 (27), 115 (31). HRMS: 230.1307
(C15H18Oϩ2 ; Calc 230.1325).
Ethyl (cyclohexen-3-yl)acetate (3a).37 IR (CHCl3): 1708s.
1H NMR (400 MHz, CDCl3): 1.24–1.28 (m, 2H); 1.41–1.59
(m, 2H); 1.60–1.77 (m, 3H); 1.78–2.10 (m, 4H); 4.13–4.15
(q, Jˆ8 Hz, 2H); 4.40–4.53 (m, 1H); 5.65–5.75 (m, 1H);
5.88–5.98 (m, 1H).
2,6-Di-tert-butyl-4-methylphenyl (cyclohexen-3-yl)ace-
tate (3b).12 IR (CHCl3): 1703s. 1H NMR (400 MHz,
CDCl3): 1.26 (s, 18H); 1.98–2.02 (m, 6H); 2.32 (s, 3H);
2.61–2.63 (m, 2H); 5.68–5.74 (m, 2H); 7.11 (s, 1H); 7.27
(s, 1H). 13C NMR (100 MHz): 21.0 (t); 21.5 (q); 25.1 (t);
r-7-Methoxycarbonyl-t-7-p-nitrophenyl-t-bicyclo[4.1.0]-
heptane (4f). IR (CHCl3): 1700s. 1H NMR (400 MHz,

¨
P. Muller, S. Tohill / Tetrahedron 56 (2000) 1725–1731
1730
CDCl3): 0.52–0.65 (m, 2H); 0.99–1.15 (m, 2H); 1.69–1.81
(m, 2H); 1.86–2.04 (m, 4H); 3.69 (s, 3H); 7.49 (m, 2H);
8.19 (m, 2H).
Acknowledgements
Financial support of this work by the Swiss National
Science Foundation (Grant No. 20-45255.95 and
20-48156.96) and by the University of Geneva is gratefully
acknowledged.
Methyl 2-cyclohexylphenylacetate (5)6 via catalytic
hydrogenation of 3e or 7e. To a stirred solution of olefin
(20.0 mg, 0.086 mmol) in MeOH (3.0 mL) was added Pd/C.
The mixture was stirred under H2 at room temperature until
completion of the reaction (monitoring by GC). Yield
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