Methylenecyclopropanes in elimination and addition reactions: Quantification of the effects of strain

Article abstract of DOI:10.1080/10426500902947856

The effect of strain in 1,2-elimination reactions that form methylenecyclopropanes has been evaluated for a series of leaving groups. The worse the leaving group, the greater is the inhibitory effect of strain build-up, which reaches 50% of the excess enthalpy differential for the poorest leaving group studied. In nucleophilic addition to an electrophilic methylenecyclopropane, comparison of strained and unstrained systems shows that about 60% of the excess enthalpy differential promotes the reactivity of the strained system.

Full text of DOI:10.1080/10426500902947856

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Methylenecyclopropanes
in Elimination and Addition
Reactions: Quantification of
the Effects of Strain
Luca Volta a & Charles J. M. Stirling a
a Department of Chemistry , The University of
Sheffield , Sheffield, UK
Published online: 06 Jun 2009.
To cite this article: Luca Volta & Charles J. M. Stirling (2009) Methylenecyclopropanes
in Elimination and Addition Reactions: Quantification of the Effects of Strain,
Phosphorus, Sulfur, and Silicon and the Related Elements, 184:6, 1508-1522, DOI:
10.1080/10426500902947856
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Phosphorus, Sulfur, and Silicon, 184:1508–1522, 2009
Copyright © Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500902947856
Methylenecyclopropanes in Elimination and Addition
Reactions: Quantification of the Effects of Strain
Luca Volta and Charles J. M. Stirling
Department of Chemistry, The University of Sheffield, Sheffield, UK
The effect of strain in 1,2-elimination reactions that form methylenecyclopropanes
has been evaluated for a series of leaving groups. The worse the leaving group, the
greater is the inhibitory effect of strain build-up, which reaches 50% of the excess
enthalpy differential for the poorest leaving group studied.
In nucleophilic addition to an electrophilic methylenecyclopropane, comparison
of strained and unstrained systems shows that about 60% of the excess enthalpy
differential promotes the reactivity of the strained system.
Keywords Addition; elimination; methylenecyclopropane; strain
INTRODUCTION
The effect of strain on the rates of a range of reactions is qualitatively
familiar.2 Nucleophilic ring openings of epoxides, for example, occur
readily under conditions in which unstrained ethers are inert.3 We have
previously quantified the effect of strain on elimination reactions.4,5 In
the systems chosen, the results showed that around 50% of the excess
enthalpy difference6 was expressed in acceleration of the reactions.
Rate enhancements were of the order of 1011, but the results depended,
because of the huge accelerations involved, on estimations of the reac-
tivity of unstrained comparator systems. We now report on behavior in
a system in which we can accurately quantify the reactivity of strained
and unstrained systems under identical conditions. For eliminations in
the strained systems on which we now report, the reactivity, instead of
being increased, is inhibited by the accumulation of strain in the tran-
sition structure. As well as being able to quantify the effect of strain
on an elimination reaction, we have been able to examine and measure
Received 12 January 2008; accepted 6 March 2008.
Dedicated to Professor Marian Mikolajczyk, CBMiM PAN in Lo´dz´, Poland, on the
ꢀ
ꢀ
occasion of his 70th birthday.
Address correspondence to Prof. Charles J. M. Stirling, Department of Chemistry, The
University of Sheffield, Sheffield S3 7HF, UK. E-mail: C.Stirling@sheffield.ac.uk
1508

Methylenecyclopropanes
1509
the effect of strain in the acceleration of nucleophilic addition to an
electrophilic alkene.
There are strict requirements to be met if meaningful conclusions
are to be drawn from comparison of the reactivities of strained and
unstrained systems. First, the comparison of strained and unstrained
systems must be for reactions with the same unambiguous mecha-
nism. Second, the strain energy differential must be accurately known,
preferably from thermochemical measurements. Third, reactions must
proceed in high yields, preferably to give a single product.
We have chosen to investigate the systems in Scheme 1. The
behavior of sulfones in elimination reactions has been extensively
studied in the past.7,8 Sulfone carbon-acids have very high deproto-
nation/reprotonation rates,9 so that in alkene-forming eliminations ac-
tivated by sulfonyl groups, the very high deprotonation rates favor
the (E1cB)R mechanism. In this mechanism, departure, k2, of the β -
leaving group becomes rate-determining as the pre-equilibrium k1/k
−1
is rapidly established. This enables direct comparison both of ease of de-
parture of leaving groups and attachment of nucleophiles10 (Scheme 2).
SCHEME 1
Strain in methylenecyclopropanes has been discussed.11 The
strained angles of the cyclopropane ring—nominally 60 degrees—are
even more strained in methylenecyclopropanes by the attachment of
SCHEME 2

1510
L. Volta and C. J. M. Stirling
the methylene group with sp2 hybridization requiring a nominal C-C-C
ring angle of 120 degrees. The resulting difference in strain between
cyclopropane and methylenecyclopropane12 is 54 kJmol−1. In such sys-
tems, strain in the transition structure for an elimination reaction such
as (2) in Scheme 1, presumably increases as the carbon–carbon double
bond of the methylenecyclopropane is formed. Expression of strain dif-
ferential will be reflected in the extent of double bond formation, and so
the potential for inhibition of reactivity is considerable. The comparator
system is reaction (1) in Scheme 1.
METHODS AND RESULTS
Substrates
In Scheme 3, the unstrained open chain halides 1 were obtained by
homolytic addition of benzenesulfonyl halides to 2-methylpropene ini-
tiated by AIBN. Addition of thiophenol to the alkene 2 obtained by
treatment of 1 with mild base gave the sulfide 3. Subsequent oxidation
gave the bis-sulfone 4.
The strained systems were derived from methylenecyclopropane.
The addition of halogens gave the dihalides 12, and subsequent dis-
placement with thiophenoxide gave the sulfides 13. These, on oxida-
tion, gave the sulfones 6, which were also obtained by direct homolytic
addition of sulfonyl halides to methylenecyclopropane.
DISCUSSION
Eliminations
For the strained systems, formation of the alkene by activated 1,2-
elimination increases the strain energy—excess enthalpy differential—
by the difference in enthalpy between the starting material and the
product. This differential amounts to 54 kJ mol−1 and raises the ques-
tion of the effect of the strain differential on the reactivity of the sub-
strate. Data are in Table I. The expected products have been isolated
in high yields, and the unstrained comparator substrates have been
subjected to identical conditions.
Pathways of the Reactions
The possibility exists that for the sulfone leaving group, for exam-
ple, the reaction with the base involves direct substitution rather than
elimination–addition. The latter pathway has been shown to operate.
Treatment of sulfone 9 with piperidine in ethanol gave no reaction,

Methylenecyclopropanes
1511
SCHEME 3
but when sodium ethoxide was added, the product was the piperidino-
sulfone 10. We conclude that piperidine is not sufficiently basic to cause
elimination, but that when the methylenecyclopropane 7 is generated
by the stronger base, ethoxide, 10 is formed, as piperidine is more
nucleophilic than ethoxide ion. Earlier work13 from another labora-
tory states that a different pathway is followed for the bis-sulfone 9,
which on treatment with methanolic sodium methoxide, gives the open-
chain product 14 in low yield. In our work, we obtain high yields of
the elimination-addition products 11, R OEt and 11, R OMe, and we
have X-ray crystal structures for 9, 11, R OEt and 11, R OMe. The

1512
L. Volta and C. J. M. Stirling
properties of our specimen of 9 are quite different from those reported,
but unfortunately a direct comparison has not been possible.13
The integrity of the cyclopropane ring under the reaction conditions
was checked with sulfone 6, Hal=H. There was no reaction.
Mechanisms of the Reactions
Evaluation of the effect of strain requires that the rate-determining
step of the reaction considered involves a process in which differential
strain is felt. In the case of 1,2-eliminations activated by a β-sulfonyl
group, earlier work has shown that, in an appropriate base-solvent
system, for good leaving groups such as halogen, the reactions are
either concerted (E2) or ionization (k1) that determines the rate.10
For poor leaving groups, the pre-equilibrium is rapidly established.
This allows the step, k2, in which the leaving group departs, to be
rate-determining. In the present systems, for the base-solvent system
TABLE I Elimination to Form Unstrained and Strained Alkenes1
Rate constants/mol.−1dm3 s−1
Leaving Group
Open Chain
Cyclopropane
Z
krel unstrained:strained
ac
abc
ac
abc
kobs
kion
kobs
kion
Br
Cl
SO2Ph
SPh
OMe
2.3·102
7.8·101
3·44
2.3·101
4.1·101
8.8·102
4.8·10−1
3·1
0.7
1.4
229
6168
28666
3.2·102
3.2·101
1.5·102
5.7·101
1.5·10−2 1.2·103
1.0·10−5 6.7·10−1
1.5·10−9 5.3·10−1
6.6·10−2
4.3·10−5
aUnits: m−1dm3s−1 bSee text; cFor reactions in EtONa–EtOH at 25◦C.
;

Methylenecyclopropanes
1513
2
sodium ethoxide-ethanol, we have examined all of the reactions by H
NMR for the incorporation of deuterium in the starting material from
deuteriated solvent. Another criterion we have used for the diagnosis
of the mechanism is to interpolate the ionization rate of the series of
methylenecyclopropanes. In earlier work,14 ionisation rates were de-
termined for a series of β-substituted aryl ethyl sulfones. This informa-
tion can be applied in the present systems to the difficult distinction
between the E2 and (E1cB)I mechanisms. In Table I, the interpolated
ionization rate constants derived from a Taft plot14 of kionisation versus
the inductive constant σ*, can be compared with the overall elimina-
tion rate constants. When the leaving group is bromide, for both the
strained and unstrained systems, the elimination rates are substan-
tially greater than the ionization rates, k1, pointing to a concerted
mechanism, E2. For chloride as leaving group, in both systems, the
ionization rates are comparable with the elimination rates, suggesting,
albeit not proving, that the (E1cB)I mechanism operates. In all of the
other substrates, interpolated ionization rates are much larger than
the elimination rates, consistent with operation of the (E1cB)R mecha-
nism in which departure of the leaving group is rate-determining. This
conclusion is strengthened by the observation of deuterium incorpo-
ration in the same substrates under the conditions of the elimination
reactions.
Reactions were followed by UV spectroscopy for reactions in which
the product alkene was detectable and otherwise by gc. All reactions
were first order in substrate and first order in base. Results are in
Table I. The expected products were formed in high yields (Table II).
Evaluation of the Effect of Strain
Against this mechanistic background, the question of the involve-
ment of strain can be considered. For the halogen leaving groups,
the eliminations have either the E2 or (E1cB)I mechanisms for both
strained and unstrained substrates. Deprotonation is either coupled
TABLE II Product Analysis for Elimination Reactions
Deuterium
incorporation
Sulfone
LG
Cl
Product
Yield %a
6a
11
90
81
90
95
95
no
no
yes
yes
yes
6b
8
9
Br
SPh
SO2Ph
OMe
11
11
11
11; R Me
11; R OMe + R OEt
aOf 1-Ethoxy-1-phenylsulfonylmethylcyclopropane 11, R OEt.

1514
L. Volta and C. J. M. Stirling
with loss of the leaving group or is itself rate-determining. There can
be no evaluation of the effect of strain on these processes. For the other
leaving groups, formation of the strained alkene is rate-determining,
and the effect of strain can be commented on. The first striking fea-
ture of the results of Table I is that the reactivity ratio for the un-
strained to strained substrates changes greatly as the leaving group is
changed. In our work on nucleofugalities,7 we established ranks (nu-
cleofugalities) in β-eliminations from sulfones for a large number of
leaving groups and determined the order PhSO2 >PhSꢀOMe. In reac-
tions with halides, as in the present cases, the mechanisms followed did
not involve rate-determining loss of the leaving group. In the present
systems, the reactivity ratio for the unstrained to strained substrates
increases greatly as the leaving group is changed from phenylsulfonyl
through phenylthio to methoxy. It can reasonably be inferred that as
leaving group ability declines, as in this series, a greater double bond
order in the transition structure is required to expel the leaving group.
The associated energetic cost in this system is the involvement of an in-
creasing proportion of the excess enthalpy of the product methylenecy-
clopropane.
The important associated question relates to the extent of the ex-
pression of the strain differential between the cyclopropane starting
material and the methylenecyclopropane product. The most marked
inhibition is seen in the case of the poorest leaving group, methoxy. In
this case, a factor of 29000 between the strained and unstrained sub-
strates corresponds to transition structure energy difference of about
26 kJ mol−1 or about 50% of the strain energy differential. This state-
ment is made on the assumption that the A factors for the two reactions
are the same. Intriguingly, there is a large difference between the in-
hibitions observed with the sulfonyl and phenylthio leaving groups.
The nucleofugalities of these groups are quite similar, and so the large
difference in strain inhibition is not readily accounted for.
In an electrophilic addition to a methylenecyclopropane such as that
of bromine, there appears to be a trade-off between the additional
strain induced in the intermediate (spiro) bromonium ion and the in-
creased stability afforded by attachment of the cyclopropyl ring to the
intermediate cation.15 The rate ratio for the addition of bromine to 2-
methylpropene versus methylenecyclopropane is 102, corresponding to
a ꢀE of 11.7 kJ mol−1 against a strain energy difference of 27.2 kJmol−1
or substantially less than 50%.
Within this context of the reactivity of cyclopropyl derivatives, 4-
phenylsulphonylmethylcyclopropane (6, Hal = H) was inert to the con-
ditions that caused elimination in the substrates in which there was a
substituent in the ring as in 6, 8, 9, and 11.

Methylenecyclopropanes
1515
Nucleophilic Addition to Electrophilic Alkenes
Nucleophilic addition to alkenyl sulfones has been extensively
investigated16,17 quantitatively. Reactivity is extremely sensitive to
substituents on the carbon–carbon double bond. Thus, attachment of a
β-methyl group reduces reactivity in addition of piperidine in ethanol by
a factor of 800 and for the β,β-dimethyl member of the series, tautomer-
ization to the nonconjugated isomer 5 occurs faster than addition.16 In
the present work, we have investigated the effect of the release of strain
as the hybridization of the carbon atoms of the double bond changes
from sp2 to sp3.
The obvious comparison to make is between the strained alkene
7 and the open-chain analogue 2, acknowledging that the there is a
small steric difference between the two substrates. The methyl groups
of the open-chain alkene possibly obstruct approach of the nucle-
ophilic ethoxide ion somewhat more than the methylene groups of the
methylenecyclopropane. On the other hand, the methylene groups of
the methylenecyclopropane, in contrast to the methyl groups of the un-
strained alkene, are not free to rotate. Comparisons are further com-
plicated by the fact that direct addition to the open-chain analogue has
not been observed; with piperidine as nucleophile, isomerization to the
non-conjugated isomer is the result. In the light of these considerations,
we decided to compare the reactivities of sulfones 2, 7, and phenyl vinyl
sulfone 15 towards ethanolic sodium ethoxide. In the cases of sulfones 7
and 15, the products were those expected from simple addition, namely
11 and 2-ethoxyethyl phenyl sulfone 1618 obtained in high yields. By
contrast, sulfone 2 on treatment under the same conditions gave no
addition product, but instead an equilibrium mixture of sulfones 2 and
5 in a ratio consistent with earlier work from another laboratory.19 The
rate of equilibration was measured by the loss of the UV absorption at
230 nm. Results are in Table III.
As seen above, for a powerful nucleophile such as piperidine, ß-
methyl substitution in phenyl vinyl sulfone lowers reactivity. If it is
TABLE III Rate Constants for the Reaction of
Sodium Ethoxide with Vinyl Sulfones
Sulfone
kobs. (M−1s−1
)
Reaction
15
7
2
3.38 · 10−1
1.71 · 10−1
3.78 · 10−3
Addition
Addition
Rearrangement

1516
L. Volta and C. J. M. Stirling
assumed, even for the poorer nucleophile, ethoxide, that ß-methyl sub-
stitution has the same inhibitory effect and that a second ß-methyl
group causes a further 800-fold diminution in the rate of addition,
then the derived rate constant for the ß, ß-dimethyl sulfone 2 is 4.8
–7
· 10. On this basis, the methylenecyclopropylsulfone 7 reacts faster
by a factor of 3.5·10.5 Converted into an energy of activation difference
(assuming as before that A factors are the same), this amounts to 32
kJmol−1 or about 60% of the energy difference between the strained
and unstrained substrates.
EXPERIMENTAL
General
Solids were recrystallized to constant mp. Melting points were obtained
¨
on a Koffler hot stage and are uncorrected. Ethanol was dried by the
magnesium iodine method. Extracts were dried over sodium sulfate.
2-Bromo-2-methyl-1-phenylsulfonylpropane 1b
Benzenesulfonyl bromide (3.47 g, 15.7 mmol) and AIBN (411 mg,
2.5 mmol.) were added to isobutene (1.1 g, 19.6 mmol) in benzene (5
mL). The mixture was kept at 63–65◦C (sealed tube) for 72 h. Con-
centration of the solution gave an oil which on extraction with light
petrol (5 × 20 mL) gave the sulfone (3.05 g, 70%) mp 56–57◦C. 1H NMR
(CDCl3) δ 7.95 (d 2H, J = 8.5 Hz); 7.70–7.50 (m, 3 H); 3.80 (s, 2H), 2.15
(s 6H). IR cm−1 1321,1152 (s). MS, M+ 279. Found: C, 43.4; H, 4.8; Br,
28.8; S, 11.3. C10H13BrO2S requires C, 43.3; H, 4.7; Br, 28.8; S, 11.6%.
Reaction of 2-bromo-2-methyl-1-phenylsulfonylpropane, 1b, with
ethanolic sodium ethoxide. The base solution (0.114 M, 2 mmol) was
added to the sulfone (500 mg, 1.3 mmol) in ethanol (20 mL), and after
30 min, part (14 mL) of the mixture was quenched with saturated aque-
ous ammonium chloride (5 mL) and extracted with dichloromethane.
Evaporation gave a mixture of alkenes (123 mg, 95%), which was by 1H
NMR (CDCl3) δ 7.85–7.80 (m, 2Ha+2Hb), 7.50–7.45 (m, 2Ha + 2Hb),
6.20 (s, 1Ha), 5.05 (s, 1Hb), 3.25 (s, 2Ha), 2.15 (s, 3Ha), 1.90 (s, 3Ha +
3Hb) a 10.5:1 mixture of the α,β- and β,γ-alkenes 2 and 519. After 3h,
the alkene ratio was 1.36:1.
2-Chloro-2-methyl-1-phenylsulfonylpropane 1a
Benzenesulfonyl choride (2.77 g, 15.7 mmol) and AIBN (411 mg, 2.5
mmol) were added to isobutene (1.1 g, 19.6 mmol) in benzene (5 mL).

Methylenecyclopropanes
1517
The mixture was kept at 63–65◦C (sealed tube) for 72 h when evap-
oration gave a brown oil, which on flash chromatography yielded the
sulfone (920 mg), mp 51.5–52◦C. (Lit.20 44–45◦C). Reaction with ethano-
lic sodium ethoxide was as for 1b and gave the alkene mixture in 96%
yield.
2-Methyl-1-phenylsulfonylpropene 2
2-Bromo-2-methylpropyl phenyl sulfone 1b (0.83 g, 39 mmol) in toluene
(5 mL) was treated with triethylamine (4.5 mL, 39 mmol) in toluene (5
mL), and the mixture was boiled under reflux for 5 h. The addition of
water (25 mL) and extraction with dichloromethane and evaporation of
the extracts gave a residue, which on treatment with light petrol gave
the alkene (570 mg, 74%), mp 50–51◦C (lit.21 50◦C).
2-Methyl-1-phenylsulfonyl-2-phenylthiomethylpropane 3
Alkene 2 (1.42 g, 7.2 mmol) was added to thiophenol (1.53 mL, 4.4 mmol)
in ethanolic sodium ethoxide (5 mL, 7.2 mmol), and the mixture was
refluxed for 6 h. The mixture was diluted with water (50 mL) and ex-
tracted with dichloromethane. The extracts were washed successively
with aqueous 5% sodium hydroxide and water, and evaporation gave a
brown oil (2.22 g). Flash chromatography (50:50 ethyl acetate:petrol)
1
gave the sulfide (69%), mp 66◦C (Lit.,22 65◦C) H NMR (CDCl3)δ 7.90
(d, 2H, J = 8.5Hz), 7.71–7.30 (m, 8H), 3.35 (s, 2H), 1.60 (s, 6H); IR
1318, 1151(s); MS M+ 306. Found: C, 62.7; H, 6.0; S, 21.0. Required
for C16H18O2S2: C, 62.7; H, 5.9; S, 20.9%. Reaction of the sulfide with
ethanolic sodium ethoxide was as before to give the mixture of alkenes
(98%).
1,2-Bis-phenylsulfonyl-2-methylpropane 4
Sulfide 3 (1.71 g, 5.6 mmol) was kept at 60◦C in acetic acid (15 mL)
while 30% hydrogen peroxide (14 mL, 120 mmol) was added dropwise.
After 4h, the mixture was diluted with cold brine and extracted with
dichloromethane. The extracts were washed with saturated aqueous
sodium hydrogen carbonate and water. Evaporation gave the sulfone
(58%), mp 159–160◦C. 1H NMR (CDCl3)δ 7.90–7.85 (m, 4H), 7.75–7.55
(m, 6H), 3.55 (s, 2H), 1.65 (s, 6H). IR 1305, 1152 cm−1 (s). Found: C,
56.8; H, 5.3; S, 19.2. C16H18O4S2 requires C, 56.8; H, 5.4; S, 19.0%.
Reaction of the sulfone with ethanolic sodium ethoxide was as before
to give the mixture of alkenes (95%).

1518
L. Volta and C. J. M. Stirling
1-Chloro-1-phenysulfonylmethylcyclopropane 6a
Benzenesulfonyl chloride (4.01 g, 22.7 mmol) and AIBN (1.19 g,
7.1 mmol) were added to a solution of methylenecyclopropane (1.53 g,
28.4 mmol) in benzene (8 mL). The mixture was kept at 64◦C (sealed
tube) for 72 h, and concentration of the solution gave a brown oil, which
was dissolved in pyridine, cooled to 0◦C, treated with water (15 mL),
and extracted with dichloromethane. The extracts were washed with
dilute HCl and water to give a yellow oil (890 mg), which on flash chro-
matography gave the sulfone (218 mg., 0.94 mmol.), mp 64.5–66.0◦C.
1H NMR (CDCl3) δ 7.95 (d, 2H, J = 8.5 Hz), 7.70–7.55 (m, 3H), 3.45 (s,
2H), 1.15–1.10 (m, 2H), 1.05–1.00 (m, 2H). IR cm−1 1326, 1151 (s). MS:
(M+NH4)+ 248. Found: C, 52.3; H, 4.8; Cl, 15.2; S, 13.9. C10H11ClO2S
requires C, 52.1; H, 4.8; Cl, 15.4; S, 13.9%.
1-Bromo-1-phenylsulfonylmethylcyclopropane 6b
1-Bromomethyl-1-bromocyclopropane was obtained by the addition of
bromine to methylenecyclopropane23 at –80◦C and had bp 70–74◦C/20
mm. Hg. (lit.,24 60–70◦C/15 mm, Hg). Thiophenol (2.6 mL, 25.9 mmol)
in ethanolic sodium ethoxide (1 M, 26 mL, 26 mmol.) was added to
the dibromide (26 mmol) in ethanol (5 mL). The mixture was re-
fluxed for 2 h and was then quenched with water and extracted
with dichloromethane. The extracts were washed successively with 2M
sodium hydroxide and water, and evaporation gave the crude sulfide
(5.7 g), of which (4 g) was dissolved in acetic acid (15 mL) at 60◦C
and treated dropwise with hydrogen peroxide (30%, 14 mL, 120 mmol).
The cold mixture was diluted with saturated brine and extracted with
dichloromethane. The extracts were washed with aqueous saturated
sodium hydrogen carbonate and water. Evaporation gave the sulfone
(4.18 g), which on crystallization from ethanol had mp 52.5–54.0◦C
(1.79 g). NMR 1H (CDCl3) δ 8.00 (d, 2H, J = 8.5 Hz), 7.70–7.55 (m, 3H),
3.50 (s, 2H), 1.20–1.15 (m, 2H), 1.10–1.05 (m, 2H). MS: M+ 275. Found:
C, 43.8; H, 4.0; Br, 29.0; S, 11.6. C10H11BrO2S requires C, 43.7; H, 4.0;
Br, 29.0; S, 11.7%.
4-Phenylsulfonylmethylenecyclopropane 7
Triethylamine (10.7 mmol) was added to 1-bromo-1-phenylsulfonyl-
methylcyclopropane 6b (1.02 g, 4.34 mmol) in toluene (20 mL) at 25◦C.
After reflux for 48 h, the mixture was quenched with saturated aque-
ous ammonium chloride, and extraction with dichloromethane gave
1
the sulfone (525 mg, 62%), mp 77–77.5◦C. H NMR δ 7.90 (d, 2H, J =
8.5 Hz), 7.65–7.50 (m, 3H) 6.75 (s, 1H), 1.60–1.45 (m, 2H), 1.40–1.25

Methylenecyclopropanes
1519
(m, 2H). IR cm−1 1317, 1147 (s). MS M+ 194 Found: C, 61.7; H, 5.2; S,
16.4. C10H10O2S requires C, 61.9; H, 5.2; S, 16.5%.
Reaction of 4-Phenylsulfonylmethylenecyclopropane with
Ethanolic Sodium Ethoxide
The methylenecyclopropane (50 mg, 0.26 mmol) in ethanol (20 mL) was
treated with sodium ethoxide (2.6 mmol). The mixture was boiled under
reflux for 12 h, quenched with saturated aqueous ammonium chloride,
and extracted with dichloromethane. Evaporation of the extracts gave
1-ethoxy-1-phenylsulfonylmethylcyclopropane (48 mg, 81%), mp 114.5–
1
116.5◦C. H NMR (CDCl3)δ 8.00 (d, 2H), 7.60–7.50 (m, 3H), 3.35 (s,
2H), 3.20 (q,2H), 0.90–0.75 (m, 5H), 0.60–0.55 (m, 2H). IR cm−11308,
1155 cm−1 (s). MS: (M+NH4)+ 258 Found: C, 59.7; H, 6.9; S, 13.2.
C12H16O3S2 requires C, 60.0; H, 6.7; S, 13.3%.
1-Phenylsulfonyl-1-phenylthiomethylcyclopropane 8
Methylenecyclopropane 6b (483 mg, 2.5 mmol) in ethanol (15 mL) was
treated with thiophenol (5 mmol) and sodium ethoxide (2.5 mmol).
The mixture was refluxed for 4 h and quenched with water and ex-
tracted with dichloromethane. The extracts were washed successively
with aqueous 5% sodium hydroxide and water. Evaporation gave the
crude sulfide which was purified by HPLC to give the sulfide (550 mg,
73%). 1H NMR δ 7.95 (d, 2H, J = 8.5 Hz), 7.70–7.55 (m, 3H), 7.30–7.20
(m, 5H), 3.35 (s, H), 1.30–1.20 (m, 2H). IR cm−11319, 1151 (s). MS: M+
304. Found: C, 63.1; H, 5.4; S, 21.3. C16H16O2S2 requires 62.1; H, 5.3;
S, 21.1%.
1-Phenylsulfonylmethyl-1-phenylsulfonylcyclopropane 9
The preceding sulfide 6b (2.9 g, 5.6 mmol) was kept at 60◦C in acetic acid
(15 mL) while 30% hydrogen peroxide (8 mL, 70 mmol) was added drop-
wise. After 3 h, the mixture was diluted with cold brine and extracted
with dichloromethane. The extracts were washed with saturated aque-
ous sodium hydrogen carbonate and water. Evaporation gave the sul-
fone (61%), mp 81.5–82.5◦C from ethanol. 1H NMR (CDCl3)δ 7.85–7.75
(m, 4H), 7.70–7.65 (m, 2H), 7.60–7.50 (m, 4H), 3.60 (s, 2H), 1.75–1.70
(m, 2H), 1.70–1.65 (m, 2H). IR cm−11321, 1147 cm−1(s). MS: (M+NH4)+
354. Found: C, 57.0; H, 4.7; S, 19.2. C16H18O4S2 requires C, 57.1; H, 4.8;
S, 19.1%.

1520
L. Volta and C. J. M. Stirling
Reaction of 1-Phenylsulfonylmethyl-1-
phenylsulfonylcyclopropane 9 with Sodium Ethoxide and
Piperidine
Piperidine (1.63 mmol) and sodium ethoxide (0.75 mmol) were added
to the sulfone (100 mg, 0.3 mmol) in ethanol (10 mL) at 25◦C. After
90 min, the mixture was quenched with saturated aqueous sodium
chloride and extraction gave the piperidino-sulfone (10) (70 mg, 84%),
mp 67.5–68.5◦C. 1H NMR (CDCl3) δ 7.85 (d, 2H, J = 8.5Hz), 7.60–7.45
(m, 3H), 3.45 (s, 2H), 2.40–2.35 (m, 4H), 1.30 (s, 6H), 0.9–0.80 (m, 2H),
0.80–0.45 (m, 2H). IR cm−1 1308, 1151 (s) MS (M+H)+ Found: C, 64.5;
H, 7.5; N, 4.9; S, 11.5. C15H21NO2S requires C, 64.5; H, 7.6; N, 5.0; S,
11.5%). When the experiment was repeated without addition of sodium
ethoxide, the starting sulfone (92%) was recovered.
1-Ethoxy-1-phenylsulfonylmethylcyclopropane 11, R OEt
The bromosulfone 6b (1.01 g, 2.7 mmol) in ethanol (20 mL) was treated
with sodium ethoxide (3 mmol). After 12 h at reflux, the mixture
was quenched with aqueous ammonium chloride and extracted with
dichloromethane. Evaporation of the extracts gave the sulfone (81%),
1
mp 114.5–116.5◦C (from ethanol). H NMR (CDCl3) δ 8.00 (d, 2H, J =
8.5 Hz)), 7.60–7.50 (m, 3H), 7.60–7.50 (m, 4H), 3.35 (s, 2H), 3.20 (q, 2H,
J = 6.2 Hz), 0.90–0.75 (m, 5H), 0.60–0.55 (m, 2H). IR cm−1 1308, 1155
cm−1 (s). MS: (M+NH4)+ 258. Found: C, 59.7; H, 6.9; S, 13.2 C12H16O3S
requires C, 60.0; H, 6.7; S, 13.3%.
1-Methoxy-1-phenylsulfonylmethylcyclopropane 11, R OMe
The bromosulfone 6b (694 mg, 2.5 mmol) in methanol (20 mL) was
treated with sodium methoxide (19 mmol). After 12 h at reflux, the
mixture was treated as above to give the sulfone (74%), mp 71–72◦C
1
(from ethanol). H NMR (CDCl3) δ 7.95 (d, 2H, J = 8.5Hz), 7.55–7.40
(m, 3H), 3.30 (s, 2H), 2.95 (s, 3H)), 0.80–0.75 (m, 2H), 0.50–0.45 (m,
2H). IR cm−1 1308, 1152 cm−1 (s). MS (M+H)+ 227 Found: C, 58.2; H,
6.2; S, 14.2. C11H14O3S requires C, 58.4; H, 6.2; S, 14.2%.
Reaction of Phenylsulfonylmethylcyclopropane (6, Hal=H)
with Ethanolic Sodium Ethoxide
The sulfone25 (50 mg) was treated with 0.5 M ethanolic sodium ethoxide
(5 mL), and the mixture was kept in a sealed tube for 24 h at 150◦C

Methylenecyclopropanes
1521
and then quenched and extracted as before to give recovered sulfone
(48 mg, 96%).
Product Analyses
These were conducted as for 4-phenylsulphonylmethylenecycl-
opropane above. Results are in Table II.
Kinetics
Solutions of ethanolic sodium ethoxide were prepared by dissolu-
tion of clean sodium in dry ethanol and were standardized against hy-
drochloric acid. For reactions followed by UV spectroscopy, substrates
were used at concentrations of 10−3–10−4 M; concentrations of base
were 10 to 100 times greater. For reactions followed by gc, sealed tubes
were used, and samples were quenched with aqueous ammonium chlo-
ride and extracted with dichloromethane.
Labeling Studies
Solutions of sodium ethoxide in deuterioethanol were used so as to
have a base-substrate ratio of 0.5:1. Work-up was the same as for the
product analyses. Deuterium incorporation was measured by 2H NMR.
Incorporation results are in Table II.
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1522
L. Volta and C. J. M. Stirling
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