The first example of 2,2-dilithiocyanocyclopropanes: generation from 2-bromo-2-sulfinylcyanocyclopropanes with tert-butyllithium, property, and a synthesis of fully substituted cyanocyclopropanes

Article abstract of DOI:10.1016/j.tetlet.2006.12.148

2,2-Dilithiocyanocyclopropanes were easily generated from 2-bromo-2-(p-tolylsulfinyl)cyanocyclopropanes with tert-butyllithium in toluene at -78 °C through concomitant sulfoxide-lithium and bromine-lithium exchange reactions. The gem-dianions were found t

Full text of DOI:10.1016/j.tetlet.2006.12.148

Tetrahedron Letters 48 (2007) 1855–1858
The first example of 2,2-dilithiocyanocyclopropanes:
generation from 2-bromo-2-sulfinylcyanocyclopropanes
with tert-butyllithium, property, and a synthesis of
fully substituted cyanocyclopropanes
Iori Fukushima, Youhei Gouda and Tsuyoshi Satoh*
Department of Chemistry, Faculty of Science, Tokyo University of Science,
Ichigaya-funagawara-machi 12, Shinjuku-ku, Tokyo 162-0826, Japan
Received 17 November 2006; revised 21 December 2006; accepted 22 December 2006
Available online 5 January 2007
Abstract—2,2-Dilithiocyanocyclopropanes were easily generated from 2-bromo-2-(p-tolylsulfinyl)cyanocyclopropanes with tert-
butyllithium in toluene at À78 °C through concomitant sulfoxide–lithium and bromine–lithium exchange reactions. The gem-di-
anions were found to be stable at À78 °C for at least 30 min. Reaction of the gem-dianions with electrophiles gave fully substituted
cyanocyclopropanes in moderate yields.
Ó 2007 Elsevier Ltd. All rights reserved.
Carbanions are obviously one of the most important
reactive intermediates of carbon in synthetic organic
chemistry and innumerable studies for their generation,
property, and synthetic uses have been reported.1,2 Di-
anions with two different carbon atoms bearing the
charge have also been reported1b,3 and extensively used
in organic synthesis. However, dianions with a carbon
bearing two charges, for example geminal dilithio organ-
ic compounds 1,4 have not been extensively studied. In
addition, most of the reported geminal dilithium com-
pounds 1 have one or two carbanion-stabilizing groups
as R1 and/or R2 (Scheme 1).
vinyl p-tolyl sulfoxides 4, and a synthesis of fully
substituted cyanoallenes.7 In continuation of the studies
for the development of new synthetic methods utilizing
a-halo-a-sulfinylcyclopropanes 5, we found that the
treatment of 5 with tert-butyllithium in toluene at
À78 °C resulted in the formation of 2,2-dilithiocyanocy-
clopropanes 6 in high yields. In this Letter, the genera-
tion of gem-dianions 6 and their property and reaction
with electrophiles to give fully substituted cyanocyclo-
propanes 7 are reported.
The details of this study are described by using 2-bromo-
2-(p-tolylsulfinyl)cyanocyclopropane 9 as a representa-
tive example (see Table 1). At first, 1-chlorovinyl p-tolyl
sulfoxide 8 was synthesized from cyclopentadecanone.8
Vinyl sulfoxide 8 was treated with a-lithiopropionitrile
and the adduct was treated with t-BuOK to give a cyclo-
propyl sulfoxide, which was brominated to afford 1-
bromocyclopropyl sulfoxide 9 in a good overall yield.7
Sulfoxide 9 was obtained as a mixture of four diastereo-
mers (one main product, over 85% yield, and three other
minor diastereomers). The well crystalline main product
was used in this study.
On the other hand, the reports concerning the dianion of
cyclopropanes with a carbon bearing two charges, 1,1-
dilithiocyclopropane 2, are few. Two papers for ab initio
molecular orbital calculation of 2 were reported in the
theoretical study of its structure, the planar tetracoordi-
nate carbon.5 Only one report was published for a syn-
thesis of 1,1-dilithio-2,2,3,3-tetramethylcyclopropane 3.6
Recently, we reported a synthesis of 1-bromo-2-cyano-
cyclopropyl p-tolyl sulfoxides 5, derived from 1-chloro-
At first, bromocyclopropyl sulfoxide 9 was treated with
excess t-BuLi in THF at À78 °C for 30 min and the reac-
tion was quenched with water. We expected an allene as
the product via the Doering–LaFlamme reaction9 of the
Keywords: Geminal dianion; 1,1-Dilithiocyclopropane; Cyanocyclo-
propane; Sulfoxide–lithium exchange; Bromine–lithium exchange.
*
Corresponding author. E-mail: tsatoh@rs.kagu.tus.ac.jp
0040-4039/$ - see front matter Ó 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2006.12.148

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I. Fukushima et al. / Tetrahedron Letters 48 (2007) 1855–1858
Li Li
Li Li
Li
Li
R1
R2
H3C
H3C
CH3
CH3
1
2
3
R1 and/or R2 = PhSO2, CN, Ph
R3 CN
R3CH(Li)CN
Cl
R1
R2
t-BuLi
Toluene, -78 °C
R1
R2
S(O)Tol
Br
S(O)Tol
4
5
R3 CN
Electrophile
Li
R3 CN
R1
R1
R2
E
R2
Li
E
6
7
Scheme 1.
Table 1. Generation of 2,2-dilithiocyanocyclopropane 10 from 2-bromo-2-(p-tolylsulfinyl)cyanocyclopropane 9 and quenching of the gem-dianion
with CH3OD to give dideuteriocyanocyclopropane 11
Cl
1) CH3CH(Li)CN
TolS(O)CH2Cl
15
O
2) tert-BuOK
S(O)Tol
3) LDA-CBr4
8
H3C
H3C
CN
H3C
CN
Li
CN
t-BuLi
CH3OD
Toluene
-78 °C, 30 min
S(O)Tol
Br
Li
D(A)
D(B)
9
10
11
Entry
t-BuLi (equiv)
Conditions
Yield of 11/% (D content/%)
Solvent
Temperature (°C)
1
2
3
4
5
6
7
8
6.0
6.0
6.0
6.0
6.0
6.0
4.5
3.0
THF
THF
À78
À50
À78
À50
À30
0–rt
À78
À78
74 (A: 45, B: 72)
53 (A: 36, B: 76)
79 (A: 95, B: 88)
44 (A: 85, B: 83)
36 (A: 74, B: 86)a
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
b
—
84 (A: 93, B: 88)
91 (A: 95, B: 91)
a Allene 12 was obtained in 22% yield.
b Allene 12 was obtained in 67% yield.
O
C(CH3)3
.
15
CH3
12
lithium cyclopropylidene intermediate which was gener-
ated by the sulfoxide–lithium exchange reaction;10 how-
ever, somewhat surprisingly, cyclopropane 11 (hydrogen
instead of deuterium) in a 74% yield was obtained as a
main product. The intermediate of this interesting reac-
tion was expected to be 2,2-dilithiocyanocyclopropane
10.
To confirm the intermediate to be gem-dianion 10, the
reaction was quenched with CH3OD (Table 1, entry 1)

I. Fukushima et al. / Tetrahedron Letters 48 (2007) 1855–1858
1857
and indeed, dideuterated cyclopropane 11 was obtained.
Interestingly, the rate of deuterium incorporation at the
two positions was different (45% and 72%), although the
stereochemistry is obscure at present. The yield and deu-
terium incorporation of 11 was diminished when the
reaction was conducted at À50 °C (entry 2). The low
rate of deuterium incorporation was thought to be
attributable to the use of THF which may act as a pro-
ton source.
4). When this reaction was carried out at above
À30 °C, allenyl ketone 12 was obtained in up to a 67%
yield (entries 5 and 6). Reducing of the amount of t-
BuLi gave a better chemical yield with better deuterium
incorporation (entries 7 and 8).
As mentioned above, the gem-dianion having no carb-
anion-stabilizing group on the carbon was generally rec-
ognized to be quite difficult to generate. However, from
our results described above, it was found that 2,2-di-
lithiocyanocyclopropane having no carbanion-stabilizing
group on the carbanionic carbon could be easily pre-
pared through concomitant sulfoxide–lithium and bro-
mine–lithium exchange reactions. It is noteworthy that
The reaction was next carried out in toluene at À78 °C
(entry 3). Gratifyingly, 11 was obtained in a 79% yield
and deuterium incorporation was also quite good. The
reaction at À50 °C gave again a poorer result (entry
Table 2. Generation of 2,2-dilithiocyanocyclopropane 10 from 2-bromo-2-(p-tolylsulfinyl)cyanocyclopropane 9 and reaction with electrophiles to
afford fully substituted cyanocyclopropanes 13
H3C
H3C
CN
H3C
E
CN
Li
t-BuLi
Electrophile
CN
E
Toluene
-78 °C, 30 min
S(O)Tol
Br
Li
9
10
13
Entry
t-BuLi (equiv)
Electrophile
Conditions
13
E
Yield (%)
1
2
3
4
6.0
4.5
4.5
3.0
CH3I (30 equiv)
À78 to 0 °C, 2 ha
À78 to À50 °C, 1 h
À78 to À50 °C, 1 h
À78 °C, 1 h
CH3
CH3
CH3
COOEt
5
23
49
50
CH3OTs (15 equiv)
CH3OTf (15 equiv)
CICOOEt (3 equiv)
a CuI (40 mol %) was added as an additive.
Table 3. Synthesis of 2-bromo-2-(p-tolylsulfinyl)cyanocyclopropane 5 and treatment of 5 with tert-butyllithium followed by electrophiles to afford
fully substituted cyanocyclopropanes 14
R3 CN
R3 CN
R3 CN
R3CH(Li)CN
t-BuLi
Electrophile
R1
R2
Cl
R1
R2
Li
Li
R1
R2
E
R1
R2
S(O)Tol
Br
Toluene
-78 °C, 30 min
S(O)Tol
E
14
4
5
6
Entry
5
t-BuLi (equiv)
Electrophile
Conditions
14
R1
R2
R3
Yielda (%)
E
Yield (%)
1
2
3
4
5
6
7
8
9
–(CH2)14
–(CH2)14
–(CH2)14
–(CH2)5–
–(CH2)5–
–(CH2)5–
–
–
–
CH3(CH2)3
CH3(CH2)3
CH3(CH2)3
CH3(CH2)3
CH3(CH2)3
CH3(CH2)3
CH3
CH3
CH3
CH3(CH2)3
CH3(CH2)3
CH3(CH2)3
84
4.5
4.5
3.0
4.5
4.5
3.0
4.5
4.5
3.0
4.5
4.5
3.0
CH3OD
CH3OTf
CICOOEt
CH3OD
CH3OTf
CICOOEt
CH3OD
CH3OTf
CICOOEt
CH3OD
CH3OTf
CICOOEt
À78 °C
D
73b
34
À78 to À50 °C
À78 °C, 1 h
À78 °C
CH3
COOEt
D
CH3
COOEt
D
CH3
COOEt
D
CH3
COOEt
40
83
84c
39
À78 to À50 °C
À78 °C, 1 h
À78 °C
42
CH3(CH2)10
CH3(CH2)10
CH3(CH2)10
PhCH2CH2
PhCH2CH2
PhCH2CH2
CH3
CH3
CH3
PhCH2CH2
PhCH2CH2
PhCH2CH2
74d
65
99e
58
À78 to À50 °C
À78 °C, 1 h
À78 °C
52
10
11
12
94f
36
À78 to À50 °C
À78 °C, 1 h
41
a Three-step overall yield from 1-chlorovinyl p-tolyl sulfoxide 4.
b D-content; 91–93%.
c D-content; 94–96%.
d One of the diastereomers that was obtained by recrystallization was used in this study.
e D-content; 96%.
f D-content; 88–92%.

1858
I. Fukushima et al. / Tetrahedron Letters 48 (2007) 1855–1858
this is the first example for the generation of 2,2-
dilithiocyanocyclopropane.
moderate yields. This method contributes to a synthesis
of highly substituted cyclopropanes.
From the viewpoint of synthetic organic chemistry,
trapping of gem-dianion 10 with electrophiles is quite
interesting. Thus, at first, 9 was treated with 6 equiv of
t-BuLi in toluene at À78 °C for 30 min, and to this reac-
tion mixture was added excess iodomethane; however,
only 5% yield of the desired methylated cyclopropane
was obtained (Table 2, entry 1). The use of methyl p-tol-
uenesulfonate as the electrophile gave the desired gem-
dimethylcyclopropane 13 in a 23% yield (entry 2). Final-
ly, the desired dimethylcyclopropane was obtained in a
49% yield with methyl trifluoromethanesulfonate (entry
3). On the other hand, the reaction of the generated 2,2-
dilithiocyanocyclopropane 10 with ethyl chloroformate
gave the desired ethoxycarbonylated cyclopropane in a
50% yield. From the investigation described above, gem-
inal dianion 10 was found to have relatively low nucleo-
philic property.
Acknowledgments
This work was supported by Tokyo University of Sci-
ence, Joint Study Program in Graduate Course, which
is gratefully acknowledged.
References and notes
1. Some monographs concerning the chemistry of carb-
anions: (a) Stowell, J. C. Carbanions in Organic Synthesis;
John Wiley and Sons: New York, 1979; (b) Comprehensive
Carbanion Chemistry; Part A and B; Buncel, E., Durst, T.,
Eds.; Elsevier: Amsterdam, 1980 and 1984; (c) Wakefield,
B. J. Organolithium Methods; Academic Press: London,
1988; (d) Clayden, J. Organolithiums: Selectivity for
Synthesis; Pergamon: Amsterdam, 2002; (e) Wakefield,
B. J. Organomagnesium Methods in Organic Synthesis;
Academic Press: London, 1995; (f) Grignard Reagents New
Developments; Richey, H. G., Jr., Ed.; John Wiley and
Sons: Chichester, 2000.
2. Some selected recent reviews concerning the chemistry of
carbanions: (a) Krief, A. Tetrahedron 1980, 36, 2531; (b)
Katritzky, A. R.; Qi, M. Tetrahedron 1998, 54, 2647; (c)
Friesen, R. W. J. Chem. Soc., Perkin Trans. 1 2001, 1969;
(d) Najera, C.; Sansano, J. M.; Yus, M. Tetrahedron 2003,
59, 9255; (e) Whisler, M. C.; MacNeil, S.; Snieckus, V.;
Beak, P. Angew. Chem., Int. Ed. 2004, 43, 2206; (f)
Chinchilla, R.; Najera, C.; Yus, M. Tetrahedron 2005, 61,
3139.
Finally, generality of these reactions was investigated
using some 2-bromo-2-(p-tolylsulfinyl)cyanocyclopro-
panes and the results are summarized in Table 3. First,
four kinds of 2-bromo-2-(p-tolylsulfinyl)cyanocyclopro-
panes 5 were synthesized from cyclopentadecanone,
cyclohexanone, 2-tridecanone, and 1,5-diphenyl-3-pen-
tanone, with acetonitrile, and hexanenitrile, and the
yields from the corresponding 1-chlorovinyl p-tolyl sulf-
oxides 4 are summarized in the table. As shown in Table
3, all four 2-bromocyanocyclopropanes 5 gave 2,2-
dilithiocyanocyclopropane 6 in a high yield, which was
confirmed by the quenching of the reaction with deute-
rio methanol to give 73–99% yield of dideuterated
cyanocyclopropanes 14 with a high deuterium incorpo-
ration (entries 1, 4, 7, and 10).
3. Thompson, C. M.; Green, D. L. C. Tetrahedron 1991, 47,
4223.
4. Marek, I.; Normant, J.-F. Chem. Rev. 1996, 96, 3241.
5. (a) Collins, J. B.; Dill, J. D.; Jemmis, E. D.; Apeloig, Y.;
Schleyer, Paul von R.; Seeger, R.; Pople, J. A. J. Am.
Chem. Soc. 1976, 98, 5419; (b) Frenking, G. Chem. Phys.
Lett. 1984, 111, 529; (c) Watts, J. D.; Stamper, J. G.
Tetrahedron 1987, 43, 1019.
Dimethylation of dianions 6 with methyl trifluoro-
methanesulfonate gave dimethylcyclopropanes 14 in up to
a 58% yield (entries 2, 5, 8, and 11). The yields for diest-
ers 14 (E = COOEt) were found to be from 40% to 52%.
6. Kawa, H.; Manley, B. C.; Lagow, R. J. J. Am. Chem. Soc.
1985, 107, 5313.
7. Satoh, T.; Gouda, Y. Tetrahedron Lett. 2006, 47, 2835.
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K.; Koyama, M. Tetrahedron 1998, 54, 5557; (b) Satoh, T.;
Kawashima, T.; Takahashi, S.; Sakai, K. Tetrahedron
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Name Reactions; Springer: Berlin, 2002.
In conclusion, we have found that 2,2-dilithiocyano-
cyclopropanes 6 were unexpectedly easily generated
from
2-bromo-2-(p-tolylsulfinyl)cyanocyclopropanes
with t-BuLi in toluene at À78 °C. The gem-dianions
were found to be stable in toluene at À78 °C for at least
30 min. The nucleophilic property was found to be
rather low; however, the dianions react with methyl
trifluoromethanesulfonate and ethyl chloroformate to
afford the fully substituted cyanocyclopropanes in
10. (a) Satoh, T. J. Synth. Org. Chem. Jpn. 1996, 54, 481; (b)
Hitchcock, P. B.; Rowlands, G. J.; Parmar, R. Chem.
Commun. 2005, 4219.