A novel synthetic method for alkylidenecyclopropanes based on the reaction of magnesium cyclopropylidenes with lithium α-sulfonyl carbanions

Article abstract of DOI:10.1016/j.tetlet.2003.10.162

Treatment of 1-chlorocyclopropyl phenyl sulfoxides with isopropylmagnesium chloride at low temperature gave magnesium cyclopropylidenes. The reaction of the generated carbenoids with lithium α-sulfonyl carbanions was found to afford alkylidenecyclopropane

Full text of DOI:10.1016/j.tetlet.2003.10.162

Tetrahedron
Letters
Tetrahedron Letters 45 (2004) 347–350
A novel synthetic method for alkylidenecyclopropanes based
on the reaction of magnesium cyclopropylidenes with
lithium a-sulfonyl carbanions
Tsuyoshi Satoh* and Shinya Saito
Department of Chemistry, Faculty of Science, Tokyo University of Science, Kagurazaka, Shinjuku-ku, Tokyo 162-8601, Japan
Received 1 October 2003; revised 23 October 2003; accepted 24 October 2003
Abstract—Treatment of 1-chlorocyclopropyl phenyl sulfoxides with isopropylmagnesium chloride at low temperature gave mag-
nesium cyclopropylidenes. The reaction of the generated carbenoids with lithium a-sulfonyl carbanions was found to afford
alkylidenecyclopropanes in moderate to good yields. This reaction offers a novel, unprecedented, and versatile method for a syn-
thesis of several alkylidenecyclopropanes from olefins in relatively short steps.
Ó 2003 Elsevier Ltd. All rights reserved.
H
Alkylidenecyclopropanes 1, including methylenecyclo-
propanes (1; R1, R2 ¼ H), are structurally highly
strained; however, usually they are present as stable
compounds at room temperature. On account of the
strain of the alkylidenecyclopropanes, they show high
reactivity with the proper choice of reaction conditions
and are widely used in organic synthesis.1 A variety of
methods for the synthesis of the alkylidenecyclopro-
panes 1 have been reported.2 Representative examples
are the reaction of alkylidene carbenes 2 with olefins2;3
and the reaction of carbenes with allenes2 3 (Scheme 1).
R2
R1
R1
R2
R1
R2
R
R
C :
.
:
3
2
R
1
O
R1R2CSO2Ph
Cl SAr
Cl MgCl
i-PrMgCl
Li
6
R
4
R
5
We recently reported a new method for the generation
of magnesium cyclopropylidenes 54 from 1-chlorocy-
clopropyl phenyl sulfoxide 4 and a Grignard reagent via
the sulfoxide–metal exchange reaction.5 The magnesium
cyclopropylidenes 5 were found to be stable at below
)60 °C and a new method for the synthesis of allenes
was realized.4 In continuation of our interest in the
development of new synthetic methods by utilizing the
generated magnesium cyclopropylidenes 5 in organic
synthesis, we investigated the reaction of 5 with several
nucleophiles and found that the reaction of 5 with lith-
ium a-sulfonyl carbanions 6 gave alkylidenecyclopro-
panes 1 in moderate to good yields.
Scheme 1.
Our investigation is described by using 1-chlorocyclo-
propyl phenyl sulfoxide 8 as a representative example
shown in Scheme 2. Commercially available cyclopropyl
phenyl sulfide 7 was first oxidized with 3-chloroper-
oxybenzoic acid (MCPBA) and the resultant sulfoxide
was chlorinated with N-chlorosuccinimide (NCS) in
CCl4 to afford 1-chlorocyclopropyl phenyl sulfoxide 8 in
93% overall yield.4;6 The sulfoxide 8 is a quite stable
compound.
Keywords: Alkylidenecyclopropane; Magnesium cyclopropylidene;
Magnesium carbenoid; Sulfoxide; Sulfoxide–magnesium exchange.
* Corresponding author. Tel.: +81-5228-8272; fax: +81-3235-2214;
e-mail: tsatoh@ch.kagu.tus.ac.jp
The sulfoxide 8 was treated with 2.5 equiv of i-PrMgCl
at )78 °C. The sulfoxide–magnesium exchange reaction
of 8 was found to take place quite rapidly at )78 °C
0040-4039/$ - see front matter Ó 2003 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2003.10.162

348
T. Satoh, S. Saito / Tetrahedron Letters 45 (2004) 347–350
O
O
PhSCH2Cl
50% NaOH
2.5 equiv
1) MCPBA
SPh
SPh
Cl
Cl MgCl
Cl SPh
SPh
i-PrMgCl
1) MCPBA
TEBACl
CH2Cl2
Lit.7
2) NCS
74%
2) NCS
93%
THF, -78 ˚C
12
13
15
7
8
9
R1R2CSO2Ph
R2
R1R2CSO2Ph
Li
R2
R1
R1
i-PrMgCl
THF, -78 ˚C
R1
R2
SO2Ph
6
Li
MgCl
Cl
6
-
14
11a R1=1-Naphthyl, R2=H
11b R1, R2=Phenyl
10
Sulfone 6
15
Sulfone
11
Entry
Conditions
Entry
Conditions
R1
R2
Yield /%
R1
R2
Yield / %
1
2
3
4
-78 ˚C, 3 h
trace
15
H
1
2
3
4
-78 ˚C, 3 h
39
43
61
50
H
-78 ˚C~-50 ˚C, then -50 ˚C, 3 h
-78 ˚C~-60 ˚C, then -60 ˚C, 3 h
-78 ˚C~-30 ˚C, then -30 ˚C, 3 h
-78 ˚C~ room temp. 4 h
63
-78 ˚C~-50 ˚C, then -50 ˚C, 3 h
-78 ˚C~-40 ˚C, then -40 ˚C, 3 h
64
Scheme 3.
5
6
7
8
-78 ˚C, 3 h
3
19
48
25
-78 ˚C~-60 ˚C, then -60 ˚C, 3 h
-78 ˚C~-50 ˚C, then -50 ˚C, 3 h
-78 ˚C~-40 ˚C, then -40 ˚C, 3 h
yield. The temperature of the reaction mixture was
allowed to warm to )30 °C and the temperature was
kept for 3 h (entry 3) to give a much better yield. Finally,
the conditions described in entry 4 were found to be the
most convenient for our purpose and 64% yield of the
desired alkylidenecyclopropane was obtained. From
these results the best conditions were found to be
somewhat characteristic for the generated magnesium
cyclopropylidenes.
Scheme 2.
within 1 min to give the magnesium cyclopropylidene 9.
After 5 min, 3 equiv of lithium carbanion of (1-naph-
thyl)methyl phenyl sulfone at )78 °C was added to the
solution of the carbenoid through a cannular, and the
temperature of the reaction mixture was slowly allowed
to warm to room temperature. We obtained an oily
product, which has C14H12 as the molecular formula.
From detailed inspection of the spectral data, the
product was determined to be the alkylidenecyclopro-
pane 11a (R1 ¼ 1-naphthyl, R2 ¼ H). The yield was
about 50%.
The examples for the synthesis of alkylidenecyclopro-
panes 15 from 1-chlorocyclopropyl phenyl sulfoxide 13
are summarized in Table 1. Entries 1 and 2 indicate that
the reaction of the carbenoid 14 and lithium a-sulfonyl
carbanions 6 proceeds smoothly when the sulfones
have an aromatic group on the carbanion carbon.
Even diphenyl-substituted alkylidenecyclopropane was
obtained in 50% yield (entry 3). In contrast to this, the
carbanion having an alkyl group (entry 5) gave mark-
edly decreased yield (32%). The triple bond-conjugated
alkylidenecyclopropane could be obtained by this
method albeit in low yield (entry 4).
We investigated the proper conditions of this reaction,
and the results are summarized in the table in Scheme 2.
Entries 1 and 5 indicate that the reaction of the mag-
nesium carbenoid 9 and lithium a-sulfonyl carbanions 6
took place rather slowly at )78 °C. Entries 2 and 6
indicate that the reaction proceeds better at )60 °C than
at )78 °C. Entries 4 and 8 show that the carbenoid 9 is
not stable at )40 °C and gave lower yields. So far, the
best conditions were found to be those in entries 3 and 7,
and we obtained the alkylidenecyclopropanes 11a and
11b in 61% and 48% yields, respectively.
Finally, monosubstituted 1-chlorocyclopropyl phenyl
sulfoxide 16 was synthesized from the corresponding
olefin. We examined the synthesis of alkylidenecyclo-
propane 17 and, at the same time, the feasibility of the
reaction for generation of allene 18 as a by-product. The
allene 18 is expected to generate by the Doering–
Moore–Skattebol reaction4;8 from the intermediate
magnesium cyclopropylidene (Table 2).
In order to know the universality of this reaction with
1-chlorocyclopropyl phenyl sulfoxides, the chloro-sulf-
oxide 13 was synthesized from cyclohexene through the
sulfide 127 (Scheme 3). The chloro-sulfoxide 13 was
treated with i-PrMgCl followed by the lithium a-carb-
anion of sulfones 6 under the best conditions described
in Scheme 2 (entry 2 in Scheme 3); however, the desired
alkylidenecyclopropane 15 was obtained in only 15%
In any event, 16 was first treated with 2.5 equiv of
i-PrMgCl at )78 °C and then lithium a-sulfonyl carb-
anion derived from (1-naphthyl)methyl phenyl sulfone
was added to the reaction mixture. The temperature of
the reaction mixture was gradually allowed to warm to
room temperature (Table 2, entry 1). This reaction gave

T. Satoh, S. Saito / Tetrahedron Letters 45 (2004) 347–350
349
Table 1. Synthesis of alkylidenecyclopropanes 15 from 1-chlorocyclopropyl phenyl sulfoxide 13 and lithium a-sulfonyl carbanions
Entry
Sulfone 6
Alkylidenecyclopropane 15
Yield (%)
R1
R2
H
1
64
H
Ph
H
2
3
4
5
Ph
Ph
H
73
50
25
32
Ph
Ph
Ph
H
C5H11
C
C
H11
C5
H
OCH3
CH3O
CH2CH2
H
H
Table 2. Synthesis of alkylidenecyclopropanes 17 from 2-substituted-
1-chlorocyclopropyl phenyl sulfoxide 16 and lithium a-sulfonyl car-
banions
From a careful inspection of the products of this reac-
tion, we found that the expected allene 18 was present
albeit in trace amount. This result implied that the re-
action of the a-sulfonyl carbanion reacts faster with the
magnesium cyclopropylidenes than the isomerization to
allene 18 (Doering–Moore–Skattebol reaction). Other
examples are shown in Table 2. As shown in Table 2, the
magnesium cyclopropylidene generated from the sulf-
oxide 16 showed high reactivity with the lithium a-sul-
fonyl carbanions 6. The carbanion derived from benzyl
phenyl sulfone gave the desired alkylidenecyclopropane
in high yield (entry 2). Even the carbanion having an
alkyl group (in this case a methyl group) gave the
desired product in 56% yield (entry 3). Diphenyl-
substituted alkylidenecyclopropane was obtained; how-
ever, the yield was somewhat lower compared with the
case in Table 1. Even in this case, the allene 18 was
observed in trace amount (entry 4). The carbanion
having both methyl and phenyl groups also gave the
desired product in 49% yield (entry 5).
O
R2
R1
1) i-PrMgCl
THF, -78 ˚C
Cl SPh
2) R1R2CSO2Ph CH3O
CH3O
17
16
6
Li
-78 ˚C ~ r.t.
CH3O
.
18
Entry
Sulfone
17
R1
R2
H
Yield (%)
1
2
78a;b
H
H
91a;c
3
4
CH3
56a;d
34
In conclusion, we have found that the reaction of the
magnesium cyclopropylidenes with lithium a-sulfonyl
carbanions gave alkylidenecyclopropanes. This is the
first example of the synthesis of alkylidenecyclopropanes
by the alkenylation of the activated cyclopropane moi-
ety with nucleophiles (carbanions) and offers a novel
and relatively short synthesis of alkylidenecyclopro-
panes from olefins.
5
CH3
49a;e
a A mixture of two diastereomers. The structure has not been deter-
mined yet.
b The ratio 7:1.
c The ratio 25:1.
d The ratio 2:1.
e The ratio 3:1.
Acknowledgements
This work was supported by a grant from the Ministry
of Education, Culture, Sports, Science and Technology
of Japan to promote multi-disciplinary research project,
which is gratefully acknowledged.
a quite good result and the desired alkylidenecyclo-
propane 17 was obtained as a mixture of two diastereo-
mers.

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T. Satoh, S. Saito / Tetrahedron Letters 45 (2004) 347–350
985; (k) Patient, L.; Berry, M. B.; Kilburn, J. D.
Tetrahedron Lett. 2003, 44, 1015.
References and Notes
2. An excellent review: Brandi, A.; Goti, A. Chem. Rev. 1998,
98, 589.
3. Sasaki, A.; Aoyama, T.; Shioiri, T. Tetrahedron 1999, 55,
3687.
4. Satoh, T.; Kurihara, T.; Fujita, K. Tetrahedron 2001, 57,
5369.
5. (a) Satoh, T.; Yamakawa, K. Rev. Heteroatom Chem.
1992, 6, 218; (b) Satoh, T. J. Syn. Org. Chem. Jpn. 1996,
54, 481; (c) Satoh, T. J. Syn. Org. Chem. Jpn. 2003, 61, 98.
6. Masuda, T.; Furukawa, N.; Oae, S. Chem. Lett. 1977,
1103.
7. Bhupathy, M.; Cohen, T. Tetrahedron Lett. 1987, 28, 4797.
8. (a) Doering, W. von E.; LaFlamme, P. M. Tetrahedron
1958, 2, 75; (b) Moore, W. R.; Ward, H. R. J. Org. Chem.
1960, 25, 2073; (c) Skattebol, L. Tetrahedron Lett. 1961, 2,
167; (d) Moore, W. R.; Ward, H. R. J. Org. Chem. 1962,
27, 4179.
1. Some recent reports for the use of alkylidenecyclopro-
panes in organic synthesis: (a) Motherwell, W.; Shipman,
M. Tetrahedron Lett. 1991, 32, 1103; (b) Penfold, D.; Pike,
K.; Genge, A.; Anson, M.; Kitteringham, J.; Kilburn, J.
D. Tetrahedron Lett. 2000, 41, 10347; (c) Watson, F. C.;
Kilburn, J. D. Tetrahedron Lett. 2000, 41, 10341; (d)
Nakamura, I.; Saito, S.; Yamamoto, Y. J. Am. Chem. Soc.
2000, 122, 2661; (e) Oh, B. H.; Nakamura, I.; Saito, S.;
Yamamoto, Y. Tetrahedron Lett. 2001, 42, 6203; (f)
Nakamura, I.; Oh, B. H.; Saito, S.; Yamamoto, Y. Angew.
Chem., Int. Ed. 2001, 40, 1298; (g) Nakamura, I.;
Siriwardana, A. I.; Saito, S.; Yamamoto, Y. J. Org.
Chem. 2002, 67, 3445; (h) Shi, M.; Chen, Y.; Xu, B.; Tang,
J. Tetrahedron Lett. 2002, 43, 8019; (i) Camacho, D.;
Nakamura, I.; Oh, B. H.; Saito, S.; Yamamoto, Y.
Tetrahedron Lett. 2002, 43, 2903; (j) Siriwardana, A. I.;
Nakamura, I.; Yamamoto, Y. Tetrahedron Lett. 2003, 44,