Catalytic cyclopropanation of electron deficient alkenes mediated by chiral and achiral sulfides: Scope and limitations in reactions involving phenyldiazomethane and ethyl diazoacetate

Article abstract of DOI:10.1039/b004367m

Phenyldiazomethane reacts with electron deficient alkenes in the presence of catalytic amounts of transition metal catalyst [Rh₂(OAc)₄ was better than Cu(acac)₂] and catalytic amounts of sulfide to give cyclopropanes. Pentamethylene sulfide was found to be superior to tetrahydrothiophene and the optimum solvent was toluene. Under these optimised conditions a range of enones were cyclopropanated in high yields. Cyclic enones and acrylates were not successful in this process. The use of the chiral 1,3-oxathiane derived from camphorsulfonyl chloride in 2 steps in this process furnished cyclopropanes in good yield and very high enantiomeric excess (>97% ee). The absolute stereochemistry of cyclopropane 10 was proven by X-ray analysis and the origin of the stereochemical induction has been rationalised. Extension of this work to include diazoesters was partially successful. Again pentamethylene sulfide was found to be superior to tetrahydrothiophene, but this time both Rh₂(OAc)₄ and Cu(acac)₂ were found to be equally effective. Enones, fumarates and unsaturated nitro compounds worked well but simple acrylates and unsaturated aldehydes were not effective substrates. Control experiments were conducted in which the stabilised ylide was isolated and reacted with the less successful substrates and, whilst unsaturated aldehydes still gave low yields, simple acrylates gave high yields of the corresponding cyclopropane. The use of the chiral 1,3-oxathiane was not successful with these more stable diazo compounds.

Full text of DOI:10.1039/b004367m

View Article Online / Journal Homepage / Table of Contents for this issue
Catalytic cyclopropanation of electron deficient alkenes mediated
by chiral and achiral sulfides: scope and limitations in reactions
involving phenyldiazomethane and ethyl diazoacetate
1
Varinder K. Aggarwal,*a† Helen W. Smith,a George Hynd,a Ray V. H. Jones,b Robin Fieldhouseb
and Sharon E. Speya
a Department of Chemistry, University of Sheffield, Brook Hill, Sheffield, UK S3 7HF
b ZENECA Agrochemicals, Process Technology Dept., Earls Road, Grangemouth, Stirlingshire,
UK FK3 8XG
Received (in Cambridge, UK) 1st June 2000, Accepted 8th August 2000
First published as an Advance Article on the web 19th September 2000
Phenyldiazomethane reacts with electron deficient alkenes in the presence of catalytic amounts of transition
metal catalyst [Rh2(OAc)4 was better than Cu(acac)2] and catalytic amounts of sulfide to give cyclopropanes.
Pentamethylene sulfide was found to be superior to tetrahydrothiophene and the optimum solvent was toluene.
Under these optimised conditions a range of enones were cyclopropanated in high yields. Cyclic enones and
acrylates were not successful in this process. The use of the chiral 1,3-oxathiane derived from camphorsulfonyl
chloride in 2 steps in this process furnished cyclopropanes in good yield and very high enantiomeric excess
(>97% ee). The absolute stereochemistry of cyclopropane 10 was proven by X-ray analysis and the origin of
the stereochemical induction has been rationalised. Extension of this work to include diazoesters was partially
successful. Again pentamethylene sulfide was found to be superior to tetrahydrothiophene, but this time both
Rh2(OAc)4 and Cu(acac)2 were found to be equally effective. Enones, fumarates and unsaturated nitro compounds
worked well but simple acrylates and unsaturated aldehydes were not effective substrates. Control experiments
were conducted in which the stabilised ylide was isolated and reacted with the less successful substrates and, whilst
unsaturated aldehydes still gave low yields, simple acrylates gave high yields of the corresponding cyclopropane.
The use of the chiral 1,3-oxathiane was not successful with these more stable diazo compounds.
Introduction
Methods for the catalytic asymmetric synthesis of cyclo-
propanes from acyclic precursors have received considerable
attention due to the prevalence of such motifs in biologically
important molecules.1 Towards this goal, high enantioselectivity
has been achieved in reactions of diazo compounds with
alkenes in the presence of chiral transition metal complexes
(Cu–Schiff base,2 Cu–semicorrin,3 Cu–bis(oxazoline),4 Cu–
bipyridine,5 Co–bis(dioxime),6 Co–Salen,7 Rh2(5S-MEPY)4,8
Scheme 1
and Ru–Pybox9). Advances have also been made in asymmetric
Simmons–Smith cyclopropanation of allylic alcohols using
alkylborane complexes of tartaramides as promoters.10 How-
Results and discussion
We initially tested (E)-chalcone 1 and 4-phenylbut-3-en-2-one
ever, in all the above cases, the metal carbenoid only reacts
efficiently with electron rich alkenes.11 Methods are therefore
required for the cyclopropanation of electron deficient alkenes.
The asymmetric cyclopropanation of electron deficient alkenes
has been achieved using stoichiometric amounts of sulfonium12
and aminosulfoxonium ylides,13 but in the latter case the
reagent cannot be recycled.
2 with phenyldiazomethane (slow addition) using a stoichio-
metric amount of tetrahydrothiophene and catalytic amounts
of Cu(acac)2 under conditions that were similar to the success-
ful epoxidation–aziridination process (Table 1, entries 1, 2), but
were surprised at the lack of success in cyclopropanation. Only
stilbenes and benzaldehyde azine were isolated, along with
recovered enone and sulfide. However, a marked improvement
was observed using Rh2(OAc)4 in place of Cu(acac)2 (Table 1,
entries 3, 4). Unlike epoxidation and aziridination where
copper or rhodium based catalysts can be used, cyclopropan-
ation seems to require rhodium. This observation may be due to
the lower reactivity of enones coupled with the ability of copper
salts to react with sulfur ylides to give back metal carbenes.17
Indeed, this reaction has been utilised to cyclopropanate elec-
tron rich alkenes with sulfur ylides.17 Thus, with Cu(acac)2, a
higher concentration of metal carbene can be expected based
We previously described a new catalytic process for recycling
sulfur ylides and used this technology in catalytic asymmetric
epoxidation14 and aziridination15 of carbonyl and imine com-
pounds, respectively. We therefore considered the potential
application of this chemistry to catalytic asymmetric cyclo-
propanation of electron deficient alkenes (Scheme 1). In this
paper we describe the realisation of this process, and our results
in full.16
† Current address: School of Chemistry, University of Bristol,
Cantock’s Close, Bristol, UK BS8 1TS.
DOI: 10.1039/b004367m
J. Chem. Soc., Perkin Trans. 1, 2000, 3267–3276
This journal is © The Royal Society of Chemistry 2000
3267

View Article Online
Table 1 Effect of metal catalyst and solvent on yield in enone cyclopropanationa
Entry
Enone
R1
Metal catalyst
Solvent
Yield (%)b
Isomeric ratioc
1
2
3
4
5
6
7
8
1
2
1
2
1
1
1
1
Ph
Me
Ph
Me
Ph
Ph
Ph
Ph
Cu(acac)2
Cu(acac)2
Rh2(OAc)4
Rh2(OAc)4
Rh2(OAc)4
Rh2(OAc)4
Rh2(OAc)4
Rh2(OAc)4
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
Toluene
MeCN
THF
0
0
—
—
40
41
40
30
41
17
1:1
1:1
1:1
1:1
1:1
1:1
Hexane
a Phenyldiazomethane (1.5 eq.) added over 3 h to mixture of enone (1 eq.), tetrahydrothiophene (1 eq.), Rh2(OAc)4 (0.01 eq.) or Cu(acac)2 (0.05 eq.)
in appropriate solvent (1 M in enone). b Combined yield of cis and trans isomers. c Ratio determined by 1H NMR spectroscopy.
Table 2 Effect of solvent, stoichiometry and addition time on yield in enone cyclopropanationa
Entry
Enone
R1
R2
t/h
Sulfide (equiv.)
Yield (%)b
Isomeric ratioc
1
2
3
4
5
6
7
1
2
1
1
2
5
6
Ph
Me
Ph
Ph
Me
Ph
Ph
Ph
Ph
Ph
Ph
Me
Me
3
3
3
12
12
12
12
1.0
1.0
0.2
0.2
0.2
0.2
0.2
92
80
20
70
82
50
30
4:1
4:1
4:1
4:1
4:1
1:1:1
1:1:1
Me
a Phenyldiazomethane (1.5 eq.) added over 3 or 12 h to a mixture of enone (1 eq.), pentamethylene sulfide (1 eq./0.2 eq.), Rh2(OAc)4 (0.01 eq.) in
toluene (1 M in enone). b Combined yield of diastereoisomers. c Ratio determined by 1H NMR spectroscopy.
on the above precedent and this will lead to greater amount of
stilbenes and benzaldehyde azine (Scheme 2).
Scheme 2
Scheme 3
A brief survey of solvents (Table 1, entries 4–8) revealed that
there was little influence on yield and diastereoselectivity,
providing the reaction was homogeneous [the reaction was
heterogeneous in hexane (Table 1, entry 8)]. Toluene became the
solvent of choice as it gave comparable results to that obtained
with dichloromethane and as phenyldiazomethane is prepared
as a toluene solution,18 this simplified the experimental
procedure.
We were surprised at the moderate yields obtained in the
cyclopropanation reactions (Table 1), since the related epoxid-
ation and aziridination reactions proceeded in much higher
yield. Further examination of the reaction indicated that in
addition to the cyclopropane, sulfide 3 had also been formed.
This sulfide presumably results from ylide equilibration fol-
lowed by a Sommelet–Hauser rearrangement (Scheme 3).19
Sulfide 4 resulting from a Stevens rearrangement was not
observed.19 The rearranged sulfide 3 had not been previously
observed in epoxidation and aziridination. We presume that the
slower reacting enones provided time for ylide equilibration and
rearrangement to occur.
In an effort to reduce the extent of this side reaction we
sought sulfides which had a lower propensity for ylide equilib-
ration and were guided by Fava’s studies on the rate of deuter-
ium exchange of the α-protons of cyclic sulfonium salts.20
He showed that the rate of exchange of the α-protons in a
five membered ring was 4.3 × 10Ϫ5 MϪ1 Ϫ1, whilst in a six
s
membered ring the rate was an order of magnitude slower at
6.3 × 10Ϫ6 MϪ1 sϪ1. We therefore replaced tetrahydrothiophene
with pentamethylene sulfide and observed
a remarkable
increase in yield of cyclopropanes (Table 2, entries 1, 2). In
addition, a notable increase in diastereoselectivity was also
observed.
We next explored the use of sub-stoichiometric quantities of
sulfide. Initially, the same conditions employed for the stoichio-
metric reactions were used (Table 2, entry 1), but this led to low
3268
J. Chem. Soc., Perkin Trans. 1, 2000, 3267–3276

View Article Online
Table 3 Enantioselective cyclopropanation of enonesa
Entry
Enone
R1
Sulfide (equiv.)
Yield (%)b
Isomeric ratioc
Ee (%)d
[α]D25 e
Ϫ136
Ϫ136
Ϫ65
1
2
3
4
5
1
1
2
2
9
Ph
Ph
Me
Me
1.0
0.2
1.0
0.2
1.0
60
38
55
14
35
4:1
4:1
4:1
4:1
4:1
97
97
>98
>98
>98
Ϫ65
Ϫ105
p-BrC6H4
a Phenyldiazomethane (1.5 eq.) added over 12 h to mixture of enone (1 eq.), sulfide (0.2 or 1 eq.), Rh2(OAc)4 (0.01 eq.) in toluene (1 M in enone).
b Combined yield of both diastereoisomers. c Ratio determined by 1H NMR spectroscopy. d Determined using HPLC. e Conditions: c = 1.0, CH2Cl2.
yields of cyclopropane (Table 2, entry 3) and large quantities
of stilbenes and benzaldehyde azine. Sulfur ylide formation is
dependent on sulfide concentration and as the concentration
is reduced, side reactions of the metal carbenoid with phenyl-
diazomethane, to form stilbenes and benzaldehyde azine, begin
to compete (Scheme 4). By increasing the addition time of
There is one example of the use of a benzylsulfonium ylide
for the cyclopropanation of ethyl acrylate, in which a high yield
and stereoselectivity were achieved.12 In this example, ylide
equilibration is blocked on one side of the sulfur moiety and sig-
nificantly retarded by the oxygen on the other side (Scheme 6).
Scheme 6
These factors presumably contribute to the success of this
reaction.
Having developed the catalytic cyclopropanation reaction of
enones, we sought to render the process asymmetric through the
use of chiral sulfides. The sulfide chosen was the 1,3-oxathiane
8, which had been shown to be a very effective sulfide for
asymmetric epoxidation14 and aziridination.15 Sulfide 8 was
tested with (E)-chalcone 1 and enone 2 using stoichiometric
and catalytic quantities of sulfide. Cyclopropanes were
obtained in moderate to good yields, with the same diastereo-
selectivity as observed with pentamethylene sulfide and with
excellent levels of enantioselectivity (Table 3). The yields were
invariably lower when sub-stoichiometric amounts of sulfide
were employed, but the enantioselectivities were identical, indi-
cating that no background (non-sulfur ylide mediated) cyclo-
propanation was occurring. Indeed, in the absence of sulfide no
cyclopropanation occurred, proving that all the cyclopropane is
derived from the intermediacy of the sulfur ylide. The reduced
yields with sub-stoichiometric amounts of sulfide indicate that
the sulfide is not turning over efficiently and it is believed that
some decomposition/alternative transformation of the sulfide
also occurs. Indeed, although the sulfide 8 could be reisolated
from the reaction in 80% using stoichiometric amounts of sul-
fide, it was only recovered in less than 5% yield when using 20
mol% sulfide. The use of the chiral sulfide with enones 1-phenyl-
but-2-en-1-one 5 and pent-3-en-2-one 6 was unsuccessful.
In order to determine the absolute stereochemistry of
the cyclopropanes the p-bromo derivative of (E)-chalcone21
was used, and treatment with phenyldiazomethane yielded the
corresponding cyclopropanes (Table 3, entry 5). The major
diastereomer (2RS,3RS)-10 was then subjected to X-ray anal-
ysis and the absolute stereochemistry of the cyclopropane ring
was determined to be (2R,3R) (Fig. 1).
Scheme 4
the phenyldiazomethane, the concentration of phenyldiazo-
methane is reduced and more time is allowed for turnover of
sulfide. Indeed, when longer addition times were employed a
significant increase in yield of the cyclopropane was obtained,
with a concomitant reduction in the quantity of stilbene and
benzaldehyde azine (Table 2, entry 4).
Having achieved cyclopropanation of (E)-chalcone 1 in high
yields with catalytic quantities of sulfide we decided to extend
the methodology to include other Michael acceptors and
moderate to good yields were obtained (Table 2, entries 5–7).
With enones 5 and 6 a small amount of the rearranged sulfide 7
was observed, indicating that these enones must be less electro-
philic than 1 and 2 (Scheme 5). In all reactions, starting material
Scheme 5
To account for the excellent enantioselectivity the following
model is proposed (Scheme 7). The sulfur ylide preferentially
adopts conformations in which the filled orbital on carbon is
orthogonal to the lone pair on sulfur and of these two con-
formers 11a is preferred over 11b due to 1,3-diaxial interactions.
The ylide reacts with high face selectivity as a result of both
was recovered and the yields of the cyclopropanes were quanti-
tative when calculated by mass balance. Cyclopent-2-en-1-
one, cyclohex-2-en-1-one, 4-methylpent-3-en-2-one, and several
acrylates did not undergo cyclopropanation; only the re-
arranged sulfide 7 was isolated.
J. Chem. Soc., Perkin Trans. 1, 2000, 3267–3276
3269

View Article Online
Fig. 2
include diazoesters as there were numerous examples of the
reactions of ester-stabilised sulfonium ylides with electron
deficient alkenes.22 Furthermore, as a large number of biologic-
ally important cyclopropanes have acid functional groups
directly attached to them (Fig. 2), we were particularly keen to
explore this chemistry. Although the formation of stabilised
ylides from the reaction of ethyl diazoacetate with a sulfide is
well documented and the reaction of the corresponding ylide
with Michael acceptors reported, the compatibility of the two
processes in the same reaction remained to be established.
(E)-Chalcone 1 was selected as our test substrate using ethyl
diazoacetate. Reactions had to be performed at 60 ЊC as no
decomposition of ethyl diazoacetate occurred at lower temper-
atures with either Cu(acac)2 or Rh2(OAc)4. In contrast to the
use of phenyldiazomethane, ethyl diazoacetate gave similar
results for the cyclopropanation of (E)-chalcone 1 with
Rh2(OAc)4 and Cu(acac)2 and so further studies were con-
ducted with Cu(acac)2. In order to find the optimum conditions
for cyclopropanation, sulfide structure, solvents and the period
of addition of ethyl diazoacetate were varied (Table 4). As with
phenyldiazomethane, pentamethylene sulfide was found to be
superior to tetrahydrothiophene but the difference was not as
marked (compare entries 1, 2 with 3, 4). Longer addition times
of ethyl diazoacetate were found to increase yields presumably
because this led to a lower concentration of ethyl diazoacetate
and higher concentration of sulfide (allowing time for the
sulfide to turnover) (Table 4, entries 5–8). Both of these factors
would increase the likelihood of ylide formation and reduce the
likelihood of fumarate/maleate formation (Scheme 9). Indeed
when the yields were low, large quantities of diethyl fumarate
and diethyl maleate were formed.
Fig. 1 ORTEP drawing of cyclopropane (2R,3R)-10.
steric and electronic control and indeed the face selectivity is
believed to be complete. The minor enantiomer is believed to
originate from the less favoured conformer 11b, which again
reacts with the same high face selectivity. The same model was
used to rationalise the outcome of epoxidation reactions using
the same sulfide.14 The higher enantioselectivity observed in
cyclopropanation compared to epoxidation must be due to a
bigger difference in the rates of cyclopropanations of 11a and
11b, which in turn result from using less reactive electrophiles
(enones being less reactive than aldehydes). To account for
the diastereoselectivity we need to consider which face of the
enone (Re or Si face) is preferentially attacked. Two possible
approaches of the enone to the ylide are given in Scheme 8 and
these lead to the two diastereomeric betaines which will then
ring close to give the cyclopropane. Path A places the largest
groups opposite each other and will therefore be preferred
over path B. This accounts for the formation of the major
diastereoisomer.
We also considered the possibility of extending the process to
Scheme 7
Scheme 8
3270
J. Chem. Soc., Perkin Trans. 1, 2000, 3267–3276

View Article Online
Table 4 Effect of addition time and solvent on yield in cyclopropan-
Table 5 Cyclopropanation of Michael acceptors with ethyl diazo-
acetatea
ation of chalconea
Sulfide
(n)
Yield
(%)b
Isomeric
ratioc
Michael
acceptor
Sulfide
(eq.)
Yield
(%)b
Isomeric
ratioc
Entry
t/h
Solvent
Entry
Product
1
2
3
4
5
6
7
8
9
1
1
2
2
2
2
2
2
2
2
3
6
3
6
3
THF
THF
THF
THF
THF
THF
THF
THF
12
20
15
38
10
38
70
71
70
72
4:2:1
4:2:1
4:2:1
4:2:1
4:2:1
4:2:1
4:2:1
4:2:1
4:2:1
4:2:1
1
2
3
4
5
6
7
8
1
1
1.0
0.2
1.0
0.2
1.0
0.2
1.0
1.0
20
20
21
21
22
22
23
24
72
77
64
43
68
68
5
4:2:1
4:2:1
>95:5
>95:5
>95:5
>95:5
>95:5
5:4:2
12
12
13
13
14
15
6
16
24
24
24
38
MeCN
1,2-DCE
a Ethyl diazoacetate (1 eq.) added to mixture of enone (1 eq.), sulfide
(1 eq.), Cu(acac)2 (0.05 eq.) in 1,2-dichloroethane (1 M in enone).
b Combined yield of all isomers. c Ratio determined by 1H NMR
spectroscopy.
10
a Ethyl diazoacetate (1 eq.) added to mixture of enone (1 eq.), sulfide
(1 eq.) and Cu(acac)2 (0.05 eq.) in the appropriate solvent (1 M in
enone). b Combined yield of all isomers. c Ratio determined by 1H
NMR spectroscopy.
clearly efficient): the ylide 30 was formed from (ethoxycarbonyl-
methyl)pentamethylenesulfonium bromide by conventional
chemistry, isolated, and reacted with Michael acceptors at both
room temperature and at 65 ЊC (which is the temperature of the
catalytic process) (Table 6). Although unsaturated aldehyde 17
and ketone 14 gave a low yield in cyclopropanation, mirroring
their ineffectiveness in our catalytic system, unsaturated
ketone 12, fumarate 13 and acrylates 18, 19 gave good yields at
both room and elevated temperatures. Payne25 has similarly
shown that dimethyl-λ4-sulfanylideneacetate reacts efficiently
with ethyl acrylate although lower yields were observed with
unsaturated aldehydes. Although it may seem that substrates
which are particularly prone to polymerisation (unsaturated
aldehydes 16, 17 and acrylates 18, 19) are not compatible with
our catalytic process, other substrates, for example methyl vinyl
ketone 12 are compatible. It is therefore difficult to generalise
which substrates are compatible with our in situ generated
sulfur ylide process. The relative stereochemistry of the adducts
derived from (E)-chalcone 1 and nitrostyrene 15 was deter-
mined by NOE (Fig. 4).
Scheme 9
The application of oxathiane 8 to asymmetric cyclopropan-
ation of (E)-chalcone using ethyl diazoacetate under our opti-
mised conditions was not successful: only a small amount of
product was obtained and the sulfide was not recovered. This
suggested that the intermediate stabilised ylide, which clearly
has lower reactivity than that derived from phenyldiazo-
methane, undergoes competitive rearrangement–hydrolysis
reactions faster than reaction with (E)-chalcone. More stable
chiral sulfides are therefore required to promote this asym-
metric process.
Fig. 3
Conclusion
As with phenyldiazomethane, the choice of solvent did not
influence the yield or diastereoselectivities of the process
significantly and 1,2-dichloroethane was chosen for further
studies. Having found conditions that gave high yields for
cyclopropanation, we tested a range of Michael acceptors with
stoichiometric and catalytic loadings of sulfide (Table 5). Sub-
strates that worked well with stoichiometric amounts of sulfide
(1, 12, 13, Fig. 3) also worked well under catalytic conditions.
Unsaturated ketone 14 and nitrostyrene 15 also gave the corre-
sponding cyclopropane, but in low yields. However, unsaturated
aldehydes 16, 17 and acrylates 18, 19 did not give any cyclo-
propane. With substrates which were ineffective in our catalytic
process, control experiments were conducted to test the effi-
ciency of the final step of the process (ylide formation was
Cyclopropanation of enones using phenyldiazomethane
and catalytic quantities of sulfide has been achieved and the
use of the chiral sulfide 8 furnishes products with high enantio-
selectivity. Reactions are limited to relatively reactive enones as
with less reactive Michael acceptors, ylide equilibration and
rearrangement occurs. Cyclopropanation of a broader range
of Michael acceptors using ethyl diazoacetate and catalytic
quantities of sulfides has also been achieved, although the
reaction is limited to enones, fumarates and nitrostyrenes;
simple acrylates and unsaturated aldehydes were not com-
patible with our process. 1,3-Oxathiane 8 derived from
camphorsulfonyl chloride was not a suitable chiral sulfide
for use with ethyl diazoacetate and more stable sulfides are
currently being sought.
J. Chem. Soc., Perkin Trans. 1, 2000, 3267–3276
3271

View Article Online
Table 6 Cyclopropanation of Michael acceptors using preformed ylide
Michael
acceptor
Yield
(%)a
Isomeric
ratiob
Entry
Solvent
T/ЊC
Product
1
2
3
4
5
6
7
8
9
12
17
18
19
12
13
14
17
18
19
1,2-DCE
MeCN
20
20
20
20
65
65
65
65
65
65
21
25
26
27
21
22
23
25
26
27
99
17
99
99
83
99
Trace
28
99
>95:5
1:1
>95:5
>95:5
>95:5
>95:5
—
1:1
>95:5
>95:5
1,2-DCE
1,2-DCE
1,2-DCE
1,2-DCE
1,2-DCE
MeCN
1,2-DCE
1,2-DCE
10
69
a Combined yield of all isomers. b Ratio determined by 1H NMR spectroscopy.
Fig. 4
0.5% (w/v) aqueous solution of potassium permanganate or
anisaldehyde (9.2 mL of anisaldehyde, 3.7 mL of acetic acid,
12.5 mL of concentrated sulfuric acid dissolved in 340 mL of
95% ethanol), followed by warming of the TLC plate with a
heat gun. Chromatographic purification of compounds was
achieved by flash chromatography using Kieselgel 60 F254. All
reagents used were commercially available unless otherwise
stated.
Experimental
General
1H and 13C magnetic resonance spectra were recorded using a
Bruker ACS-250 and a Bruker AMX-2 400 spectrometer sup-
ported by an Aspect 2000 data system. The chemical shifts are
reported in ppm. All coupling constants are measured in hertz
and rounded to one decimal place. 1H chemical shifts were
measured relative to the residual signal of chloroform at 7.25
ppm. 13C chemical shifts were measured from the central peak
of chloroform at 77.0 ppm. Mass spectra were obtained using
either a Kratos MS 25 or MS 80 instrument supported by a DS
55 data system operating in EI, CI and ϩve FAB mode. Melting
points (mp) were determined using a Kofler Hot Stage Micro
Melting Point Apparatus and stand uncorrected. Elemental
micro analyses were carried out using a Perkin-Elmer 2400
Elemental Analyser CHN, involving classical wet analysis for
anions (Br, Cl, I, S). Infrared spectra were recorded in the 4000–
600 cmϪ1 range using a Perkin-Elmer 157G Grating Infra Red
FT Spectrophotometer. Optical rotations ([α]D20) were measured
using a Perkin-Elmer 141 Polarimeter. [α]D20 values are given in
10Ϫ1 deg cm2 gϪ1. Enantiomeric excesses (ee) were determined
by chiral HPLC using a Highchrom -phenylglycine column
with a detector wavelength of 240 nm. Gas chromatography
was performed using a Perkin-Elmer Autosystem XL sup-
The following starting materials were made according to
literature procedures: 4-phenylbut-3-en-2-one 2,26 trans-2-nitro-
styrene 1427 and phenyldiazomethane.18
General procedure for the synthesis of 3 and 7
For characterisation purposes, sulfides 3 and 7 were prepared
independently by the following method. NaH (60% dispersion
in mineral oil) (80 mg, 2 mmol) was washed with hexane
(2 × 0.5 mL) and dried under vacuum. The NaH was flushed
with N2 and dimethyl sulfoxide (5 mL) added. Upon com-
pletion of the evolution of gas the benzylsulfonium salt,
1-benzyltetrahydrothiophenium perchlorate or 1-benzyltetra-
hydro-2H-thiopyranium perchlorate (0.5 mmol) was added and
stirred for 20 min. The reaction was quenched with water (10
mL) and extracted with hexane (3 × 5 mL). The combined
organics were washed with water (2 × 5 mL), dried (Na2SO4)
and reduced in vacuo to furnish the desired sulfide as a clear
oil.
ported by a Turbochrom 4.0 data system. Solvents and reagents
were dried and purified prior to use according to standard pro-
cedures. TLC plates were visualised when possible by ultraviolet
light, wavelength 254 nm, and by treatment with a solution of
phosphomolybdic acid (5.0 g in 100 mL 95% absolute alcohol),
2-(2-Methylphenyl)tetrahydrothiophene 3. Using 1-benzyl-
tetrahydrothiophenium perchlorate (0.14 g, 0.5 mmol) the title
compound was obtained as a clear oil (88 mg, 99%), Rf 0.2
3272
J. Chem. Soc., Perkin Trans. 1, 2000, 3267–3276

View Article Online
(petrol); νmax (thin film)/cmϪ1 3028–2824 (CH), 1603, 1461
(ArH); H (250 MHz; CDCl3) 1.88–2.12 (2 H, m, CH2), 2.16–
m, 2 × CH), 3.40 (2 H, ddd, J 12.0, 7.5, 3.5, SCHeq), 3.59 (2 H,
1
ddd, J 12.0, 8.5, 3.5, SCHax), 4.24 (2 H, q, J 7.0, CO2CH2), 4.74
(2 H, s, SCH2CO2Et); 13C (63 MHz; DMSO-d6) 14.3, 20.3, 24.5,
27.8, 28.5, 63.2, 165.2; m/z (EI) 268 (Mϩ, 1%), 189 (49), 102
(100), 87 (93) (Found: Mϩ, 268.0132. C9H17SO2Br requires Mϩ,
268.0133).
2.35 (2 H, m, CH2), 2.37 (1 H, s, CH3), 2.95–3.05 (1 H, m,
SCH), 3.09–3.20 (1 H, m, SCH), 4.73 (1 H, dd, J 8.0, 6.0,
SCHAr), 7.08–7.25 (3 H, m, ArH), 7.60 (1 H, d, J 7.0, ArH);
13C (63 MHz; CDCl3) 19.7, 29.7, 30.8, 38.6, 48.6, 126.3, 126.7,
126.8, 130.3, 135.8, 140.8; m/z (EI) 178 (Mϩ, 100%), 163 (48),
135 (55), 131 (64), 117 (20), 115 (25), 91 (27) (Found: Mϩ,
178.0816. C11H14S requires Mϩ, 178.0816).
Ethyl pentamethylene-ꢀ4-sulfanylideneacetate 30
(Ethoxycarbonylmethyl)pentamethylenesulfonium
bromide
(0.54 g, 2.0 mmol) was stirred in CHCl3 (1.6 mL) under N2 at
0 ЊC. A solution of saturated K2CO3 (1.2 mL) and NaOH (0.16
mL, 50% w/v) was added and the resulting suspension stirred at
room temperature for 20 min. The mixture was then filtered
through Celite and the filtrate dried (K2CO3) and concentrated
in vacuo to give title compound as a white crystalline solid
2-(2-Methylphenyl)tetrahydro-2H-thiopyran 7. Using 1-
benzyltetrahydro-2H-thiopyranium perchlorate (0.15 g, 0.5
mmol) the title compound was obtained as a clear oil (95 mg,
99%), Rf 0.3 (petrol); νmax (thin film)/cmϪ1 3023–2924 (CH),
1
1601 (ArH); H (250 MHz; CDCl3) 1.50–1.80 (2 H, m, CH2),
(0.37 g, 99%), mp 40–41 ЊC; νmax (KBr disc)/cmϪ1 2970–2924
2.00–2.15 (4 H, m, CH2), 2.50 (3 H, s, CH3), 2.65–2.76 (1 H, m,
SCHeq), 2.93 (1 H, ddd, J 13.0, 11.7, 2.2, SCHax), 4.05 (1 H, dd,
J 10.5, 3.3, SCHAr), 7.15–7.27 (3 H, m, ArH), 7.44 (1 H, d,
J 7.0, ortho-ArH); 13C (63 MHz; CDCl3) 19.3, 27.1, 27.5, 31.1,
34.5, 43.5, 126.4, 126.7, 127.0, 130.4, 135.5, 140.9; m/z (CI) 193
(MHϩ, 78%), 159 (27), 105 (8), 101 (100), 87 (13) (Found: Mϩ,
192.0967. C12H16S requires Mϩ, 192.0973).
1
(CH), 1623 (C᎐O); H (250 MHz; CDCl ) 1.20 (3 H, t, J 7.0,
᎐
3
CH3), 1.35–1.51 (2 H, m, CH2), 1.63–1.79 (2 H, m, 2 × CH),
2.03–2.17 (2 H, m, 2 × CH), 2.64–2.78 (2 H, m, 2 × CHS), 3.21
(1 H, s, CHCO2Et), 3.56–3.72 (2 H, m, 2 × CHS), 4.00 (2 H, q,
J 7.0, CO2CH2); 13C (63 MHz; CDCl3) 15.0, 23.6, 24.2, 36.9,
42.1, 57.8, 170.2; m/z (CI) 189 (MHϩ, 100%), 143 (8), 52 (36)
(Found: MHϩ, 189.0951. C9H17SO2 requires MHϩ, 189.0949).
(E)-1-(4-Bromophenyl)-3-phenylprop-2-en-1-one 9.21 Aqueous
NaOH (2.5 M, 8.0 mL, 20 mmol) was added dropwise to a
stirred solution of 4-bromoacetophenone (0.60 g, 3.0 mmol),
benzaldehyde (0.30 mL, 3.0 mmol) and absolute EtOH (8 mL)
at 0 ЊC, under N2 and stirred for 1 h. The precipitate was col-
lected, washed with ice cold water and dried to yield the crude
product as a pale yellow solid (0.83 g, 97%) which was recrystal-
lised (hexane–EtOAc, 19:1) to furnish the title compound as off-
white needles (0.71 g, 82%), mp 96 ЊC (hexane–EtOAc, 19:1)
[lit.,21 101–102 ЊC (hexane–EtOAc, 20:1)]; Rf 0.6 (CH2Cl2–
General procedure for neutral ylide reactions (Table 6)
Ethyl pentamethylene-λ4-sulfanylideneacetate 30 (0.10 g, 0.55
mmol) was stirred in solvent (0.5 mL) under N2. Substrate
(0.5 mmol) was added dropwise and the reaction stirred at 20
or 65 ЊC for 30 min. The reaction was then purified by flash
column chromatography.
1-Benzoyl-2,3-diphenylcyclopropane28
1
petrol, 1:1); H (250 MHz; CDCl3) 7.41–7.44 (5 H, m, ArH),
(Table 3, entries 1, 2) Using (E)-chalcone (0.208 g, 1.0 mmol)
the reaction mixture was purified by flash column chromato-
graphy (eluent CH2Cl2–petrol, 4:6) to furnish the title
compound as a white solid, which was a mixture of two
diastereoisomers (4:1, 2R,3R:meso) (0.18 g, 60%), mp 144–
146 ЊC (EtOH) [lit. 2RS,3RS,28 148–149 ЊC (EtOH)]; [α]D25 Ϫ136
7.47 (1 H, d, J 15.5, CHPh), 7.64 (2 H, d, J 8.5, meta-ArHBr),
7.82 (1 H, d, J 15.5, CHCOPh), 7.89 (2 H, d, ortho-ArHBr); 13
C
(101 MHz; CDCl3) 121.4, 127.9, 128.5, 129.0, 130.0, 130.8,
131.9, 134.7, 136.9, 145.4, 189.4.
General procedure for the optimised reaction used in Tables 2 and
3, with phenyldiazomethane
1
(c, 1.0, CH2Cl2); Rf 0.6 (CH2Cl2–petrol, 1:1); H (250 MHz;
CDCl3) 2R,3R 3.28 (1 H, dd, J 7.0, 5.5, CHPh), 3.38 (1 H, dd,
J 9.5, 7.0, CHPh), 3.65 (1 H, dd, J 9.5, 5.5, CHCOPh), 7.00–
7.65 (13 H, m, ArH), 7.95 (2 H, dd, ortho-ArHCO); meso 3.33
(2 H, d, J 5.5, CHPh), 3.55 (1 H, t, J 5.5, CHCOPh), 7.00–7.65
(13 H, m, ArH), 8.20 (2 H, dd, ortho-ArHCO); 13C (63 MHz;
CDCl3) 30.0, 32.4, 36.3, 36.6, 37.9, 126.6, 126.7, 126.9, 127.0,
128.0, 128.1, 128.2, 128.3, 128.5, 128.7, 128.8, 129.0, 132.8,
133.2, 135.6, 136.2, 137.8, 138.4, 140.0, 195.0, 198.6; Chiracel
OD, i-PrOH–light petroleum (0.7:99.3), flow rate of 2 mL
minϪ1. Retention times: meso isomer 5.4 min, trans isomer
(2R,3R) enantiomer, 6.1 min; (2S,3S) 6.7 min, separations
performed at 10 ЊC.
Rh2(OAc)4 (1 mol%), sulfide (1.0 mmol or 0.2 mmol) and sub-
strate (1.0 mmol) were stirred in toluene (1 mL), under N2, at
room temperature. Phenyldiazomethane (1.5 mmol in 1 mL
toluene) was added via an inverted syringe pump over the time
period indicated in Tables 2 or 3 and the reaction stirred for a
further hour. The crude mixture was then purified by flash
column chromatography.
General procedure for the optimised reaction used in Tables 4 and
5 with ethyl diazoacetate
Cu(acac)2 (5 mol%), sulfide (1.0 mmol or 0.2 mmol) and sub-
strate (1.0 mmol) were stirred in 1,2-DCE (0.5 mL) under N2
and warmed to 65 ЊC. Ethyl diazoacetate (1 mmol in 0.5 mL
1,2-DCE) was added via a syringe pump over the time period
indicated in Tables 4 or 5 and the reaction stirred for a further
hour. After cooling the mixture was purified by flash column
chromatography.
1-Acetyl-2,3-diphenylcyclopropane
(Table 3, entries 3, 4) Using 4-phenylbut-3-en-2-one, the reaction
mixture was purified by flash column chromatography (eluent
CH2Cl2–petrol, 3:7) to furnish the title compound as a white
solid, which was a mixture of two diastereoisomers (4:1,
2R,3R:meso), mp 78–80 ЊC (EtOH); Rf 0.4 (CH2Cl2–petrol,
3:7) (Found: C, 86.42; H, 6.85. C17H16O requires C, 86.44; H,
6.78%); [α]D25 Ϫ65 (c, 1.0, CH2Cl2); νmax (KBr disc)/cmϪ1 3087–
(Ethoxycarbonylmethyl)pentamethylenesulfonium bromide
Pentamethylene sulfide (4.2 mL, 40 mmol) and ethyl bromo-
acetate (4.5 mL, 40 mmol) were stirred in acetone (5 mL), under
N2 for 18 h. The resulting solid was collected and washed with
cold acetone (5 mL) to yield the title compound as a white
powder (8.2 g, 77%), mp 140–142 ЊC (Found: C, 40.24; H, 6.46;
S, 11.91; Br, 29.94. C9H17SO2Br requires C, 40.16; H, 6.32; S,
11.90; Br, 29.71%); νmax (KBr disc)/cmϪ1 2982–2890 (CH), 1717
3032 (CH), 1694 (C᎐O), 1602, 1582 (ArH); 1H (250 MHz;
᎐
CDCl3) 2R,3R 2.12 (3 H, s, CH3), 2.72 (1 H, dd, J 9.5, 5.5,
CHCOCH3), 3.08 (1 H, dd, J 9.5, 7.5, CHPh), 3.32 (1 H, dd,
J 7.5, 5.5, CHPh), 7.15–7.40 (10 H, m, ArH); meso 2.47 (3 H, s,
CH3), 2.86 (1 H, t, J 5.5, CHCOCH3), 3.12 (2 H, d, J 5.5,
CHPh), 7.15–7.40 (10 H, m, ArH); 13C (63 MHz; CDCl3) 2R,3R
29.9, 31.6, 37.1, 39.8, 126.6, 126.7, 127.0, 128.2, 128.6, 129.1,
135.5, 139.8, 203.0; meso 31.2, 35.8, 35.9, 127.6, 128.0, 128.9,
(C᎐O); 1H (250 MHz; DMSO-d ) 1.26 (3 H, t, J 7.0, CH ), 1.53–
᎐
6
3
1.62 (2 H, m, CH2), 1.76–1.92 (2 H, m, 2 × CH), 2.00–2.15 (2 H,
J. Chem. Soc., Perkin Trans. 1, 2000, 3267–3276
3273

View Article Online
131.3, 135.9, 206.7; m/z (EI) 236 (Mϩ, 14%), 193 (100), 178 (33),
115 (75) (Found: Mϩ, 236.1196. C17H16O requires Mϩ,
236.1201); Chiracel OD, i-PrOH–light petroleum (0.7:99.3),
flow rate of 2 mL minϪ1. Retention times: meso isomer 3.9 min,
trans isomer (2R,3R) enantiomer, 8.6 min; (2S,3S) 9.1 min,
separations performed at 10 ЊC.
20.70%); νmax/cmϪ1 3062–2921 (CH), 1666 (C᎐O), 1495–1364
᎐
(ArH); 1H (250 MHz; CDCl3) 2R,3R 3.30 (2 H, d, J 6.0,
2 × CHPh), 3.61 (1 H, d, J 6.0, CHCOPh), 7.13–7.97 (15 H, m,
ArH); meso 3.31 (2 H, d, J 5.0, 2 × CHPh), 3.45 (1 H, d, J 5.0,
CHCOPh), 7.13–7.97 (15 H, m, ArH); 13C (101 MHz; CDCl3)
29.9, 32.3, 36.4, 36.5, 37.9, 126.6, 126.8, 127.0, 127.9, 128.1,
128.3, 128.5, 128.6, 128.9, 129.0, 129.4, 129.5, 129.6, 130.0,
132.0, 135.2, 135.9, 137.0, 139.7, 145.4, 193.9, 197.5; m/z (EI)
376 (Mϩ, 5%), 287 (89), 207 (47), 193 (100), 185 (49), 178 (35),
131 (34), 115 (33), 77 (33) (Found: Mϩ, 376.0453. C22H17OBr
requires Mϩ, 376.0463); Chiracel OD, i-PrOH–light petroleum
(0.7:99.3), flow rate of 2 mL minϪ1. Retention times: meso
isomer 7.4 min, trans isomer (2R,3R) enantiomer, 8.6 min;
(2S,3S) 9.1 min, separations performed at 10ЊC.
1-Benzoyl-2-phenyl-3-methylcyclopropane29
(Table 2, entry 6) Using 1-phenylbut-2-en-1-one (0.15 g, 1.0
mmol), the reaction was purified by flash column chromato-
graphy (eluent EtOAc–petrol, 5:95) to furnish the title
compound as a white solid which was a mixture of three
diastereoisomers [eluting a and b followed by b and c (1:1:1,
a:b:c)], (0.14 g, 50%), mp 42–44 ЊC (EtOH); Rf 0.4, 0.5
(EtOAc–petrol, 1:9); νmax (KBr disc)/cmϪ1 3059–2868 (CH),
Crystal structure of (2R,3R)-10‡
1
1665 (C᎐O), 1598–1448 (aromatic); H (250 MHz; CDCl ) a
᎐
3
Crystal data for C22.5H19BrO1.5 (including a half occupancy
CH3OH); M = 393.29, crystallises from acetone–n-pentane–
methanol as colourless blocks; crystal dimensions 0.30 ×
0.20 × 0.10 mm3. Monoclinic, a = 24.604(8), b = 5.8049(18),
c = 14.597(4) Å, β = 111.784(6)Њ, U = 1935.9(10) Å3, Z = 4,
Dc = 1.349 Mg mϪ3, space group C2, Mo-Kα radiation (λ =
0.71073 Å), µ(Mo-Kα) = 2.132 mmϪ1, F(000) = 804.
1.35 (3 H, d, J 6.0, CH3), 2.06 (1 H, dqd, J 9.5, 6.0, 4.3,
CHCH3), 2.88 (1 H, dd, J 4.8, 4.3, CHPh), 3.04 (1 H, dd, J 9.5,
4.8, CHCOPh), 7.10–7.60 (8 H, m, ArH), 7.88 (2 H, dd, J 8.0,
2.0, ortho-ArHCO); b 1.05 (3 H, d, J 6.0, CH3), 2.46 (1 H, dqd,
J 7.0, 6.0, 5.0, CHCH3), 2.67 (1 H, dd, J 9.0, 7.0, CHPh), 2.83
(1 H, dd, J 9.0, 5.0, CHCOPh), 7.10–7.60 (8 H, m, ArH), 8.05
(2 H, dd, J 2.0, 8.0, ortho-ArHCO); c 1.28 (3 H, d, J 6.5, CH3),
2.05 (1 H, dqd, J 9.3, 6.5, 6.5, CHCH3), 2.82 (1 H, dd, J 6.5, 5.0,
CHCOPh), 2.99 (1 H, dd, J 9.3, 5.0, CHPh), 7.10–7.60 (8 H, m,
ArH), 7.88 (2 H, dd, J 8.0, 2.0, ortho-ArHCO); 13C (101 MHz;
CDCl3) a and b 12.9, 17.6, 20.4, 26.9, 31.8, 35.3, 35.7, 38.5,
126.5, 127.8, 127.9, 128.0, 128.2, 128.4, 128.5, 128.6, 128.9,
129.0, 132.4, 132.8, 136.2, 136.8, 138.0, 138.7, 196.2, 199.4;
c 11.6, 28.9, 32.9, 34.8, 126.2, 126.3, 128.0, 128.5, 128.6, 132.7,
138.7, 140.9, 197.4; m/z (EI) 236 (Mϩ, 35%), 221 (34), 131 (19),
105 (100), 91 (16), 77 (42), 51 (11) (Found: Mϩ, 236.1203.
C17H16O requires Mϩ, 236.1201).
Ethyl 2-benzoyl-3-phenylcyclopropane-1-carboxylate 2032
(Table 5, entries 1, 2) Using (E)-chalcone 1 (0.208 g, 1.0 mmol),
the reaction mixture was purified by flash column chromato-
graphy (eluent EtOAc–petrol, 5:95) to yield the title compound
as a white solid, which was a mixture of three diastereoisomers
(20a:20b:20c, 4:1:2) (0.22 g, 72%) mp 90–91 ЊC (EtOH); Rf
0.2 (petrol–EtOAc, 9:1) (Found: C, 77.27; H, 6.39. C19H18O3
requires C, 77.55; H, 6.12%); νmax (KBr disc)/cmϪ1 3056–2898
(CH), 1722, 1683 (C᎐O), 1460–1431 (Ar); 1H (250 MHz;
᎐
CDCl3) 20a 1.32 (3 H, t, J 7.0, CH3), 3.22 (1 H, dd, J 6.0, 5.0,
CHPh), 3.35 (1 H, dd, J 10.0, 6.0, CHCO2Et), 3.57 (1 H, dd,
J 10.0, 5.0, CHCOPh), 4.23 (2 H, q, J 7.0, CO2CH2), 7.18–7.37
(5 H, m, Ar), 7.39–7.67 (3 H, m, meta and para-ArHCO), 7.95
(2 H, dd, J 8.0, 1.5, ortho-ArHCO); 20b 1.07 (3 H, t, J 7.0,
CH3), 2.86 (1 H, dd, J 10.0, 5.0, CHCO2Et), 3.26 (1 H, dd,
J 10.0, 6.0, CHPh), 3.85 (1 H, dd, J 6.0, 5.0, CHCOPh), 3.99
(2 H, 2 × q, J 7.0, 2 × CO2CH), 7.18–7.37 (5 H, m, Ar), 7.39–
7.67 (3 H, m, meta and para-ArHCO), 8.12 (2 H, dd, J 8.0, 1.5,
ortho-ArHCO); 20c 1.13 (3 H, t, J 7.0, CH3), 2.64 (1 H, dd,
J 10.0, 6.0, CHCO2Et), 3.09 (1 H, dd, J 10.0, 6.5, CHCOPh),
3.36 (1 H, dd, J 6.5, 6.0, CHPh), 4.09 (2 H, q, J 7.0, CH2), 7.20–
7.39 (5 H, m, Ar), 7.42–7.60 (3 H, m, meta and para-ArHCO),
8.02 (2 H, dd, J 8.0, 1.5, ortho-ArHCO); 13C (101 MHz; CDCl3)
20a and 20b 14.0, 14.2, 25.9, 29.6, 32.1, 35.0, 35.0, 35.8, 60.9,
61.3, 127.2, 127.3, 128.0, 128.1, 128.2, 128.3, 128.6, 128.8,
128.9, 133.1, 133.5, 133.7, 134.7, 137.0, 137.4, 168.7, 172.2,
193.2, 196.7; 20c 14.0, 29.7, 31.6, 35.1, 61.1, 126.5, 127.1, 128.4,
128.6, 128.7, 133.3, 136.9, 138.0, 169.2, 193.7; m/z (EI) 294
(Mϩ, 6%), 249 (8), 221 (100), 189 (12), 115 (19), 105 (51), 77 (25)
(Found: Mϩ, 294.1256 C19H18O3 requires Mϩ, 294.1244).
1-Acetyl-2-phenyl-3-methylcyclopropane30
(Table 2, entry 7) Using pent-3-en-2-one (97 µL, 1.0 mmol),
the reaction was purified by flash column chromatography
(eluent EtOAc–petrol, 5:95) to furnish the title compound as a
pale yellow oil, which was a mixture of three diastereoisomers
[eluting a and b followed by b and c (1:1:1, a:b:c)] (95 mg,
30%), bp 200 ЊC (20 mmHg) (Kugelrohr); Rf a 0.6, b and c 0.5
(EtOAc–petrol, 1:9); νmax (thin film)/cmϪ1 3027–2869 (CH),
1
1697 (C᎐O), 1498–1357 (Ar); H (250 MHz; CDCl ) a 1.25
᎐
3
(3 H, d, J 6.5, CH3), 1.85 (1 H, dqd, J 9.0, 6.5, 6.5 CHCH3),
2.29 (3 H, s, COCH3), 2.34 (1 H, dd, J 9.0, 5.0, CHPh), 2.54 (1
H, dd, J 6.5, 5.0, CHCOCH3), 7.16–7.30 (5 H, m, ArH); b 0.94
(3 H, d, J 6.5, CH3), 1.86 (1 H, dqd, J 9.5, 6.5, 4.8, CHCH3),
2.34 (3 H, s, COCH3), 2.17 (1 H, m, CHPh), 2.81 (1 H, dd, J 9.5,
4.8, CHCOCH3), 7.16–7.34 (5 H, m, ArH); c 1.25 (3 H, d, J 5.5,
CH3), 2.0 (3 H, s, COCH3), 2.17 (2 H, m, CHCH3 CHPh), 2.47
(1 H, dd, J 8.5, 7.5, CHCOCH3), 7.16–7.34 (5 H, m, ArH); 13
C
(63 MHz; CDCl3) a 11.4, 28.5, 32.3, 33.5, 37.9, 126.0, 126.2,
128.6, 131.3, 205.6; b 12.7, 26.1, 30.9, 34.7, 35.6, 126.6, 128.2,
128.9, 136.5, 207.6; c 17.8, 20.4, 31.4, 37.3, 39.0, 126.5, 128.0,
129.0, 136.2, 204.3; m/z (EI) 174 (Mϩ, 32%), 159 (21), 131 (100),
91 (46), 77 (9) (Found: Mϩ, 174.1045 C12H14O requires Mϩ,
174.1046).
Ethyl (1RS,2RS)-2-acetylcyclopropanecarboxylate 2125
(Table 5, entries 3, 4; Table 6, entries 1, 5) Using methyl vinyl
ketone (83 µL, 1.0 mmol) the reaction mixture was purified by
flash column chromatography (eluent EtOAc–petrol, 5:95) to
yield the title compound as a colourless oil (0.10 g, 64%), Rf 0.5
(EtOAc–petrol, 4:1) (Found: C, 61.09; H, 7.65. C8H12O3
2,3-Diphenylcyclopropyl(4-bromophenyl)methanone 10
(Table 3, entry 5) Using 1-(4-bromophenyl)-3-phenylpropan-1-
one (0.29 g, 1.0 mmol) and sulfide 8 (0.21 g, 1.0 mmol), the
reaction was purified by flash column chromatography, eluent
(CH2Cl2–petrol, 1:4) to furnish the title compound as pale
yellow needles which was a mixture of two diastereoisomers
(4:1, 2R,3R:meso) (0.11 g, 35%), mp 102–104 ЊC (EtOH) [lit.
2RS,3RS,31 113–115 ЊC (hexane–benzene)]; [α]D25 Ϫ105 (c, 1.0,
CHCl3); Rf 0.6 (CH2Cl2–petrol, 1:1) (Found: C, 68.40; H, 4.68;
Br, 20.70. C22H17OBrؒ1/2H2O requires C, 68.41; H, 4.66; Br,
requires C, 61.54; H, 7.69%); νmax (thin film)/cmϪ1 3621–2984
1
(CH), 1707, 1730 (C᎐O); H (250 MHz; CDCl ) 1.26 (3 H, t,
᎐
3
J 7.0, CH3), 1.35–1.44 (2 H, m, 2 × CH), 2.16 (1 H, ddd, J 8.3,
6.0, 3.8, CHCO2Et), 2.30 (3 H, s, CH3), 2.45 (1 H, ddd, J 8.3,
‡ CCDC reference number 207/467. See http://www.rsc.org/suppdata/
p1/b0/b004367m/ for crystallographic files in .cif format.
3274
J. Chem. Soc., Perkin Trans. 1, 2000, 3267–3276

View Article Online
6.0, 3.8, CHCOCH3), 4.14 (2 H, q, J 7.0, CO2CH2); 13C (63
MHz; CDCl3) 14.1, 17.1, 24.2, 29.5, 30.8, 61.0, 172.0, 205.3;
m/z (EI) 156 (Mϩ, 21%), 141 (100), 113 (23), 111 (57), 85 (61),
82 (42), 68 (41), 57 (39), 55 (74) (Found: Mϩ, 156.0779. C8H12O3
requires Mϩ, 156.0786).
EtOAc–petrol, 5:95) to yield the title compound as a colourless
oil (0.18 g, 99%), Rf 0.6 (EtOAc–petrol, 4:1) (Found: C, 57.83;
H, 7.14. C9H14O4 requires C, 58.06; H, 7.53%); νmax (thin film)/
cmϪ1 2984 (CH), 1725 (C᎐O); 1H (250 MHz; CDCl ) 1.25 (6 H,
᎐
3
t, J 7.0, 2 × CH3), 1.41 (2 H, dd, J 8.8, 6.8, 2 × CH), 2.14 (2 H,
dd, J 8.8, 6.8, 2 × CHCO2Et), 4.14 (4 H, 2 q, J 7.0, 2 ×
CO2CH2); 13C (63 MHz; CDCl3) 14.2, 15.3, 22.4, 61.2, 171.8;
m/z (EI) 186 (Mϩ, 11%), 159 (8), 141 (100), 113 (29), 85 (36), 68
(18), 55 (14) (Found: Mϩ, 186.0892 C9H14O4 requires Mϩ,
186.0892).
trans,meso-1,2,3-Triethyl cyclopropanetricarboxylate 2225
(Table 5, entries 5, 6; Table 6, entry 6) Using diethyl fumarate
(0.16 mL, 1.0 mmol), the reaction was purified by flash column
chromatography (eluent EtOAc–petrol, 5:95) to yield the title
compound as a colourless oil (0.18 g, 68%), Rf 0.4 (EtOAc–
petrol, 4:1) (Found: C, 55.78; H, 6.93. C12H18O6 requires C,
55.81; H, 6.98%); νmax (thin film)/cmϪ1 3450–2984 (CH), 1728
Phenyl 2-ethyl trans-cyclopropane-1,2-dicarboxylate 27
(Table 6, entries 4, 10) Using phenyl acrylate (80 µL, 0.5 mmol),
the reaction was purified by flash column chromatography
(eluent EtOAc–petrol, 5:95) to yield the title compound as a
white solid (0.16 g, 69%), mp 48–49 ЊC (EtOH); Rf 0.4 (EtOAc–
petrol, 1:4) (Found: C, 66.37; H, 6.11. C13H14O4 requires C,
66.67; H, 5.98%); νmax (KBr disc)/cmϪ1 3099–2874 (CH), 1750,
(C᎐O); 1H (250 MHz; CDCl ) 1.24 (6 H, t, J 7.0, 2 × CH ), 1.27
᎐
3
3
(3 H, t, J 7.0, CH3), 2.52 (2 H, d, J 5.5, 2 × CH), 2.75 (1 H, t,
J 5.5, CH), 4.14 (4 H, q, J 7.0, 2 × CO2CH2), 4.16 (2 H, q, J 7.0,
CH2); 13C (63 MHz; CDCl3) 14.1, 25.7, 28.5, 61.5, 61.6, 167.6;
m/z (EI) 258 (Mϩ, 29%), 213 (100), 185 (95), 157 (44), 140 (38),
112 (38), 84 (39) (Found: Mϩ, 258.1101 C12H18O6 requires Mϩ,
258.1103).
1
1720 (C᎐O), 1599, 1494, 1479 (ArH); H (250 MHz; CDCl )
᎐
3
1.30 (3 H, t, J 7.0, CH3), 1.54–1.62 (2 H, m, 2 × CH), 2.28–2.44
(2 H, m, CHCO2Ph and CHCO2Et), 4.19 (2 H, q, J 7.0, CH2),
7.09 (2 H, dd, J 1.5, 8.0, ortho-ArH), 7.23 (1 H, m, para-ArH),
7.38 (2 H, m, meta-ArH); 13C (63 MHz; CDCl3) 14.2, 15.9, 22.2,
23.0, 61.2, 121.3, 125.9, 129.4, 150.4, 170.4, 171.5; m/z (EI) 234
(Mϩ, 44%), 189 (20), 141 (100), 113 (16), 94 (10), 85 (23)
(Found: Mϩ, 234.0898. C13H14O4 requires Mϩ, 234.0892).
Ethyl 2-nitro-3-phenylcyclopropane-1-carboxylate 24
(Table 5, entry 8) Using trans-2-nitrostyrene (0.15 g, 1.0 mmol),
the reaction was purified by flash column chromatography
(eluent EtOAc–petrol, 5:95) to furnish the title compound as a
pale yellow oil which was a mixture of three diastereoisomers
(24a:24b:24c, 5:2:4) (94 mg, 38%), bp 150 ЊC (0.01 mmHg);
Rf 24a and 24b 0.4, 24c 0.3 (EtOAc–petrol, 1:9) (Found: C,
61.17; H, 5.78; N, 5.66. C12H13O4N requires C, 61.28; H, 5.53;
Acknowledgements
We gratefully thank AstraZeneca Process Technology Depart-
ment and Sheffield University for financial support.
N, 5.96%); νmax (thin film)/cmϪ1 2985 (CH), 1732 (C᎐O), 1550,
᎐
1368 (NO2), 1428 (ArH); 1H (250 MHz; CDCl3) 24a 1.02 (3 H,
t, J 7.0, CH3), 3.21 (1 H, dd, J 11.0, 3.5, CHCO2Et), 3.66 (1 H,
dd, J 11.0, 4.8, CHPh), 3.97 (1 H, q, J 7.0, CO2CH), 3.98 (1 H,
q, J 7.0, CO2CH), 5.18 (1 H, dd, J 4.8, 3.5, CHNO2), 7.16–7.24
(5 H, m, ArH); 24b 1.34 (3 H, t, J 7.0, CH3), 3.33 (1 H, dd, J 9.0,
8.0, CHPh), 3.40 (1 H, dd, J 8.0, 4.0, CHCO2Et), 4.25 (1 H, q,
J 7.0, CO2CH), 4.26 (1 H, q, J 7.0, CO2CH), 4.92 (1 H, dd,
J 9.0, 4.0, CHNO2), 7.16–7.24 (5 H, m, ArH); 24c 1.29 (3 H, t,
J 7.0, CH3), 2.70 (1 H, dd, J 8.5, 8.0, CHCO2Et), 3.73 (1 H, dd,
J 8.0, 4.5, CHPh), 4.24 (2 H, q, J 7.0, CO2CH2), 4.60 (1 H,
dd, J 8.5, 4.5, CHNO2), 7.24–7.37 (5 H, m, ArH); 13C (101
MHz; CDCl3) 24a and 24b 13.8, 14.1, 27.6, 32.2, 34.4, 34.7,
61.6, 62.1, 62.7, 64.7, 128.2, 128.5, 128.6, 128.7, 128.8, 128.9,
130.2, 131.2, 129.7, 168.7; 24c 14.0, 32.0, 34.7, 62.2, 64.9, 126.8,
128.2, 128.6, 134.2, 165.8; m/z (CI) 236 (MHϩ, 66%), 190 (70),
146 (38), 128 (100), 105 (43) (Found: MHϩ, 236.0931.
C12H14NO2 requires MHϩ, 236.0923).
References
1 M. P. Doyle, Chem. Rev., 1986, 86, 919; G. Mass, Top. Curr. Chem.,
1987, 137, 75; J. Salaun, Chem. Rev., 1989, 89, 1247; H. N. C. Wong,
M. Y. Hon, C. W. Tse, Y. C. Yip, J. Tanko and T. Hudlicky, Chem.
Rev., 1989, 89, 165; A. Krief, Pestic. Sci., 1994, 41, 237; M. P. Doyle,
M. A. McKervey and T. Ye, Modern catalytic methods for organic
synthesis with diazo compounds, Wiley, New York, 1997; A. Pfaltz,
Comprehensive Asymmetric Catalysis II, ed. E. N. Jacobsen,
A. Pfaltz and H. Yamamoto, 1999, 513.
2 T. Aratani, Y. Yoneyoshi and T. Nagase, Tetrahedron Lett., 1975,
1707; T. Aratani, Y. Yoneyoshi and T. Nagase, Tetrahedron Lett.,
1977, 2599; T. Aratani, Y. Yoneyoshi and T. Nagase, Tetrahedron
Lett., 1982, 23, 685; T. Aratani, Pure Appl. Chem., 1985, 57,
1839.
3 H. Fritschi, U. Leutenegger and A. Pfaltz, Angew. Chem., Int. Ed.
Engl., 1986, 25, 1005; H. Fritschi, U. Leutenegger and A. Pfaltz,
Helv. Chim. Acta, 1988, 71, 1553; U. Leutenegger, G. Umbricht,
C. Fahrni, P. von Matt and A. Pfaltz, Tetrahedron Lett., 1992, 48,
2143; A. Pfaltz, Acc. Chem. Res., 1993, 26, 339.
4 R. E. Lowenthal, A. Abiko and S. Masamune, Tetrahedron Lett.,
1990, 31, 6005; D. Muller, G. Umbricht, B. Weber and A. Pfaltz,
Helv. Chim. Acta, 1991, 74, 232; D. A. Evans, K. A. Woerpel,
M. M. Hinman and M. M. Faul, J. Am. Chem. Soc., 1991, 113, 726;
D. A. Evans, M. M. Faul and M. T. Bilodeau, J. Org. Chem., 1991,
56, 6744; R. E. Lowenthal and S. Masamune, Tetrahedron Lett.,
1991, 32, 7373; D. A. Evans, K. A. Woerpel and M. J. Scott, Angew.
Chem., Int. Ed. Engl., 1992, 31, 430.
Ethyl 2-formyl-3-methylcyclopropane-1-carboxylate 2525
(Table 6, entries 2, 8) Using crotonaldehyde (83 µL, 1 mmol) the
reaction mixture was purified by flash column chromatography
(eluent EtOAc–petrol, 5:95) to furnish the title compound as a
pale yellow oil which was a mixture of two diastereoisomers
(1:1, 1RS,2RS,3SR:1SR,2RS,3RS) (45 mg, 28%), Rf 0.3
(EtOAc–petrol, 1:4); νmax (thin film)/cmϪ1 2982–2936 (CH),
1
5 K. Ito and T. Katsuki, Synlett, 1993, 638; K. Ito and T. Katsuki,
Tetrahedron Lett., 1993, 34, 2661; K. Ito, M. Yoshitake and
T. Katsuki, Heterocycles, 1996, 42, 305.
6 A. Nakamura, A. Konishi, Y. Tatsuno and S. Otsuka, J. Am. Chem.
Soc., 1978, 100, 3443; A. Nakamura, A. Konishi, R. Tsujitani,
M. Kudo and S. Otsuka, J. Am. Chem. Soc., 1978, 100, 3449;
A. Nakamura, Pure Appl. Chem., 1978, 50, 37.
1726, 1712 (C᎐O); H (250 MHz; CDCl ) 1.23 (3 H, d, J 6.5,
᎐
3
CHCH3), 1.25 (3 H, t, J 7.0, CH2CH3), 1.26 (3 H, t, J 7.0,
CH2CH3), 1.28 (3 H, d, J 6.5, CHCH3), 1.78–1.95 (1 H, m,
CHCHO), 1.99 (1 H, dd, J 8.5, 6.5, CHCO2Et), 4.14 (2 H, q,
J 7.0, CO2CH2CH3), 4.15 (2 H, 2 q, J 7.0, 2 × CO2CH), 9.35
(1 H, d, J 3.8, CHO), 9.58 (1 H, d, J 3.8, CHO); 13C (63 MHz;
CDCl3) 11.1, 14.2, 14.3, 16.6, 22.5, 24.1, 28.3, 30.8, 37.1, 38.7,
61.1, 61.3, 169.4, 169.5, 198.7, 199.5.
7 T. Fukuda and T. Katsuki, Synlett, 1995, 825; T. Fukuda and
T. Katsuki, Tetrahedron, 1997, 53, 7201.
8 M. P. Doyle, B. D. Brandes, A. P. Kazala, R. J. Pieters, M. B.
Jarstfer, L. M. Watkins and C. T. Eagle, Tetrahedron Lett., 1990,
31, 6613; M. P. Doyle, R. J. Pieters, S. F. Martin, R. E. Austin,
C. J. Oalmann and P. Mueller, J. Am. Chem. Soc., 1991, 113, 1423;
M. P. Doyle, A. van Oeveren, L. J. Westrum, M. N. Protopopova
and T. W. Clayton Jr., J. Am. Chem. Soc., 1991, 113, 8982;
Diethyl trans-cyclopropane-1,2-dicarboxylate 2633
(Table 6, entries 3, 9) Using ethyl acrylate (54 µL, 0.5 mmol) the
reaction was purified by flash column chromatography (eluent
J. Chem. Soc., Perkin Trans. 1, 2000, 3267–3276
3275

View Article Online
P. Muller, D. Fernandez, P. Nury and J.-C. Rossier, Helv. Chim.
Acta, 1999, 82, 935.
M. P. Doyle, W. R. Winchester, J. A. A. Hoorn, V. Lynch, S. H.
Simonsen and R. Ghosh, J. Am. Chem. Soc., 1993, 115, 9968;
S. F. Martin, C. J. Oalmann and S. Liras, Tetrahedron Lett., 1992, 33,
6727; W. G. Dauben, R. T. Hendricks, M. J. Luzzio and H. P. Ng,
Tetrahedron Lett., 1990, 31, 6969.
9 H. Nishiyama, Y. Itoh, H. Matsumoto, S.-B. Park and K. Itoh,
J. Am. Chem. Soc., 1994, 116, 2223; H. Nishiyama, Y. Itoh,
Y. Sugawara, H. Matsumoto, K. Aoki and K. Itoh, Bull. Chem. Soc.
Jpn., 1995, 68, 1247.
10 A. B. Charette and H. Juteau, J. Am. Chem. Soc., 1994, 116, 2651.
11 For an example of metal carbenoid addition to an electron deficient
alkene, see T. Hudlicky and R. P. Short, J. Org. Chem., 1982,
47, 1522. However, in this example the reaction is intramolecular,
which no doubt facilitates this process. It was also noted in
this example that marginally higher yields were obtained in the
presence of sulfides, suggesting the possible intermediacy of a sulfur
ylide.
18 D. S. Wulfman, S. Yousefian and J. M. White, Synth. Commun.,
1988, 18, 2349.
19 E. Block, The Chemistry of the Sulphonium Group, ed. C. J. M.
Stirling and S. Patai, Wiley, New York, 1982, p. 673; I. E. Marko,
Comprehensive Organic Synthesis, ed. B. M. Trost and I. Fleming,
Pergamon, Oxford, 1991, vol. 3, p. 913.
20 G. Barbarella, A. Garbesi and A. Fava, Helv. Chim. Acta, 1971, 54,
2297.
21 A. M. Echavarren and J. K. Stille, J. Am. Chem. Soc., 1988, 110,
1557.
22 E. J. Corey and M. Chaykovsky, J. Am. Chem. Soc., 1965, 87, 1353;
I. Collado, C. Dominguez, J. Ezquerra, C. Pedregal and J. A. Monn,
Tetrahedron Lett., 1997, 38, 2133.
23 A. Krief, W. Dumont, P. Pasau and P. Lecomte, Tetrahedron, 1989,
45, 3039.
12 A. Solladié-Cavallo, A. Diep-Vohuule and T. Isarno, Angew. Chem.,
Int. Ed., 1998, 37, 1689.
13 C. R. Johnson and C. W. Schroeck, J. Am. Chem. Soc., 1973, 95,
7418; S. G. Pyne, Z. Dong, B. W. Skelton and A. H. White, J. Org.
Chem., 1997, 62, 2337.
24 C. Dominguez, J. Ezquerra, R. S. Baker, S. Borrelly, L. Prieto,
M. C. Espada and C. Pedregel, Tetrahedron Lett., 1998, 39, 9305.
25 G. B. Payne, J. Org. Chem., 1967, 32, 3353.
26 D. A. Oare, M. A. Henderson, M. A. Sanner and C. H. Heathcock,
J. Org. Chem., 1990, 55, 132.
14 V. K. Aggarwal, J. G. Ford, A. Thompson, R. V. H. Jones and
M. C. H. Standen, J. Am. Chem. Soc., 1996, 118, 7004; V. K.
Aggarwal, H. Abdel-Rahman, F. Li, R. V. H. Jones and M. C. H.
Standen, Chem. Eur. J., 1996, 2, 1024.
15 V. K. Aggarwal, A. Thompson, R. V. H. Jones and M. C. H.
Standen, J. Org. Chem., 1996, 61, 8368.
16 For a preliminary report see V. K. Aggarwal, H. W. Smith, R. V. H.
Jones and R. Fieldhouse, Chem. Commun., 1997, 1785.
17 T. Cohen, G. Herman, T. M. Chapman and D. Kuhn, J. Am. Chem.
Soc., 1974, 96, 5627; B. Cimetiere and M. Julia, Synlett, 1991, 271;
27 C. F. H. Allen and F. W. Spangler, Org. Synth., 1945, 25, 42.
28 M. Hetschko and J. Gosselck, Chem. Ber., 1973, 106, 996.
29 C. R. Johnson and E. R. Janiga, J. Am. Chem. Soc., 1973, 95,
7692.
30 T. Sato and S. Nagatsuka, Synlett, 1995, 653.
31 F. S. Guziec Jr. and F. A. Luzzio, J. Org. Chem., 1983, 48, 2434.
32 K. M. Lokanatha Rai, C. Anjanamurthy and P. M. Radhakrishna,
Synth. Commun., 1990, 20, 1273.
33 M. P. Doyle, R. L. Dorow and W. H. Tamblyn, J. Org. Chem., 1982,
47, 4059.
3276
J. Chem. Soc., Perkin Trans. 1, 2000, 3267–3276