A new synthesis, including asymmetric synthesis, of alkylidenecyclopropanes by 1,2-CC insertion of cyclobutylmagnesium carbenoides as the key reaction

Article abstract of DOI:10.1016/j.tetlet.2009.04.038

Treatment of 1-chlorovinyl p-tolyl sulfoxides, derived from ketones and chloromethyl p-tolyl sulfoxide, with lithium enolate of carboxylic acid tert-butyl esters gave adducts in high yields. The adducts were converted to 1-chlorocyclobutyl p-tolyl sulfoxi

Full text of DOI:10.1016/j.tetlet.2009.04.038

Tetrahedron Letters 50 (2009) 4212–4216
Contents lists available at ScienceDirect
Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
A new synthesis, including asymmetric synthesis, of alkylidenecyclopropanes
by 1,2-CC insertion of cyclobutylmagnesium carbenoides as the key reaction
*
Nobuhito Nakaya, Shimpei Sugiyama, Tsuyoshi Satoh
Department of Chemistry, Faculty of Science, Tokyo University of Science, Ichigaya-funagawara-machi 12, Shinjuku-ku, Tokyo 162-0826, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
Treatment of 1-chlorovinyl p-tolyl sulfoxides, derived from ketones and chloromethyl p-tolyl sulfoxide,
with lithium enolate of carboxylic acid tert-butyl esters gave adducts in high yields. The adducts were
converted to 1-chlorocyclobutyl p-tolyl sulfoxides in four steps in high overall yields. Treatment of the
1-chlorocyclobutyl p-tolyl sulfoxides with cyclopentylmagnesium chloride in THF at ꢀ40 °C resulted in
the formation of cyclobutylmagnesium carbenoids. The magnesium carbenoid 1,2-CC insertion reaction
took place smoothly from the cyclobutylmagnesium carbenoids to afford alkylidenecyclopropanes in
good to high yields. An asymmetric synthesis of optically active alkylidenecyclopropane was successfully
achieved starting from optically active 1-chlorovinyl p-tolyl sulfoxide.
Received 21 March 2009
Revised 7 April 2009
Accepted 9 April 2009
Available online 14 April 2009
Keywords:
Alkylidenecyclopropane
Sulfoxide–magnesium exchange
Magnesium carbenoid
Cyclobutylmagnesium carbenoid
1,2-CC insertion
Ó 2009 Elsevier Ltd. All rights reserved.
1. Introduction
converted to an iodide group under conventional reactions to give
iodides 4, which are treated with a base to afford 1-chlorocyclobu-
Alkylidenecyclopropanes, including methylenecyclopropanes,
are quite interesting compounds. They are structurally highly
strained; however, usually present as stable compounds at room
temperature. Because of their highly strained nature, alkylidenecy-
clopropanes show various reactivities and have long been used
widely in organic synthesis.1 Moreover, some biologically active
compounds comprising an alkylidenecyclopropane moiety as a
basic skeleton, such as G1499-2, amphimic acids, and 9-hydrox-
ymethylcyclopropylidene-methylenyladenine,2 have been known.
Therefore, new methods for the synthesis of alkylidenecyclopro-
panes are very much desired.
tyl p-tolyl sulfoxides 5 in high yields. Finally, sulfoxides 5 are
treated with cyclopentylmagnesium chloride to give alkylidenecy-
clopropanes 6 in good yields. When optically active 1-chlorovinyl
p-tolyl sulfoxide 2 was used in this procedure, an asymmetric syn-
thesis of optically active alkylidenecyclopropane 6 was achieved. In
this Letter we report the above-mentioned procedure.
2. Results and discussion
At first, representative example of this procedure is shown
using 1-chlorovinyl p-tolyl sulfoxide 7, which was derived from
cyclohexanone, as the starting material (Scheme 2). Thus, 1-chloro-
vinyl p-tolyl sulfoxide 77a was treated with lithium enolate of tert-
butyl 3-phenylpropionate to afford adduct 8 in a quantitative
yield.8 Stereochemistry of adduct 8 (syn-relationship between the
chlorine atom and the benzyl group) was determined based on
our previous study.9 The adduct was treated with trifluoroacetic
acid in dichloromethane to give a carboxylic acid, which was re-
duced with BH3–THF in THF at 0 °C to give alcohol 9 in 91% overall
yield from 8. Attempt to direct reduction of ester 8 with DIBAL to
alcohol 9 resulted in low yield (up to 60%). The hydroxyl group
in 9 was converted to iodide group under the conventional reaction
and the resultant iodide was treated with 2 equiv of KHMDS to give
the desired 1-chlorocyclobutyl p-tolyl sulfoxide 10 in 94% overall
yield from 9 as a single product.10 Stereochemistry of 10 was deter-
mined by NOESY spectrum of the desulfinylated compound 13
(vide infra).
A variety of the methods for synthesis of alkylidenecyclopro-
panes have been reported;3 however, synthesis of optically active
alkylidenecyclopropanes is limited.4 We are also interested in the
chemistry of alkylidenecyclopropanes and reported their synthesis
based on the reaction of cyclopropylmagnesium carbenoids with
lithium
a
-sulfonyl carbanions.5 In continuation of our interest in
the chemistry of magnesium carbenoids in organic synthesis,6 re-
cently, we developed a new method for a synthesis, including
asymmetric synthesis, of alkylidenecyclopropanes by our original
method as shown in Scheme 1.
Thus, 1-chlorovinyl p-tolyl sulfoxides 2, synthesized from
ketones 1,7 are treated with lithium enolate of tert-butyl carboxyl-
ates to give adducts 3 in high yields. The tert-butyl ester moiety is
* Corresponding author. Tel.: +81 3 5228 8272; fax: +81 3 5261 4631.
E-mail address: tsatoh@rs.kagu.tus.ac.jp (T. Satoh).
0040-4039/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2009.04.038

N. Nakaya et al. / Tetrahedron Letters 50 (2009) 4212–4216
4213
O
R1 R2
O
R3
R1
R2
Cl
O
TolS(O)CH2Cl
OBu-t
S(O)Tol
R1
R2
t-BuO
LDA / THF, -78 °C
S(O)Tol
R3 Cl
3 steps
1
2
3
R1, R2 = Alkyl
R2
R1
R2
R1
R1 R2
MgCl
KHMDS
S(O)Tol
S(O)Tol
I
R3
Cl
R3 Cl
3 steps
*
R3
5
4
6
Scheme 1.
O
O
Cl
Ph
OBu-t
, LDA
O
S(O)Tol
t-BuO
PhCH2
THF, -78 °C
99 %
S(O)Tol
3 steps
Cl
7
8
1) TFA, CH2Cl2
1) Ph3P, Imid., I2, THF
S(O)Tol
S(O)Tol
Cl
HO
2) BH3-THF, THF, 0 °C
2) KHMDS, THF, 0 °C
94 % (2 steps)
PhCH2
PhCH2
91 % from 8
Cl
10
9
(Single isomer)
1,2-CC
Insertion
iPrMgCl (3 eq)
THF, -78 °C, 15 min
H
+
H
1
MgCl
Cl
PhCH2
CH2
Cl
PhCH2
PhCH2
PhCH2
13
24 %
14
11
12
48 %
Scheme 2.
The key reaction was carried out as follows. A solution of
i-PrMgCl in ether (3 equiv) was added to a solution of 1-chlorocyc-
lobutyl p-tolyl sulfoxide 10 in THF at ꢀ78 °C under Ar atmosphere.
After the reaction mixture was stirred for 15 min, the reaction was
quenched with satd aq NH4Cl. The reaction mixture was rather
clean and two products were obtained. The main product was
determined to be 2-benzyl(cyclopropylidene)cyclohexane 12
(48%) and the minor product was desulfinylated chlorocyclobutane
13 (24%). Alkylidenecyclopropane 12 is the expected product from
1,2-CC insertion reaction of the cyclobutylmagnesium carbenoid
11, which was derived from 10 by the sulfoxide–magnesium
exchange reaction, and 13 is the protonated product of 11. Quite
interestingly, methylenecyclopropane 14, which is another
expected product from the 1,2-CC insertion reaction of the magne-
sium carbenoid intermediate 11, was not observed at all. Configura-
tion of 13 was determined from its 1H NMR spectrum, especially by
NOESY spectrum (NOE was observed between the hydrogens on the
carbons bearing the chlorine atom and the benzyl group). Configu-
ration of the starting material 10 was determined to be as shown in
Scheme 2 from the stereochemistry of 13.11
investigated and the results are summarized in Table 1. Entries
1–4 show the effects of four Grignard reagents other than i-PrMgCl
at ꢀ78 °C for 15 min. The sulfoxide–magnesium exchange reaction
did not take place with MeMgCl and PhMgCl. EtMgCl and cyclopen-
tylmagnesium chloride gave 12 in better yields compared to that of
i-PrMgCl (48%; see Scheme 2). We concluded that cyclopentylmag-
nesium chloride is the Grignard reagent of choice in this reaction.
Entries 5–9 show the effect of the temperature of the reaction
with cyclopentylmagnesium chloride in THF for 15 min. As shown,
when the reaction was carried out at ꢀ40 °C, the best yield (87%)
was obtained (entry 6). Entries 10–13 show the results for the
reaction time in THF at ꢀ40 °C. Both shortening and prolonging
of the reaction time did not give better results. Finally, we investi-
gated the effect of the solvent (entries 14 and 15) and found that
both ether and toluene were not effective to this reaction. We con-
cluded that the conditions in entry 6 are the conditions of choice in
this reaction.
Next, generality of this procedure was examined and the results
are summarized in Table 2. As the starting material for the synthe-
sis of 1-chlorocyclobutyl p-tolyl sulfoxides 15a–15g, cyclopenta-
none, cycloheptanone, cyclopentadecanone, and cyclohexanone
were used as cyclic ketones (entries 1–4). Acetone and 4-phenyl-
2-butanone were used as acyclic ketones (entries 5–7). tert-Butyl
As we recognized that the above-mentioned procedure would
become quite interesting and new way for a synthesis of alkylid-
enecyclopropanes, the proper conditions to the key reaction were

4214
N. Nakaya et al. / Tetrahedron Letters 50 (2009) 4212–4216
Table 1
Examination of the optimum conditions for the synthesis of alkylidenecyclopropane 12 through the magnesium carbenoid 1,2-CC insertion reaction
Grignard Reagent (3 eq)
S(O)Tol
Cl
H
+
Conditions
PhCH2
Cl
PhCH2
PhCH2
10
13
12
Entry
Grignard reagent
Conditions
Yield (%)
Temp (°C)
Time (min)
Solvent
12
13
a
1
2
3
MeMgCl
PhMgCl
EtMgCl
ꢀ78
ꢀ78
ꢀ78
15
15
15
THF
THF
THF
—
—
—
19
a
—
54
4
ꢀ78
15
THF
56
29
MgCl
5
6
7
8
9
ꢀ60
ꢀ40
ꢀ20
0
15
15
15
15
15
THF
THF
THF
THF
THF
76
87
73
71
73
15
1
MgCl
MgCl
MgCl
MgCl
MgCl
2
2
rt
1
10
11
12
13
ꢀ40
ꢀ40
ꢀ40
ꢀ40
5
10
30
60
THF
THF
THF
THF
74
85
80
75
6
3
1
2
MgCl
MgCl
MgCl
MgCl
14
ꢀ40
ꢀ40
15
15
Et2O
39b
27c
Trace
Trace
MgCl
MgCl
15
Toluene
a
No reaction was observed and the starting material was quantitatively recovered.
The starting material was recovered in 58%.
The starting material was recovered in 69%.
b
c
3-phenylpropionate, tert-butyl 4-phenylbutyrate, and tert-butyl
propionate were used as esters.
The sulfoxide–magnesium exchange reaction was carried out
under the best conditions as mentioned above (Table 1, entry 6).
As shown in Table 2, all 1-chlorocyclobutyl p-tolyl sulfoxides 15,
except one case (entry 2), gave the desired alkylidenecyclopro-
panes 16 in 62–86% yields. From these results, the procedure pre-
sented herein proved to be quite useful for obtaining various
alkylidenecyclopropanes. When diastereomers 15f and 15g were
treated with cyclopentylmagnesium chloride, a mixture of two
geometrical isomers was obtained (entries 6 and 7). These results
suggested that this 1,2-CC insertion would not be a concerted reac-
tion but a stepwise reaction.
Table 2
Synthesis of alkylidenecyclopropanes 16 from 1-chlorocyclobutyl p-tolyl sulfoxides
15 through the magnesium carbenoid 1,2-CC insertion reaction
As an application of this procedure, an asymmetric synthesis of
optically active alkylidenecyclopropanes was investigated (Scheme
3). Thus, optically active 1-chlorovinyl p-tolyl sulfoxide 17 was
synthesized from cyclohexanone with (R)-chloromethyl p-tolyl
sulfoxide.12 Addition reaction of 17 with lithium enolate of tert-bu-
tyl 3-phenylpropionate gave adduct 18 and all the absolute stereo-
chemistry were unambiguously determined as shown in Scheme 3
based on our previous work.9,13 Optically active 18 was converted
to optically active (1R,3S,Rs)-1-chloro-3-benzyl-1-(p-tolylsulfi-
nyl)spiro[3.5]nonane 19 in the same reaction described above.
Finally, optically active 19 was treated with cyclopentylmagne-
sium chloride in THF at ꢀ40 °C to give optically active (S)-2-ben-
zylcyclopropylidenecyclohexane 20 in 87% yield.14 The optical
purity of 20 was easily determined to be over 97% by using a chiral
stationary column (CHIRALCEL OD (Daicel); hexane as a developing
solvent). As the optical purity of the starting material, (R)-chloro-
methyl p-tolyl sulfoxide, was 97–99%,12 the procedure shown in
Scheme 3 is thought to proceed without racemization.
R1
R2
R2
S(O)Tol
R1
R3
(3 eq)
MgCl
THF, -40 °C, 15 min
Cl
R3
15
16
16
Entry
15
R1
R2
R3
Yield (%)
1
2
3
4
5
6
7
15a
15b
15c
15d
15e
15f
–(CH2)4–
–(CH2)6–
–(CH2)14
–(CH2)5–
CH3
PhCH2
PhCH2
PhCH2
PhCH2CH2
PhCH2
CH3
62
39a
73
–
86
CH3
CH3
77
PhCH2CH2
CH3
82b
75c
15g
PhCH2CH2
CH3
a
b
c
The structure of the other products could not be determined.
A 2:1 mixture of two geometrical isomers was obtained.
A 1:1 mixture of two geometrical isomers was obtained.

N. Nakaya et al. / Tetrahedron Letters 50 (2009) 4212–4216
4215
Delanghe, P. H. M. J. Am. Chem. Soc. 1994, 116, 8526; Synthesis from optically
active epoxyalcohols: (a) Achmatowicz, B.; Kabat, M. M.; Krajewski, J.; Wicha, J.
Tetrahedron 1992, 48, 10201; (b) Lai, M.-t.; Oh, E.; Shih, Y.; Liu, H.-w. J. Org.
Chem. 1992, 57, 2471; (c) Ramaswamy, S.; Prasad, K.; Repic, O. J. Org. Chem.
1992, 57, 6344; (d) Baldwin, J. E.; Adlington, R. M.; Bebbington, D.; Russell, A. T.
Tetrahedron 1994, 50, 12015; (e) Nemoto, T.; Ojika, M.; Sakagami, Y.
Tetrahedron Lett. 1997, 38, 5667; Synthesis from enantiomerically pure
cyclopropenylcarbinols: (a) Simaan, S.; Masarwa, A.; Bertus, P.; Marek, I.
Angew. Chem., Int. Ed. 2006, 45, 3963; (b) Marek, I.; Simaan, S.; Masarwa, A.
Angew. Chem., Int. Ed. 2007, 46, 7364; (c) Masarwa, A.; Stanger, A.; Marek, I.
Angew. Chem., Int. Ed. 2007, 46, 8039; Other methods: (a) Chevtchouk, T.;
Ollivier, J.; Salaun, J. Tetrahedron: Asymmetry 1997, 8, 1005; (b) Zohar, E.;
Stanger, A.; Marek, I. Synlett 2005, 2239.
Cl
S
H2C
(R)
Tol
O
Cl
S
O
O
Tol
O
17
O
5. Satoh, T.; Saito, S. Tetrahedron Lett. 2004, 45, 347.
PhCH2
O
OBu-t
(R)
S
6. (a) Satoh, T. Chem. Soc. Rev. 2007, 36, 1561; (b) Satoh, T. In The Chemistry of
Organomagnesium Compounds; Rappoport, Z., Marek, I., Eds.; John Wiley and
Sons: Chichester, UK, 2008; pp 717–769.
7. (a) Satoh, T.; Kawashima, T.; Takahashi, S.; Sakai, K. Tetrahedron 2003, 59, 9599;
(b) Sugiyama, S.; Satoh, T. Tetrahedron: Asymmetry 2005, 16, 665.
4 steps; see
in Scheme 2
To l
t-BuO
LDA / THF, -78 °C
99%
(S)
(R)
Cl
PhCH2
18
8. Adduct 8 was obtained as a mixture of two diastereomers (the ratio 93:7) with
respect to the stereogenic carbon bearing the chlorine atom.
O
9. Sugiyama, S.; Nakaya, N.; Satoh, T. Tetrahedron: Asymmetry 2008, 19, 401.
10. Experimental procedure for the synthesis of 3-benzyl-1-chloro-1-(p-
tolylsulfinyl)spiro[3.5]nonane 10. tert-Butyl 3-phenylpropionate (3.8 g;
18.6 mmol) was added to a solution of LDA (18.6 mmol) in 69 mL of dry THF
at ꢀ78 °C with stirring under argon atmosphere. The solution was stirred for
15 min, and a solution of 7 (1.0 g; 3.7 mmol) in THF (5 mL) was added. The
reaction mixture was stirred for 15 min, and the reaction was quenched by
adding satd aq NH4Cl. The whole was extracted with CHCl3. The organic layer
was dried over MgSO4 and concentrated in vacuo. The product was purified by
silica gel column chromatography to afford 8 (1.75 g; 99%) as colorless oil; IR
(neat) 3028, 2976, 2931, 1722 (CO), 1597, 1494, 1456, 1367, 1254, 1221, 1144,
1083, 1056 (SO); 1H NMR d 1.20 (9H, s), 1.23–1.45 (2H, m), 1.45–1.63 (2H, m),
1.66–1.86 (3H, m), 1.87–2.07 (1H, m), 2.09–2.21 (1H, m), 2.45 (3H, s), 2.66–
2.79 (1H, m), 2.99–3.18 (1H, m), 3.28–3.46 (2H, m), 5.07 (1H, s), 7.14–7.29 (5H,
m), 7.34 (2H, d, J = 8.1 Hz), 7.77 (2H, d, J = 8.1 Hz). MS m/z (%) 474 (M+, trace),
457 (7), 401 (14), 281 (16), 279 (48), 243 (63), 242 (16), 197 (39), 161 (31), 141
(27), 140 (100), 141 (28), 91 (96). Calcd for C27H35ClO3S: M, 474.1996. Found;
m/z 474.1995.
(3 eq)
MgCl
S
Tol
(S)
THF, -40 °C, 15 min
87 %
(S)
Cl
PhCH2
PhCH2
20
19
97% ee
[α]D28= +50.5 (c 0.9, EtOH)
Scheme 3.
In conclusion, we have developed a new method for a synthesis
of alkylidenecyclopropanes from 1-chlorovinyl p-tolyl sulfoxides.
In addition, by using optically active 1-chlorovinyl p-tolyl sulfox-
ides asymmetric synthesis of them can be realized. Synthesis of
alkylidenecyclopropanes from 1,1-dibromocyclobutanes with
methyllithium has been known.15 The presented procedure is the
first example for the synthesis of alkylidenecyclopropanes through
the 1,2-CC insertion of cyclobutylmagnesium carbenoids with one-
carbon contraction.
TFA (0.92 mL; 12.4 mmol) was added to a solution of 8 (1.18 g; 2.5 mmol) in
25 mL of CH2Cl2 with stirring. The solution was stirred for 1 day and the
reaction was quenched with satd aq NaHCO3. The whole was extracted with
CH2Cl2, and the organic layer was dried over MgSO4. The solvent was
evaporated to afford crude carboxylic acid. A solution of BH3–THF complex
(12.4 mmol) in 11.7 mL of THF was added dropwise to a solution of the crude
carboxylic acid in 25 mL of THF under argon atmosphere with stirring. The
solution was stirred for 1 day and the reaction was quenched with satd aq
NH4Cl. The whole was extracted with CHCl3, and the organic layer was dried
over MgSO4. The solvent was evaporated and the residue was purified by silica
gel column chromatography to afford alcohol 9 (918 mg; 91% from 8) as
colorless crystals. Mp 108–109 °C (AcOEt–hexane); IR (KBr) 3445 (OH), 3060,
Acknowledgments
3026, 2927, 1738, 1597, 1495, 1455, 1399, 1304, 1244, 1082, 1050 (SO) cmꢀ1
;
1H NMR d 1.37–1.56 (3H, m), 1.63–1.87 (4H, m), 1.91–2.05 (1H, m), 2.12–2.25
(1H, m), 2.34–2.48 (2H, m), 2.45 (3H, s), 2.86 (1H, dd, J = 13.4, 11.5 Hz), 3.19
(1H, dd, J = 13.4, 2.8 Hz), 3.68–3.81 (1H, m), 3.88–4.00 (1H, m), 4.95 (1H, s),
7.17–7.27 (1H, m), 7.28–7.39 (6H, m), 7.72–7.79 (2H, m). MS m/z (%) 405
([M+H]+, trace), 387(5), 230 (12), 229 (72), 211 (16), 199 (6), 155 (5), 140 (66),
141 (28), 117 (34), 90 (29), 91 (100). Calcd for C23H30ClO2S: M+H,
405.1646.Found; m/z 405.1650.
This work was supported by a Grant-in-Aid for Scientific
Research No. 19590018 from the Ministry of Education, Culture,
Sports, Science and Technology, Japan, and TUS Grant for Research
Promotion from Tokyo University of Science, which are gratefully
acknowledged. We thank Professor Shinichi Saito of this depart-
ment for his helpful suggestion.
Ph3P (2.97 g; 11.3 mmol) and I2 (1.44 g; 11.3 mmol) were added to a solution
of 9 (918 mg; 2.3 mmol) in 23 mL of THF with stirring. After the solution was
stirred for 10 min, imidazole (771 mg; 11.3 mmol) was added to the reaction
mixture. After 15 min of stirring, the reaction was quenched with satd aq
Na2SO3. The whole was extracted with CHCl3, and the organic layer was dried
over MgSO4. The solvent was evaporated and the residue was purified by silica
gel column chromatography to give the desired iodide. A solution of KHMDS
(4.5 mmol) in 9.1 mL of toluene was added dropwise to a solution of the iodide
in 91 mL of THF at 0 °C under argon atmosphere with stirring. The reaction
mixture was stirred for 15 min and the reaction was quenched with satd aq
NH4Cl. The whole was extracted with CHCl3, and the organic layer was dried
over MgSO4. The solvent was evaporated and the residue was purified by silica
gel column chromatography to afford 10 (822 mg; 94% in two steps) as
colorless oil; IR (neat) 3026, 2928, 2856, 1598, 1495, 1454, 1086, 1059
References and notes
1. Some recent reviews and papers with regard to the use of
alkylidenecyclopropanes in organic synthesis: (a) Ferrara, M.; Cordero, F. M.;
Goti, A.; Brandi, A.; Estieu, K.; Paugam, R.; Ollivier, J.; Salaun, J. Eur. J. Org. Chem.
1999, 2725; (b) Binger, P.; Buch, H. M. Top. Curr. Chem. 1987, 135, 77; (c)
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Cicchi, S.; Cordero, F. M.; Goti, A. Chem. Rev. 2003, 103, 1213; (e) Chowdhury, M.
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Castedo, L.; Mascarenas, J. L. Org. Lett. 2005, 7, 5693; (g) Rubin, M.; Rubina, M.;
Gevorgyan, V. Chem. Rev. 2007, 107, 3117; (h) Sethofer, S. G.; Staben, S. T.;
Hung, O. Y.; Toste, F. D. Org. Lett. 2008, 10, 4315; (i) Komagawa, S.; Yamasaki,
R.; Saito, S. J. Synth. Org. Chem. Jpn. 2008, 66, 974.
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C.; Shimo, T.; Somekawa, K.; Baba, M. Tetrahedron 1998, 54, 2031.
3. An excellent review and some recent papers for the synthesis of
alkylidenecyclopropanes: (a) Brandi, A.; Goti, A. Chem. Rev. 1998, 98, 589; (b)
Danheiser, R. L.; Lee, T. W.; Menichincheri, M.; Brunelli, S.; Nishiuchi, M. Synlett
1997, 469; (c) Sakai, A.; Aoyama, T.; Shioiri, T. Tetrahedron 1999, 55, 3687; (d)
Bernard, A. M.; Frongia, A.; Piras, P. P.; Secci, F. Synlett 2004, 1064.
(SO) cmꢀ1 1H NMR d 1.34–1.60 (4H, m), 1.66–1.95 (4H, m), 1.96–2.15 (2H, m),
;
2.18–2.31 (1H, m), 2.34–2.49 (2H, m), 2.39 (3H, s), 2.72–2.86 (1H, m), 3.05 (1H,
dd, J = 13.6, 4.1 Hz), 7.08–7.15 (2H, m), 7.15–7.31 (5H, m), 7.46–7.54 (2H, m).
MS m/z (%) 386 (M+, trace), 247 (10), 212 (12), 211 (61), 201 (5), 169 (5), 155
(6), 143 (15), 140 (54), 129 (17), 107 (32), 91 (100). Calcd for C23H27ClOS: M,
386.1471. Found; m/z 386.1478.
11. The sulfoxide–magnesium exchange reaction is known to take place with
retention of configuration of the carbon bearing a sulfinyl group (a) Satoh, T.;
Kobayashi, S.; Nakanishi, S.; Horiguchi, K.; Irisa, S. Tetrahedron 1999, 55, 2515;
(b) Hoffmann, R. W.; Holzer, B.; Knopff, O.; Harms, K. Angew. Chem., Int. Ed.
2000, 39, 3072; (c) Satoh, T.; Matsue, R.; Fujii, T.; Morikawa, S. Tetrahedron
2001, 57, 3891; (d) Hoffmann, R. W. Chem. Soc. Rev. 2003, 32, 225.
4. Asymmetric cyclopropanation of allenes: Aratani, T.; Nakanisi, Y.; Nozaki, H.
Tetrahedron 1968, 26, 1675; Cyclopropanation of chiral-allenic alcohols: (a)
Lautens, M.; Delanghe, P. H. M. J. Org. Chem. 1993, 58, 5037; (b) Lautens, M.;
12. Satoh, T.; Oohara, T.; Ueda, Y.; Yamakawa, K. J. Org. Chem. 1989, 54, 3130.

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N. Nakaya et al. / Tetrahedron Letters 50 (2009) 4212–4216
13. Kido, M.; Sugiyama, S.; Satoh, T. Tetrahedron: Asymmetry 2007, 18, 1934.
14. A solution of cyclopentylmagnesium chloride (0.23 mmol) was added to a
solution of 19 (30 mg; 0.08 mmol) in 0.78 mL of THF at ꢀ40 °C with stirring
under Ar atmosphere. The solution was stirred for 15 min and the reaction
was quenched with satd aq NH4Cl. The whole was extracted with CHCl3 and
the organic layer was dried over MgSO4. The solvent was evaporated and the
residue was purified by silica gel column chromatography to afford 20
(14.3 mg; 87%) as colorless oil; IR (neat) 3028, 2929, 2853, 1604, 1496, 1447,
1.45–1.59 (6H, m), 1.63–1.75 (1H, m), 2.05–2.16 (2H, m), 2.16–2.27 (2H, m),
2.55 (1H, dd, J = 14.3, 7.7 Hz), 2.76 (1H, dd, J = 14.3, 6.1 Hz), 7.13–7.33 (5H,
m). MS m/z (%) 212 (M+, 69), 197 (11), 183 (24), 169 (21), 155 (18), 143 (21),
130 (43), 129 (100), 128 (33), 121 (59), 115 (24), 104 (41), 93 (41), 91 (99).
Calcd for C16H21
EtOH).
:
M, 212.1565. Found; m/z 212.1555. ½ ꢁ +50.5 (c 0.9,
a 2D8
15. (a) Brinker, U. H.; Boxberger, M. Angew. Chem., Int. Ed. 1984, 23, 974; (b)
Brinker, U. H.; Weber, J. Tetrahedron Lett. 1986, 27, 5371; (c) Nordvik, T.;
Mieusset, J.-L.; Brinker, U. H. Org. Lett. 2004, 6, 715.
1260, 1238, 737, 698 cmꢀ1 1H NMR d 0.73–0.81 (1H, m), 1.14–1.24 (1H, m),
;